The hypothalamic-pituitary-thyroid axis in subjects with subclinical thyroid diseases: the impact of the negative feedback mechanism.

OBJECTIVE: To evaluate the hypothalamus-pituitary-thyroid (HPT) axis in patients with subclinical thyroid dysfunction recently reported to have either symptoms or organ involvements with potential morbidity, in order to better differentiate these patients with respect to controls.

PATIENTS: Sixtythree patients with subclinical hyperthyroidism (HyperT), 178 normal subjects (EuT) and 106 patients with subclinical hypothyroidism (HypoT) were enrolled; the groups presented normal thyroid hormone (FT4, FT3) levels and, respectively, reduced (HyperT), normal (EuT) and increased (HypoT) TSH levels. The negative feedback was simultaneously evaluated by multiple linear regression.

RESULTS: The mean TSH, FT4 and FT3 levels were significantly different in the three groups. The negative correlation between thyroid hormones (FT4 and FT3) and TSH secretion was significant (p<0.001 in HyperT; p<0.01 in EuT; p<0.000001 in HypoT group). FT4 mostly contributed to the negative correlation with TSH. The normal ranges of TSH values was accurately defined on the basis of the regression equation in the EuT group, due to the combining influence of both thyroid hormones (FT3 and FT4). No patient of the HyperT or HypoT group fell inside the range of estimated values of the normal group.

CONCLUSIONS: The HPT axis in patients with subclinical hyper- and hypo-thyroidism is significantly modified with respect to normal subjects. The status of the axis, as evaluated by the relationship between the three hormones (FT4, FT3, TSH) together considered, is characteristic of the normal or pathologic condition. A reliable method based on the regression analysis is proposed to correctly evaluate the status of the HPT axis.