Clinico-pathological study of symptomatic hyperparathyroidism: is it a different phenotype expression of hyperparathyroidism?

Clinico-pathological study of symptomatic hyperparathyroidism: is it a different phenotype expression of hyperparathyroidism? | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Clinico-pathological study of symptomatic hyperparathyroidism: is it a different phenotype expression of hyperparathyroidism? Riju Ramachandran Menon, Gopalakrishnan C Nair, Anoop Vasudevan Pillai, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3762644/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Purpose : Symptomatic PHPT is common in Asian countries, with the musculoskeletal system affected frequently, unlike Western literature, with a high prevalence of urinary stone disease. The concept of an asymptomatic disorder progressing over time to a symptomatic disease was not proven. The study aimed to assess the demographic, clinical, and pathological features of primary hyperparathyroidism and to compare these features with those of asymptomatic disorders in North American countries. Methods : This is an observational study on a cohort of patients operated on for hyperparathyroidism from 2005 to 2020 at the endocrine surgery division of a tertiary referral center in south India. Secondary hyperthyroidism was excluded. Case records were reviewed. Continuous variables were evaluated by chi-square or Fisher's exact test as appropriate (p<0.05). All discrete variables are noted as mean with standard deviation. Results : We had 301 patients in the study after excluding 45. There were 279 (92.7%) patients with symptomatic PHPT and 22 with asymptomatic disorders. The asymptomatic patients in the present study cohort were a decade older (p<0.011). Symptomatic patients had higher corrected calcium (p<0.16), lower vitamin D levels, and more elevated serum PTH levels (p<0.001), and the musculoskeletal system was more commonly affected. Conclusion The study cohort's serum calcium and PTH levels were higher and subtly impacted target organs. The musculoskeletal system was more commonly affected than the renal system in our cohort, possibly due to lower vitamin D levels in our population, unlike the patients from Western countries. Introduction The profile of primary hyperparathyroidism has changed to an asymptomatic endocrine disorder among the American and European Union population. This radical change in clinical presentation is attributed to introduction of autoanalyzer which enabled early detection of hypercalcaemia. In spite of the widespread use of autoanalyzer, pick up of asymptomatic PHPT is scanty in India. The actual incidence of PHPT in India is not available since there was no systematic community survey. A large case series analysis from Massachusetts general hospital recorded significantly high prevalence of urinary stone disease over skeletal involvement (1). Majority of case series analysis from Asian countries recorded high incidences of symptomatic PHPT and the commonest presenting symptoms were related to musculo-skeletal system. (2,3). Analysing a large cohort of PHPT patients spreading over 2 decades, Shah et al concluded that PHPT continues as a symptomatic disease in India and the characteristic features have not changed significantly (4). Paradoxically another large group analysis showed changes in clinical and biochemical profiles with less frequent occurrence of musculoskeletal complications and a reduction in the levels of serum calcium and PTH (5). The concept of asymptomatic disorder progressing over time to symptomatic disease was not proven. The disease progression of asymptomatic PHPT was rare and slow as evidenced in observational studies [6,7]. The present study analyses a cohort of surgically proved PHPT cases of the last 15 years in a single centre. The aim of the study was to assess the demographic, clinical and pathological features of primary hyperparathyroidism and to compare these features with those of asymptomatic disorders in North American countries. Study design: Case records of patients who were operated on for hyperparathyroidism during 2005 to 2020 were reviewed. Exclusion criterion included secondary hyperparathyroidism, evidences (biochemical, imaging, or histological) of multiple endocrine neoplasia 1 and II. PHPT was confirmed by concurrent estimation of serum albumin-corrected calcium, serum phosphate (PO4) and serum intact parathyroid hormone (PTH) and calcium creatinine clearance ratio. The magnitude of target organ damage was assessed by bone mineral density studies (wrists, hip and lumbar spine) and ultrasound or computerised tomography of the urinary tract. Serum levels of creatinine, alkaline phosphatase, and 25 (OH) vitamin D were estimated routinely. Dual-phase 99m Tc-sestamibi parathyroid scintigraphy was the primary imaging for localization followed by Ultrasound imaging of the neck on the day of the operation. Other imaging modalities like 4D CT, MRI and Fluro-choline PET CT were done selectively when primary imaging failed to localize or when ectopic lesions were suspected. Focused parathyroidectomy was the usual surgical procedure when localization studies were successful and concordant. Total neck exploration was resorted to in patients with failed or discordant localization studies, multiple lesions, and concurrent thyroidectomy was planned. Intraoperative PTH assay was a routine intraoperative adjunct. The data collected included clinical and demographic features; biochemical studies (Serum corrected calcium, serum inorganic phosphate, serum intact PTH, serum creatinine, serum alkaline phosphatase, serum 25(OH)D,) and the details of localization studies. Details of operative findings and histological features were reviewed. The estimation techniques of biochemical features are noted as an annexure to table-I. There were upgradation and change in the automation of the analyser but the estimation techniques and reference ranges did not alter significantly. The data were collected from the prospective database maintained by the Endocrine surgery division. Approval was obtained for the study from the institutional research committee. Statistics: Nominal variables and their impact were analysed by cross-tabulation. Continuous variables were evaluated by chi-square or Fisher's exact test as appropriate. (p = 0.05). Statistical analysis was performed using IBM SPSS Statistics for Windows, version 20.0 (IBM Corp., Armonk, Newyork, USA). The manuscript was prepared a per the STROBE guidelines. There was no funding source for this study. Results Case records of 346 patients who were operated on for hyperparathyroidism were analysed. We excluded 22 patients with evidence of MEN- I and 4 patients with MEN- II and 19 patients with secondary hyperparathyroidism. The study group included 301 patients with a mean age of 48.58 years (SD:14.793) (median 50; range-11-80). The cohort included 173 (57.5%) females and 128 (42.5%) males and the mean age of the gender groups did not show a significant difference. (48.29 (15.275) Vs 48.98 (14.165). p = .421) The BMI of the group was 24.90 kg/m2 and the estimated GFR- was 99.37 ml/minute (sd: 343.54). Table 1 Biochemical features Feature Mean values Standard deviation Reference ranges Serum Ca. 12.12 1.628 8.6–10 mg/dl Serum PTH 702.93 712.289 15-65pg/ml Serum PO4 2.521 0.812 2.6-4.5mg/dl 25 OHD 19.06 13.501 30 to 50 ng/ml ALP 302.78 590.861 0.0-130 IU/L Corrected calcium -Estimated by NM-BAPTA assay (automated) and adjusted to serum albumin. PTH- Intact-PTH electrochemiluminescence immunoassay (ECLIA; Roche) (automated) PO4- Inorganic Phosphate – phosphomolybdic- (automated.) 