Endocrine Abstracts

Aim: To asses the significance of single 60 min serum cortisol level compared to conventional approach in short synacthen test (SST).Methods: Retrospective analysis of cortisol values in SST. Serum cortisol values at baseline, 30 min and 60 min were recorded. Rise of serum cortisol level to >550 nmol/l and a rise of >200 nmol/l from baseline is considered to be a negative test for hypoadrenalism.Results: About 168 patients ...

Oxidative stress is a principle cause of the development of aging and diseases such as inflammation, infection, cancer, and cardiovascular disorders 1–3. Steroids are used as progestational, anabolic, antitumor agents, oral contraceptives and sedatives. Hydroxylated estrogens are important therapeutic agents used in the treatment of breast tumors etc. However, synthesis of these hydroxylated estrogens is difficult to achieve. We have investigated a bacterial tr...

The aim of this retrospective study was to assess hydrocortisone replacement therapy in patients with adrenal insufficiency, by correlating hydrocortisone regimens and doses to that of serum and urine cortisol levels.Method: We studied the case notes of 83 patients, whose records contained the results of at least one valid hydrocortisone day curve and 24 h urine free cortisol level. Twenty-seven patients were on twice daily, and 56 were on thrice daily r...

Deoxycorticosterone (DOC: a weak mineralocorticoid) is the precursor to corticosterone (B: the major glucocorticoid in rodents) and aldosterone. Cyp11b1 encodes 11β-hydroxylase which catalyses the conversion of DOC to B in rodents. The aim of this study is to develop sensitive and specific ELISA methods to estimate urinary DOC and B levels in mice. Antibodies against DOC and B were raised in rabbits by our laboratories as previously described and HRP-Goat anti-Rabbit IgG ...

The majority of immunoassays used to measure aldosterone (most potent mineralocorticoid) levels are still based on radio-iodinated tracer, lack sensitivity and specificity and there is a definite need for their improvement. The aim of this project is to develop a highly sensitive and specific ELISA method for urinary aldosterone estimation in samples obtained from wild type and cyp11b1 knockout mice. Antibodies against aldosterone were raised in sheep as previously described. ...

Glucocorticoids mediate the stress response, regulated via the hypothalamic–pituitary–adrenal (HPA) axis. The HPA axis is down-regulated and its responsiveness to stress is impaired in cholestasis. The mechanisms are unknown, but may involve reduced glucocorticoid clearance. Hepatic 5beta-reductase is involved in glucocorticoid inactivation and bile acid biosynthesis. We showed previously that bile acids are potent competitive inhibitors and transcriptional regulator...

Introduction: Systemic steroids have an established role in the management of numerous medical conditions across all specialities. Osteoporosis predisposing to osteoporotic fracture is a well known adverse effect of long term steroid treatment, which can affect at an early stage of the treatment. Established steroid induced osteoporosis is associated with significant co-morbidity and is difficult to reverse.Aim: To determine the frequency of osteoporosis...

Nebido (testosterone undecanoate, 1000 mg) is a new, long acting, intramuscular (IM) preparation of testosterone (T) that can be administered every 10–14 weeks. We conducted a study to evaluate the factors that influence serum T levels after commencing Nebido and may therefore help clinicians estimate dosing frequency for this therapy.Following the recommended loading regimen, 51 hypogonadal men (35, 68.6% secondary hypogonadism) had two injections ...

Gram negative bacterial meningitis with consequent meningeal inflammation is a major cause of death and morbidity worldwide. Meningitis denotes infection of the blood brain barrier (BBB) including the choroid plexus (CP), the site of secretion of cerebrospinal fluid (CSF). We propose that 1α 25-dihydroxyvitamin D3 (1α25-(OH)2D3), an important immunomodulator, may suppress CP inflammation thereby reducing morbidity. We aimed to assess ...

A 21-year-old gentleman, with known congenital adrenal hyperplasia (CAH) due to 21-hydroxylase-enzyme deficiency, presented to Genito Urinary Medicine clinic with dysuria. Examination of testes revealed bilateral firm lumps. Ultrasound scan showed bilateral testicular hypoechoic masses suspicious of malignancy. A second opinion ultrasound scan done at a tertiary care centre confirmed the same findings with the possibility of tumours being either seminoma or teratoma in origin....

Acute adrenal insufficiency requires immediate treatment with high-dose glucocorticoid and represents a life-threatening emergency. Previous research suggests that primary hypoadrenalism patients (Addison’s disease) are more vulnerable to adrenal emergency than steroid-dependent pituitary patients (Arlt & Allolio 2003).In 2006, we surveyed the membership of the UK Addison’s disease Self-Help Group, comprising 982 hypoadrenalism patients, an...

Introduction: Short synacthen tests (SST) are widely performed as a screening test in patients with suspected hypoadrenalism. However, the timing of sampling and interpretation of cortisol levels remain a matter of controversy. Though known to be inferior to 30 min cortisol levels, some centres continue to analyse 60 min values (along with 30 min levels) to avoid resource-intensive tests like insulin stress tests and glucagon stimulation tests.Objective:...

