TSH reference intervals in Sub-Saharan adults: A pilot study in Cameroon

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In many African countries, access to diagnostic tools and medical expertise is limited, and reference intervals appropriate for the African population are lacking. Thyroid-stimulating hormone (TSH) is the primary marker used to diagnose thyroid dysfunction; however, reference values for TSH remain undefined in sub-Saharan Africa. This study aimed to establish reference ranges for serum uric acid and TSH levels in adults residing in Yaoundé. Materials and Methods: From November 2019 to June 2020, we conducted a cross-sectional study of 292 individuals aged 18 to 65 years. The assays were performed on a Cobas 6000® machine. Using Stata 15 and SPSS 26, we determined the upper and lower limits of normal at the 2.5th and 97.5th percentiles, respectively. We assessed the effects of sex, age, ethnicity, and educational level. Results: The mean age of the 292 volunteers was 31.51 years, with a sex ratio of 1.7 females to males. The majority had a university degree (66.1%). The overall TSH reference range was 0.2 to 2.9 mIU/L, which was consistent with the American Association of Clinical Endocrinologists ranging from 92% of the time. TSH values were significantly influenced by university education (p = 0.005), with a specific reference interval of 0.25 to 3.13 mIU/L. Conclusion: Our results are broadly in line with those of American learned societies. These results could be used in routine practice by African practitioners based on clinical features and could serve as a pilot study for other sub-Saharan countries. Reference intervals TSH Sub-Saharan Africa Figures Figure 1 Highlights • Overall, the TSH reference intervals in Cameroon were lower than the data from the manufacturer's reagent kits available in our setting. • University-level education significantly influenced TSH levels. • There was a 92% level of agreement between our reference intervals and the data from the American Association of Clinical Endocrinologists. 1. Introduction Thyroid hormones play crucial roles in cellular metabolism and the maintenance of homeostasis [1]. Their secretion is regulated by the anterior pituitary gland through thyrotropin, also known as thyroid-stimulating hormone (TSH) [2]. Compared with thyroid hormones, TSH, particularly ultrasensitive TSH, serves as a reliable marker for assessing thyroid gland dysfunction. It offers the highest sensitivity and specificity for diagnosing both clinical and subclinical functional disorders [3]. Furthermore, regular TSH measurement is essential for monitoring treatments for thyroid disorders, especially in cases involving secretory tumors [4]. The synthesis and levels of ultrasensitive TSH are influenced by various factors, including age, pregnancy, coexisting medical conditions, ongoing inflammatory processes, certain medications, and iodine intake [5]. In the literature, the reference ranges for the serum level of ultrasensitive TSH (TSH-us) remain a topic of considerable controversy [6]. On the one hand, the methods of calculation and estimation vary across studies [7]. On the other hand, there is no established consensus on the selection criteria for the reference population [8]. The National Academy of Clinical Biochemistry (NACB) recommends determining TSH reference values within a 95% confidence interval, on the basis of a population of at least 120 healthy individuals with no personal or family history of thyroid dysfunction, no goiter, no detectable thyroid autoantibodies, and no medication use [9]. Implementing this recommendation is challenging because of the required technical resources, time, and financial costs. Consequently, most researchers refer to the joint guidelines of the International Federation of Clinical Chemistry (IFCC) and the Clinical and Laboratory Standards Institute (CLSI), which propose percentiles method to determine values at the 2.5th and 97.5th percentiles, or robust tests when the study population consists of more or fewer than 120 healthy individuals [10]. To date, very few studies in Africa have focused on establishing reference values for biochemical markers, particularly ultrasensitive TSH. However, ISO 15189 mandates that each laboratory define reference intervals specific to the population being tested [11]. Given that ultrasensitive TSH is the most reliable marker for detecting changes in thyroid function, determining its reference values is essential. In many countries, including Cameroon, biologists often rely on reference values provided by autoanalyzer manufacturers rather than locally established data [12,13]. Therefore, this study aimed to determine the reference intervals for serum TSH levels in Cameroonian adults aged 18 to 65 years. 2. Materials and methods Type and population of study We conducted a cross-sectional study on Cameroonian adults of both sexes and without comorbidities residing in Yaoundé, aged 18 to 65 years. The study period spanned from November 2019 to August 2020. A total of 292 individuals in apparent good health were selected on the basis of clinical and biological criteria. Sampling Before the study, we informed the population of Yaoundé about multiple screening campaigns that were taking place in the churches and markets. After providing informed consent, the participants were interviewed regarding chronic diseases, conditions that could influence their serum TSH levels and iodine status (Table 1 ). Their iodine status were evaluated by the UK dietitians iodine-specific diet questionnaire (I-FFQ). A daily iodine intake of approximately 150 mcg was required for selected participants. On the basis of this preliminary assessment, the participants were classified into two groups: Group 1 (N = 240): Individuals with at least one comorbidity potentially affecting their serum TSH levels. Group 2 (N = 400): Individuals without condition impacting their serum TSH levels. Table 1 Clinical exclusion criteria Anamnesis Physical examination Autoimmune disease Abdominal mass Cancer Abnormal cardiac auscultation Cardiovascular disease Altered mental status Combined oral contraceptives use Fever or infectious syndrome Current use of medication High blood pressure Diabete mellitus Jaundice Goiter Neck swelling Gout Overweight (BMI ≥ 25 Kg/m 2 ) or Obesity (BMI ≥ 30Kg/m 2 ) Macroscopic hematuria Tremors Heart failure Tachycardia Heart rhythm disorders History of paraneoplastic syndrome HIV infection Excessive iodine consumption Liver disease Palpitations Personal or family history of thyroid disease Pregnancy Renal insufficiency Weight loss Members of Group 2 underwent biological analyses. Of the 400 people tested, 108 were excluded on the basis of biological criteria (Table 2 ). Table 2 Biological exclusion criteria Reasons for exclusion Dosage methods Positive thyroperoxydase or thyroglobulin autoantibodies Electrochimiluminescence immune assay Blood glucose > 110mg/dL Enzymatic ALT > 40IU/L Colorimetric enzymatic, direct selective detergent CRP > 0.6/dL Estimated from CKD-EPI formula GFR < 60ml/min/1.73m 2 Immunoturbidimetry HDL-cholesterol 1.0g/L Enzymatic, colorimetric end point (GPO-PAP 4th Generation) Serum creatinine > 1.30 mg/dL Colorimetric Kinetic (Jaffe’s Method). Serum uric acid > 70mg/L in males or > 60mg/L in females Colorimetric enzymatic, direct selective detergent Total cholesterol > 2.5g/L Spectrophotometry/immunoturbidimetry Triglyceridemia > 1.5g/L Colorimetric enzymatic UV Positive AgHbs Rapid test by Determine® Positive AcHCV Rapid test by Determine® CHOD-PAP : cholestérol Oxydase - Peroxydase ; GPO-PAP: glycerol phosphatase-peroxydase The remaining 292 individuals formed Group 3 and were considered the reference population.These participants were normal euthyroid volunteers, as determined by the following characteristics established by the National Academy of Clinical Biochemistry: (1) no detectable levels of thyroid autoantibodies, anti-thyroid peroxidase antibodies (TPOAbs), or anti-thyroglobulin antibodies (TgAbs), as measured by sensitive immunoassays; (2) no personal or family history of thyroid dysfunction; (3) no visible or palpable goiter; and (4) no use of medications (except estrogen). Additionally, they had no other biochemical disorders (Table 2 ). Sample collection procedure For the assays, blood samples were collected from participants who had fasted for a minimum of 12 hours and a maximum of 16 hours. Following a 15-minute rest period, 5 mL of venous blood was drawn from a superficial vein at the elbow crease, with rigorous asepsis measures observed. The blood was placed in a tube with a gel separator and transported in secure transport