What are the features of adrenal insufficiency?

Features of Adrenal Insufficiency

Adrenal insufficiency presents with characteristic features including fatigue, unintentional weight loss, anorexia, postural hypotension, muscle and abdominal pain, hyponatremia, and in primary adrenal insufficiency, skin hyperpigmentation and salt craving. 1, 2

Types and Distinguishing Characteristics

Primary and secondary adrenal insufficiency have distinct clinical and laboratory features:

Type	ACTH Level	Cortisol Level	Electrolytes	Hyperpigmentation
Primary	High	Low	↓Na, ↑K	Present
Secondary	Low	Low	Generally normal	Absent

Primary Adrenal Insufficiency

• Hormone deficiencies: Deficiency of all adrenocortical hormones (cortisol, aldosterone, and adrenal androgens) 1
• Causes: Autoimmune destruction, congenital adrenal hyperplasia, pharmacological inhibition (e.g., high-dose azole antifungals), infections (tuberculosis, fungal), or surgical removal of adrenal tissue 1
• Unique features:
  • Skin hyperpigmentation (due to high ACTH levels)
  • Salt craving
  • Volume depletion
  • Hyperkalemia (↑K)
  • Hyponatremia (↓Na) 3, 1, 4

Secondary Adrenal Insufficiency

• Hormone deficiencies: Primarily cortisol deficiency (mineralocorticoid function preserved) 1
• Causes: Pituitary disorders (tumors, hemorrhage, inflammatory conditions), surgery, radiation therapy, or medications suppressing ACTH (e.g., opioids) 1
• Unique features:
  • No hyperpigmentation
  • Generally normal electrolytes
  • May have other pituitary hormone deficiencies 3, 1

Glucocorticoid-Induced Adrenal Insufficiency

• Most common form of adrenal insufficiency 1
• Caused by suppression of the hypothalamic-pituitary-adrenal axis from exogenous glucocorticoid use 1
• Risk related to dose and duration of glucocorticoid therapy 4

Common Clinical Manifestations

General Symptoms (All Types)

• Fatigue (50%-95% of patients)
• Nausea and vomiting (20%-62%)
• Anorexia and weight loss (43%-73%)
• Profound weakness
• Postural hypotension
• Reduced quality of life and work capacity 3, 1, 2

Laboratory Findings

• Primary AI: Low morning cortisol (<5 μg/dL), high ACTH, low DHEAS 1
• Secondary/Glucocorticoid-induced AI: Low/intermediate morning cortisol (5-10 μg/dL), low/low-normal ACTH and DHEAS 1

Adrenal Crisis

Adrenal crisis is a life-threatening complication characterized by:

• Hypotension and shock
• Hyponatremia
• Altered mental status
• Can be fatal if untreated 1

Precipitating factors include:

• Inadequate glucocorticoid therapy
• Acute illness
• Physical stress
• Abrupt withdrawal of glucocorticoid therapy 1, 4

Diagnostic Approach

Early diagnosis is crucial but often delayed due to non-specific presentation 2. Key diagnostic tests include:

• Early-morning (8 AM) serum cortisol, ACTH, and DHEAS measurements 1
• Corticotropin stimulation testing for patients with intermediate cortisol levels (5-10 μg/dL)
  • Measure cortisol before and 60 minutes after administration of cosyntropin (250 μg) 1

Clinical Pitfalls and Considerations

• Diagnosis is frequently delayed due to non-specific initial symptoms 2
• Physician awareness must be improved to prevent adrenal crisis 2
• All patients with known or suspected adrenal insufficiency require glucocorticoid prophylaxis before any surgical procedure (major or minor) 4
• Hydrocortisone should be used for stress dosing, not cortisone acetate 4
• Patients on chronic glucocorticoid therapy should not abruptly discontinue treatment due to risk of adrenal crisis 4

By recognizing these characteristic features of adrenal insufficiency, clinicians can make earlier diagnoses and implement appropriate treatment to prevent potentially life-threatening adrenal crises.