TSH secretion and regulation in endemic goiter and endemic cretinism

In endemic goiter patients living in a chronic iodide deficiency area (less than 50ug/day) TSH basal levels and the TSH response to TRH is significantly higher (31 +/- 8uU/ml) than in normal controls (10 +/- 4uU/ml). There is a negative correlation between levels of iodine intake and serum TSH concentration and thyrotropin is thus increased when iodine decreased. Also it was shown that serum TSH levels correlate inversely with the serum concentration of T4 (r=0.69) but not with the usually normal or elevated serum concentration of T3 in endemic goiter patients. It has been postulated that in the absence of appropriate serum levels of T4 the pituitary thyrotrophs have an abnormally low T4 to T3 conversion and the pituitary-nuclear/serum T3 ratio does not increase sufficiently to compensate this phenomenon. On the other hand nuclear receptor saturation of T3 in tissues such as liver and kidney would remain at euthyroid levels due to the higher serum T3 concentrations. Endemic goiter patients when moving to an urban area where iodine intake is higher (greater than 150ug/day) than in the rural villages, had a blunted TSH response to TRH (15/23 subjects) or developed a mild clinical and laboratory picture of hyperthyroidism (7/23 individuals). Serum TSH levels and the TSH response to TRH is abnormally elevated in the myxedematous type of endemic cretinism but more than one third of the neurological goitrous cretins (euthyroid) have an exaggerated and sustained TSH response to TRH. This has been considered as a decreased thyroid reserve. Measurement of alpha subunits and TSH-beta in both types of endemic cretinism demonstrated that although these patients have a marked enlargement of the sella turcica the alpha subunits, although higher than normal (1.7-3.4 ng/ml) were not suggestive of a pituitary tumour. The pituitary enlargement was probably secondary to the long standing untreated thyroid failure.