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Adrenal insufficiency

adrenal insufficiency, adrenal insufficiency symptoms
Adrenal insufficiency is a condition in which the adrenal glands do not produce adequate amounts of steroid hormones, primarily cortisol; but may also include impaired production of aldosterone a mineralocorticoid, which regulates sodium conservation, potassium secretion, and water retention Craving for salt or salty foods due to the urinary losses of sodium is common

Addison's disease and congenital adrenal hyperplasia can manifest as adrenal insufficiency If not treated, adrenal insufficiency may result in severe abdominal pains, vomiting, profound muscle weakness and fatigue, depression, extremely low blood pressure hypotension, weight loss, kidney failure, changes in mood and personality, and shock adrenal crisis An adrenal crisis often occurs if the body is subjected to stress, such as an accident, injury, surgery, or severe infection; death may quickly follow

Adrenal insufficiency can also occur when the hypothalamus or the pituitary gland does not make adequate amounts of the hormones that assist in regulating adrenal function This is called secondary or tertiary adrenal insufficiency and is caused by lack of production of ACTH in the pituitary or lack of CRH in the hypothalamus, respectively


  • 1 Types
  • 2 Signs and symptoms
  • 3 Causes
    • 31 Corticosteroid withdrawal
    • 32 Adrenal dysgenesis
    • 33 Impaired steroidogenesis
    • 34 Adrenal destruction
  • 4 Pathophysiology
  • 5 Diagnosis
    • 51 Effects
  • 6 Treatment
  • 7 See also
  • 8 References
  • 9 External links


There are three major types of adrenal insufficiency

  • Primary adrenal insufficiency is due to impairment of the adrenal glands
    • 80% are due to an autoimmune disease called Addison's disease or autoimmune adrenalitis
    • One subtype is called idiopathic, meaning of unknown cause
    • Other cases are due to congenital adrenal hyperplasia or an adenoma tumor of the adrenal gland
  • Secondary adrenal insufficiency is caused by impairment of the pituitary gland or hypothalamus Its principal causes include pituitary adenoma which can suppress production of adrenocorticotropic hormone ACTH and lead to adrenal deficiency unless the endogenous hormones are replaced; and Sheehan's syndrome, which is associated with impairment of only the pituitary gland
  • Tertiary adrenal insufficiency is due to hypothalamic disease and a decrease in the release of corticotropin releasing hormone CRH Causes can include brain tumors and sudden withdrawal from long-term exogenous steroid use which is the most common cause overall

Signs and symptoms

Signs and symptoms include: hypoglycemia, dehydration, weight loss, and disorientation Additional signs and symptoms include weakness, tiredness, dizziness, low blood pressure that falls further when standing orthostatic hypotension, cardiovascular collapse, muscle aches, nausea, vomiting, and diarrhea These problems may develop gradually and insidiously Addison's disease can present with tanning of the skin that may be patchy or even all over the body Characteristic sites of tanning are skin creases eg of the hands and the inside of the cheek buccal mucosa Goitre and vitiligo may also be present Eosinophilia may also occur


Causes of acute adrenal insufficiency are mainly sudden withdrawal of long-term corticosteroid therapy, Waterhouse-Friderichsen syndrome, and stress in people with underlying chronic adrenal insufficiency The latter is termed critical illness–related corticosteroid insufficiency

For chronic adrenal insufficiency, the major contributors are autoimmune adrenalitis Addison's Disease, tuberculosis, AIDS, and metastatic disease Minor causes of chronic adrenal insufficiency are systemic amyloidosis, fungal infections, hemochromatosis, and sarcoidosis

Autoimmune adrenalitis may be part of Type 2 autoimmune polyglandular syndrome, which can include type 1 diabetes, hyperthyroidism, and autoimmune thyroid disease also known as autoimmune thyroiditis, Hashimoto's thyroiditis, and Hashimoto's disease Hypogonadism may also present with this syndrome Other diseases that are more common in people with autoimmune adrenalitis include premature ovarian failure, celiac disease, and autoimmune gastritis with pernicious anemia

