Subclinical hypothyroidism (SCH) is a biochemical condition defined by elevated serum thyroid-stimulating hormone (TSH) levels with normal free thyroxine (FT4) and free triiodothyronine (FT3) levels. It is one of the most common thyroid disorders, particularly affecting older adults and females. The prevalence of SCH varies significantly across populations, ranging from 1% to 11% globally, with higher rates observed in individuals over the age of 60. Women are disproportionately affected, with prevalence rates reaching up to 22% in postmenopausal females [1,2].

Thyroid hormones play a crucial role in regulating metabolism, cardiovascular function, and glucose homeostasis. Even mild thyroid dysfunction, such as SCH, has been associated with metabolic disturbances, including insulin resistance, dyslipidemia, and endothelial dysfunction [3,4]. These metabolic alterations can have significant implications for patients with type 2 diabetes mellitus (T2DM) and hypertension (HTN), two of the most prevalent chronic diseases worldwide [5].

The relationship between SCH and T2DM is complex and bidirectional. On one hand, T2DM may alter thyroid function through mechanisms such as insulin resistance and chronic hyperglycemia, which can affect TSH secretion and peripheral thyroid hormone metabolism [6]. On the other hand, SCH may worsen glycemic control by impairing insulin sensitivity and lipid metabolism, thereby increasing the risk of diabetes-related complications [7,8].

Similarly, SCH has been implicated in the pathogenesis of hypertension. Thyroid dysfunction can lead to increased systemic vascular resistance, arterial stiffness, and dysregulation of the renin-angiotensin-aldosterone system, all of which contribute to elevated blood pressure [9]. Patients with SCH have been found to have a higher prevalence of hypertension and cardiovascular morbidity compared to euthyroid individuals [10].

Despite the growing body of evidence linking SCH to metabolic and cardiovascular disorders, data on its prevalence and impact in rural populations remain limited. In resource-limited settings, endocrine disorders such as SCH often go undiagnosed due to a lack of routine screening and limited healthcare accessibility. The epidemiology of SCH in rural India may differ significantly from urban populations due to variations in lifestyle, dietary habits, genetic predisposition, and healthcare-seeking behavior [11,12].

This study aims to address this gap by investigating the prevalence of SCH in patients with T2DM and HTN attending a tertiary care hospital in rural North India. Additionally, we seek to evaluate the association of SCH with obesity and age, providing a better understanding of its metabolic and cardiovascular implications in this specific demographic.

Study Design and Population: This cross-sectional study was conducted over 18 months at FH Medical College and Hospital in rural North India. The study included 460 participants, categorized into four groups: T2DM (n=105), HTN (n=101), T2DM + HTN (n=104), and healthy controls (n=150).

Inclusion Criteria:

• Patients diagnosed with T2DM and/or HTN as per standard guidelines.
• Age ≥18 years.
• Participants willing to provide informed consent.

Exclusion Criteria:

• History of thyroid disorders or medications affecting thyroid function.
• Acute illness affecting thyroid hormone status.
• Patients with malignancies or recent history of cancer treatment.

Data Collection and Laboratory Investigations: Demographic and clinical details, including age, sex, BMI, blood pressure, and glycemic markers (fasting plasma glucose [FPG], postprandial glucose [PPG], HbA1c), were recorded. Thyroid function tests (TSH, FT4, FT3) were measured using chemiluminescent microparticle immunoassay (CMIA). SCH was defined as TSH >4.2 mIU/L with normal FT4 levels.

Statistical Analysis: Data were analyzed using SPSS version 20. Continuous variables were expressed as mean ± SD and compared using the Student’s t-test. Categorical variables were analyzed using the Chi-square test. Logistic regression was used to determine the association between SCH and clinical parameters. A p-value <0.05 was considered statistically significant

Table 1: Demographic and Anthropometric Characteristics of Study Participants

This table presents the demographic distribution of the study population. The mean age was significantly higher in the T2DM + HTN group (p<0.001). BMI was significantly elevated in the hypertensive and diabetic groups, with the highest mean BMI observed in the T2DM + HTN group (26.91 ± 4.41 kg/m²) compared to the control group (24.89 ± 4.56 kg/m²) (p = 0.0005). Waist circumference also showed a statistically significant difference among groups (p = 0.04), with the highest mean values in the T2DM + HTN group.

