Adrenal insufficiency overview

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Ayeesha Kattubadi, M.B.B.S[2]

Overview

Adrenal insufficiency is a clinical state where there is reduced production of adrenocortical hormones. The adrenal cortex is divided into three zones- zona glomerulosa, zona fasciculata and zona reticularis producing mineralocorticoids, glucocorticoids and androgens respectively. Adrenal insufficiency causes glucocorticoid and mineralocorticoid deficiency. Its classified as primary, secondary and tertiary. Its presentation depends on the rapidity and degree of hormone depletion. It can present acutely as adrenal crisis, especially when the body is under stress due infections, trauma etc. If it presents chronically it is called Addisons disease. Treatment consists of lifelong glucocorticoid and mineralocorticoid replacement.

Historical Perspective

Adrenal insufficiency was first discovered by Thomas Addison in 1849. [1]

Classification

Adrenal insufficiency may be classified according to location of pathology into three subtypes primary adrenal insufficiency, secondary adrenal insufficiency, and tertiary adrenal insufficiency. [2]

Pathophysiology

It is thought that adrenal insufficiency is the result of multiple etiologies like autoimmune adrenalitis, X-linked adrenoleukodystrophy, chronic glucocorticoid use, adrenal hemoorage etc. The pathophysiology depends on each etiological subtype. [3] [4][5] [6][7] [8]

Causes

Common causes of adrenal insufficiency include autoimmune adrenalitis and chronic glucocorticoid use. [2] [9]

Differentiating adrenal insufficiency from Other Diseases

Addison's disease must be differentiated from other diseases that cause hypotension, skin pigmentation, and abdominal pain such as myopathies, celiac disease, Peutz-Jeghers syndrome, anorexia nervosa, syndrome of inappropriate antidiuretic hormone (SIADH), neurofibromatosis, porphyria cutanea tarda, salt-depletion nephritis and bronchogenic carcinoma.

Epidemiology and Demographics

Adrenal insufficiency is a rare disorder. It may present in patients of all age groups. The incidence of autoimmune adrenalitis is more common in females in the age groups of 30 to 50 compared to males. Whereas, adrenal crisis does not show any female to male predilection. The most common cause of primary adrenal insufficiency in the developed world is autoimmune adrenalitis. Whereas, in the developing world it is Tuberculosis. The most common cause of central adrenal insufficiency is chronic glucocorticoid use. [10] [11]

Risk Factors

Common risk factors in the development of adrenal insufficiency include chronic glucocorticoid use, tuberculosis, anticoagulant use, etc. [12].

Screening

There is insufficient evidence to recommend routine screening for adrenal insufficiency. [13]

Natural History, Complications, and Prognosis

Common complications of adrenal insufficiency include cardiovascular complications, disturbed sleep, reduced bone mineral density. Prognosis is generally excellent with replacement therapy. [14][4]

Diagnosis

Diagnostic Study of Choice

The ACTH stimulation test is considered the diagnostic test of choice.

History and Symptoms

The hallmark of adrenal insufficiency is fatigue. Most patients with adrenal insufficiency present with non specific symptoms. A positive history of fatigue,nausea and abdominal pain is suggestive of adrenal insufficiency. The most common symptoms of adrenal insufficiency include fatigue, anorexia, and weight loss. Common symptoms of adrenal insufficiency include abdominal pain, nausea, and vomiting. Less common symptoms of adrenal insufficiency include diarrhea, arthralgia, and myalgia. [15][13]

Physical Examination

Patients with adrenal insufficiency usually appear dehydrated and weak. Physical examination of patients with primary adrenal insufficiency is usually remarkable for hyperpigmentation of skin. [15][16]

Laboratory Findings

Laboratory findings consistent with the diagnosis of primary adrenal insufficiency include hyponatremia, hyperkalemia, and hypercalcemia, normocytic normochromic anemia, eosinophilia.[13]

Electrocardiogram

ECG findings seen in adrenal insufficiency are due to hyperkalemia. These changes include peaked T waves, short QT interval, prolonged PR interval, loss of P wave, widened QRS complex. [17]

X-ray

X-ray may be helpful in the diagnosis of etiology of adrenal insufficiency, which include tuberculosis, sarcoidosis. [2]

Echocardiography and Ultrasound

There are no echocardiography findings associated with adrenal insufficiency. However, an echocardiography may be helpful in the diagnosis of cardiovascular complications of adrenal insufficiency, which include ischemic heart disease, heart failure, and dilated cardiomyopathy. [18]

CT scan

CT scan may be helpful in the diagnosis of etiology of adrenal insufficiency, which include adrenal hemorrhage, tuberculous adrenalitis, and adrenal metastasis.[2]

MRI

An MRI may be helpful in the diagnosis of etiology of adrenal insufficiency, which include tuberculous adrenalitis, autoimmune adrenalitis. [2]

Treatment

Medical Therapy

Pharmacologic medical therapy is recommended among patients with adrenal insufficiency Pharmacologic medical therapies for adrenal insufficiency include lifelong glucocorticoid and mineralocorticoid replacement therapy. Mineralocorticoid replacement therapy is only used in patients with primary adrenal insufficiency. [9] [19][20]

Surgery

Surgical intervention is not recommended for the management of adrenal insufficiency. [21]

Primary Prevention

There are no established measures for the primary prevention of adrenal insufficiency. [22]

Secondary Prevention

There are no established measures for the secondary prevention of adrenal insufficiency.

