Fertility and pregnancy in adrenal insufficiency.

Despite the availability of adrenal hormone replacement therapy, patients with adrenal insufficiency can be affected by reduced fertility and parity. Patients with well-managed adrenal insufficiency are expected to have uneventful pregnancies and favourable outcomes, but an increased risk of maternal and neonatal complications has been reported in some cases. Many physiological changes occur to the hypothalamic-pituitary-adrenal (HPA) axis during pregnancy, often making a new diagnosis and management of adrenal insufficiency challenging. The management of adrenal insufficiency also needs to reflect the physiologic changes of pregnancy, often requiring increased doses of glucocorticoid as pregnancy progresses and in some circumstances mineralocorticoid replacement (in primary adrenal insufficiency patients only), especially in the third trimester. To date, there are no prospective data guiding management of adrenal insufficiency in pregnancy. In this review, we focus on the impact of adrenal insufficiency on fertility and parity based on the aetiology of adrenal insufficiency and provide a practical approach to the management of patients with adrenal insufficiency before and during pregnancy.

Distinct inflammatory signatures of upper and lower body adipose tissue and adipocytes in women with normal weight or obesity.

Introduction: Upper and lower body fat accumulation poses an opposing obesity-related cardiometabolic disease risk. Depot-differences in subcutaneous adipose tissue (SAT) function may underlie these associations. We aimed to investigate the inflammatory signatures of abdominal (ABD) and femoral (FEM) SAT in postmenopausal women with normal weight or obesity. Methods: We included 23 postmenopausal women with normal weight (n = 13) or obesity (n = 10). In vivo secretion of adipokines from ABD and FEM SAT was measured using the arterio-venous balance technique. Adipokine gene expression and adipocyte morphology were examined in ABD and FEM SAT. Furthermore, adipokine expression and secretion were investigated in vitro using differentiated human primary ABD and FEM subcutaneous adipocytes derived from the study participants. Results: Plasma leptin and plasminogen activator inhibitor (PAI)-1 concentrations were higher, and ABD and FEM adipocytes were larger in women with obesity than normal weight. No differences in adipocyte size and blood flow were apparent between ABD and FEM SAT. We found significant release of leptin and monocyte chemoattractant protein (MCP)-1 from ABD and FEM SAT, with higher fractional release of MCP-1 from ABD than FEM SAT. Gene expression of leptin, PAI-1, and tumor necrosis factor-α was lower in ABD than FEM SAT and higher in women with obesity than normal weight. In ABD adipocytes, interleukin-6, PAI-1, and leptin gene expression were higher, while adiponectin and dipeptidyl-peptidase-4 gene expression were lower than in FEM adipocytes. Finally, ABD adipocytes secreted less MCP-1 compared to FEM adipocytes. Discussion: These findings demonstrate that upper and lower body SAT and adipocytes are characterized by distinct inflammatory signatures in postmenopausal women, which seem independent of adipocyte size.

Tissue Glucocorticoid Metabolism in Adrenal Insufficiency: A Prospective Study of Dual-release Hydrocortisone Therapy.

BACKGROUND: Patients with adrenal insufficiency (AI) require life-long glucocorticoid (GC) replacement therapy. Within tissues, cortisol (F) availability is under the control of the isozymes of 11ß-hydroxysteroid dehydrogenase (11ß-HSD). We hypothesize that corticosteroid metabolism is altered in patients with AI because of the nonphysiological pattern of current immediate release hydrocortisone (IR-HC) replacement therapy. The use of a once-daily dual-release hydrocortisone (DR-HC) preparation, (Plenadren®), offers a more physiological cortisol profile and may alter corticosteroid metabolism in vivo. STUDY DESIGN AND METHODS: Prospective crossover study assessing the impact of 12 weeks of DR-HC on systemic GC metabolism (urinary steroid metabolome profiling), cortisol activation in the liver (cortisone acetate challenge test), and subcutaneous adipose tissue (microdialysis, biopsy for gene expression analysis) in 51 patients with AI (primary and secondary) in comparison to IR-HC treatment and age- and BMI-matched controls. RESULTS: Patients with AI receiving IR-HC had a higher median 24-hour urinary excretion of cortisol compared with healthy controls (72.1 µg/24 hours [IQR 43.6-124.2] vs 51.9 µg/24 hours [35.5-72.3], P = .02), with lower global activity of 11ß-HSD2 and higher 5-alpha reductase activity. Following the switch from IR-HC to DR-HC therapy, there was a significant reduction in urinary cortisol and total GC metabolite excretion, which was most significant in the evening. There was an increase in 11ß-HSD2 activity. Hepatic 11ß-HSD1 activity was not significantly altered after switching to DR-HC, but there was a significant reduction in the expression and activity of 11ß-HSD1 in subcutaneous adipose tissue. CONCLUSION: Using comprehensive in vivo techniques, we have demonstrated abnormalities in corticosteroid metabolism in patients with primary and secondary AI receiving IR-HC. This dysregulation of pre-receptor glucocorticoid metabolism results in enhanced glucocorticoid activation in adipose tissue, which was ameliorated by treatment with DR-HC.

