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Endocrinology

Addison Disease (Primary Adrenal Insufficiency)

Autoimmune (most common) or infectious destruction of the adrenal cortex causes cortisol, aldosterone and androgen deficiency. Presents with fatigue, hyperpigmentation, hyponatraemia and hyperkalaemia.

Last reviewed 19 May 2026 - MedicoMedics editorial team

Adrenal cortex destruction leading to cortisol and aldosterone deficiency

Pathophysiology

Autoimmune adrenalitis (80%, often part of polyglandular autoimmune syndrome) destroys the adrenal cortex; other causes include TB, disseminated fungal infection, HIV, metastases, adrenal haemorrhage (Waterhouse-Friderichsen) and congenital adrenal hyperplasia. Loss of cortisol removes negative feedback on ACTH; ACTH surges cause hyperpigmentation via MSH activity on melanocytes. Aldosterone loss causes sodium wasting and potassium retention.

Sources: Endocrine Society Primary Adrenal Insufficiency CPG (J Clin Endocrinol Metab 2016;101:364); NEJM 2019;381:852 - Adrenal Insufficiency

Clinical presentation

Insidious fatigue, weight loss, anorexia, myalgia, nausea, salt craving, postural hypotension, hyperpigmentation (buccal mucosa, palmar creases, scars). Women: loss of axillary/pubic hair. Adrenal crisis: hypotension, shock, hyponatraemia, hyperkalaemia, hypoglycaemia and fever precipitated by illness, surgery or missed steroid dose.

Sources: Endocrine Society Primary Adrenal Insufficiency CPG (J Clin Endocrinol Metab 2016;101:364); NEJM 2019;381:852 - Adrenal Insufficiency

Diagnosis

Morning cortisol <3 µg/dL with elevated ACTH is diagnostic; 8 AM cortisol >18 µg/dL virtually excludes primary AI. Definitive: 250 µg cosyntropin (ACTH) stimulation test - cortisol <18 µg/dL 30-60 min post-injection confirms adrenal insufficiency. High renin and low aldosterone confirm mineralocorticoid deficiency. Autoimmune: 21-hydroxylase antibodies. Investigate cause with adrenal imaging and infection screen when appropriate.

Sources: Endocrine Society Primary Adrenal Insufficiency CPG (J Clin Endocrinol Metab 2016;101:364); NEJM 2019;381:852 - Adrenal Insufficiency

Treatment

Hydrocortisone 15-25 mg/day in divided doses (mimics diurnal rhythm) plus fludrocortisone 0.05-0.2 mg/day. Educate on stress dosing: double or triple oral dose during minor illness; IM hydrocortisone at home for vomiting; parenteral hydrocortisone 100 mg for major stress/surgery. Provide medical alert identification.

Sources: Endocrine Society Primary Adrenal Insufficiency CPG (J Clin Endocrinol Metab 2016;101:364); NEJM 2019;381:852 - Adrenal Insufficiency

Adrenal crisis

IV hydrocortisone 100 mg bolus then 200 mg/24 h continuous or 50 mg q6h, aggressive IV normal saline and dextrose, treat precipitant, correct electrolytes. Do NOT wait for confirmatory testing; take cortisol and ACTH samples and treat empirically.

Sources: Endocrine Society Primary Adrenal Insufficiency CPG (J Clin Endocrinol Metab 2016;101:364); NEJM 2019;381:852 - Adrenal Insufficiency

Sample USMLE-style MCQs

Try 5 questions on this topic. Practice hundreds more free with a trial.

Question 1

Which electrolyte pattern is classic in Addison disease?

Question 2

Which test confirms primary adrenal insufficiency?

Question 3

A patient in adrenal crisis with hypotension should first receive?

Question 4

Which is the most common cause of Addison disease in the developed world?

Question 5

Why is fludrocortisone unnecessary in secondary adrenal insufficiency?

References

Primary guidelines and peer-reviewed sources used for this entry. Reviewed 19 May 2026 by MedicoMedics editorial team.

Frequently asked

Why does Addison disease cause hyperpigmentation but secondary insufficiency does not?

Primary AI has very high ACTH (and its precursor POMC), which stimulates melanocyte MSH receptors. In secondary AI ACTH is low.

How much hydrocortisone should a patient take during vomiting illness?

If unable to keep oral doses down, administer IM hydrocortisone 100 mg and seek urgent care.

Do secondary adrenal insufficiency patients need mineralocorticoid?

No. Aldosterone production is intact because the renin-angiotensin system is preserved; only glucocorticoid replacement is required.

Which autoimmune syndrome is Addison often part of?

Autoimmune polyglandular syndrome type 2 (Addison + type 1 diabetes ± autoimmune thyroid disease); type 1 includes hypoparathyroidism and mucocutaneous candidiasis.

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