25 OHD- Enzyme linked immunosorbent assay (ELISA) (Automated.) ALP (Serum Alkaline Phosphatase) PNPP Kinetic The study group included 279 (92.7%) patients with symptomatic PHPT and 22 with the asymptomatic disorder. Symptomatic patients: Two hundred and seventy-nine (92.7%) patients. The presenting symptoms of123 (41%) were related to the musculoskeletal system and those of 98 (33%) were related to kidneys. The rest of patients presented with gastrointestinal diseases (n: 34, 11%), metabolic alterations (n: 22, 7%) and depression (n:1, .3%). Three patients presented with neck swelling though they had associated skeletal manifestations. The median age at which the first symptom manifested was 46 years. Asymptomatic patients: Of the 22 patients 11 had serum ALP levels above the normal reference range and 6 (27%) showed a T score > -2.5 (wrists) on BMD studies. Ultrasound examination showed the presence of urinary stones in two patients. The demographic and biochemical features are noted in Tables 2 and 3 respectively. Serum calcium levels were raised more than 1 mg above the normal reference ranges in 13 (60%) of these patients and the serum PTH levels showed a more than a threefold increase in 9(41%) patients. Details of clinical and demographic features are noted in table 2 and the laboratory studies in Table 3 . Table-2. Demographic features of symptomatic and asymptomatic patients Features Symptomatic Asymptomatic Significance Age years (SD) 47.98(14.917) 56.27 (10.665) 0.011 Male gender 117 (41.9%) 11 (50%) .302 BMI (Kg/Sq meter) 24.83 (3.869) 25.90(2.58) .200 GFR ml/minute* 100.28(356.827) 87.32(18.709) .868 CAD 15(5.4%) 2 (13.6%) .135 Diabetes 64 (22.9%) 2(9%) .101 Hypertension 98(35%) 13 (59%) . 024 Total 279 22 *eGFR- Calculated based on ‎Cockcroft-Gault Formula Table 3 Biochemical features of symptomatic and asymptomatic patients. Features Symptomatic Asymptomatic Significance Serum corrected calcium (mg/dl) 12.19 (1.664) 11.32 (.612) .016 PTH (pg/ml) 741.20 (725.438) 217.67 (122.889) .001 The number of patients with threefold elevated PTH. 222 (79.6%) 9 (40.9%) .001 Serum 25 OH D ng/ml 18.85 ((13.621) 21.69 (11.949) .342 Number of patients with Vit D deficiency 185 (66%) 10 (45.5%) .043 ALP (IU/ml) 319.05 (610.817) 98.63 (30.398) .092 PO4 (mg/dl) 2.52 (.839) 2.50 (.445) .904 Vitamin D deficiency/ insufficiency was found in 82% of patients but the serum calcium and serum PTH levels did not vary considerably among the groups. Table- 4. Table-4 Vitamin D levels and clinical and biochemical impact 25 OHD level Number Serum i PTH Serum calcium ALP > 30 55 (18%) 815.4 (811.20) 12.5 (2.181) 370.0 (749.50) 20–30 64 (21%) 575.6 (568.87) 11.9 (1.201) 186.4 (230.19) 10–20 97 (32%) 580.9 (656.09) 11.9 (1.321) 280.4 (393.13) < 10 85 (28%) 865.2 (769.66) 12.2(1.621) 371.4 (804.69) Total 301 702.9 (590.69) 12.1 (1.62) 302.9 (590.69) Surgical treatment: Tc99 MIBI parathyroid scintigraphy was diagnostic as a primary localization study in 283 (94%) patients and the efficacy was not different between symptomatic and asymptomatic patients. (263 (94.3%) Vs 20 (91%) p = .386). A multi-glandular disease was found in 16 (5%) of the patients. Persistent hypercalcaemia occurred in 9 (2.9%) and all of them underwent a second successful exploration. Final histology: - Adenoma- 245 (81.3%); Hyperplasia- 27 (9%); Atypical adenoma – 15 (5%); Carcinoma- 14 (4.7%). Chief cell lesions were noted in 276 (91.7%) oxyphil cells in 17 (5.6%) and clear cell in 8 (2.7%). Histology of asymptomatic patients showed adenoma in all patients but 3 of them had atypical features. Discussion A recent systematic review analysing publications from developing countries found approximately 79.6% (49%-100%) of PHPT patients were symptomatic (7). Case series from countries like Thailand, Iran, India, South Africa, and Pakistan had more than 90% symptomatic diseases (2,3,8,9,10.) In India, there is an increase in the pickup of asymptomatic disorders but there were no systematic community surveys. Analysing 1088 patients from 6 published Indian case series spanning across 2005 to 2018, there were 4.2% (n:46) asymptomatic subjects. (11,12,13,14,15,16.). The usual presentation of PHPT in India and in many Asian countries was found related to the skeletal system though the incidences of fragility fractures had decreased (11,12). Contrarily, of the 334 PHPT patients in Massachusetts series during the early decades of the 20 th century there was a 56.9% prevalence of renal stone disease and a 23.3% prevalence of bone diseases (1). This disparity in the clinical presentation may be attributed to the widespread prevalence of vitamin D deficiency in India. Approximately 20% Indian population is vitamin D deficient (< 30 ng/ml) and studies showed a mean level of serum 25(OH)D was 14.16 ng/ml (sd: 13.27) among the apparently healthy Indian population (17,18). But in South India, where the study was done the mean level of 25(OH)D was considerably high (17.45 ng/ml) (18). The present study showed a high prevalence of vitamin D deficiency/ insufficiency but the disease severity indices did not correlate with the 25(OH)D level. We did not find a significant difference in 25(OH)D levels between patients with the skeletal disease and renal stones. (17.60 ng/ml and 19.25ng/ml respectively) The classic demographic features of asymptomatic PHPT were postmenopausal women in the 6 th decade without symptoms related to target organ damage. The females outnumbered the males equalling a ratio of 3:1 (F: M) (19,20). Indian patients were generally younger (mean age 36.38 to 48.1 years) with a higher prevalence of males (23% to 42%) (6,7,8,9,10,11). The symptomatic patients in other developing countries were also younger than the asymptomatic counterparts in developed nations (7). The asymptomatic patients of the present study cohort were a decade older than the symptomatic patients. Similarly, the asymptomatic patients in other Asian countries were older and fall in line with European or American counterparts. Traditionally, the serum calcium levels of the asymptomatic patients remained < 1mg of the upper limit of normal ranges and PTH levels not more than 1.5 t0 2 times of upper limit of reference ranges (19). The serum calcium and