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Journal: European journal of endocrinology / European Federation of Endocrine Societies


Cytochrome P450 side-chain cleavage enzyme (CYP11A1) catalyses the first and rate-limiting step of steroidogenesis, the conversion of cholesterol to pregnenolone. CYP11A1 deficiency is commonly associated with adrenal insufficiency, and in 46,XY individuals, with variable degrees of disorder of sex development (DSD).

Concepts: Testosterone, Cytochrome P450, Steroid, CYP17A1


Primary aldosteronism (PA) secondary to excessive and/or autonomous aldosterone secretion from the renin angiotensin system (RAS) accounts for approximately 10% of cases of hypertension and is primarily caused by bilateral adrenal hyperplasia (BAH) or aldosterone-producing adenomas (APAs). Although the diagnosis has traditionally been supported by low serum potassium levels, normokalemic and even normotensive forms of PA have been identified expanding further the clinical phenotype. Morever, recent evidence has shown that serum aldosterone correlates with increased blood pressure in the general population and even moderately raised aldosterone levels are linked to increased cardiovascular morbidity and mortality. In addition, aldosterone antagonists are effective in blood pressure control even in patients without evidence of dysregulated aldosterone secretion. These findings indicate a higher prevalence of aldosterone excess among hypertensive patients than previously considered that could be attributed to disease heterogeneity, aldosterone level fluctuations related to an adrenocorticotropin (ACTH) effect, or inadequate sensitivity of current diagnostic means to identify apparent aldosterone excess. In addition, functioning aberrant receptors expressed in the adrenal tissue have been found in a subset of PA cases that could also be related to its pathogenesis. Recently a number of specific genetic alterations, mainly involving ion homeostasis across the membrane of zona glomerulosa, have been detected in approximately 50% of patients with APAs. Although specific genotype/phenotype correlations have not been clearly identified, differential expression of these genetic alterations could also account for the wide clinical phenotype, variations in disease prevalence and performance of diagnostic tests. In the present review, we critically analyze current means used to diagnose PA along with the role that ACTH, aberrant receptor expression and genetic alterations may exert, and provide evidence for an increased prevalence of aldosterone dysregulation in patients with essential hypertension and pre-hypertension.

Concepts: Kidney, Hypertension, Blood pressure, Aldosterone, Cortisol, Renin-angiotensin system, Renin, Hyperaldosteronism


Background: Though it is well appreciated that insulin plays an important role in regulating muscle protein metabolism, there is much discrepancy in the literature on the capacity of exogenous insulin administration to increase muscle protein synthesis rates in vivo in humans. Objective: To assess whether exogenous insulin administration increases muscle protein synthesis rates in young and older adults. Design: A systematic review of clinical trials was performed and the presence or absence of an increase in muscle protein synthesis rate was reported for each individual study arm. In a stepwise manner, multiple models where constructed that excluded study arms based on the following conditions: model 1) concurrent hyperaminoamino-acidemia, model 2) insulin-induced hypoaminoacidemia, model 3) supraphysiological insulin concentrations, and model 4) older, more insulin resistant, subjects. Conclusions: From the presented data in the current systematic review, we conclude that 1) exogenous insulin and amino acid administration effectively increase muscle protein synthesis, however this effect is attributed to the hyperaminoacidemia, 2) exogenous insulin administrated systemically induces hypoaminoacidemia which obviates any insulin-stimulatory effect on muscle protein synthesis, 3) exogenous insulin resulting in supraphysiological insulin levels exceeding 50,000 pmol/L may effectively augment muscle protein synthesis, 4) exogenous insulin may have a diminished effect on muscle protein synthesis in older adults due to age related anabolic resistance, and 5) exogenous insulin administrated systemically does not increase muscle protein synthesis in healthy, young adults.

Concepts: Protein, Amino acid, Metabolism, Insulin, Glucose, Insulin resistance, Glycogen, Peptide synthesis


Pubertal onset is usually defined by breast development in girls and testicular growth in boys. Pubarche is defined as the attainment of pubic hair and is considered as a sign of pubertal transition. Pubarche is preceded by a gradual increase in production of adrenal androgens, DHEA and Δ4-androstenedione (Adione), a process termed adrenarche.

Concepts: Hypothalamus, Androgen, Puberty, Endocrine system, Adrenarche, Thelarche, Pubarche, Pubic hair


BACKGROUND: The Bone Morphogenetic Proteins (BMPs) are growth factors involved in the folliculogenesis. Alteration in their expression may compromise the reproductive process in disease such as the polycystic ovary syndrome (PCOS). The present study investigated the expression and role of granulosa cell BMP from normal cycling and PCOS women. METHODS AND RESULTS: This prospective study was performed in granulosa cells obtained from 14 patients undergoing IVF : (i) 6 women with normal ovulatory cycles and tubal or male infertility and (ii) 8 women with PCOS. BMP-2, BMP-4, BMP-5, BMP-6, BMP-7 and BMP-8A, and their receptors BMPR-IA, BMPR-IB and BMPR-II were identified by RT-PCR in granulosa cells from normally cycling and PCOS women. BMP-4, 6 and 7 expression were confirmed by immunohistochemistry, Quantitative transcript analysis showed the predominant expression of BMP-6. In granulosa cells from PCOS women, an over-expression of BMP-6 (p<0.01) and BMPR-IA mRNA (p<0.05) were observed. Granulosa cell culture experiments demonstrated that basal estradiol (E2) production was 3-fold higher but FSH-induced E2 increment 2-fold lower in PCOS compared to controls. In PCOS, BMP-6 and 7 exerted a stimulatory effect on basal E2 production while BMP-4 and 6 inhibited FSH-induced E2 production. FSH receptor and aromatase expression were not different between both groups. CONCLUSION: The BMP system is expressed in human granulosa cells from normal cycling and PCOS women. The BMP may be involved in reproductive abnormalities found in PCOS.

