Close
New

Medscape is available in 5 Language Editions – Choose your Edition here.

 

Pediatric Adrenal Insufficiency (Addison Disease) Clinical Presentation

  • Author: Phyllis W Speiser, MD; Chief Editor: Stephen Kemp, MD, PhD  more...
 
Updated: Jun 19, 2016
 

History

Patients with adrenal insufficiency (Addison disease) may have hypoglycemia, and most have hypotension. Orthostatic changes in blood pressure and pulse are cardinal signs of adrenal insufficiency. Symptoms of hypoglycemia are common in small children. Altered mental status, even without hypoglycemia, is common in affected patients with acute adrenal insufficiency.

In infants, acute adrenal insufficiency may occur in the context of serious illness (eg, sepsis), prolonged and difficult labor, or traumatic delivery. Tuberculosis (TB), meningococcemia, or any severe septicemia may also result in adrenal insufficiency. However, adrenal insufficiency may occur without concomitant illness when it is due to congenital adrenal hyperplasia or congenital adrenal hypoplasia.

Chronic adrenal insufficiency

Patients with chronic adrenal insufficiency (Addison disease) usually have chronic fatigue, anorexia, asthenia, nausea, vomiting, loss of appetite, weight loss, recurring abdominal pain, and weakness and a lack of energy. Increased skin pigmentation and salt craving are common among individuals with chronic primary adrenal insufficiency. Salt craving is a symptom typical of patients with dysfunction of the zona glomerulosa; this craving may be the first sign of autoimmune adrenal destruction.

Excess melanocyte-stimulating hormone (MSH) activity from adrenocorticotropic hormone (ACTH) causes the hyperpigmentation. Hyperpigmentation is not noted in patients with secondary or central adrenal insufficiency due to ACTH or corticotropin-releasing hormone (CRH) deficiency, because these conditions do not elevate serum ACTH concentrations. If the defect lies in the pituitary or hypothalamus, aldosterone production is not altered, because the renin-angiotensin system adequately stimulates the adrenal zona glomerulosa to ensure sufficient aldosterone concentrations and to prevent salt wasting.

Patients who have recently received long-term pharmacologic doses of glucocorticoids are prone to develop symptoms of adrenal insufficiency (Addison disease) when they are stressed because of an illness or trauma. In this setting, adrenal insufficiency is due to chronic suppression of CRH and ACTH by exogenous glucocorticoids. As a consequence, patients are unable to mount an appropriate cortisol response to stress. Patients in this situation are not hyperpigmented because ACTH concentrations are not elevated, and they do not waste sodium because their renin-angiotensin system maintains aldosterone secretion. Recovery of the hypothalamic-pituitary-adrenal axis may take weeks to months and is related to how long the patient was exposed to pharmacologic glucocorticoids.

Autoimmune adrenal insufficiency, adrenal insufficiency from adrenoleukodystrophy

In general, autoimmune adrenal insufficiency or adrenal insufficiency due to adrenoleukodystrophy (Online Mendelian Inheritance in Man [OMIM 300100]), chronic infections (eg, human immunodeficiency virus [HIV] infection, TB, fungal infection), or infiltrative lesions usually present with chronic symptoms (eg, fatigue, anorexia, abdominal pain). However, an acute adrenal crisis may exacerbate the symptoms.

See also Adrenal Crisis and Adrenal Insufficiency and Adrenal Crisis.

Next

Physical Examination

Patients with acute adrenal insufficiency (Addison disease) generally present with acute dehydration, hypotension (especially orthostatic hypotension and tachycardia), symptomatic hypoglycemia, or altered mental status. These signs may occur in conjunction with acute sepsis or disseminated intravascular coagulation or in a patient after a traumatic delivery.

As previously discussed, hyperpigmentation may be seen in primary adrenal insufficiency due to adrenocorticotropic hormone (ACTH) overproduction by the pituitary. The ACTH molecule contains the sequence for alpha-melanocyte-stimulating hormone (MSH), which stimulates melanocytes.

Note increased skin pigmentation, particularly in the areolae and genitalia, as well as any scars or moles. Recent scars are typically affected more than old scars. In addition, areas unexposed to sun (eg, palmar creases, axillae, areolae) are often hyperpigmented, which may help to distinguish hyperpigmentation from sun tan. The patient may also have pigmentary lines in the gums. See the images below.