PTH levels of study cohort were higher and had subtle impact on target organs. The vitamin D deficiency status was not significantly different between the symptomatic and asymptomatic groups. The histological study of parathyroid glands was based on WHO guidelines (20). An atypical adenoma is a relatively rare histological category characterised by the presence of histological features like capsular and vascular invasion without infiltration to neighbouring tissues (21,22,23). Atypical adenoma stands close to carcinoma and may be considered an early form of cancer. Commonest of parathyroid glandular pathologies associated with PHPT was a single gland adenoma and cancer was found in 0.74% instances (24). Atypical adenoma and parathyroid cancer were more frequently found (5% and 4.7% respectively) in the present series. A systematic review of Indian PHPT patients in 2011 enrolling 366 patients reported a 4.37% prevalence of cancers. (25). The demographic profile, clinical features, and parathyroid glandular pathology of symptomatic PHPT in Asian countries are different from those of asymptomatic disorders frequented in North American and EU countries. The major shortcoming of the present study is the lack of the analysis of molecular genetic features which could have established the true identity of the disease. Conclusion The primary hyperparathyroidism seen in India and other Asian countries is a different clinical phenotype and differ widely from asymptomatic variant popular in American and EU population. Declarations Author Contribution All authors contributed to the study conception and design. Material preparation was done by Riju R, C Gopalakrishnan Nair, data collection by Anoop, Sidhu, Misha, and Revathy, and analysis were performed by Riju R, C Gopalakrishnan Nair, and Pradeep Jacob. The first draft of the manuscript was written by C Gopalakrishnan Nair and Riju R and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript. References Cope O. The study of hyperparathyroidism at the Massachusetts General Hospital. N Engl J Med. 1966; 274:1174–1182. Prasarttong-Osoth P, Wathanaoran P, Imruetaicharoenchoke W, Rojananin S. Primary hyperparathyroidism: 11-year experience in a single institute in Thailand. Int J Endocrinol. 2012:952426. doi:10.1155/2012/952426 Meng L, Liu S, Al-Dayyeni A, Sheng Z, Zhou Z, Wang X. Comparison of Initial Clinical Presentations between Primary Hyperparathyroidism Patients from New Brunswick and Changsha. Int J Endocrinol. 2018 Sep 18; 2018:6282687. doi: 10.1155/2018/6282687. PMID: 30363962; PMCID: PMC6186333. Shah VN, Bhadada S, Bhansali A, Behera A, Mittal BR. Changes in clinical & biochemical presentations of primary hyperparathyroidism in India over a period of 20 years. Indian J Med Res. 2014;139(5):694-699. Yadav SK, Mishra SK, Mishra A, Mayilvagnan S, Chand G, Agarwal G. et al. Changing Profile of Primary Hyperparathyroidism Over Two and Half Decades: A Study in Tertiary Referral Center of North India. World J Surg. 2018;42(9):2732-2737. doi: 10.1007/s00268-018-4575-0 Silverberg SJ, Shane E, Jacobs TP, Siris E, Bilezikian JP. A 10-year prospective study of primary hyperparathyroidism with or without parathyroid surgery. N Engl J Med. 1999. 21;341(17):1249-55. Rubin MR, Bilezikian JP, McMahon DJ, Jacobs T, Shane E, Siris E, et al. The natural history of primary hyperparathyroidism with or without parathyroid surgery after 15 years. J Clin Endocrinol Metab. 2008. 93(9):3462-70 Bhadada SK, Arya AK, Mukhopadhyay S, Khadgawat R, Sukumar S, Lodha S, et al. Primary hyperparathyroidism: insights from the Indian PHPT registry. J Bone Miner Metab. 2018;36(2):238-45. Paruk IM, Esterhuizen TM, Maharaj S, Pirie FJ, Motala AA. Characteristics, management and outcome of primary hyperparathyroidism in South Africa: a single-centre experience. Postgrad Med J. 2013;89(1057):626-31. Bahrami A, Montazeri V, Barband AR, Poorzand A, Mobaseri M. Advanced Bone Diseases the Most Common Clinical Presentation of Primary Hyperparathyroidism in Iranians: Clinical And Laboratory Features of 62 Patients from North-Western Iran. Int J Endocrinol Metab.2006;4:19-29. Bhansali A, Masoodi SR, Somashekara Reddy KS, Behera A, Radotra Bd, Mittal BR, Katariya RN, Dash RJ. Primary hyperparathyroidism in north India: A description of 52 cases. Ann Saudi Med 2005; 25:29-35 Primary hyperparathyroidism: A changing scenario in India. Jha S, Jayaraman M, Jha A, Jha R, Modi KD, Kelwadee JV. Primary hyperparathyroidism: A changing scenario in India. Indian J Endocrinol Metab. 2016;20(1):80–83. doi:10.4103/2230-8210.172237 Shah VN, Bhadada S, Bhansali A, Behera A, Mittal BR. Changes in clinical & biochemical presentations of primary hyperparathyroidism in India over a period of 20 years. Indian J Med Res. 2014; 139:694–9. Primary hyperparathyroidism in India: A cocktail of contemporary and classical presentations: Lesson from 47 cases. Maskey R, Panchani R, Varma T, Goyal A. Indian J Endocrinol Metab. 2013 Oct;17(Suppl 1):S209-11 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. Mallikarjuna VJ, Mathew V, Ayyar V, Bantwal G, Ganesh V, George B, Hemanth GN, Vinotha P.Indian J Endocrinol Metab. 2018 May-Jun;22(3):355-361. Clinical profile of primary hyperparathyroidism from western India: a single center experience. Gopal RA, Acharya SV, Bandgar T, Menon PS, Dalvi AN, Shah NS. J Postgrad Med. 2010 Apr-Jun;56(2):79-84 Amren K, Scherkl M, Hoffman M, Neuwersch- Sommeregger S, Kostenberger M, Tmava Berisha A, Martucci G, Pilz S, Malle O. Vitamin D deficiency 2.0: an update on current status worldwide. Eu J Clin Nutr 2020 74 (11) 1498-1513 Selvaraman S, Gunaseelan V, Anandbasker N, Xavier AS, Srinivasamoorthy S,Kamalanathan SK, Sahoo JP. Systematic review on Vitamin D level in Apparently healthy Indian Population and analysis of its associated factors. Indian Journal Of Endocrinology. 2017 Sep (5) 765-775. John P Bilezikian, Primary Hyperparathyroidism, The Journal of Clinical Endocrinology & Metabolism, Volume 103, Issue 11, November 2018, Pages 3993–4004. Brandi ML (ed): Parathyroid Disorders. Focusing on Unmet Needs. Front Horm Res. Basel, Karger, 2019, vol 51, pp 13–22 (DOI: 10.1159/000491035 DeLellis R. A, Parathyroid carcinoma. In Pathology and Genetics of Tumours of Endocrine Organs, World Health Organization Classification of Tumours 2004; Lyon, France. 124–7) Hundahl SA, Fleming ID, Fremgen AM, Menck HR. Cancer. 1999 Aug 1; 86(3):538-44). Atypical parathyroid adenomas: challenging lesions in the differential diagnosis of endocrine tumors Filomena Cetani1, Claudio Marcocci2, Liborio Torregrossa3 and Elena Pardi. Endocrine-Related Cancer (2019) 26, R441–R464) Cetani F, Marcocci C, Torregrossa L, Pardi E, Atypical parathyroid adenomas: challenging lesions in differential diagnosis of Endocrine tumors. Endocr Relat Cancer. 