Endocrine Abstracts

Introduction: In a Phase II study, osilodrostat, a potent oral 11β-hydroxylase inhibitor, normalized mean urinary free cortisol (mUFC) in most patients with CD. We report the efficacy and safety of osilodrostat in a large CD patient population (NCT02180217).Methods: In this study, open-label osilodrostat was initiated at 2 mg bid in 137 adults with CD and mUFC > 1.5 × ULN, with dose adjustments every 2 weeks (range 1–30 mg bid) up to ...

Background: The phase 3, open-label SONICS study of levoketoconazole demonstrated sustained reduction in mean urinary free cortisol (mUFC) in adults with endogenous Cushing’s syndrome (CS). The extended evaluation phase (Ext) of SONICS reported here further assessed long-term safety, tolerability, and benefit/risk of this treatment.Methods: SONICS consisted of dose-titration (150 – 600 mg BID to attain maximally tolerated dose for mUFC normal...

Pasireotide (PAS) has a safety profile similar to first-generationsomatostatin analogues (SSA), except for a higher frequency of hyperglycaemia-related adverse events (AEs). However, consensus on the best management of PAS-induced hyperglycaemia in acromegalic patients has still to be defined. The current study aims at investigating the effects of long-term PAS treatment on glucose metabolism, by evaluating the clinical management of hyperglycemia-relatedAEs in acromegalic pat...

Propose: To screen for the presence of putative targets for new treatments in a large cohort of advanced adrenocortical cancer (ACC)Experimental design: In 40 adult stage III-IV ACC primary samples, we used comparative genomic hybridization (CGH) and hotspot gene sequencing (with Ion Torrent) to describe the presence of copy number abnormalities and mutations in more than 40 genes involved in cancer development and putative drug sensitivity (HER2; EGFR; ...

Normosmic congenital hypogonadotropic hypogonadism (nCHH) is a rare reproductive disease leading to lack of puberty and infertility. Loss-of-function mutations of GNRH1 gene are a very rare cause of autosomal recessive nCHH. R31C GNRH1 is the only missense mutation that affects the conserved GnRH decapeptide sequence. This mutation was identified in a CpG islet in nine nCHH subjects from four unrelated families, giving evidence for a putative ‘hot spot&#...

The pathogenesis of pheochromocytomas (pheo) is poorly understood and malignant pheo need new treatment options. mTOR inhibitors, as sirolimus (S) and everolimus (E), are new promising antineoplastic drugs.Aim: To evaluate whether the IGF/mTOR pathways have a role in the pathogenesis and whether S and E may have antiproliferative effects in pheo.In 24 human pheo and two normal adrenal medulla (NM), we evaluated the mRNA expression ...

Background: Adrenocortical carcinoma (ACC) is an uncommon malignancy with a still scantily understood pathogenesis and generally poor prognosis. Many patients with ACC need new treatment options. mTOR inhibitors, as sirolimus (S) and temsirolimus (T), are promising antineoplastic drugs in several kinds of tumors.Methods: In three human ACC cell lines (H295, HAC15 and SW13), we evaluated the mTOR and IGF2 expression at mRNA level (by qPCR) and at protein ...

Chronic exposure to hypercortisolism has a significant impact on patient’s health and Health-Related Quality of Life (HRQoL), as demonstrated with generic questionnaires. Objective: Develop and validate a disease-generated questionnaire to evaluate HRQoL in patients with Cushing’s syndrome-CS- (Cushing QoL). Methods: After a literature review, interviews with expert endocrinologists and 10 patients identified HRQoL domains and clinical aspects of the disease; an anal...

GH hypersection results in biventricular concentric hypertrophy and a progressive contractile impairment whereas cardiac hypotrophy and impaired diastolic filling and left ventricular function have been reported in GH deficiency (GHD). No information on cardiac performances and structure are available about those acromegalic patients in whom successful treatment made their GH and IGF-I secretion similar to those in GHD patients. In order to study the functional and structural ...

Acromegaly is a disorder characterized by overproduction of growth hormones (GH), which causes tissue growth in the body and comorbidities and symptoms. While prior studies examined comorbidities commonly associated with acromegaly, few have long follow-up periods necessary to characterize the long-term comorbidity profile of patients with acromegaly. There is limited literature on real-world treatment patterns of patients with acromegaly. This study describes the long-term pr...