Endocrine Abstracts

Glucocorticoid (GC) excess, whether exogenously- or endogenously-derived, induces many adverse effects in skin including thinning, decreased cellularity and reduced collagen synthesis. Consequently, skin exhibits reduced dermal structural integrity, increased atrophy/fragility/bruising and impaired wound healing, effects that perfectly mimic skin ageing. Local GC levels are regulated in a tissue-specific manner by 11β-hydroxysteroid dehydrogenase (11β-HSD) isozymes i...

Background: Primary Aldosteronism (PA) is common and associates with excess cardiovascular morbidity independent of blood pressure. Animal and in vitro studies have demonstrated that exposure to aldosterone and sodium leads to cardiac fibrosis and hypertrophy and this may, partly, be mediated by inflammation and oxidative stress. We aimed to clarify the effects of aldosterone excess on myocardial structure and composition in humans using contrast-enhanced cardiac MRI as well a...

A counter-regulatory rise in GC levels is important to the inflammatory response, that when impaired is associated with high mortality in inflammatory states. 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) regenerate’s intracellular glucocorticoids (GC), amplifying their actions, and has been postulated to play a role in the development of inflammation-associated arthritis, obesity and myopathy. Pro-inflammatory cytokines (e.g. TNF-α) increase expressio...

Glucocorticoid excess is associated with increased anxiety and accelerated cognitive decline. Concentrations of glucocorticoids within tissues, including the brain, are influenced by local metabolism. 5α-Reductase 1 (5αR1), expressed in brain, converts corticosterone to its A-ring reduced metabolites, which have a different spectrum of activities. Here, we investigated if mice homozygous for disrupted 5αR1 alleles (5αR1-KO) experience heightened anxiety and...

In congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency a genotype-phenotype correlation exists for paediatric cohorts, helping to predict the severity of disease expression. Data on the correlation in adults is lacking. Here we report the genetic analysis of the UK CaHASE cohort, comprising CAH adults seen at 17 endocrine tertiary care centres. CYP21A2 mutation analysis was performed in 153 patients (median age 35 (range 18–69) yrs; 103 f, 50 m) by multi...

Intra-abdominal adiposity is associated with insulin resistance and increased cardiovascular morbidity and mortality. Consequently, there is a need to identify factors involved in adipose tissue distribution. Patients with glucocorticoid (GC) excess develop a classic phenotype characterized by central, but not peripheral, obesity. Differences in gene expression between omental (om) and subcutaneous (sc) adipose tissue have been described, however, the molecular mechanisms unde...

Patients with growth hormone deficiency (GHD) have many clinical features in common with Cushing’s syndrome (glucocorticoid excess) - notably visceral obesity, insulin resistance, osteoporosis and increased vascular mortality. Within key metabolic tissues, 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) converts cortisone to the active glucocorticoid, cortisol, and thus amplifies local glucocorticoid action. We hypothesise that 11β-HSD1 expression is neg...

Context: Congenital adrenal hyperplasia (CAH) is caused by 21-hydroxylase deficiency in 95% of the cases. This leads to accumulation of steroid precursors prior to the enzymatic block and increased adrenal androgen production; accordingly serum concentrations of 17-hydroxyprogesterone (17OHP), androstenedione and testosterone are elevated in affected patients.Objective: To analyse the effect of 17OHP, androstenedione and testosterone on aldosterone-media...

Background: Triple A Syndrome is a rare, autosomal recessive cause of adrenal failure that usually manifests in the first decade. Most cases have isolated glucocorticoid deficiency, but this is accompanied by mineralocorticoid deficiency in approximately 10% of cases. Additional features include alacrima (~90%), achalasia of the oesophageal cardia (~75%), and a progressive neurodegenerative process (~60%). The AAAS gene product is the nuclear pore complex protein ALADIN...

Background: The melanocortin 2 receptor (MC2R)/melanocortin 2 receptor accessory protein (MRAP) are critical components of the hypothalamo-pituitary-adrenal axis (HPA). MRAP2, homologue of MRAP, can also regulate the MC2R in vitro, however, the physiological significance of this is unclear. We studied the expression of the MRAPs and MC2R in a well-defined rat model of endotoxin induced septic shock. These animals have been shown to have higher ACTH and corticosterone le...

Introduction: The repercussions of long-term exposure to low level mixtures of endocrine disrupting compounds (EDCs) which are present, ubiquitously, in the environment are not well understood. Heat-treated sewage sludge, an EDC-rich product used as fertiliser, has been shown to compromise testicular and ovarian development. However, to date, there has been limited investigation in exposed animals of the adrenal glands, the steroid hormone products of which play key roles in f...

