The Importance of Adrenocortical Glucocorticoids for Adrenomedullary and Physiological Response to Stress: A Study in Isolated Glucocorticoid Deficiency

Zuckerman‐Levin, Nehama

doi:10.1210/jc.86.12.5920

Cited by 35 publications

(49 citation statements)

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“…However, the catecholamine secretion pattern differs between these two hyperandrogenic conditions; CAH patients have decreased E and normal NE concentrations (28), whereas our SAA children show normal E and increased NE concentrations. Instead, patients with isolated glucocorticoid deficiency also show low E concentrations (46). Thus, our study is concordant with earlier findings that the low intra-adrenal glucocorticoid but not the high androgen concentration leads to reduced E production.…”

Section: Discussionsupporting

confidence: 93%

Continuum of phenotypes and sympathoadrenal function in premature adrenarche

Utriainen¹,

Voutilainen²,

Jääskeläinen³

2009

European Journal of Endocrinology

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Objectives: Premature adrenarche (PA), the early rise in adrenal androgen (AA) production, can manifest with different clinical signs of androgen effect. Premature pubarche defined as appearance of pubic hair before the age of 8/9 years in girls/boys, is the most prominent clinical sign of PA and often erroneously described as a synonym of PA. Our aim was to determine the association of circulating AA concentrations with different prepubertal signs of androgen action (SAA). Secondly, we tested whether adrenomedullary function is altered in children with SAA, as it is in congenital adrenal hyperplasia (CAH) also causing adrenal hyperandrogenism. Design and methods: We examined 73 Finnish prepubertal children with any hyperandrogenic sign(s) having appeared before the age of 8/9 years (girls/boys) (35 with pubic and/or axillary hairZPAH; 38 withoutZnonPAH), and 98 age-and sex-matched controls. Circulating adrenal steroid and catecholamine concentrations were measured and correlated with clinical parameters. Results: None of the children with SAA had CAH or virilizing tumor. Serum dehydroepiandrosterone, dehydroepiandrosterone sulfate, and androstenedione concentrations overlapped between the SAA and control children, and they were lower in the nonPAH than PAH group (P!0.01). SAA children had similar plasma epinephrine but higher norepinephrine (NE) concentrations than their controls (mean (95% confidence interval) 1.61 (1.44, 1.77) versus 1.39 (1.30, 1.49) nmol/l, PZ0.03). Conclusions: PA forms a continuum with more pronounced increase in circulating androgens in children with PAH than in those without. Some children show SAA with fairly low androgen concentrations. The clinical significance of elevated NE concentrations associated with SAA needs to be confirmed in further studies.

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Section: Discussionsupporting

confidence: 93%

Continuum of phenotypes and sympathoadrenal function in premature adrenarche

Utriainen¹,

Voutilainen²,

Jääskeläinen³

2009

European Journal of Endocrinology

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“…Norepinephrine responses to insulin-induced hypoglycemia were only marginal in these patients. Similar norepinephrine reserve to that in control subjects have been found in patients with 21-hydroxylase deficiency and/or with isolated glucocorticoid deficiency (24)(25)(26). However, increased norepinephrine secretion has been demonstrated in patients with Addison's disease (30) and in those who had undergone bilateral adrenalectomy (24), suggesting that some compensatory increases occur during sympathetic nerve activity.…”

Section: Discussionsupporting

confidence: 52%

“…Glucocorticoids are required for the survival and maintenance of adrenomedullary chromaffin cells and their production of epinephrine (22,23). In fact, adrenomedullary hypofunction was observed in patients with 21-hydroxylase deficiency (24,25) and those with isolated glucocorticoid deficiency (26). In these patients, plasma epinephrine concentrations at baseline and in response to stimuli such as exercise, upright posture and cold pressure, were reduced (24)(25)(26).…”

Section: Discussionmentioning

confidence: 99%

“…In fact, adrenomedullary hypofunction was observed in patients with 21-hydroxylase deficiency (24,25) and those with isolated glucocorticoid deficiency (26). In these patients, plasma epinephrine concentrations at baseline and in response to stimuli such as exercise, upright posture and cold pressure, were reduced (24)(25)(26). Adrenomedullary dysfunction was characterized by incomplete formation of the adrenal medulla and a depletion of secretory vesicles in chromaffin cells (24).…”

Section: Discussionmentioning

confidence: 99%

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Reduced epinephrine reserve in response to insulin-induced hypoglycemia in patients with pituitary adenoma