Cardiometabolic and psychological effects of dual-release hydrocortisone: a cross-over study.

BACKGROUND: Adrenal insufficiency (AI) is associated with increased cardiovascular morbidity and mortality and reduced quality of life (QoL). Optimum glucocorticoid (GC) dosing and timing are crucial in the treatment of AI, yet the natural circadian secretion of cortisol is difficult to mimic. The once-daily dual-release hydrocortisone (DR-HC) preparation (Plenadren®), offers a more physiological cortisol profile and may address unmet needs. METHODS: An investigator-initiated, prospective, cross-over study in patients with AI. Following baseline assessment of cardiometabolic risk factors and QoL, patients switched from their usual hydrocortisone regimen to a once-daily dose equivalent of DR-HC and were reassessed after 12 weeks of treatment. RESULTS: Fifty-one patients (21 PAI/30 SAI) completed the study. Mean age was 41.6 years (s.d. 13), and 58% (n = 30) were male. The median daily HC dose before study entry was 20 mg (IQR 15-20 mg). After 3 months on DR-HC, the mean SBP decreased by 5.7 mmHg, P = 0.0019 and DBP decreased by 4.5 mmHg, P = 0.0011. There was also a significant reduction in mean body weight (-1.23 kg, P = 0.006) and BMI (-0.3 kg/m2, P = 0.003). In a sub-analysis, there was a greater reduction in SBP observed in patients with SAI when compared to PAI post-DR-HC. Patients reported significant improvements in QoL using three validated QoL questionnaires, with a greater improvement in PAI. CONCLUSION: Dual-release hydrocortisone decreases BP, weight and BMI compared with conventional HC treatment, even at physiological GC replacement doses. Additionally, DR-HC confers significant improvements in QoL compared to immediate-release HC, particularly in patients with PAI, which is also reflected in the patient preference for DR-HC.

The effects of acute hyponatraemia on bone turnover in patients with subarachnoid haemorrhage: A preliminary report.

CONTEXT: Animal data and cross-sectional human studies have established that chronic hyponatraemia predisposes to osteoporosis; the effects of acute hyponatraemia on bone turnover have not been determined. Our objective was to test the hypothesis that acute hyponatraemia leads to dynamic effects on bone turnover. DESIGN: A prospective observational pilot study. METHODS: Bone turnover markers [C-terminal crosslinking telopeptide of type 1 collagen (CTX-1), N-propeptide of type 1 collagen (P1NP) and osteocalcin] were measured prospectively over one week in 22 eunatraemic patients with subarachnoid haemorrhage. Patients treated with glucocorticoids were excluded. RESULTS: Eight patients developed acute hyponatraemia, median nadir plasma sodium concentration 131 mmol/L (IQR 128-132), and 14 remained eunatraemic, nadir plasma sodium concentration 136 mmol/L (IQR 133-137). Significant main effects of hyponatraemia were found for P1NP (p = .02) and P1NP:CTX-1 ratio (p = .02), both fell in patients with acute hyponatraemia, with significant interaction between hyponatraemia and time from baseline for P1NP (p = .02). Significant main effects of time from baseline (p < .001) but not hyponatraemia (p = .07) were found for osteocalcin. For CTX-1, significant main effects of time from baseline (p = .001) but not hyponatraemia (p = .65) were found. There was a positive correlation between change in P1NP:CTX-1 ratio and nadir plasma sodium concentration, r = +.43, p = .04. Median serum cortisol (measured on days 1, 3 and 7) was higher in the hyponatraemia group than in those who remained eunatraemic, 545 nmol/L (IQR 373-778) versus 444 nmol/L (IQR 379-542) p = .03. CONCLUSION: These data suggest that acute mild hyponatraemia is associated with a reduction in bone formation activity.