Background: Through out history, pomegranate symbolizes fertility and has been postulated to enhance sexual function and drive. Recently, we have shown that pomegranate juice rich in polyphenolic antioxidants can alleviate stress and cardiovascular risk factors by reducing systolic and diastolic blood pressure and inhibiting 11βHSD1 activity. The aim of this study was to investigate whether pomegranate juice intake influences mood and salivary testosterone levels in healt...

Introduction: Aldosterone is a potent adrenal steroid hormone which regulates renal sodium reabsorption and potassium secretion. Clinically, measurement of aldosterone is important to identify patients with primary hyperaldosteronism, and has traditionally been performed by immunoassay. The specificity of immunoassays is often poor due to antibody cross reactivity to other structurally related steroid hormones, resulting in falsely elevated concentrations. To overcome these li...

We have previously investigated the ability of glucocorticoids secreted by the adrenal cortex to directly influence gonadal function. In contrast, the primary aim of the present study was to assess whether increased progesterone output from the corpus luteum on day 14 of the ovine oestrous cycle can alter adrenal metabolism (and hence output) of cortisol relative to oestrous cycle day 5. Since cortisol-cortisone inter-conversion by the cloned 11β-hydroxysteroid dehydrogen...

Within target cells, cortisol-cortisone inter-conversion is catalysed by both a NADP(H)-dependent, bidirectional type 1 11β-hydroxysteroid dehydrogenase (11βHSD1) enzyme and by a NAD+-dependent, unidirectional type 2 11βHSD (11βHSD2) isoenzyme. Since several published studies have reported altered glucocorticoid metabolism in polycystic ovary syndrome (PCOS), the current study assessed whether prenatal exposure of lambs to testosterone propionate...

Objective: Mitotane (o,p’DDD) is an effective adrenolytic agent for treatment of advanced adrenocortical carcinoma (ACC). Suppression of cortisol biosynthesis, including inhibition of 11β-hydroxylation, has been described. Decreased cortisol bioavailability is indicated by increased dose requirement for hydrocortisone replacement during mitotane treatment. Urinary excretion of common cortisol metabolites (CM) has been reported to be normal but with increase of 6&#946...

High altitude exposure leads to a marked natriuresis and diuresis facilitated by a reduced resting and subdued post-exercise aldosterone. There is a strong correlation between aldosterone and cortisol at high altitude and although most, but not all, investigators report a rise in cortisol with ascent very little data exist regarding the post-exercise response in cortisol. We therefore measured salivary cortisol in a cohort of 45 subjects post-exercise and 20 subjects at rest w...

Cyclical Cushing’s syndrome is typically detected by collecting sequential daily early morning urine (EMU) samples for cortisol to creatinine ratio over a 28 day period. More recently nocturnal salivary cortisol (NSC) measurement has been shown to be a sensitive means of screening for Cushing’s syndrome. The Endocrine Society have suggested that NSC may be used to assess patients for cyclical Cushing’s however there is limited evidence that it correlates with th...

Aberrant and upregulated eutopic receptors have been identified in vitro in patients with primary aldosteronism (PA). We previously identified an exaggerated aldosterone response to synacthen in patients with PA versus healthy controls. In this study we aimed to evaluate whether the synacthen test differentiates between patients with PA and essential hypertension (EH). The 250 mcg intramuscular synacthen test was performed after 30 minutes recumbency in the morning and off int...

Sialic acid acetylesterase (SIAE) has been found to be essential for the maintenance of immune tolerance in mice by negatively regulating B lymphocyte antigen receptor signalling. Recently, numerous rare heterozygous loss-of-function germline variants and a homozygous functionally defective variant of the SIAE gene (M89V) have been identified as conferring a strong genetic susceptibility to several autoimmune disorders, including T1DM and rheumatoid arthritis. We performed a c...

Context: Patients with adrenal insufficiency (AI) receive glucocorticoid replacement therapy, which tries to imitate physiological adrenal secretion. However, the first glucocorticoid dose is usually given after waking in the morning resulting in a 3–5 h delay compared to physiological secretion. Impaired quality of life (QoL) might be, in part, due to this delayed dose scheme. Therefore, modified-release glucocorticoid preparations might have therapeutical advantages.</p...

Glucocorticoids (Gc) are the most potent anti-inflammatory agents known. A major factor limiting their clinical use is the wide variation in responsiveness to treatment between individuals and over time. Generating a reversible model of Gc resistance in vitro that will mimic the cellular microenvironment in vivo is critical in (i) defining biomarkers that predict patient steroid responsiveness; (ii) provide a model to screen new GR modulators capable of potentiating GR ...

