Endocrine Abstracts

Background: Improving physical manifestations of hypercortisolism is an important treatment goal for patients with Cushing’s disease (CD). In the Phase III LINC 3 study (NCT02180217), osilodrostat therapy, a potent oral 11β-hydroxylase inhibitor, rapidly normalised mean urinary free cortisol (mUFC) in most patients with CD and sustained control of mUFC over a median treatment period of 130 weeks (W). Here we describe concomitant improvements in physical manifestation...

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...

Background: 5-Cytosine methylation of DNA is a means of encoding epigenetic information. In the testis, the generation of de novo methylation is conducted by the enzymes DNMT3a and 3b and the co-enzyme DNMT3L. Epigenetic marks made to the DNA of germ cells are important as a potential means of trans-generational carriage of environmental information. In fetal life, germ cell demethylation and remethylation are important physiological events and these overlap with key ...

Testicular dysgenesis syndrome (TDS) is a group of associated conditions (testicular germ cell tumours (TGCT), cryptorchidism, hypospadias and low sperm counts) that are thought to have a common origin in fetal life. Exposure of fetal rats to environmental chemicals such as the endocrine disrupting chemical di(n-butyl) phthalate (DBP) results in a TDS-like syndrome. However, exposed rats do not develop TGCT and the rodent is a poor model in this context. The effects of ...

Recent data suggest that critically-ill medical patients might not obtain as much benefit from insulin therapy as cardiothoracic patients. This may be because medical patients are more insulin resistant. We have investigated this in both groups.10 medical patients (age 67.0±4.4 y; 7M:3F, BMI 24.0±1.7 kg/m2; studied within 36 hours of admission to the ICU) and 7 post-operative cardiothoracic patients (age 71.4±3.8 y; 5M:2F, BMI 2...

Background: Osilodrostat (potent oral 11β-hydroxylase inhibitor) provided rapid normalisation of mean urinary free cortisol (mUFC) in Cushing’s disease (CD) patients during the 48-week (W) core period of LINC 4 (NCT02697734) and was well tolerated. We report long-term efficacy and safety results from the LINC 4 core and extension phases.Methods: 73 adults with CD and mUFC >1.3 upper limit of normal (ULN) were enrolled. LINC 4 comprised a 12...

Introduction: In many endocrine centres the 250μg Short Synacthen (Cosyntropin) Test (SST) is the reference standard for the diagnosis of adrenal insufficiency (AI) 1, but it is time consuming, expensive, and requires hospital attendance and venepuncture. The morning physiological peak of cortisol shortly after waking is a good predictor for a negative SST; however, a morning serum cortisol requires venepuncture. Serum cortisol and salivary cortisone correlate ...

Background: Cushing’s disease (CD) is associated with hypercortisolism-induced cardiovascular morbidity and mortality and impaired patient quality of life (QoL). We report long-term effects of osilodrostat (potent 11β-hydroxylase inhibitor) on cardiovascular/metabolic-related risk factors, physical features of hypercortisolism and QoL in CD patients following the core and extension phases of the LINC 4 study (NCT02697734).Methods: LINC 4 compri...

Introduction: The 250µg Short Synacthen test (SST) is the reference standard for a diagnosis of adrenal insufficiency (AI) in most endocrine centres. The test is expensive and time consuming, requiring clinic attendance. We hypothesised that a cheaper home waking salivary cortisone (WSC) is predictive of the SST 30-minute cortisol >430 nmol/l cut-off and carried out a diagnostic accuracy study to assess the predictive value of the WSC in diagnosing and excluding AI. W...

Background: Cushing’s syndrome (CS) has numerous comorbidities, including diabetes mellitus (DM). Levoketoconazole is a ketoconazole stereoisomer in clinical trials for treatment of CS.Methods: SONICS is a prospective, open-label, phase 3 maintenance-of-benefit study in adults with confirmed CS and mean urinary free cortisol (mUFC) of ≥1.5x upper limit of normal (ULN). Repeated hospitalization due to hyperglycemia or any complication related t...