Characteristics, Management and Outcomes of Primary Hyperparathyroidism from 2009 to 2021: a single centre report from South Africa.

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Kamal Govind, Imran M. Paruk, Ayesha A. Motala This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3873001/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 24 Apr, 2024 Read the published version in BMC Endocrine Disorders → Version 1 posted 4 You are reading this latest preprint version Abstract Background: There has been a notable shift towards the diagnosis of less severe and asymptomatic primary hyperparathyroidism (PHPT) in developed countries. However, there is a paucity of recent data from sub-Saharan Africa (SSA), and also, no reported data from SSA on the utility of intra-operative parathyroid hormone (IO-PTH) monitoring. In an earlier study from Inkosi Albert Luthuli Central Hospital (IALCH), Durban, South Africa (2003–2009), majority of patients (92.9%) had symptomatic disease. The aim of this study was to evaluate the clinical profile and management outcomes of patients presenting with PHPT at IALCH. Methods: A retrospective chart review of patients with PHPT attending the Endocrinology clinic at IALCH between July 2009 and December 2021. Clinical presentation, laboratory results, radiologic findings, surgical notes and histology were recorded. Results: Analysis included 110 patients (87% female) with PHPT. Median age at presentation was 57 (44; 67.5) years. Symptomatic disease was present in 62.7% (n:69); 20.9% (n:23) had a history of nephrolithiasis and 7.3% (n:8) presented with previous fragility fractures. Mean serum calcium was 2.87 ± 0.34 mmol/l; median serum-PTH was 23.3 (15.59;45.38) pmol/l, alkaline phosphatase 117.5 (89;145.5) U/l and 25-hydroxyvitamin-D 42.9 (33.26;62.92) nmol/l. Sestamibi scan (n:106 patients) identified an adenoma in 83.02%. Parathyroidectomy was performed on 84 patients with a cure rate of 95.2%. Reasons for conservative management (n:26) included: no current surgical indication (n:7), refusal (n:5) or deferral of surgery (n:5), loss to follow-up (n:5) and assessed as high anaesthetic risk (n:4). IO-PTH measurements performed on 28 patients indicated surgical success in 100%, based on Miami criteria. Histology confirmed adenoma in 88.1%, hyperplasia in 7.1% and carcinoma in 4.8%. Post-operative hypocalcaemia developed in 30 patients (35.7%), of whom, 14 developed hungry bone syndrome (HBS). In multivariate analysis, significant risk factors associated with HBS included male sex (OR 7.01; 95% CI 1.28, 38.39; p 0.025) and elevated pre-operative PTH (OR 1.01; 95% CI 1.00, 1.02; p 0.008) Conclusions: The proportion of asymptomatic PHPT has increased at this centre over the past decade but symptomatic disease remains the dominant presentation. Parathyroidectomy is curative in the majority of patients. IO-PTH monitoring is valuable in ensuring successful surgery. Primary Hyperparathyroidism hypercalcaemia parathyroid hormone hungry bone syndrome parathyroidectomy intra-operative parathyroid hormone monitoring Figures Figure 1 Introduction Primary Hyperparathyroidism (PHPT) is a disorder of calcium homeostasis defined by hypercalcaemia and elevated or inappropriately normal levels of parathyroid hormone (PTH)(1-3). From available reports, there is a high incidence in the western world, as high as 8.2/1000 person-years in the United States of America (USA) with a female preponderance (F:M; 3-4:1)(1). Solitary benign parathyroid adenoma accounts for the majority (± 80%) of PHPT, with multiglandular disease accounting for 15-20% (1, 3, 4). Symptomatic PHPT presents with a multitude of complications including skeletal, renal, neuropsychiatric and cardiovascular manifestations, classically described as “bones, stones, groans and moans”(1, 3, 4). The clinical presentation in developed countries has evolved from one of symptomatic severe disease to asymptomatic and often incidentally discovered(1, 3). Earlier diagnosis through adoption of routine calcium testing in the 1970’s(2) and an increase in screening for osteoporosis in the late 1990’s(3), may account for the lower frequency of symptomatic disease. As routine tests are also increasingly available in developing countries, there has been a shift in the spectrum towards less severe and asymptomatic disease, as reported in recent studies from India and China(5, 6). Vitamin D deficiency is frequently found in patients with PHPT, with a reported incidence of 91% to 100%(7). The relationship between vitamin D deficiency and PHPT remains unclear. Although vitamin D deficiency is usually associated with secondary hyperparathyroidism, it has been postulated that vitamin D deficiency may lead to parathyroid hyperplasia or adenomatous change and possibly greater disease severity in PHPT(3, 5, 7, 8). Despite the changes in disease presentation, parathyroidectomy is still the only cure for PHPT, especially for symptomatic patients(3). The use of intraoperative parathyroid hormone (IO-PTH) monitoring during parathyroidectomy has become valuable in assisting surgeons to ascertain if all hyperfunctioning parathyroid tissue was excised. IO-PTH has been shown to be highly sensitive and specific in predicting operative success. (9) There is a paucity of data on patients with PHPT from Africa, and only two previous reports from South Africa (10, 11). In a study from our centre (Inkosi Albert Luthuli Central Hospital (IALCH)) in Durban, the characteristics and outcome of PHPT were analysed in 28 patients over 6 years (2003 – 2009). The majority (92.9%) of patients had symptomatic disease and surgery was successful in 94.7% of patients (10). A more recent report from Cape Town also reviewed BMD findings, rates of vertebral fractures and osteitis fibrosa cystica in patients with PHPT who had parathyroidectomy; 50% of post-menopausal women and older men had osteoporosis and 21% of patients had vertebral fractures (11). The limited information highlights the need for further reports from South Africa and sub-Saharan Africa (SSA) regarding the frequency of asymptomatic disease presentation, vitamin D status of patients with PHPT and the utility of intra-operative PTH (IO-PTH) monitoring. This study was undertaken to determine the clinical, laboratory and radiologic features and outcomes of management of patients presenting with PHPT between 2009 and 2021; also to determine whether there was a change over the past decade. Research Design and Methods Study design and study population: This was a retrospective chart review of all patients with primary hyperparathyroidism referred to the adult endocrinology clinic at IALCH from July 2009 to December 2021. Patients with familial hypocalciuric hypercalcaemia, tertiary hyperparathyroidism, lithium-related hypercalcaemia, diuretic-associated hypercalcaemia and those patients under 12 years of age were excluded. Data Collection: The files of all patients with PHPT were accessed on the electronic health record (EHR) system at IALCH. Data recorded for each patient included demographic details, symptomatology, past medical history and clinical parameters. Pre-operative laboratory results recorded included: serum PTH, corrected calcium, phosphate, magnesium, urea, creatinine, alkaline phosphatase (ALP), 25-hydroxyvitamin D, 1,25-hydroxyvitamin D, lipid profile and HbA 1C . Estimated glomerular filtration rate (eGFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation(12). Twenty-four hour urine calcium excretion and spot urine calcium to creatinine excretion ratio were also recorded. Serum PTH was analysed using chemiluminescence immunoassay (normal reference range: 2.0-8.5 pmol/l). Definitions: Where IO-PTH monitoring was undertaken, blood was drawn before and 10 minutes after resection of the adenomas. Surgical success was defined using the Miami criteria, i.e. a > 50% drop in PTH levels at 10 minutes after the excision of all hyperfunctioning parathyroid gland(s)(9, 13). Vitamin D deficiency was defined as a serum 25-OH-Vitamin D level of < 30nmol/l. Hungry bone syndrome (HBS) was defined as profound (corrected serum calcium -2.5 below the young adult mean or Z-score > -2.5 below the mean for males < 50 years and premenopausal females. Pre-operative radiological data recorded included skeletal survey, bone mineral density (BMD) scan using dual-energy X-ray absorptiometry (DEXA), renal ultrasound and technetium (Tc-99m) sestamibi scan. Surgical notes were reviewed to note if a culprit lesion was identified at surgery and histology reports were reviewed for a final diagnosis (parathyroid adenoma, hyperplasia or carcinoma). Post-operative evaluation: Laboratory results recorded within the first 24 hours post-operatively included serum PTH, corrected calcium, phosphate, magnesium and ALP. The corrected calcium, phosphate and magnesium were recorded daily for up to 6 days/until time of discharge as part of evaluation for post-operative hypocalcaemia and/or HBS. The results at discharge were also recorded and used in the final analyses. Where available, repeat BMD results during outpatient follow-up were documented with areal BMD (aBMD) values used to monitor changes post-operatively. Statistical Analysis: Statistical analysis was performed using SPSS (Statistics Package for the Social Sciences) version 28. Data are presented as mean ± SD, median (Interquartile Range - IQR) or %. For univariate and bivariate analysis, continuous variables were compared using the Student’s t-test and categorical variables compared with Pearson′s Chi-Square (Χ 2 ) test. Multivariate analysis for predictors (risk factors) for HBS was undertaken using logistic regression and reported as OR(95% CI)p. The performance of sestamibi scan in predicting successful resection of the culprit lesion was assessed by correlating sestamibi scan results with surgeon’s finding at surgery, by cross-tabulation. A p value of <0.05 was considered statistically significant. Results Demography and Clinical Presentation: The study population included 110 patients, with median age 57 (44; 66.8) years; 87.3% were female and the majority were of African or Indian ethnicity (Table 1). The median BMI was 27.4 (23.39; 32.85) kg/m 2 and median blood pressure 130 (116; 146) mmHg systolic and 75 (66; 82) mmHg diastolic. A past history suggestive of PHPT was reported in 39.1% (n:43) with nephrolithiasis (n: 23) the most frequent. In 10 patients with a history of malignancy, 4 patients had previously treated breast cancer (Table 1). At presentation, 37.3% (n:41) were asymptomatic while 62.7% (n:69) were symptomatic; the most common symptoms were constipation (25.7%) and weight loss (20.9%) (Figure 1a). Baseline biochemistry and radiology: Table 1 shows the baseline biochemistry results. Mean serum calcium was 2.87±0.34 mmol/l and mean phosphate 0.87±0.12 mmol/l; median ALP 117.5 (89; 145.5) U/L and median PTH 23.3 (15.95; 45.38) pmol/l. Median 24-hour urine calcium excretion was 3.33 (1.58; 5.41) mmol/24 hours. Median 25-hydroxyvitamin D was 42.9 (33.26; 62.92) nmol/l. The most frequently reported abnormality on x-ray was osteitis fibrosa cystica (23.3%) (Figure 1b). Osteoporosis was found in 54.9% (51/93) on BMD with mean T-score -2.74 ± 1.83 and mean Z-score -1.65 ± 2.01 at distal ⅓ of radius. In 106 patients who had Sestamibi scans, 83% (n:88) had evidence of a parathyroid adenoma; the remainder were negative. Management: Surgery was undertaken in the majority (76.4%; n:84) of patients; 26 patients were managed conservatively, for the following reasons: no current surgical indication (n:7), refusal (n:5) or deferral of surgery (n:5), loss to follow-up (n:5) and deemed a high anaesthetic risk (n:4). Of the surgical group, 40% (n:34) received intravenous bisphosphonates pre-operatively. Operative and Post-operative: At surgery, a resectable lesion was identified in 95.2% (n:80) (80/84). On histology, the majority (n:73) of patients were confirmed to have single parathyroid adenoma; one patient had 2 adenomas. 