Adrenoleukodystrophy can also cause adrenal insufficiency

Adrenal insufficiency can also result when a patient has a craniopharyngioma, which is a histologically benign tumor that can damage the pituitary gland and so cause the adrenal glands not to function This would be an example of secondary adrenal insufficiency syndrome

Causes of adrenal insufficiency can be categorized by the mechanism through which they cause the adrenal glands to produce insufficient cortisol These are adrenal dysgenesis the gland has not formed adequately during development, impaired steroidogenesis the gland is present but is biochemically unable to produce cortisol or adrenal destruction disease processes leading to glandular damage

Corticosteroid withdrawal

Use of high-dose steroids for more than a week begins to produce suppression of the person's adrenal glands because the exogenous glucocorticoids suppress hypothalamic corticotropin-releasing hormone CRH and pituitary adrenocorticotropic hormone ACTH With prolonged suppression, the adrenal glands atrophy physically shrink, and can take months to recover full function after discontinuation of the exogenous glucocorticoid During this recovery time, the person is vulnerable to adrenal insufficiency during times of stress, such as illness, due to both adrenal atrophy and suppression of CRH and ACTH release Use of steroids joint injections may also result in adrenal suppression after discontinuation

Adrenal dysgenesis

All causes in this category are genetic, and generally very rare These include mutations to the SF1 transcription factor, congenital adrenal hypoplasia due to DAX-1 gene mutations and mutations to the ACTH receptor gene or related genes, such as in the Triple A or Allgrove syndrome DAX-1 mutations may cluster in a syndrome with glycerol kinase deficiency with a number of other symptoms when DAX-1 is deleted together with a number of other genes

Impaired steroidogenesis

To form cortisol, the adrenal gland requires cholesterol, which is then converted biochemically into steroid hormones Interruptions in the delivery of cholesterol include Smith-Lemli-Opitz syndrome and abetalipoproteinemia

Of the synthesis problems, congenital adrenal hyperplasia is the most common in various forms: 21-hydroxylase, 17α-hydroxylase, 11β-hydroxylase and 3β-hydroxysteroid dehydrogenase, lipoid CAH due to deficiency of StAR and mitochondrial DNA mutations Some medications interfere with steroid synthesis enzymes eg ketoconazole, while others accelerate the normal breakdown of hormones by the liver eg rifampicin, phenytoin

Adrenal destruction

Autoimmune adrenalitis is the most common cause of Addison's disease in the industrialised world Autoimmune destruction of the adrenal cortex is caused by an immune reaction against the enzyme 21-hydroxylase a phenomenon first described in 1992 This may be isolated or in the context of autoimmune polyendocrine syndrome APS type 1 or 2, in which other hormone-producing organs, such as the thyroid and pancreas, may also be affected

Adrenal destruction is also a feature of adrenoleukodystrophy ALD, and when the adrenal glands are involved in metastasis seeding of cancer cells from elsewhere in the body, especially lung, hemorrhage eg in Waterhouse-Friderichsen syndrome or antiphospholipid syndrome, particular infections tuberculosis, histoplasmosis, coccidioidomycosis, or the deposition of abnormal protein in amyloidosis


Hyponatremia can be caused by glucocorticoid deficiency Low levels of glucocorticoids leads to systemic hypotension one of the effects of cortisol is to increase peripheral resistance, which results in a decrease in stretch of the arterial baroreceptors of the carotid sinus and the aortic arch This removes the tonic vagal and glossopharyngeal inhibition on the central release of ADH: high levels of ADH will ensue, which will subsequently lead to increase in water retention and hyponatremia

Differently from mineralocorticoid deficiency, glucocorticoid deficiency does not cause a negative sodium balance in fact a positive sodium balance may occur


The best diagnostic tool to confirm adrenal insufficiency is the ACTH stimulation test; however, if a patient is suspected to be suffering from an acute adrenal crisis, immediate treatment with IV corticosteroids is imperative and should not be delayed for any testing, as the patient's health can deteriorate rapidly and result in death without replacing the corticosteroids

