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Addison’s disease

Adrenal insufficiency is the clinical manifestation of deficient production or action of glucocorticoids , with or without deficiency also in mineralocorticoids and adrenal androgens
Primary adrenal insufficiency is called Addison’s disease


A rare disease AAFP quotes estimated prevalance at 1 in 20,000 persons in the US and Western Europe Wass J et al ( 2013 ) have reported that AD affects 1 in 10,000 in the UK and throughout Europe In children – boys are affected predominantly 
 ( about 75 % of cases ) In adults majority who suffer with AD are women Presentation can be at any age


Primary – due to disease which is intrinsic to adrenal gland


Secondary-from pituitary disease that hampers the release of corticotrophin from a lack of responsiveness of the adrenal glands to the hormone.

Secondary adrenal insufficiency is more common than AD


Tertiary – impaired synthesis or action of corticotrophin releasing hormone , arginine vasopressin or both from the hypothalamus which in turn inhibits secretion of corticotrophin ( ACTH ) from ant pituitary.


Most common cause of secondary adrenal insufficiency is exogenous steroid administration which induces atrophy pituitary corticotroph cells



Developed world- Autoimmune destruction of adrenal 
cortex in about 70 % of cases Other papers quote an even higher number ie 80-90 % of cases due to autoimmune adrenalitis Autoimmune adrenalitis can be a part of an autoimmune polyendocrinopathy syndrome or happen in isolated form


Infectious disease – In low and middle income countries Tuberculosis ( common cause during the 1st half of the 20th century ) and still remains the most common cause worldwide Fungal infections as histoplasmosis , cryptococcosis Disseminated gonococcal infection Opportunistic infections as AIDS- CMV , mycobacterium intracellulare , Cryptococcus


Others -These are rare and can include
 malignancy for e.g adrenal metastases infiltration ( for e.g amyloid ) B/L adrenal haemorrhagia in patients with antiphospholipid syndrome ( infarction ) vascular haemorrhage Congenital adrenal hyperplasia iatrogenic for e.g adrenalectomy or drug related Pituitary apoplexy / Sheehan’s syndrome.


Chronic presentation- Presentation can be insidious and gradual ( progress slowly over yrs or months ) with non-specific symptoms which are often missed- a delayed diagnosis is common Often the diagnosis would be established following an acute addisonian crisis which is precipitated by an episode such as infection , trauma , surgery , vomiting and diarrhoea Symptoms ( fatigue , anorexia , weight loss , lethargy and orthostatic hypotension ) often overlap with other conditions A high index of suspicion is necessary as a presentation with addisonian crisis can be fatal The presentation will be based on the degree of deficiency of cortisol , mineralocorticoid and adrenal androgens Hyperpigmentation of skin and mucous membranes is characteristic of AD but this can be absent in about 10 % of cases A high index of suspicion is also warranted as the disease may present atypically.


Non-specific symptoms – fatigue ( always tired ) anorexia weight loss myalgia arthralgia dizziness nausea , vomiting , diarrhoea orthostatic hypotension , dizziness fever hyperpigmentation of the skin creases and buccal mucosa arthralgia , myalgia ↓ axillary and pubic hairs salt craving ( primary adrenal insufficiency only )


Other situations when to suspect include
 delayed puberty in children a diagnosis of hypothyroidism and treatment with thyroxine worsens patient condition patients with pre-existing type 1 diabetes who experience a deterioration of glycemic control with recurrent hypoglycemia psychiatric symptoms as memory impairment , confusion , apathy , depression and psychosis.