Medicago sativa plants are commonly used as green fodder. In this study, estrogen-like activity of ethanolic extract of Medicago sativa plants and its possible effects on serum biochemical metabolites in immature female rats were investigated. Crude extract of dried Medicago sativa plants was prepared in 90% ethanol using Soxhlet’s apparatus. Fifteen immature female rats were divided into 3 equal groups. Rats of groups A and B were given the extract at the dose of 250 (lo...

There are limited morbidity data regarding patients with adrenal insufficiency. We undertook a retrospective study to examine the aetiology and frequency of emergency hospital admissions. We identified 69 patients receiving hydrocortisone replacement for adrenal insufficiency. 50 medical records were obtained; 20 patients had primary adrenal failure (including CAH) and 30 patients had ACTH deficiency. All emergency admissions that occurred within the last 10 years were reviewe...

Recent epidemiological studies of primary adrenal insufficiency (Addison's disease) in Scandinavia have identified an average age at diagnosis of less than 40 (Bergthorsdottir 2006 n=1675, Erichsen 2009 n=426). They also found a broader range of ages than earlier UK studies, which had suggested that the majority of diagnoses occur in the third to fifth decades of life (Kong 1994, n=86). We analysed all membership records for the UK Addison’s Disease S...

Case History: We report the case history of a 64-year-old woman who was admitted to hospital for evaluation of unsteadiness associated with postural hypotension. There was no history of headache, visual blurring, weight loss, diarrhoea or steroid treatment. She was taking high dose medroxyprogesterone acetate (MPA) 100 mg three times per day for 5 years following diagnosis of complex hyperplasia on endometrial biopsy for postmenopausal bleeding. Her past history included ischa...

Case Report: A lady of 43 presented with an insidious onset of weight loss, lethargy, muscle pains, and more recently; polydipsia, nausea and vomiting. She had been recently started on levothyroxine for primary hypothyroidism. She was hypotensive and tachycardic. Investigations revealed Sodium 123 mmol/L (133–146), Potassium 5.0 mmol/L (3.5–5.3), Urea 16.2 mmol/L (2.5–7.8), Creatinine 153 umol/L (45–90) and calcium 3.4 mmol/L (2.1–2.6). PTH was <0....

A 60 year old female from Zimbabwe with an eight year history of HIV infection presented with malaise and facial swelling. She had been established on antiretroviral treatment (Kivexa (lamivudine / abacavir) and Kaletra (lopinivir / ritonavir)) since shortly after her initial diagnosis. One month earlier she had received an injection of intramuscular triamcinolone acetate to treat an inflammatory polyarthropathy. She was also prescribed inhaled salmeterol xinafoate 50 mcg/flut...

Isolated hypoaldosteronism is a rare condition. It can present with postural hypotension with or without significant hyponatraemia, hyperkalemia or heart block. For patients with Hypoaldosteronism, pregnancy raises issues regarding management of hyperkalemia and adequate blood pressure maintenance. A 17 yr girl presented with symptoms of tiredness, dizziness and routine blood test revealed marked isolated hyperkalemia (Serum potassium 7.1 mmol/L) with normal renal function. Sh...

Rapid and appropriate response to an Adrenal crisis is a matter of life and death. Could greater patient and professional awareness together with modern technology assist in preventing mortality? Patients often first present with adrenal crisis in A&E departments. Whether the cause is primary or secondary adrenal failure, the initial treatment remains the same. Our objective was threefold: Educate and give greater awareness of steroid therapy to hospital staff, educate and...

Background: Primary hypoadrenalism with bilateral adrenal enlargement is a relatively rare condition. We present four such patients. Case 1: 60 year old male presented with malaise, weight loss and hyponatremia. Short synacthen test was abnormal and ACTH was raised (309 ng/L). CT adrenals showed bilateral adrenal enlargement with uniform texture and low attenuation with no change in repeat CT. FNAC of adrenal gland showed infarcts. Further tests confirmed antiphospholipid anti...

Exogenous glucocorticoids lead to suppression of the HPA axis via negative feedback on the hypothalamus and pituitary and may be associated with increased morbidity and mortality (Wei L. Ann Intern Med. 2004). Many patients whose steroids are no longer required for their underlying disease find withdrawal challenging. Presentations: Case 1: 68-year old male treated with steroids for hepatic graft versus host disease following a stem cell transplant for EBV-lymphoproliferative ...

The potent effects of glucocorticoids (GCs) upon carbohydrate metabolism are well described. However, their actions upon lipid metabolism are poorly characterized. Patients with GC excess (Cushing’s syndrome) develop central obesity, insulin resistance and hepatic steatosis in up to 20% of cases. The A-ring reductases (5α-reductase type 1 [5αR1] and type 2 [5αR2]), inactivate cortisol as well as generate dihydrotestosterone (DHT) from testosterone (T) and a...