Left photograph shows hyperpigmentation on the dor Left photograph shows hyperpigmentation on the dorsum of a patient's hand before the treatment of primary adrenal insufficiency. Right photograph shows normal pigmentation after treatment.
Left photograph shows a patient with Addison disea Left photograph shows a patient with Addison disease who has prominent pigmentation in areas not exposed to the sun, such as the palmar creases. Right photograph shows normal pigmentation after treatment.
Left photograph shows vitiligo in a patient with a Left photograph shows vitiligo in a patient with autoimmune adrenalitis. Right photograph shows an area of hyperpigmentation surrounding the vitiligo.

Signs of weight loss may be evident. If the patient is not frankly hypotensive, he or she may have orthostatic hypotension.

Some patients lose pubic and axillary hair because adrenal androgens support growth of body hair in these areas.

Previous
 
 
Contributor Information and Disclosures
Author

Phyllis W Speiser, MD Chief, Division of Pediatric Endocrinology, Steven and Alexandra Cohen Children's Medical Center of New York; Professor of Pediatrics, Hofstra-North Shore LIJ School of Medicine at Hofstra University

Phyllis W Speiser, MD is a member of the following medical societies: American Association of Clinical Endocrinologists, Endocrine Society, Pediatric Endocrine Society, Society for Pediatric Research

Disclosure: Nothing to disclose.

Coauthor(s)

Thomas A Wilson, MD Professor of Clinical Pediatrics, Chief and Program Director, Division of Pediatric Endocrinology, Department of Pediatrics, The School of Medicine at Stony Brook University Medical Center

Thomas A Wilson, MD is a member of the following medical societies: Endocrine Society, Pediatric Endocrine Society, Phi Beta Kappa

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Barry B Bercu, MD Professor, Departments of Pediatrics, Molecular Pharmacology and Physiology, University of South Florida College of Medicine, All Children's Hospital

Barry B Bercu, MD is a member of the following medical societies: American Academy of Pediatrics, American Association of Clinical Endocrinologists, American Medical Association, American Pediatric Society, Association of Clinical Scientists, Endocrine Society, Florida Medical Association, Pediatric Endocrine Society, Society for Pediatric Research, Southern Society for Pediatric Research, Society for the Study of Reproduction, American Federation for Clinical Research, Pituitary Society

Disclosure: Nothing to disclose.

Chief Editor

Stephen Kemp, MD, PhD Former Professor, Department of Pediatrics, Section of Pediatric Endocrinology, University of Arkansas for Medical Sciences College of Medicine, Arkansas Children's Hospital

Stephen Kemp, MD, PhD is a member of the following medical societies: American Academy of Pediatrics, American Association of Clinical Endocrinologists, American Pediatric Society, Endocrine Society, Phi Beta Kappa, Southern Medical Association, Southern Society for Pediatric Research

Disclosure: Nothing to disclose.

Additional Contributors

Karl S Roth, MD Retired Professor and Chair, Department of Pediatrics, Creighton University School of Medicine

Karl S Roth, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics, American College of Nutrition, American Pediatric Society, American Society for Nutrition, American Society of Nephrology, Association of American Medical Colleges, Medical Society of Virginia, New York Academy of Sciences, Sigma Xi, Society for Pediatric Research, Southern Society for Pediatric Research

Disclosure: Nothing to disclose.

References
  1. Stewart, PM. The adrenal cortex. Kronenberg HM, Melmed S, Polonsky KS, Larsen RP, eds. Williams Textbook of Endocrinology. 11th ed. Philadelphia, PA: Saunders; 2008. Chapter 14.

  2. Orme LM, Bond JD, Humphrey MS, Zacharin MR, Downie PA, Jamsen KM. Megestrol acetate in pediatric oncology patients may lead to severe, symptomatic adrenal suppression. Cancer. 2003 Jul 15. 98(2):397-405. [Medline].

  3. Gibb FW, Stewart A, Walker BR, Strachan MW. Adrenal insufficiency in patients on long-term opioid analgesia. Clin Endocrinol (Oxf). 2016 Jun 4. [Medline].