The contribution of serum cortisone and glucocorticoid metabolites to detrimental bone health in patients receiving hydrocortisone therapy.

BACKGROUND: Glucocorticoid therapy is the most common cause of iatrogenic osteoporosis. Less is known regarding the effect of glucocorticoids when used as replacement therapy on bone remodelling in patients with adrenal insufficiency. Enhanced intracellular conversion of inactive cortisone to active cortisol, by 11 beta-hydroxysteroid dehydrogenase type 1(11ß-HSD1) and other enzymes leading to alterations in glucocorticoid metabolism, may contribute to a deleterious effect on bone health in this patient group. METHODS: Study design: An open crossover prospective study randomizing ten hypopituitary men, with severe ACTH deficiency, to three commonly used hydrocortisone dose regimens. MEASUREMENTS: Following 6 weeks of each regimen, patients underwent 24-h serum cortisol/cortisone sampling, measurement of bone turnover markers, and a 24-h urine collection for measurement of urinary steroid metabolites by gas chromatography-mass spectrometry (GC-MS). Serum cortisone and cortisol were analysed by liquid chromatography-mass spectrometry (LC-MS). RESULTS: Dose-related and circadian variations in serum cortisone were seen to parallel those for cortisol, indicating conversion of ingested hydrocortisone to cortisone. The median area under the curve (AUC) of serum cortisone was significantly higher in patients on dose A (20 mg/10 mg) [670.5 (IQR 621-809.2)] compared to those on dose C (10 mg/5 mg) [562.8 (IQR 520.1-619.6), p = 0.01]. A negative correlation was observed between serum cortisone and bone formation markers, OC [1-49] (r = - 0.42, p = 0.03), and PINP (r = - 0.49, p = 0.01). There was a negative correlation between the AUC of night-time serum cortisone levels with the bone formation marker, OC [1-49] (r = - 0.41, p = 0.03) but there were no significant correlations between day-time serum cortisone or cortisol with bone turnover markers. There was a negative correlation between total urinary cortisol metabolites and the bone formation markers, PINP (r = - 0.39, p = 0.04), and OC [1-49] (r = - 0.35, p = 0.06). CONCLUSION: Serum cortisol and cortisone and total urinary corticosteroid metabolites are negatively associated with bone turnover markers in patients receiving replacement doses of hydrocortisone, with nocturnal glucocorticoid exposure having a potentially greater influence on bone turnover. TRIAL REGISTRATION: Irish Medicines Board Clinical Trial Number - CT900/459/1 and EudraCT Number - 2007-005018-37 . Registration date: 07-09-2007.

Fluid Restriction Therapy for Chronic SIAD; Results of a Prospective Randomized Controlled Trial.

