Androgens correlate with increased erythropoiesis in women with congenital adrenal hyperplasia.

OBJECTIVE: Hyperandrogenism in congenital adrenal hyperplasia (CAH) provides an in vivo model for exploring the effect of androgens on erythropoiesis in women. We investigated the association of androgens with haemoglobin (Hb) and haematocrit (Hct) in women with CAH. DESIGN: Cross-validation study PATIENTS: Women with CAH from Sheffield Teaching Hospitals, UK (cohort 1, the training set: n=23) and National Institutes of Health, USA (cohort 2, the validation set: n=53). MEASUREMENTS: Androgens, full blood count and basic biochemistry, all measured on the same day. Demographic and anthropometric data. RESULTS: Significant age-adjusted correlations (P<0.001) were observed for Ln testosterone with Hb and Hct in cohorts 1 and 2 (Hb r=0.712 & 0.524 and Hct r=0.705 & 0.466), which remained significant after adjustments for CAH status, glucocorticoid treatment dose and serum creatinine. In the combined cohorts Hb correlated with androstenedione (P=0.002) and 17-hydroxyprogesterone (P=0.008). Hb and Hct were significantly higher in cohort 1 than those in cohort 2, while there were no group differences in androgen levels, glucocorticoid treatment dose or body mass index. In both cohorts, women with Hb and Hct in the highest tertile had significantly higher testosterone levels than women with Hb and Hct in the lowest tertile. CONCLUSIONS: In women with CAH, erythropoiesis may be driven by androgens and could be considered a biomarker for disease control

A prospective study of children aged 0–8 years with CAH and adrenal insufficiency treated with hydrocortisone granules

Context Children with congenital adrenal hyperplasia (CAH) and adrenal insufficiency (AI) require daily hydrocortisone replacement with accurate dosing. Objective Prospective study of efficacy and safety of hydrocortisone granules in children with AI and CAH monitored by 17-OHP (17-hydroxyprogesterone) saliva profiles. Methods Seventeen children with CAH (9 male) and 1 with hypopituitarism (male), aged from birth to 6 years, had their hydrocortisone medication changed from pharmacy compounded capsules to hydrocortisone granules. Patients were followed prospectively for 2 years. In children with CAH, the therapy was adjusted by 17-OHP salivary profiles every 3 months. The following parameters were recorded: hydrocortisone dose, height, weight, pubertal status, adverse events, and incidence of adrenal crisis. Results The study medication was given thrice daily, and the median duration of treatment (range) was 795 (1–872) days, with 150 follow-up visits. Hydrocortisone doses were changed on 40/150 visits, with 32 based on salivary measurements and 8 on serum 17-OHP levels. The median daily mg/m2 hydrocortisone dose (range) at study entry for the different age groups 2–8 years, 1 month to 2 years, <28 days was 11.9 (7.2–15.5), 9.9 (8.6–12.2), and 12.0 (11.1–29.5), respectively, and at end of the study was 10.2 (7.0–14.4), 9.8 (8.9–13.1), and 8.6 (8.2–13.7), respectively. There were no trends for accelerated or reduced growth. No adrenal crises were observed despite 193 treatment-emergent adverse events, which were mainly common childhood illnesses. Interpretation This first prospective study of glucocorticoid treatment in children with AI and CAH demonstrates that accurate dosing and monitoring from birth results in hydrocortisone doses at the lower end of the recommended dose range and normal growth, without occurrence of adrenal crises

Medical treatment achieves similar quality of life to surgically treated acromegaly patients in remission: the QuaLAT study

Background: Quality of life (QOL) in acromegaly has been a subject of interest in several published studies; however, there is no consensus on how QOL in patients who require medical treatment after surgery compares with those who achieve remission by surgery only. Aim: Quality of life after acromegaly treatment (QuaLAT) is a case-control questionnaire-based study with the aim to compare the QOL in those who were treated with surgery only with those who required medical treatment after surgery at a single tertiary centre for acromegaly. Methods: Patients with acromegaly attending endocrinology clinics were identified via our database. These were matched on the duration of disease into those who underwent surgery and went into disease remission biochemically (Group 1), and those who did not achieve biochemical remission after surgery and therefore required further medical treatment to control the disease (Group 2). Participants were then asked to fill three questionnaires to measure their QOL; Acromegaly Quality of Life Questionnaire (ACROQOL), and two generic questionnaires; 36-Item Short Form Survey (SF36) v2, and Fatigue Severity Scale (FSS). Results: 20 patients from each group participated in the study. The mean±SD duration of acromegaly (years) was similar in the two groups (9.8±6.9 vs 9.7±6.9 p=0.653). The majority of patients in the medical group were on somatostatin analogues, either alone or in combination (n=14), with four and two patients on cabergoline and pegvisomant alone respectively. There was no difference in QOL scores between groups 1 & 2, as measured by ACROQOL (mean score±SD 54.4±24.8 vs 55.3±26.1 p=0.765), SF36v2 (Physical component score 40.1± 11.1 vs 45.6±12.0 p=0.235; mental component score 41.7±13.0 vs 43.1±16.4 p=0.601), or FSS (mean score±SD 4.4±2.2 vs 4.5±2.0 p=0.985) questionnaires. There was no difference in ages between both groups and there were 75% females in group 1 and 45% in group 2. When compared with healthy controls as reported in the published literature, all three QOL scores were lower in our cohort [1-3]. Conclusions: Medical treatment achieves similar QOL to surgically treated acromegaly patients in remission in the long term. When compared with healthy controls, QOL remains worse in treated acromegaly patients

Leptin Indirectly Activates Human Neutrophils via Induction of TNF-α

Leptin, the satiety hormone, appears to act as a link between nutritional status and immune function. It has been shown to elicit a number of immunoregulatory effects, including the promotion of T cell proliferative responses, and the induction of proinflammatory cytokines. Leptin deficiency is associated with an increased susceptibility to infection. As polymorphonuclear neutrophils (PMN) play a major role in innate immunity and host defense against infection, this study evaluated the influence of leptin on PMN activation. The presence of leptin receptor in human PMN was determined both at mRNA and protein levels, and the effect of leptin on PMN activation, as assessed by CD11b expression, was evaluated using flow cytometry. In contrast to monocytes, which express both the short and long forms of the leptin receptor (Ob-Ra and Ob-Rb, respectively), PMN expressed only Ob-Ra. Leptin up-regulated the expression of CD11b, an early marker of PMN activation, on PMN in whole blood, yet it had no effect on purified PMN, even those treated by submaximal doses of TNF-α or PMA. The kinetics of leptin-induced activation in whole blood were consistent with an indirect effect mediated by monocytes, and 71% of the leptin-stimulatory effect on PMN was blocked by a TNF-α inhibitor. Leptin-mediated induction of CD11b expression was observed when purified PMN were coincubated with purified monocytes. In conclusion, although leptin activates PMN, it does so indirectly via TNF-α release from monocytes. These findings provide an additional link among the obesity-derived hormone leptin, innate immune function, and infectious disease