Diagnosis

Adrenal insufficiency

  • Primary: Destruction of adrenal cortex

  • Secondary: Failure due to hypothalamic or pituitary abnormalities

  • Addisonian Crisis: Acute situation due to some extrinsic stressor such as infection, surgery or sudden cessation of long-term glucocorticoid therapy

Also known as: Addison's disease, Autoimmune adrenalitis, Primary adrenal insufficiency

Etiology

Primary adrenal insufficiency [moh]

  1. Infections leading to adrenalitis: Tuberculosis, HIV, CMV, Cryptococcosis, Histoplasmosis, Coccidiomycosis, Candidiasis, African trypanomiasis, Treponema pallidum

  2. Bilateral adrenal hemorrhage: Septic shock (Waterhouse-Friderichsen syndrome), Anticoagulants, Trauma

  3. Adrenal infarction: Primary antiphospholipid syndrome, Anti-cardiolipin syndrome, Lupus anti-coagulant syndrome

  4. Adrenal infiltration: Autoimmune (Addison’s Disease), Adrenal metastases, Primary adrenal lymphoma, Sarcoidosis, Amyloidosis, Hemochromatosis

  5. Bilateral adrenalectomy: Cushing's disease, ectopic ACTH, renal cancer, pheochromocytoma

  6. Drug-induced adrenal insufficiency: side-effect due to steroid synthesis inhibition, GC antagonist or increased cortisol metabolism

    • Mifepristone, Abiraterone acetate, Trilostane, Etomidate, Ketaconazole/fluconazole, Suramin, Aminoglutethiamide, Phenytoin, Phenobarbital, Rifampicin,  CTLA-4 inhibitors

Secondary adrenal insufficiency

  1. Iatrogenic: Exogenous steroid treatment (adrenal suppression), hypersecretion due to Cushing's syndrome, Following TSS surgery for ACTH producing adenoma, Pituitary irradiation and radiotherapy for brain tumors and craniospinal irradiation for other tumors

  2. Tumors: Pituitary adenoma (rarely carcinoma), Craniopharyngioma, meningioma, ependymoma, intra/suprasellar metastasis

  3. Infiltration/deposition: Tuberculosis, actinomycosis, sarcoidosis, histiocytosis X, Wegener’s granulomatosis, Hemochromatosis

  4. Autoimmune: Autoimmune hypophysitis (pregnancy)

  5. Infarction/hemorrahage: Pituitary apoplexy/necrosis, Postpartum pituitary infarction (Sheehan's syndrome)

  6. Trauma: Pituitary stalk lesions, Traumatic brain injury

  7. Genetic causes: Familial Glucocorticoid deficiency, Cholesteryl ester storage disease, Smih-Lemi Opitz disease, Kearns–Sayre syndrome, Refsum disease, Congenital adrenal hypoplasia, IMAGe syndrome, MIRAGE syndrome, Combined pituitary hormone deficiency.

Pathophysiology [sau]

  1. Destruction of the bilateral adrenal cortex

  2. Decreased adrenocortical hormones (cortisol, aldosterone, and androgens)

Epidemiology

Incidence per 100.000 [uak][fkw][ygg][sau]

Epidemiology chart for Incidence

Prevalence per 100.000 [uak][fkw][ygg][sau]

Epidemiology chart for Prevalence

Symptoms & findings

Symptoms

Amenorrhea, Arthralgia, Confusion, Dizziness, Fatigue, Fever, Hyperpigmentation, Hypotension, Lethargy, Myalgia, Nausea, Tachycardia, Vomiting, Weakness, Weight loss

Clinical findings

Decreased Cortisol, Hyperkalemia, Hyponatremia, Shock

Anamneses

None listed.

Localized findings

Pain
Radiates
Abdomen
Onset
Subacute (hours)Gradual (days)
Pattern
Constant
Severity
Mild (1-3)Moderate (4-7)Severe (8-10)

Approach

Treatment

  1. Acute adrenal crisis: [sau]

    • NaCl i.v. to restore volume deficit and correct hypotension

    • Dextrose: to correct hypoglycemia

    • Correction of the hormone deficiency: both glucocorticoid and mineralocorticoid

      • Hydrocortisone 100 mg intravenous (IV) bolus

      • Followed by 50 to 100 mg IV every 6 hours over 24 hours

  2. Maintenance Phase Therapy:

    • Glucocorticoid

      • Hydrocortisone 5 to 25 mg/day divided into 2 or 3 doses

      • Prednisone 3 to 5 mg/day

    • Mineralocorticoid

      • Fludrocortisone 0.05 to 0.2 mg daily

      • Hydrocortisone (in children) 8 mg/m2/day orally initially, divided into 3 or 4 doses

Differential diagnoses

Fibromyalgia, Histoplasmosis, Hyperkalemia, Hypothyroidism, Hypovolemia, Mononucleosis, Sarcoidosis, Sepsis, Shock, Syndrome of inappropriate antidiuretic hormone secretion, Tuberculosis

References

[1] Hasenmajer V, Ferrigno R, Minnetti M, Pellegrini B, Isidori AM, Lenzi A, Salerno M, Cappa M, Chan L, De Martino MC, Savage MO. Rare forms of genetic paediatric adrenal insufficiency: Excluding congenital adrenal hyperplasia. Rev Endocr Metab Disord. 2023 Apr;24(2):345-363.

[2] Munir et al. Addison Disease. 2024 Jan 30. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan–. PMID: 28723023.

[3] Løvås K, Husebye ES. High prevalence and increasing incidence of Addison's disease in western Norway. Clin Endocrinol (Oxf). 2002 Jun;56(6):787-91.

[4] https://emedicine.medscape.com/article/116467-overview?form=fpf#a6

[5] https://emedicine.medscape.com/article/1096911-overview?form=fpf#a6

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