  4. Tsigos C, Arai K, Hung W, Chrousos GP. Hereditary isolated glucocorticoid deficiency is associated with abnormalities of the adrenocorticotropin receptor gene. J Clin Invest. 1993 Nov. 92(5):2458-61. [Medline]. [Full Text].

  5. Clark A, Weber A. Molecular insights into inherited ACTH resistance syndromes. Trends Endocrinol Metab. 1994. 5:209-14. [Full Text].

  6. Handschug K, Sperling S, Yoon SJ, Hennig S, Clark AJ, Huebner A. Triple A syndrome is caused by mutations in AAAS, a new WD-repeat protein gene. Hum Mol Genet. 2001 Feb 1. 10(3):283-90. [Medline].

  7. Grant DB, Barnes ND, Dumic M, Ginalska-Malinowska M, Milla PJ, von Petrykowski W. Neurological and adrenal dysfunction in the adrenal insufficiency/alacrima/achalasia (3A) syndrome. Arch Dis Child. 1993 Jun. 68(6):779-82. [Medline].

  8. Perry R, Kecha O, Paquette J, Huot C, Van Vliet G, Deal C. Primary adrenal insufficiency in children: twenty years experience at the Sainte-Justine Hospital, Montreal. J Clin Endocrinol Metab. 2005 Jun. 90(6):3243-50. [Medline]. [Full Text].

  9. Purandare A, Godil MA, Prakash D, Parker R, Zerah M, Wilson TA. Spontaneous adrenal hemorrhage associated with transient antiphospholipid antibody in a child. Clin Pediatr (Phila). 2001 Jun. 40(6):347-50. [Medline].

  10. Laureti S, Casucci G, Santeusanio F, Angeletti G, Aubourg P, Brunetti P. X-linked adrenoleukodystrophy is a frequent cause of idiopathic Addison's disease in young adult male patients. J Clin Endocrinol Metab. 1996 Feb. 81(2):470-4. [Medline]. [Full Text].

  11. Korenke GC, Roth C, Krasemann E, Hufner M, Hunneman DH, Hanefeld F. Variability of endocrinological dysfunction in 55 patients with X-linked adrenoleucodystrophy: clinical, laboratory and genetic findings. Eur J Endocrinol. 1997 Jul. 137(1):40-7. [Medline]. [Full Text].

  12. Andersson HC, Frentz J, Martínez JE, Tuck-Muller CM, Bellizaire J. Adrenal insufficiency in Smith-Lemli-Opitz syndrome. Am J Med Genet. 1999 Feb 19. 82(5):382-4. [Medline].

  13. Vinclair M, Broux C, Faure P, et al. Duration of adrenal inhibition following a single dose of etomidate in critically ill patients. Intensive Care Med. 2008 Apr. 34(4):714-9. [Medline].

  14. Peter M, Viemann M, Partsch CJ, Sippell WG. Congenital adrenal hypoplasia: clinical spectrum, experience with hormonal diagnosis, and report on new point mutations of the DAX-1 gene. J Clin Endocrinol Metab. 1998 Aug. 83(8):2666-74. [Medline]. [Full Text].

  15. Ferraz-de-Souza B, Achermann JC. Disorders of adrenal development. Endocr Dev. 2008. 13:19-32. [Medline].

  16. Kempna P, Fluck CE. Adrenal gland development and defects. Best Pract Res Clin Endocrinol Metab. 2008 Feb. 22(1):77-93. [Medline].

  17. Lalli E, Sassone-Corsi P. DAX-1 and the adrenal cortex. Curr Opin Endocrinol Diabetes. 1999. 6:185-90. [Full Text].

  18. Baker BY, Lin L, Kim CJ, et al. Nonclassic congenital lipoid adrenal hyperplasia: a new disorder of the steroidogenic acute regulatory protein with very late presentation and normal male genitalia. J Clin Endocrinol Metab. 2006 Dec. 91(12):4781-5. [Medline].

  19. Kim CJ, Lin L, Huang N, et al. Severe combined adrenal and gonadal deficiency caused by novel mutations in the cholesterol side chain cleavage enzyme, P450scc. J Clin Endocrinol Metab. 2008 Mar. 93(3):696-702. [Medline].