CONTEXT: Fluid restriction (FR) is the recommended first-line treatment for syndrome of inappropriate antidiuresis (SIAD), despite the lack of prospective data to support its efficacy. DESIGN: A prospective nonblinded randomized controlled trial of FR versus no treatment in chronic SIAD. INTERVENTIONS AND OUTCOME: A total of 46 patients with chronic asymptomatic SIAD were randomized to either FR (1 liter/day) or no specific hyponatremia treatment (NoTx) for 1 month. The primary endpoints were change in plasma sodium concentration (pNa) at days 4 and 30. RESULTS: Median baseline pNa was similar in the 2 groups [127 mmol/L (interquartile range [IQR] 126-129) FR and 128 mmol/L (IQR 126-129) NoTx, P = 0.36]. PNa rose by 3 mmol/L (IQR 2-4) after 3 days FR, compared with 1 mmol/L (IQR 0-3) NoTx, P = 0.005. There was minimal additional rise in pNa by day 30; median pNa increased from baseline by 4 mmol/L (IQR 2-6) in FR, compared with 1 mmol/L (IQR 0-1) NoTx, P = 0.04. After 3 days, 17% of FR had a rise in pNa of ≥5 mmol/L, compared with 4% NoTx, RR 4.0 (95% CI 0.66-25.69), P = 0.35. After 3 days, 61% of FR corrected pNa to ≥130 mmol/L, compared with 39% of NoTx, RR 1.56 (95% CI 0.87-2.94), P = 0.24. CONCLUSION: FR induces a modest early rise in pNa in patients with chronic SIAD, with minimal additional rise thereafter, and it is well-tolerated. More than one-third of patients fail to reach a pNa ≥130 mmol/L after 3 days of FR, emphasizing the clinical need for additional therapies for SIAD in some patients.

Adrenal Incidentaloma.

An adrenal incidentaloma is now established as a common endocrine diagnosis that requires a multidisciplinary approach for effective management. The majority of patients can be reassured and discharged, but a personalized approach based upon image analysis, endocrine workup, and clinical symptoms and signs are required in every case. Adrenocortical carcinoma remains a real concern but is restricted to <2% of all cases. Functional adrenal incidentaloma lesions are commoner (but still probably <10% of total) and the greatest challenge remains the diagnosis and optimum management of autonomous cortisol secretion. Modern-day surgery has improved outcomes and novel radiological and urinary biomarkers will improve early detection and patient stratification in future years to come.

The management of glucocorticoid deficiency: Current and future perspectives.

Glucocorticoid deficiency is the clinical state characterised by inadequate cortisol production. It may occur due to the primary failure of the adrenal cortex or to lack of stimulation of the adrenal cortex by adrenocorticotropic hormone. The aim of treatment of glucocorticoid deficiency is to mimic the normal physiological secretion of cortisol, in order to normalise quality of life and reverse pathological sequelae. However, the diurnal rhythm of cortisol secretion is difficult to reproduce with exogenous glucocorticoid therapy. There is wide inter- and intra-individual variability of in the dynamics of physiological glucocorticoid secretion, and glucocorticoid preparations that are currently available cannot reproduce physiological profiles. In addition, there are no reliable biomarkers to determine the adequacy of treatment. The treatment of acute glucocorticoid deficiency/ adrenal crisis involves prompt recognition and administration of parenteral hydrocortisone, rehydration, and management of electrolyte abnormalities. In the management of chronic glucocorticoid deficiency, the prevention of adrenal crisis must be balanced with avoidance of the long-term adverse effects of over-replacement. This requires close collaboration with the patient, for whom education and empowerment in the management of glucocorticoid deficiency, and the prevention of crises, are crucial.

Adrenal insufficiency: Physiology, clinical presentation and diagnostic challenges.

Adrenal insufficiency (AI) is a serious condition, which can arise from pathology affecting the adrenal gland itself (primary adrenal insufficiency, PAI), hypothalamic or pituitary pathology (secondary adrenal insufficiency, SAI), or as a result of suppression of the hypothalamic-pituitaryadrenal (HPA) axis by exogenous glucocorticoid therapy (tertiary adrenal insufficiency, TAI). AI is associated with an increase in morbidity and mortality and a reduction in quality of life. In addition, the most common cause of PAI, autoimmune adrenalitis, may be associated with a variety of other autoimmune disorders. Untreated AI can present with chronic fatigue, weight loss and vulnerability to infection. The inability to cope with acute illness or infection can precipitate life-threatening adrenal crisis. It is therefore a critical diagnosis to make in a timely fashion, in order to institute appropriate management, aimed at reversing chronic ill health, preventing acute crises, and restoring quality of life. In this review, we will describe the normal physiology of the HPA axis and explain how knowledge of the physiology of this axis helps us understand the clinical presentation of AI, and forms the basis for the biochemical investigations which lead to the diagnosis of AI.