7.1% (n:6) had hyperplasia and 4.8% (n:4) had parathyroid carcinoma (Table 2). The surgeon’s macroscopic finding of an adenoma correlated with histology in 91.3% (73/80) of patients; in 3 (3.8%) patients, histology showed hyperplasia and in 4 (5%) carcinoma. Of the 4 patients with no resectable lesion identified during surgery, histology from sub-total parathyroidectomy confirmed a single adenoma in 1 patient and hyperplasia in 3 patients. At discharge post-surgery, there was a reduction in median serum calcium from 2.90 (2.67; 3.13) to 2.25 (2.15; 2.35) mmol/l and PTH from 24.65 (16.78; 56.58) to 4.45 (2.1; 8.75) pmol/l) with increase in mean serum phosphate from 0.83±0.196 to 1.15±0.68 mmol/l. Post-operative hypocalcaemia developed in 35.7% (30/84) of patients; 16.6% (n:14) developed hungry bone syndrome (HBS), requiring intravenous calcium supplementation. Hypocalcaemia was transient in 20.2% (n:17) and permanent in 15.5% (n:13). Most patients with post-operative hypocalcaemia (n:19) were on oral calcium replacement at discharge; 13 patients (43.3%) required additional 1-alpha calcidiol therapy (Table 3). Post-operative BMD done on 20 patients (median follow-up 15.5 months) showed significant improvement only at the spine (+6.5%). The surgical cure rate was 95.2% (n: 80) (Table 2). Reasons for failed surgery (n:4) included persistent PHPT due to incomplete excision (n:2) and recurrent disease with evidence of a new adenoma at follow-up 1 year after first surgery (n:2). At presentation, when compared with patients who did not develop HBS, patients with HBS were significantly younger and leaner, had higher serum PTH and ALP and lower phosphate; eGFR was higher and HbA 1C lower. Mean BMD was lower at all sites (Table 4). In multivariate analysis, significant predictive risk factors for HBS included male sex (OR 7.01; 95% CI 1.28, 38.39; p 0.025) and pre-operative serum PTH (OR 1.008; 95% CI 1.00, 1.02; p 0.008) (Table 5). Compared to patients without Vitamin D deficiency, patients with Vitamin D deficiency (n: 16) were significantly younger (42 vs. 59 years)(p = 0.008), and had higher median pre-operative calcium (2.95 vs. 2.83 mmol/l)(p = 0.029) and ALP (202 vs. 103 U/l)(p = 0.00); median BMD T-scores were lower at the hip (-2.0 vs. -1.1)(p=0.033), spine (-3.3 vs. -1.8)(p=0.013) and radius (-4.5 vs. -2.4)(p=0.006) (Table 6). In bivariate analysis, significant predictors for Vitamin D deficiency were non-trauma or fragility fractures (p = 0.032) and osteitis fibrosa cystica (p < 0.001). Preoperative sestamibi scans (in 82 of 84 patients) had a sensitivity of 93.9%, specificity of 100% and positive predictive value of 100% for successful location and resection of culprit lesion. There was a 100% cure rate in the 28 patients who had IO-PTH monitoring, while patients who did not have IO-PTH monitoring had a 92.9% cure rate (Table 2). When compared with our previous report in 2009 (10), there was a significantly higher frequency of asymptomatic presentation of PHPT (37.3 vs 7.1%) [p=0 0,003]. Discussion In this study, there was a higher proportion of asymptomatic PHPT compared to the previous study at the same centre, but the prevalence of symptomatic disease is still high and parathyroid adenoma remains the major cause of PHPT. IO-PTH monitoring is valuable in confirming successful surgery. The increase in asymptomatic disease from 7.1% reported in our previous study in 2009 ( 10 ) to 37.3% in the present study, although lower than the predominantly asymptomatic PHPT found in developed countries( 1 , 3 ), is similar to that observed in other developing countries such as China and India ( 15 , 16 ). This can be explained by wider implementation of routine serum calcium measurement as part of biochemical screening, even in developing countries. The finding that the major cause of PHPT in this study was a solitary benign parathyroid adenoma is compatible with most other studies reported globally( 1 , 3 – 6 ). Parathyroid carcinoma accounted for 4.8% of histological diagnoses in this group. This is similar to rates reported in India and China ( 5 , 6 ). In this study, IO-PTH confirmed surgical success of focused parathyroidectomy in all cases (100%) and highlights the accuracy of the Miami criterion for predicting surgical cure. This is higher than that reported in other studies (97–98%) ( 9 , 17 ) and may largely be explained by having a highly experienced dedicated parathyroid surgeon. However, IO-PTH was only done in one third of the surgical group, highlighting the need to confirm this in a larger group and to evaluate emerging alternate criteria( 9 , 17 – 19 ). As reported in other studies ( 16 , 20 – 22 ), nephrolithiasis was the most common presenting feature; the prevalence of osteoporosis was lower compared with studies reporting similar rates of symptomatic PHPT ( 5 , 6 , 16 , 21 , 22 ) and may be explained by less frequent screening for hypercalcaemia at primary levels of care. As in other studies, hypercalcaemia was present in the majority of patients ( 15 ). The proportion (15.6%) with normocalcaemic PHPT (NPHPT) is higher than the reported prevalence of 0.1–8.9% ( 23 ). These may be patients with mild PHPT or alternatively a variant of PHPT that has variable rates of progression to hypercalcaemia and is unlikely due to Vitamin D deficiency ( 24 , 25 ). Vitamin D deficiency was found in 16.8% (n:16/95) of patients in this study; this is similar to rates reported in both developed and developing countries( 26 , 27 ). Patients with vitamin D deficiency were younger, had higher pre-operative calcium, higher ALP levels and lower median BMD scores at all sites than those without Vitamin D deficiency. Vitamin D deficiency has been associated with severe disease ( 8 , 28 ) and these findings could indicate that it may be associated with greater skeletal disease burden and, thus, lower BMD. However, the low prevalence of Vitamin D deficiency makes it difficult to draw such conclusions. The high rate of surgical cure in this study (95.2%) is comparable to rates in other studies with highly skilled, dedicated surgeons using minimally-invasive techniques guided by preoperative localization imaging ( 29 , 30 ). In our centre, preoperative localization with Tc-99 sestamibi was highly sensitive and specific in predicting successful resection of the culprit lesion and is consistent with findings in developed as well as other developing countries such as India ( 31 , 32 ). Post-operatively, HBS developed in 16.6% of patients, which is similar to other reports from Europe and the Middle East ( 33 – 35 ), but higher than rates observed in a recent report from Singapore ( 36 ). Significant predictors for HBS included male sex and a higher pre-operative PTH level, which were also found in recent reports ( 33 – 35 ). Identifaction of patients with these risk factors may enable prompt perioperative treatment and decrease morbidity and hospitalisation. The observation that post-operative increase in BMD was only significant at the spine is in keeping with results of recent studies from China with similar follow-up intervals ( 37 , 38 ). This may be explained by rates of bone turnover being higher in cancellous bone, resulting in rapid and lasting improvement in BMD ( 37 , 38 ). However, since less than 24% of patients had repeat BMD measurements post-operatively, the results need to be interpreted with caution and requires further investigation. Comparison with the earlier study from this centre showed that patients’ clinical characteristics, biochemical findings and cure rate are largely similar. This highlights the need for increased routine biochemical testing at primary care centres in order to detect more patients with asymptomatic PHPT. The strength of this study is that it is the largest clinical study done on PHPT in South Africa and that it can be compared to the previous study at our centre. There are several limitations including the retrospective nature, limited number of patients who had IO-PTH monitoring, and follow-up BMD measurements post-surgery. Further studies are needed in other centres in South Africa and other African countries to confirm the findings of this study, ascertain trends in BMD changes post-operatively as well as assess the utility and cost-effectiveness of IO-PTH monitoring. CONCLUSION The proportion of asymptomatic PHPT has increased at this centre over the past decade but symptomatic disease remains the dominant presentation and is higher than that reported in developed countries. Parathyroid adenoma is the commonest cause of PHPT with parathyroidectomy being curative in the majority of patients. IO-PTH monitoring is valuable in guaranteeing successful surgery. Abbreviations PHPT Primary Hyperparathyroidism SSA Sub-Saharan Africa IO-PTH Intraoperative parathyroid hormone IALCH Inkosi Albert Luthuli Central Hospital PTH Parathyroid hormone USA United States of America EHR Electronic health record ALP Alkaline phosphatase eGFR Estimated glomerular filtration rate CKD-EPI Chronic Kidney Disease Epidemiology Collaboration HBS Hungry Bone Syndrome BMD Bone Mineral Density DEXA Dual-Energy X-ray Absorptiometry Tc-99m Technetium SPSS Statistics Package for the Social Sciences IQR Interquartile range OR Odds Ratio 95% CI 95% confidence interval BMI Body mass index NPHPT Normocalcaemic primary hyperparathyroidism Declarations Ethics approval and consent to participate: The study was approved by the University of KwaZulu-Natal Biomedical Research Ethics committee (BREC) [reference number: BREC/00001483/2020]. Individual participant consent was waived as this was a retrospective chart review and patients were not put at risk. Consent was waived to Inkosi Albert Luthuli Central Hospital (IALCH) and KwaZulu-Natal Department of Health, both of which granted permission to access patient information. Consent for publication: Not applicable Availability of data and materials: The datasets generated and/or analysed during the current study are not publicly available due to patient confidentialty, but are available from the corresponding author on reasonable request. Competing interests: None Funding: None Authors' contributions: KG contributed to the conception and design of this study, collection and interpretation of data and drafted the manuscript. IMP and AAM contributed to the design of the study, analysis of data and revised the article critically. All authors read and approved the final manuscript. Acknowledgements: We thank Dr Ines Buccimazza (Head of Clinical Unit, Breast and Endocrine Surgery at Inkosi Albert Luthuli Central Hospital) for her assisstance with data collection. 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Tables Table 1: Clinical and biochemical characteristics of the total study group at presentation (n: 110) N % Sex (M : F) 14 : 96 12.7 : 87.3 Ethnicity Indian 48 43.6 African 45 40.9 White 16 14.5 Mixed Race (Coloured) 1 1 Range Age (years) 57 (44; 66.8) 13-84 BMI (kg/m 2 ) 27.4 (23.4; 32.9) 14.55-49.98 Systolic Blood Pressure (mmHg) 130 (116; 146) 92-186 Diastolic Blood Pressure (mmHg) 75 (66; 82) 46-104 N % Past History Attributable To PHPT 43 39.1 Nephrolithiasis 23 20.9 Non-trauma fracture 8 7.3 Osteoporosis 7 6.4 Peptic Ulcer Disease 6 5.5 Depression 3 2.7 Pancreatitis 2 2 Psychosis 1 1 Other Medical History N % Hypertension 66 60.5 Diabetes Mellitus 29 26.4 Dyslipidaemia 31 28.2 Malignancy 10 9.1 Baseline Biochemistry Normal Reference Range Serum Calcium (mmol/l) 2.87 ± 0.34 2.15-2.50 Serum Magnesium (mmol/l) 0.82 ± 0.12 0.63-1.05 Serum Phosphate (mmol/l) 0.87 ± 0.20 0.78-1.42 Serum Creatinine (μmol/l) 71 (58; 95) 49-90 eGFR (CKD-EPI) (ml/min/1.73m 2 ) 85.9 ± 33.4 >60 Serum ALP (U/L) 117.5 (89; 145.5) 42-98 Serum PTH (pmol/l) 23.3 (16.0; 45.4) 2.0-8.5 *Serum 25-OH Vitamin D (nmol/l) (n:95) 42.9 (33.3; 62.9) >50 Vitamin D deficiency (n;%) 16; 16.8 24-hour urine calcium (mmol/day) 3.3 (1.6; 5.4) 2.5-7.5 Data are presented as Mean ± SD or Median (IQR) or %. BMI: body mass index. Vitamin D Deficiency: serum 25-OH-vitamin D < 30 nmol/l. * Serum 25-OH Vitamin D available in 95 patients Table 2: Outcomes of surgery, intra-operative parathyroid hormone (IO-PTH) monitoring and histopathology (n:84) n % Parathyroidectomy 84 100 Cure 80 95.2 No cure 4 4.8 IO-PTH Monitoring IO-PTH 28 33.3 Success/Cure 28 100 No IO-PTH 56 66.7 Success/Cure 52 92.9 Histological Diagnosis Adenoma 74 88.1 Hyperplasia 6 7.1 Carcinoma 4 4.8 IO-PTH: Intra-operative parathyroid hormone monitoring. Table 3: Frequency of post-operative complications and replacement therapy n % Complication 84 Hypocalcaemia 30 35.7 Transient 17 20.2 Permanent 13 15.5 Hungry Bone Syndrome 14 16.6 Recurrent laryngeal nerve injury 0 0 Bleeding 0 0 Infection 0 0 Treatment for Hypocalcaemia n:30 35.7 Intravenous Calcium 14 46.7 Oral Calcium 19 63.3 One-Alpha Calcidiol 13 43.3 No replacement 11 36.7 Table 4: Characteristics at presentation in patients with and without Hungry Bone Syndrome (HBS) (n:84) Pre-operative HBS (n:14) No HBS (n:70) P Age (years) 39.5 (20.8; 56) 58 (47; 67) 0.012 BMI (kg/m 2 ) 22.7 (17.8; 24.1) 27.4 (23.7; 32.4) 0.005 Serum: PTH (pmol/l) 172.7 (71.2; 230) 23.1 (15.95; 38.9) <0.00 ALP (U/L) 900 (174.8; 1540.3) 117 (88; 140.3) 0.000 Calcium (mmol/l) 3.06 ± 0.45 2.88 ± 0.30 0.084 Magnesium (mmol/l) 0.78 ± 0.13 0.82 ± 0.11 0.304 Phosphate (mmol/l) 0.73 ± 0.16 0.87 ± 