[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [Conditions](https://durgical.com/en/conditions/) › Adrenal insufficiency [Conditions](https://durgical.com/en/conditions/) · [Abdomen](https://durgical.com/en/anatomy/region/abdomen/) # Adrenal insufficiency Adrenal insufficiency means the body makes too little cortisol, from disease of the adrenal glands (Addison disease) or of the [pituitary gland](https://durgical.com/en/anatomy/pituitary-gland/). Updated 2026-10-29 ## Structures involved Tap one to see what it is and open it in 3D. - [Right adrenal gland](https://durgical.com/en/anatomy/suprarenal-gland-abdomen/) - [Left adrenal gland](https://durgical.com/en/anatomy/suprarenal-gland/) - [Adrenal arteries](https://durgical.com/en/anatomy/middle-suprarenal-artery/) - [Kidneys](https://durgical.com/en/anatomy/kidney/) - [Left renal vein](https://durgical.com/en/anatomy/right-renal-vein/) - [Inferior vena cava](https://durgical.com/en/anatomy/inferior-vena-cava/) ## In biochemistry - [Catecholamine synthesis and breakdown: Step 4 · Phenylethanolamine N-methyltransferase (PNMT)](https://durgical.com/en/biochemistry/pathways/catecholamine-synthesis-and-breakdown/#paso-4) - [Adrenal cortisol synthesis: Step 1 · Cholesterol side-chain cleavage enzyme (CYP11A1, P450scc), with StAR](https://durgical.com/en/biochemistry/pathways/adrenal-cortisol-synthesis/#paso-1) - [Steroid hormone synthesis (overview)](https://durgical.com/en/biochemistry/topics/steroid-hormone-synthesis/) - [Adrenal enzymes and congenital adrenal hyperplasia](https://durgical.com/en/biochemistry/topics/adrenal-enzymes-and-congenital-adrenal-hyperplasia/) - [21-Hydroxylase (CYP21A2)](https://durgical.com/en/biochemistry/enzymes/21-hydroxylase/) - [Cortisol](https://durgical.com/en/biochemistry/molecules/cortisol/) - [Aldosterone](https://durgical.com/en/biochemistry/molecules/aldosterone/) ## In immunology - [Immune tolerance and how autoimmunity begins](https://durgical.com/en/immunology/immune-tolerance-and-how-autoimmunity-begins/) ## In histology - [Adrenal cortex zones and medulla](https://durgical.com/en/histology/adrenal-cortex-zones-and-medulla/) ## In the clinical exam - [Cushing syndrome and adrenal insufficiency: the signs](https://durgical.com/en/clinical-exam/cushing-syndrome-and-adrenal-insufficiency-the-signs/) ## In physiology - [The hypothalamic–pituitary system: overview](https://durgical.com/en/physiology/the-hypothalamic-pituitary-system-overview/) - [The HPA axis and its circadian rhythm](https://durgical.com/en/physiology/the-hpa-axis-and-its-circadian-rhythm/) - [Actions of cortisol](https://durgical.com/en/physiology/actions-of-cortisol/) - [Aldosterone: actions and control](https://durgical.com/en/physiology/aldosterone-actions-and-control/) - [Measuring hormones: stimulation and suppression tests](https://durgical.com/en/physiology/measuring-hormones-stimulation-and-suppression-tests/) - [The adrenal cortex: zones, hormones and androgens](https://durgical.com/en/physiology/the-adrenal-cortex-zones-hormones-and-androgens/) - [The endocrine stress response](https://durgical.com/en/physiology/the-endocrine-stress-response/) - [The physiological response to hypoglycemia](https://durgical.com/en/physiology/the-physiological-response-to-hypoglycemia/) - [Distal tubule and collecting duct](https://durgical.com/en/physiology/distal-tubule-and-collecting-duct/) - [Potassium balance](https://durgical.com/en/physiology/potassium-balance/) - [Fluid shifts between compartments](https://durgical.com/en/physiology/fluid-shifts-between-compartments/) ## Why it happens - [Atrophy](https://durgical.com/en/general-pathology/atrophy/) ## What it is Inadequate production of cortisol, with or without aldosterone, from disease of the adrenal glands (primary, Addison disease) or from lack of ACTH from the pituitary or [hypothalamus](https://durgical.com/en/anatomy/hypothalamus/) (secondary or tertiary). ## Who gets it Primary adrenal insufficiency is rare. Overall, the commonest cause is suppression of the [axis](https://durgical.com/en/anatomy/axis/) by long-term glucocorticoids. Autoimmune adrenalitis predominates in high-income countries, while tuberculosis remains an important cause in Latin America and other regions where it is common; HIV-related infections also contribute. ## Causes - Primary (Addison disease): autoimmune adrenalitis, alone or in autoimmune polyglandular syndromes - Primary: infections (tuberculosis, fungal infections, HIV-related cytomegalovirus) and metastases - Primary: adrenal haemorrhage in sepsis or anticoagulation, including meningococcal sepsis (Waterhouse–Friderichsen syndrome) - Primary: congenital adrenal hyperplasia and drugs that block steroid synthesis - Secondary: pituitary tumours, surgery, radiotherapy, apoplexy or postpartum necrosis (Sheehan syndrome) - Tertiary: axis suppression by long-term exogenous glucocorticoids (the most common cause overall) ## Risk factors - Long-term glucocorticoid treatment, especially if stopped abruptly - Other autoimmune diseases (type 1 diabetes, autoimmune thyroid disease, vitiligo) - Tuberculosis or HIV infection - Anticoagulation and sepsis (adrenal haemorrhage) - Pituitary disease or surgery ## Pathophysiology Lack of cortisol impairs gluconeogenesis, vascular tone and the stress response. In primary disease aldosterone is also lost, causing salt wasting, hyponatraemia, hyperkalaemia and volume depletion, and high ACTH with related peptides causes hyperpigmentation. In secondary disease the renin–angiotensin system keeps aldosterone going, so hyperkalaemia