Outcomes of the short Synacthen test: what is the role of the 60 min sample in clinical practice?

In recent years, the short Synacthen test (SS) has become the most widely used test to assess adrenal reserve. Despite its frequent use, there are still several areas related to the short Synacthen test (SST), which have no consensus including the optimum sampling times, that is, whether a 60 min post-Synacthen administration cortisol is necessary or not. METHODOLOGY: We performed a retrospective data analysis of 492 SSTs performed on adult patients in a tertiary referral teaching hospital in Ireland. The SSTs were performed in the inpatient and outpatient setting and included patients across all medical disciplines and not exclusively to the endocrinology department. RESULTS: 313 patients had 0, 30 and 60 min samples available for analysis. A total of 270/313 (82%) were deemed to pass the test, that is, cortisol ≥500 nmol/L at both 30 and 60 min. Of the 313 patients, 19 (6%) patients had an indeterminate response, cortisol <500 nmol/L at 30 min, but rising to ≥500 nmol/L on the 60 min sample. Of these 19 patients, only 9/19 patients had a serum cortisol level at 30 min <450 nmol/L, requiring clinical treatment with glucocorticoid replacement. All 24/313 (8%) patients who had insufficient responses at 60 min were also insufficient at 30 min sampling. No individuals passed (≥500 nmol/L) at 30 min and then failed (<500 nmol/L) at 60 min. CONCLUSION: Using the 30 min cortisol sample post-Synacthen administration alone identifies clinically relevant adrenal insufficiency in the majority of cases. A small subset of patients have a suboptimal response at 30 min but have a 60 min cortisol concentration above the threshold for a pass. Data regarding the long-term outcomes and management of such patients are lacking and require further study.

Adrenal crisis: prevention and management in adult patients.

Adrenal crisis is an acute life-threatening emergency contributing to the excess mortality that is reported in patients with adrenal insufficiency. The incidence of adrenal crisis is estimated to be 8 per 100 patient years in patients with adrenal insufficiency. Patients with adrenal crisis present systemically unwell with nonspecific signs and symptoms often leading to misdiagnosis and delayed treatment. An adrenal crisis may be the first presentation of adrenal insufficiency or can occur in patients who have been established on glucocorticoid replacement therapy. Infections are the major precipitating factor, but other causes include physical stress such as a surgical procedure or trauma, forgetting or discontinuing glucocorticoid therapy, pronounced physical activity, and psychological stress. The emergency treatment involves prompt recognition and administration of parenteral hydrocortisone, rehydration and management of electrolyte abnormalities. Prevention is centred around patient education. All patients should be educated on stress dosing and parenteral glucocorticoid administration. They should carry a steroid dependency alert card and wear a medical alert bracelet or similar identification. Despite many improvements in the management of patients with adrenal insufficiency, adrenal crisis continues to occur and represents a major source of morbidity, mortality and distress for patients. Improved patient and clinician education and measures to facilitate parenteral hydrocortisone self-administration in impending crisis are central to the management of this life-threatening event.

Continuous Versus Bolus Infusion of Hypertonic Saline in the Treatment of Symptomatic Hyponatremia Caused by SIAD.

BACKGROUND: Acute hyponatremia is a medical emergency that confers high mortality, attributed primarily to cerebral edema. Expert guidelines advocate the use of intravenous boluses of hypertonic saline rather than traditional continuous infusion to achieve a faster initial rise in plasma sodium (pNa) concentration. However, there is a limited evidence base for this recommended policy change. METHODS: We prospectively assessed the clinical and biochemical outcomes in patients treated for symptomatic hyponatremia caused by syndrome of inappropriate antidiuresis in response to intravenous bolus treatment with 3% saline (100 mL, repeated up to two more times) and compared the outcomes to retrospective data from patients treated with continuous intravenous infusion of low-dose (20 mL/h) 3% saline. RESULTS: Twenty-two patients were treated with bolus infusion and 28 with continuous infusion. Three percent saline bolus caused more rapid elevation of pNa at 6 hours [median (range) 6 (2 to11) vs 3 (1 to 4) mmol/L, P < 0.0001], with a concomitant improvement in Glasgow Coma Scale (GCS) [median (range) 3 (1 to 6) vs 1 (-2 to 2), P < 0.0001] at 6 hours. Median pNa concentration was similar at 24 hours in the two treatment groups. The administration of a third saline bolus was associated with greater need for dextrose/dDAVP to prevent overcorrection (OR 24; P = 0.006). There were no cases of osmotic demyelination in either group. CONCLUSION: Three percent saline bolus produces faster initial elevation of pNa than continuous infusion with quicker restoration of GCS, and without osmotic demyelination. Frequent electrolyte monitoring, and judicious intervention with dDAVP is required to prevent overcorrection with bolus therapy.