0.19 0.018 aBMD Hip (g.cm 2 ) 0.6 ± 0.3 0.8 ± 0.2 0.015 aBMD Spine (g.cm 2 ) 0.7 ± 0.2 0.8 ± 0.2 0.013 aBMD Radius (g.cm 2 ) 0.4 ± 0.1 0.6 ± 0.1 0.002 eGFR (CKD-EPI) (ml/min/1.73m 2 ) 114 ± 39.1 83.5 ± 30.5 0.002 HbA1c (%) 5.4 (5.3; 5.8) 6.3 (5.8; 7.9) 0.008 Data are presented as Mean ± SD or Median (IQR). BMI: Body Mass Index; PTH: Parathyroid Hormone; ALP: Alkaline phosphatase. Table 5: Logistic regression analysis for predictors (risk factors) for hungry bone syndrome (HBS). Variable OR (95% C.I) P PTH 1.0 (1.0, 1.02) 0.008 Male Gender 7.0 (1.3, 38.4) 0.025 24-hour urine calcium 1.2 (1.0, 1.5) 0.107 Phosphate 0.02 (0.0, 2.8) 0.239 PTH: Parathyroid Hormone. OR (95% C.I.): Odds Ratio (95% confidence interval). Table 6: Comparison of clinical parameters, biochemistry and cure rate between 2009 (n:28) and current (n:110) study 2009 n:28 2021 n:110 P Symptomatic (%) 92.9 62.7 0.002 BMI (kg/m 2 ) 28.1 (26.1; 31.1) 27.3 (23.4; 32.9) 0.462 Pre-operative Serum Calcium (mmol/l) 3.00 (2.9; 3.2) 2.83 (2.6; 3.1) 0.010 Serum PTH (pmol/l) 16.85 (9.9; 40.7) 23.3 (16.0; 45.4) 0.824 25-OH Vit D (nmol/l) 39 (26; 47.9) 42.9 (33.3; 62.9) 0.488 Serum ALP (U/l) 98 (79; 125) 117.5 (89; 145.5) 0.133 24-hour urine calcium (mmol/day) 5.1 (2.5; 6.1) 3.34 (1.59; 5.4) 0.654 Post-operative Serum PTH (pmol/l) 2.3 (1.1; 4.5) 4.4 (2.1; 8.8) 0.044 Serum Calcium (mmol/l) 2.31 (2.2; 2.4) 2.25 (2.15; 2.4) 0.233 Cure (%) 94.7 95.2 0.819 Data are presented as Median (IQR) or % BMI: body mass index; PTH: Parathyroid Hormone, 25-OH Vit D: 25-hydroxyvitamin D; ALP: Alkaline phosphatase Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 24 Apr, 2024 Read the published version in BMC Endocrine Disorders → Version 1 posted Editorial decision: Revision requested 22 Jan, 2024 Submission checks completed at journal 19 Jan, 2024 Editor assigned by journal 19 Jan, 2024 First submitted to journal 17 Jan, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-3873001","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":268493720,"identity":"f441cd99-6542-4a47-aac1-76278ae2cd52","order_by":0,"name":"Kamal Govind","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABBklEQVRIiWNgGAWjYBACCRDxAEQwAzkJPDZAFmPjAYJaEmBaPsikgbQ0EKkFCCRn2BwGM/BqkWw/nfghgaFWzuA478HbPDnn7da2HwbaUmMTjUuLNE/uZokEhuPGBof5kq15ztxO3nYmEajlWFpuAw4tcgy5G4BajiXObOYxk+btuZ1sdgCohbHhMG4t/G83/0Bo+Xcu2ez8Q/xapCVytwFtqUnsZ+Yxk5zBc8DO7AYBWyRnvN1mkWBwwJifmcfY4gNPcoLZDaAtCXj8InE+d/ONDxV1cmz8ZwxvJPDY2ZudT3/44EONDU4tEGBwGM5MBKtMwKscDOrgLHvCikfBKBgFo2CkAQBvF1/IeQRJTwAAAABJRU5ErkJggg==","orcid":"","institution":"University of KwaZulu-Natal","correspondingAuthor":true,"prefix":"","firstName":"Kamal","middleName":"","lastName":"Govind","suffix":""},{"id":268493721,"identity":"e5de08f1-5c8d-48fc-9756-a785e0741bed","order_by":1,"name":"Imran M. Paruk","email":"","orcid":"","institution":"University of KwaZulu-Natal","correspondingAuthor":false,"prefix":"","firstName":"Imran","middleName":"M.","lastName":"Paruk","suffix":""},{"id":268493722,"identity":"e8261d7b-89da-4f38-a9b5-a57b309e9c6c","order_by":2,"name":"Ayesha A. Motala","email":"","orcid":"","institution":"University of KwaZulu-Natal","correspondingAuthor":false,"prefix":"","firstName":"Ayesha","middleName":"A.","lastName":"Motala","suffix":""}],"badges":[],"createdAt":"2024-01-17 13:15:33","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3873001/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3873001/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12902-024-01583-8","type":"published","date":"2024-04-25T00:40:18+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":50116143,"identity":"9a0590c6-0508-4d02-a80e-6e2dad5f279f","added_by":"auto","created_at":"2024-01-24 18:48:23","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":43858,"visible":true,"origin":"","legend":"\u003cp\u003ePrevalence of symptoms at presentation (n:110)(Figure 1a), and radiological abnormalities on plain x-rays at presentation (n:103)(Figure 1b).\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-3873001/v1/21f2e8ab43d966d1c4652ab2.png"},{"id":55697586,"identity":"a0fc28b4-6810-4450-84a2-ccd086494ea3","added_by":"auto","created_at":"2024-05-02 02:13:51","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":605519,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3873001/v1/8d4ba63a-ffba-4e8b-b3b1-fb9cbb2b245d.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Characteristics, Management and Outcomes of Primary Hyperparathyroidism from 2009 to 2021: a single centre report from South Africa.","fulltext":[{"header":"Introduction","content":"\u003cp\u003ePrimary Hyperparathyroidism (PHPT) is a disorder of calcium homeostasis defined by hypercalcaemia and elevated or inappropriately normal levels of parathyroid hormone (PTH)(1-3). \u0026nbsp;From available reports, there is a high incidence in the western world, as high as 8.2/1000 person-years in the United States of America (USA) with a female preponderance (F:M; 3-4:1)(1). \u0026nbsp;Solitary benign parathyroid adenoma accounts for the majority (± 80%) of PHPT, with multiglandular disease accounting for 15-20%\u0026nbsp;(1, 3, 4).\u003c/p\u003e\n\u003cp\u003eSymptomatic PHPT presents with a multitude of complications including skeletal, renal, neuropsychiatric and cardiovascular manifestations, classically described as “bones, stones, groans and moans”(1, 3, 4). The clinical presentation in developed countries has evolved from one of symptomatic severe disease to asymptomatic and often incidentally discovered(1, 3). Earlier diagnosis through adoption of routine calcium testing in the 1970’s(2)\u0026nbsp;and an increase in screening for osteoporosis in the late 1990’s(3), may account for the lower frequency of symptomatic disease. As routine tests are also increasingly available in developing countries, there has been a shift in the spectrum towards less severe and asymptomatic disease, as reported in recent studies from India and China(5, 6).\u003c/p\u003e\n\u003cp\u003eVitamin D deficiency is frequently found in patients with PHPT, with a reported incidence of 91% to 100%(7). The relationship between vitamin D deficiency and PHPT remains unclear. Although vitamin D deficiency is usually associated with secondary hyperparathyroidism, it has been postulated that vitamin D deficiency may lead to parathyroid hyperplasia or adenomatous change and possibly greater disease severity in PHPT(3, 5, 7, 8).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eDespite the changes in disease presentation, parathyroidectomy is still the only cure for PHPT, especially for symptomatic patients(3). The use of intraoperative parathyroid hormone (IO-PTH) monitoring during parathyroidectomy has become valuable in assisting surgeons to ascertain if all hyperfunctioning parathyroid tissue was excised. IO-PTH has been shown to be highly sensitive and specific in predicting operative success.\u0026nbsp;(9)\u003c/p\u003e\n\u003cp\u003eThere is a paucity of data on patients with PHPT from Africa, and only two previous reports from South Africa\u0026nbsp;(10, 11). In a study from our centre (Inkosi Albert Luthuli Central Hospital (IALCH)) in Durban, the characteristics and outcome of PHPT were analysed in 28 patients over 6 years (2003 – 2009). The majority (92.9%) of patients had symptomatic disease and surgery was successful in 94.7% of patients\u0026nbsp;(10). A more recent report from Cape Town also reviewed BMD findings, rates of vertebral fractures and osteitis fibrosa cystica in patients with PHPT who had parathyroidectomy; 50% of post-menopausal women and older men had osteoporosis and 21% of patients had vertebral fractures\u0026nbsp;(11). The limited information highlights the need for further reports from South Africa and sub-Saharan Africa (SSA) regarding the frequency of asymptomatic disease presentation, vitamin D status of patients with PHPT and the utility of intra-operative PTH (IO-PTH) monitoring.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThis study was undertaken to determine the clinical, laboratory and radiologic features and outcomes of management of patients presenting with PHPT between 2009 and 2021; also to determine whether there was a change over the past decade.\u003c/p\u003e"},{"header":"Research Design and Methods","content":"\u003cp\u003e\u003cstrong\u003eStudy design and study population:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis was a retrospective chart review of all patients with primary hyperparathyroidism referred to the adult endocrinology clinic at IALCH from July 2009 to December 2021. Patients with familial hypocalciuric hypercalcaemia, tertiary hyperparathyroidism, lithium-related hypercalcaemia, diuretic-associated hypercalcaemia and those patients under 12 years of age were excluded.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Collection:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe files of all patients with PHPT were accessed on the electronic health record (EHR) system at IALCH. Data recorded for each patient included demographic details, symptomatology, past medical history and clinical parameters. Pre-operative laboratory \u0026nbsp;results recorded included: serum PTH, corrected calcium, phosphate, magnesium, urea, creatinine, alkaline phosphatase (ALP), 25-hydroxyvitamin D, 1,25-hydroxyvitamin D, lipid profile and HbA\u003csub\u003e1C\u003c/sub\u003e. Estimated glomerular filtration rate (eGFR) was calculated using the\u0026nbsp;Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation(12). Twenty-four hour urine calcium excretion and spot urine calcium to creatinine excretion ratio were also recorded. Serum PTH was analysed using\u0026nbsp;chemiluminescence immunoassay (normal reference range: 2.0-8.5 pmol/l).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDefinitions:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWhere\u0026nbsp;IO-PTH monitoring was undertaken, blood was drawn before and 10 minutes after resection of the adenomas. Surgical success was defined using the Miami criteria, i.e. a \u0026gt; 50% drop in PTH levels at 10 minutes after the excision of all hyperfunctioning parathyroid gland(s)(9, 13).\u0026nbsp;\u0026nbsp;Vitamin D deficiency was defined as a serum 25-OH-Vitamin D level of \u0026lt; 30nmol/l.\u0026nbsp;Hungry bone syndrome (HBS) was defined as profound (corrected serum calcium \u0026lt; 2.1 mmol/l) and prolonged (longer than four days post-operatively) hypocalcaemia following parathyroidectomy(14). Osteoporosis was defined as BMD T-score \u0026gt; -2.5 below the young adult mean or Z-score \u0026gt; -2.5 below the mean for males \u0026lt; 50 years and premenopausal females.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003ePre-operative radiological data recorded included skeletal survey, bone mineral density (BMD) scan using dual-energy X-ray absorptiometry (DEXA), renal ultrasound and technetium (Tc-99m) sestamibi scan. Surgical notes were reviewed to note if a culprit lesion was identified at surgery and histology reports were reviewed for a final diagnosis (parathyroid adenoma, hyperplasia or carcinoma).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePost-operative evaluation:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eLaboratory results recorded within the first 24 hours post-operatively included serum PTH, corrected calcium, phosphate, magnesium and ALP. The corrected \u0026nbsp; calcium, phosphate and magnesium were recorded daily for up to 6 days/until time of discharge as part of evaluation for post-operative hypocalcaemia and/or HBS. The results at discharge were also recorded and used in the final analyses.\u0026nbsp;Where available, repeat BMD results during outpatient follow-up were documented with areal BMD (aBMD) values used to monitor changes post-operatively.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical Analysis:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eStatistical analysis was performed using SPSS\u0026nbsp;(Statistics Package for the Social Sciences)\u0026nbsp;version 28. Data are presented as mean ± SD, median (Interquartile Range - IQR) or %. For univariate and bivariate analysis, continuous variables were compared using the Student’s t-test and categorical variables compared with\u0026nbsp;Pearson′s Chi-Square (Χ\u003csup\u003e2\u003c/sup\u003e) test. Multivariate analysis for predictors (risk factors) for HBS was undertaken using logistic regression and reported as OR(95% CI)p. The performance of sestamibi scan in predicting successful resection of the culprit lesion was assessed by correlating sestamibi scan results with surgeon’s finding at surgery, by cross-tabulation. A p value of \u0026lt;0.05 was considered statistically significant.