Concepts: Protein, Signal transduction, Menstrual cycle, Polycystic ovary syndrome, Folliculogenesis, Anovulation, Granulosa cells, Bone morphogenetic protein


To explore the relationship between family history of diabetes and frequency of diabetic ketoacidosis (DKA) at diagnosis and to analyze the possible association between HLA genotypes and DKA.

Concepts: Diabetes mellitus, Diabetes mellitus type 1, Diabetes, Ketone bodies, Hyperglycemia, Ketoacidosis, Diabetic ketoacidosis, Maturity onset diabetes of the young


Generalized glucocorticoid resistance is characterized by impaired cortisol signaling, resulting from mutations of the glucocorticoid receptor (GR) gene NR3C1. The objective of our study was to identify the causative mutation in a patient with clinical manifestations compatible with generalized glucocorticoid resistance and to determine the functional consequences of the mutation. The possible occurrence of NR3C1 mutations in a selected group of hypertensive subjects with low plasma renin and aldosterone levels was also explored.

Concepts: DNA, Genetics, Evolution, Hypertension, Cortisol, Nuclear receptor, Mineralocorticoid receptor, Glucocorticoid receptor


Studies suggest an association between a high TSH and (individual components of) the metabolic syndrome. Only a few studies have been performed in the general older population.

Concepts: Thyroid


CONTEXT: Prevalence of Cushing’s syndrome (CS) in patients presenting with hirsutism is not well-known. OBJECTIVE: Screening of CS in patients with hirsutism. SETTING: Referral hospital PATIENTS AND OTHER PARTICIPANTS: This study was carried out on 105 patients who admitted to Endocrinology Department with the complaint of hirsutism. INTERVENTION: All the patients were evaluated with low dose dexamethasone suppression test (LDDST) for CS. MAIN OUTCOME MEASURE: Response to LDDST in patients presenting with hirsutism RESULTS: All the patients had suppressed cortisol levels following low dose dexamethasone administration excluding CS. The etiology of hirsutism were polycystic ovary syndrome in 79%, idiopathic hirsutism in 13%, idiopathic hyperandrogenemia in 6% and non-classical congenital hyperplasia in 2% of the patients. CONCLUSION: Routine screening for CS in patients with a referral diagnosis of hirsutism is not required. For the time being, diagnostic tests for CS in hirsute patients should be limited to patients who have accompanying clinical stigmata of hypercortisolism.

Concepts: Obesity, Glucocorticoid, Cortisol, Spironolactone, Polycystic ovary syndrome, Cushing's syndrome, Hirsutism, Dexamethasone suppression test


ABSTRACTOBJECTIVE: Contradictory reports ascribe neonatal hyperthyrotropinemia to prematurity or small weight for gestational age. We aimed to evaluate the association between neonatal hyperthyrotropinemia and birth-weight, recovery rate of the disorder and possible association with perinatal stress. DESIGN: Based on neonatal screening database, a retrospective twin-study was designed where within-pair differences in thyroid function were evaluated while controlling for differences in gestational age and thyroid affecting environmental confounders. METHODS: 2595 twin pairs that were screened both for TSH and T4 over three years were included. TSH and T4 levels were evaluated along with birth-weight, birth order, gender and 17-hydroxyprogesterone that was considered as a surrogate marker for stress. RESULTS: 7.2% of the twin pairs had neonatal hyperthyrotropinemia. Among 156 pairs, hyperthyrotropinemia was more prevalent in the smaller twins (64%; p<0.001), especially in the discordant pairs (76%; p=0.001). 75% of the twins demonstrated a recovery within the first few weeks of life. 17-hydroxyprogesterone levels were similarly distributed between twins with and without hyperthyrotropinemia. In a cohort of 1534 twin pairs with normal thyroid function, mean TSH levels were significantly higher in the smaller- than in the larger-twin in the whole group (4.1±3.2 vs. 3.8±2.9 mIU/L; p<0.001) and especially among discordant twins (4.7±3.4 vs. 3.8±3.0 mIU/L; p<0.001). CONCLUSIONS: Elevated TSH levels are associated with low birth-weight, both in infants with hyperthyrotropinemia and in normal neonates. A rapid recovery rate is expected in most cases.

Concepts: Pregnancy, Childbirth, Infant, Fetus, Thyroid-stimulating hormone, Obstetrics, Pediatrics, Birth mass