Endocrine Abstracts

The mechanisms regulating aldosterone secretion in primary aldosteronism (PA) independently from the renin-angiotensin axis include diverse genetic and molecular mechanisms. One mechanism results from the activation of aberrantly expressed GPCR which are diverse and highly prevalent in adrenal tissues of patients with PA, either from aldosteronoma or bilateral adrenal hyperplasia. The levels of expression of GPCR vary greatly between different PA tissues particularly for ACTH ...

The mechanisms regulating cortisol production when ACTH of pituitary origin is suppressed in primary adrenal causes of Cushing’s syndrome (CS) include diverse genetic and molecular mechanisms. These can lead either to constitutive activation of the cAMP system and steroidogenesis or to its regulation exerted by the aberrant adrenal expression of several hormone receptors, particularly G-protein coupled hormone receptors (GPCR) and their ligands. Screening for aberrant exp...

Case: A 56-year-old patient was referred to our endocrinology unit for management of severe hypercalcemia. He had complained initially from asthenia, intractable nausea and vomiting and weight loss (10 kg), but now also suffered from polyuria-polydipsia, bradypsychia and bradylalia, and diffuse joint pain with loss of strength in the lower limbs. Initial laboratory investigations showed a parathyroid crisis with marked increases of parathyroid hormone (PTH) at 2138.5 pg/ml (45...

Background: Twice-daily formulation of pasireotide, a pituitary-directed therapy, is approved for treatment of Cushing’s disease. Here we present data from a phase III study designed to evaluate the more convenient once-monthly long-acting release (LAR) formulation of pasireotide (approved for acromegaly) in patients with Cushing’s disease.Methods: Patients with persistent, recurrent, or de novo Cushing’s disease (not candidates for surger...

Background: 24-h mean urinary free cortisol (mUFC) and late-night salivary cortisol (LNSC) levels are complementary parameters recommended for screening and monitoring treatment response in patients with Cushing’s disease (CD). In the published core period of the Phase III LINC 3 study (NCT02180217), therapy with osilodrostat (potent oral 11β-hydroxylase inhibitor) produced rapid, sustained reductions in mUFC and LNSC alongside improvements in clinical signs of hyper...

ARMC5 mutations are associated with PBMAH risks, but the ARMC5 action mechanism remains unknown. We discovered that ARMC5 was part of a novel ubiquitin ligase (E3) specific for RPB1, the largest Pol II subunit. ARMC5 deletion significantly reduced RPB1 ubiquitination and increased RPB1 accumulation. Surprisingly, the degradation of not only RPB1 but all the 12 subunits of Pol II was compromised in the absence of ARMC5, suggesting that this E3 acts on RPB1 and molecules in its ...

Background: Lamin A/C mutations show heterogeneous phenotypes expanding from cardiopathies to lipodystrophies. LMNA-related heart disease has recently been shown to be associated with a high incidence of phenotypic progression and adverse arrhythmic and non-arrhythmic events. Anticipatory planning to prevent sudden death has been recommended in a multicentric cardiologic recruitment. Nevertheless the specific cardiac prognosis of R482-LMNA mutated patients, the hot-spot for pa...

Introduction: A monthly, long-acting formulation of pasireotide normalized or reduced mean urinary free cortisol (mUFC) in most patients with Cushing’s disease (CD) in a multicentre, double-blind, Phase III study. The effects of long-acting pasireotide on signs and symptoms of CD are reported here.Methods: Patients with persistent/recurrent (n=123) or de novo (non-surgical candidates; n=27) CD and mUFC≥1.5–5xULN...

Lipodystrophy (LD) and obesity are opposites in terms of a deficiency versus excess of adipose tissue mass, yet these conditions are accompanied by similar metabolic consequences. VAT has not been well quantified in LD. The aim of this study was to compare the metabolic profile and VAT in different kinds of LD. Six-eight adult patients (45 females) referred for LD were classified in four groups: 23 LMNA-mutated patients (LMNA), 14 non-mutated related to the LMNA-...

Objectives: The aim of this prospective study was to compare the diagnostic performance of 99mTc-sestaMIBI SPECT scintigraphy (sestaMIBI), 18F-fluorocholine PET/CT or PET/MR (FCH) for preoperative localization of hyperfunctioning parathyroid gland.Materials and Methods: 60 patients with biochemical evidence of primary (n=57) or tertiary (n=3 kidney transplanted patients) hyperparathyroidism were imaged prospectivel...