An invasive TSH-secreting adenoma inducing mild hyperthyroidism was diagnosed in a 16-year-old male. Initial surgical treatment led to a temporary clinical and biological improvement. Recurrence of the thyrotoxicosis was treated with the somatostatin analogue, SMS 201-995 (octreotide) with normalization of the serum thyroid hormone levels with a dose of 200 \g=m\gper day. With immunoelectron microscopy, the tumour cells appeared poorly granulated with small secretory granules located at the periphery of the cells; only part of those were immunoreactive with an anti-TSH\g=b\ monoclonal antibody. No specific TRH binding site was found in a tumour membrane preparation. By quantitative autoradiography, somatostatin specific binding sites were as numerous in the TSH-secreting tumour as in control GH-secreting tumours. Binding kinetics and guanosine triphosphate dependency of the binding were equivalent in the TSH and GH tumours tested. Although all of the tumour cells displayed the same ultrastructural features, some were non\x=req-\ immunoreactive, suggesting that they could secrete an altered form of TSH. The absence of TRH receptors in the tumour cells is in accordance with previous reports on this type of tumour. We confirm the efficiency of octreotide treatment in this case of neoplastic TSH inappropriate secretion. The therapeutic effect of octreotide goes along with the presence of a high density of guanine nucleotide-dependent somatostatin binding sites in the tumour cells.TSH-secreting adenomas represent less than one percent of the pituitary tumours and are a rare cause of hyperthyroidism (1,2). The clinical features have been well characterised (1-3), however the treatment of these aggressive and invasive tu¬ mours remains difficult. Combined surgery and ra¬ diotherapy cures only 41% of patients (2-4) and among complementary medical treatments the long-acting somatostatin analogue, SMS 201-995, is often effective (5,6).The presence of somatostatin (SRIH) receptors has been demonstrated in different types of pitu¬ itary tumours. They have been found in GHsecreting adenomas, often with a high density, and also in PRL-secreting tumours and in some endo¬ crine-inactive adenomas (7,8). In GH secreting adenomas, the density of SRIH binding sites cor¬ relates inversely with plasma GH levels before sur¬ gery (7) and recent data suggest that the therapeu¬ tic efficiency of SMS 201-995 correlates with the presence of a high density of SRIH binding sites in the tumour (9).In the present study we report a 16-year-old patient with hyperthyroidism owing to a TSH-se¬ creting pituitary macroadenoma. Adenomatous tissue was examined by immunoelectron micro¬ scopy. TRH and SRIH binding by the tumour was evaluated. Using an autoradiographic technique we demonstrated the presence of numerous SRIH binding sites on the tumour which may explain the succesful treatment of this patient with somatosta¬ tin analogue SMS 201-995 (octreotide).

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The orphan nuclear receptor, steroidogenic factor 1 (SF-1), plays a major role in adrenal and gonadal development, as well as in sexual differentiation. It has been demonstrated that the expression of a number of genes regulated by SF-1 is inhibited by the transforming growth factor, (TGF-beta). To date, however, the influence of TGF-beta on the expression of SF-1 gene has not been reported. A Northern blot analysis with the use of a radiolabeled cDNA probe, and immunodetection with antibodies directed against SF-1, demonstrated that the Sf-1 transcript and the SF-1 protein levels were lowered by TGF-beta in Y-1 adrenocortical cells, both in untreated and adenylyl cyclase activator, forskolin-treated cells. An examination of the Sf-1 transcript stability in the presence of actinomycin D revealed no influence of TGF-beta on the rate of Sf-1 mRNA decay. Inhibition of Sf-1 expression by TGF-beta was abolished by cycloheximide, suggesting that the growth factor inhibitory effect requires ongoing protein synthesis. We conclude that in Y-1 cells TGF-beta inhibits the expression of SF-1 gene at a transcriptional level, and we postulate that the inhibitory effect of TGF-beta on steroid hormone synthesis in the adrenal cortex could be due to an attenuated transcription of Sf-1.

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