Adrenal insufficiency (AI) is the insufficient secretions of corticosteroids that may cause partial or complete destruction of the adrenal glands.
Primary AI or Addison’s disease is due to the inability of the adrenal gland to produce steroid hormones even when the stimulus by the pituitary gland via corticotrophin is adequate or increased.
Secondary AI is due to disorders of the pituitary gland that causes production of low levels of adrenocorticotropic hormone that will result to reduced cortisol levels.
Tertiary AI is the inability of the hypothalamus to produce sufficient amount of corticotropin releasing hormone.
Signs and symptoms are usually nonspecific with insidious onset.
Common signs and symptoms are fatigue, weakness, salt craving, orthostatic hypotension, nausea, vomiting, abdominal pain, diarrhea, anorexia and weight loss.

Adrenal%20insufficiency Signs and Symptoms


  • Adrenal insufficiency (AI) is the inability of the adrenal gland to produce sufficient adrenocortical steroid hormones


  • Rapid withdrawal of steroids in patients with adrenal atrophy due to chronic steroid therapy
    • Most common cause of acute adrenal insufficiency (AI)
  • Rapid intensification of chronic primary adrenal insufficiency caused by sepsis or acute major stress
  • May occur in patients receiving glucocorticoids if mineralocorticoid requirements are not met
  • Rare in patients with secondary or tertiary adrenal insufficiency
  • Destruction of both adrenal glands caused by acute hemorrhage
    • In children, may be caused by septicemia
    • In adults, may be caused by anticoagulant therapy or a coagulation disorder
  • Patients with congenital adrenal hyperplasia who are given drugs that inhibit steroid synthesis or increase steroid metabolism

Primary Adrenal Insufficiency (AI)

  • Progressive destruction of the adrenals which is most commonly caused by idiopathic atrophy (probably autoimmune in nature), tuberculosis (TB), fungal infections, adrenal hemorrhage, acquired immune deficiency syndrome (AIDS), etc
  • May also be caused by insufficient hormone production caused by congenital adrenal hyperplasia, enzyme inhibitors (eg Metyrapone), or cytotoxic agents (eg Mitotane), adrenal surgery

Secondary and Tertiary Adrenal Insufficiency (AI)

  • Pituitary or hypothalamic disorders
  • Suppression of the hypothalamic-pituitary axis by exogenous steroid (ie long-term glucocorticoid therapy) or endogenous steroid (eg tumor)
    • Exogenous glucocorticoid doses of 5 mg or higher Prednisolone or equivalent for >4 weeks either inhaled, injected, oral or topical, is the most common cause of drug-induced adrenal insufficiency

Signs and Symptoms

  • Usually nonspecific with insidious onset 

Primary Adrenal Insufficiency (AI):

  • Hyperpigmentation - most characteristic
  • Hyperkalemia, hyponatremia
  • Autoimmune thyroid disease
  • Vitiligo

Secondary and Tertiary Adrenal Insufficiency (AI):

  • Manifestations usually begin in the first 48 hours after steroid medication has been discontinued 
  • Similar to primary AI except that hyperpigmentation and dehydration are absent; gastrointestinal (GI) symptoms and hypotension are less prominent
  • Hyponatremia and volume expansion may be present
  • Hypoglycemia is more commonly seen than in primary AI
  • Pale skin without significant anemia
  • Prepubertal growth deficiency, delayed puberty
  • May present with clinical manifestations of pituitary or hypothalamic tumor, eg diabetes insipidus (DI)
  • Secondary hypothyroidism
  • Decreased libido and potency, amenorrhea
  • Visual symptoms, headache

Primary, Secondary and Tertiary Adrenal Insufficiency (AI):

  • Fatigue
  • Weakness
  • Salt craving
  • Orthostatic hypotension, dizziness, hypovolemic shock
  • Nausea and vomiting (N/V); abdominal pain, tenderness and guarding
  • Fever
  • Diarrhea
  • Anorexia, weight loss
  • Confusion, somnolence
  • In severe cases, delirium or coma

Signs & Symptoms of Acute Adrenal Insufficiency (AI)

  • Acute adrenal insufficiency (AI) or adrenal crisis usually occurs with concomitant injury or illness and is difficult to diagnose

Signs and symptoms may be non-specific 

  • Shock or unexplained catecholamine-resistant hypotension is the most predominant manifestation
  • Fatigue
  • Diarrhea
  • Weakness
  • Lethargy
  • Fever
  • Confusion
  • Coma
  • Anorexia
  • Nausea and vomiting
  • Metabolic acidosis
  • Abdominal pain
Patient with underlying chronic adrenal insufficiency (AI) who presents in crisis may show common symptoms of adrenal insufficiency (AI)
  • Hyperpigmentation
  • Vitiligo
  • Sparse pubic and axillary hair
  • Hyponatremia or hyperkalemia
Digital Edition
Asia's trusted medical magazine for healthcare professionals. Get your MIMS Endocrinology - Malaysia digital copy today!
Sign In To Download
Editor's Recommendations
Most Read Articles
11 May 2020
This second issue revisits the impact EMPA-REG OUTCOME had on clinical practice and helps readers discover how it gives life back to patients through its cardiovascular indication. Learn how it was approved and the possible mechanisms for its cardiovascular benefits.
Stephen Padilla, 22 Jul 2019
Zinc supplementation significantly lowers key glycaemic indicators, particularly fasting glucose (FG) in individuals with diabetes and in those who received an inorganic supplement, results of a systematic review and meta-analysis have shown.
Elaine Soliven, 15 Oct 2020

Higher levels of exercise appear to be associated with a lower risk of all-cause mortality in adults with type 2 diabetes (T2D) compared with no exercise at all, according to a study presented at EASD 2020.

Elvira Manzano, 07 Oct 2020
Exendin-4 imaging targeting GLP-1* receptor (GLP-1R) ably detects residual, dysfunctional pancreatic beta cells in individuals with long-standing type 1 diabetes (T1D), according to a study presented at EASD 2020. This breakthrough brings research closer to the possibility of restoring insulin-producing cells depleted in T1D.