2019;26 (7): R 441-R464. Doi 10.1530/ERC-19-0135. Ruda JM, Hollenbeak CS, Stack BC Jr. A systematic review of the diagnosis and treatment of primary hyperparathyroidism from 1995 to 2003. Otolaryngol Head Neck Surg. 2005;132(3):359-72. P. V. Pradeep, B. Jayashree, Anjali Mishra, S. K. Mishra, "Systematic Review of Primary Hyperparathyroidism in India: The Past, Present, and the Future Trends", International Journal of Endocrinology, vol. 2011, Article.ID 921814, 7 pages, 2011. https://doi.org/10.1155/2011/921814. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted 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 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-3762644","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":260334977,"identity":"408ec392-68c0-48c0-9636-5babf50b5f56","order_by":0,"name":"Riju Ramachandran Menon","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA0ElEQVRIiWNgGAWjYDACZoYEGOsAkJCQIUULG4ghwUOKfTwGYJKgOvN2hmfSlTk2efzSPZ9f3aix4GFgP3x0Az4tMocZ0iTPbksrlpxzdpt1zjGgw3jS0m7g0yLBDNTSuO1w4oYbuduMc9iAWiR4zIjR8h+oJeeZcc4/4rUcAGlhfpzbRpyWZMvGbcmJM2ekmTHn9knwsBH0C/+ZxJuN2+wS+yWSH3/O+VYnx89++BheLcCISICx2CTAJH7lIMB+AMZi/kBY9SgYBaNgFIxEAACIO0MiVOYHagAAAABJRU5ErkJggg==","orcid":"","institution":"Amrita Institute of Medical Sciences and Research Centre","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Riju","middleName":"Ramachandran","lastName":"Menon","suffix":""},{"id":260334978,"identity":"f2107119-67a4-43f8-81c2-5956241d73aa","order_by":1,"name":"Gopalakrishnan C Nair","email":"","orcid":"","institution":"Amrita Institute of Medical Sciences and Research Centre","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Gopalakrishnan","middleName":"C","lastName":"Nair","suffix":""},{"id":260334979,"identity":"2177976b-b3df-4b55-b5ab-7e7aa8a91704","order_by":2,"name":"Anoop Vasudevan Pillai","email":"","orcid":"","institution":"Amrita Institute of Medical Sciences and Research Centre","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Anoop","middleName":"Vasudevan","lastName":"Pillai","suffix":""},{"id":260334980,"identity":"c8ced249-290b-46c2-8323-d85d3ebe077e","order_by":3,"name":"Sidhu Sekhar","email":"","orcid":"","institution":"Amrita Institute of Medical Sciences and Research Centre","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Sidhu","middleName":"","lastName":"Sekhar","suffix":""},{"id":260334981,"identity":"682f2591-b643-4ea4-ad45-9ee0933e65e4","order_by":4,"name":"Misha JC Babu","email":"","orcid":"","institution":"Amrita Institute of Medical Sciences and Research Centre","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Misha","middleName":"JC","lastName":"Babu","suffix":""},{"id":260334982,"identity":"ee034fa5-815c-4824-9ebb-047597b5562b","order_by":5,"name":"Revathy AK Nair","email":"","orcid":"","institution":"Amrita Institute of Medical Sciences and Research Centre","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Revathy","middleName":"AK","lastName":"Nair","suffix":""},{"id":260334983,"identity":"160f13be-2c86-45f0-a058-aa66ae08af88","order_by":6,"name":"Pradeep Jacob","email":"","orcid":"","institution":"Amrita Institute of Medical Sciences and Research Centre","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Pradeep","middleName":"","lastName":"Jacob","suffix":""}],"badges":[],"createdAt":"2023-12-16 09:14:46","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3762644/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3762644/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":51578264,"identity":"72fe6433-a5d0-4303-8f33-4fac8b8ac014","added_by":"auto","created_at":"2024-02-24 07:07:40","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":234988,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3762644/v1/5e75e9d2-90cb-41a3-a773-a50861046e6e.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":" Clinico-pathological study of symptomatic hyperparathyroidism: is it a different phenotype expression of hyperparathyroidism?","fulltext":[{"header":"Introduction","content":"\u003cp\u003eThe profile of primary hyperparathyroidism has changed to an asymptomatic endocrine disorder among the American and European Union population. This radical change in clinical presentation is attributed to introduction of autoanalyzer which enabled early detection of hypercalcaemia. In spite of the widespread use of autoanalyzer, pick up of asymptomatic PHPT is scanty in India. The actual incidence of PHPT in India is not available since there was no systematic community survey. A large case series analysis from Massachusetts general hospital recorded significantly high prevalence of urinary stone disease over skeletal involvement (1). Majority of case series analysis from Asian countries recorded high incidences of symptomatic PHPT and the commonest presenting symptoms were related to musculo-skeletal system. (2,3). Analysing a large cohort of PHPT patients spreading over 2 decades, Shah et al concluded that PHPT continues as a symptomatic disease in India and the characteristic features have not changed significantly (4). Paradoxically another large group analysis showed changes in clinical and biochemical profiles with less frequent occurrence of musculoskeletal complications and a reduction in the levels of serum calcium and PTH (5).\u003c/p\u003e \u003cp\u003eThe concept of asymptomatic disorder progressing over time to symptomatic disease was not proven. The disease progression of asymptomatic PHPT was rare and slow as evidenced in observational studies [6,7].\u003c/p\u003e \u003cp\u003eThe present study analyses a cohort of surgically proved PHPT cases of the last 15 years in a single centre. The aim of the study was to assess the demographic, clinical and pathological features of primary hyperparathyroidism and to compare these features with those of asymptomatic disorders in North American countries.\u003c/p\u003e \u003cp\u003e Study design: Case records of patients who were operated on for hyperparathyroidism during 2005 to 2020 were reviewed. Exclusion criterion included secondary hyperparathyroidism, evidences (biochemical, imaging, or histological) of multiple endocrine neoplasia 1 and II.\u003c/p\u003e \u003cp\u003ePHPT was confirmed by concurrent estimation of serum albumin-corrected calcium, serum phosphate (PO4) and serum intact parathyroid hormone (PTH) and calcium creatinine clearance ratio. The magnitude of target organ damage was assessed by bone mineral density studies (wrists, hip and lumbar spine) and ultrasound or computerised tomography of the urinary tract. Serum levels of creatinine, alkaline phosphatase, and 25 (OH) vitamin D were estimated routinely. Dual-phase \u003csup\u003e99m\u003c/sup\u003eTc-sestamibi parathyroid scintigraphy was the primary imaging for localization followed by Ultrasound imaging of the neck on the day of the operation. Other imaging modalities like 4D CT, MRI and Fluro-choline PET CT were done selectively when primary imaging failed to localize or when ectopic lesions were suspected. Focused parathyroidectomy was the usual surgical procedure when localization studies were successful and concordant. Total neck exploration was resorted to in patients with failed or discordant localization studies, multiple lesions, and concurrent thyroidectomy was planned. Intraoperative PTH assay was a routine intraoperative adjunct.