The GIP/GIPR axis is functionally linked to GH-secretion increase in a significant proportion of gsp(-) somatotropinomas

Glucose-dependent insulinotropic polypeptide receptor (GIPR) overexpression has been recently described in a proportion of gsp(-) somatotropinomas and suggested to be associated with the paradoxical increase of GH (GH-PI) during an oral glucose load

Cyclic Cushing's syndrome: an overview.

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Idiopathic primary hyperaldosteronism: normalization of plasma aldosterone after one month withdrawal of long-term therapy with aldosterone-receptor antagonist potassium canrenoate

We have re-evaluated 15 patients with idiopathic primary aldosteronism one month after withdrawal of therapy with aldosterone-receptor antagonist potassium canrenoate. Therapy had lasted for 3 to 24 yr. Median blood pressure (BP) in the sitting position at the time of diagnosis was 160/100 (ranges 150-200/95-110 mmHg); while 1 month after withdrawal of therapy median BP was 145/90 (ranges 125-160/80-100 mmHg). One month after withdrawal, the ratio aldosterone (ng/dl)/plasma renin activity (ng/ml/h) in the upright position was increased only in 3 cases (median 18, range 6.1-125). We found a significant inverse correlation between the upright aldosterone/plasma renin activity (aldo/PRA) ratio, 1 month after withdrawal, and the number of years of therapy with potassium canrenoate. We conclude that long-term therapy with the aldosterone-receptor blocker, potassium canrenoate, can normalize the aldo/PRA ratio in many cases of idiopathic primary hyperaldosteronism after one-month withdrawal of the drug. These data are consistent with possible regression of idiopathic primary hyperaldosteronism after long-term therapy with potassium canrenoate, or in alternative to a persistent effect of potassium canrenoate, on aldosterone synthesis

Therapeutic strategies for Cushing's syndrome: An update

ntroduction: Endogenous Cushing's syndrome (CS) is a severe clinical condition caused by excess cortisol secretion. The treatment goals (with surgery, radiotherapy or medical therapy) are to normalize cortisol levels, reverse the clinical symptoms and remove the secreting neoplasm. Areas covered: Medical treatments are increasingly used in CS, especially when surgery fails or is not indicated, or while waiting for radiotherapy to take effect. This review summarizes the different medical approaches for treating CS (adrenal- or pituitary-directed drugs, glucocorticoid receptor antagonist), alone or in combination. Expert opinion: Adrenal steroidogenesis inhibitors have been the mainstay of medical treatment for CS: the most used are ketoconazole (or fluconazole), which inhibits adrenal steroidogenic enzymatic activities; metyrapone and LCI699 that inhibit 11 beta-hydroxylase (the latter is still an experimental compound); mitotane, used in adrenocortical carcinoma. The available glucocorticoid receptor antagonist is mifepristone, recently approved for use in controlling hyperglycemia secondary to hypercortisolism. There has recently been a lot of interest in using agents directly targeting the pituitary corticotroph cells to reduce Adreno Cortico Tropic Hormone secretion and, if possible, control the volume of pituitary adenomas. This is because corticotroph cells contain dopamine receptors (targets of bromocriptine and cabergoline), retinoic acid receptors, PPAR-gamma or somatostatin receptors, the target of the first drug developed and approved for Cushing's disease (pasireotide)

Hypercortisolism and pregnancy upregulate von Willebrand factor through different mechanisms: report on a pregnant patient with Cushing's syndrome.

Von Willebrand factor (VWF) is reportedly increased in pregnancy and Cushing's syndrome, inducing a hypercoagulable state. In Cushing's syndrome, VWF gene promoter polymorphisms modulate cortisol-dependent VWF upregulation, haplotype 1 (GCAG) and short GT-repeats (GT)(S) being the susceptible, and haplotype 2 (CTGA) and long GT-repeats (GT)(L) the protective pattern. We report on a Cushing's syndrome patient who became pregnant under hypercortisolism, in whom we monitored the evolution of her hypercoagulable state. During the active phase of Cushing's syndrome, the patient's VWF and factor VIII concentrations were normal, despite high urinary-free cortisol levels consistent with the presence of haplotype 2 and (GT)(L) alleles in the VWF gene promoter. VWF and factor VIII increased significantly and progressively after she became pregnant and peaked just before delivery, returning to normal 5 months later, while her hypercortisolism persisted. Our data indicate that two different mechanisms upregulate VWF under hypercortisolism and pregnancy, the latter being independent of the VWF promoter haplotypes sensitive to cortisol excess

A case of primary aldosteronism in pregnancy: do LH and GNRH receptors have a potential role in regulating aldosterone secretion?

OBJECTIVE: The mechanisms inducing steroidogenesis in primary aldosteronism (PA) remain poorly defined. It was recently demonstrated that some G-protein-coupled receptors are abnormally expressed in aldosterone-producing adenomas (APA). We evaluated the potential role of LH and GNRH receptors (LHR (or LHCGR) and GNRHR) in regulating aldosterone secretion in a patient with APA arising during pregnancy (index case) and in a subset of other patients with PA. PATIENTS AND METHODS: GNRH test was performed in the index case, 11 other PA, and 5 controls. GNRHR and LHR expressions were examined in 23 APA and 6 normal tissues. RESULTS: Aldosterone response increased significantly (114%) in the index case after GNRH test was performed preoperatively, while it was blunted after adrenalectomy. Aldosterone also increased after human chorionic gonadotropin and triptorelin stimulation. A partial aldosterone response to GNRH was observed in other 7/11 PA, while a significant response was observed in two patients. Controls did not respond to GNRH test. GNRHR was overexpressed and LHR expression was moderate in the APA tissue from the index case. Moreover, LHR was found in normal adrenals and overexpressed in 6/22 APA. GNRHR was overexpressed in 6/22 APA, 2 of them with a 95- and 109-fold higher expression than normal. A correlation between the clinical and molecular findings was observed in five out of seven patients. CONCLUSION: We describe a case of PA diagnosed during pregnancy, which appeared to correlate with aberrant LHR and GNRHR expression. Our findings suggest that a subset of patients with PA has aberrant LHR and GNRHR expression, which could modulate aldosterone secretion