Endocrine Abstracts

Context: Nicotinamide nucleotide transhydrogenase (NNT) is a NADPH-generating mitochondrial proton pump with a central role in mitochondrial antioxidant pathways. Recent studies revealed inactivating NNT mutations in patients with familial glucocorticoid deficiency, indicating a selective susceptibility of the adrenal cortex to NNT deficiency and oxidative stress. Here we explored the potential value of NNT as a therapeutic target in adrenocortical cancer.<p class="abstext...

Context: Polycystic ovarian syndrome (PCOS) is the most common endocrine disorder in women of classic androgen synthesis. Recent work has highlighted that impaired DHEA sulfation results in enhanced androgen production. Here, we evaluated the relationship between DHEA and DHEAS and androgen excess and metabolic phenotype in PCOS.Patients and methods: We compared 65 women with PCOS to 35 healthy women matched for age and body mass index (BMI). All subject...

Background: Cushing’s syndrome (CS) is caused by endogenous cortisol excess and is associated with significant morbidity. Twenty-four-hour urinary cortisol is one of the most useful tools to diagnose CS although it has limitations, especially in “mild” and “subclinical” forms of cortisol excess. We hypothesized that given the diurnal rhythm of physiological cortisol secretion, night-time urinary glucocorticoid excretion should be lower than day-time ex...

Nicotinamide nucleotide transhydrogenase (NNT) is a highly conserved inner mitochondrial membrane protein, which supplies high concentrations of NADPH for detoxification of reactive oxygen species (ROS) by glutathione and thioredoxin pathways. In humans, loss-of-function mutations in NNT cause familial glucocorticoid deficiency, a potentially fatal, adrenal specific disorder characterized by increased levels of ACTH and low levels of cortisol. Nnt−...

Nicotinamide nucleotide transhydrogenase (NNT) is a NADPH-generating mitochondrial proton pump with a central role in mitochondrial antioxidant pathways. Recent studies revealed inactivating NNT mutations in patients with familial glucocorticoid deficiency, indicating a selective susceptibility of the adrenal cortex to NNT deficiency and oxidative stress. Here we explored the potential value of NNT as a therapeutic target in adrenocortical cancer. We delineated the distinct ef...

Introduction: Idiopathic intracranial hypertension (IIH) occurs in young obese women (>90%) but little is known about the metabolic characteristics in these patients. We aimed to characterise IIH fat distribution, metabolic phenotype and evaluate alterations following weight loss.Methods: IIH and matched (BMI/sex) healthy obese controls were recruited. Metabolic indices (fasting lipid, glucose, insulin), anthropological measures and body composition ...

Insulin resistance and androgen excess are the cardinal features of polycystic ovary syndrome (PCOS). The severity of hyperandrogenism and metabolic dysfunction in PCOS are closely correlated, but underlying mechanisms remain poorly understood. Aldoketoreductase type 1C3 (AKR1C3) is an important source of adipose androgen generation, activating androstenedione to testosterone (T). We postulated that AKR1C3 plays a critical role linking androgen metabolism and...

Introduction: Measuring serum cortisol to evaluate the normal circadian rhythm and adequacy of hydrocortisone replacement levels requires multiple readings; an expensive, cumbersome process. Conversely, salivary cortisone, a surrogate marker for free cortisol levels is non-invasive and well suited for out-patient settings. We hypothesised that salivary cortisone predicts circulating cortisol levels and can be used as an alternative marker of serum cortisol in a physiological s...

Introduction: Prostate cancer (PC) is dependent on androgen receptor (AR) activation by its canonical ligands testosterone and 5α-dihydrotestosterone (DHT). Intratumoural androgens persisting after castration give rise to castration-resistant PC (CRPC). These intraprostatic androgen levels are hypothesized to result from either adrenal androgen conversion or intratumoural de novo DHT synthesis through the classic or alternative pathways. Quantifying the steroid f...

Introduction: Testicular leydig cell tumours (LCTs) are rare stromal tumors often associated with androgen excess. Metastatic malignant LCTs typically show resistance to radiotherapy and cytotoxic chemotherapy, calling for alternative management options. Here we describe our experience with treatment of two patients with metastatic LCTs with the adrenolytic drug Mitotane.Patients/methods: Case 1: A 51-year-old patient presented with a 6 month hi...