\u003c/p\u003e \u003cp\u003eThe data collected included clinical and demographic features; biochemical studies (Serum corrected calcium, serum inorganic phosphate, serum intact PTH, serum creatinine, serum alkaline phosphatase, serum 25(OH)D,) and the details of localization studies. Details of operative findings and histological features were reviewed. The estimation techniques of biochemical features are noted as an annexure to table-I. There were upgradation and change in the automation of the analyser but the estimation techniques and reference ranges did not alter significantly.\u003c/p\u003e \u003cp\u003eThe data were collected from the prospective database maintained by the Endocrine surgery division. Approval was obtained for the study from the institutional research committee.\u003c/p\u003e \u003cp\u003eStatistics: Nominal variables and their impact were analysed by cross-tabulation. Continuous variables were evaluated by chi-square or Fisher's exact test as appropriate. (p\u0026thinsp;=\u0026thinsp;0.05). Statistical analysis was performed using IBM SPSS Statistics for Windows, version 20.0 (IBM Corp., Armonk, Newyork, USA).\u003c/p\u003e \u003cp\u003e The manuscript was prepared a per the STROBE guidelines. There was no funding source for this study.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eCase records of 346 patients who were operated on for hyperparathyroidism were analysed. We excluded 22 patients with evidence of MEN- I and 4 patients with MEN- II and 19 patients with secondary hyperparathyroidism.\u003c/p\u003e \u003cp\u003eThe study group included 301 patients with a mean age of 48.58 years (SD:14.793) (median 50; range-11-80). The cohort included 173 (57.5%) females and 128 (42.5%) males and the mean age of the gender groups did not show a significant difference. (48.29 (15.275) Vs 48.98 (14.165). p\u0026thinsp;=\u0026thinsp;.421)\u003c/p\u003e \u003cp\u003eThe BMI of the group was 24.90 kg/m2 and the estimated GFR- was 99.37 ml/minute (sd: 343.54).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eBiochemical features\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFeature\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMean values\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eStandard deviation\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eReference ranges\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSerum Ca.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e12.12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.628\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8.6\u0026ndash;10 mg/dl\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSerum PTH\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e702.93\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e712.289\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e15-65pg/ml\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSerum PO4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2.521\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.812\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.6-4.5mg/dl\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e25 OHD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e19.06\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e13.501\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e30 to 50 ng/ml\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eALP\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e302.78\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e590.861\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.0-130 IU/L\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eCorrected calcium -Estimated by NM-BAPTA assay (automated) and adjusted to serum albumin.\u003c/p\u003e \u003cp\u003ePTH- Intact-PTH electrochemiluminescence immunoassay (ECLIA; Roche) (automated)\u003c/p\u003e \u003cp\u003ePO4- Inorganic Phosphate \u0026ndash; phosphomolybdic- (automated.)\u003c/p\u003e \u003cp\u003e25 OHD- Enzyme linked immunosorbent assay (ELISA) (Automated.)\u003c/p\u003e \u003cp\u003eALP (Serum Alkaline Phosphatase) PNPP Kinetic\u003c/p\u003e \u003cp\u003eThe study group included 279 (92.7%) patients with symptomatic PHPT and 22 with the asymptomatic disorder.\u003c/p\u003e \u003cp\u003eSymptomatic patients: Two hundred and seventy-nine (92.7%) patients. The presenting symptoms of123 (41%) were related to the musculoskeletal system and those of 98 (33%) were related to kidneys. The rest of patients presented with gastrointestinal diseases (n: 34, 11%), metabolic alterations (n: 22, 7%) and depression (n:1, .3%). Three patients presented with neck swelling though they had associated skeletal manifestations. The median age at which the first symptom manifested was 46 years.\u003c/p\u003e \u003cp\u003eAsymptomatic patients: Of the 22 patients 11 had serum ALP levels above the normal reference range and 6 (27%) showed a T score \u0026gt; -2.5 (wrists) on BMD studies. Ultrasound examination showed the presence of urinary stones in two patients. The demographic and biochemical features are noted in Tables\u0026nbsp;2 and \u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e3\u003c/span\u003e respectively. Serum calcium levels were raised more than 1 mg above the normal reference ranges in 13 (60%) of these patients and the serum PTH levels showed a more than a threefold increase in 9(41%) patients. Details of clinical and demographic features are noted in table 2 and the laboratory studies in Table \u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e3\u003c/span\u003e.\u003c/p\u003e \u003cp\u003eTable-2. Demographic features of symptomatic and asymptomatic patients\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"No\" id=\"Taba\" border=\"1\"\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFeatures\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSymptomatic\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAsymptomatic\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eSignificance\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge years (SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e47.98(14.917)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e56.27 (10.665)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.011\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale gender\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e117 (41.