Dexamethasone should be used as the corticosteroid if the plan is to do the ACTH stimulation test at a later time as it is the only corticosteroid that will not affect the test results

If not performed during crisis, then labs to be run should include: random cortisol, serum ACTH, aldosterone, renin, potassium and sodium A CT of the adrenal glands can be used to check for structural abnormalities of the adrenal glands An MRI of the pituitary can be used to check for structural abnormalities of the pituitary However, in order to check the functionality of the Hypothalamic Pituitary Adrenal HPA Axis the entire axis must be tested by way of ACTH stimulation test, CRH stimulation test and perhaps an Insulin Tolerance Test ITT In order to check for Addison’s Disease, the auto-immune type of primary adrenal insufficiency, labs should be drawn to check 21-hydroxylase autoantibodies


Type Hypothalamus
Adrenal glands
Underlying causes Abrupt steroid withdrawal, Tumor of the hypothalamus adenoma, antibodies, environment ie toxins, head injury Tumor of the pituitary adenoma, antibodies, environment, head injury, surgical removal6, Sheehan's syndrome Tumor of the adrenal adenoma, stress, antibodies, environment, Addison's disease, trauma, surgical removal resection, miliary tuberculosis of the adrenal
CRH low high2 high
ACTH low low high
DHEA low low high
DHEA-S low low high
Cortisol low3 low3 low4
Aldosterone low normal low
Renin low low high
Sodium Na low low low
Potassium K low normal high
1 Automatically includes diagnosis of secondary hypopituitarism
2 Only if CRH production in the hypothalamus is intact
3 Value doubles or more in stimulation
4 Value less than doubles in stimulation
5 Most common, does not include all possible causes
6 Usually because of very large tumor macroadenoma
7 Includes Addison's disease


  • Adrenal crisis
    • Intravenous fluids
    • Intravenous steroid Solu-Cortef/injectable hydrocortisone later hydrocortisone, prednisone or methylpredisolone tablets
    • Rest
    Cortisol deficiency primary and secondary
    • Hydrocortisone Cortef
    • Prednisone Deltasone
    • Prednisolone Delta-Cortef
    • Methylprednisolone Medrol
    • Dexamethasone Decadron
    Mineralocorticoid deficiency low aldosterone
    • Fludrocortisone acetate

To balance sodium, potassium and increase water retention

See also

  • Addison's disease – primary adrenocortical insufficiency
  • Cushing's syndrome – overproduction of cortisol
  • Insulin tolerance test – another test used to identify sub-types of adrenal insufficiency
  • Adrenal fatigue hypoadrenia – a term used in alternative medicine to describe a believed exhaustion of the adrenal glands