Table 2: Thyroid Function Test Distribution among Study Groups

The prevalence of SCH was significantly higher in the T2DM group (20%), followed by T2DM + HTN group(15.38%) and HTN group(14.85%) , compared to controls (p=0.005). Overt hypothyroidism was also more frequent in patients with T2DM(14.29%) , followed by T2DM + HTN group(12.50%) and HTN group(11.88%) (p=0.002).

In the present study, a total number of 460 participants were included and categorised into four groups, viz T2DM group (T2DM, n=105) HTN group (HTN, n=101),T2DM+HTN group (T2DM+HTN, n=104) and Control group (Control, n=150)

In the present study, out of 460 patients 255 (55.43%) were female and 205 (44.57%) were male patients. In contrast, Fakhroo et al., (2023) and others [13, 14,15] also reported similar patterns of female predominance.

The present study also demonstrated that the T2DM group had a nearly equal gender distribution, with a slightly higher prevalence among males (52.38%) while HTN group (53.47%), T2DM+HTN group (52.88%) and Control group (64%) showed female preponderance which align with the findings of Peng C, et al. and others[16 ,17]who also found a higher female preponderance.

In T2DM group, the mean age of participants were 49.7 ± 12.05 years. Fakhroo A, et al. and others [13,18,19,20]reported a slightly higher mean age (above 50) as compared with our study . These variations in age across the studies could be attributed due to differences in sample populations, regional influences and study methodologies. Therefore, the suspicion of SCH in T2DM should be made at a much earlier age in and early interventions can be done.

In HTN group, the mean age of participants were 50.12 ± 12.46 years, while Wang X, et al., and others[21,22,17]reported a slightly lower mean age and Liu FH, et al.,[23] (2018) recorded a slightly higher mean age of 52.9 ± 11.0 years. T2DM+HTN group also showed similar mean age of 54.22 ±11.11 years.

These findings imply that there is increased risk of SCH in hypertensive and diabetic patients in 4th and 5th decade of their life. The study conducted by Javeedh S, et al. and others[19,24] also demonstrated an association between SCH and advancing age in hypertensive and diabetic patient , supporting the potential role of age as a contributing factor in the development of this condition.

In the present study, in T2DM group the mean BMI was recorded as 25.3 ± 4.18 kg/m² among 105 cases. Asuti S, et al. and others[25,18,19,26] reported similar BMI in the population. HTN group showed mean BMI of 26.88 ±4.44 kg/m² which was comparable with previous study done by Singhai A, et al., (2016).[27]T2DM+HTN group had mean BMI of 26.91 ±4.41 kg/m² indicating a trend towards overweight and obesity. These findings suggest a strong association between excess body weight and the coexistence of diabetes and hypertension (p value <0.05, Table no. 10,11,12) , reinforcing the need for targeted metabolic and cardiovascular risk assessment and  management strategies in this population. . Regular monitoring of BMI, blood pressure, and thyroid function is crucial for optimizing long-term health in this population. This was comparable with previous study done by Wang X, et al., (2021)[21]the prevalence of diabetes, BMI, and waist circumference still showed significant statistical differences (P<0.05).

In contrast, the Control group had a significantly lower prevalence of obesity (6.7%) and overweight individuals (16.7%), with a majority (70%) having a normal BMI. The difference between the Control T2DM groupnd the other groups (T2DM, Hypertension, and T2DM+Hypertension) was statistically significant (p < 0.0001, Table no. 10, 11, 12). These findings indicate a strong correlation between metabolic disorders (diabetes and hypertension), increased BMI, and the risk of thyroid dysfunction.

The parameters studied in the present study, provide a crucial foundation for understanding the metabolic profile of hypertensive and diabetic individuals and their potential association with SCH by comparing them with the metabolic profile of control group. These findings endorse the need for routine thyroid function screening in hypertensive and diabetic patients with abnormal metabolic profile to enable early detection and management of SCH, ultimately improving clinical outcomes.

