Plasma Adrenocorticotropin, Cortisol, and Dehydroepiandrosterone Response to Corticotropin-Releasing Factor in Normal Children during Pubertal Development

Abstract

ABSTRACT. The adrenocorticotropin (ACTH), cortisol, and dehydroepiandrosterone responses to synthetic human corticotropin-releasing factor (CRF) were studied in 28 endocrinologically healthy children (age 1-16 yr) and in six adult volunteers (age 24-42 yr). CRF was given as an intravenous bolus (I pg/kg body weight) between 0900 and 1000 hr. Significant increments in ACTH and cortisol levels after CRF were observed in all subjects, with an ACTH peak value of 48.2 2 3.4 pg/ml at 10 min Cp < 0.001). The ACTH and cortisol response patterns after CRF did not change with age or pubertal maturation and did not differ in children and in adults. In contrast, the dehydroepiandrosterone response to CRF clearly was related to the stage of pubertal development. The peak value after CRF significantly increased from puberty stage 1 to puberty stage 5 (164 +. 18 versus 779 +. 86 ng/100 ml, p < 0.001). In adults, the mean dehydroepiandrosterone peak value after CRF did not differ from that of P5 children.These results show that CRF can be given safely to children. The absence of age-dependent ACTH and cortisol responses and a dehydroepiandrosterone response changing with pubertal maturation points to the existence of factors involved in the control of adrenal androgen production other than ACTH. CRF, corticotropin-releasing factorSince the isolation and characterization of CRF (1)(2)(3) several studies of its use in humans have been published (4-1 1). Synthetic CRF 1-41 has been reported to be highly potent in stimulating the release of ACTH-and proopiomelanocortinderived peptides from the pituitary of rodents and of humans (12, 13). Furthermore, the CRF-induced ACTH increase stimulates the concomitant release of cortisol and aldosterone from the adrenals (4-1 1, 14). Because of these effects and of its relative safety during clinical studies, CRF provides a powerful tool for studying ACTH secretion in normal as well as pathological situations. Several recent studies describe use of the CRF test in the evaluation of Cushing syndrome (1 5-1 7), Nelson syndrome (1 9, isolated pituitary ACTH deficiency and adrenal insufficiency (19,20). Data on the administration of CRF to children are limited so far to two reports (2 1, 22). In one study, Ross et al.(21) could find no age-dependent changes in the ACTH or cortisol responses to CRF in a group of normal children.In the present study, CRF was administered to hospitalized but endocrinologically healthy children, and the CRF-induced activation of the pituitary-adrenal axis was studied in relation to pubertal maturation. DHEA responses as well as ACTH and cortisol responses to CRF were assessed since the maturation of adrenal androgen production is associated with pubertal development (23-26). SUBJECTS AND METHODS Subjects.Approval for studies was obtained from the ethical committees of the three pediatric clinics in Tiibingen, Bonn, and Parma. The parents of all hospitalized but endocrinologically healthy children gave informed consent before the test was done. The normal children had...

Corticotropin Releasing Hormone Stimulation Test and Nocturnal Cortisol Levels in Normal Children

“…Although the majority of children in our study had peak ACTH levels by 15 min, we speculate that peak ACTH response may occur even earlier based on past studies of cortisol response at 10 min (22). These results are also consistent with the findings of Attanasio et al (16), who reported peak ACTH at 10 min and peak cortisol at 15-30 min. Among the most intriguing findings from this study were the significant correlations among the three different stress measures (nocturnal cortisol, CRH-F, and sleep maintenance).…”

“…Exaggerated ACTH responses to CRH stimulation help differentiate Cushing's disease from other causes of hypercortisolism, including primary affective disorders (4, 10-12). Previous reports have described responses in normal children (1 3) to ovine CRH administered in the evening, and responses in obese children or "normal" short children to human CRH administered in the morning (14)(15)(16). This report provides well-controlled normative data on ACTH and cortisol response to human CRH administered in the evening as well as baseline nocturnal cortisol levels.…”

The GH, prolactin, ACTH and cortisol responses to Hexarelin, a synthetic hexapeptide, undergo different age-related variations

“…Our present findings showing that the ACTH-releasing activity of HEX increases at puberty, goes down in adulthood and then shows again a trend toward increase in aging, strengthen the hypothesis that a CRH-mediated mechanism does not mediate the ACTH-releasing activity of HEX. In fact, the CRHinduced ACTH response has been reported to be similar in prepubertal and pubertal children as well as in young adults (45). On the other hand, estrogens could play a role even in the increased corticotrope response to GHRPs at puberty; in fact, in animals there is evidence pointing to a role of sex steroids in the regulation of the HPA axis (31,32).…”

A comparison of pituitary-adrenal responses to corticotropin-releasing hormone, hypoglycaemia and metyrapone in children with brain tumours and growth hormone deficiency

“…Corticotropin-releasing hormone (CRH) is a useful agent for evaluating the function of the hypothalamic-pituitaryadrenal axis and has been applied to normal subjects as well as patients with disorders of the hypothalamus, pituitary gland and adrenals [1,7,15,16,18]. There are few reports regarding hormonal assessments in children with brain neoplasms using CRH other than in those with Cushing disease [4,20].…”