Endocrine Abstracts

PAPS (3′-phospho-adenosine-5′-phosphosulfate) synthases provide the cofactor PAPS for all human sulfation pathways. The cytoplasmic sulfotransferase SULT2A1 uses PAPS mainly to sulfate the androgen precursor DHEA (dehydroepiandrosterone). Apparent SULT2A1 deficiency is caused by mutations in the gene coding for PAPSS2; suggesting some form of PAPS synthase-sulfotransferase pairing. Knockdown studies within human adrenocortical NCI-295R ce...

In the clinic, glucocorticoids are widely used due to their anti-inflammatory properties. Despite their huge benefits, prolonged use is often associated with severe side effects as well as the development of glucocorticoid resistance in some cases. Mutations in an important SWI/SNF subunit, ARID1a, have previously been linked to glucocorticoid resistance and are associated with a vast number of human cancers. Determining the functional role of ARID1a...

The hypothalamic-pituitary-adrenal axis is the primary neuroendocrine system activated to establish homeostasis during the stress of critical illness and surgery. However, such critical states also trigger a systemic inflammatory activation that usually precedes the release of adrenocorticotrophic hormone (ACTH) and cortisol. Systemically or locally induced inflammation of the adrenal gland had been described during critical illness. This facilitates...

Measuring circulating androgen and gestagen concentrations is essential for the diagnosis and treatment monitoring of pathological conditions caused by abnormal steroidogenesis, such as congenital adrenal hyperplasia (CAH) and polycystic ovary syndrome (PCOS). Saliva collection represents a simple and non-invasive technique advantageous for multi sample profiling. We therefore developed a liquid chromatography-tandem mass spectrometry assay for the s...

Cortisol conversion to 20β-dihydrocortisol (20β-DHF) has been reported in many tissues and cells, including skin, muscle, thrombocytes and fibroblasts, although the enzyme responsible is poorly characterised. We have attributed 20β-DHF generation to carbonyl reductase 1 and shown increased activity of this pathway in adipose tissue in obesity in humans, horses and mice. This study addressed the hypothesis that 20β-DHF activates gl...

Glucocorticoids (GC) have potent anti-inflammatory effects, acting mainly through the glucocorticoid receptor (GR). However GCs have debilitating side effects and a safer alternative is required. 5α-tetrahydrocorticosterone (5αTHB, a metabolite of the natural rodent glucocorticoid corticosterone) may provide a solution: 5αTHB is anti-inflammatory in vivo, effective topically to suppress irritant dermatitis, but with fewer syst...

Background: Serum total cortisol responses to the short Synacthen® test (SST) are used to confirm or refute a diagnosis of adrenal insufficiency. Salivary cortisol measurement offers a non-invasive alternative and has the potential advantage of evaluating free, bioavailable cortisol. However, reference ranges and its performance in the investigation of suspected hypoadrenalism (SH) have not been firmly established.Aims: 1....

The utility of renin measurement in guiding mineralocorticoid replacement is unclear. To address this we retrospectively examined the parameters and treatment of 97 patients with Addison’s disease over a five year period.Methods: Adrenal replacement, blood pressure (BP), orthostatic BP response, urea, sodium, potassium and renin levels of 97 patients attending our clinic were collected over the period 2012–2016. Data ...

Glucocorticoid hormones (cortisol in man, corticosterone in rodent; CORT) are vital for maintaining normal homeostasis in multiple systems ((e.g., the cardiovascular, metabolic, and immune systems), and for an optimal response to acute and chronic stress. Plasma CORT is released from the adrenal zona fasciculata (ZF) in response to circulating levels of pituitary-derived adrenocorticotropin hormone (ACTH). ACTH binds to the MC2-receptor on the membra...

Introduction: Catheterisation of the right adrenal vein when performing adrenal vein sampling (AVS) is challenging. The AVS Accuracy Kit (AAK) (Trust Medical, Kasai, Japan) enables point-of-care confirmation of accuracy of AVS by rapid cortisol assay. We investigated whether use of AAK during AVS would impact upon procedural success, number of venous samples taken, radiation dose and screening time.Methods: 0.5 ml of each venous blood sample was centrifu...

Background: Hydrocortisone day curves (HCDCs) are commonly used to assess hydrocortisone replacement for patients with adrenal insufficiency (AI).Methods: HCDCs were obtained for 216 adrenally insufficient patients between 2004 and 2012 at Imperial College Healthcare NHS Trust. The area under the curve (AUC) was calculated for each patient’s day profile. Lipid profiles and glycated haemoglobin (HbA1c) values were recorded for each patient at both th...