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cstrong\u003eDemography and Clinical Presentation:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study population included 110 patients, with median age 57 (44; 66.8) years; 87.3% were female and the majority were of African or Indian ethnicity (Table 1). The median BMI was 27.4 (23.39; 32.85) kg/m\u003csup\u003e2\u003c/sup\u003e and median blood pressure 130 (116; 146) mmHg systolic and 75 (66; 82) mmHg diastolic.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eA past history suggestive of PHPT was reported in 39.1% (n:43) with nephrolithiasis (n: 23) the most frequent. In 10 patients with a history of malignancy, 4 patients had previously treated breast cancer (Table 1). At presentation, 37.3% (n:41) were asymptomatic while 62.7% (n:69) were symptomatic; the most common symptoms were constipation (25.7%) and weight loss (20.9%) (Figure 1a).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eBaseline biochemistry and radiology:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTable 1 shows the baseline biochemistry results. Mean serum calcium was 2.87±0.34 mmol/l and mean phosphate 0.87±0.12 mmol/l; median ALP 117.5 (89; 145.5) U/L and median PTH 23.3 (15.95; 45.38) pmol/l. Median 24-hour urine calcium excretion was 3.33 (1.58; 5.41) mmol/24 hours. Median 25-hydroxyvitamin D was 42.9 (33.26; 62.92) nmol/l.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe most frequently reported abnormality on x-ray was osteitis fibrosa cystica (23.3%) (Figure 1b). Osteoporosis was found in 54.9% (51/93) on BMD with mean T-score -2.74 ± 1.83 and mean Z-score -1.65 ± 2.01 at distal ⅓ of radius. In 106 patients who had Sestamibi scans, 83% (n:88) had evidence of a parathyroid adenoma; the remainder were negative.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eManagement:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSurgery was undertaken in the majority (76.4%; n:84) of patients; 26 patients were managed conservatively, for the following reasons: no current surgical indication (n:7), refusal (n:5) or deferral of surgery (n:5), loss to follow-up (n:5) and deemed a high anaesthetic risk (n:4). Of the surgical group, 40% (n:34) received intravenous bisphosphonates pre-operatively.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eOperative and Post-operative:\u003c/p\u003e\n\u003cp\u003eAt surgery, a resectable lesion was identified in 95.2% (n:80) (80/84). On histology, the majority (n:73) of patients were confirmed to have single parathyroid adenoma; one patient had 2 adenomas. 7.1% (n:6) had hyperplasia and 4.8% (n:4) had parathyroid carcinoma (Table 2). The surgeon’s macroscopic finding of an adenoma correlated with histology in 91.3% (73/80) of patients; in 3 (3.8%) patients, histology showed hyperplasia and in 4 (5%) carcinoma. \u0026nbsp;Of the 4 patients with no resectable lesion identified during surgery, histology from sub-total parathyroidectomy confirmed a single adenoma in 1 patient and hyperplasia in 3 patients.\u003c/p\u003e\n\u003cp\u003eAt discharge post-surgery, there was a reduction in median serum calcium from 2.90 (2.67; 3.13) to 2.25 (2.15; 2.35) mmol/l and PTH from 24.65 (16.78; 56.58) to 4.45 (2.1; 8.75) pmol/l) with increase in mean serum phosphate from 0.83±0.196 to 1.15±0.68 mmol/l.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003ePost-operative hypocalcaemia developed in 35.7% (30/84) of patients; 16.6% (n:14) developed hungry bone syndrome (HBS), requiring intravenous calcium supplementation. Hypocalcaemia was transient in 20.2% (n:17) and permanent in 15.5% (n:13). Most patients with post-operative hypocalcaemia (n:19) were on oral calcium replacement at discharge; 13 patients (43.3%) required additional 1-alpha calcidiol therapy (Table 3).\u003c/p\u003e\n\u003cp\u003ePost-operative BMD done on 20 patients (median follow-up 15.5 months) showed significant improvement only at the spine (+6.5%).\u003c/p\u003e\n\u003cp\u003eThe surgical cure rate was 95.2% (n: 80) (Table 2). Reasons for failed surgery (n:4) included persistent PHPT due to incomplete excision (n:2) and recurrent disease with evidence of a new adenoma at follow-up 1 year after first surgery (n:2).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAt presentation, when compared with patients who did not develop HBS, patients with HBS were significantly younger and leaner, had higher serum PTH and ALP and lower phosphate; eGFR was higher and HbA\u003csub\u003e1C\u003c/sub\u003e lower. Mean BMD was lower at all sites (Table 4). In multivariate analysis, significant predictive risk factors for HBS included male sex (OR 7.01; 95% CI 1.28, 38.39; p 0.025) and pre-operative serum PTH (OR 1.008; 95% CI 1.00, 1.02; p 0.008) (Table 5).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eCompared to patients without Vitamin D deficiency, patients with Vitamin D deficiency (n: 16) were significantly younger (42 vs. 59 years)(p = 0.008), and had higher median pre-operative calcium (2.95 vs. 2.83 mmol/l)(p = 0.029) and ALP (202 vs. 103 U/l)(p = 0.00); median BMD T-scores were lower at the hip (-2.0 vs. -1.1)(p=0.033), spine (-3.3 vs. -1.8)(p=0.013) and radius (-4.5 vs. -2.4)(p=0.006) (Table 6). In bivariate analysis, significant predictors for Vitamin D deficiency were non-trauma or fragility fractures (p = 0.032) and osteitis fibrosa cystica (p \u0026lt; 0.001).\u003c/p\u003e\n\u003cp\u003ePreoperative sestamibi scans (in 82 of 84 patients) had a sensitivity of 93.9%, specificity of 100% and positive predictive value of 100% for successful location and resection of culprit lesion.\u003c/p\u003e\n\u003cp\u003eThere was a 100% cure rate in the 28 patients who had IO-PTH monitoring, while patients who did not have IO-PTH monitoring had a 92.9% cure rate (Table 2).\u003c/p\u003e\n\u003cp\u003eWhen compared with our previous report in 2009 (10), there was a significantly higher frequency of asymptomatic presentation of PHPT (37.3 vs 7.1%) [p=0 0,003].\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this study, there was a higher proportion of asymptomatic PHPT compared to the previous study at the same centre, but the prevalence of symptomatic disease is still high and parathyroid adenoma remains the major cause of PHPT. IO-PTH monitoring is valuable in confirming successful surgery.\u003c/p\u003e \u003cp\u003eThe increase in asymptomatic disease from 7.1% reported in our previous study in 2009 (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e) to 37.3% in the present study, although lower than the predominantly asymptomatic PHPT found in developed countries(\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e), is similar to that observed in other developing countries such as China and India (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e). This can be explained by wider implementation of routine serum calcium measurement as part of biochemical screening, even in developing countries.\u003c/p\u003e \u003cp\u003eThe finding that the major cause of PHPT in this study was a solitary benign parathyroid adenoma is compatible with most other studies reported globally(\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan additionalcitationids=\"CR4 CR5\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). Parathyroid carcinoma accounted for 4.8% of histological diagnoses in this group. This is similar to rates reported in India and China (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIn this study, IO-PTH confirmed surgical success of focused parathyroidectomy in all cases (100%) and highlights the accuracy of the Miami criterion for predicting surgical cure. This is higher than that reported in other studies (97\u0026ndash;98%) (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e) and may largely be explained by having a highly experienced dedicated parathyroid surgeon. However, IO-PTH was only done in one third of the surgical group, highlighting the need to confirm this in a larger group and to evaluate emerging alternate criteria(\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan additionalcitationids=\"CR18\" citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eAs reported in other studies (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan additionalcitationids=\"CR21\" citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e), nephrolithiasis was the most common presenting feature; the prevalence of osteoporosis was lower compared with studies reporting similar rates of symptomatic PHPT (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e) and may be explained by less frequent screening for hypercalcaemia at primary levels of care.\u003c/p\u003e \u003cp\u003eAs in other studies, hypercalcaemia was present in the majority of patients (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e). The proportion (15.6%) with normocalcaemic PHPT (NPHPT) is higher than the reported prevalence of 0.1\u0026ndash;8.9% (\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e). These may be patients with mild PHPT or alternatively a variant of PHPT that has variable rates of progression to hypercalcaemia and is unlikely due to Vitamin D deficiency (\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eVitamin D deficiency was found in 16.8% (n:16/95) of patients in this study; this is similar to rates reported in both developed and developing countries(\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e). Patients with vitamin D deficiency were younger, had higher pre-operative calcium, higher ALP levels and lower median BMD scores at all sites than those without Vitamin D deficiency. Vitamin D deficiency has been associated with severe disease (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e) and these findings could indicate that it may be associated with greater skeletal disease burden and, thus, lower BMD. However, the low prevalence of Vitamin D deficiency makes it difficult to draw such conclusions.\u003c/p\u003e \u003cp\u003eThe high rate of surgical cure in this study (95.2%) is comparable to rates in other studies with highly skilled, dedicated surgeons using minimally-invasive techniques guided by preoperative localization imaging (\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e). In our centre, preoperative localization with Tc-99 sestamibi was highly sensitive and specific in predicting successful resection of the culprit lesion and is consistent with findings in developed as well as other developing countries such as India (\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e).\u003c/p\u003e \u003cp\u003ePost-operatively, HBS developed in 16.6% of patients, which is similar to other reports from Europe and the Middle East (\u003cspan additionalcitationids=\"CR34\" citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e), but higher than rates observed in a recent report from Singapore (\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e). Significant predictors for HBS included male sex and a higher pre-operative PTH level, which were also found in recent reports (\u003cspan additionalcitationids=\"CR34\" citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e). Identifaction of patients with these risk factors may enable prompt perioperative treatment and decrease morbidity and hospitalisation.\u003c/p\u003e \u003cp\u003eThe observation that post-operative increase in BMD was only significant at the spine is in keeping with results of recent studies from China with similar follow-up intervals (\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e, \u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e). This may be explained by rates of bone turnover being higher in cancellous bone, resulting in rapid and lasting improvement in BMD (\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e, \u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e). However, since less than 24% of patients had repeat BMD measurements post-operatively, the results need to be interpreted with caution and requires further investigation.\u003c/p\u003e \u003cp\u003eComparison with the earlier study from this centre showed that patients\u0026rsquo; clinical characteristics, biochemical findings and cure rate are largely similar. This highlights the need for increased routine biochemical testing at primary care centres in order to detect more patients with asymptomatic PHPT.\u003c/p\u003e \u003cp\u003eThe strength of this study is that it is the largest clinical study done on PHPT in South Africa and that it can be compared to the previous study at our centre. There are several limitations including the retrospective nature, limited number of patients who had IO-PTH monitoring, and follow-up BMD measurements post-surgery. Further studies are needed in other centres in South Africa and other African countries to confirm the findings of this study, ascertain trends in BMD changes post-operatively as well as assess the utility and cost-effectiveness of IO-PTH monitoring.