bags to the PRIMA Sarl laboratory. The samples were subsequently centrifuged at 3,000 rpm for 10 minutes before analysis [14]. TSH assay method Serum TSH levels were estimated via electrochemiluminescence immunoassay (ECLIA) using a Cobas® 6000 analyzer (Roche Diagnostics, France, 2020). This fully automated method has a detection limit of 0.03 mIU/L. [15]. Variables and statistical analysis In the reference population, we assessed socio-demographic parameters, including age, sex, level of education, area of residence, and ethnic cultural habits, as well as body mass index (BMI), calculated as weight divided by height squared, and serum uric acid (SUA) levels. The collected data were compiled into a database via Excel 2013 and analyzed via SPSS version 26 and STATA 15. TSH values were summarized using the median and interquartile range. Boxplots and the Grubbs test were employed to identify and exclude outliers. Age, sex, education level, ethnicity, and place of residence were reported in numbers and frequencies. Differences in TSH medians across categorical variables were assessed via either the Mann-Whitney test or the Kruskal-Wallis test, depending on the number of classes. Reference intervals were set at the 2.5th percentile (lower limit of normal) and 97.5th percentile (upper limit of normal), following CLSI and IFCC guidelines [9,10]. Logistic regression was used to examine the influence of age, sex, ethnicity, education level, and place of residence on TSH values. Spearman’s correlation test was used to evaluate the relationship between age and TSH levels, represented graphically in a scatter plot. A p-value < 0.05 was considered statistically significant. Quality control We ensured quality control by conducting external quality assessments (EQA) by the Laboratory Quality Assurance (ASQUALAB) and internal quality controls (CIQ-CIL). Strict precautions were applied during preanalytical, analytical, and postanalytical phases to ensure the reliability of the tests. 3. Results Of the 292 individuals in the reference population, 185 were women and 107 were men, resulting in a sex ratio of 0.60. The mean age was 31.51 years with confidence interval of 30.29 to 32.74 years old. The age group of 25 to 40 years was the most prevalent (46.6%). A vast majority of the participants resided in urban areas (99.3%), and most held a university-level education (66.1%). In overall, the median serum TSH-us level was 1.14 with confidence interval of 0.69 to 1.69 mIU/L, with range of 0.11 to 3.85 mIU/L. There was a significant difference about median serum TSH-us levels based on education level ( P = 0.005). Neither sex, ethnic origin nor place of residence did not significantly affect serum TSH-us levels. Table 3 Comparisons in median TSH-us according to sociodemographic characteristics Variables Frequencies (T = 292) Percentages (%) Medians of TSH-us [IIQ]* in mIU/L p-value Sex Female 185 63.3 1.29 [0.89–1.76] 0.224 Male 107 36.7 1.12 [0.63–1.60] Levels of education University 193 66.1 1.25 [0.82–1.75] 0.005 Others** 99 33.9 0.96 [0.63–1.48] Place of residence Urban 290 99.3 0.98 [0.66–1.30] 0.633 Rural 2 0.7 1.14 [0.69–1.70] Ethnic groups Bantu 122 41.8 1.12 [0.66–1.67] 0.138 Semi-Bantu 139 47.6 1.19 [0.82–1.73] Sudanese 31 10.6 1.07 [0.65–1.54] *=Interquartile range ; **=Never attended, primary, secondary education levels Concerning the relationship between age and TSH-us levels, there was no significant correlation with P = 0.112 and Spearman coefficient of -0.08 (Fig. 1 ). There was also no significant association between BMI and TSH-us levels in the reference population. Overall, the reference interval for serum TSH-us levels was ranged from 0.25 to 2.94 mIU/L. This reference range was moderately in agreement with data from the US National Academy of Clinical Biochemistry (k = 58.8%) and strongly concordance with the guidelines of American Association of Clinical Endocrinologists (k = 92.0%). After multivariate analysis, level of education remained an independent factor influencing TSH levels. People with a university education had significantly higher TSH-us values than those with lower level of education (0.25 to 2.66 mIU/L vs 0.16 to 2.39 mIU/L). Table 4 TSH-us reference intervals and degrees of agreement with learned societies Variables Lower limit of normal (95% CI) in mIU/L Upper limit of normal (95% CI) in mIU/L 50th percentile (95% CI) in mIU/L NACB* TSH RI in mIU/L AACE** TSH RI in mIU/L* Overall 0.25 (0.18–0.33) 2.94 (2.59–3.55) 1.14 (1.07–1.27) 0.4 to 2.5 0.2 to 3 p < 0.0001 p < 00001 k = 58.8% k = 92.0% Level of education University 0.25 (0.18–0.34) 3.13 (2.65–3.72) 1.25 (1.12–1.38) −(NA) - NA Secondary or less 0.16 (0.11–0.34) 2.56 (2.33–2.62) 0.96 (0.81–1.14) - NA - NA *=National Academy of Clinical Biochemistry; **= American Association of Clinical Endocrinologists ; RI = Reference interval - NA = Not applicable, the above learned societies have no data available in this category ; k = Cohen's kappa coefficient 4. Discussion Thyroid hormone assay techniques have evolved significantly over the years, transitioning from radioimmunological methods to immunometric approaches. These advancements have increased both sensitivity and specificity, leading to periodic adjustments in the upper and lower limits of normal [16]. The International Federation of Clinical Chemistry (IFCC) and the US National Academy of Clinical Biochemistry (NACB) recommend that each laboratory establish its TSH reference ranges using a reference population of at least 120 euthyroid volunteers [9,10]. These individuals must undergo rigorous screening to exclude thyroid autoimmunity, personal or family history of thyroid disorders, the presence of a visible or palpable goiter, and the use of medications except estrogen [17]. Few studies in sub-Saharan Africa have focused on establishing reference intervals for TSH values. To date, no research on this subject has been leaded in Cameroon. To contribute to the African medical literature, this study aimed to determine reference values for serum TSH levels in Cameroonian adults. The study followed a cross-sectional design and included adults aged 18 to 65 years, residing in Yaoundé, of both sexes, and without comorbidities. The reference intervals for serum TSH-us levels ranged from 0.25 to 2.94 mIU/L, with a median of 1.14 mIU/L. These results are strongly aligned with data from American Association of Clinical Endocrinologists (AACE), which established reference ranges between 0.3 and 3 mIU/L [18]. However, our reference intervals are moderately consistent with those of the US NACB. Furthermore, the NACB advocated lowering the upper limit of normal to 2.5 mIU/L [17]. The slight difference between the AACE and NACB studies could be attributed to the greater ethnic diversity of the AACE study population. Additionally, the AACE study included a higher percentage of Black Americans compared to the NACB study. Nevertheless, our selection criteria were more stringent to minimize the risk of overlooking occult thyroid pathology among participants according to criteria of the US NACB. Based on the findings of the Third National Health and Nutrition Examination Survey (NHANES III), the American Thyroid Association (ATA) established an overall reference range of 0.45 to 4.12 mIU/L for the United States and non-iodine-deficient regions [19]. This study examined TSH reference ranges in a large, multiracial U.S. population [20]. The median TSH level of 1.18 mIU/L in Black participants was similar to the overall median in this study. Furthermore, the NHANES III study revealed a significantly lower median TSH level in Black American participants than in White (1.45 mIU/L) and Mexican (1.37 mIU/L) participants. Additionally, 80% of Black participants had a lower limit of normal TSH below 0.4 mIU/L and an upper limit of normal TSH below 4.5 mIU/L [20, 21]. Currently, there are no available data on reference intervals in the African literature for comparison with our results. Neither sex nor ethnic origin significantly influenced serum TSH levels, contrast with earlier studies that reported significantly higher TSH levels in women than in men [20,22]. However, a recent study revealed no statistically significant difference in TSH reference intervals between men and women [23]. Their male-to-female ratio was 0.9, which is comparable to that found in our study. However, older publications reported more balanced gender distributions. Regarding the relationship between age and TSH levels, this study did not observe a significant correlation between participant age and serum TSH levels, which contradicts previous literature findings [24]. This result may be due to the large