  20. Miller WL. Minireview: regulation of steroidogenesis by electron transfer. Endocrinology. 2005 Jun. 146(6):2544-50. [Medline].

  21. Pandey AV, Fluck CE, Huang N, Tajima T, Fujieda K, Miller WL. P450 oxidoreductase deficiency: a new disorder of steroidogenesis affecting all microsomal P450 enzymes. Endocr Res. 2004 Nov. 30(4):881-8. [Medline].

  22. Fluck CE, Tajima T, Pandey AV, Arlt W, Okuhara K, Verge CF. Mutant P450 oxidoreductase causes disordered steroidogenesis with and without Antley-Bixler syndrome. Nat Genet. 2004 Mar. 36(3):228-30. [Medline].

  23. Lamberts SW, Bruining HA, de Jong FH. Corticosteroid therapy in severe illness. N Engl J Med. 1997 Oct 30. 337(18):1285-92. [Medline].

  24. Pizarro CF, Troster EJ, Damiani D, Carcillo JA. Absolute and relative adrenal insufficiency in children with septic shock. Crit Care Med. 2005 Apr. 33(4):855-9. [Medline].

  25. Fleseriu M, Loriaux DL. "Relative" adrenal insufficiency in critical illness. Endocr Pract. 2009 Sep-Oct. 15(6):632-40. [Medline].

  26. Hsieh S, White PC. Presentation of primary adrenal insufficiency in childhood. J Clin Endocrinol Metab. 2011 Jun. 96(6):E925-8. [Medline].

  27. Willis AC, Vince FP. The prevalence of Addison's disease in Coventry, UK. Postgrad Med J. 1997 May. 73(859):286-8. [Medline].

  28. Laureti S, Vecchi L, Santeusanio F, Falorni A. Is the prevalence of Addison's disease underestimated? [letter]. J Clin Endocrinol Metab. 1999 May. 84(5):1762. [Medline]. [Full Text].

  29. Olafsson AS, Sigurjonsdottir HA. Increasing prevalence of Addison disease: results from a nationwide study. Endocr Pract. 2016 Jan. 22 (1):30-5. [Medline].

  30. Arlt W, Allolio B. Adrenal insufficiency. Lancet. 2003 May 31. 361(9372):1881-93. [Medline].

  31. Besser GM, Thorner MO. Adrenal insufficiency. Clinical Endocrinology. St Louis, Mo: Mosby-Year Book; 1996. [CD-ROM]:

  32. Dellinger RP, Levy MM, Carlet JM, et al. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008. Crit Care Med. 2008 Jan. 36(1):296-327. [Medline].

  33. Clark L, Preissig C, Rigby MR, Bowyer F. Endocrine issues in the pediatric intensive care unit. Pediatr Clin North Am. 2008 Jun. 55(3):805-33, xiii. [Medline].

  34. Kamoi K, Tamura T, Tanaka K, Ishibashi M, Yamaji T. Hyponatremia and osmoregulation of thirst and vasopressin secretion in patients with adrenal insufficiency. J Clin Endocrinol Metab. 1993 Dec. 77(6):1584-8. [Medline]. [Full Text].

  35. Lashansky G, Saenger P, Fishman K, Gautier T, Mayes D, Berg G. Normative data for adrenal steroidogenesis in a healthy pediatric population: age- and sex-related changes after adrenocorticotropin stimulation. J Clin Endocrinol Metab. 1991 Sep. 73(3):674-86. [Medline].

  36. Neary N, Nieman L. Adrenal insufficiency: etiology, diagnosis and treatment. Curr Opin Endocrinol Diabetes Obes. 2010 Apr 6. [Medline].

  37. Heckmann M, Hartmann MF, Kampschulte B, Gack H, Bodeker RH, Gortner L. Cortisol production rates in preterm infants in relation to growth and illness: a noninvasive prospective study using gas chromatography-mass spectrometry. J Clin Endocrinol Metab. 2005 Oct. 90(10):5737-42. [Medline]. [Full Text].