Addison’s disease (AD) has an estimated prevalence of 126–144 per million among Northern European populations. Average age at diagnosis is 39, but AD may be diagnosed from pre-teens to 80 year olds.AD may occur in isolation or as part of autoimmune polyendocrine syndromes. Previous studies identified significant associations with autoimmune thyroid disease (predominantly hypothyroidism), type 1 diabetes mellitis, vitiligo, vitamin B12 deficienc...

Background: Short synacthen tests (SSTs) are routinely performed for the investigation of adrenal insufficiency (AI), but are costly and time consuming. The frequency of SST testing could be reduced by prioritising testing for specific indications (based on likelihood of failure of the test), and also by identification of an assay-specific 9am cortisol level that obviates the need to proceed to SST.Methods: Retrospective review...

Once daily oral prednisolone has been shown to mimic the normal circadian rhythm better than other glucocorticoids. Our advice is to take prednisolone first thing on waking and before breakfast to try to mimic the normal circadian rhythm as closely as possible. The leaflet that comes with prednisolone suggests that it should be taken with food. Enteric-coated prednisolone (EC) is believed to be kinder on the stomach, but there is no evidence for its use. We compared EC with st...

Background: Studies suggest that glucocorticoid hypersecretion alongside primary hyperaldosteronism (PA) is common and may contribute to the adverse metabolic phenotype. Adrenal crisis post-surgery for PA is rare.Aim: To determine the prevalence of cortisol co-secretion in PA in patients at Imperial College London NHS Trust, Hammersmith Hospital (a tertiary referral centre for adrenal tumours).Methods: Am...

Background: Characterisation of large adrenal lesion is challenging. There is no single robust imaging marker in defining benignity, especially for lesions which are greater than 4cm and are believed to carry increased risk of malignancy.A radiolabelled cholesterol analog tracer, I-131-Norcholesterol (NP-59), localises to adrenal cortical lesions. It has an established role in Conn’s syndrome. It is not expected to concent...

Introduction: We offer patients needing glucocorticoid replacement in primary and secondary adrenal insufficiency the choice of either once daily prednisolone or thrice daily hydrocortisone. A recent European study found no difference between prednisolone and hydrocortisone users in several markers, including glucose, weight, body mass index (BMI), systolic and diastolic blood pressure and waist circumference, although they did suggest an increase in cholesterol and low densit...

Background: Glucocorticoid-induced osteoporosis is one of the major clinical concerns of long-term steroid treatment. Previous studies have shown that immunosuppressive doses of glucocorticoid can lead to osteoporosis. This study investigated whether there is a relationship between cortisol exposure and the development of osteoporosis in patients receiving replacement doses.Methods: Hydrocortisone day curves (HCDCs) performed a...

The Endocrine Society recommends urinary or plasma metanephrines as first choice screening tests for phaeochromocytoma due to their high sensitivity. Test specificity is limited by the influence of many commonly prescribed medications resulting in false positive results and additional investigations. The aims of this retrospective study were to (1) Determine the diagnostic accuracy of urinary metanephrines using current cut-off values and (2) Evaluat...

Aims: The short synacthen test (SST) is considered as the gold standard test to assess the viability of the hypothalamic-pituitary-adrenal axis. This study explores the appropriateness of its clinical use in a district general hospital. Furthermore, it assesses the effectiveness of the alternate use of 9AM cortisol in excluding hypoadrenalism and the cost-effectiveness of sampling both 30 and 60 minutes serum cortisol in SST.Me...

The androgen receptor (AR) is required for the development of the male phenotype and traits. Some compounds, including diphenylethers and diphenylamines, inhibit AR activity by binding to a surface cleft named binding function 3 (BF-3). Such inhibitors bind by hydrophobic interactions between the two phenyl groups and the BF-3 site. A similar diphenyl group structure is found in 4,4′ DDT, 4,4′ DDE, 4,4′ DDD, and 2,4′ DDD, whic...

Evaluating patients with adrenal disease is uniquely challenging as biochemical parameters for assessing disease control or adequacy of hormone replacement are imprecise or lacking. QOL measures are increasingly being used to assess patients with adrenal disease, using a range of generic and disease specific measures. Reduced quality of life has been observed in patients with adrenal disease, even when biochemical cure is possible. We performed a sys...