\u003c/p\u003e"},{"header":"CONCLUSION","content":"\u003cp\u003eThe proportion of asymptomatic PHPT has increased at this centre over the past decade but symptomatic disease remains the dominant presentation and is higher than that reported in developed countries. Parathyroid adenoma is the commonest cause of PHPT with parathyroidectomy being curative in the majority of patients. IO-PTH monitoring is valuable in guaranteeing successful surgery.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ePHPT\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ePrimary Hyperparathyroidism\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eSSA\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eSub-Saharan Africa\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eIO-PTH\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eIntraoperative parathyroid hormone\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eIALCH\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eInkosi Albert Luthuli Central Hospital\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ePTH\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eParathyroid hormone\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eUSA\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eUnited States of America\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eEHR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eElectronic health record\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eALP\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eAlkaline phosphatase\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eeGFR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eEstimated glomerular filtration rate\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCKD-EPI\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eChronic Kidney Disease Epidemiology Collaboration\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eHBS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eHungry Bone Syndrome\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eBMD\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eBone Mineral Density\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eDEXA\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eDual-Energy X-ray Absorptiometry\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eTc-99m\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eTechnetium\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eSPSS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eStatistics Package for the Social Sciences\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eIQR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eInterquartile range\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eOR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eOdds Ratio\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e95% CI\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003e95% confidence interval\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eBMI\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eBody mass index\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eNPHPT\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eNormocalcaemic primary hyperparathyroidism\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003eEthics approval and consent to participate:\u003c/p\u003e\n\u003cp\u003eThe study was approved by the University of KwaZulu-Natal Biomedical Research Ethics committee (BREC) [reference number: BREC/00001483/2020]. Individual participant consent was waived as this was a retrospective chart review and patients were not put at risk. Consent was waived to Inkosi Albert Luthuli Central Hospital (IALCH) and KwaZulu-Natal Department of Health, both of which granted permission to access patient information.\u003c/p\u003e\n\u003cp\u003eConsent for publication: Not applicable\u003c/p\u003e\n\u003cp\u003eAvailability of data and materials:\u003c/p\u003e\n\u003cp\u003eThe datasets generated and/or analysed during the current study are not publicly available due to patient confidentialty, but are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003eCompeting interests: None\u003c/p\u003e\n\u003cp\u003eFunding: None\u003c/p\u003e\n\u003cp\u003eAuthors' contributions:\u003c/p\u003e\n\u003cp\u003eKG contributed to the conception and design of this study, collection and interpretation of data and drafted the manuscript. IMP and AAM contributed to the design of the study, analysis of data and revised the article critically. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003eAcknowledgements:\u003c/p\u003e\n\u003cp\u003eWe thank Dr Ines Buccimazza (Head of Clinical Unit, Breast and Endocrine Surgery at Inkosi Albert Luthuli Central Hospital) for her assisstance with data collection. We also thank Prof. Tonya M. Esterhuizen (Division of Epidemiology and Biostatistics, Stellenbosch University) for assisting with the statistical analysis.\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eBilezikian JP, Bandeira L, Khan A, Cusano NE. Hyperparathyroidism. Lancet. 2018;391(10116):168-78.\u003c/li\u003e\n \u003cli\u003eZhu CY, Sturgeon C, Yeh MW. Diagnosis and Management of Primary Hyperparathyroidism. JAMA. 2020.\u003c/li\u003e\n \u003cli\u003eWalker MD, Silverberg SJ. Primary hyperparathyroidism. 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J Clin Endocrinol Metab 2015;100(9):3443 - 51.\u003c/li\u003e\n \u003cli\u003eŞeng\u0026uuml;l Ay\u0026ccedil;i\u0026ccedil;ek G AB, Şahin M, Emral R, Erdoğan MF, G\u0026uuml;ll\u0026uuml; S, Başkal N, \u0026Ccedil;orap\u0026ccedil;ıoğlu D. The impact of vitamin D deficiency on clinical, biochemical and metabolic parameters in primary hyperparathyroidism. Endocrinol Diabetes Nutr (Engl Ed). 2023;70(1):56 - 62.\u003c/li\u003e\n \u003cli\u003eWalker MD, Cong E, Lee JA, Kepley A, Zhang C, McMahon DJ, et al. Vitamin D in Primary Hyperparathyroidism: Effects on Clinical, Biochemical, and Densitometric Presentation. The Journal of Clinical Endocrinology \u0026amp; Metabolism. 2015;100(9):3443-51.\u003c/li\u003e\n \u003cli\u003eUdelsman R LZ, Donovan P. The superiority of minimally invasive parathyroidectomy based on 1650 consecutive patients with primary hyperparathyroidism. Annals of Surgery. 2011;253(3):585-91.\u003c/li\u003e\n \u003cli\u003eNouikes Zitouni S. Monocentric experience of primary hyperparathyroidism surgery in Algeria. Surgery Open Science. 2021;4:32-6.\u003c/li\u003e\n \u003cli\u003eMallikarjuna VaM, Vivek and Ayyar, Vageesh and Bantwal, Ganapathy and Ganesh, Vaishnavi and George, Belinda and Hemanth, GN and Vinotha, P. Five-year Retrospective Study on Primary Hyperparathyroidism in South India: Emerging Roles of Minimally Invasive Parathyroidectomy and Preoperative Localization with Methionine Positron Emission Tomography-Computed Tomography Scan. Indian Journal of Endocrinology and Metabolism. 2018;22:355.\u003c/li\u003e\n \u003cli\u003eTay D, Das JP, Yeh R. Preoperative Localization for Primary Hyperparathyroidism: A Clinical Review. Biomedicines. 2021;9(4).\u003c/li\u003e\n \u003cli\u003eJakubauskas MB, Virgilijus; Strupas, Kęstutis. Risk factors of developing the hungry bone syndrome after parathyroidectomy for primary hyperparathyroidism. Acta medica Lituanica. 2018;25.\u003c/li\u003e\n \u003cli\u003eKaya C, Tam AA, Diriko\u0026ccedil; A, Kılı\u0026ccedil;yazgan A, Kılı\u0026ccedil; M, T\u0026uuml;rk\u0026ouml;lmez Ş, et al. Hypocalcemia development in patients operated for primary hyperparathyroidism: Can it be predicted preoperatively? Archives of Endocrinology and Metabolism. 2016;60.\u003c/li\u003e\n \u003cli\u003eGuill\u0026eacute;n Mart\u0026iacute;nez AJ, Smilg Nicol\u0026aacute;s C, Moraleda Deleito J, Guill\u0026eacute;n Mart\u0026iacute;nez S, Garc\u0026iacute;a-Purri\u0026ntilde;os Garc\u0026iacute;a F. Risk factors and evolution of calcium and parathyroid hormone levels in hungry bone syndrome after parthyroidectomy for primary hyperparathyroidism. Endocrinolog\u0026iacute;a, Diabetes y Nutrici\u0026oacute;n (English ed). 2020;67(5):310-6.\u003c/li\u003e\n \u003cli\u003eChandran M, Bilezikian JP, Salleh NM, Ying H, Lau J, Lee J, et al. Hungry bone syndrome following parathyroidectomy for primary hyperparathyroidism in a developed country in the Asia Pacific. A cohort study. Osteoporosis and Sarcopenia. 2022;8(1):11-6.\u003c/li\u003e\n \u003cli\u003eLu S, Gong M, Zha Y, Cui A, Chen C, Sun W, et al. Identification of independent factors affecting bone mineral density after successful parathyroidectomy for symptomatic hyperparathyroidism. BMC Endocrine Disorders. 2020;20(1):141.\u003c/li\u003e\n \u003cli\u003eLu SG, Maoqi; Zha, Yejun; Cui, Aimin; Chen, Chen; Yang, Hao; Sun, Weitong; Hua, Kehan; Tian, Wei; Jiang, Xieyuan. Changes in bone mineral density after parathyroidectomy in patients with moderate to severe primary hyperparathyroidism. Journal of International Medical Research. 2020;48.\u003cstrong\u003e\u003c/strong\u003e\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTable 1: Clinical and biochemical characteristics of the total study group at presentation (n: 110)\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"624\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"49.83974358974359%\" valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"20.512820512820515%\" valign=\"top\"\u003e\n \u003cp\u003eN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.647435897435898%\" valign=\"top\"\u003e\n \u003cp\u003e%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"49.83974358974359%\" valign=\"top\"\u003e\n \u003cp\u003eSex (M : F)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.512820512820515%\" valign=\"top\"\u003e\n \u003cp\u003e14 : 96\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.647435897435898%\" valign=\"top\"\u003e\n \u003cp\u003e12.7 : 87.3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"49.83974358974359%\" valign=\"top\"\u003e\n \u003cp\u003eEthnicity\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.512820512820515%\" valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"29.647435897435898%\" valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"49.83974358974359%\" valign=\"top\"\u003e\n \u003cp\u003eIndian\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.512820512820515%\" valign=\"top\"\u003e\n \u003cp\u003e48\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.647435897435898%\" valign=\"top\"\u003e\n \u003cp\u003e43.6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"49.83974358974359%\" valign=\"top\"\u003e\n \u003cp\u003eAfrican\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.512820512820515%\" valign=\"top\"\u003e\n \u003cp\u003e45\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.647435897435898%\" valign=\"top\"\u003e\n \u003cp\u003e40.9\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"49.83974358974359%\" valign=\"top\"\u003e\n \u003cp\u003eWhite\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.512820512820515%\" valign=\"top\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.647435897435898%\" valign=\"top\"\u003e\n \u003cp\u003e14.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"49.83974358974359%\" valign=\"top\"\u003e\n \u003cp\u003eMixed Race (Coloured)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.512820512820515%\" valign=\"top\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.647435897435898%\" valign=\"top\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"49.83974358974359%\" valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"20.512820512820515%\" valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"29.647435897435898%\" valign=\"top\"\u003e\n \u003cp\u003eRange\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"49.83974358974359%\" valign=\"top\"\u003e\n \u003cp\u003eAge (years)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.512820512820515%\" valign=\"top\"\u003e\n \u003cp\u003e57 (44; 66.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.647435897435898%\" valign=\"top\"\u003e\n \u003cp\u003e13-84\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"49.83974358974359%\" valign=\"top\"\u003e\n \u003cp\u003eBMI (kg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.512820512820515%\" valign=\"top\"\u003e\n \u003cp\u003e27.4 (23.4; 32.