Bilateral inferior petrosal sinus sampling

Simultaneous bilateral inferior petrosal sinus sampling (BIPSS) plays a crucial role in the diagnostic work-up of Cushing’s syndrome. It is the most accurate procedure in the differential diagnosis of hypercortisolism of pituitary or ectopic origin, as compared with clinical, biochemical and imaging analyses, with a sensitivity and specificity of 88–100% and 67–100%, respectively. In the setting of hypercortisolemia, ACTH levels obtained from venous drainage of the pituitary are expected to be higher than the levels of peripheral blood, thus suggesting pituitary ACTH excess as the cause of hypercortisolism. Direct stimulation of the pituitary corticotroph with corticotrophin-releasing hormone enhances the sensitivity of the procedure. The procedure must be undertaken in the presence of hypercortisolemia, which suppresses both the basal and stimulated secretory activity of normal corticotrophic cells: ACTH measured in the sinus is, therefore, the result of the secretory activity of the tumor tissue. The poor accuracy in lateralization of BIPSS (positive predictive value of 50–70%) makes interpetrosal ACTH gradient alone not sufficient for the localization of the tumor. An accurate exploration of the gland is recommended if a tumor is not found in the predicted area. Despite the fact that BIPSS is an invasive procedure, the occurrence of adverse events is extremely rare, particularly if it is performed by experienced operators in referral centres.

Chronic stress--the key to parturition?

It is clear that the timing of parturition is dependent on a cascade of endocrine signals from an intact fetal hypothalamo-pituitary-adrenal axis. What is not known, however is the nature or source of the central neural stimulation which results in the stimulation of adrenocorticotrophic hormone (ACTH) synthesis and secretion in late gestation. The changes which occur in the synthesis and posttranslational processing of the ACTH precursor, proopiomelanocortin (POMC), in the fetal anterior pituitary before birth and the consequence of these changes for expression of the corticosteroidogenic enzymes in the fetal adrenal are described in this review. Evidence for the functional heterogeneity of corticotrophic cell types in the fetal sheep pituitary and the proposal that there is a maturational change in the populations of corticotrophic cells in late gestation are discussed. Finally, the development of cortisol negative feedback in the late gestation fetal hypothalamo-pituitary axis and the relevance of chronic stress to the timing of parturition are also discussed.

The major tyrosine-sulfated protein of the bovine anterior pituitary is a secretory protein present in gonadotrophs, thyrotrophs, mammotrophs, and corticotrophs.

The anterior pituitary is a complex secretory tissue known to contain several sulfated macromolecules. In the present study, we identified the major tyrosine-sulfated protein of the bovine anterior pituitary and investigated its cellular and subcellular localization. This protein consisted of two tyrosine-sulfated polypeptides of molecular weight 86,000 and 84,000 that were highly homologous to each other. In agreement with previous biochemical studies, the tyrosine-sulfated protein of Mr 86,000/84,000 was found to be secretory, as it was observed in the matrix of secretory granules by immunoelectron microscopy. Immunofluorescence studies indicated that the tyrosine-sulfated, secretory protein of Mr 86,000/84,000, referred to as TSP 86/84, was present in all endocrine cells except for some somatotrophic cells. Higher levels of immunoreactivity for TSP 86/84 were observed in gonadotrophic and thyrotrophic than in mammotrophic and corticotrophic cells. This appeared to result from the occurrence of TSP 86/84 in all secretory granules of the former cells and in only some secretory granules of the latter cells. We discuss the possibility that TSP 86/84 may have a role in the packaging of several distinct peptides hormones into secretory granules. One, though not the only, possible function of tyrosine sulfation may concern the sorting of this protein in the Golgi complex.

ACTH and β-endorphin secretion by three corticotrophic adenomas in culture. Effects of culture time, dexamethasone, vasopressin and synthetic corticotrophin releasing factor

Dispersed corticotrophic cells of 3 patients with Nelson's syndrome were studied in tissue culture for up to 25 days. During this culture period a parallel decrease with time was seen in ACTH and β-endorphin-like immunoreactivity (LIR) release. A concomitant decline was observed for intracellular hormones. The time course of hormone release showed a parallel secretion of ACTH and β-endorphin-LIR up to 8 h. Both the release of ACTH and β-endorphin LIR were stimulated by 0.1 μm lysine vasopressin (LVP) in all three adenoma cell cultures. Dexamethasone (0.1 and 1 μm) suppressed basal hormone secretion for 4 h. Synthetic ovine corticotrophin-releasing factor (CRF) at 10 and 100 nm stimulated the secretion of ACTH and β-endorphin LIR maximally. This stimulation was higher than observed with maximal stimulative concentration of LVP (0.3 μm). The CRF-mediated hormone secretion was calcium-dependent. Dexamethasone (0.1 μm) blocked the stimulating effect of 10 nm CRF completely. Gel-filtration chromatography demonstrated the cells to secrete both β-lipotrophin (β-LPH) and β-endorphin. The ratio of β-LPH to β-endorphin released remained constant upon stimulation by LVP and CRF. HPLC studies demonstrate the possibility that several β-endorphin fragments, including α-endorphin and γ-endorphin, were secreted by cells from a Nelson tumour. CRF caused a simultaneous parallel stimulation of the release of these peptides.

The corticotrophic cells of the canine pituitary gland in pituitary-dependent hyperadrenocorticism

The distribution of specifically stained corticotrophic cells has been studied in the pituitary glands of 11 dogs with pituitary-dependent hyperadrenocorticism. The results suggest that the disease is not a single entity, and that some cases are caused by primary abnormality of the pituitary gland whereas others appear to be the result of dysfunction of the hypothalamus or central nervous system. The patterns correspond closely to those demonstrated in the human pituitary gland in Cushing's disease, and confirm that the canine disease is a useful model for the study of the pathogenesis of the variants of the condition.