number of participants in the 20–40 age group, which accounted for nearly half of all participants. In this age group, TSH values may not vary much. On the other hand, educational level significantly influenced TSH levels. However, this relationship has not been explored in prior studies. Given the statistical significance of these findings, further research in this area is warranted [25]. This study has two major strengths. First, it is the first study conducted in Central Africa aimed at establishing a TSH reference interval. Second, the electrochemiluminescence method used to determine thyroid hormone levels aligns with NACB guidelines, making it a superior reference technique compared to radioimmunoassays. Most available reference interval studies and manufacturers use radioimmunoassay measurements. However, according to IFCC and NACB standards, these measurements do not provide sufficiently low detection thresholds. This study has a few limitations. Instead of measuring ioduria, we assessed participants’ iodine status using an iodine specific diet questionnaire. We did not measure ioduria because the volunteers did not agree to come to the lab for a 24-hour urine collection. However, the World Health Organization, the UK Dietitians Association, and the Norwegian Food Council recommend diet-specific questionnaires as an effective alternative for quantifying iodine intake status when urine iodine levels cannot be assessed; these questionnaires have a strong correlation with ioduria [26, 27]. Recently, Tanticharoenkarn et al. found that iodine status did not significantly affect TSH reference intervals. Additionally, Li et al. demonstrated that an iodine-specific diet sheet is an effective method for evaluating iodine nutritional status in adults [28]. On the other hand, we could not perform a thyroid ultrasound to detect hypoechogenicity due to participant noncompliance with the radiology appointment. However, according to NACB guidelines adopted by the IFCC, thyroid ultrasounds are not recognized as a selection criterion for establishing TSH reference intervals [16–18]. Furthermore, according to the literature, thyroid ultrasounds do not significantly affect TSH reference ranges when thyroid antibodies are negative [23, 29]. 5. Conclusion The TSH reference intervals from this pilot study in sub-Saharan Africa aligned closely with the American Association of Clinical Endocrinologists' data and moderately with the National Academy of Clinical Biochemistry's. Our findings are similar to the TSH reference intervals of Black Americans in the NHANES III study. We recommend conducting a larger cohort study on TSH reference intervals in sub-Saharan Africa to compare these results with those of the present study. Declarations Competing interests All the authors declare that they have no competing interests for this research. Ethical Approval This study was approved by the Public Health Regional Center at N°CE/2112/CRERSHC/2020 and the Research Ethics Committee of the Faculty of Medicine and Biomedical Sciences at the University of Yaoundé I at N°276/UYI/FMSB/VDRC/DASSR/CDS, according to the Helsinki and Nuremberg declarations. All volunteers provided written informed consent to participate in the study before their inclusion and sampling. Consent for Publication In accordance with the guidelines of ISO 15189, all data were collected in biomedical laboratories, except those containing personal information of patients, which could be used for scientific research. Availability of Data All datasets from the current study are available via a request to the corresponding author. Funding This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Authors' contributions: Conception: SFMM, DCT, LMK, VJA-M. Design: MNYM, BEEE, NNA, RN, SZ, LMK, VJA-M. Data collection: JMT, SZ, MB, DCT. Laboratory analysis: BEEE, SZ, MB, DCT, VJA-M. Statistical analysis: SFMM, NNA, MNYM, LMK. Data interpretation: SFMM, SZ, NNA, MNYM, DCT, VJA-M. Supervision: SZ, BEEE, DCT, LMK, VJA-M Validation: BEEE, SZ, LMK, VJA-M Manuscript drafting: SFMM, MNYM, NNA, MB, DCT, BEEE. Manuscript review: SFMM, NNA, MB, BEEE, SZ, JMT, DCT, LMK, VJA-M. Accepted the final version of the manuscript All authors have approved and validated the final version of the manuscript submitted. Acknowledgments We would like to thank all the volunteers, lab technicians, and supervisors who gave their consent to take part in this study. References Brent GA. Mechanisms of thyroid hormone action. J Clin Invest. 2012; 122(9):3035-43. Cheng SY, Leonard JL, Davis PJ. Molecular aspects of thyroid hormone actions. Endocr Rev. 2010, 31(2):139 − 70. Laurberg P, Andersen S, Carlé A, Karmisholt J, Knudsen N, Pedersen IB. The TSH upper reference limit: where are we at? 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Supplementary Files Iodinespecificdietquestionnaire.pdf TSHdatabase.pdf Cite Share Download PDF Status: Published Journal Publication published 30 Apr, 2026 Read the published version in BMC Endocrine Disorders → Version 1 posted Editorial decision: Revision requested 28 Oct, 2025 Reviews received at journal 10 Oct, 2025 Reviewers agreed at journal 08 Oct, 2025 Reviews received at journal 27 Aug, 2025 Reviewers agreed at journal 19 Aug, 2025 Reviewers invited by journal 04 Aug, 2025 Editor assigned by journal 01 Jul, 2025 Submission checks completed at journal 30 Jun, 2025 First submitted to journal 30 Jun, 2025 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. 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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-6895452","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":496025902,"identity":"864edf77-9c87-4b6e-9cde-c939f2509f00","order_by":0,"name":"Stéphane Fargeon Massin MBOUNA","email":"data:image/png;base64,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","orcid":"","institution":"PRIMA SARL Laboratory","correspondingAuthor":true,"prefix":"","firstName":"Stéphane","middleName":"Fargeon Massin","lastName":"MBOUNA","suffix":""},{"id":496025903,"identity":"26af70a3-2320-4083-b0ba-fcd47c0dce5a","order_by":1,"name":"Marcelle-Nourya Ymelong MELI","email":"","orcid":"","institution":"University Teaching Hospital of Yaoundé, University of Yaoundé I","correspondingAuthor":false,"prefix":"","firstName":"Marcelle-Nourya","middleName":"Ymelong","lastName":"MELI","suffix":""},{"id":496025904,"identity":"73bdd2f3-d402-446c-98e2-eaa0f57532e2","order_by":2,"name":"Bertille Elodie EDINGA","email":"","orcid":"","institution":"National Public Health Laboratory, Ministry of Public Health","correspondingAuthor":false,"prefix":"","firstName":"Bertille","middleName":"Elodie","lastName":"EDINGA","suffix":""},{"id":496025905,"identity":"cc714e6e-c035-4e9c-9da3-c7357694afc5","order_by":3,"name":"Ngolé Néri ATABE","email":"","orcid":"","institution":"PRIMA SARL Laboratory","correspondingAuthor":false,"prefix":"","firstName":"Ngolé","middleName":"Néri","lastName":"ATABE","suffix":""},{"id":496025906,"identity":"5c70eb5a-8bcc-416b-a1e5-44221d8b5ac6","order_by":4,"name":"Stéphanie ZIBI","email":"","orcid":"","institution":"PRIMA SARL Laboratory","correspondingAuthor":false,"prefix":"","firstName":"Stéphanie","middleName":"","lastName":"ZIBI","suffix":""},{"id":496025907,"identity":"a429c984-3882-4927-a3d6-6e38f97611c0","order_by":5,"name":"Manuela BETALA","email":"","orcid":"","institution":"PRIMA SARL Laboratory","correspondingAuthor":false,"prefix":"","firstName":"Manuela","middleName":"","lastName":"BETALA","suffix":""},{"id":496025909,"identity":"19581ffc-f8e2-4fc0-9387-0a509af96715","order_by":6,"name":"Jean Maximilien TANG","email":"","orcid":"","institution":"PRIMA SARL Laboratory","correspondingAuthor":false,"prefix":"","firstName":"Jean","middleName":"Maximilien","lastName":"TANG","suffix":""},{"id":496025911,"identity":"465847bc-c8f5-46ea-b0d5-fc45a162155a","order_by":7,"name":"Danielle Cécile TANG-LIKENG","email":"","orcid":"","institution":"PRIMA SARL Laboratory","correspondingAuthor":false,"prefix":"","firstName":"Danielle","middleName":"Cécile","lastName":"TANG-LIKENG","suffix":""},{"id":496025915,"identity":"36c4c8a5-7bed-4f26-b871-baf21b024355","order_by":8,"name":"Liliane MFEKEU-KUATE","email":"","orcid":"","institution":"Central Hospital of Yaoundé","correspondingAuthor":false,"prefix":"","firstName":"Liliane","middleName":"","lastName":"MFEKEU-KUATE","suffix":""},{"id":496025916,"identity":"821b0c48-c3c4-4999-a3d8-76c7da51074f","order_by":9,"name":"Vicky Jocelyne AMA-MOOR","email":"","orcid":"","institution":"University Teaching Hospital of Yaoundé, University of Yaoundé I","correspondingAuthor":false,"prefix":"","firstName":"Vicky","middleName":"Jocelyne","lastName":"AMA-MOOR","suffix":""}],"badges":[],"createdAt":"2025-06-14 