Adrenal crisis – Adrenal crisis is a medical emergency with high mortality rates Gastrointestinal illness is consistently the largest precipitating factor for adrenal crisis , other precipitating factors include
◘ infections
◘ trauma
◘ pregnancy
◘ surgery
◘ extreme emotional stress
◘ strenuous physical activity
◘ thyrotoxicosis
◘ medications ( anti-adrenal medications )
◘ hot weather
◘ dehydration
◘ alcohol intoxication
◘ severe migraines
◘ seizures Adrenal crisis is the most important acute complication of adrenal insufficiency of any cause Review the list of medications – abrupt cessation of steroids in long term users In children -weight loss , failure to thrive , hypoglycemic crisis with seizures


shock altered consciousness fever – unexplained circulatory collapse often non responsive to measures as inotropic support hypoglycaemia hyponatraemia hyperkalaemia abdominal tenderness or guarding seizures a previous h/o abrupt stoppage of steroid use / withdrawal


Tests are carried to establish the following facts
 confirm inappropriately low cortisol production if the problem is primary or central uncover the underlying pathological process


Hyponatremia Hyperkalemia Elevated ACTH for the level of 9 AM cortisol Increased plasma renin activity Reduced thyroid hormone levels and elevated TSH Anti-adrenal antibodies


Short Synacthen test – – basal cortisol is measures and 350 mcg of ACTH is injected. Healthy response shows an increase in serum cortisol to peak conc of > 500 nmol /L.


Exogenous hormone administration does not evoke any increase in serum cortisol as the adrenal cortex is already maximally stimulated by endogenous ACTS


The level at which random cortisol excludes a possibility of AD ranges from 400 to 500 nmol / L . It should also be noted that in pregnancy , or with OCP , HRT use the interpretation of cortisol is difficult due to elevation of background CBG and delayed hepatic clearance


Self help group on Addison’s

National organization of rare disorders

NHS inform

A good overview for clinicians and patients who want to read more from Pituitary org

Patient alert for emergency treatment Addisons disease ( US )–medical-information.html



  1. Muhammed HNampoothiri RVGaspar BL, et al
    Infectious causes of Addison’s disease: 1 organ—2 organisms!
  2. Adrenal insufficiencyEvangelia Charmandari, Nicolas C Nicolaides, George P Chrousos Seminar
  3. Addison disease Diagnosis and initial management Susan O’Connell
    Aris Siafarikas
  4. Munir S, Waseem M. Addison Disease. [Updated 2020 Jul 5]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan-. Available from:
  5. Adrenal Crisis: Still a Deadly Event in the 21st Century Troy H.K. Puar, MBBS, MRCP (UK),a,bNike M.M.L. Stikkelbroeck, MD, PhD,aLisanne C.C.J. Smans, MD, PhD,cPierre M.J. Zelissen, MD, PhD,cAd. R.M.M. Hermus, MD, PhD The American Journal of Medicine, Vol 129, No 3, March 2016
  6. Burton, Claire et al. “Addison’s disease: identification and management in primary care.” The British journal of general practice : the journal of the Royal College of General Practitioners vol. 65,638 (2015): 488-90. doi:10.3399/bjgp15X686713
  7. CKS NHS Addison’s disease
  8. Addison’s Disease: A Rare Case Report Sanil Parekh1 , Prashant Melmane2 , Archana Bhate3, Amir Khan1 , Ashish Sarode1 International Journal of Scientific Study | May 2016 | Vol 4 | Issue 2 DOI: 10.17354/ijss/2016/299
  9. Dineen, Rosemary et al. “Adrenal crisis: prevention and management in adult patients.” Therapeutic advances in endocrinology and metabolism vol. 10 2042018819848218. 13 Jun. 2019, doi:10.1177/2042018819848218
  10. Dineen, Rosemary et al. “Adrenal crisis: prevention and management in adult patients.” Therapeutic advances in endocrinology and metabolism vol. 10 2042018819848218. 13 Jun. 2019, doi:10.1177/2042018819848218
  11. Elshimy G, Alghoula F, Jeong JM. Adrenal Crisis. [Updated 2020 Jun 24]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan-. Available from:
  12. Addison’s disease BMJ 2009;339:b2385
  13. Diagnosing Addison’s: A guide for GPs Disease self help group founded by Deana Kenward


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