Endocrine Abstracts

Background: In the 22-week LINC-2 study, osilodrostat (LCI699), a potent oral 11β-hydroxylase inhibitor, normalized urinary free cortisol (UFC) levels in 15 of 19 patients with Cushing’s disease (CD). The most common AEs were nausea, diarrhea, asthenia, and adrenal insufficiency (n=6 each). Here, we report the 31-month efficacy and safety results from LINC-2 extension.Methods: Patients receiving clinical benefit at week 22 could enter ...

Introduction: The clinical features and complications of Cushing’s syndrome result from chronic excess of circulating cortisol, typically quantified by 24-h urinary free cortisol (UFC). LCI699 is a potent inhibitor of 11β-hydroxylase. Since 11β-hydroxylase catalyzes the final step of cortisol synthesis, LCI699 is a potential new treatment for all forms of Cushing’s syndrome.Methods: Adult patients with mild-to-severe Cushing’s di...

ACTH-independent macronodular hyperplasia (AIMAH) affects both adrenals, and familial forms are reported, suggesting a genetic origin. Rare mutations have been reported in several genes, including Gs alpha (GNAS), Phosphodiesterase 11A (PDE11A), Fumarate Hydratase (FH), and the Glucocorticoids receptor (GR).Objective: To assess the prevalence known genes mutations, and identify new candidate genes in AIMAH.Design and methods: Germl...

Introduction: Alternative to transsphenoidal pituitary surgery (TSS) may be required in Cushing’s disease (CD), as first or second line treatment. 1,ortho-1,para′-dichloro-diphenyl-dichloroethane (o,p′DDD) has a potent anticortisolic action. Its place in CD treatment is not well defined. The aim of this study was to further evaluate the efficacy and tolerance of o,p′DDD in CD.Patients and m...

The outcome of ACTs can be determined by gene expression level at the RNA level. However RNA handling is challenging. In contrast tumor DNA is robust and therefore easier to use.Aim: To characterize the ACTs DNA alterations; to identify markers with diagnostic and prognostic value using tumor DNA.Methods: The mapping of chromosomal gains and losses of 60 ACTs (39 adenomas (ACAs), 21 carcinomas (ACCs)) was performed with CGH arrays ...

In primary adrenal insufficiency hydrocortisone or cortisone are commonly used at doses of 30–37.5 mg/day as replacement therapy, though recent studies showed that cortisol normal production is about 5.7 mg/m2, equivalent to 20 mg/day of hydrocortisone, suggesting that supraphysiological doses are used. In 19 Addison’s disease patients (8 M, 11 F, 23–71 yr) under conventional glucocorticoid replacement therapy (37.5 mg cortisone/day) with low DHEAS le...

Varicocele is a state of varicosity and tortuosity of the pampiniform plexus around the testis caused by retrograde blood flow. The association between varicocele and male subfertility has been questioned, thus the usefulness of treating varicocele in order to improve fertility is still a matter of debate. Inhibin B levels reflect the functional state of the seminiferous epithelium, and have been found to be a sensitive index of spermatogenesis. Serum inhibin B levels have bee...

Acylated ghrelin (AG) participates in the modulation of the hypothalamic-pituitary-gonadal axis functions, with a predominantly inhibitory effect upon the reproductive system in animals. Animal studies have shown that ghrelin suppresses LH secretion in vivo, decreases LH responsiveness to GnRH in vitro and partially delays the timing of puberty in males. Aim of this study was to evaluate the effects of AG infusion on spontaneous and stimulated gonadotropin secret...

Tissue samples from adrenal tumors provide the basis for standard diagnostic procedures such as pathological examination. In addition, these tumor samples have been an invaluable source for the discovery of novel molecular pathways involved in adrenal tumorigenesis. Information on the molecular phenotype are based on DNA mutation analysis and epigenetic changes, RNA and protein expression pattern and sub-cellular localization as well as post transcriptional protein modificatio...

Thyroid hormones play a central role in the regulation of bone turnover and thyrotoxicosis is an established cause of secondary osteoporosis. Increased prevalence of reduced bone mineral density (BMD) has been reported even in patients with subclinical thyrotoxicosis such as those with differentiated thyroid carcinoma undergoing long-term L-thyroxine (L-T4) TSH-suppressive therapy. Morphometric vertebral fractures (VFs) are an early and clinically...