Adrenal Insufficiency

Adrenal Insufficiency

David Ray Velez, MD

Table of Contents

Definitions
Causes
Presentation
Diagnosis
Treatment

Definitions

Adrenal Insufficiency: Insufficient Hormone Production within the Adrenal Gland

Types

  • Primary (Addison Disease): From Disease within the Adrenal Gland
  • Secondary: From Decreased Adrenocorticotrophic Hormone (ACTH) Secretion by the Pituitary Gland
  • Tertiary: From Decreased Corticotropin Releasing Hormone (CRH) Secretion by the Hypothalamus

Critical Illness-Related Corticosteroid Insufficiency (CIRCI): A Form of Adrenal Insufficiency with Dysregulated Systemic Inflammation from Inadequate Glucocorticoid-Mediated Anti-Inflammatory Activity for the Severity of Critical Illness

Causes

Primary Adrenal Insufficiency (Addison Disease)

  • Autoimmune – Most Common Primary Cause (70-90%)
  • Tuberculosis (Was Previously the Most Common Cause Before Vaccination)
  • HIV/AIDS
  • Fungal Infection
  • Adrenal Hemorrhage/Infarction
    • Can Be Caused by Infection (Pseudomonas, Meningococcemia, etc.)
    • Waterhouse-Friderichsen Syndrome – Adrenal Hemorrhage After Meningococcal Infection
  • Metastatic Cancer
  • Medication (Ketoconazole, Fluconazole, Rifampin, etc.)

Secondary Adrenal Insufficiency

  • Pituitary Adenoma
  • Pituitary Surgery
  • Pituitary Radiation
  • Pituitary Infection
  • Pituitary Infarction (Sheehan Syndrome) – Infarction Due to Postpartum Hemorrhage
    • Pituitary Hypertrophies While Pregnant
  • Pituitary Apoplexy – Sudden Hemorrhage or Infarction of the Pituitary Gland
    • May Occur in an Adenoma After Radiation

Tertiary Adrenal Insufficiency

  • Abrupt Steroid Withdrawal – Most Common Cause Overall
  • Tumor
  • Radiation
  • Infection
  • Stroke
  • Traumatic Brain Injury (TBI)

Presentation

Addisonian/Adrenal Crisis: Hemodynamic Shock Refractory to IV Fluids and Vasopressors

  • Hypotension Itself is the Most Common First Sign

Presentation

  • Abdominal Pain
  • Nausea, and Vomiting
  • Fatigue and Lethargy
  • Myalgia
  • Confusion
  • Weight Loss
  • Muscle Pain
  • Hypoglycemia

Symptoms Specific to Primary Adrenal Insufficiency

  • Skin Hyperpigmentation – ACTH Converted to Melanocyte-Stimulating Hormone (MSH)
  • Mineralocorticoid Deficiency – Salt Craving, Postural Hypotension, Hyponatremia, and Hyperkalemia

Diagnosis

Treatment for Adrenal Crisis Should Be Started Before Diagnosis is Established

Diagnosis

  • Standard Test for Diagnosis: ACTH Stimulation Test
    • Consider Morning Serum Cortisol to Screen First
  • 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

Testing

  • ACTH Stimulation Test:
    • Given 250 mcg Cosyntropin (Synthetic ACTH) and Measure Serum Cortisol After 30-60 Minutes
    • Diagnosis: Cortisol Change < 9 mcg/dL After 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
  • Random Cortisol:
    • Low: < 10 mcg/dL
    • *Generally Recommend Against Using Free Cortisol – Although Total Cortisol May Be Inaccurate if Albumin is Low, Free Cortisol is Cumbersome and Often Takes Days to Result
  • Morning Serum Cortisol
    • May Consider to Screen
    • Afternoon Cortisol Levels Have Wider Variability
    • Normal: 10-20 mcg/dL
    • Low: < 3-5 mcg/dL

Treatment

If Concerned for Adrenal Crisis, Treatment Should Be Started Before Diagnosis is Established

Primary Treatment: IV Fluids and Steroids

Steroids

  • Steroids Generally Not Required if Not in Shock
  • Typical Dosing: 200 mg Hydrocortisone Daily (Often 50 mg QID)
    • Has Glucocorticoid and Some Mineralocorticoid Effect
  • Other Steroids if Hydrocortisone Unavailable:
    • Prednisone PO
    • Prednisolone PO
    • Dexamethasone IV – No Mineralocorticoid Effect (Can Trigger an Adrenal Crisis in Primary Adrenal Insufficiency if Not Concurrently Given Fludrocortisone)
  • Can Wean/Taper Rapidly Over 48 Hours Once Resolved

Perioperative Stress Dose Steroids

  • Indicated if Given Systemic Steroids in the Last 6 Months
  • Not Suppressed/No Stress Dose Indicated:
    • Low Dose ≤ 5 mg Daily
    • Low Dose ≤ 10 mg Every Other Day
    • Any Dose for Short Duration < 3 Weeks
  • Stress Dosing:
    • Minor Surgery: Usual Dose
    • Moderate Surgery: Usual Dose + Hydrocortisone 50 mg Before and 25 mg Every 8 Hours for 24 Hours
    • Major Surgery: Usual Dose + Hydrocortisone 100 mg Before and 50 mg Every 8 Hours for 24 Hours