Endocrine: Adrenal Insufficiency

Adrenal Insufficiency

Definitions

  • Adrenal Insufficiency: Insufficient Hormone Production within the Adrenal Gland
  • Types:
    • Primary (Addison Disease): From Disease within the Adrenal Gland
    • Secondary: From Decreased ACTH Secretion by the Pituitary Gland
    • Tertiary: From Decreased CRH Secretion by the Hypothalamus

Causes

  • Primary Adrenal Insufficiency (Addison Disease)
    • Autoimmune (Most Common Primary Cause – 70-90%)
    • Tuberculosis (Was Previously the Most Common Cause Before Vaccination)
    • Fungal Infections
    • HIV/AIDS
    • Metastatic Cancer
    • Adrenal Hemorrhage/Infarction
      • Can Be Caused by Infection (Pseudomonas, Meningococcemia, etc.)
      • Waterhouse-Friderichsen Syndrome
        • Adrenal Hemorrhage After Meningococcal Infection
        • Presents as Adrenal Insufficiency After Meningitis
    • Medications (Ketoconazole, Fluconazole, Rifampin, etc.)
  • Secondary Adrenal Insufficiency
    • Pituitary Adenoma
    • Pituitary Surgery
    • Pituitary Radiation
    • Infection
    • Pituitary Infarction – Sheehan Syndrome
    • Pituitary Apoplexy
  • Tertiary Adrenal Insufficiency
    • Abrupt Steroid Withdrawal – Most Common Cause of Adrenal Insufficiency Overall
    • Tumor
    • Radiation
    • Infection
    • Stroke
    • Traumatic Brain Injury

Waterhouse-Friderichsen Syndrome; Adrenal Excision 1

Presentation

  • Addisonian/Adrenal Crisis: Hypotension/Shock Refractory to IV Fluids & Vasopressors
    • Hypotension Itself is the Most Common First Sign
  • Anorexia
  • Abdominal Pain
  • Nausea & Vomiting
  • Fatigue & Lethargy
  • Confusion
  • Weight Loss
  • Muscle Pain
  • Hypoglycemia
  • Symptoms Specific to Primary Adrenal Insufficiency:
    • Skin Hyperpigmentation – ACTH Converted to MSH (Melanocyte-Stimulating Hormone)
    • Mineralocorticoid Deficiency – Salt Craving, Postural Hypotension, Hyponatremia & Hyperkalemia

Diagnosis

  • Standard Test for Diagnosis: ACTH Stimulation Test
    • Consider Morning Serum Cortisol to Screen First
  • Treatment for Adrenal Crisis Should Be Started Before Diagnosis is Established
  • Determine Type (If Necessary):
    • First: Measure Basal ACTH
      • High ACTH: Primary Adrenal Insufficiency
      • Low ACTH: CRH Stimulation Test
    • CRH Stimulation Test:
      • Absent/Low ACTH Response: Secondary Adrenal Insufficiency
      • Exaggerated ACTH Response: Tertiary Adrenal Insufficiency

Tests

  • ACTH Stimulation Test
    • Given Cosyntropin (Synthetic ACTH) 250 mcg & Serum Cortisol is Measured After 30-60 Minutes
      • Normal Cortisol Response: ≥ 18-20 mcg/dL
    • Can Be Done at Any Time of the Day – Response in Adrenal Insufficiency Will Remain Low Regardless of Time of Day
  • Morning Serum Cortisol
    • Normal: 10-20 mcg/dL
    • Low: < 3-5 mcg/dL
    • *High Specificity, Low Sensitivity
  • Morning Salivary Cortisol
    • Normal: > 5.8 ng/mL
    • Low: < 1.8 ng/mL
  • Afternoon Cortisol Levels Have Wide Variability & Do Not Help in Diagnosis

Treatment

  • Treatment: IV Fluids & Steroids
  • Standard Glucocorticoid: Hydrocortisone
    • IV Dose: 100 mg Bolus & 50 mg Every 6 Hours or 200 mg Infusion Over 24 Hours
    • Duration of Action: Short Acting (8-12 Hours)
    • Has Glucocorticoid & Some Mineralocorticoid Effect
  • Other Steroids if Hydrocortisone Unavailable:
    • Prednisone PO
      • Duration of Action: Intermediate Acting (12-36 Hours)
    • Prednisolone PO
      • Duration of Action: Intermediate Acting (12-36 Hours)
    • Dexamethasone IV
      • Dose: 4 mg Every 12 Hours
      • Duration of Action: Long Acting (36-72 Hours)
      • Does Not Interfere with ACTH Stimulation Test
      • No Mineralocorticoid Effect – Can Trigger an Adrenal Crisis in Primary Adrenal Insufficiency if Not Concurrently Given Fludrocortisone
  • When Resolved: Can Wean/Taper Rapidly Over 48 Hours

References

  1. Hale AJ, LaSalvia M, Kirby JE, Kimball A, Baden R. Fatal purpura fulminans and Waterhouse-Friderichsen syndrome from fulminant Streptococcus pneumoniae sepsis in an asplenic young adult. IDCases. 2016 Aug 16;6:1-4. (License: CC BY-NC-ND-4.0)