Thyroid dysfunction in individuals visiting a Clinic in Lalitpur, Nepal

Thyroid dysfunction is a major global health concern, particularly in LMICs like Nepal, where limited healthcare access and iodine deficiency contribute to high prevalence.¹³ If untreated, such dysfunction can lead to severe developmental, cognitive, and cardiovascular issues.¹⁴ However, screening remains limited, especially in rural areas, leading to poorer outcomes in many LMICs. This study examined thyroid dysfunction patterns in individuals visiting a clinic to provide insights into the prevalence and support public health interventions.

In this study, among patients with thyroid disorders, the majority were aged 30-39, aligning with studies indicating higher rates of hypothyroidism and subclinical hypothyroidism within this age group.^15,16 The gender distribution indicated a significant female predominance (62.39% among healthy patients and 55.24% among those with thyroid disorders), consistent with known higher susceptibility among women, as reported in astudy.¹⁶ Subclinical hypothyroidism was notably the most prevalent type among both sexes and across age ranges, particularly within the 30-39 age group (31.55% of all cases with subclinical hypothyroidism), underscoring the condition’s asymptomatic yet widespread presence in middle-aged adults, as seen in other large-scale epidemiological studies.¹⁷ The gender distribution also varied by specific thyroid dysfunction; all cases of primary and secondary hyperthyroidism occurred exclusively among women, which aligns with patterns observed in comparative analyses of thyroid disorder gender distribution.¹⁸ The presence of euthyroid hyperthyroxinemia and hypertriiodothyroninemia among 40-49 and 10-19, respectively, suggests age-related influences on thyroid hormone dynamics and potential risk factors worthy of further study. These findings highlight the need for targeted thyroid disorder screening in the clinic-visiting population in Lalitpur, particularly focusing on middle-aged women, aligning with prior evidence suggesting tailored regional screening and intervention strategies can improve thyroid disorder detection and management.^19,20

The median TSH value in this study (2.55 µIU/ml) and mean (3.70±6.29 µIU/ml) suggest a wider variation than that observed in Western populations, where mean TSH values typically fall between 1.5 and 2.5 µIU/ml, as reported by Hollowell et al.¹⁵ This broad range of TSH values, from 0.00 to 98.70 µIU/ml, indicates potential subclinical and overt thyroid dysfunctions prevalent in this population, possibly due to iodine intake variability and limited healthcare access in the region.¹³ For T3 (2.98 pg/ml) and T4 (12.00 pg/ml), the median values were somewhat lower than those in European populations, where T4 levels average 13–14 pg/ml, as noted by Delange et al.²¹This difference may reflect regional nutritional disparities, including inconsistent iodized salt access, impacting thyroid health in LMICs such as Nepal.⁹ Our study’s upper ranges for T3 and T4, with T3 reaching 49.20 pg/ml and T4 up to 65.10 pg/ml, mirror findings in iodine-sufficient regions where hyperthyroidism, often due to autoimmune conditions like Graves’ disease, is prevalent.²²

Healthy individuals in this study showed mean FT3, FT4, and TSH levels of 2.99±0.40 pg/ml, 12.22±1.69 pg/ml, and 2.26±1.06 µIU/ml, respectively. These values are consistent with findings in iodine-sufficient regions, where normal TSH typically ranges from 0.5 to 4.5 µIU/ml.¹⁵ Comparing hyperthyroidism subtypes, individuals with primary hyperthyroidism had significantly elevated FT3 and FT4 levels (10.72±11.18 pg/ml and 26.82±11.32 pg/ml, p<0.001) and markedly low TSH (0.01±0.01 µIU/ml, p<0.001), consistent with classic hyperthyroidism patterns characterized by excess thyroid hormone production due to autoimmune factors such as Graves' disease.²² Secondary hyperthyroidism displayed similarly elevated FT3 and FT4 (5.81±1.50 pg/ml, 20.66±2.62 pg/ml, p<0.001), although TSH levels were not significantly altered (14.46±19.98 µIU/ml, p=0.104), potentially due to dysfunctions at the hypothalamic or pituitary level, which distinguishes it from primary hyperthyroidism. Herein, subclinical hyperthyroidism cases exhibited near-normal FT3 and FT4 levels (3.25±0.51 pg/ml, 17.76±5.81 pg/ml, p<0.001) with reduced TSH (1.32±1.33 µIU/ml, p<0.001), similar to findings in populations with mild iodine deficiency, where TSH suppression can occur without overt hormone elevation.²³ This trend aligns with studies indicating that subclinical hyperthyroidism, while asymptomatic, can carry risks of cardiovascular complications, underscoring the need for early detection.¹⁷

