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A 50 year old man with hyperthyroidism secondary to inappropriate secretion of TSH is described. On presentation T3 (42.1 nmol/L), T4 (265 nmol/L) and TSH (17.9 mU/L) were all markedly elevated. A diagnosis of a TSH-secreting pituitary tumor was suspected on the basis of a blunted TSH response to TRH and the absence of suppression of TSH by T3 or bromocriptine, but TSH/alpha subunit molar ratios were uncharacteristically less than 1. Nevertheless, the presence of a tumor was confirmed by computed tomography which demonstrated a 15 mm pituitary macroadenoma. The patient was treated with octreotide which resulted in normalisation of thyroid hormone levels. The duration of action of a single 100 micrograms injection of octreotide was at least 56 hours. The suppression of thyroid hormone levels was similar regardless of the treatment regimen with octreotide (100 micrograms tid, 250 micrograms bid, 100 micrograms bid and continuous subcutaneous infusion (CSI] and no escape was observed during a 16 month treatment period. TSH alpha subunit concentrations were also suppressed during long-term treatment with octreotide (3.3 micrograms/L falling to 1.1 micrograms/L), although no acute changes were noted after administration of single dose octreotide 100 micrograms. Three times the octreotide therapy was discontinued. The incremental rise in TSH and the maximum level of TSH achieved was less on each subsequent occasion, suggesting a suppressive effect of octreotide on the tumor itself. Despite suppression of TSH with octreotide over a 13 month period the pituitary tumor showed no shrinkage on repeat MRI scanning. In conclusion, this patient demonstrates that the differential diagnosis of inappropriate TSH secretion based only on biochemical test may be unreliable.(ABSTRACT TRUNCATED AT 250 WORDS)

TSH, LH and FSH, the three pituitary glycoprotein hormones, are each composed of a common alpha-subunit and a hormone specific beta-subunit. Testosterone is known to regulate all three intact hormones differently in the rodent. However, there is only one gene encoding the common alpha-subunit. In order to elucidate the effects of testosterone on TSH subunit synthesis and its regulation of the common alpha-subunit, two in vivo models were studied: castrate rat pituitary was used as a gonadotropin-enriched tissue; and mouse thyrotropic tumor was used as a thyrotropin-enriched tissue. Male castrate rats were treated with testosterone propionate, 500 micrograms/100 g BW, sc, for 11 days. Testosterone increased plasma TSH to 131% of control values (P less than 0.02), while plasma LH fell to undetectable levels, and plasma alpha-subunit fell to 14% of control values (P less than 0.001). Testosterone increased TSH-beta mRNA to 237% of control values (P less than 0.02), while alpha-subunit mRNA fell to 20% of control values (P less than 0.001). Hypothyroid mice bearing thyrotropic tumors were treated with testosterone propionate, 150 micrograms/100 g BW, sc, for 11 days. In this model plasma TSH-beta and alpha-subunit concentrations are 1000-fold higher than in non-tumor bearing animals, and the contribution of pituitary gonadotropes to plasma subunit concentrations is negligible. "Total" TSH-beta and alpha-subunit concentrations were estimated as one-half of intact TSH plus the respective free subunit concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

Triac, 3,5,3'-triiodothyroacetic acid, was administered at doses of 1, 3, 9 or 30 micrograms/100 g body weight to hypothyroid rats to determine its effects on TSH secretion and pituitary mRNA content. Triac caused a dose-dependent decrease in serum TSH 6 h after injection. Pituitary content of mRNA subunits either remained at hypothyroid levels or increased at 6 h. At 24 h after injection of the 3 micrograms dose of triac, serum TSH returned to hypothyroid levels; both alpha and beta mRNA subunits were reduced at this time. When 30 micrograms triac/100 g body weight was administered, serum TSH levels remained depressed 24 h later, while pituitary mRNA content was essentially the same as in the hypothyroid controls. These findings indicate that the initial decrease in TSH secretion in response to triac is independent of the availability of TSH mRNA transcripts and suggest that TSH secretion and synthesis may be differentially controlled.