and pigmentation are absent. ## Classification - Primary (Addison disease): adrenal failure; ACTH high, cortisol and aldosterone low - Secondary: pituitary ACTH deficiency - Tertiary: hypothalamic deficiency, mainly after glucocorticoid treatment - Chronic, or acute (adrenal crisis) ## Symptoms and signs - Fatigue, weakness and weight loss - Loss of appetite, nausea, vomiting and abdominal pain - Dizziness on standing and low blood pressure - Salt craving (primary) - Hyperpigmentation of [skin](https://durgical.com/en/anatomy/skin/), palmar creases, scars and gums (primary only) - Hypoglycaemia, especially in children - Muscle and joint aches ## Red flags - Adrenal crisis: shock or hypotension not responding to fluids, vomiting, abdominal pain, confusion - Severe hyponatraemia or hyperkalaemia - Hypoglycaemia - Known adrenal insufficiency or steroid use with intercurrent illness, vomiting or surgery - Fever with purpura and shock (meningococcal adrenal haemorrhage) ## Diagnosis **Clinical** Suspected from vague symptoms with hypotension, hyponatraemia, hyperkalaemia or pigmentation, or in any unexplained shock. In a suspected crisis, treatment is not delayed for tests: blood is drawn and hydrocortisone is given at once. **Tests** A low early-morning cortisol with a high ACTH suggests primary disease; the ACTH stimulation test (synthetic ACTH) confirms it when cortisol fails to rise. Renin and aldosterone, sodium, potassium and glucose; 21-hydroxylase antibodies for autoimmune disease. **Imaging** Adrenal CT in non-autoimmune primary disease (enlarged or calcified glands in tuberculosis, haemorrhage, metastases); pituitary MRI in secondary disease. ## Differential diagnosis - Septic or hypovolaemic shock from another cause - Gastroenteritis and other causes of vomiting and weight loss - Hypothyroidism - Depression or chronic fatigue - SIADH and other causes of hyponatraemia - Cancer or anorexia nervosa (weight loss) ## Goal of treatment Recognise and treat adrenal crisis at once, replace the missing hormones for life at physiological levels, and teach patients how crises are prevented during illness. ## Treatment **Acute** Adrenal crisis is an emergency: immediate parenteral hydrocortisone, rapid intravenous isotonic saline with glucose, and treatment of the trigger, without waiting for results. **Medical** Lifelong glucocorticoid replacement, with hydrocortisone as the classic agent, given in divided doses that mimic the daily cortisol rhythm. **Medical** Mineralocorticoid replacement with a synthetic mineralocorticoid in primary disease, adjusted by blood pressure, potassium and renin. **Lifestyle** Sick-day rules: patients learn to increase the glucocorticoid during fever or illness, carry an emergency card or bracelet, and have injectable hydrocortisone for vomiting. **Medical** Stress-dose glucocorticoids around surgery, labour and severe illness; treatment of the cause (e.g. tuberculosis). **Follow-up** Regular review of symptoms, weight, blood pressure and electrolytes, and screening for associated autoimmune diseases. ## Drugs for this condition - [Hydrocortisone](https://durgical.com/en/pharmacology/hydrocortisone/) - [Fludrocortisone](https://durgical.com/en/pharmacology/fludrocortisone/) ## Complications - Adrenal crisis and death - Hypoglycaemia - Over-replacement: weight gain, osteoporosis, diabetes - Fatigue and reduced quality of life despite treatment - Associated autoimmune disorders ## Prognosis With lifelong replacement and education most patients lead normal lives, but adrenal crises still occur and cause excess mortality, especially when the condition is unrecognised. ## Prevention - Gradual tapering of long-term glucocorticoids - Stress dosing and sick-day education - Medical alert identification ## Test yourself Think of the answer, then tap the question to see it. ## Which examination finding separates primary from secondary adrenal insufficiency? Hyperpigmentation, caused by high ACTH, occurs only in primary disease. ## Why is hyperkalaemia absent in secondary adrenal insufficiency? Aldosterone is controlled by the renin–angiotensin system, which is intact. ## What is the first step in a suspected adrenal crisis? Draw blood, then give parenteral hydrocortisone and intravenous saline at once, without waiting for results. ## Which test confirms adrenal insufficiency? The ACTH stimulation test: cortisol fails to rise adequately after synthetic ACTH. ## Which infection is an important cause of Addison disease in Latin America? Tuberculosis of the adrenal glands. [Add to my cards (5)](https://durgical.app/estudiar/?add=/en/conditions/adrenal-insufficiency/) ## Related conditions - [Cushing syndrome](https://durgical.com/en/conditions/cushing-syndrome/) - [Tuberculosis](https://durgical.com/en/conditions/tuberculosis/) - [HIV infection and AIDS](https://durgical.com/en/conditions/hiv-infection-and-aids/) - [Sepsis and septic shock](https://durgical.com/en/conditions/sepsis-and-septic-shock/) - [Hypothyroidism](https://durgical.com/en/conditions/hypothyroidism/) - [Type 1 diabetes mellitus](https://durgical.com/en/conditions/type-1-diabetes-mellitus/) Educational information, not medical advice. For any symptom, see a health professional. Sources: [Adrenal Insufficiency](https://www.ncbi.nlm.nih.gov/books/NBK441832/) (StatPearls (NCBI Bookshelf), 2023). [← All conditions](https://durgical.com/en/conditions/) ## **Spotted a mistake?** We are always improving for the community. Tell us what is wrong and our team will review it. 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