In this study, individuals with primary hypothyroidism had significantly reduced FT3 and FT4 levels (2.76±0.80 pg/ml, 10.38±6.18 pg/ml, p<0.001) coupled with elevated TSH (22.07±25.31 µIU/ml, p<0.001), a typical profile for primary thyroid failure where the gland cannot produce sufficient hormones, often due to autoimmune thyroiditis.¹⁶ Secondary hypothyroidism patients displayed lower FT3 and FT4 levels (1.53±0.40 pg/ml, 6.65±2.21 pg/ml, p<0.001) with reduced TSH (1.22±1.18 µIU/ml, p<0.001), which likely indicates hypothalamic-pituitary axis dysfunction, as seen in central hypothyroidism.²⁴ Subclinical hypothyroidism cases showed TSH elevation (7.92±7.95 µIU/ml, p<0.001) with normal FT3 and FT4 (3.00±0.52 pg/ml, 11.87±1.82 pg/ml, p<0.001), which aligns with global findings on its prevalence in aging populations and the increased risk of progression to overt hypothyroidism.²⁵

Abnormal conditions, such as euthyroid hyperthyroxinemia, showed elevated FT3 and FT4 (7.31±6.26 pg/ml, 23.15±5.08 pg/ml, p<0.001) but normal TSH (2.38±1.35 µIU/ml, p=0.578). This condition may reflect transient or non-thyroidal influences on thyroid hormone levels, commonly observed in acute illnesses or as a response to medications like corticosteroids.²⁶Hypertriiodothyroninemia cases presented mildly elevated FT3 (3.75±4.12 pg/ml, p=0.028) with normal T4 and slightly reduced TSH (1.88±1.19 µIU/ml, p<0.001), suggesting possible early or mild thyroid dysregulation, as noted in some thyroid nodular diseases.¹³ Finally, non-thyroidal illness syndrome displayed significantly lower FT4 (8.13±1.15 pg/ml, p<0.001) with slightly lower TSH (2.58±1.10 µIU/ml, p=0.002) but maintained normal FT3, supporting findings that NTIS is common in critically ill patients and is associated with alterations in thyroid hormone metabolism rather than intrinsic thyroid dysfunction.²⁷ Collectively, these patterns emphasize the complexity of thyroid regulation and the varied etiologies underlying thyroid dysfunction in this cohort, reflecting a range of genetic, nutritional, and systemic health factors characteristic of LMIC populations.

In this study, the FT4 and FT3 scatter plots showed limited correlation with TSH, as evidenced by the correlation statistics in Table 4. A weak negative correlation was observed between TSH and FT3 (Pearson correlation=-0.022, p=0.060) and a slightly stronger inverse correlation with FT4 (Pearson correlation=-0.123, p<0.01), suggesting that higher TSH levels do not directly correspond to lower FT3 or FT4 values in this cohort. This is consistent with previous studies from global settings that report weak correlations among these biomarkers in both hyperthyroid and hypothyroid patients.^28,29 Our analyses imply that thyroid dysfunction in this cohort may be multifactorial, possibly influenced by iodine intake variability, nutritional status, and genetic predispositions common in LMIC populations.¹³ Nonetheless, further studies are warranted to explore environmental and lifestyle factors contributing to these distinct thyroid patterns, aiming to improve screening and intervention strategies in resource-limited settings like Nepal.

This study is limited by its single-center design, which may not fully represent the broader Nepalese population due to regional healthcare access and demographic differences. Sample bias is likely, as participants are clinic-visiting individuals, potentially skewing the prevalence of thyroid dysfunction. Certain subgroups, particularly young (<20) and elderly (≥80) patients, are underrepresented in key thyroid dysfunction categories like hyperthyroidism, reducing the statistical power in these age ranges. Gender differences, while observed, lack further data on confounders, such as menopausal status, which could clarify gender-specific risk factors. Additionally, the use of single-instance thyroid biomarkers may not capture temporary versus chronic thyroid dysfunction, especially in cases like non-thyroidal illness syndrome, where TSH suppression might be transient. Multicenter studies and longitudinal designs are needed to enhance the validity of these findings and improve the understanding of thyroid disorder prevalence in Nepal.