References

  1. BISHOP PM (1950). "The history of the discovery of Addison's disease". Proc R Soc Med. 43 (1): 35–42. PMC 2081266. PMID 15409948.
  2. 2.0 2.1 2.2 2.3 2.4 Feingold KR, Anawalt B, Boyce A, Chrousos G, de Herder WW, Dungan K; et al. (2000). "Endotext". PMID 25905309.
  3. "StatPearls". 2020. PMID 28722862.
  4. 4.0 4.1 Erichsen, Martina M.; Løvås, Kristian; Skinningsrud, Beate; Wolff, Anette B.; Undlien, Dag E.; Svartberg, Johan; Fougner, Kristian J.; Berg, Tore J.; Bollerslev, Jens; Mella, Bjarne; Carlson, Joyce A.; Erlich, Henry; Husebye, Eystein S. (2009). "Clinical, Immunological, and Genetic Features of Autoimmune Primary Adrenal Insufficiency: Observations from a Norwegian Registry". The Journal of Clinical Endocrinology & Metabolism. 94 (12): 4882–4890. doi:10.1210/jc.2009-1368. ISSN 0021-972X.
  5. Huffnagel, Irene C; Laheji, Fiza K; Aziz-Bose, Razina; Tritos, Nicholas A; Marino, Rose; Linthorst, Gabor E; Kemp, Stephan; Engelen, Marc; Eichler, Florian (2019). "The Natural History of Adrenal Insufficiency in X-Linked Adrenoleukodystrophy: An International Collaboration". The Journal of Clinical Endocrinology & Metabolism. 104 (1): 118–126. doi:10.1210/jc.2018-01307. ISSN 0021-972X.
  6. Berger J, Forss-Petter S, Eichler FS (2014). "Pathophysiology of X-linked adrenoleukodystrophy". Biochimie. 98: 135–42. doi:10.1016/j.biochi.2013.11.023. PMC 3988840. PMID 24316281.
  7. Feingold KR, Anawalt B, Boyce A, Chrousos G, de Herder WW, Dungan K; et al. (2000). "Endotext". PMID 25905379.
  8. Younes, Areej K.; Younes, Noor K. (2017). "Recovery of steroid induced adrenal insufficiency". Translational Pediatrics. 6 (4): 269–273. doi:10.21037/tp.2017.10.01. ISSN 2224-4336.
  9. 9.0 9.1 Bornstein, Stefan R.; Allolio, Bruno; Arlt, Wiebke; Barthel, Andreas; Don-Wauchope, Andrew; Hammer, Gary D.; Husebye, Eystein S.; Merke, Deborah P.; Murad, M. Hassan; Stratakis, Constantine A.; Torpy, David J. (2016). "Diagnosis and Treatment of Primary Adrenal Insufficiency: An Endocrine Society Clinical Practice Guideline". The Journal of Clinical Endocrinology & Metabolism. 101 (2): 364–389. doi:10.1210/jc.2015-1710. ISSN 0021-972X.
  10. Melmed, Shlomo (2020). Williams textbook of endocrinology. Philadelphia, PA: Elsevier. ISBN 9780323555968.
  11. Elshimy G, Alghoula F, Jeong JM. PMID 29763143. Missing or empty |title= (help)
  12. "www.amjmed.com".
  13. 13.0 13.1 13.2 Chanson, Philippe; Guignat, Laurence; Goichot, Bernard; Chabre, Olivier; Boustani, Dinane Samara; Reynaud, Rachel; Simon, Dominique; Tabarin, Antoine; Gruson, Damien; Reznik, Yves; Raffin Sanson, Marie-Laure (2017). "Group 2: Adrenal insufficiency: screening methods and confirmation of diagnosis". Annales d'Endocrinologie. 78 (6): 495–511. doi:10.1016/j.ando.2017.10.005. ISSN 0003-4266.
  14. "www.amjmed.com".
  15. 15.0 15.1 Pazderska, Agnieszka; Pearce, Simon HS (2017). "Adrenal insufficiency – recognition and management". Clinical Medicine. 17 (3): 258–262. doi:10.7861/clinmedicine.17-3-258. ISSN 1470-2118.
  16. Lause M, Kamboj A, Fernandez Faith E (2017). "Dermatologic manifestations of endocrine disorders". Transl Pediatr. 6 (4): 300–312. doi:10.21037/tp.2017.09.08. PMC 5682371. PMID 29184811.
  17. Levis, Joel (2013). "ECG Diagnosis: Hyperkalemia". The Permanente Journal. 17 (1): 69–69. doi:10.7812/TPP/12-088. ISSN 1552-5767.
  18. Rahvar, Amir-Hossein; Haas, Christian S.; Danneberg, Sven; Harbeck, Birgit (2017). "Increased Cardiovascular Risk in Patients with Adrenal Insufficiency: A Short Review". BioMed Research International. 2017: 1–5. doi:10.1155/2017/3691913. ISSN 2314-6133.
  19. Oprea, Alina; Bonnet, Nicolas C. G.; Pollé, Olivier; Lysy, Philippe A. (2019). "Novel insights into glucocorticoid replacement therapy for pediatric and adult adrenal insufficiency". Therapeutic Advances in Endocrinology and Metabolism. 10: 204201881882129. doi:10.1177/2042018818821294. ISSN 2042-0188.
  20. https://www.elsevier.es/index.php?p=revista&pRevista=pdf-simple&pii=S2173509314700698
  21. https://www.elsevier.es/index.php?p=revista&pRevista=pdf-simple&pii=S2173509314700698
  22. Dineen, Rosemary; Thompson, Christopher J; Sherlock, Mark (2019). "Adrenal crisis: prevention and management in adult patients". Therapeutic Advances in Endocrinology and Metabolism. 10: 204201881984821. doi:10.1177/2042018819848218. ISSN 2042-0188.


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