Ocular and orbital tissues are extremely susceptible to damage by immune-mediated inflammatory conditions, such as thyroid-associated-ophthalmopathy (TAO). Recent studies have implicated fibroblasts in the development of chronic inflammation. Once activated by inflammatory cytokines, fibroblasts secrete pro-inflammatory cytokines perpetuating the inflammatory process, causing significant tissue damage. Synovial fibroblasts have been reported to regulate inflammation by increas...

Introduction: Androgens are known to play an important role in renal tubular epithelial cell growth, hypertrophy and erythropoetin production, however the exact mechanisms are not clear yet. 5α-dihydrotestosterone is synthesized primarily in gonads and skin, and is the most used androgen in studies. However, little is known about testosterone effects in non-gonadal tissues.Methods: Male Wistar rats aged 8–10 weeks were orchiectomized and put on...

Objective: There is evidence that current replacement regimens fail to restore well-being in patients with adrenal insufficiency (AI). No data is available on the effect of different therapeutical regimes (hydrocortisone, prednisolone and cortisone acetate) on the quality of life in these patients.Methods: Eight hundred and eighty three patients with adrenal insufficiency were contacted, 526 patients participated (60%) and received a disease specific que...

Salivary cortisol (SalC) potentially has advantages over serum cortisol (SerC) as it is easier to collect and possibly reflects unbound (free) cortisol. SalC levels are approximately 10 times lower than SerC and require high measurement precision best addressed by liquid chromatography–tandem mass spectrometry (LC-MS/MS), which in contrast to previously used radioimmunoassays eliminates cross-reactivity by other steroids. We describe the use of LC-MS/MS to evaluate the po...

Itraconazole increases glucocorticoid levels through inhibition of CYP3A4 in the liver. Recent case-reports have shown that the co-administration of itraconazole with inhaled glucocorticoids in asthmatics may result in suppression of their HPA axis and a Cushing’s phenotype. We have evaluated the impact of this interaction on the cortisol axis in a double-blind randomised placebo-controlled study.Twenty-seven patients with severe asthma (17 women; m...

Congenital adrenal hyperplasia (CAH) screening programs are based on 17 OH-progesterone (17OHP) assay in dried blood spots sampled 3d after birth (samples >50 nmol/l are retested as duplicates and the alert threshold is 60 nmol/l). These programs have improved the diagnostic rate of the salt-wasting form. Confronted to delayed hyperandrogenic diagnosis in older children physicians sometimes request retesting years old dried blood spots to rule out erroneous initial true ne...

A 63-year-old lady was admitted with a 10 day history of central abdominal pain associated with constipation and vomiting. She was diagnosed with myelodyplasia 11 years previously and required regular blood transfusions but was otherwise fit and well. On this presentation, she was apyrexial with a heart rate of 72 beats per minute and blood pressure of 170/74. Her abdomen was soft with mild periumbilical tenderness. Routine blood investigations showed haemoglobin of 10.2 g/dl ...

With age, sex hormones concentrations undergo changes but may continue to have a significant impact: several studies have shown the association of low levels of bioavailable estradiol (BE2) with osteoporosis in man. In postmenopausal women, estradiol levels may influence cognitive function or breast cancer risk.A better approach of sex hormones profiles related to age becomes necessary. We evaluated BE2 concentrations and its variation with age in men, a...

Congenital adrenal hyperplasia (CAH) due to steroid 21-hydroxylase (CYP21A2) deficiency is the commonest inborn error in steroid hormone biosynthesis and the most frequent cause of congenital adrenal hyperplasia. The classic forms of 21-hydroxylase deficiency, salt-wasting (SW) and simple virilising (SV), usually present in the neonatal period with some simple virilising patients presenting later in childhood with precocious pseudopuberty. The non-classic form (NCCAH) mostly m...

Sleep and cortisol cycles have a complex inter-relationship that is not fully understood. Slow wave sleep appears to have an inhibitory effect on cortisol production but the effect of other stages is not so clear. From diseases, such as Addisons disease and Cushings syndrome, we know that cortisol levels have an impact on the quality of sleep. In insomnia and depression, both sleep and cortisol is altered.To investigate this relationship properly a minim...

High dose glucocorticoids are effective in suppressing inflammatory synovitis but have adverse effects on other connective tissues. In inflammatory arthritis glucocorticoids suppress the capacity of synovial fibroblasts (SFs) to recruit leukocytes to the joint whereas poor skin healing is due to impaired dermal fibroblast (DF) function. It is unknown whether these clinical differences are due to similar or distinct effects of glucocorticoids on fibroblast function.<p class...