• Distribution according to Thyroid function test in T2DM:

In T2DM group, 69 (65.71%) of the participants exhibited normal thyroid function, while 36 (34.29%) had abnormal thyroid profile in which 21 (58.33%) had subclinical thyroid dysfunction, and 15 (41.67%) had overt thyroid dysfunction in comparison to Control group (p value <0.05, Table 22). In comparison, the study by Asuti S, et al., (2023)[18] reported that 191 (76.4%) of patients were euthyroid, while 59 (23.6%) had thyroid dysfunction out of which 40 (67.79%) had subclinical hypothyroidism, 16 (27.11%) had overt hypothyroidism, and 3 (5.10%) had overt hyperthyroidism, with no cases of subclinical hyperthyroidism. Similarly, Sharma P, et al. and others[28,29,26] also observed similar results. The prevalence of subclinical hypothyroidism and overt hypothyroidism is comparatively higher in our study which signifies the north Indian rural population is more susceptible and underdiagnosed for the same. This can be attributed to iodine deficiency or excess iodine used in iodised salt, diet low in essential nutrients like, zinc, and iron which are important for thyroid function. Also, the consumption of foods containing goitrogens (e.g., cruciferous vegetables), lack of awareness and limited healthcare access may contribute to increase in incidence of SCH.

Distribution according to Thyroid function test in hypertension:

In HTN group (N=101), thyroid function tests revealed that the majority, 74 individuals (73.27%), had normal thyroid function. However, 27 individuals (26.73%) exhibited abnormal thyroid function in which 15 (55.56%) had subclinical hypothyroidism and 12 (44.44%) had overt hypothyroidism compared to Control group (p value <0.05, Table 23), indicating a significant prevalence of thyroid dysfunction within this group. The findings of the present study were consistent with those reported by Singhai et al. and others[27,16,30] who concluded that individuals with subclinical hypothyroidism have a higher tendency to develop hypertension compared to euthyroid individuals. These findings signify the association between hypertension and thyroid abnormalities, particularly subclinical hypothyroidism, which has been linked to increased cardiovascular risk. Routine thyroid function screening in hypertensive individuals may facilitate early identification and management of thyroid dysfunction, potentially improving overall cardiovascular outcomes.

Conversely, a larger meta-analysis conducted in 2014, which included 50,147 study participants, was unable to establish a definitive relationship between subclinical hypothyroidism and blood pressure levels by Ye et al., 2014).[31] Further, in a case-control study by González-Gil and de la Sierra (2017)[32], which examined 240 patients with subclinical hypothyroidism and 480 euthyroid controls, no significant difference in the prevalence of hypertension between the two groups was observed. These conflicting findings suggest the need for further large-scale, well-designed studies to clarify the relationship between subclinical hypothyroidism and hypertension.

In T2DM+HTN group (N=104), thyroid function tests revealed that the majority, 75 individuals (72.115%), had normal thyroid function. However, 29 individuals (27.885%) exhibited abnormal thyroid function in which 16 (55.172%) had subclinical hypothyroidism and 13 (44.828%) had overt hypothyroidism compared to Control group (p value <0.05, Table 24), indicating a significant prevalence of thyroid dysfunction within this T2DM groupnd a synergistic effect of T2DM and HTN on the prevalence of SCH.

We also compared the thyroid function tests T2DM group and HTN group individuals which highlighted that the abnormal thyroid function values are more in diabetics (34.29%) than in hypertensive (26.73%) individuals. The numbers suggest that the risk of hypothyroidism is comparatively higher in Diabetic population. In T2DM, insulin resistance and components of metabolic syndrome can impact thyroid hormone metabolism and action, potentially contributing to thyroid dysfunction. Chronic low-grade inflammation, also plays role, as inflammatory cytokines can interfere with thyroid hormone synthesis and metabolism, increasing the risk of hypothyroidism. Insulin resistance in T2DM disrupts glucose metabolism and impairs thyroid function through altered deiodinase activity, reducing T3 levels while increasing reverse T3 (rT3). Metabolic syndrome components, including central obesity, dyslipidemia and hyperglycemia, exacerbate thyroid hormone dysregulation via leptin-mediated suppression of the hypothalamic-pituitary-thyroid axis and impaired peripheral thyroid hormone conversion. Chronic low-grade inflammation in T2DM further compromises thyroid function. Pro-inflammatory cytokines such as TNF-α, IL-6, and IFN-γ inhibit thyroid peroxidase activity, impair iodine uptake, and alter deiodinase-mediated thyroid hormone metabolism, leading to increased rT3 and reduced T3 levels. Heightened type 3 deiodinase (D3) activity exacerbates this imbalance, contributing to subclinical or overt hypothyroidism.

This association between insulin resistance, metabolic syndrome and inflammation emphasized that, the need for routine thyroid function assessment in T2DM and hypertensive patients to allow early intervention and reduce adverse metabolic outcomes.