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.647435897435898%\" valign=\"top\"\u003e\n \u003cp\u003e14.55-49.98\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"49.83974358974359%\" valign=\"top\"\u003e\n \u003cp\u003eSystolic Blood Pressure (mmHg)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.512820512820515%\" valign=\"top\"\u003e\n \u003cp\u003e130 (116; 146)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.647435897435898%\" valign=\"top\"\u003e\n \u003cp\u003e92-186\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"49.83974358974359%\" valign=\"top\"\u003e\n \u003cp\u003eDiastolic Blood Pressure (mmHg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.512820512820515%\" valign=\"top\"\u003e\n \u003cp\u003e75 (66; 82)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.647435897435898%\" valign=\"top\"\u003e\n \u003cp\u003e46-104\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"49.83974358974359%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.512820512820515%\" valign=\"top\"\u003e\n \u003cp\u003eN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.647435897435898%\" valign=\"top\"\u003e\n \u003cp\u003e%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"49.83974358974359%\" valign=\"top\"\u003e\n \u003cp\u003ePast History Attributable To PHPT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.512820512820515%\" valign=\"top\"\u003e\n \u003cp\u003e43\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.647435897435898%\" valign=\"top\"\u003e\n \u003cp\u003e39.1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"49.83974358974359%\" valign=\"top\"\u003e\n \u003cp\u003eNephrolithiasis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.512820512820515%\" valign=\"top\"\u003e\n \u003cp\u003e23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.647435897435898%\" valign=\"top\"\u003e\n \u003cp\u003e20.9\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"49.83974358974359%\" valign=\"top\"\u003e\n \u003cp\u003eNon-trauma fracture\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.512820512820515%\" valign=\"top\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.647435897435898%\" valign=\"top\"\u003e\n \u003cp\u003e7.3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"49.83974358974359%\" valign=\"top\"\u003e\n \u003cp\u003eOsteoporosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.512820512820515%\" valign=\"top\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.647435897435898%\" valign=\"top\"\u003e\n \u003cp\u003e6.4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"49.83974358974359%\" valign=\"top\"\u003e\n \u003cp\u003ePeptic Ulcer Disease\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.512820512820515%\" valign=\"top\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.647435897435898%\" valign=\"top\"\u003e\n \u003cp\u003e5.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"49.83974358974359%\" valign=\"top\"\u003e\n \u003cp\u003eDepression\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.512820512820515%\" valign=\"top\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.647435897435898%\" valign=\"top\"\u003e\n \u003cp\u003e2.7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"49.83974358974359%\" valign=\"top\"\u003e\n \u003cp\u003ePancreatitis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.512820512820515%\" valign=\"top\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.647435897435898%\" valign=\"top\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"49.83974358974359%\" valign=\"top\"\u003e\n \u003cp\u003ePsychosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.512820512820515%\" valign=\"top\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.647435897435898%\" valign=\"top\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"49.83974358974359%\" valign=\"top\"\u003e\n \u003cp\u003eOther Medical History\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.512820512820515%\" valign=\"top\"\u003e\n \u003cp\u003eN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.647435897435898%\" valign=\"top\"\u003e\n \u003cp\u003e%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"49.83974358974359%\" valign=\"top\"\u003e\n \u003cp\u003eHypertension\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.512820512820515%\" valign=\"top\"\u003e\n \u003cp\u003e66\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.647435897435898%\" valign=\"top\"\u003e\n \u003cp\u003e60.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"49.83974358974359%\" valign=\"top\"\u003e\n \u003cp\u003eDiabetes Mellitus\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.512820512820515%\" valign=\"top\"\u003e\n \u003cp\u003e29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.647435897435898%\" valign=\"top\"\u003e\n \u003cp\u003e26.4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"49.83974358974359%\" valign=\"top\"\u003e\n \u003cp\u003eDyslipidaemia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.512820512820515%\" valign=\"top\"\u003e\n \u003cp\u003e31\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.647435897435898%\" valign=\"top\"\u003e\n \u003cp\u003e28.2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"49.83974358974359%\" valign=\"top\"\u003e\n \u003cp\u003eMalignancy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.512820512820515%\" valign=\"top\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.647435897435898%\" valign=\"top\"\u003e\n \u003cp\u003e9.1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"49.83974358974359%\" valign=\"top\"\u003e\n \u003cp\u003eBaseline Biochemistry\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.512820512820515%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.647435897435898%\" valign=\"top\"\u003e\n \u003cp\u003eNormal Reference Range\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"49.83974358974359%\" valign=\"top\"\u003e\n \u003cp\u003eSerum Calcium (mmol/l)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.512820512820515%\" valign=\"top\"\u003e\n \u003cp\u003e2.87 \u0026plusmn; 0.34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.647435897435898%\" valign=\"top\"\u003e\n \u003cp\u003e2.15-2.50\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"49.83974358974359%\" valign=\"top\"\u003e\n \u003cp\u003eSerum Magnesium (mmol/l)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.512820512820515%\" valign=\"top\"\u003e\n \u003cp\u003e0.82 \u0026plusmn; 0.12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.647435897435898%\" valign=\"top\"\u003e\n \u003cp\u003e0.63-1.05\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"49.83974358974359%\" valign=\"top\"\u003e\n \u003cp\u003eSerum Phosphate (mmol/l)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.512820512820515%\" valign=\"top\"\u003e\n \u003cp\u003e0.87 \u0026plusmn; 0.20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.647435897435898%\" valign=\"top\"\u003e\n \u003cp\u003e0.78-1.42\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"49.83974358974359%\" valign=\"top\"\u003e\n \u003cp\u003eSerum Creatinine (\u0026mu;mol/l)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.512820512820515%\" valign=\"top\"\u003e\n \u003cp\u003e71 (58; 95)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.647435897435898%\" valign=\"top\"\u003e\n \u003cp\u003e49-90\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"49.83974358974359%\" valign=\"top\"\u003e\n \u003cp\u003eeGFR (CKD-EPI) (ml/min/1.73m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.512820512820515%\" valign=\"top\"\u003e\n \u003cp\u003e85.9 \u0026plusmn; 33.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.647435897435898%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026gt;60\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"49.83974358974359%\" valign=\"top\"\u003e\n \u003cp\u003eSerum ALP (U/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.512820512820515%\" valign=\"top\"\u003e\n \u003cp\u003e117.5 (89; 145.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.647435897435898%\" valign=\"top\"\u003e\n \u003cp\u003e42-98\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"49.83974358974359%\" valign=\"top\"\u003e\n \u003cp\u003eSerum PTH (pmol/l)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.512820512820515%\" valign=\"top\"\u003e\n \u003cp\u003e23.3 (16.0; 45.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.647435897435898%\" valign=\"top\"\u003e\n \u003cp\u003e2.0-8.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"49.83974358974359%\" valign=\"top\"\u003e\n \u003cp\u003e*Serum 25-OH Vitamin D (nmol/l) (n:95)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.512820512820515%\" valign=\"top\"\u003e\n \u003cp\u003e42.9 (33.3; 62.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.647435897435898%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026gt;50\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"49.83974358974359%\" valign=\"top\"\u003e\n \u003cp\u003eVitamin D deficiency (n;%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.512820512820515%\" valign=\"top\"\u003e\n \u003cp\u003e16; 16.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.647435897435898%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"49.83974358974359%\" valign=\"top\"\u003e\n \u003cp\u003e24-hour urine calcium (mmol/day)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.512820512820515%\" valign=\"top\"\u003e\n \u003cp\u003e3.3 (1.6; 5.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.647435897435898%\" valign=\"top\"\u003e\n \u003cp\u003e2.5-7.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eData are presented as Mean \u0026plusmn; SD or Median (IQR) or %.\u003c/p\u003e\n\u003cp\u003eBMI: body mass index.\u003c/p\u003e\n\u003cp\u003eVitamin D Deficiency: serum 25-OH-vitamin D \u0026lt; 30 nmol/l.\u003c/p\u003e\n\u003cp\u003e* Serum 25-OH Vitamin D available in 95 patients\u003c/p\u003e\n\u003cp\u003eTable 2: Outcomes of surgery, intra-operative parathyroid hormone (IO-PTH) monitoring and histopathology (n:84)\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\"\u003e\n \u003cp\u003en\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\"\u003e\n \u003cp\u003e%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\"\u003e\n \u003cp\u003eParathyroidectomy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\"\u003e\n \u003cp\u003e84\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\"\u003e\n \u003cp\u003e100\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\"\u003e\n \u003cp\u003eCure\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\"\u003e\n \u003cp\u003e80\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\"\u003e\n \u003cp\u003e95.2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\"\u003e\n \u003cp\u003eNo cure\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\"\u003e\n \u003cp\u003e4.8\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\"\u003e\n \u003cp\u003eIO-PTH Monitoring\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\"\u003e\n \u003cp\u003eIO-PTH\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\"\u003e\n \u003cp\u003e28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\"\u003e\n \u003cp\u003e33.3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\"\u003e\n \u003cp\u003eSuccess/Cure\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\"\u003e\n \u003cp\u003e28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\"\u003e\n \u003cp\u003e100\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\"\u003e\n \u003cp\u003eNo IO-PTH\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\"\u003e\n \u003cp\u003e56\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\"\u003e\n \u003cp\u003e66.7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\"\u003e\n \u003cp\u003eSuccess/Cure\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\"\u003e\n \u003cp\u003e52\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\"\u003e\n \u003cp\u003e92.9\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\"\u003e\n \u003cp\u003eHistological Diagnosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\"\u003e\n \u003cp\u003eAdenoma\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\"\u003e\n \u003cp\u003e74\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\"\u003e\n \u003cp\u003e88.1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\"\u003e\n \u003cp\u003eHyperplasia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\"\u003e\n \u003cp\u003e7.1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\"\u003e\n \u003cp\u003eCarcinoma\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"top\"\u003e\n \u003cp\u003e4.8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eIO-PTH: Intra-operative parathyroid hormone monitoring.