disorder characterized by deficient production or action of the thyroid hormones thyroxine (T4) and triiodothyronine (T3), and generally requires lifelong management. Most T4 is produced by the thyroid gland, whereas only about 20% of T3 is produced directly by the gland and the remainder is formed by peripheral conversion of T4 to T3.¹⁻³ Based on the site of dysfunction, hypothyroidism is classified as primary, secondary, or tertiary, resulting from thyroid, pituitary, or hypothalamic dysfunction, respectively.³ Primary hypothyroidism accounts for approximately 99.9% of cases.⁴⁻⁵ Common causes include iodine deficiency, autoimmune thyroid disease, thyroid irradiation or surgery, congenital abnormalities, and pituitary or hypothalamic disorders. The global prevalence of hypothyroidism is estimated at 4–5% in developed countries, while subclinical hypothyroidism affects approximately 4–15% of the population.⁶⁻⁷ In iodine-replete populations, spontaneous hypothyroidism occurs in approximately 1–2% of individuals and is considerably more common among women.⁸ In India, the prevalence of hypothyroidism has been reported to be approximately 10.95%, indicating a substantial burden of disease.⁹⁻¹² Hypothyroidism often has an insidious onset, and its clinical manifestations may remain unrecognized because many symptoms are nonspecific.¹³ Common manifestations include fatigue, weight gain, cold intolerance, dry skin, hair changes, joint and muscle pain, menstrual abnormalities, and depression.²⁻³,¹⁴ Untreated hypothyroidism can affect multiple organ systems, including the cardiovascular, gastrointestinal, musculoskeletal, neurological, and dermatological systems.¹⁵⁻¹⁶ Severe untreated disease may progress to myxedema, a potentially life-threatening form of decompensated hypothyroidism.¹⁵⁻¹⁶ Thyroid function tests, particularly serum T3, T4 and thyroid-stimulating hormone (TSH), are central to the diagnosis and assessment of hypothyroidism.¹⁷ TSH is considered a sensitive marker for the early diagnosis of primary hypothyroidism, although its levels are influenced by circadian variation and other physiological factors.⁴,¹²,¹⁸⁻¹⁹ Although thyroid function tests provide an objective basis for diagnosis and management, laboratory values may occasionally show poor correlation with the clinical presentation. Physiological changes and concomitant medications may also influence test results.¹⁷ Furthermore, repeated laboratory testing may be inconvenient in a chronic condition requiring lifelong follow-up. Therefore, a reliable clinical scoring system based on signs and symptoms may provide a useful adjunct for assessing disease severity and monitoring patients. The present study was undertaken to compare thyroid function test parameters with the clinical presentation of hypothyroidism and to assess clinical severity using a validated clinical scoring system. AIM To compare thyroid function test parameters with the clinical presentation of hypothyroidism and assess clinical severity using a validated scoring system. OBJECTIVES 1. To assess the clinical manifestations and severity of hypothyroidism using a validated clinical scoring system. 2. To assess the thyroid function test parameters among patients with hypothyroidism. 3. To compare thyroid function test parameters with clinical presentation and severity of hypothyroidism.

A hospital-based cross-sectional study was conducted from September 2020 to April 2022 at A.J. Institute of Medical Sciences and Research Centre, a tertiary care hospital. The study included known cases of hypothyroidism attending the outpatient department or admitted to the inpatient wards. Patients of either sex, aged >18 years, with a diagnosis of hypothyroidism and willing to provide written informed consent were included. Patients receiving antiarrhythmic drugs such as amiodarone and those with diabetes mellitus were excluded because of the potential overlap of clinical manifestations, particularly neuropathies. The sample size was calculated based on a previous study by Bajaj S et al.³⁴, assuming a prevalence of 34.1%, 95% confidence level, and 10% absolute allowable error. The estimated sample size was 89.9, which was rounded to 90. After accounting for a 10% non-response rate, the final sample size was 99. Participants were recruited using convenience sampling. After obtaining approval from the Institutional Ethics Committee and the concerned authorities, eligible participants were approached and informed about the study using a patient information sheet. Written informed consent was obtained before enrolment. Data were collected using a predesigned semi-structured questionnaire that included socio-demographic characteristics and relevant medical history, with particular emphasis on symptoms of hypothyroidism. Vital signs, general physical examination, and systemic examination were performed and documented. Clinical severity was assessed using a pre-validated scoring system consisting of 11 symptom-based and 10 sign-based items. Each item was assigned one point, giving a total possible score ranging from 0 to 21. The symptoms assessed were cold intolerance, constipation, weight gain, poor memory, lethargy, reduced appetite, hoarseness of voice, morning somnolence, reduced sweating, paraesthesia, and behavioural changes. The clinical signs assessed were Wolffmann's sign, bradycardia, pallor, periorbital puffiness, slow movements, coarse skin, alopecia, dry hair, madarosis, and xanthelasma. Thyroid function parameters, including serum T3, T4, free T4, and thyroid-stimulating hormone (TSH), were measured using a chemical electrochemiluminescence immunoassay analyzer (Elecsys 2010). Data were entered into Microsoft Excel and analyzed using appropriate statistical methods. Categorical variables were expressed as frequencies and percentages, while quantitative variables were summarized using mean, median, mode, range, and standard deviation. The chi-square test was used to assess associations between categorical variables. Pearson's correlation test was used to assess the correlation between clinical scores and thyroid function parameters. The strength of correlation was classified as negligible (0.00 to ±0.30), low (±0.30 to ±0.50), moderate (±0.50 to ±0.70), high (±0.70 to ±0.90), and very high (±0.90 to ±1.00). A p-value <0.05 was considered statistically significant.