Pregnancy in acromegaly is safe and is associated with improvements in IGF-1 concentrations.

Pregnancy is rarely reported in acromegaly. Many patients are diagnosed in later life and younger patients may have subfertility due to hypopituitarism. We present a case series of 17 pregnancies in 12 women with acromegaly. Twelve women with acromegaly who completed pregnancy were identified from centres involved in the Irish Pituitary Study. Eleven women had pituitary macroadenomas and one woman had a microadenoma. Only 5/17 pregnancies had optimal biochemical control of acromegaly preconception, as defined by IGF-1 concentration in the age-related reference level and plasma GH concentration of <2 µg/L. In 6/17 pregnancies, dopamine agonist treatment was continued during pregnancy; all other acromegaly treatments were discontinued during pregnancy. Effect of pregnancy on acromegaly: No patient developed new visual field abnormalities, or symptoms suggestive of tumour expansion during pregnancy. In 9/12 patients, plasma IGF-1 concentrations that were elevated preconception normalised during pregnancy. There was a reduction in plasma IGF-1 concentrations, though not into the normal range, in a further two pregnancies. Effect of acromegaly on pregnancy: 15 healthy babies were born at term; one patient underwent emergency C-section at 32 weeks for pre-eclampsia, and one twin pregnancy had an elective C-section at 35 weeks' gestation. Blood pressure remained within normal limits in the remainder of the pregnancies. Gestational diabetes did not develop in any pregnancy. Our data suggests that pregnancy in women with acromegaly is generally safe, from a maternal and foetal perspective. Furthermore, biochemical control tends to improve despite the withdrawal of somatostatin analogue therapy during pregnancy.

Factors impacting on the action of glucocorticoids in patients receiving glucocorticoid therapy.

Glucocorticoids (GCs) are steroid hormones, which are essential for life. They are secreted by the adrenal cortex under the control of the hypothalamic-pituitary-adrenal (HPA) axis. Glucocorticoids are essential for the normal function of most organ systems and, in both, excess and deficiency can lead to significant adverse consequences. Adrenal insufficiency (AI) is a rare, life-threatening disorder characterized by insufficient production of corticosteroid hormones. Primary AI is defined by the inability of the adrenal cortex to produce sufficient amounts of glucocorticoids and/or mineralocorticoids despite normal or increased adrenocorticotropin hormone (ACTH). Secondary AI is adrenal hypofunction due to insufficient amount of ACTH produced by the pituitary gland. Conventional treatment of both primary and secondary adrenal insufficiencies involves lifelong glucocorticoid replacement therapy. The role of cortisol deficiency and the impact of hydrocortisone replacement on morbidity and mortality in this patient group are under increasing scrutiny. Established glucocorticoid replacement regimens do not completely mirror endogenous hormonal production, and their monitoring to ensure optimum therapy is hampered by the lack of reliable biomarkers of hormone sufficiency. A further confounding issue is the tissue-specific regulation of glucocorticoid through the two isozymes of 11ß-hydroxysteroid dehydrogenase (11ß-HSD) with research focusing on the role of this prereceptor regulation in the development of adverse metabolic features in patients. This review defines the factors influencing glucocorticoid action in patients with adrenal insufficiency receiving glucocorticoid therapy.

Rates of abnormal aldosterone/renin ratio in African-origin compared to European-origin patients: A retrospective study.