19:08:13","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6895452/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6895452/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12902-026-02295-x","type":"published","date":"2026-04-30T15:57:09+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":88416818,"identity":"fdd85a80-d596-4a73-99ad-409d12a08a46","added_by":"auto","created_at":"2025-08-06 09:03:56","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":49550,"visible":true,"origin":"","legend":"\u003cp\u003eStudy of the relationship between age and serum TSH-us levels\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-6895452/v1/0ab0aab8233821eba7278670.png"},{"id":108439270,"identity":"f33f5063-8092-431e-bd02-018e35bb308e","added_by":"auto","created_at":"2026-05-04 16:18:28","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":322791,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6895452/v1/af288439-6275-4c07-80ae-587bf4684718.pdf"},{"id":88416821,"identity":"9c5a1c2c-f076-4ee9-a1f0-f3fd6ea66f68","added_by":"auto","created_at":"2025-08-06 09:03:56","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":325971,"visible":true,"origin":"","legend":"","description":"","filename":"Iodinespecificdietquestionnaire.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6895452/v1/fe3bdcf3dc78527c84f2a241.pdf"},{"id":88421281,"identity":"068677c4-6956-42b6-ba1d-06aa7010b2ef","added_by":"auto","created_at":"2025-08-06 09:27:56","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":426713,"visible":true,"origin":"","legend":"","description":"","filename":"TSHdatabase.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6895452/v1/915d08ee423187f7c49fe332.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003eTSH reference intervals in Sub-Saharan adults: A pilot study in Cameroon\u003c/p\u003e","fulltext":[{"header":"Highlights","content":"\u003cp\u003e\u0026bull; Overall, the TSH reference intervals in Cameroon were lower than the data from the manufacturer's reagent kits available in our setting.\u003c/p\u003e\u003cp\u003e\u0026bull; University-level education significantly influenced TSH levels.\u003c/p\u003e\u003cp\u003e\u0026bull; There was a 92% level of agreement between our reference intervals and the data from the American Association of Clinical Endocrinologists.\u003c/p\u003e"},{"header":"1. Introduction","content":"\u003cp\u003eThyroid hormones play crucial roles in cellular metabolism and the maintenance of homeostasis [1]. Their secretion is regulated by the anterior pituitary gland through thyrotropin, also known as thyroid-stimulating hormone (TSH) [2]. Compared with thyroid hormones, TSH, particularly ultrasensitive TSH, serves as a reliable marker for assessing thyroid gland dysfunction. It offers the highest sensitivity and specificity for diagnosing both clinical and subclinical functional disorders [3]. Furthermore, regular TSH measurement is essential for monitoring treatments for thyroid disorders, especially in cases involving secretory tumors [4]. The synthesis and levels of ultrasensitive TSH are influenced by various factors, including age, pregnancy, coexisting medical conditions, ongoing inflammatory processes, certain medications, and iodine intake [5].\u003c/p\u003e\u003cp\u003eIn the literature, the reference ranges for the serum level of ultrasensitive TSH (TSH-us) remain a topic of considerable controversy [6]. On the one hand, the methods of calculation and estimation vary across studies [7]. On the other hand, there is no established consensus on the selection criteria for the reference population [8]. The National Academy of Clinical Biochemistry (NACB) recommends determining TSH reference values within a 95% confidence interval, on the basis of a population of at least 120 healthy individuals with no personal or family history of thyroid dysfunction, no goiter, no detectable thyroid autoantibodies, and no medication use [9]. Implementing this recommendation is challenging because of the required technical resources, time, and financial costs. Consequently, most researchers refer to the joint guidelines of the International Federation of Clinical Chemistry (IFCC) and the Clinical and Laboratory Standards Institute (CLSI), which propose percentiles method to determine values at the 2.5th and 97.5th percentiles, or robust tests when the study population consists of more or fewer than 120 healthy individuals [10].\u003c/p\u003e\u003cp\u003eTo date, very few studies in Africa have focused on establishing reference values for biochemical markers, particularly ultrasensitive TSH. However, ISO 15189 mandates that each laboratory define reference intervals specific to the population being tested [11]. Given that ultrasensitive TSH is the most reliable marker for detecting changes in thyroid function, determining its reference values is essential. In many countries, including Cameroon, biologists often rely on reference values provided by autoanalyzer manufacturers rather than locally established data [12,13]. Therefore, this study aimed to determine the reference intervals for serum TSH levels in Cameroonian adults aged 18 to 65 years.\u003c/p\u003e"},{"header":"2. Materials and methods","content":"\u003cp\u003e\u003cem\u003eType and population of study\u003c/em\u003e\u003c/p\u003e\u003cp\u003eWe conducted a cross-sectional study on Cameroonian adults of both sexes and without comorbidities residing in Yaound\u0026eacute;, aged 18 to 65 years. The study period spanned from November 2019 to August 2020. A total of 292 individuals in apparent good health were selected on the basis of clinical and biological criteria.\u003c/p\u003e\u003cp\u003e\u003cem\u003eSampling\u003c/em\u003e\u003c/p\u003e\u003cp\u003eBefore the study, we informed the population of Yaound\u0026eacute; about multiple screening campaigns that were taking place in the churches and markets. After providing informed consent, the participants were interviewed regarding chronic diseases, conditions that could influence their serum TSH levels and iodine status (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Their iodine status were evaluated by the UK dietitians iodine-specific diet questionnaire (I-FFQ). A daily iodine intake of approximately 150 mcg was required for selected participants. On the basis of this preliminary assessment, the participants were classified into two groups:\u003c/p\u003e\u003cp\u003e\u003cul\u003e\u003cli\u003e\u003cp\u003e\u003cem\u003eGroup 1 (N\u0026thinsp;=\u0026thinsp;240): Individuals with at least one comorbidity potentially affecting their serum TSH levels.\u003c/em\u003e\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003e\u003cem\u003eGroup 2 (N\u0026thinsp;=\u0026thinsp;400): Individuals without condition impacting their serum TSH levels.\u003c/em\u003e\u003c/p\u003e\u003c/li\u003e\u003c/ul\u003e\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\u003eClinical exclusion criteria\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"2\"\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\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAnamnesis\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003ePhysical examination\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAutoimmune disease\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAbdominal mass\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCancer\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAbnormal cardiac auscultation\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCardiovascular disease\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAltered mental status\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCombined oral contraceptives use\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eFever or infectious syndrome\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCurrent use of medication\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eHigh blood pressure\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDiabete mellitus\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eJaundice\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGoiter\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eNeck swelling\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGout\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eOverweight (BMI\u0026thinsp;\u0026ge;\u0026thinsp;25 Kg/m\u003csup\u003e2\u003c/sup\u003e) or Obesity (BMI\u0026thinsp;\u0026ge;\u0026thinsp;30Kg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMacroscopic hematuria\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eTremors\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHeart failure\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eTachycardia\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHeart rhythm disorders\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHistory of paraneoplastic syndrome\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHIV infection\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eExcessive iodine consumption\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLiver disease\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePalpitations\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePersonal or family history of thyroid disease\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePregnancy\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRenal insufficiency\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eWeight loss\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eMembers of Group 2 underwent biological analyses. Of the 400 people tested, 108 were excluded on the basis of biological criteria (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\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 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eBiological exclusion criteria\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"2\"\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\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eReasons for exclusion\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eDosage methods\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePositive thyroperoxydase or thyroglobulin autoantibodies\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eElectrochimiluminescence immune assay\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBlood glucose\u0026thinsp;\u0026gt;\u0026thinsp;110mg/dL\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eEnzymatic\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eALT\u0026thinsp;\u0026gt;\u0026thinsp;40IU/L\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eColorimetric enzymatic, direct selective detergent\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCRP\u0026thinsp;\u0026gt;\u0026thinsp;0.6/dL\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eEstimated from CKD-EPI formula\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGFR\u0026thinsp;\u0026lt;\u0026thinsp;60ml/min/1.73m\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eImmunoturbidimetry\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHDL-cholesterol\u0026thinsp;\u0026lt;\u0026thinsp;0.34/L\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eEnzymatic, colorimetric End point (CHOD-PAP 2th Generation)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLDL cholesterol\u0026thinsp;\u0026gt;\u0026thinsp;1.0g/L\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eEnzymatic, colorimetric end point (GPO-PAP 4th Generation)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSerum creatinine\u0026thinsp;\u0026gt;\u0026thinsp;1.30 mg/dL\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eColorimetric Kinetic (Jaffe\u0026rsquo;s Method).\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSerum uric acid\u0026thinsp;\u0026gt;\u0026thinsp;70mg/L in males or \u0026gt;\u0026thinsp;60mg/L in females\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eColorimetric enzymatic, direct selective detergent\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTotal cholesterol\u0026thinsp;\u0026gt;\u0026thinsp;2.5g/L\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eSpectrophotometry/immunoturbidimetry\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTriglyceridemia\u0026thinsp;\u0026gt;\u0026thinsp;1.5g/L\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eColorimetric enzymatic UV\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePositive AgHbs\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eRapid test by Determine\u0026reg;\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePositive AcHCV\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eRapid test by Determine\u0026reg;\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"2\"\u003eCHOD-PAP : cholest\u0026eacute;rol Oxydase - Peroxydase ; GPO-PAP: glycerol phosphatase-peroxydase\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eThe remaining 292 individuals formed Group 3 and were considered the reference population.These participants were normal euthyroid volunteers, as determined by the following characteristics established by the National Academy of Clinical Biochemistry: (1) no detectable levels of thyroid autoantibodies, anti-thyroid peroxidase antibodies (TPOAbs), or anti-thyroglobulin antibodies (TgAbs), as measured by sensitive immunoassays; (2) no personal or family history of thyroid dysfunction; (3) no visible or palpable goiter; and (4) no use of medications (except estrogen). Additionally, they had no other biochemical disorders (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003cem\u003eSample collection procedure\u003c/em\u003e\u003c/p\u003e\u003cp\u003eFor the assays, blood samples were collected from participants who had fasted for a minimum of 12 hours and a maximum of 16 hours. Following a 15-minute rest period, 5 mL of venous blood was drawn from a superficial vein at the elbow crease, with rigorous asepsis measures observed. The blood was placed in a tube with a gel separator and transported in secure transport bags to the PRIMA Sarl laboratory. The samples were subsequently centrifuged at 3,000 rpm for 10 minutes before analysis [14].\u003c/p\u003e\u003cp\u003e\u003cem\u003eTSH assay method\u003c/em\u003e\u003c/p\u003e\u003cp\u003eSerum TSH levels were estimated via electrochemiluminescence immunoassay (ECLIA) using a Cobas\u0026reg; 6000 analyzer (Roche Diagnostics, France, 2020). This fully automated method has a detection limit of 0.03 mIU/L. [15].\u003c/p\u003e\u003cp\u003e\u003cem\u003eVariables and statistical analysis\u003c/em\u003e\u003c/p\u003e\u003cp\u003eIn the reference population, we assessed socio-demographic parameters, including age, sex, level of education, area of residence, and ethnic cultural habits, as well as body mass index (BMI), calculated as weight divided by height squared, and serum uric acid (SUA) levels.\u003c/p\u003e\u003cp\u003eThe collected data were compiled into a database via Excel 2013 and analyzed via SPSS version 26 and STATA 15. TSH values were summarized using the median and interquartile range. Boxplots and the Grubbs test were employed to identify and exclude outliers. Age, sex, education level, ethnicity, and place of residence were reported in numbers and frequencies. Differences in TSH medians across categorical variables were assessed via either the Mann-Whitney test or the Kruskal-Wallis test, depending on the number of classes. Reference intervals were set at the 2.5th percentile (lower limit of normal) and 97.5th percentile (upper limit of normal), following CLSI and IFCC guidelines [9,10]. Logistic regression was used to examine the influence of age, sex, ethnicity, education level, and place of residence on TSH values. Spearman\u0026rsquo;s correlation test was used to evaluate the relationship between age and TSH levels, represented graphically in a scatter plot. A p-value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant.\u003c/p\u003e\u003cp\u003e\u003cem\u003eQuality control\u003c/em\u003e\u003c/p\u003e\u003cp\u003eWe ensured quality control by conducting external quality assessments (EQA) by the Laboratory Quality Assurance (ASQUALAB) and internal quality controls (CIQ-CIL). Strict precautions were applied during preanalytical, analytical, and postanalytical phases to ensure the reliability of the tests.\u003c/p\u003e"},{"header":"3. Results","content":"\u003cp\u003eOf the 292 individuals in the reference population, 185 were women and 107 were men, resulting in a sex ratio of 0.60. The mean age was 31.51 years with confidence interval of 30.29 to 32.74 years old. The age group of 25 to 40 years was the most prevalent (46.6%). A vast majority of the participants resided in urban areas (99.3%), and most held a university-level education (66.1%).\u003c/p\u003e\u003cp\u003eIn overall, the median serum TSH-us level was 1.14 with confidence interval of 0.69 to 1.69 mIU/L, with range of 0.11 to 3.85 mIU/L. There was a significant difference about median serum TSH-us levels based on education level (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.005). Neither sex, ethnic origin nor place of residence did not significantly affect serum TSH-us levels.