Also, after comparing T2DM group and T2DM+HTN group, the abnormal thyroid values were 34.29% and 27.885% respectively. When HTN group and T2DM+HTN group were compared, the abnormal thyroid values were 26.73% and 27.885%, which show marginally the latter one has increased risk of developing hypothyroidism.

While previous studies have established an increased prevalence of thyroid dysfunction in both diabetes and hypertension, while our study shows that diabetes causes a higher risk of hypothyroidism compared to hypertensive patients.

The present study showed that, the significant prevalence of SCH among patients with T2DM and HTN in a rural North Indian setting, emphasizing the strong association between metabolic disorders and thyroid dysfunction. Our findings revealed, a higher prevalence of SCH in diabetics (34.29%) compared to hypertensive individuals (26.73%), suggesting that, diabetes may be a stronger contributor to thyroid dysfunction than hypertension. Additionally, obesity emerged as a key factor influencing SCH, with a notably higher prevalence among patients with T2DM and/or HTN compared to the control group. The observed variations in blood pressure further reinforce the link between SCH, metabolic disturbances, and cardiovascular risk. Also, we observed that, the higher risk of SCH in diabetics and hypertensive patients, therefore routine thyroid function screening should be integrated into diabetes management, particularly for obese and uncontrolled diabetic patients. While current guidelines do not mandate universal screening for SCH in diabetics and hypertensive patients, our study emphasized that the need for a more rigorous approach to early detection and intervention to prevent complications such as insulin resistance, cardiovascular disease, and metabolic dysregulation. Consequently, routine thyroid function screening is recommended, for all patients with T2DM and hypertension, to enable early diagnosis of subclinical hypothyroidism so that timely intervention can be done in order to reduce the associated cardiovascular and metabolic complications.

