Fixing the broken clock in adrenal disorders: focus on glucocorticoids and chronotherapy.

The circadian rhythm derives from the integration of many signals that shape the expression of clock-related genes in a 24-h cycle. Biological tasks, including cell proliferation, differentiation, energy storage, and immune regulation, are preferentially confined to specific periods. A gating system, supervised by the central and peripheral clocks, coordinates the endogenous and exogenous signals and prepares for transition to activities confined to periods of light or darkness. The fluctuations of cortisol and its receptor are crucial in modulating these signals. Glucocorticoids and the autonomous nervous system act as a bridge between the suprachiasmatic master clock and almost all peripheral clocks. Additional peripheral synchronizing mechanisms including metabolic fluxes and cytokines stabilize the network. The pacemaker is amplified by peaks and troughs in cortisol and their response to food, activity, and inflammation. However, when the glucocorticoid exposure pattern becomes chronically flattened at high- (as in Cushing's syndrome) or low (as in adrenal insufficiency) levels, the system fails. While endocrinologists are well aware of cortisol rhythm, too little attention has been given to interventions aimed at restoring physiological cortisol fluctuations in adrenal disorders. However, acting on glucocorticoid levels may not be the only way to restore clock-related activities. First, a counterregulatory mechanism on the glucocorticoid receptor itself controls signal transduction, and second, melatonin and/or metabolically active drugs and nutrients could also be used to modulate the clock. All these aspects are described herein, providing some insights into the emerging role of chronopharmacology, focusing on glucocorticoid excess and deficiency disorders.

Two cases of neonatal adrenal hemorrhage presenting with persistent jaundice.

The adrenal hemorrhage is a relatively rare event in newborns but must be considered in the presence of a persistent unexplained jaundice, especially in presence of predisposing factors. Serial ultrasonography is the modality of choice for initial diagnosis and follow-up of neonatal adrenal hemorrhage. We report two cases of neonatal adrenal hemorrhage presenting with persistent jaundice. The causes of the neonatal adrenal hemorrhages were a difficult vaginal delivery in macrosomic infant and a neonatal infection.

Adrenal disorders in pregnancy.

Adrenal disorders may manifest during pregnancy de novo, or before pregnancy undiagnosed or diagnosed and treated. Adrenal disorders may present as hormonal hypofunction or hyperfunction, or with mass effects or other nonendocrine effects. Pregnancy presents special problems in the evaluation of the hypothalamic-pituitary-adrenal axis in addition to the usual considerations. The renin-angiotensin-aldosterone axis undergoes major changes during pregnancy. Nevertheless, the common adrenal disorders are associated with morbidity during pregnancy and their management is more complicated. A high index of suspicion must be maintained for these disorders lest they go unrecognized and untreated.

[Adrenal haemorrhage in neonates: risk factors and diagnostic and clinical procedure]. / Wylew do nadnerczy u noworodków: czynniki ryzyka i postepowanie diagnostyczno-kliniczne.

UNLABELLED: Prenatal and neonatal adrenal haemorrhage is being increasingly frequently reported. We present a group of 13 neonates with adrenal haemorrhage, hospitalised in the Department of Paediatrics and Endocrinology of Warsaw Medical University from 2003 to 2007. THE AIM: of this study was to analyse: the perinatal history, haemorrhage predisposing factors, its size, localization and progress estimated by ultrasonography, as well as clinical, biochemical and hormonal findings indicating adrenal insufficiency. MATERIAL AND METHODS: the study group comprised 13 neonates hospitalised in the Department of Paediatrics and Endocrinology, Warsaw Medical University, from 2003 to 2007, due to adrenal haemorrhage diagnosed by ultrasonography in the first week of life. RESULTS: all neonates were born at term, there was a male predominance. Twelve neonates had risk factors such as: birth trauma, intrauterine infection, perinatal asphyxia. No risk factors were found only in 1 neonate. One neonate had bilateral adrenal haemorrhage, others were unilateral - predominantly right-sided. In the study group clinical presentation was asymptomatic in 3 neonates, 1 of the patients had anaemia, 9 persistent jaundice, 2 bluish discoloration of the scrotum. Only one patient with bilateral adrenal haemorrhage showed sings of adrenal insufficiency and supplementation with glyco- and mineralcorticoids was necessary. Complete resolution of adrenal haemorrhage was reported after an average time of 3.5 months of observation. CONCLUSIONS: 1. Adrenal haemorrhage in neonates rarely leads to development of adrenal insufficiency. 2. In neonates with bilateral adrenal haemorrhage an extended hormonal diagnosis is required. 3. All patients require a systematic clinical and sonographic follow-up. Unilateral haemorrhage should be differentiated from neuroblastoma. 4. Scrotal haematoma may be a symptom of adrenal haemorrhage.