  1. ^ a b Eileen K Corrigan 2007 "Adrenal Insufficiency Secondary Addison's or Addison's Disease" NIH Publication No 90-3054 
  2. ^ Adrenal Insufficiency at the US National Library of Medicine Medical Subject Headings MeSH
  3. ^ Ten S, New M, Maclaren N 2001 "Clinical review 130: Addison's disease 2001" J Clin Endocrinol Metab 86 7: 2909–22 doi:101210/jc8672909 PMID 11443143 
  4. ^ a b c d e f Ashley B Grossman, MD 2007 "Addison's Disease" Adrenal Gland Disorders 
  5. ^ Brender E, Lynm C, Glass RM 2005 "JAMA patient page Adrenal insufficiency" JAMA 294 19: 2528 doi:101001/jama294192528 PMID 16287965 
  6. ^ "Dorlands Medical Dictionary:adrenal insufficiency" 
  7. ^ "Secondary Adrenal Insufficiency: Adrenal Disorders: Merck Manual Professional" 
  8. ^ "hypopituitary" WebMD 2006 
  9. ^ http://wwwendotextorg/adrenal/adrenal13/adrenal13htm
  10. ^ "Causes of secondary and tertiary adrenal insufficiency in adults" Retrieved 10 November 2016 
  11. ^ Montgomery ND, Dunphy CH, Mooberry M, Laramore A, Foster MC, Park SI, Fedoriw YD 2013 "Diagnostic complexities of eosinophilia" Archives of Pathology & Laboratory Medicine 137 2: 259–69 doi:105858/arpa2011-0597-RA PMID 23368869 
  12. ^ a b c Table 20-7 in: Mitchell, Richard Sheppard; Kumar, Vinay; Abbas, Abul K; Fausto, Nelson Robbins Basic Pathology Philadelphia: Saunders ISBN 1-4160-2973-7  8th edition
  13. ^ Thomas A Wilson, MD 2007 "Adrenal Insufficiency" Adrenal Gland Disorders 
  14. ^ Bornstein SR, Allolio B, Arlt W, Barthel A, Don-Wauchope A, Hammer GD, et al 2016 "Diagnosis and Treatment of Primary Adrenal Insufficiency: An Endocrine Society Clinical Practice Guideline" J Clin Endocrinol Metab Practice Guideline Review 101 2: 364–89 doi:101210/jc2015-1710 PMC 4880116  PMID 26760044 
  15. ^ Thomas A Wilson, MD 1999 "Adrenoleukodystrophy" 
  16. ^ a b c d Ten S, New M, Maclaren N 2001 "Clinical review 130: Addison's disease 2001" The Journal of Clinical Endocrinology and Metabolism 86 7: 2909–2922 doi:101210/jc8672909 PMID 11443143 CS1 maint: Uses authors parameter link
  17. ^ Kaminstein, David S William C Shiel Jr, ed "Steroid Drug Withdrawal" MedicineNet Retrieved 10 April 2013 
  18. ^ Dernis, E; Ruyssen-Witrand, A; Mouterde, G; Maillefert, JF; Tebib, J; Cantagrel, A; Claudepierre, P; Fautrel, B; Gaudin, P; Pham, T; Schaeverbeke, T; Wendling, D; Saraux, A; Loët, XL October 2010 "Use of glucocorticoids in rheumatoid arthritis - pratical modalities of glucocorticoid therapy: recommendations for clinical practice based on data from the literature and expert opinion" Joint, bone, spine : revue du rhumatisme 77 5: 451–7 doi:101016/jjbspin200912010 PMID 20471886 
  19. ^ Stitik, Todd P 2010 Injection Procedures: Osteoarthritis and Related Conditions Springer Science & Business Media p 47 ISBN 9780387765952 
  20. ^ Winqvist O, Karlsson FA, Kämpe O June 1992 "21-Hydroxylase, a major autoantigen in idiopathic Addison's disease" The Lancet 339 8809: 1559–62 doi:101016/0140-67369291829-W PMID 1351548 CS1 maint: Uses authors parameter link
  21. ^ Husebye ES, Perheentupa J, Rautemaa R, Kämpe O May 2009 "Clinical manifestations and management of patients with autoimmune polyendocrine syndrome type I" Journal of Internal Medicine 265 5: 514–29 doi:101111/j1365-2796200902090x PMID 19382991 CS1 maint: Uses authors parameter link
  22. ^ Kennedy, Ron "Addison's Disease" The Doctors' Medical Library 
  23. ^ Schrier, R W 2006 "Body Water Homeostasis: Clinical Disorders of Urinary Dilution and Concentration" Journal of the American Society of Nephrology 17 7: 1820–32 doi:101681/ASN2006030240 PMID 16738014 
  24. ^ Addison Disease~workup at eMedicine

External links

Classification V · T · D
  • ICD-10: E271-E274
  • ICD-9-CM: 2554
  • MeSH: D000309
External resources
  • eMedicine: emerg/16

  • CAH - Congenital adrenal hyperplasia
  • Bornstein, SR; Allolio, B; Arlt, W; Barthel, A; Don-Wauchope, A; Hammer, GD; Husebye, ES; Merke, DP; Murad, MH; Stratakis, CA; Torpy, DJ February 2016 "Diagnosis and Treatment of Primary Adrenal Insufficiency: An Endocrine Society Clinical Practice Guideline" The Journal of Clinical Endocrinology and Metabolism 101 2: 364–89 doi:101210/jc2015-1710 PMC 4880116  PMID 26760044 

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