A total of 99 participants with hypothyroidism were included in the study. Of these, 59 (59.6%) were female and 40 (40.4%) were male. Participants were aged 15–70 years, with a mean age of 35.4 ± 19.0 years. The largest proportion belonged to the 15–30-year age group (43.4%). The mean pulse rate was 61.5 ± 10.3 beats/min, with bradycardia observed in 68.7% of participants. The mean BMI was 25.4 ± 2.97 kg/m², and 51.5% of participants were overweight. Table 1: Sociodemographic and clinical characteristics of study participants Characteristic Frequency (n) Percentage (%) Gender Male 40 40.4 Female 59 59.6 Age group (years) 15–30 43 43.4 31–45 32 32.3 46–60 18 18.2 Above 60 6 6.1 Pulse rate (beats/min) <60 68 68.7 60–100 31 31.3 Body mass index (kg/m²) 18.5–24.99 41 41.4 25–29.99 51 51.5 30–35.99 7 7.1 Mean age: 35.4 ± 19.0 years; age range: 15–70 years. Mean pulse rate: 61.5 ± 10.3 beats/min; range: 45–82 beats/min. Mean BMI: 25.4 ± 2.97 kg/m²; range: 21–32.3 kg/m². The most frequently reported symptoms were cold intolerance (79.8%), constipation (68.7%), weight gain (54.5%), and poor memory (47.5%). Among clinical signs, bradycardia was present in 68.7%, while Woltman's sign was observed in 68%. Pallor and periorbital puffiness were each present in 54.5% of participants. Table 2: Distribution of participants according to symptoms and clinical signs Symptoms and signs Frequency (n) Percentage (%) Symptoms Cold intolerance 79 79.8 Constipation 68 68.7 Weight gain 54 54.5 Poor memory 47 47.5 Lethargy 40 40.4 Reduced appetite 30 30.3 Hoarseness 30 30.3 Morning somnolence 29 29.3 Reduced sweating 22 22.2 Paraesthesia 18 18.2 Behavioral change 10 10.1 Clinical signs Woltman's sign 68 68 Bradycardia 68 68.7 Pallor 54 54.5 Periorbital puffiness 54 54.5 Slow movements 44 44.4 Coarse skin 33 33.3 Alopecia 32 32.3 Dry hair 26 26.3 Madarosis 15 15.2 Xanthelasma 6 6.1 The mean T3, T4, TSH, and free T4 concentrations were 0.71 ± 0.37 nmoles/L, 2.81 ± 0.89 µg/dl, 12.26 ± 4.85 uIU/ml, and 0.57 ± 0.97 ng/dl, respectively. All participants had low T4 and high TSH. The mean severity score was 8.35 ± 1.99, with scores ranging from 4–12. TSH showed a very strong positive correlation with the severity score (r=0.862, p=0.000), whereas correlations with T3, T4, and free T4 were very weak and non-significant. Table 3: Thyroid profile, severity scores, and correlation with clinical severity A. Thyroid profile and classification Parameter Range Mean ± SD Median Low n (%) Normal n (%) High n (%) T3 (nmoles/L) 0.12–2.00 0.71 ± 0.37 0.75 66 (66.7%) 33 (33.3%) – T4 (µg/dl) 1.07–4.32 2.81 ± 0.89 2.76 99 (100%) – – TSH (uIU/ml) 5.00–27.00 12.26 ± 4.85 11.20 – – 99 (100%) Free T4 (ng/dl) 0.12–9.8 0.57 ± 0.97 0.44 78 (78.8%) 20 (20/2%) 1 (1%) Normal ranges: T3: 0.89–2.44 nmoles/L; T4: 4.8–11.7 mcg/dl; TSH: 0.35–4.94 uIU/ml; Free T4: 0.70–1.48 ng/dl. B. Thyroid profile according to severity score Severity score T3 (nmoles/L), Mean ± SD T4 (mcg/dl), Mean ± SD TSH (uIU/ml), Mean ± SD Free T4 (ng/dl), Mean ± SD 4 0.64 ± 0.45 2.32 ± 0.31 5.05 ± 0.70 0.51 ± 0.55 5 0.76 ± 0.56 2.39 ± 0.76 6.72 ± 0.86 0.41 ± 0.33 6 0.50 ± 0.23 3.01 ± 0.93 8.18 ± 1.19 0.49 ± 0.26 7 0.60 ± 0.35 2.50 ± 0.64 8.72 ± 0.76 0.53 ± 0.23 8 0.82 ± 0.31 2.88 ± 1.07 11.09 ± 2.26 0.44 ± 0.30 9 0.81 ± 0.38 2.89 ± 0.96 12.79 ± 1.89 0.53 ± 0.27 10 0.52 ± 0.38 2.95 ± 0.77 13.88 ± 3.36 1.06 ± 2.41 11 0.80 ± 0.14 3.10 ± 0.84 20.59 ± 1.44 0.46 ± 0.20 12 0.84 ± 0.40 2.69 ± 1.09 22.52 ± 2.60 0.48 ± 0.25 C. Correlation between thyroid profile and severity score Parameter Correlation coefficient (r) p-value Interpretation T3 0.090 0.378 Very weak and non-significant T4 0.140 0.166 Very weak and non-significant TSH 0.862 0.000 Very strong and significant Free T4 0.081 0.424 Very weak and non-significant The severity scoring system ranged from 0–21; however, the observed scores in the study ranged from 4–12, with a mean score of 8.35 ± 1.99. TSH demonstrated an increasing trend with increasing severity score, whereas T3, T4, and free T4 showed variable patterns. Pearson's correlation analysis demonstrated a very strong and statistically significant correlation between severity score and TSH (r=0.862, p=0.000). In contrast, the correlations between severity score and T3 (r=0.090, p=0.378), T4 (r=0.140, p=0.166), and free T4 (r=0.081, p=0.424) were very weak and statistically non-significant.