INTRODUCTION: The aldosterone/renin ratio is the initial screening test for primary hyperaldosteronism (PHA), but little data exists regarding ethnic variations in this. METHODS: Following clinical observation of a high prevalence of abnormal aldosterone/renin ratio (ARR) in patients of African-origin, we retrospectively reviewed all ARR measurements in a single centre over 10 years. Rates of hypokalaemia, intraventricular septal thickness (IVS, by echocardiography) and adrenal imaging were recorded when available. RESULTS: Aldosterone/renin ratio was available in 1473 patients, and abnormal in 374 (25.4%). Abnormal ARR was observed in 305/1349 (22.6%) of European-origin and 69/124 (55.6%) of African-origin patients (P < 0.001). Among those with abnormal ARR, hypokalaemia (<3.5 mmol/L) was documented on at least one occasion in 171/305 (56.1%) European-origin and 43/69 (62.3%) African-origin patients (P = 0.35). Median (range) IVS was 1.57 (0.78-2.80) cm in African-origin and 1.20 (0.69-2.18) cm in European-origin patients (P < 0.002); IVS did not correlate with aldosterone or ARR however. Adrenal adenoma was identified in 41/170 (24.1%) of European-origin and 4/29 (13.7%) African-origin patients (P = 0.15), while hyperplasia was identified in 35/170 (20.5%) of European and 8/29 (27.5%) African patients (P = 0.39). CONCLUSION: In summary, ARR was abnormal in 55.6% of African-origin patients screened at an Irish hospital. Rates of hypokalaemia were similar between European-origin and African-origin patients. These findings have implications for the use of current screening guidelines for ARR in African-origin patients and also for the mechanistic role of aldosterone in hypertensive complications in African-origin patients.

Hyponatraemia - presentations and management.

Hyponatraemia is the most common electrolyte disturbance encountered in clinical practice. It is associated with -significant morbidity and mortality, thus appropriate investigation and treatment is essential. Hyponatraemia presents with a spectrum of clinical presentations ranging from no symptoms to life-threatening neurological sequelae. Hyponatraemia has multiple aetiologies and distinguishing the underlying aetiology facilitates appropriate treatment. This review provides an overview of the presentations and approaches to management of this common clinical condition.

ACTH and gonadotropin deficiencies predict mortality in patients treated for nonfunctioning pituitary adenoma: long-term follow-up of 519 patients in two large European centres.

CONTEXT AND OBJECTIVE: Nonfunctioning pituitary adenomas (NFPAs) are the most common subtype of pituitary tumour. Hypopituitarism is observed in NFPAs due to tumour- or treatment-related factors and may increase mortality risk. Here, we analysed the associations of hypopituitarism, hormone replacement and mortality in a large NFPA cohort derived from two large European centres. DESIGN, SETTING AND PARTICIPANTS: Case note review of all patients treated for NFPA in University Hospitals Birmingham and Beaumont Hospital Dublin between 1999 and 2014 was performed. MAIN OUTCOME MEASURES: Clinical presentation, treatment strategies, pituitary function and vitality status were recorded in each patient. A multivariate Cox regression model was used to examine the association between hypopituitarism, hormone replacement and premature mortality. RESULTS: A total of 519 patients were included in the analysis. Median duration of follow-up was 7·0 years (0·5-43). A total of 81 deaths were recorded (15·6%). On multivariate analysis, adrenocorticotropic hormone (ACTH) and gonadotropin (Gn) deficiencies were associated with an increased relative risk of death (OR 2·26, 95% CI 1·15-4·47, P = 0·01 and OR 2·56, 95% CI 1·10-5·96, P = 0·01, respectively). Increased hydrocortisone (HC) (P-trend = 0·02) and lower levothyroxine (LT4) doses (P-trend = 0·03) were associated with increased risk of death. Mortality increased with the degree of pituitary failure observed (P-trend = 0·04). CONCLUSION: ACTH and gonadotropin-deficient patients have higher mortality rates compared to those with intact hormonal axes. Excessive HC and suboptimal LT4 replacement may also increase risk of death. Complex associations between hormone deficiency and replacement underpin the increased mortality risk in NFPA patients.