Hemorragia suprarrenal neonatal. Consideraciones diagnósticas y de actitud clínica / Neonatal adrenal hemorrhage. Diagnostic considerations and clinical attitude

Se presenta una serie de 3 casos diagnosticados en nuestro Servicio de hemorragia suprarrenal unilateral. En dos de los casos el diagnóstico es en período neonatal y en el tercer caso se sospecha de forma retrospectiva, por encontrar en una radiografía abdominal calcificaciones suprarrenales. En los dos recién nacidos, la causa de ingreso es ictericia, acompañada en uno de ellos de masa abdominal. Los dos casos son varones sin antecedentes familiares de interés, procedentes de una primera gestación a término y sin incidencias. Parto prolongado en ambos, siendo instrumental en el primero. El período neonatal inmediato, somatometría y exploraciones complementarias al ingreso son normales. En ambos niños se realiza ecografía abdominal en la que se detecta masa suprarrenal con áreas anecoicas, compatible con hemorragia suprarrenal derecha. En ambos casos se mantiene una actitud expectante, con observación clínica estricta y centrada en la aparición de signos de insuficiencia suprarrenal (hipotensión, hipoglucemia, hipercaliemia, hiponatremia, acidosis, convulsiones, coma), hemorragia masiva o signos de indicación quirúrgica. La determinación de hormonas adrenales y el ionograma en suero y orina son normales. Los dos niños permanecen asintomáticos, no precisando otro tratamiento que fototerapia. Se realizan controles ecográficos seriados, que constituyen la base de la confirmación del diagnóstico y del diagnóstico diferencial con otras entidades como el neuroblastoma quístico, quiste cortical o absceso adrenal. Hemos querido añadir un tercer caso de diagnóstico retrospectivo probable. Es un varón de 8 años con calcificaciones suprarrenales derechas de hallazgo casual, sugerentes de antigua hemorragia suprarrenal, que presentó en período neonatal ingreso por ictericia sin sospecha de hemorragia suprarrenal. Los tres casos clínicos nos permiten revisar una entidad relativamente frecuente en el recién nacido, que cursa habitualmente de forma unilateral y asintomática, si bien en ocasiones puede producir un importante compromiso clínico con insuficiencia suprarrenal aguda, hemorragia masiva o muerte neonatal, obligando a un tratamiento precoz y enérgico (AU)

Three cases diagnosed at our Service of unilateral adrenal hemorrhage are presented. The diagnosis was at neonatal period in two cases and the third case should be suspected later by abdominal radiography revealed an adrenal calcifications. The first and second newborn was admitted to hospital by jaundice and the abdominal examination revealed a palpable mass in the first. Both cases are men. Families’ histories were no pertinent; they have been born at term after a normal pregnancy. The childbirth course was complicated by prolonged labor; it was Instrumental childbirth in the first. The neonatal period, anthropometric and laboratory studies were normal. In both children abdominal ultrasound revealed adrenal mass with anechoic areas, it is suggesting adrenal hemorrhage. In both cases was conservative man-agement, and clinical observation in the appearance of signs of adrenal insufficiency (hypotension, hypoglycemia, hyperkaliema, hyponatremia, acidose, convulsions, and comma), massive hemorrhage or signs of surgical indication. The hormonal determination, levels electrolytes blond and urine were normal. Both young they remain asymptomatic, treatment was phototherapy and serial ultrasounds. Follow up ultrasound is needed for diagnosis and differential diagnosis with neuroblastoma, cortical cyst or adrenal abscess. A third case the diagnosis was made later incidentally, suggestive adrenal calcifications of old adrenal hemorrhage. He was 8 years old boy. He was admitted to hospital by jaundice at newborn period. The three clinical cases allow to review an usually common disorder in the newborn period, that attends habitually an asyntomatic form; however sometimes it can produce an important clinical commitment with acute adrenal insufficiency, Massive adrenal hemorrhage or neonative death, forcing a precocious and energetic treatment (AU)

Ultrasound in screening for neonatal adrenal hemorrhage.

Neonatal adrenal hemorrhage is common. Relatively large size and extensive vascularity of the gland results in its vulnerability to trauma and traumatic asphyxial injuries. The reported incidence from necropsies is 1.7 per 1000 births. Ultrasound scans were performed on each of 8374 consecutive newborns delivered throughout 48 months ending December 31, 1993, in the Department of Obstetrics and Gynaecology. During our screening, 16 cases of adrenal hemorrhage (10 males and 6 females) were noted at an incidence of 1.9 per 1000. All of the cases of adrenal hemorrhages remained intracapsular with spontaneous resolution. Thirteen cases were right sided, two cases were left sided, and one case was bilateral. None required surgical exploration. Neonatal treatment included further phototherapy in 12 cases, blood transfusions in five cases, and antibiotics in three cases. Signs of transient adrenocortical insufficiency were observed in one child.