The present study evaluated the clinical manifestations of hypothyroidism and their relationship with biochemical thyroid parameters, with the aim of developing and assessing a clinical severity scoring system. The proposed score consisted of 11 symptom-based and 10 sign-based parameters, with one point assigned to each parameter and a total possible score ranging from 0 to 21. The mean clinical severity score was 8.35 ± 1.99. The principal finding of the study was a strong positive correlation between the total clinical severity score and TSH (r = 0.862, p = 0.000), whereas the correlations with T3, T4 and free T4 were weak and non-significant. These findings suggest that systematic clinical assessment may provide useful information regarding the severity of hypothyroidism and may have potential as an adjunct to biochemical assessment. The participants in the present study were predominantly female (59.6%), with a male-to-female ratio of 1:1.5, and the mean age was 35.4 ± 19.0 years. The female predominance is consistent with previous Indian epidemiological studies. Unnikrishnan A et al. reported a significantly higher prevalence of hypothyroidism among females than males (15.86% vs. 5.02%) in an epidemiological study conducted across eight cities in India.7 In a community-based study, a higher prevalence was reported in the 45–60-year age group, while Deshmukh V et al. observed that most cases belonged to the 35–54-year age group.20 The relatively younger age distribution in the present study may be explained by its hospital-based nature and differences in the population attending the study setting. The clinical manifestations observed in the present study were variable, reflecting the well-known non-specific and insidious presentation of hypothyroidism. The most frequent symptoms were cold intolerance (79.8%), constipation (68.7%), weight gain (54.5%), poor memory (47.5%) and lethargy (40.4%). Other symptoms included reduced appetite (30.3%), hoarseness of voice (30.3%), morning somnolence (29.3%), reduced sweating (22.2%), paresthesia (18.2%) and behavioural change (10.1%). These findings are broadly comparable with previous studies. El-Shafie KT reported fatigue and constipation among the commonest symptoms of hypothyroidism.21 Savery DM et al. from Puducherry reported fatigue (83.6%), weight gain (66.7%), dry/coarse skin (52.1%) and voice change (50.7%) as common presenting complaints.22 Similarly, fatigue, weight gain and poor appetite were frequently reported in a multicentre medical record study of newly diagnosed hypothyroidism by Sethi B et al.23 and in a tertiary hospital-based study by Vairamanikandan A et al.24 Paudel K et al. reported cold intolerance and constipation as the commonest symptoms, each occurring in 58.5% of patients.25 The higher frequency of constipation in the present study is noteworthy, as this symptom was not assessed or reported consistently in several earlier studies. Among the clinical signs, the most frequent findings were bradycardia (68.7%), Woltman's sign (68%), pallor (54.5%), periorbital puffiness (54.5%) and slow movements (44.4%). Other observed signs included coarse skin (33.3%), alopecia (32.3%), dry hair (26.3%), madarosis (15.2%) and xanthelasma (6.1%). The relatively high frequency of Woltman's sign supports the importance of assessing deep tendon reflexes during clinical examination of patients with suspected hypothyroidism. Houston CS reported Woltman's sign in approximately 75% of patients with hypothyroidism.26 Furthermore, the positive predictive value of this sign has been reported to be as high as 92% in overt hypothyroidism.27 Brusseau V et al., in a meta-analysis of 17 studies involving 11,438 patients, reported significant alterations in heart rate variability in hypothyroidism, further supporting the presence of clinically detectable cardiovascular manifestations in the disease.28 Collectively, these findings emphasize that careful assessment of both symptoms and physical signs remains an important component of clinical evaluation. Clinical scoring systems are defined as algorithms designed to predict outcomes, assist decision-making, support treatment options, manage clinical risk or improve efficiency.29 An effective clinical score should ideally be simple, user-friendly, generalisable and patient-centred. The present scoring system was developed with these principles in mind and incorporated a broad range of symptoms and signs that can be assessed during routine clinical