The main finding of this study is that aside from the conventional and expected differences in the expression of thyroid tests, including iodine and TPOab, patients with hypothyroid dysfunction also exhibited obesity and elevated levels of triglycerides as compared to controls. How subclinical hypothyroid dysfunction influences weight gain can be explained via the peripheral effects of thyroid hormones and their local regulation of central nervous system (CNS) in the physiologic regulation of appetite that is independent of their conventional role in basal energy expenditure as well as regulation of resting energy expenditure [8, 9]. With respect to obesity per se, it has been found out that visceral adipose tissue has a direct effect in TSH levels among obese, and this is independent of insulin resistance . Regarding triglycerides, our results were in accordance with the study of Wanjia and colleagues, who also observed elevated TSH levels among patients with hypertriglyceridemia . The exact mechanisms accountable for the effects of thyroid function with respect to lipid profile are unclear. Nevertheless it is almost established that TSH receptors are present in tissues other than the thyroid gland which include kidneys, bone marrow and adipose tissue, and that variations ion TSH levels among euthyroid patients are partially explained by lipid components and hypercholesterolemia which are independent of thyroid hormones [12, 13]. Furthermore, there are several factors not accounted for in this study that may influence thyroid function and lipid profile, including smoking and insulin resistance , as well as obesity and abnormalities in glucose tolerance.
One striking and unexpected finding in this study is the significantly higher mean 25(OH) vitamin D levels among patients with subclinical hypothyroid dysfunction than controls despite the presence of established risk factors for vitamin D deficiency including obesity and hypetriglyceridemia [15–17]. Calcium levels while also significantly different, still fall within normal range, although the possibility of other causes such as malabsorption or decreased dietary calcium intake in some subjects cannot be ruled out. Furthermore, PTH levels were higher, although not significant in the case group than controls. These differences this can be attributed to several confounders unaccounted for in the study which include differences in dietary calcium and vitamin D intake, undocumented comorbidities such as malabsorption and existing renal disorders which were not evident at the time of selection, as well as sun exposure, and needs further investigation. Nevertheless, while the vitamin D status of cases was significantly higher as compared to controls, both mean levels were still far below sufficiency levels and the corresponding PTH levels were not significantly different from one another, and as such the interpretation is comparable. Furthermore we recently observed that PTH levels do not correlate with 25(OH) vitamin D levels in Saudis despite severely low levels .
The association of PTH with lipid concentrations, specifically the cholesterol levels was demonstrated earlier and we suggest that this is mainly due to the positive association of PTH to body composition and adiposity, rather than the cholesterol itself [19, 20]. Also, the inverse association of FT3 to circulating levels of 25(OH)D should be interpreted with caution. It was previously reported that higher vitamin D status was associated with low TSH only among younger individuals and not in adults . Furthermore, while vitamin D deficiency has been implicated in several autoimmune thyroid diseases, no association was elicited between the antibodies measured in the present study and vitamin D, confirming a recent study among Dutch natives about the lack of correlation of low vitamin D levels and the early stages of thyroid auto-immunity . Similarly, polymorphisms of vitamin D alpha-hydroxylase (CYP)1alpha, a key enzyme for regulating both systemic and tissue levels of 1, 25-dihydroxyvitamin D3 , did not correlate with known auto-immune disorders such as type 1 diabetes mellitus, Grave’s disease and Hashimoto’s thyroidits among Caucasian pedigrees . In this context, it should be taken into account that TSH may have direct and independent effects on bone metabolism regardless of thyroid hormones [25, 26].
The authors acknowledge several limitations. The cross-sectional nature of the study and the small sample size limits the findings of the study to at best, suggestive. Several major confounders were also not included including season which has a counterintuitive effect in the vitamin D status of citizens residing in the Gulf region . Gender difference could not be elicited due to the big discrepancy in the numbers between male and female subjects. Nevertheless, the study has its own strength as being the first to document several metabolic differences among Saudi patients with and without hypothyroid dysfunction and the first to associate vitamin D status in relation to thyroid function profile.