1. Hollowell JG, Staehling NW, Flanders WD, et al. Serum TSH, T(4), 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):489-499.
2. Surks MI, Ortiz E, Daniels GH, et al. Subclinical thyroid disease: scientific review and guidelines for diagnosis and management. JAMA. 2004;291(2):228-238.
3. Duntas LH, Orgiazzi J, Brabant G. The interface between thyroid and diabetes mellitus. Clin Endocrinol (Oxf). 2011;75(1):1-9.
4. Hage M, Zantout MS, Azar ST. Thyroid disorders and diabetes mellitus. J Thyroid Res. 2011;2011:439463.
5. Tunbridge WM, Evered DC, Hall R, et al. The spectrum of thyroid disease in a community: The Whickham survey. Clin Endocrinol (Oxf). 1977;7(6):481-493.
6. Kim B. Thyroid hormone as a determinant of energy expenditure and the basal metabolic rate. Thyroid. 2008;18(2):141-144.
7. Chaker L, Bianco AC, Jonklaas J, Peeters RP. Hypothyroidism. Lancet. 2017;390(10101):1550-1562.
8. Anil C, Akkurt A, Ayturk S, Kut A, Gursoy A. Evaluation of altered thyroid hormone metabolism in patients with impaired glucose tolerance. Endocr J. 2010;57(8):577-581.
9. Rodondi N, Newman AB, Vittinghoff E, et al. Subclinical hypothyroidism and the risk of heart failure, other cardiovascular events, and death. Arch Intern Med. 2005;165(21):2460-2466.
10. Razvi S, Weaver JU, Butler TJ, Pearce SH. Levothyroxine treatment of subclinical hypothyroidism, fatal and nonfatal cardiovascular events, and mortality. Arch Intern Med. 2012;172(10):811-817.
11. Biondi B, Cooper DS. The clinical significance of subclinical thyroid dysfunction. Endocr Rev. 2008;29(1):76-131.
12. Garmendia Madariaga A, Santos Palacios S, Guillén-Grima F, Galofré JC. The incidence and prevalence of thyroid dysfunction in Europe: a meta-analysis. J Clin Endocrinol Metab. 2014;99(3):923-931.
13. Fakhroo A, Elhadary MR, Elsayed B, Al-Kuwari A, Aly R, Mesilhy R, Bakalaf A, Al-Maadhadi M, Al-Dehaimi AA, Chivese T, Rathnaiah Babu G. Association of subclinical hypothyroidism with type 2 diabetes mellitus in Qatar: a cross-sectional study. Diabetes Metab Syndr Obes. 2023 Oct 28;16:3373–9.
14. Veltri F, Rocha FO, Willems D, Praet JP, Grabczan L, Kleynen P, et al. Prevalence of thyroid dysfunction and autoimmunity in the older population and implications of age-specific reference ranges. Clin Chim Acta. 2017;465:34-9.
15. Mariscal Hidalgo AI, Lozano Alonso JE, Vega Alonso T; Grupo de Investigación del HipotiroidismoSubclínicoen Castilla y León. Prevalence and clinical characteristics of subclinical hypothyroidism in an opportunistic sample in the population of Castile-León (Spain). Gac Sanit. 2015;29:105-11.
16. Cai P, Peng Y, Chen Y, Li L, Chu W, Wang Y, et al. Association of thyroid function with white coat hypertension and sustained hypertension. J Clin Hypertens (Greenwich). 2019;21(5):674–83.
17. Liu D, Jiang F, Shan Z, et al. A cross-sectional survey of relationship between serum TSH level and blood pressure. J Hum Hypertens. 2010;24:134-8. doi: 10.1038/jhh.2009.44.
18. Asuti S, Purad S, Hosamani P. Pattern of thyroid dysfunction in type II diabetes mellitus patients in a tertiary care center: a cross-sectional study. J Med Sci Health. 2023;9(2):204–10.
19. Javeedh S, Vidya TA. Study of subclinical thyroid disorders in type 2 diabetes mellitus. J Evid Based Med Healthc. 2021;8(02):103–7.
20. Sharma P, Sinha R, Prasad A, Mitra JK. Lack of association between poor glycemic control in T2DM and subclinical hypothyroidism. J Thyroid Res. 2020 Sep 8;2020:8121395.
21. Wang X, Wang H, Yan L, Yang L, Xue Y, Yang J, et al. The positive association between subclinical hypothyroidism and newly diagnosed hypertension is more explicit in female individuals younger than 65. Endocrinol Metab (Seoul). 2021 Aug;36(4):778-89.
22. Zhang J, Huang C, Meng Z, Fan Y, Yang Q, Zhang W, et al. Gender-specific differences on the association of hypertension with subclinical thyroid dysfunction. Int J Endocrinol. 2019;2019:6053068.
23. Liu FH, Hwang JS, Kuo CF, Ko YS, Chen ST, Lin JD. Subclinical hypothyroidism and metabolic risk factors association: a health examination-based study in northern Taiwan. Biomed J. 2018 Feb;41(1):52-8.
24. Stott DJ, Rodondi N, Kearney PM, Ford I, Westendorp RGJ, Mooijaart SP, et al. Thyroid hormone therapy for older adults with subclinical hypothyroidism. N Engl J Med. 2017;376:2534-44.
25. Kumari M, Banait S, Salunkhe P, Jain J. Magnitude of subclinical hypothyroidism in type 2 diabetes mellitus – a hospital-based cross-sectional study. J Datta Meghe Inst Med Sci Univ. 2021 Jan-Mar;16(1):57-62
26. Furukawa S, Yamamoto S, Todo Y, Maruyama K, Miyake T, Ueda T, et al. Association between subclinical hypothyroidism and diabetic nephropathy in patients with type 2 diabetes mellitus. Endocr J. 2014;61(10):1011–8.
27. Singhai A, Gupta D. A study of systemic hypertension with subclinical hypothyroidism. Int J Med Res Health Sci. 2016;5(10):198–9.
28. Shabnam S, Mallikarjuna CR, Pinjar PM. Study of subclinical hypothyroidism among patients with type-2 diabetes mellitus. J Clin Sci Res. 2015;4:195–8.
29. Ramulu P, Rao UR, Shaik RS. A study of prevalence of subclinical hypothyroidism in patients of type 2 diabetes mellitus. Int J Contemp Med Res. 2016;3(10):3114–7.
30. VelkoskaNakova V, Krstevska B, Bosevski M, Dimitrovski C, Serafimoski V. Dyslipidaemia and hypertension in patients with subclinical hypothyroidism. Prilozi. 2009;30(2):93–102.
31. Ye Y, Xie H, Zeng Y, Zhao X, Tian Z, Zhang S. Association between subclinical hypothyroidism and blood pressure: a meta-analysis of observational studies. EndocrPract. 2014;20(2):150–8.
32. Gonzalez Gil L, de la Sierra A. Prevalence of hypertension and other cardiovascular risk factors in subjects with subclinical hypothyroidism. Med Clin (Barc). 2017;148(8):351–3.