Marialberta Battocchio

Ovarian tumors secreting insulin.

AbstractCombined ovarian germ cell and neuroendocrine tumors are rare. Only few cases of hyperinsulinism due to ovarian ectopic secretion have been hypothesized in the literature. An ovarian tumor was diagnosed in a 76-year-old woman, referred to our department for recurrent hypoglycemia with hyperinsulinism. In vivo tests, in particular fasting test, rapid calcium infusion test, and Octreotide test were performed. Ectopic hyperinsulinemic hypoglycemia was demonstrated in vivo and hypoglycemia disappeared after hysteroadnexectomy. Histological exam revealed an ovarian germ cell tumor with neuroendocrine and Yolk sac differentiation, while immunostaining showed insulin positivity in neuroendocrine cells. A cell culture was obtained by tumoral cells, testing Everolimus, and Pasireotide. Insulin was detected in cell culture medium and Everolimus and Pasireotide demonstrated their potentiality in reducing insulin secretion, more than controlling cell viability. Nine cases of hyperinsulinism due to ovarian ectopic secretion reported in literature have been reviewed. These data confirm the ovarian tissue potentiality to induce hyperinsulinemic hypoglycemic syndrome after neoplastic transformation.

Ambulatory Arterial Stiffness Indexes in Cushing’s Syndrome

Long-standing exposure to endogenous cortisol excess is associated with high cardiovascular risk. The aim of our study was to investigate arterial stiffness, which has been recognized as an independent predictor of adverse cardiovascular outcome, in a group of patients with Cushings syndrome. Twenty-four patients with Cushings syndrome (3 males, mean age 49±13 years; 20 pituitary-dependent Cushings disease and 4 adrenal adenoma) underwent 24-h ambulatory blood pressure monitoring (ABPM) and evaluation of cardiovascular risk factors. The Ambulatory Arterial Stiffness Index (AASI) and symmetric AASI (sAASI) were derived from ABPM tracings. Cushing patients were divided into 8 normotensive (NOR-CUSH) and 16 hypertensive (HYP-CUSH) patients, and were compared with 8 normotensive (NOR-CTR) and 16 hypertensive (HYP-CTR) control subjects, matched for demographic characteristics, 24-h ABPM and cardiometabolic risk factors. The AASI and sAASI indexes were significantly higher in Cushing patients than in controls, either in the normotensive (p=0.048 for AASI and p=0.013 for sAASI) or in the hypertensive (p=0.004 for AASI and p=0.046 for sAASI) group. No difference in metabolic parameters was observed between NOR-CUSH and NOR-CTR or between HYP-CUSH and HYP-CTR groups. AASI and sAASI were both correlated with urinary cortisol in patients with endogenous hypercortisolism (Spearmans rho=0.40, p=0.05, and 0.61, p=0.003, respectively), while no correlation was found in controls. Both AASI and sAASI are increased in Cushing syndrome, independent of BP elevation, and may represent an additional cardiovascular risk factor in this disease. The role of excess cortisol in arterial stiffness has to be further clarified.

Cushing in a Leaf: Endocrine Disruption From a Natural Remedy

BACKGROUND Information regarding the safety of herbal drugs is often not reported. We describe the case of a 65-year-old woman referred to us for a iatrogenic hypercortisolism, who denied any previous steroid consumption. She reported only a chronic application of a phytocosmetic cream, containing ethanol extract of the Cardiospermum halicacabum (CH) plant. Adrenal insufficiency occurred after the cream application was stopped. CH is used in traditional and Western medicine for its documented anti-inflammatory properties. Once the presence of synthetic glucocorticoids was ruled out in the phytocosmetic product, we investigated whether and how its chronic application could have caused the iatrogenic hypercortisolism. METHODS Liquid chromatography high-resolution mass spectrometry (LC-HRMS) was performed to exclude the presence of known glucocorticoids in the cream. ELISA assay and Western blot analysis were employed to assess ACTH secretion and the glucocorticoid receptor expression respectively in murine ACTH-secreting pituitary adenoma cells AtT-20/D16v-F2, treated with dexamethasone, CH tincture, and mifepristone alone or in combination. To detect specific interaction of CH extract with the glucocorticoid receptor, we performed a dual-luciferase reporter assay in HEK293 cells. RESULTS In AtT-20/D16v-F2 cells, CH extract showed to significantly reduce basal and CRH-induced ACTH secretion and the glucocorticoid receptor expression, similarly to dexamethasone; these effects were counteracted by mifepristone. In HEK293 cells, dexamethasone significantly induced luciferase activity after 24- and 36-hour treatment and CH tincture only after 36 hours; these effects were antagonized by mifepristone. CONCLUSIONS CH extract displays a glucocorticoid-like activity, by means of a direct binding to the glucocorticoid receptor.

Evolution of computed tomography-detectable adrenal nodules in patients with bilateral primary aldosteronism

Computed tomography (CT) appearance of adrenals in primary aldosteronism (PA) ranges from normal to bilateral diffuse enlargement or nodular glands. Idiopathic hyperaldosteronism (IHA) due to bilateral autonomous production of aldosterone (bilateral PA) is the most common subtype of PA, accounting for 50–70 % of PA patients [1, 2]. Regardless of adrenal image findings, IHA is diagnosed by adrenal venous sampling (AVS) in PA patients who do not show lateralization of aldosterone secretion [3], and is treated by long-term medical therapy using mineralocorticoid receptor antagonists. The other common PA subtypes, aldosterone-producing adenoma (APA) and unilateral adrenal hyperplasia, display lateralization of aldosterone secretion at AVS and are treated by unilateral adrenalectomy. Natural course of adrenal mass lesions in IHA patients has not yet been fully clarified. The aim of our study was to assess the over time evolution of CTdetectable adrenal nodule(s) in bilateral PA. Materials and methods