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eComparisons in median TSH-us according to sociodemographic characteristics\u003c/p\u003e\u003c/div\u003e\u003c/caption\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=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVariables\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eFrequencies (T\u0026thinsp;=\u0026thinsp;292)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003ePercentages (%)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eMedians of TSH-us [IIQ]* in mIU/L\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003ep-value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e\u003cp\u003eSex\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFemale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e185\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e63.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1.29 [0.89\u0026ndash;1.76]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e\u003cem\u003e0.224\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e107\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e36.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1.12 [0.63\u0026ndash;1.60]\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e\u003cp\u003eLevels of education\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eUniversity\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e193\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e66.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1.25 [0.82\u0026ndash;1.75]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e\u003cb\u003e0.005\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eOthers**\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e99\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e33.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.96 [0.63\u0026ndash;1.48]\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e\u003cp\u003ePlace of residence\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eUrban\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e290\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e99.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.98 [0.66\u0026ndash;1.30]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e\u003cem\u003e0.633\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRural\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1.14 [0.69\u0026ndash;1.70]\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e\u003cp\u003eEthnic groups\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBantu\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e122\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e41.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1.12 [0.66\u0026ndash;1.67]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003e\u003cem\u003e0.138\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSemi-Bantu\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e139\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e47.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1.19 [0.82\u0026ndash;1.73]\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSudanese\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e31\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e10.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1.07 [0.65\u0026ndash;1.54]\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"5\"\u003e*=Interquartile range ; **=Never attended, primary, secondary education levels\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eConcerning the relationship between age and TSH-us levels, there was no significant correlation with \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.112 and Spearman coefficient of -0.08 (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). There was also no significant association between BMI and TSH-us levels in the reference population.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eOverall, the reference interval for serum TSH-us levels was ranged from 0.25 to 2.94 mIU/L. This reference range was moderately in agreement with data from the US National Academy of Clinical Biochemistry (k\u0026thinsp;=\u0026thinsp;58.8%) and strongly concordance with the guidelines of American Association of Clinical Endocrinologists (k\u0026thinsp;=\u0026thinsp;92.0%). After multivariate analysis, level of education remained an independent factor influencing TSH levels. People with a university education had significantly higher TSH-us values than those with lower level of education (0.25 to 2.66 mIU/L vs 0.16 to 2.39 mIU/L).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eTSH-us reference intervals and degrees of agreement with learned societies\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"6\"\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=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVariables\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eLower limit of normal\u003c/p\u003e\u003cp\u003e(95% CI)\u003c/p\u003e\u003cp\u003ein mIU/L\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eUpper limit of normal\u003c/p\u003e\u003cp\u003e(95% CI)\u003c/p\u003e\u003cp\u003ein mIU/L\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003e50th percentile\u003c/p\u003e\u003cp\u003e(95% CI)\u003c/p\u003e\u003cp\u003ein mIU/L\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eNACB* TSH RI\u003c/p\u003e\u003cp\u003ein mIU/L\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003eAACE** TSH RI\u003c/p\u003e\u003cp\u003ein mIU/L*\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003eOverall\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003e0.25 (0.18\u0026ndash;0.33)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003e2.94 (2.59\u0026ndash;3.55)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003e1.14 (1.07\u0026ndash;1.27)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.4 to 2.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.2 to 3\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003ep\u0026thinsp;\u0026lt;\u0026thinsp;0.0001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u003cb\u003ep\u0026thinsp;\u0026lt;\u0026thinsp;00001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003ek\u0026thinsp;=\u0026thinsp;58.8%\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u003cb\u003ek\u0026thinsp;=\u0026thinsp;92.0%\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"6\" nameend=\"c6\" namest=\"c1\"\u003e\u003cp\u003eLevel of education\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eUniversity\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.25 (0.18\u0026ndash;0.34)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3.13 (2.65\u0026ndash;3.72)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1.25 (1.12\u0026ndash;1.38)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003csup\u003e\u0026minus;(NA)\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e-\u003csup\u003eNA\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSecondary or less\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.16 (0.11\u0026ndash;0.34)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2.56 (2.33\u0026ndash;2.62)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.96 (0.81\u0026ndash;1.14)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e-\u003csup\u003eNA\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e-\u003csup\u003eNA\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"6\"\u003e*=National Academy of Clinical Biochemistry; **= American Association of Clinical Endocrinologists ; RI\u0026thinsp;=\u0026thinsp;Reference interval\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"6\"\u003e-\u003csup\u003eNA\u003c/sup\u003e= Not applicable, the above learned societies have no data available in this category ; k\u0026thinsp;=\u0026thinsp;Cohen's kappa coefficient\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e"},{"header":"4. Discussion","content":"\u003cp\u003eThyroid hormone assay techniques have evolved significantly over the years, transitioning from radioimmunological methods to immunometric approaches. These advancements have increased both sensitivity and specificity, leading to periodic adjustments in the upper and lower limits of normal [16]. The International Federation of Clinical Chemistry (IFCC) and the US National Academy of Clinical Biochemistry (NACB) recommend that each laboratory establish its TSH reference ranges using a reference population of at least 120 euthyroid volunteers [9,10]. These individuals must undergo rigorous screening to exclude thyroid autoimmunity, personal or family history of thyroid disorders, the presence of a visible or palpable goiter, and the use of medications except estrogen [17].