\u003c/p\u003e\n\u003cp\u003eTable 3: Frequency of post-operative complications and replacement therapy\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"597\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"51.75879396984924%\" valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"23.283082077051926%\" valign=\"top\"\u003e\n \u003cp\u003en\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.958123953098827%\" valign=\"top\"\u003e\n \u003cp\u003e%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"51.75879396984924%\" valign=\"top\"\u003e\n \u003cp\u003eComplication\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.283082077051926%\" valign=\"top\"\u003e\n \u003cp\u003e84\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.958123953098827%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"51.75879396984924%\" valign=\"top\"\u003e\n \u003cp\u003eHypocalcaemia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.283082077051926%\" valign=\"top\"\u003e\n \u003cp\u003e30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.958123953098827%\" valign=\"top\"\u003e\n \u003cp\u003e35.7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"51.75879396984924%\" valign=\"top\"\u003e\n \u003cp\u003eTransient\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.283082077051926%\" valign=\"top\"\u003e\n \u003cp\u003e17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.958123953098827%\" valign=\"top\"\u003e\n \u003cp\u003e20.2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"51.75879396984924%\" valign=\"top\"\u003e\n \u003cp\u003ePermanent\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.283082077051926%\" valign=\"top\"\u003e\n \u003cp\u003e13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.958123953098827%\" valign=\"top\"\u003e\n \u003cp\u003e15.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"51.75879396984924%\" valign=\"top\"\u003e\n \u003cp\u003eHungry Bone Syndrome\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.283082077051926%\" valign=\"top\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.958123953098827%\" valign=\"top\"\u003e\n \u003cp\u003e16.6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"51.75879396984924%\" valign=\"top\"\u003e\n \u003cp\u003eRecurrent laryngeal nerve injury\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.283082077051926%\" valign=\"top\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.958123953098827%\" valign=\"top\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"51.75879396984924%\" valign=\"top\"\u003e\n \u003cp\u003eBleeding\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.283082077051926%\" valign=\"top\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.958123953098827%\" valign=\"top\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"51.75879396984924%\" valign=\"top\"\u003e\n \u003cp\u003eInfection\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.283082077051926%\" valign=\"top\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.958123953098827%\" valign=\"top\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"51.75879396984924%\" valign=\"top\"\u003e\n \u003cp\u003eTreatment for Hypocalcaemia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.283082077051926%\" valign=\"top\"\u003e\n \u003cp\u003en:30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.958123953098827%\" valign=\"top\"\u003e\n \u003cp\u003e35.7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"51.75879396984924%\" valign=\"top\"\u003e\n \u003cp\u003eIntravenous Calcium\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.283082077051926%\" valign=\"top\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.958123953098827%\" valign=\"top\"\u003e\n \u003cp\u003e46.7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"51.75879396984924%\" valign=\"top\"\u003e\n \u003cp\u003eOral Calcium\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.283082077051926%\" valign=\"top\"\u003e\n \u003cp\u003e19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.958123953098827%\" valign=\"top\"\u003e\n \u003cp\u003e63.3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"51.75879396984924%\" valign=\"top\"\u003e\n \u003cp\u003eOne-Alpha Calcidiol\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.283082077051926%\" valign=\"top\"\u003e\n \u003cp\u003e13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.958123953098827%\" valign=\"top\"\u003e\n \u003cp\u003e43.3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"51.75879396984924%\" valign=\"top\"\u003e\n \u003cp\u003eNo replacement\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.283082077051926%\" valign=\"top\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.958123953098827%\" valign=\"top\"\u003e\n \u003cp\u003e36.7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTable 4: Characteristics at presentation in patients with and without Hungry Bone Syndrome (HBS) (n:84)\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"554\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.101083032490976%\" valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"50.90252707581227%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003ePre-operative\u003c/p\u003e\n \u003cp\u003eHBS (n:14) \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;No HBS (n:70)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.99638989169675%\" valign=\"top\"\u003e\n \u003cp\u003eP\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.101083032490976%\" valign=\"top\"\u003e\n \u003cp\u003eAge (years)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.71480144404332%\" valign=\"top\"\u003e\n \u003cp\u003e39.5 (20.8; 56)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.187725631768952%\" valign=\"top\"\u003e\n \u003cp\u003e58 (47; 67)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.99638989169675%\" valign=\"top\"\u003e\n \u003cp\u003e0.012\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.101083032490976%\" valign=\"top\"\u003e\n \u003cp\u003eBMI (kg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.71480144404332%\" valign=\"top\"\u003e\n \u003cp\u003e22.7 (17.8; 24.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.187725631768952%\" valign=\"top\"\u003e\n \u003cp\u003e27.4 (23.7; 32.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.99638989169675%\" valign=\"top\"\u003e\n \u003cp\u003e0.005\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.101083032490976%\" valign=\"top\"\u003e\n \u003cp\u003eSerum:\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.71480144404332%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.187725631768952%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.99638989169675%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.101083032490976%\" valign=\"top\"\u003e\n \u003cp\u003ePTH (pmol/l)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.71480144404332%\" valign=\"top\"\u003e\n \u003cp\u003e172.7 (71.2; 230)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.187725631768952%\" valign=\"top\"\u003e\n \u003cp\u003e23.1 (15.95; 38.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.99638989169675%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0.00\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.101083032490976%\" valign=\"top\"\u003e\n \u003cp\u003eALP (U/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.71480144404332%\" valign=\"top\"\u003e\n \u003cp\u003e900 (174.8; 1540.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.187725631768952%\" valign=\"top\"\u003e\n \u003cp\u003e117 (88; 140.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.99638989169675%\" valign=\"top\"\u003e\n \u003cp\u003e0.000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.101083032490976%\" valign=\"top\"\u003e\n \u003cp\u003eCalcium (mmol/l)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.71480144404332%\" valign=\"top\"\u003e\n \u003cp\u003e3.06 \u0026plusmn; 0.45\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.187725631768952%\" valign=\"top\"\u003e\n \u003cp\u003e2.88 \u0026plusmn; 0.30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.99638989169675%\" valign=\"top\"\u003e\n \u003cp\u003e0.084\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.101083032490976%\" valign=\"top\"\u003e\n \u003cp\u003eMagnesium (mmol/l)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.71480144404332%\" valign=\"top\"\u003e\n \u003cp\u003e0.78 \u0026plusmn; 0.13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.187725631768952%\" valign=\"top\"\u003e\n \u003cp\u003e0.82 \u0026plusmn; 0.11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.99638989169675%\" valign=\"top\"\u003e\n \u003cp\u003e0.304\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.101083032490976%\" valign=\"top\"\u003e\n \u003cp\u003ePhosphate (mmol/l)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.71480144404332%\" valign=\"top\"\u003e\n \u003cp\u003e0.73 \u0026plusmn; 0.16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.187725631768952%\" valign=\"top\"\u003e\n \u003cp\u003e0.87 \u0026plusmn; 0.19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.99638989169675%\" valign=\"top\"\u003e\n \u003cp\u003e0.018\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.101083032490976%\" valign=\"top\"\u003e\n \u003cp\u003eaBMD Hip (g.cm\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.71480144404332%\" valign=\"top\"\u003e\n \u003cp\u003e0.6 \u0026plusmn; 0.3\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.187725631768952%\" valign=\"top\"\u003e\n \u003cp\u003e0.8 \u0026plusmn; 0.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.99638989169675%\" valign=\"top\"\u003e\n \u003cp\u003e0.015\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.101083032490976%\" valign=\"top\"\u003e\n \u003cp\u003eaBMD Spine (g.cm\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.71480144404332%\" valign=\"top\"\u003e\n \u003cp\u003e0.7 \u0026plusmn; 0.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.187725631768952%\" valign=\"top\"\u003e\n \u003cp\u003e0.8 \u0026plusmn; 0.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.99638989169675%\" valign=\"top\"\u003e\n \u003cp\u003e0.013\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.101083032490976%\" valign=\"top\"\u003e\n \u003cp\u003eaBMD Radius (g.cm\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.71480144404332%\" valign=\"top\"\u003e\n \u003cp\u003e0.4 \u0026plusmn; 0.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.187725631768952%\" valign=\"top\"\u003e\n \u003cp\u003e0.6 \u0026plusmn; 0.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.99638989169675%\" valign=\"top\"\u003e\n \u003cp\u003e0.002\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.101083032490976%\" valign=\"top\"\u003e\n \u003cp\u003eeGFR (CKD-EPI) (ml/min/1.73m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.71480144404332%\" valign=\"top\"\u003e\n \u003cp\u003e114 \u0026plusmn; 39.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.187725631768952%\" valign=\"top\"\u003e\n \u003cp\u003e83.5 \u0026plusmn; 30.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.99638989169675%\" valign=\"top\"\u003e\n \u003cp\u003e0.002\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.101083032490976%\" valign=\"top\"\u003e\n \u003cp\u003eHbA1c (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.71480144404332%\" valign=\"top\"\u003e\n \u003cp\u003e5.4 (5.3; 5.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.187725631768952%\" valign=\"top\"\u003e\n \u003cp\u003e6.3 (5.8; 7.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.99638989169675%\" valign=\"top\"\u003e\n \u003cp\u003e0.008\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eData are presented as Mean \u0026plusmn; SD or Median (IQR).\u003c/p\u003e\n\u003cp\u003eBMI: Body Mass Index; PTH: Parathyroid Hormone; ALP: Alkaline phosphatase.\u003c/p\u003e\n\u003cp\u003eTable 5: Logistic regression analysis for predictors (risk factors) for hungry bone syndrome (HBS).\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"499\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"38.35341365461847%\" valign=\"top\"\u003e\n \u003cp\u003eVariable\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"42.7710843373494%\" valign=\"top\"\u003e\n \u003cp\u003eOR (95% C.I)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.87550200803213%\" valign=\"top\"\u003e\n \u003cp\u003eP\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"38.35341365461847%\" valign=\"top\"\u003e\n \u003cp\u003ePTH\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"42.7710843373494%\" valign=\"top\"\u003e\n \u003cp\u003e1.0 (1.0, 1.02)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.87550200803213%\" valign=\"top\"\u003e\n \u003cp\u003e0.008\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"38.35341365461847%\" valign=\"top\"\u003e\n \u003cp\u003eMale Gender\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"42.7710843373494%\" valign=\"top\"\u003e\n \u003cp\u003e7.0 (1.3, 38.