  38. Kronenberg HM, Melmed S, Polonsky KS, Larson PR, eds. Williams Textbook of Endocrinology. 11th ed. Philadelphia, PA: Saunders; 2008. 229.

  39. Kazlauskaite R, Evans AT, Villabona CV, et al. Corticotropin tests for hypothalamic-pituitary- adrenal insufficiency: a metaanalysis. J Clin Endocrinol Metab. 2008 Nov. 93(11):4245-53. [Medline].

  40. Thaler LM. Comment on the low-dose corticotropin stimulation test is more sensitive than the high-dose test. [letter]. J Clin Endocrinol Metab. 1998 Dec. 83(12):4530-1; author reply 4532-3. [Medline].

  41. Tordjman K, Jaffe A, Greenman Y, Stern N. Comments on the comparison of low and high dose corticotropin stimulation tests in patients with pituitary disease. J Clin Endocrinol Metab. 1998 Dec. 83(12):4530; author reply 4532-3. [Medline].

  42. Mayenknecht J, Diederich S, Bahr V, Plockinger U, Oelkers W. Comparison of low and high dose corticotropin stimulation tests in patients with pituitary disease. J Clin Endocrinol Metab. 1998 May. 83(5):1558-62. [Medline]. [Full Text].

  43. Dickstein G. Commentary to the article: Comparison of low and high dose corticotropin stimulation tests in patients with pituitary disease [letter]. J Clin Endocrinol Metab. 1998 Dec. 83(12):4531-3. [Medline]. [Full Text].

  44. Neary N, Nieman L. Adrenal insufficiency: etiology, diagnosis and treatment. Curr Opin Endocrinol Diabetes Obes. 2010 Jun. 17(3):217-23. [Medline]. [Full Text].

  45. Libe R, Barbetta L, Dall'Asta C, et al. Effects of dehydroepiandrosterone (DHEA) supplementation on hormonal, metabolic and behavioral status in patients with hypoadrenalism. J Endocrinol Invest. 2004 Sep. 27(8):736-41. [Medline].

  46. van Thiel SW, Romijn JA, Pereira AM, et al. Effects of dehydroepiandrostenedione, superimposed on growth hormone substitution, on quality of life and insulin-like growth factor I in patients with secondary adrenal insufficiency: a randomized, placebo-controlled, cross-over trial. J Clin Endocrinol Metab. 2005 Jun. 90(6):3295-303. [Medline].

  47. Merke DP, Chrousos GP, Eisenhofer G, et al. Adrenomedullary dysplasia and hypofunction in patients with classic 21-hydroxylase deficiency. N Engl J Med. 2000 Nov 9. 343(19):1362-8. [Medline].

  48. Coutant R, Maurey H, Rouleau S, et al. Defect in epinephrine production in children with craniopharyngioma: functional or organic origin?. J Clin Endocrinol Metab. 2003 Dec. 88(12):5969-75. [Medline].

  49. Frank GR, Speiser PW, Griffin KJ, Stratakis CA. Safety of medications and hormones used in pediatric endocrinology: adrenal. Pediatr Endocrinol Rev. 2004 Nov. 2 Suppl 1:134-45. [Medline].

 
Previous
Next
 
Regulation of the adrenal cortex. ACTH = adrenocorticotropic hormone; CRF = corticotropin-releasing factor; neg. = negative.
Left photograph shows hyperpigmentation on the dorsum of a patient's hand before the treatment of primary adrenal insufficiency. Right photograph shows normal pigmentation after treatment.
Left photograph shows a patient with Addison disease who has prominent pigmentation in areas not exposed to the sun, such as the palmar creases. Right photograph shows normal pigmentation after treatment.
Left photograph shows vitiligo in a patient with autoimmune adrenalitis. Right photograph shows an area of hyperpigmentation surrounding the vitiligo.
Left photomicrograph shows autoimmune adrenalitis. Right photomicrograph shows tuberculous adrenalitis. Note the caseous granuloma.
Computed tomography scan shows enlarged adrenal glands in a patient with early active autoimmune adrenalitis. Patients with chronic disease present with the opposite picture of hypotrophic adrenals.
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2016 by WebMD LLC. This website also contains material copyrighted by 3rd parties.