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11 (50%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e.302\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBMI (Kg/Sq meter)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e24.83 (3.869)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e25.90(2.58)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e.200\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGFR ml/minute*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e100.28(356.827)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e87.32(18.709)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e.868\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCAD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15(5.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (13.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e.135\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiabetes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e64 (22.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2(9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e.101\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHypertension\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e98(35%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13 (59%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e.\u003cb\u003e024\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e279\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003e*eGFR- Calculated based on \u0026lrm;Cockcroft-Gault Formula\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eBiochemical features of symptomatic and asymptomatic patients.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFeatures\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSymptomatic\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAsymptomatic\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eSignificance\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSerum corrected calcium (mg/dl)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12.19 (1.664)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e11.32 (.612)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e.016\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePTH (pg/ml)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e741.20 (725.438)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e217.67 (122.889)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eThe number of patients with threefold elevated PTH.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e222 (79.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e9 (40.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSerum 25 OH D ng/ml\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18.85 ((13.621)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e21.69 (11.949)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e.342\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of patients with Vit D deficiency\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e185 (66%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e10 (45.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e.043\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eALP (IU/ml)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e319.05 (610.817)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e98.63 (30.398)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e.092\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePO4 (mg/dl)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.52 (.839)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2.50 (.445)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e.904\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eVitamin D deficiency/ insufficiency was found in 82% of patients but the serum calcium and serum PTH levels did not vary considerably among the groups. Table- 4.\u003c/p\u003e \u003cp\u003eTable-4 Vitamin D levels and clinical and biochemical impact\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"No\" id=\"Tabb\" border=\"1\"\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003e25 OHD level\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNumber\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSerum i PTH\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eSerum calcium\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eALP\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e55 (18%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e815.4 (811.20)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e12.5 (2.181)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e370.0 (749.50)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e20\u0026ndash;30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e64 (21%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e575.6 (568.87)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e11.9 (1.201)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e186.4 (230.19)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e10\u0026ndash;20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e97 (32%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e580.9 (656.09)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e11.9 (1.321)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e280.4 (393.13)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e85 (28%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e865.2 (769.66)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e12.2(1.621)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e371.4 (804.69)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e301\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e702.9 (590.69)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e12.1 (1.62)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e302.9 (590.69)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eSurgical treatment:\u003c/p\u003e \u003cp\u003eTc99 MIBI parathyroid scintigraphy was diagnostic as a primary localization study in 283 (94%) patients and the efficacy was not different between symptomatic and asymptomatic patients. (263 (94.3%) Vs 20 (91%) p\u0026thinsp;=\u0026thinsp;.386). A multi-glandular disease was found in 16 (5%) of the patients. Persistent hypercalcaemia occurred in 9 (2.9%) and all of them underwent a second successful exploration.\u003c/p\u003e \u003cp\u003eFinal histology: - Adenoma- 245 (81.3%); Hyperplasia- 27 (9%); Atypical adenoma \u0026ndash; 15 (5%); Carcinoma- 14 (4.7%). Chief cell lesions were noted in 276 (91.7%) oxyphil cells in 17 (5.6%) and clear cell in 8 (2.7%). Histology of asymptomatic patients showed adenoma in all patients but 3 of them had atypical features.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eA recent systematic review analysing publications from developing countries found approximately 79.6% (49%-100%) of PHPT patients were symptomatic (7). Case series from countries like Thailand, Iran, India, South Africa, and Pakistan had more than 90% symptomatic diseases (2,3,8,9,10.) In India, there is an increase in the pickup of asymptomatic disorders but there were no systematic community surveys. Analysing 1088 patients from 6 published Indian case series spanning across 2005 to 2018, there were 4.2% (n:46) asymptomatic subjects. (11,12,13,14,15,16.).