Pediatric Adrenal Insufficiency (Addison Disease) Differential Diagnoses

  • Author: Phyllis W Speiser, MD; Chief Editor: Stephen Kemp, MD, PhD   more...
 
Updated: Jun 10, 2011
 
 

Diagnostic Considerations

Adrenal insufficiency (Addison disease) may be difficult to differentiate from other conditions (eg, chronic fatigue syndrome, depression) if its onset is gradual.[28, 29]

Physicians must consider adrenal insufficiency (Addison disease) in the differential diagnosis of patients with suggestive symptoms, such as chronic fatigue, anorexia, nausea, vomiting, diarrhea, unexplained weight loss, dehydration, hypoglycemia, and hypotension. Other conditions that should be considered include adrenocorticotropic hormone (ACTH) receptor defect, adrenoleukodystrophy and adrenomyeloneuropathy, autoimmune polyglandular endocrinopathy syndromes, infectious adrenalitis (eg, in association with human immunodeficiency [HIV] infection or tuberculosis [TB]), adrenal hemorrhage, lipoid adrenal hyperplasia, and Wolman disease.

Antiphospholipid syndrome occasionally results in acute adrenal insufficiency (Addison disease) secondary to bilateral adrenal hemorrhage.[8]

Differential Diagnoses

Proceed to Workup
 
 
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, Lawson-Wilkins Pediatric Endocrine Society, and 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, Lawson-Wilkins Pediatric Endocrine Society, and Phi Beta Kappa

Disclosure: Nothing to disclose.

Specialty Editor Board

Karl S Roth, MD  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 Clinical 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, and Southern Society for Pediatric Research

Disclosure: Nothing to disclose.

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 Federation for Clinical Research, American Medical Association, American Pediatric Society, Association of Clinical Scientists, Endocrine Society, Florida Medical Association, Lawson-Wilkins Pediatric Endocrine Society, Pituitary Society, Society for Pediatric Research, Society for the Study of Reproduction, and Southern Society for Pediatric Research

Disclosure: Nothing to disclose.

Chief Editor

Stephen Kemp, MD, PhD  Professor, Department of Pediatrics, Section of Pediatric Endocrinology, University of Arkansas College of Medicine and 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, and Southern Society for Pediatric Research

Disclosure: Nothing to disclose.

References

  1. Stewart, PM. The adrenal cortex. In: 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. Jul 15 2003;98(2):397-405. [Medline].

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

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

  5. 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. Feb 1 2001;10(3):283-90. [Medline].

  6. 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. Jun 1993;68(6):779-82. [Medline].

  7. 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. Jun 2005;90(6):3243-50. [Medline]. [Full Text].

  8. 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). Jun 2001;40(6):347-50. [Medline].

  9. 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. Feb 1996;81(2):470-4. [Medline]. [Full Text].

  10. 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. Jul 1997;137(1):40-7. [Medline]. [Full Text].

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

  12. 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. Apr 2008;34(4):714-9. [Medline].

  13. 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. Aug 1998;83(8):2666-74. [Medline]. [Full Text].

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

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

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

  17. 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. Dec 2006;91(12):4781-5. [Medline].

  18. 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. Mar 2008;93(3):696-702. [Medline].

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

  20. 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. Nov 2004;30(4):881-8. [Medline].

  21. 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. Mar 2004;36(3):228-30. [Medline].

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

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

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

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

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

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

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

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

  30. 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. Jan 2008;36(1):296-327. [Medline].

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

  32. 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. Dec 1993;77(6):1584-8. [Medline]. [Full Text].

  33. 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. Sep 1991;73(3):674-86. [Medline].

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

  35. 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. Oct 2005;90(10):5737-42. [Medline]. [Full Text].

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

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

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

  39. 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. Dec 1998;83(12):4530; author reply 4532-3. [Medline].

  40. 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. May 1998;83(5):1558-62. [Medline]. [Full Text].

  41. 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. Dec 1998;83(12):4531-3. [Medline]. [Full Text].

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

  43. 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. Sep 2004;27(8):736-41. [Medline].

  44. 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. Jun 2005;90(6):3295-303. [Medline].

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

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

  47. Frank GR, Speiser PW, Griffin KJ, Stratakis CA. Safety of medications and hormones used in pediatric endocrinology: adrenal. Pediatr Endocrinol Rev. Nov 2004;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 © 1994-2012 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.