Causes and clinical manifestations of central adrenal insufficiency in children
- Patricia A Donohoue, MD
Patricia A Donohoue, MD
- Professor of Pediatrics
- Medical College of Wisconsin
Adrenal insufficiency is defined by the impaired synthesis and release of adrenocortical hormones. It is classified based upon the mechanism:
●Primary adrenal insufficiency results from disease intrinsic to the adrenal cortex. These patients may present with deficiencies of one or more of the classes of hormones produced in the adrenal cortex (glucocorticoids, mineralocorticoids, and androgens).
●Central adrenal insufficiency can be caused by impaired production of adrenocorticotropic hormone (ACTH). It can be caused by either pituitary disease that impairs release of ACTH (secondary adrenal insufficiency (table 1)); or by interference with corticotropin-releasing hormone (CRH) production from the hypothalamus (tertiary adrenal insufficiency (table 2)). These patients have only glucocorticoid deficiency and not mineralocorticoid deficiency. In addition, they may have other pituitary hormone deficiencies, depending on the underlying central nervous system disease.
The causes and clinical manifestations of central adrenal insufficiency in children will be reviewed here. The causes of primary adrenal insufficiency and its manifestations, diagnosis, and treatment in children are discussed elsewhere. (See "Causes and clinical manifestations of primary adrenal insufficiency in children" and "Diagnosis of adrenal insufficiency in children" and "Treatment of adrenal insufficiency in children".)
The signs and symptoms of central adrenal insufficiency are caused by glucocorticoid deficiency, often combined with symptoms caused by underlying central nervous system (CNS) disease including other pituitary hormone deficiencies:To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:
- de Moraes DC, Vaisman M, Conceição FL, Ortiga-Carvalho TM. Pituitary development: a complex, temporal regulated process dependent on specific transcriptional factors. J Endocrinol 2012; 215:239.
- Constine LS, Woolf PD, Cann D, et al. Hypothalamic-pituitary dysfunction after radiation for brain tumors. N Engl J Med 1993; 328:87.
- Kanumakala S, Warne GL, Zacharin MR. Evolving hypopituitarism following cranial irradiation. J Paediatr Child Health 2003; 39:232.
- Huang KE, Mittelman SD, Coates TD, et al. A significant proportion of thalassemia major patients have adrenal insufficiency detectable on provocative testing. J Pediatr Hematol Oncol 2015; 37:54.
- Shi C, Wang F, Tong A, et al. NFKB2 mutation in common variable immunodeficiency and isolated adrenocorticotropic hormone deficiency: A case report and review of literature. Medicine (Baltimore) 2016; 95:e5081.
- Lal RA, Bachrach LK, Hoffman AR, et al. A Case Report of Hypoglycemia and Hypogammaglobulinemia: DAVID Syndrome in a Patient With a Novel NFKB2 Mutation. J Clin Endocrinol Metab 2017; 102:2127.
- Jackson RS, Creemers JW, Farooqi IS, et al. Small-intestinal dysfunction accompanies the complex endocrinopathy of human proprotein convertase 1 deficiency. J Clin Invest 2003; 112:1550.
- Farooqi IS, Volders K, Stanhope R, et al. Hyperphagia and early-onset obesity due to a novel homozygous missense mutation in prohormone convertase 1/3. J Clin Endocrinol Metab 2007; 92:3369.
- CLEVELAND WW, GREEN OC, MIGEON CJ. A case of proved adrenocorticotropin deficiency. J Pediatr 1960; 57:376.
- Grugni G, Beccaria L, Corrias A, et al. Central adrenal insufficiency in young adults with Prader-Willi syndrome. Clin Endocrinol (Oxf) 2013; 79:371.
- Gold PW, Gwirtsman H, Avgerinos PC, et al. Abnormal hypothalamic-pituitary-adrenal function in anorexia nervosa. Pathophysiologic mechanisms in underweight and weight-corrected patients. N Engl J Med 1986; 314:1335.
- Rensen N, Gemke RJ, van Dalen EC, et al. Hypothalamic-pituitary-adrenal (HPA) axis suppression after treatment with glucocorticoid therapy for childhood acute lymphoblastic leukaemia. Cochrane Database Syst Rev 2017; 11:CD008727.
- Kim MS, Donohoue PA. Adrenal disorders. In: Pediatric Practice: Endocrinology, 2nd ed, Kappy MS, Allen DB, Geffner ME (Eds), McGraw-Hill Medical, New York 2014. p.169.
- Norman PS, Winkenwerder WL, Agbayani BF, Migeon CJ. Adrenal function during the use of dexamethasone aerosols in the treatment of ragweed hay fever. J Allergy 1967; 40:57.
- Burch PG, Migeon CJ. Systemic absorption of topical steroids. Arch Ophthalmol 1968; 79:174.
- Hollman GA, Allen DB. Overt glucocorticoid excess due to inhaled corticosteroid therapy. Pediatrics 1988; 81:452.
- Russell G. Inhaled corticosteroids and adrenal insufficiency. Arch Dis Child 2002; 87:455.
- Wolfgram PM, Allen DB. Effects of Inhaled Corticosteroids on Growth, Bone Metabolism, and Adrenal Function. Adv Pediatr 2017; 64:331.
- Levin C, Maibach HI. Topical corticosteroid-induced adrenocortical insufficiency: clinical implications. Am J Clin Dermatol 2002; 3:141.
- Kenny FM, Preeyasombat C, Migeon CJ. Cortisol production rate. II. Normal infants, children, and adults. Pediatrics 1966; 37:34.
- Ballard PL, Gluckman PD, Liggins GC, et al. Steroid and growth hormone levels in premature infants after prenatal betamethasone therapy to prevent respiratory distress syndrome. Pediatr Res 1980; 14:122.
- CLINICAL MANIFESTATIONS
- SECONDARY ADRENAL INSUFFICIENCY
- - Congenital causes
- - Acquired causes
- Isolated ACTH deficiency
- TERTIARY ADRENAL INSUFFICIENCY
- Hypopituitarism due to impaired hypothalamic function
- - Congenital causes
- - Acquired causes
- Isolated ACTH deficiency from suppressed hypothalamic function
- - Cessation of glucocorticoid therapy
- - Maternal glucocorticoid therapy
- - Resection of adrenal tumor
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