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.87550200803213%\" valign=\"top\"\u003e\n \u003cp\u003e0.025\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"38.35341365461847%\" valign=\"top\"\u003e\n \u003cp\u003e24-hour urine calcium\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"42.7710843373494%\" valign=\"top\"\u003e\n \u003cp\u003e1.2 (1.0, 1.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.87550200803213%\" valign=\"top\"\u003e\n \u003cp\u003e0.107\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"38.35341365461847%\" valign=\"top\"\u003e\n \u003cp\u003ePhosphate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"42.7710843373494%\" valign=\"top\"\u003e\n \u003cp\u003e0.02 (0.0, 2.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.87550200803213%\" valign=\"top\"\u003e\n \u003cp\u003e0.239\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003ePTH: Parathyroid Hormone.\u003c/p\u003e\n\u003cp\u003eOR (95% C.I.): Odds Ratio (95% confidence interval).\u003c/p\u003e\n\u003cp\u003eTable 6: Comparison of clinical parameters, biochemistry and cure rate between 2009 (n:28) and current (n:110) study\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"583\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.893470790378004%\" valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"21.993127147766323%\" valign=\"top\"\u003e\n \u003cp\u003e2009\u003c/p\u003e\n \u003cp\u003en:28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.68041237113402%\" valign=\"top\"\u003e\n \u003cp\u003e2021\u003c/p\u003e\n \u003cp\u003en:110\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.43298969072165%\" valign=\"top\"\u003e\n \u003cp\u003eP\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.893470790378004%\" valign=\"top\"\u003e\n \u003cp\u003eSymptomatic (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.993127147766323%\" valign=\"top\"\u003e\n \u003cp\u003e92.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.68041237113402%\" valign=\"top\"\u003e\n \u003cp\u003e62.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.43298969072165%\" valign=\"top\"\u003e\n \u003cp\u003e0.002\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.893470790378004%\" valign=\"top\"\u003e\n \u003cp\u003eBMI (kg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.993127147766323%\" valign=\"top\"\u003e\n \u003cp\u003e28.1 (26.1; 31.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.68041237113402%\" valign=\"top\"\u003e\n \u003cp\u003e27.3 (23.4; 32.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.43298969072165%\" valign=\"top\"\u003e\n \u003cp\u003e0.462\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.893470790378004%\" valign=\"top\"\u003e\n \u003cp\u003ePre-operative\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.993127147766323%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.68041237113402%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.43298969072165%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.893470790378004%\" valign=\"top\"\u003e\n \u003cp\u003eSerum Calcium (mmol/l)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.993127147766323%\" valign=\"top\"\u003e\n \u003cp\u003e3.00 (2.9; 3.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.68041237113402%\" valign=\"top\"\u003e\n \u003cp\u003e2.83 (2.6; 3.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.43298969072165%\" valign=\"top\"\u003e\n \u003cp\u003e0.010\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.893470790378004%\" valign=\"top\"\u003e\n \u003cp\u003eSerum PTH (pmol/l)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.993127147766323%\" valign=\"top\"\u003e\n \u003cp\u003e16.85 (9.9; 40.7)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.68041237113402%\" valign=\"top\"\u003e\n \u003cp\u003e23.3 (16.0; 45.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.43298969072165%\" valign=\"top\"\u003e\n \u003cp\u003e0.824\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.893470790378004%\" valign=\"top\"\u003e\n \u003cp\u003e25-OH Vit D (nmol/l)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.993127147766323%\" valign=\"top\"\u003e\n \u003cp\u003e39 (26; 47.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.68041237113402%\" valign=\"top\"\u003e\n \u003cp\u003e42.9 (33.3; 62.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.43298969072165%\" valign=\"top\"\u003e\n \u003cp\u003e0.488\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.893470790378004%\" valign=\"top\"\u003e\n \u003cp\u003eSerum ALP (U/l)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.993127147766323%\" valign=\"top\"\u003e\n \u003cp\u003e98 (79; 125)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.68041237113402%\" valign=\"top\"\u003e\n \u003cp\u003e117.5 (89; 145.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.43298969072165%\" valign=\"top\"\u003e\n \u003cp\u003e0.133\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.893470790378004%\" valign=\"top\"\u003e\n \u003cp\u003e24-hour urine calcium (mmol/day)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.993127147766323%\" valign=\"top\"\u003e\n \u003cp\u003e5.1 (2.5; 6.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.68041237113402%\" valign=\"top\"\u003e\n \u003cp\u003e3.34 (1.59; 5.4)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.43298969072165%\" valign=\"top\"\u003e\n \u003cp\u003e0.654\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.893470790378004%\" valign=\"top\"\u003e\n \u003cp\u003ePost-operative\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.993127147766323%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.68041237113402%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.43298969072165%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.893470790378004%\" valign=\"top\"\u003e\n \u003cp\u003eSerum PTH (pmol/l)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.993127147766323%\" valign=\"top\"\u003e\n \u003cp\u003e2.3 (1.1; 4.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.68041237113402%\" valign=\"top\"\u003e\n \u003cp\u003e4.4 (2.1; 8.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.43298969072165%\" valign=\"top\"\u003e\n \u003cp\u003e0.044\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.893470790378004%\" valign=\"top\"\u003e\n \u003cp\u003eSerum Calcium (mmol/l)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.993127147766323%\" valign=\"top\"\u003e\n \u003cp\u003e2.31 (2.2; 2.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.68041237113402%\" valign=\"top\"\u003e\n \u003cp\u003e2.25 (2.15; 2.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.43298969072165%\" valign=\"top\"\u003e\n \u003cp\u003e0.233\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.893470790378004%\" valign=\"top\"\u003e\n \u003cp\u003eCure (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.993127147766323%\" valign=\"top\"\u003e\n \u003cp\u003e94.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.68041237113402%\" valign=\"top\"\u003e\n \u003cp\u003e95.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.43298969072165%\" valign=\"top\"\u003e\n \u003cp\u003e0.819\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eData are presented as Median (IQR) or %\u003c/p\u003e\n\u003cp\u003eBMI: body mass index; PTH: Parathyroid Hormone, 25-OH Vit D: 25-hydroxyvitamin D; ALP: Alkaline phosphatase\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-endocrine-disorders","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bend","sideBox":"Learn more about [BMC Endocrine Disorders](http://bmcendocrdisord.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bend/default.aspx","title":"BMC Endocrine Disorders","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Primary Hyperparathyroidism, hypercalcaemia, parathyroid hormone, hungry bone syndrome, parathyroidectomy, intra-operative parathyroid hormone monitoring","lastPublishedDoi":"10.21203/rs.3.rs-3873001/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3873001/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cb\u003eBackground:\u003c/b\u003e\u003c/p\u003e \u003cp\u003eThere has been a notable shift towards the diagnosis of less severe and asymptomatic primary hyperparathyroidism (PHPT) in developed countries. However, there is a paucity of recent data from sub-Saharan Africa (SSA), and also, no reported data from SSA on the utility of intra-operative parathyroid hormone (IO-PTH) monitoring. In an earlier study from Inkosi Albert Luthuli Central Hospital (IALCH), Durban, South Africa (2003\u0026ndash;2009), majority of patients (92.9%) had symptomatic disease. The aim of this study was to evaluate the clinical profile and management outcomes of patients presenting with PHPT at IALCH.\u003c/p\u003e\u003cp\u003e\u003cb\u003eMethods:\u003c/b\u003e\u003c/p\u003e \u003cp\u003e A retrospective chart review of patients with PHPT attending the Endocrinology clinic at IALCH between July 2009 and December 2021. Clinical presentation, laboratory results, radiologic findings, surgical notes and histology were recorded.\u003c/p\u003e\u003cp\u003e\u003cb\u003eResults:\u003c/b\u003e\u003c/p\u003e \u003cp\u003eAnalysis included 110 patients (87% female) with PHPT. Median age at presentation was 57 (44; 67.5) years. Symptomatic disease was present in 62.7% (n:69); 20.9% (n:23) had a history of nephrolithiasis and 7.3% (n:8) presented with previous fragility fractures. Mean serum calcium was 2.87\u0026thinsp;\u0026plusmn;\u0026thinsp;0.34 mmol/l; median serum-PTH was 23.3 (15.59;45.38) pmol/l, alkaline phosphatase 117.5 (89;145.5) U/l and 25-hydroxyvitamin-D 42.9 (33.26;62.92) nmol/l. Sestamibi scan (n:106 patients) identified an adenoma in 83.02%. Parathyroidectomy was performed on 84 patients with a cure rate of 95.2%. Reasons for conservative management (n:26) included: no current surgical indication (n:7), refusal (n:5) or deferral of surgery (n:5), loss to follow-up (n:5) and assessed as high anaesthetic risk (n:4). IO-PTH measurements performed on 28 patients indicated surgical success in 100%, based on Miami criteria. Histology confirmed adenoma in 88.1%, hyperplasia in 7.1% and carcinoma in 4.8%. Post-operative hypocalcaemia developed in 30 patients (35.7%), of whom, 14 developed hungry bone syndrome (HBS). In multivariate analysis, significant risk factors associated with HBS included male sex (OR 7.01; 95% CI 1.28, 38.39; p 0.025) and elevated pre-operative PTH (OR 1.01; 95% CI 1.00, 1.02; p 0.008)\u003c/p\u003e\u003cp\u003e\u003cb\u003eConclusions:\u003c/b\u003e\u003c/p\u003e \u003cp\u003eThe proportion of asymptomatic PHPT has increased at this centre over the past decade but symptomatic disease remains the dominant presentation. Parathyroidectomy is curative in the majority of patients. IO-PTH monitoring is valuable in ensuring successful surgery.\u003c/p\u003e","manuscriptTitle":"Characteristics, Management and Outcomes of Primary Hyperparathyroidism from 2009 to 2021: a single centre report from South Africa.","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-01-24 18:48:19","doi":"10.21203/rs.3.rs-3873001/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-01-22T08:06:28+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-01-20T03:42:21+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-01-20T03:42:21+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Endocrine Disorders","date":"2024-01-17T13:08:31+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-endocrine-disorders","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bend","sideBox":"Learn more about [BMC Endocrine Disorders](http://bmcendocrdisord.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bend/default.aspx","title":"BMC Endocrine Disorders","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"92b3a09f-6fbe-42bb-bc23-51e4029d25fe","owner":[],"postedDate":"January 24th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2024-05-02T00:40:18+00:00","versionOfRecord":{"articleIdentity":"rs-3873001","link":"https://doi.org/10.1186/s12902-024-01583-8","journal":{"identity":"bmc-endocrine-disorders","isVorOnly":false,"title":"BMC Endocrine Disorders"},"publishedOn":"2024-04-25 00:40:18","publishedOnDateReadable":"April 25th, 2024"},"versionCreatedAt":"2024-01-24 18:48:19","video":"","vorDoi":"10.1186/s12902-024-01583-8","vorDoiUrl":"https://doi.org/10.1186/s12902-024-01583-8","workflowStages":[]},"version":"v1","identity":"rs-3873001","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3873001","identity":"rs-3873001","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}