examination. Unlike approaches relying on a single clinical manifestation, the composite score attempts to capture the cumulative clinical burden of hypothyroidism. The biochemical findings demonstrated that all participants had low T4 and elevated TSH. The mean T3, T4, TSH and free T4 concentrations were 0.71 ± 0.37 nmoles/L, 2.81 ± 0.89 µg/dl, 12.26 ± 4.85 uIU/ml and 0.57 ± 0.97 ng/dl, respectively. Low T3 was observed in 66.6% of participants and low free T4 in 77.8%. With increasing clinical severity score, TSH also increased. Importantly, the total clinical severity score showed a very weak and non-significant correlation with T3 (r = 0.090), T4 (r = 0.140) and free T4 (r = 0.081), whereas a strong and statistically significant positive correlation was observed with TSH (r = 0.862, p = 0.000). This suggests that the clinical manifestations represented by the scoring system were more closely associated with variation in TSH than with circulating thyroid hormone concentrations in the study population. The strong association between the clinical score and TSH is clinically relevant because TSH is considered an important and sensitive biochemical indicator in the assessment of primary hypothyroidism. Sheehan MT et al. noted that TSH is the best, and in some circumstances the only, indicator required for assessment of thyroid function.18 In contrast, the findings of the present study differ from those reported by Zulewski H et al., whose clinical scoring system demonstrated significant correlations with free T3 (r = −0.52, P < 0.0004) and T3 (r = −0.56, P < 0.0001), but showed poor correlation with TSH.30 These differences may be related to variations in study populations, disease severity, scoring methodology and biochemical characteristics of the participants. The present findings therefore suggest that clinical scoring may reflect biochemical severity, but the relationship may not be uniform across all thyroid parameters. The strong correlation observed between the clinical score and TSH should not, however, be interpreted as evidence that the clinical score can replace biochemical testing. Rather, the score may have potential as an adjunct to biochemical assessment and as a structured method of quantifying clinical severity. This distinction is particularly important because symptoms and signs of hypothyroidism are non-specific and may overlap with several other medical conditions. Biochemical testing therefore remains essential for establishing the diagnosis and for appropriate clinical management. An important limitation of the present study is that participants had deranged thyroid profiles and a euthyroid comparison group was not included. Consequently, the ability of the score to distinguish hypothyroidism from euthyroid states could not be established. In addition, diagnostic cut-off values, sensitivity, specificity and discriminative performance of the score could not be determined. The study was also conducted in a hospital-based population, which may limit generalisability to community populations and different age groups. These limitations highlight the need for further studies involving euthyroid controls and larger, diverse populations. Despite these limitations, the proposed scoring system provides a simple framework for systematically documenting the clinical manifestations of hypothyroidism. Its potential usefulness may be greater in peripheral or resource-limited settings where access to laboratory investigations is delayed or limited. However, before clinical implementation, the score should undergo external validation across different healthcare settings and age groups, with determination of appropriate cut-off values and diagnostic accuracy. Future studies should also evaluate whether the score can predict treatment response and changes in clinical severity following normalization of thyroid function.

The clinical severity score showed a strong correlation with TSH and may serve as a simple adjunct for clinical assessment of hypothyroidism. It provides a structured approach to assessing the clinical burden of disease using readily identifiable symptoms and signs. Further validation in euthyroid and independent populations is warranted to establish appropriate cut-off values and diagnostic utility. This tool may have potential value in settings where access to laboratory testing is limited.

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