\u003c/p\u003e\u003cp\u003eFew studies in sub-Saharan Africa have focused on establishing reference intervals for TSH values. To date, no research on this subject has been leaded in Cameroon. To contribute to the African medical literature, this study aimed to determine reference values for serum TSH levels in Cameroonian adults. The study followed a cross-sectional design and included adults aged 18 to 65 years, residing in Yaound\u0026eacute;, of both sexes, and without comorbidities.\u003c/p\u003e\u003cp\u003eThe reference intervals for serum TSH-us levels ranged from 0.25 to 2.94 mIU/L, with a median of 1.14 mIU/L. These results are strongly aligned with data from American Association of Clinical Endocrinologists (AACE), which established reference ranges between 0.3 and 3 mIU/L [18]. However, our reference intervals are moderately consistent with those of the US NACB. Furthermore, the NACB advocated lowering the upper limit of normal to 2.5 mIU/L [17]. The slight difference between the AACE and NACB studies could be attributed to the greater ethnic diversity of the AACE study population. Additionally, the AACE study included a higher percentage of Black Americans compared to the NACB study. Nevertheless, our selection criteria were more stringent to minimize the risk of overlooking occult thyroid pathology among participants according to criteria of the US NACB.\u003c/p\u003e\u003cp\u003eBased on the findings of the Third National Health and Nutrition Examination Survey (NHANES III), the American Thyroid Association (ATA) established an overall reference range of 0.45 to 4.12 mIU/L for the United States and non-iodine-deficient regions [19]. This study examined TSH reference ranges in a large, multiracial U.S. population [20]. The median TSH level of 1.18 mIU/L in Black participants was similar to the overall median in this study. Furthermore, the NHANES III study revealed a significantly lower median TSH level in Black American participants than in White (1.45 mIU/L) and Mexican (1.37 mIU/L) participants. Additionally, 80% of Black participants had a lower limit of normal TSH below 0.4 mIU/L and an upper limit of normal TSH below 4.5 mIU/L [20, 21]. Currently, there are no available data on reference intervals in the African literature for comparison with our results.\u003c/p\u003e\u003cp\u003eNeither sex nor ethnic origin significantly influenced serum TSH levels, contrast with earlier studies that reported significantly higher TSH levels in women than in men [20,22]. However, a recent study revealed no statistically significant difference in TSH reference intervals between men and women [23]. Their male-to-female ratio was 0.9, which is comparable to that found in our study. However, older publications reported more balanced gender distributions.\u003c/p\u003e\u003cp\u003eRegarding the relationship between age and TSH levels, this study did not observe a significant correlation between participant age and serum TSH levels, which contradicts previous literature findings [24]. This result may be due to the large number of participants in the 20\u0026ndash;40 age group, which accounted for nearly half of all participants. In this age group, TSH values may not vary much. On the other hand, educational level significantly influenced TSH levels. However, this relationship has not been explored in prior studies. Given the statistical significance of these findings, further research in this area is warranted [25].\u003c/p\u003e\u003cp\u003eThis study has two major strengths. First, it is the first study conducted in Central Africa aimed at establishing a TSH reference interval. Second, the electrochemiluminescence method used to determine thyroid hormone levels aligns with NACB guidelines, making it a superior reference technique compared to radioimmunoassays. Most available reference interval studies and manufacturers use radioimmunoassay measurements. However, according to IFCC and NACB standards, these measurements do not provide sufficiently low detection thresholds.\u003c/p\u003e\u003cp\u003eThis study has a few limitations. Instead of measuring ioduria, we assessed participants\u0026rsquo; iodine status using an iodine specific diet questionnaire. We did not measure ioduria because the volunteers did not agree to come to the lab for a 24-hour urine collection. However, the World Health Organization, the UK Dietitians Association, and the Norwegian Food Council recommend diet-specific questionnaires as an effective alternative for quantifying iodine intake status when urine iodine levels cannot be assessed; these questionnaires have a strong correlation with ioduria [26, 27]. Recently, \u003cem\u003eTanticharoenkarn et al.\u003c/em\u003e found that iodine status did not significantly affect TSH reference intervals. Additionally, \u003cem\u003eLi et al.\u003c/em\u003e demonstrated that an iodine-specific diet sheet is an effective method for evaluating iodine nutritional status in adults [28]. On the other hand, we could not perform a thyroid ultrasound to detect hypoechogenicity due to participant noncompliance with the radiology appointment. However, according to NACB guidelines adopted by the IFCC, thyroid ultrasounds are not recognized as a selection criterion for establishing TSH reference intervals [16\u0026ndash;18]. Furthermore, according to the literature, thyroid ultrasounds do not significantly affect TSH reference ranges when thyroid antibodies are negative [23, 29].\u003c/p\u003e"},{"header":"5. Conclusion","content":"\u003cp\u003eThe TSH reference intervals from this pilot study in sub-Saharan Africa aligned closely with the American Association of Clinical Endocrinologists' data and moderately with the National Academy of Clinical Biochemistry's. Our findings are similar to the TSH reference intervals of Black Americans in the NHANES III study. We recommend conducting a larger cohort study on TSH reference intervals in sub-Saharan Africa to compare these results with those of the present study.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll the authors declare that they have no competing interests for this research.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical Approval\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was approved by the Public Health Regional Center at N\u0026deg;CE/2112/CRERSHC/2020 and the Research Ethics Committee of the Faculty of Medicine and Biomedical Sciences at the University of Yaound\u0026eacute; I at N\u0026deg;276/UYI/FMSB/VDRC/DASSR/CDS, according to the Helsinki and Nuremberg declarations. All volunteers provided written informed consent to participate in the study before their inclusion and sampling.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for Publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn accordance with the guidelines of ISO 15189, all data were collected in biomedical laboratories, except those containing personal information of patients, which could be used for scientific research.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of Data\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll datasets from the current study are available via a request to the corresponding author.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eConception: SFMM, DCT, LMK, VJA-M.\u003c/p\u003e\n\u003cp\u003eDesign: MNYM, BEEE, NNA, RN, SZ, LMK, VJA-M.\u003c/p\u003e\n\u003cp\u003eData collection: JMT, SZ, MB, DCT.\u003c/p\u003e\n\u003cp\u003eLaboratory analysis: BEEE, SZ, MB, DCT, VJA-M.\u003c/p\u003e\n\u003cp\u003eStatistical analysis: SFMM, NNA, MNYM, LMK.\u003c/p\u003e\n\u003cp\u003eData interpretation: SFMM, SZ, NNA, MNYM, DCT, VJA-M.\u003c/p\u003e\n\u003cp\u003eSupervision: SZ, BEEE, DCT, LMK, VJA-M\u003c/p\u003e\n\u003cp\u003eValidation: BEEE, SZ,\u0026nbsp;LMK, VJA-M\u003c/p\u003e\n\u003cp\u003eManuscript drafting: SFMM, MNYM, NNA, MB, DCT, BEEE.\u003c/p\u003e\n\u003cp\u003eManuscript review: SFMM, NNA, MB, BEEE, SZ, JMT, DCT, LMK, VJA-M.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAccepted the final version of the manuscript\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors have approved and validated the final version of the manuscript submitted.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe would like to thank all the volunteers, lab technicians, and supervisors who gave their consent to take part in this study.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eBrent GA. Mechanisms of thyroid hormone action. J Clin Invest. 2012; 122(9):3035-43.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eCheng SY, Leonard JL, Davis PJ. Molecular aspects of thyroid hormone actions. Endocr Rev. 2010, 31(2):139\u0026thinsp;\u0026minus;\u0026thinsp;70.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLaurberg P, Andersen S, Carl\u0026eacute; A, Karmisholt J, Knudsen N, Pedersen IB. The TSH upper reference limit: where are we at? Nat Rev Endocrinol. 