Morita¹,

Otsuki²,

Izumi³

et al. 2007

eur j endocrinol

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Objective: Hypoglycemia induces rapid secretion of counterregulatory hormones such as catecholamine, glucagon, cortisol, and GH. Insulin-induced hypoglycemia is used for evaluating GH-IGF-I and ACTHadrenal axes in patients with pituitary disorders. The aim of this study was to determine whether the response of catecholamine secretion to hypoglycemia is disrupted in patients with pituitary adenoma. Methods: The study population comprised 23 patients with pituitary adenoma (non-functioning adenoma or prolactinoma). An insulin tolerance test was performed and serum catecholamines as well as plasma GH and serum cortisol were measured. Results: The study patients showed diminished response of plasma epinephrine to insulin-induced hypoglycemia. With the cutoff level of peak epinephrine for defining severe impairment set at 400 pg/ml, more patients with secondary adrenal insufficiency showed severe impairment of the epinephrine response than did those without it. Peak epinephrine levels to insulin-induced hypoglycemia were significantly correlated with peak cortisol levels. In patients with secondary hypothyroidism, secondary hypogonadism, GH deficiency, or diabetes insipidus, the prevalence of severe impairment of the epinephrine response was similar to that in patients without these deficiencies. Conclusions: Impaired epinephrine secretion in response to insulin-induced hypoglycemia was frequently observed in patients with pituitary adenoma. This disorder was especially severe in patients with secondary adrenal insufficiency.

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“…These changes, in concert with increases in steroidogenic gene expression, may contribute to the stimulation of corticosterone production. An interesting possibility is that increased corticosterone during hypoxia may alter adrenomedullary gene expression and function via paracrine effects (37). Additional studies will be required to evaluate this possible mechanism.…”

Section: Discussionmentioning

confidence: 99%

Microarray and real-time PCR analysis of adrenal gland gene expression in the 7-day-old rat: effects of hypoxia from birth

Bruder

Lee

Widmaier

et al. 2007

Physiological Genomics

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Bruder ED, Lee JJ, Widmaier EP, Raff H. Microarray and real-time PCR analysis of adrenal gland gene expression in the 7-day-old rat: effects of hypoxia from birth. Physiol Genomics 29: 193-200, 2007. First published January 9, 2007; doi:10.1152/physiolgenomics.00245.2006.-We hypothesize that changes in adrenal gene expression mediate the increased plasma corticosterone and steroidogenesis in rat pups exposed to hypoxia from birth. In the current study, rat pups (with their dams) were exposed to hypoxia from birth and compared with pups from normoxic dams fed ad libitum or pair fed to match the decreased maternal food intake that occurs during hypoxia. Microarray analysis was performed, followed by verification with real-time PCR. Furthermore, the expression of selected genes involved in adrenal function was analyzed by real-time PCR, regardless of microarray results. Hypoxia increased plasma ACTH and corticosterone, while food restriction had no effect. Microarray revealed that many of the genes affected by hypoxia encode proteins that require molecular oxygen (monooxygenases, oxidoreductases, and electron transport), whereas only a few genes known to be involved in adrenal steroidogenesis were affected. Interestingly, the expression of genes involved in mitochondrial function and intermediary metabolism was increased by hypoxia. Real-time PCR detected a small but significant increase in the expression of Cyp21a1 mRNA in the hypoxic adrenal. When decreased maternal food intake was controlled for, the effects of hypoxia were more pronounced, in that real-time PCR detected significant increases in the expression of Star (244%), Cyp21a1 (208%), and Ldlr (233%). The present study revealed that increased plasma corticosterone in rat pups was due to hypoxia per se, and not as a result of decreased food intake by the hypoxic dam. Furthermore, hypoxia induced changes in gene expression that account for more productive and efficient steroidogenesis. steroidogenesis; neonatal; mRNA; adrenal cortex; corticosterone; ACTH SYSTEMIC HYPOXIA IS A CONDITION frequently encountered in the neonatal intensive care unit, is often a complication of preterm birth, and is associated with significant morbidity and mortality (9, 19). The ability to survive a hypoxic episode depends on coordinated physiological responses by a number of systems. These responses include, but are not limited to, adaptations in metabolic, hemodynamic, digestive, and cardiorespiratory function (8,10,13,17,22). A coordinated endocrine response is also a critical component (23,26). The ability of the neonatal hypothalamic-pituitary-adrenal (HPA) axis to mount a response to low oxygen is of paramount importance. A majority of preterm infants lack the capacity for an adrenocortical response to exogenous ACTH and physiological stressors, and this leads to enhanced inflammation and decreased pulmonary function requiring ventilation (15, 35).In the neonatal rat, there is a unique developmental aspect to the maturation of the adrenocortical response to stressors such a...

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The Importance of Adrenocortical Glucocorticoids for Adrenomedullary and Physiological Response to Stress: A Study in Isolated Glucocorticoid Deficiency

Cited by 35 publications

References 0 publications

Continuum of phenotypes and sympathoadrenal function in premature adrenarche

Continuum of phenotypes and sympathoadrenal function in premature adrenarche

Reduced epinephrine reserve in response to insulin-induced hypoglycemia in patients with pituitary adenoma

Microarray and real-time PCR analysis of adrenal gland gene expression in the 7-day-old rat: effects of hypoxia from birth

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