Growth promoting effect of human plasma ultrafiltrate bioactive fraction (TBP) for human non-functioning pituitary adenoma cells in vitro.

We described before that the chromatographically purified "human plasma ultrafiltrate bioactive fraction" (humoral factor tentatively denoted as tumor basic protein--TBP) regulates in vitro release of ACTH from pituitary adenomas stimulating the hormone release from the tumors showing low hormonal activity in vitro and inhibiting ACTH production in vitro by highly hormonally active pituitary tumors. In this study we describe growth promoting effects (determined by 3H-TdR incorporation assay) of TBP (5 microg/l, i.e. 10% w/v plasma equivalent concentration) for 10 non-functioning pituitary tumors. The effects of TBP appeared to negatively correlate with the in vitro growth abilities of the tumors that were otherwise dependent on the duration of the clinical symptoms of the tumor presence. Hence, similar to its effects on hormonal activity of the pituitary tumors, TBP stimulated the growth of the tumors which did not express high spontaneous 3H-TdR intensity, but did not stimulate the cells with high capacity of spontaneous 3H-TdR incorporation. Moreover, all the tumors that were stimulated by TBP were nononcocytic adenomas while oncocytoma cells were not stimulated at all. Thus, TBP shows activity of humoral (plasma) factor involved in the growth regulation of pituitary adenomas that might be used to define the growth abilities of these tumors, especially in case of null cell adenomas and oncocytomas as were the tumors used in this study.

[Low-renin hypertension and inherited mineralocorticoid diseases]. / Niskoreninska hipertenzija i nasljedne bolesti mineralokortikoida.

Liddle's syndrome, apparent mineralocorticoid excess (AME) and glucocorticoid remediable aldosteronism (GRA) are inherited diseases characterized by hypertension and low plasma renin activity. Constitutive activation of distal renal epithelial sodium channel (Liddle's syndrome), defect in 11 beta-hydroxysteroid dehydrogenase activity (AME) and unequal crossing over, fusing regulatory sequences of 11 beta-hydroxylase gene to coding sequences of aldosterone synthase gene and forming a new chimeric gene (GRA), cause apparent or real mineralocorticoid excess. This diseases are often being unrecognized and classified as essential hypertension, especially in patients with normal serum potassium level. Family history of hypertension and characteristic serum and urine++ steroid profile direct us to diagnosis, and genetic analysis will confirm it.

Clinical and morphological features of undifferentiated monomorphous GH/TSH-secreting pituitary adenoma.

A 41-year-old male presented with progressive visual defects, acromegaly and hyperthyroidism. After clinical evaluation a giant GH/TSH-secreting pituitary adenoma was diagnosed. Administration of the somatostatin analog octreotide at doses of 150 microg s.c. per day inhibited the secretion of both GH and TSH. A three-week treatment with octreotide prior to surgery led to slight visual improvement and CT scan showed some new necrotic areas within the tumor mass. Transcranial surgery was performed. By immunohistochemical analyses of the adenoma tissue GH, prolactin and beta-chorionic gonadotropin were detected; TSH was negative. Electron microscopy revealed an undifferentiated, monomorphous adenoma with morphological features of an acidophil stem cell adenoma such as the presence of misplaced exocytoses, fibrous bodies and mitochondrial gigantism. However, the tumor cells contained small secretory granules (up to 250 nm) accumulated along the cell membrane characteristic of thyrotrope cells. Furthermore, some adenoma cells were fusiform with long cytoplasmic processes resembling thyrotropes. Two months after the operation CT scan revealed a large residual tumor. Serum GH and TSH levels had increased again and the TSH level was even higher than before the treatment. The patient died suddenly, most probably of lethal arrhythmia. Specimens of the adenoma tissue obtained at autopsy confirmed the previous findings with the exception of positive immunostaining for TSH which was found in less than 1% of the adenoma cells. This undifferentiated, monomorphous GH/TSH-secreting pituitary adenoma represents an entity that is unusual both in its ultrastructural features and clinical manifestations suggesting a cytogenesis from an early, undifferentiated stem cell.