\u003c/p\u003e\n\u003cp\u003eThe usual presentation of PHPT in India and in many Asian countries was found related to the skeletal system though the incidences of fragility fractures had decreased (11,12). Contrarily, of the 334 PHPT patients in Massachusetts series during the early decades of the 20\u003csup\u003eth\u003c/sup\u003e century there was a\u0026nbsp;56.9% prevalence of renal stone disease and a 23.3% prevalence of bone diseases (1). This disparity in the clinical presentation may be attributed to the widespread prevalence of vitamin D deficiency in India. Approximately 20% Indian population is vitamin D deficient (\u0026lt; 30 ng/ml) and studies showed a mean level of serum 25(OH)D was 14.16 ng/ml (sd: 13.27) among the apparently healthy Indian population (17,18). But in South India, where the study was done the mean level of 25(OH)D was considerably high (17.45 ng/ml) (18). The present study showed a high prevalence of vitamin D deficiency/ insufficiency but the disease severity indices did not correlate with the 25(OH)D level. We did not find a significant difference in 25(OH)D levels between patients with the skeletal disease and renal stones. (17.60 ng/ml and 19.25ng/ml respectively)\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;The classic demographic features of asymptomatic PHPT were postmenopausal women in the 6\u003csup\u003eth\u003c/sup\u003e decade without symptoms related to target organ damage. The females outnumbered the males equalling a ratio of 3:1 (F: M) (19,20). Indian patients were generally younger (mean age 36.38 to 48.1 years) with a higher prevalence of males (23% to 42%) (6,7,8,9,10,11). The symptomatic patients in other developing countries were also younger than the asymptomatic counterparts in developed nations (7).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;The asymptomatic patients of the present study cohort were a decade older than the symptomatic patients. Similarly, the asymptomatic patients in other Asian countries were older and fall in line with European or American counterparts. \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;Traditionally, the serum calcium levels of the asymptomatic patients remained \u0026lt; 1mg of the upper limit of normal ranges and PTH levels not more than 1.5 t0 2 times of upper limit of reference ranges (19). The serum calcium and PTH levels of study cohort were higher and had subtle impact on target organs. The vitamin D deficiency status was not significantly different between the symptomatic and asymptomatic groups.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;The histological study of parathyroid glands was based on WHO guidelines (20). An atypical adenoma is a relatively rare histological category characterised by the presence of histological features like capsular and vascular invasion without infiltration to neighbouring tissues (21,22,23). Atypical adenoma stands close to carcinoma and may be considered an early form of cancer. Commonest of parathyroid glandular pathologies associated with PHPT was a single gland adenoma and cancer was found in 0.74% instances (24). \u0026nbsp;Atypical adenoma and parathyroid cancer were more frequently found (5% and 4.7% respectively) in the present series. A systematic review of Indian PHPT patients in 2011 enrolling 366 patients reported a 4.37% prevalence of cancers. (25).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe demographic profile, clinical features, and parathyroid glandular pathology \u0026nbsp; of symptomatic PHPT in Asian countries are different from those of asymptomatic disorders frequented in North American and EU countries.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe major shortcoming of the present study is the lack of the analysis of molecular genetic features which could have established the true identity of the disease. \u0026nbsp;\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThe primary hyperparathyroidism seen in India and other Asian countries is a different clinical phenotype and differ widely from asymptomatic variant popular in American and EU population.\u0026nbsp;\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eAll authors contributed to the study conception and design. Material preparation was done by Riju R, C Gopalakrishnan Nair, data collection by Anoop, Sidhu, Misha, and Revathy, and analysis were performed by Riju R, C Gopalakrishnan Nair, and Pradeep Jacob. The first draft of the manuscript was written by C Gopalakrishnan Nair and Riju R and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eCope O. The study of hyperparathyroidism at the Massachusetts General Hospital. N Engl J Med. 1966; 274:1174\u0026ndash;1182.\u003c/li\u003e\n \u003cli\u003ePrasarttong-Osoth P, Wathanaoran P, Imruetaicharoenchoke W, Rojananin S. Primary hyperparathyroidism: 11-year experience in a single institute in Thailand.\u0026nbsp;Int J Endocrinol. 2012:952426. doi:10.1155/2012/952426\u003c/li\u003e\n \u003cli\u003eMeng L, Liu S, Al-Dayyeni A, Sheng Z, Zhou Z, Wang X. Comparison of Initial Clinical Presentations between Primary Hyperparathyroidism Patients from New Brunswick and Changsha. Int J Endocrinol. 2018 Sep 18; 2018:6282687. doi: 10.1155/2018/6282687. PMID: 30363962; PMCID: PMC6186333.\u003c/li\u003e\n \u003cli\u003eShah VN, Bhadada S, Bhansali A, Behera A, Mittal BR. Changes in clinical \u0026amp; biochemical presentations of primary hyperparathyroidism in India over a period of 20 years.\u0026nbsp;Indian J Med Res. 2014;139(5):694-699.\u003c/li\u003e\n \u003cli\u003eYadav SK, Mishra SK, Mishra A, Mayilvagnan S, Chand G, Agarwal G. et al. Changing Profile of Primary Hyperparathyroidism Over Two and Half Decades: A Study in Tertiary Referral Center of North India. World J Surg. 2018;42(9):2732-2737. doi: 10.1007/s00268-018-4575-0\u003c/li\u003e\n \u003cli\u003eSilverberg SJ, Shane E, Jacobs TP, Siris E, Bilezikian JP. A 10-year prospective study of primary hyperparathyroidism with or without parathyroid surgery. N Engl J Med. 1999. 21;341(17):1249-55.\u003c/li\u003e\n \u003cli\u003eRubin MR, Bilezikian JP, McMahon DJ, Jacobs T, Shane E, Siris E, et al. The natural history of primary hyperparathyroidism with or without parathyroid surgery after 15 years. J Clin Endocrinol Metab. 2008. 93(9):3462-70\u003c/li\u003e\n \u003cli\u003eBhadada SK, Arya AK, Mukhopadhyay S, Khadgawat R, Sukumar S, Lodha S, et al. Primary hyperparathyroidism: insights from the Indian PHPT registry. J Bone Miner Metab. 2018;36(2):238-45.\u003c/li\u003e\n \u003cli\u003eParuk IM, Esterhuizen TM, Maharaj S, Pirie FJ, Motala AA. Characteristics, management and outcome of primary hyperparathyroidism in South Africa: a single-centre experience. Postgrad Med J. 2013;89(1057):626-31.\u003c/li\u003e\n \u003cli\u003eBahrami A, Montazeri V, Barband AR, Poorzand A, Mobaseri M. Advanced Bone Diseases the Most Common Clinical Presentation of Primary Hyperparathyroidism in Iranians: Clinical And Laboratory Features of 62 Patients from North-Western Iran. Int J Endocrinol Metab.2006;4:19-29.