Background: Virilising congenital adrenal hyperplasia (CAH) is the most common cause of genital ambiguity, and 90–95% of CAH cases are caused by 21-hydroxylase deficiency. Associated inefficient cortisol synthesis results in increased CRH and ACTH levels, leading to production of excess sex hormone precursors. These are further metabolized to active androgens and to a lesser extent oestrogens. We recently reported that one of these androgens, DHEA-S or its metabolites sig...

Glucocorticoid (GC) excess is characterized by increased adiposity, skeletal myopathy and insulin resistance. Despite the increasing use of GCs as therapeutic agents, the molecular mechanisms that underpin GC mediated changes in insulin signalling are not clear. Within skeletal muscle, the microsomal enzyme, 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) converts inactive GC, 11-dehydrocorticosterone (A) to active corticosterone (B) and thus regulates GC availabi...

Introduction: We report a case of adrenal insufficiency as the first clinical manifestation of antiphospholipid syndrome.Case report: A 56-year-old male with no previous history of thrombosis was admitted with 3 stone weight loss and feeling generally unwell. He was hypotensive, pigmented and had a slate grey pigmentation of the nose. Chest auscultation revealed reduced breath sounds. Investigations revealed low sodium and high potassium levels with meta...

Stress results in activation of the hypothalamic–pituitary–adrenal axis with increased circulating cortisol. It has been argued that a syndrome of ‘relative adrenal insufficiency’ is common in critically ill patients. Patients who fail to increase their cortisol by >250 nmol/30 min following the administration of 250 μg ACTH in the short synacthen test (SST) have been reported to have a higher mortality (JAMA 2000, 283 1038–1045)...

Aldosterone plays a key role regulating electrolyte homeostasis and blood pressure. An elevated aldosterone to renin ratio is present in 15% of hypertensive patients but the causes of aldosterone excess are not fully understood. There is evidence of interaction between the polymorphisms in the aldosterone synthase gene (CYP11B2) and aldosterone levels in plasma and urine. However, the most consistent associations between variation at this locus and altered steroid synth...

Familial glucocorticoid deficiency (FGD) is a rare autosomal recessive disease due in ∼25% of cases to defects in the ACTH receptor (melcanocortin 2 receptor -MC2R). Slow progress in characterization of these mutations has been made in view of the difficulty in establishing a functional heterologous cell transfection system for the MC2R, and the best available models relate to the mouse Y6/OS3 cell lines. However we have shown previously that the melanocortin 2 receptor ...

Type 2 diabetes manifests when pancreatic β-cells secrete inadequate insulin in response to elevated glucose. A known culprit in metabolic diseases is excessive exposure to glucocorticoids (GCs). GCs increase hepatic gluconeogenesis, decrease insulin sensitivity in skeletal muscle and adipose tissue and suppress the development of β-cells. In rodents, inactive GC 11-dehydrocorticosterone (A) is converted to active corticosterone (B) by the enzyme 11β-hydroxyster...

Background: Glucocorticoids play a key role in determining body fat distribution. Excess circulating glucocorticoids lead to intrahepatic fat accumulation. Obesity is associated with enhanced glucocorticoid production but this is offset by enhanced degradation such that circulating steroid concentrations are normal. However, tissue-specific pathways may lead to different degrees of cortisol exposure in different organs. Local steroid exposure in the liver is determined by the ...

Adrenal insufficiency (AI) patients who are deprived of regular steroid replacement therapy rapidly become unwell. However, the interval for which AI patients might safely be withdrawn from steroid medication for clinical purposes, such as re-assessment of adrenal reserve, is largely a matter of speculation, since it would be difficult to construct an ethical trial on this matter. Valuable insights into this dilemma can be gained from the case studies of an early clinical rese...

Several hormones, including cortisol, have a circadian rhythm in plasma and saliva. Salivary cortisol is now extensively used for screening and following patients with various conditions where the regulation of hypothalamo–pituitary–adrenal axis is abnormal, for example in major depression where salivary cortisol levels show a disruption or loss of circadian rhythm. Annexin 1 is a glucocorticoid-induced protein, which is responsible for mediating several anti-inflamm...

CYP17A1 is a key enzyme of human steroidogenesis, which is unique in that it catalyses two reactions, 17-hydroxylase activity converting pregnenolone and progesterone to 17-hydroxypregnenolone (17Preg) and 17-hydroxy-progesterone, respectively, and 17,20 lyase activity, responsible for the conversion of 17Preg to dehydroepiandrosterone the crucial precursor of human sex steroid biosynthesis. 17-hydroxylase deficiency, a variant of congenital adrenal hyperplasia, results in glu...

A 40-year-old male presented with blackouts. This was associated with transient loss of consciousness with complete subsequent recovery. He did not have any warning signs, tongue biting or urinary incontinence. There was no history of alcohol or elicit drug abuse. He was admitted to MAU.Past medical history: HIV diagnosed 18 months previously. Cutaneous and oral Kaposi’s sarcoma successfully treated with chemotherapy. Hepatitis C, asthma.<p clas...