A human TSH-secreting adenoma: Endocrine, biochemical and morphological studies. Evidence of somatostatin receptors by using quantitative autoradiography. Clinical and biological improvement by SMS 201-995 treatment

Abstract

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).

Expression of Type 5 Somatostatin Receptor in TSH-secreting Pituitary Adenomas: A Possible Marker for Predicting Long-term Response to Octreotide Therapy

“…Previous reports that TSHomas expressed somatostatin receptors support OCT therapy for TSHdependent hyperthyroidism [8,[17][18][19][20][21]. According to these reports, OCT suppressed TSH levels in more than 90% of patients with TSHomas and it also decreased serum thyroid hormone levels to normal ranges in 70% of the patients.…”

Factors predicting relapse of nonfunctioning pituitary macroadenomas after neurosurgery: a study of 142 patients

“…Four-micrometer sections were prepared for histological and immunocytochemical studies. All immunocytochemical analyses (FSH, LH, a-subunit, TSH, ACTH, GH, and PRL) and the final immunopathological classification of the NFMAs were done, as previously described (19)(20)(21)(22), by the same pathologist (M K) who was blinded to the clinical data. Complete immunohistochemical analysis was possible in 130 cases.…”

Treatment of Thyrotropin-Secreting Pituitary Adenomas with Octreotide.

“…3G) and reinstallation of octreotide again promptly decreased the size of the tumor (Fig. 3H) [18][19][20]. There was a good correlation between 125I-SRIF binding capacity and the magnitude of SRIF inhibition of adenylyl cyclase in these tumors [20].…”