\u003c/li\u003e\n\u003c/ol\u003e\n\u003col\u003e\n \u003cli\u003eBhansali A, Masoodi SR, Somashekara Reddy KS, Behera A, Radotra Bd, Mittal BR, Katariya RN, Dash RJ. Primary hyperparathyroidism in north India: A description of 52 cases. Ann Saudi Med 2005; 25:29-35\u0026nbsp;\u003c/li\u003e\n \u003cli\u003ePrimary hyperparathyroidism: A changing scenario in India. \u0026nbsp;Jha S, Jayaraman M, Jha A, Jha R, Modi KD, Kelwadee JV. Primary hyperparathyroidism: A changing scenario in India. Indian J Endocrinol Metab. 2016;20(1):80\u0026ndash;83. doi:10.4103/2230-8210.172237\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eShah VN, Bhadada S, Bhansali A, Behera A, Mittal BR. Changes in clinical \u0026amp; biochemical presentations of primary hyperparathyroidism in India over a period of 20 years.\u0026nbsp;Indian J Med Res.\u0026nbsp;2014; 139:694\u0026ndash;9.\u003c/li\u003e\n \u003cli\u003ePrimary hyperparathyroidism in India: A cocktail of contemporary and classical presentations: Lesson from 47 cases. Maskey R, Panchani R, Varma T, Goyal A.\u0026nbsp;Indian J Endocrinol Metab. 2013 Oct;17(Suppl 1):S209-11\u003c/li\u003e\n \u003cli\u003eFive-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.\u0026nbsp;Mallikarjuna VJ, Mathew V, Ayyar V, Bantwal G, Ganesh V, George B, Hemanth GN, Vinotha P.Indian J Endocrinol Metab. 2018 May-Jun;22(3):355-361.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eClinical profile of primary hyperparathyroidism from western India: a single center experience.\u0026nbsp;Gopal RA, Acharya SV, Bandgar T, Menon PS, Dalvi AN, Shah NS. J Postgrad Med. 2010 Apr-Jun;56(2):79-84\u003c/li\u003e\n \u003cli\u003e\u0026nbsp;Amren K, Scherkl M, Hoffman M, Neuwersch- Sommeregger S, Kostenberger M, Tmava Berisha A, Martucci G, Pilz S, Malle O. \u0026nbsp;Vitamin D deficiency 2.0: an update on current status worldwide. Eu J Clin Nutr 2020 74 (11) 1498-1513\u003c/li\u003e\n \u003cli\u003eSelvaraman S, Gunaseelan V, Anandbasker N, Xavier AS, Srinivasamoorthy S,Kamalanathan SK, Sahoo JP. Systematic review on Vitamin D level in Apparently healthy Indian Population and analysis of its associated factors. Indian Journal Of Endocrinology. 2017 Sep (5) 765-775.\u003c/li\u003e\n \u003cli\u003eJohn P Bilezikian, Primary Hyperparathyroidism, The Journal of Clinical Endocrinology \u0026amp; Metabolism, Volume 103, Issue 11, November 2018, Pages 3993\u0026ndash;4004. \u0026nbsp;\u003c/li\u003e\n \u003cli\u003eBrandi ML (ed): Parathyroid Disorders. Focusing on Unmet Needs. Front Horm Res. Basel, Karger, 2019, vol 51, pp 13\u0026ndash;22 (DOI: 10.1159/000491035 \u0026nbsp;\u003c/li\u003e\n \u003cli\u003eDeLellis R. A, Parathyroid carcinoma. In Pathology and Genetics of Tumours of Endocrine Organs, World Health Organization Classification of Tumours 2004; Lyon, France. 124\u0026ndash;7)\u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eHundahl SA, Fleming ID, Fremgen AM, Menck HR. Cancer. 1999 Aug 1; 86(3):538-44). \u0026nbsp;Atypical parathyroid adenomas: challenging lesions in the differential diagnosis of endocrine tumors Filomena Cetani1, Claudio Marcocci2, Liborio Torregrossa3 and Elena Pardi. \u0026nbsp;Endocrine-Related Cancer (2019) 26, R441\u0026ndash;R464)\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eCetani F, Marcocci C, Torregrossa L, Pardi E, Atypical parathyroid adenomas: challenging lesions in differential diagnosis of Endocrine tumors. Endocr Relat Cancer. 2019;26 (7): R 441-R464. Doi 10.1530/ERC-19-0135. \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eRuda JM, Hollenbeak CS, Stack BC Jr. A systematic review of the diagnosis and treatment of primary hyperparathyroidism from 1995 to 2003. Otolaryngol Head Neck Surg. 2005;132(3):359-72.\u003c/li\u003e\n \u003cli\u003eP. V. Pradeep, B. Jayashree, Anjali Mishra, S. K. Mishra, \u0026quot;Systematic Review of Primary Hyperparathyroidism in India: The Past, Present, and the Future Trends\u0026quot;, International Journal of Endocrinology, vol. 2011, Article.ID 921814, 7 pages, 2011. https://doi.org/10.1155/2011/921814.\u0026nbsp;\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-3762644/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3762644/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003ePurpose\u003c/strong\u003e: Symptomatic PHPT is common in Asian countries, with the musculoskeletal system affected frequently, unlike Western literature, with a high prevalence of urinary stone disease. The concept of an asymptomatic disorder progressing over time to a symptomatic disease was not proven. The study aimed to assess the demographic, clinical, and pathological features of primary hyperparathyroidism and to compare these features with those of asymptomatic disorders in North American countries.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e: This is an observational study on a cohort of patients operated on for hyperparathyroidism from 2005 to 2020 at the endocrine surgery division of a tertiary referral center in south India. Secondary hyperthyroidism was excluded. Case records were reviewed. Continuous variables were evaluated by chi-square or Fisher's exact test as appropriate (p\u0026lt;0.05). All discrete variables are noted as mean with standard deviation.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e: We had 301 patients in the study after excluding 45. There were 279 (92.7%) patients with symptomatic PHPT and 22 with asymptomatic disorders. The asymptomatic patients in the present study cohort were a decade older (p\u0026lt;0.011). Symptomatic patients had higher corrected calcium (p\u0026lt;0.16), lower vitamin D levels, and more elevated serum PTH levels (p\u0026lt;0.001), and the musculoskeletal system was more commonly affected.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion\u0026nbsp; \u003c/strong\u003eThe study cohort's serum calcium and PTH levels were higher and subtly impacted target organs. The musculoskeletal system was more commonly affected than the renal system in our cohort, possibly due to lower vitamin D levels in our population, unlike the patients from Western countries.\u003c/p\u003e","manuscriptTitle":" Clinico-pathological study of symptomatic hyperparathyroidism: is it a different phenotype expression of hyperparathyroidism?","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2023-12-19 06:01:46","doi":"10.21203/rs.3.rs-3762644/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"25c581a8-304e-4934-b844-4b28e89f94e3","owner":[],"postedDate":"December 19th, 2023","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-02-24T06:59:33+00:00","versionOfRecord":[],"versionCreatedAt":"2023-12-19 06:01:46","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-3762644","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3762644","identity":"rs-3762644","version":["v1"]},"buildId":"afDZ1USd8LLqUjqjB8QhT","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}