2011; 7(4):232-9.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eCho JW, Lee Y, Lee YH, Hong SJ, Yoon JH. Dynamic risk stratification system in post-lobectomy low-risk and intermediate-risk papillary thyroid carcinoma patients. Clin Endocrinol (Oxford). 2018; 89(1):100-9.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eTaylor PN, Razvi S, Pearce SH, Dayan CM. A review of the clinical consequences of variation in thyroid function within the reference range. 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Clin Endocrinol. 2003; 58(2):138\u0026thinsp;\u0026minus;\u0026thinsp;40.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eNational Academy of Clinical Biochemistry NACB laboratory medicine practice guidelines. Available on www.nacb.org/lmpg/main.stm\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBaskin HJ, Cobin RH, Duick DS, Hennessey JV, Klein I, Mechanick JI et al. American Association of Clinical Endocrinologists medical guidelines for clinical practice for the evaluation and treatment of hyperthyroidism and hypothyroidism. Endocr Pract. 2002;8(6):457\u0026ndash;469\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eGarber JR, Cobin RH, et al. Clinical Practice Guidelines for Hypothyroidism in Adults: Cosponsored by the American Association of Clinical Endocrinologists and the American Thyroid Association, Thyroid. Endocr Pract. 2012; 18(6):988\u0026ndash;1028.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHollowell JG, Normann SW, \u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eFlanders WD, Hannon\u003c/span\u003e WH, \u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eGunter\u003c/span\u003e WE, \u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eSpencer\u003c/span\u003e CA et al. Serum TSH, T4, and Thyroid Antibodies in the United States Population (1988 to 1994): National Health and Nutrition Examination Survey (NHANES III). J Clin Endocrinol Metab. 2002; 87(2):489\u0026thinsp;\u0026minus;\u0026thinsp;99.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKratzsch J, Fiedler GM, Leichtle A, Br\u0026uuml;gel M, Buchbinder S, Otto L et al. New Reference Intervals for Thyrotropin and Thyroid Hormones Based on National Academy of Clinical Biochemistry Criteria and Regular Ultrasonography of the Thyroid. Endocrinology and Metabolism. Clin Chem. 2005; 51:8 1480-6.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHickman PE, Koerbin G, Simpson A, Potter JM, Hughes DG, Abhayaratna WP, et al. Using a thyroid disease-free population to define the reference interval for TSH and free T4 on the Abbott Architect analyser. Clin Endocrinol. 2017; 86(1):108\u0026thinsp;\u0026minus;\u0026thinsp;12.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eTanticharoenkarn S, Pipatnavakij P, Piyasuwanying L, Srichomkwan P, Snabboon T, Ganokroj P. Reference interval of thyroid hormones in individuals with negative thyroid autoantibodies and normal thyroid ultrasound by age and gender. eJIFCC. 2025; 36(2):154\u0026thinsp;\u0026minus;\u0026thinsp;64.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLu Y, Zhang WX, Li DH, Wei LH, Zhang YJ, Shi FN, et al. Thyroid Hormone Reference Intervals among Healthy Individuals In Lanzhou, China. Endocrinol Metab. 2023; 38(3):347\u0026thinsp;\u0026minus;\u0026thinsp;56.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eXing D, Liu D, Li R, Zhou Q, Xu J. Factors influencing the reference interval of thyroid-stimulating hormone in healthy adults: A systematic review and metaanalysis. Clin Endocrinol. 2021; 95(3):378\u0026ndash;389.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eN\u0026aelig;ss S, Aakre I, Kjellevold M, Dahl L, Nerhus I, Midtbo LK et. Validation and reproducibility of a new iodine specific food frequency questionnaire for assessing iodine intake in Norwegian pregnant women. Nutrition Journal. 2019; 18:62\u0026ndash;74.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAbuduwaili G, Huang J, Ma Y and Sun H. Adult dietary patterns and their association with iodine nutrition levels and thyroid function: a cross-sectional study. Public Health Nutrition. 2025; 28(4):1\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLi S, Guo W, Tan L, Fan L, Zhu M, Wei H et al. The simplified iodine-specific food frequency questionnaire can evaluate iodine intake in Chinese adults. Nutrition Research. 2023; 109(2023):47\u0026ndash;57.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eTam AA, Kaya C, \u0026Uuml;\u0026ccedil;ler R, Diriko\u0026ccedil; A, Ersoy R, \u0026Ccedil;akır B. Correlation of normal thyroid ultrasonography with thyroid tests. Quant Imaging Med Surg. 2015; 5(4):569\u0026thinsp;\u0026minus;\u0026thinsp;74.\u003c/span\u003e\u003c/li\u003e\u003c/ol\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":"Reference intervals, TSH, Sub-Saharan Africa","lastPublishedDoi":"10.21203/rs.3.rs-6895452/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6895452/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eIntroduction: \u003c/strong\u003eThyroid disorders are widespread across Africa, with iodine deficiency disorders being the most prevalent subtype. In many African countries, access to diagnostic tools and medical expertise is limited, and reference intervals appropriate for the African population are lacking. Thyroid-stimulating hormone (TSH) is the primary marker used to diagnose thyroid dysfunction; however, reference values for TSH remain undefined in sub-Saharan Africa. This study aimed to establish reference ranges for serum uric acid and TSH levels in adults residing in Yaoundé.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMaterials and Methods: \u003c/strong\u003eFrom November 2019 to June 2020, we conducted a cross-sectional study of 292 individuals aged 18 to 65 years. The assays were performed on a Cobas 6000® machine. Using Stata 15 and SPSS 26, we determined the upper and lower limits of normal at the 2.5th and 97.5th percentiles, respectively. We assessed the effects of sex, age, ethnicity, and educational level.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults: \u003c/strong\u003eThe mean age of the 292 volunteers was 31.51 years, with a sex ratio of 1.7 females to males. The majority had a university degree (66.1%). The overall TSH reference range was 0.2 to 2.9 mIU/L, which was consistent with the American Association of Clinical Endocrinologists ranging from 92% of the time. TSH values were significantly influenced by university education (p = 0.005), with a specific reference interval of 0.25 to 3.13 mIU/L.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion: \u003c/strong\u003eOur results are broadly in line with those of American learned societies. These results could be used in routine practice by African practitioners based on clinical features and could serve as a pilot study for other sub-Saharan countries.\u003c/p\u003e","manuscriptTitle":"TSH reference intervals in Sub-Saharan adults: A pilot study in Cameroon","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-08-06 09:03:51","doi":"10.21203/rs.3.rs-6895452/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-10-28T06:58:11+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-10-10T10:50:52+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"270569801652049404218083692517750019991","date":"2025-10-08T08:40:31+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-08-27T18:17:18+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"323413355937103039983088001368794939558","date":"2025-08-19T17:53:07+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-08-05T01:51:06+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-07-01T10:35:16+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-06-30T14:44:54+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Endocrine Disorders","date":"2025-06-30T14:42:23+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":"358853bf-3d88-4195-b6dc-cff0ce89ae13","owner":[],"postedDate":"August 6th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2026-05-04T16:18:24+00:00","versionOfRecord":{"articleIdentity":"rs-6895452","link":"https://doi.org/10.1186/s12902-026-02295-x","journal":{"identity":"bmc-endocrine-disorders","isVorOnly":false,"title":"BMC Endocrine Disorders"},"publishedOn":"2026-04-30 15:57:09","publishedOnDateReadable":"April 30th, 2026"},"versionCreatedAt":"2025-08-06 09:03:51","video":"","vorDoi":"10.1186/s12902-026-02295-x","vorDoiUrl":"https://doi.org/10.1186/s12902-026-02295-x","workflowStages":[]},"version":"v1","identity":"rs-6895452","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6895452","identity":"rs-6895452","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}