Introduction: We report a rare case of hyperandrogenism associated with portal hypertension as a result of Alagille syndrome.Case report: 21-yr old female presented with primary amenorrhoea and mild hirsutism. There was no history of delayed puberty or acne. Past medical history: Alagille syndrome (biliary tree hypoplasia, liver disease, portal hypertension, splenomegaly, Barrett’s oesophagus and pulmonary stenosis). Drug ...

Phaeochromocytoma/paragangliomas (PPGLs) are relatively rare tumours and the health burden of such tumours is not very well known.Aim: This population based study aims to characterise all the phaeochromocytomas, paragangliomas and adrenal medullary hyperplasia diagnosed between 2007 and 2016 in Malta; looking into presentation, hormonal analysis, imaging characteristics and histology findings.Results: 16 ...

Ipilimumab is an anti-CTLA-4 monoclonal antibody licensed for metastatic melanoma.A 70-year-old female with metastatic malignant melanoma presented with anorexia, malaise and confusion two weeks after her fourth dose of Ipilimumab. She had a low serum sodium of 124 pmol/L on proton pump inhibitor and selective serotonin reuptake inhibitors, which were stopped and she was fluid restricted to 1.5 litres/day. Her urinary sodium wa...

Introduction: Traditionally the long synacthen test (LST) is used in some centres to assess hypothalamic/ pituitary and adrenal (HPA) axis. Evidence that it offers advantage over short synacthen test (SST) is lacking. Whilst changing our local protocol we evaluated 27 patients who had both tests in our trust. We compared the impact of the results in clinical decision making.Results: Mean age was 53 years. The indications for th...

Adrenal incidentalomas is a common referral to endocrine department. We retrospectively looked at the number of referrals to the endocrine services with it over 1 year and their eventual outcomes. There were a total of 37 patients referred with adrenal incidentalomas to our department out of which 28 patients (76%) were non secretory, while 1 (3%) had catecholamine excess. 1 (3%) had mixed cortisol + catecholamine excess. 7(19%) patients either did n...

Case: A 33 year old gentleman presented with significantly raised testosterone levels, testicular pain, erectile dysfunction and weight loss. He denied use of anabolic steroids. Upon physical examination he looked muscular and tanned. Left testicle was tender with no palpable mass. Raised androgen levels (Siemens immunoassay) were confirmed by liquid chromatography tandem mass spectrometry (LC-MS/MS), ruling out assay interference. In view of his ongoing denial of substance mi...

Introduction: Low levels of vitamin D are associated with higher mortality in critically ill patients. Studies on vitamin D levels in adult burn patients and their influence on clinical outcomes are scarce. Therefore, vitamin D status following thermal injury is often overlooked as its clinical implications are poorly understood.Aim: To examine the relationship of major thermal injury on the vitamin D axis and the influence of ...

Background: Diagnosis of adrenal hypofunction requires a high index of suspicion. A frequent cause is iatrogenic glucocorticosteroid prescribing hence the need for a clinical review after a prolonged course.Aim: A review of glucocorticosteroid prescribing and auditing SST outcomes in a large private hospital.Methods: Electronic records over an 18 month period were analysed for SST results, patient demogra...

Introduction: Adrenocortical carcinomas (ACCs) are rare; incidence is approximately 1–2 per million population per year. These arefrequently aggressive tumours that may or may not be functional. The primary potentially curative treatment for ACC is surgery with currently mixed opinion among experts regardingadjuvant Mitotane treatment.The Case: 60 years old female was seen in clinic for work up of incidental adrenal mass. ...

Long-term exposure to cortisol carry health risk and its important to establish the cause and exclude exogenous steroid use before starting investigation for endogenous causes, we present a young man with clinical picture of Cushing but low random cortisol.16 years old studying for his AS examinations at the time, presented to his GP with 5-week history of fatigue, weight gain of 2 stone in 18 months, insomnia, diarrhoea, left ...

Introduction: Ectopic ACTH syndrome (EAS) is a rare condition, accounting for approximately 10% of all Cushing’s syndrome (CS). We assessed the experience managing this condition in our centre.Methods: 171 patients (105 female, 66 male) with elevated plasma ACTH concentrations were identified from local IT systems at a tertiary centre (University Hospitals Birmingham NHS Foundation Trust) between 2002 and 2015. An electron...