Clinical profile and comorbidity patterns in subclinical thyroid disorders

INTRODUCTION

Subclinical thyroid disorders represent a state of mild thyroid dysfunction characterized by abnormal thyroid-stimulating hormone (TSH) levels, with normal free thyroxine (FT4) and free triiodothyronine (FT3) levels.^[1] These conditions have gained significant attention due to their potential impact on various health outcomes and quality of life. The clinical significance of these disorders lies in their association with various cardiovascular, metabolic, and cognitive complications.

Subclinical hypothyroidism (SCH) is defined by elevated TSH with normal FT4 levels, while subclinical hyperthyroidism (SCHyper) is characterized by suppressed TSH with normal FT4 and FT3 levels.^[2] The prevalence of these conditions varies significantly across different populations, with SCH being more common, affecting 3-16.9% of the general Indian population,^[3-9] and SCHyper affecting around 0.2-11.3% of the global population^[10] and around 1.6% of the Indian population.^[3] The prevalence increases with age and is higher in women. Varying prevalence rates in some regions could be due to iodine deficiency and autoimmune thyroid disorders.^[4] A major epidemiological study conducted in eight cities of India reported an overall prevalence of thyroid dysfunction of 10.95%, with SCH being the most common presentation.^[3] However, comprehensive data on the clinical profile of patients with subclinical thyroid disorders from North India remains limited.

The clinical significance of subclinical thyroid disorders remains a subject of ongoing debate, particularly regarding the threshold for treatment initiation. Various studies have suggested associations between these conditions and adverse cardiovascular outcomes, cognitive decline, osteoporosis, metabolic disturbances and adverse pregnancy outcomes.^[11-15] Understanding the clinical profile and associated comorbidities becomes crucial for appropriate management decisions.

The clinical significance of these subclinical disorders lies in their potential progression to overt thyroid dysfunction and the associated health risks. Early detection through screening can facilitate timely interventions, potentially preventing complications and improving overall health outcomes.^[16] However, the absence of specific symptoms often leads to these conditions going undetected, highlighting the importance of routine screening, especially in high-risk populations.

This study aimed to analyze the clinical presentation, biochemical parameters, and associated comorbidities in patients with SCH and SCHyper at a tertiary care center in North India. The findings may help in better characterization of these disorders in the Indian population and guide management strategies.

MATERIAL AND METHODS

RESULTS

Demographic characteristics

Of 385 patients screened, 68 (17.7%) had SCH and 14 (3.6%) had SCHyper. The mean age was 46.8±12.4 and 49.2±13.8 years for SCH and SCHyper patients. Female predominance was observed in both groups (SCH: 72.1%, SCHyper: 64.3%), as shown in Table 1. The age distribution showed a peak in the 41-50 years age group for both conditions [Figure 1].

Table 1: Demographic and biochemical characteristics of the study participants

Characteristic	Subclinical hypothyroidism (SCH)	Subclinical hyperthyroidism (SCHyper)
Number of patients	68	14
Females	49 (72.1%)	9 (64.3%)
Males	19 (27.9%)	5 (35.7%)
Mean age (in years)	46.8±12.4	49.2±13.8
Mean TSH (μIu/mL)	7.3±1.9	0.24±0.11
Mean FT3 (pg/mL)	3.3±0.2	4.2±0.4
Mean FT4 (pmol/L)	15.91±1.9	21.2±1.9
Anti-TPO Ab positive (%)	45.6%	28.6%

TSH: Thyroid stimulating hormone, FT3: Free triiodothyronine, FT4: Free thyroxine, Anti-TPO Ab: Anti-thyroid peroxidase antibody

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Figure 1:

Age distribution of subclinical thyroid disorders. SCH: Subclinical hypothyroidism, SCHyper: Subclinical hyperthyroidism.

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Clinical features

In patients with SCH (n=68), the most common symptoms were dry skin (69.1%), fatigue (51.5%), and cold intolerance (39.7%). Other significant symptoms included constipation (29.4%), weight gain (23.5%), hair loss (17.6%), memory impairment (14.7%), and depression (11.8%), as shown in Figure 2. Among female patients with SCH, 30.6% reported menstrual irregularities. For SCHyper patients (n=14), the predominant symptoms were palpitations (42.9%), anxiety (35.7%), and heat intolerance (28.6%). Additional symptoms included weight loss and tremors (both 21.4%), sleep disturbances and muscle weakness (both 14.3%), as shown in Figure 3. Menstrual irregularities were reported by 22.2% of female patients with SCHyper.

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Figure 2:

Clinical features in patients of subclinical hypothyroidism.

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Figure 3:

Clinical features in patients of subclinical hyperthyroidism.

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DISCUSSION

This comprehensive study of subclinical thyroid disorders provides significant insights into their clinical presentation and associated comorbidities in the North Indian population. The findings have important implications for screening and management strategies.

