Adrenal insufficiency resident survival guide

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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 can cause glucocorticoid and mineralocorticoid deficiency. It is classified as primary, secondary and tertiary. It's 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. The common causes include chronic glucocorticoid use and autoimmune adrenalitis. It is diagnosed using serum basal cortisol measurement and ACTH stimulation test. Treatment consists of lifelong glucocorticoid and mineralocorticoid replacement. [1] [2]

Causes

Life Threatening Causes

Life-threatening causes include conditions that may result in death or permanent disability within 24 hours if left untreated.[3]

Common Causes

Common causes of adrenal insufficiency may include:[4][5]

Less common causes:

Diagnosis

Shown below is an algorithm summarizing the diagnosis of adrenal insufficiency.[5][6]


 
 
 
 
 
 
 
 
 
 
 
 
 
Adrenal Insufficiency suspected
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Serum basal cortisol
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
<5 µg/dL
 
 
 
 
 
 
 
5-18 µg/dL
 
 
 
 
 
 
>18 µg/dL
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Confirms Adrenal Insufficiency
 
 
 
 
 
 
 
Dynamic tests
 
 
 
 
 
 
Rules out Adrenal Insufficiency
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Primary Adrenal Insufficiency suspected
 
 
 
 
 
 
 
 
 
 
 
 
 
Secondary Adrenal Insufficiency suspected
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
ACTH stimulation test
 
 
 
 
 
 
 
 
 
 
 
 
 
ACTH stimulation test
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Serum cortisol <18 µg/dL
 
Serum cortisol >18µg/dL
 
 
 
 
 
 
Serum cortisol <18 µg/dL
 
 
Serum cortisol 18-23µg/dL
 
 
Serum cortisol >23 µg/dL
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Confirms Adrenal Insufficiency
 
Rules out Adrenal Insufficiency
 
 
 
 
 
 
Confirms Adrenal Insufficiency
 
 
Indeterminate
 
 
Rules out Adrenal Insufficiency
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Insulin hypoglycemic test
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Serum cortisol <18µg/dL
 
Serum cortisol >18µg/dL
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Confirms Adrenal Insufficiency
 
Rules out Adrenal Insufficiency
 
 

Treatment

Shown below is an algorithm summarizing the treatment of adrenal insufficiency. [5][7][8]

 
 
 
 
 
Primary adrenal insufficiency
 
 
 
 
 
 
 
Secondary adrenal insufficiency
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Lifelong Glucocorticoid and Mineralocorticoid replacement therapy
 
 
 
 
 
 
 
Lifelong Glucocorticoid replacement therapy
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Mineralocorticoid
replacement therapy:

9 α-Fludrocortisone 0.05-0.2 mg/day PO
single dose in the morning
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Glucocorticoid
replacement therapy:

1. Hydrocortisone 15-25mg PO
in two or three divided doses
2. Cortisone acetate 20-25mg PO
single dose in the morning
 
 
 
 
 
 
 

Do's

  • In the diagnosis of Adrenal insufficiency plasma cortisol to be measured between 8:00-9:00 AM, after the early morning peak which happens between 6:00-8:00 AM.
  • Hydrocortisone (preferred glucocorticoid) to be given in two or three divided doses to mimic the circadian rhythm.
  • Glucocorticoid dose to be titrated based on symptom improvement. The least possible dose of glucocorticoid has to be used.
  • Mineralocorticoid dose to be titrated based on symptom improvement (salt craving, postural hypotension, edema) and electrolytes.
  • After adjusting the dose follow up to be continued annually.
  • Patients to be educated to self increase the dose of glucocorticoid in the presence of other illnesses like fever, wounds.
  • Patients to be educated to carry steroid emergency and medical alert identification in the event of adrenal crisis for early detection and treatment.
  • Patients to be educated on carrying and injecting glucocorticoid in case of an emergency.[9][5]

Don'ts

References

  1. Feingold KR, Anawalt B, Boyce A, Chrousos G, de Herder WW, Dungan K, Grossman A, Hershman JM, Hofland J, Kaltsas G, Koch C, Kopp P, Korbonits M, McLachlan R, Morley JE, New M, Purnell J, Singer F, Stratakis CA, Trence DL, Wilson DP, Nicolaides NC, Chrousos GP, Charmandari E. PMID 25905309. Missing or empty |title= (help)
  2. Huecker MR, Dominique E. PMID 28722862. Missing or empty |title= (help)
  3. https://www.ncbi.nlm.nih.gov/books/NBK499968/
  4. Feingold KR, Anawalt B, Boyce A, Chrousos G, de Herder WW, Dungan K; et al. (2000). "Endotext". PMID 25905309.
  5. 5.0 5.1 5.2 5.3 5.4 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.
  6. https://www.elsevier.es/index.php?p=revista&pRevista=pdf-simple&pii=S2173509314700698
  7. 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.
  8. https://www.elsevier.es/index.php?p=revista&pRevista=pdf-simple&pii=S2173509314700698
  9. https://www.elsevier.es/index.php?p=revista&pRevista=pdf-simple&pii=S2173509314700698
  10. https://www.elsevier.es/index.php?p=revista&pRevista=pdf-simple&pii=S2173509314700698

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