The demographic characteristics observed in our study align with previous research, showing a female predominance and higher prevalence in middle-aged adults.^[11] This gender disparity may be attributed to autoimmune factors and hormonal influences, particularly estrogen’s role in modulating thyroid function.

The prevalence rates in our tertiary care setting, 17.7% for SCH and 3.6% for SCHyper, exceed those reported in general population studies across India (3-16.9% for SCH^[3-9] and 1.6% for SCHyper^[3]). This difference likely stems from referral bias, as symptomatic patients are more frequently directed to specialty centers. While our SCHyper prevalence exceeds Indian averages, it remains within global ranges (0.2-11.3%),^[10] possibly reflecting regional variations in iodine intake or autoimmunity patterns.

The substantial symptom burden in our patients challenges the traditional “subclinical” designation. In SCH, the high prevalence of dry skin (69.1%), fatigue (51.5%), and cold intolerance (39.7%) suggests that even mild thyroid hormone deficiency significantly affects peripheral tissue metabolism. Comparing our findings with other Indian studies, we observed comparable symptom profiles but with some regional variations. For instance, Deshmukh et al.^[4] reported slightly higher rates of fatigue (69.2%) in their Mumbai cohort but found a lower prevalence of dry skin (40%) and cold intolerance (33.8%) compared to our North Indian population.

Similarly, in SCHyper patients, the predominance of palpitations (42.9%), anxiety (35.7%), and heat intolerance (28.6%) indicates that seemingly minor thyroid hormone excess produces discernible clinical effects. The significant association between SCHyper and anxiety disorders (28.6%, p=0.011) underscores the need for psychological evaluation in these patients.

The comorbidity analysis reveals distinct patterns with important clinical implications. In SCH, we identified significant associations with dyslipidemia (41.2%, p=0.008), obesity (32.4%, p=0.016), and metabolic syndrome (27.9%, p=0.023). These findings support Zhao et al.’s^[17] conclusion that even mild thyroid hormone deficiency can disrupt lipid metabolism and energy homeostasis, potentially accelerating atherosclerosis as described in the Rotterdam Study.^[13] When compared with Indian data, our observed association between SCH and dyslipidemia (41.2%) is markedly lower than the 61.25% reported by Chowdhury et al.^[9] in their cohort, suggesting potential regional variations in metabolic responses to thyroid dysfunction or differences in dietary and lifestyle factors.

For SCHyper, the significant associations with atrial fibrillation (21.4%, p=0.014) and osteoporosis (14.3%, p=0.032) reinforce the findings of Delitala^[12] and Blum et al.^[18] The atrial fibrillation link has particular clinical relevance given its implications for stroke risk and anticoagulation decisions. The osteoporosis association highlights the need for bone health monitoring, especially in postmenopausal women.

The high prevalence of anti-TPO antibodies in SCH (45.6%) suggests autoimmune etiology as a major underlying cause, consistent with previous Indian studies.^[3,4] This finding aligns closely with the 47.6% positivity rate reported by Deshmukh et al.^[4] in their Mumbai cohort, but is lower than the 65% reported by Chowdhury et al.,^[9] possibly reflecting regional variations in autoimmune thyroid disease patterns. This finding has implications for disease progression and management decisions, particularly regarding the initiation of replacement therapy.

The cardiovascular associations observed in both conditions merit particular attention. While SCHyper is linked to arrhythmias (particularly atrial fibrillation), SCH is associated with metabolic risk factors for atherosclerosis. These distinct pathways suggest that subclinical thyroid disorders may contribute to cardiovascular risk through different mechanisms, supporting Cooper and Biondi’s^[1] assertion that these conditions warrant careful clinical evaluation.

Importantly, the non-significant trends observed in hypertension (23.5%, p=0.062 in SCH; 21.4%, p=0.078 in SCHyper) and type 2 diabetes (17.6%, p=0.093 in SCH; 14.3%, p=0.212 in SCHyper) suggest potential associations that might reach significance in larger cohorts, highlighting areas for further investigation.

These findings have several clinical implications. First, they support a more proactive approach to patient evaluation, considering both biochemical parameters and clinical manifestations. Second, they suggest that targeted screening may be beneficial in high-risk populations, particularly middle-aged women. Third, they indicate that management decisions should consider the patient’s comorbidity profile, especially regarding cardiovascular and metabolic risk.

CONCLUSION

This comprehensive study reveals that subclinical thyroid disorders manifest with distinct clinical features and significant comorbidity associations, challenging the “subclinical” terminology. The high prevalence of symptoms and associated conditions, particularly the link between SCH and metabolic disorders, and SCHyper with cardiovascular complications, emphasizes the need for systematic screening and monitoring in high-risk populations. The findings support a more proactive approach to patient evaluation and management, considering both biochemical parameters and clinical manifestations. Future research should focus on long-term outcomes and optimal treatment strategies through multicenter studies with larger cohorts.