What is secondary adrenal insufficiency and how is it managed in a patient with symptoms of fatigue, weight loss, and hypotension?

Understanding Secondary Adrenal Insufficiency: Patient Explanation

Secondary adrenal insufficiency occurs when your pituitary gland (a small gland at the base of your brain) doesn't produce enough ACTH hormone to signal your adrenal glands to make cortisol—you have enough cortisol-producing capacity in your adrenal glands, but they're not receiving the proper signal to make it. 1, 2

What's Happening in Your Body

The Key Difference from Primary Adrenal Insufficiency:

• In secondary adrenal insufficiency, your pituitary gland fails to produce adequate ACTH (the hormone that tells your adrenal glands to make cortisol), resulting in low cortisol levels with low or inappropriately normal ACTH 1, 2
• Critically, you continue to produce aldosterone normally through the renin-angiotensin system, which remains intact—this is why you typically won't have the severe salt-wasting and high potassium levels seen in primary adrenal insufficiency 1, 2
• Your adrenal glands themselves are healthy but have become "sleepy" or atrophied from lack of ACTH stimulation 3

Common Causes You Should Know About

Most Common Cause:

• Long-term use of steroid medications (prednisone, dexamethasone, inhaled steroids like fluticasone) suppresses your natural cortisol production—this is called glucocorticoid-induced or iatrogenic secondary adrenal insufficiency 1, 4

Other Causes:

• Pituitary tumors, surgery, or radiation to the pituitary area 4, 5
• Medications that suppress ACTH production, particularly opioids 4
• Inflammatory conditions affecting the pituitary (hypophysitis, sarcoidosis) 4
• Pituitary hemorrhage or damage from head trauma 4

Your Symptoms Explained

Why You Feel This Way:

• Fatigue and weakness (occurs in 50-95% of patients): Without adequate cortisol, your body cannot maintain normal energy metabolism and blood sugar regulation 4
• Weight loss and poor appetite (43-73% of patients): Cortisol deficiency impairs your body's ability to maintain weight and stimulate appetite 4
• Low blood pressure/dizziness when standing: While less severe than in primary adrenal insufficiency (because your aldosterone is intact), cortisol deficiency still affects blood pressure regulation 2, 4
• Nausea and vomiting (20-62% of patients): Cortisol deficiency directly affects gastrointestinal function 1, 4
• Low sodium (hyponatremia): Present in 90% of newly diagnosed cases—cortisol deficiency impairs your kidneys' ability to excrete free water, causing dilutional hyponatremia that can look identical to SIADH 2, 6

Important Distinction:

• You typically will NOT have the severe skin darkening (hyperpigmentation) seen in primary adrenal insufficiency, because your ACTH levels are low rather than high 1
• You typically will NOT have high potassium levels or severe salt craving, because your aldosterone production is preserved 1, 2

How We Diagnose This Condition

Initial Blood Tests (Done in Early Morning, Around 8 AM):

• Morning cortisol and ACTH levels: Low cortisol (<5-10 µg/dL) with low or inappropriately normal ACTH confirms secondary adrenal insufficiency 1, 2, 4
• DHEA-S levels: Typically low in secondary adrenal insufficiency 3, 4
• Electrolytes: Checking for low sodium (very common) and confirming normal or near-normal potassium 2, 6

Confirmatory Testing When Needed:

• Cosyntropin (ACTH) stimulation test: We give you a synthetic ACTH injection and measure your cortisol response at 30 and 60 minutes—a peak cortisol <500 nmol/L (<18 µg/dL) confirms adrenal insufficiency 7, 2, 6, 4
• This test shows whether your adrenal glands can respond when properly stimulated 6, 5

Critical Diagnostic Pitfall:

• If you're currently taking any steroid medications (prednisone, hydrocortisone, inhaled steroids), cortisol testing is not interpretable—we must wait until you've been off steroids with adequate washout time before testing 1, 7, 8

Treatment: What You Need to Take

Daily Glucocorticoid Replacement (Lifelong):

• Hydrocortisone 15-25 mg daily in divided doses is the preferred treatment, typically given as 10 mg at 7 AM, 5 mg at noon, and 2.5-5 mg at 4 PM to mimic your body's natural cortisol rhythm 7, 4
• Alternative: Prednisone 3-5 mg daily in the morning 7, 4
• You do NOT need fludrocortisone (mineralocorticoid replacement) because your aldosterone production is intact—this is a key difference from primary adrenal insufficiency 1, 9, 4

Stress Dosing—Critical for Your Safety:

• During illness, fever, or physical stress: Double or triple your usual dose 7, 10
• For minor procedures not requiring anesthesia: Double your morning dose before the procedure 1
• For major surgery or severe illness: You need IV hydrocortisone 100 mg immediately, followed by continuous infusion or repeated doses 1

Life-Threatening Emergency: Adrenal Crisis

What Is Adrenal Crisis?

• A medical emergency that occurs when your body's cortisol needs exceed what you're taking, causing severe hypotension, shock, altered mental status, and potentially death if untreated 1, 4
• Occurs 6-8 times per 100 patient-years in people with adrenal insufficiency 1

Warning Signs You Must Recognize:

• Severe vomiting or diarrhea that prevents you from taking your medication 1
• Severe weakness, confusion, or loss of consciousness 7
• Severe abdominal pain 7
• Unexplained collapse or very low blood pressure 7

Emergency Treatment:

• Immediate IV hydrocortisone 100 mg plus IV saline infusion at 1 liter per hour—treatment should NEVER be delayed for diagnostic testing 1, 7, 6
• You should carry an emergency injectable hydrocortisone 100 mg IM kit and know how to self-inject 7, 4

Essential Safety Measures

You Must:

• Wear a medical alert bracelet stating "adrenal insufficiency" so emergency personnel know to give you stress-dose steroids 1, 7, 4
• Carry an emergency injection kit (hydrocortisone 100 mg IM) and know how to use it 7, 4
• Never abruptly stop your hydrocortisone—this is lifelong replacement therapy for confirmed adrenal insufficiency 7
• Inform all healthcare providers about your condition before any procedure or surgery 7

Drug Interactions to Know:

• Medications that increase your hydrocortisone needs: Anti-seizure medications (phenytoin, carbamazepine), rifampin, barbiturates 7
• Medications that decrease your needs: Grapefruit juice, licorice—avoid these 7

Long-Term Monitoring

Annual Follow-Up Should Include:

• Assessment of symptoms, weight, blood pressure 7
• Serum electrolytes (sodium, potassium) 7
• Screening for other autoimmune conditions: Thyroid function, diabetes, vitamin B12, celiac disease (if you have frequent diarrhea) 7
• Bone density monitoring every 3-5 years to assess for osteoporosis from glucocorticoid therapy 7

Special Consideration: If You Also Have Hypothyroidism

Critical Safety Rule:

• If you need both thyroid hormone and cortisol replacement, you must start hydrocortisone several days BEFORE starting thyroid hormone—starting thyroid hormone first can precipitate a life-threatening adrenal crisis by increasing cortisol metabolism 1, 7

Recovery Potential (For Steroid-Induced Cases Only)

If Your Secondary Adrenal Insufficiency Was Caused by Taking Steroid Medications:

• Your HPA axis may recover after stopping glucocorticoids, but this typically takes 6-12 months and can be variable 8
• Do not attempt diagnostic testing until you've been off steroids with adequate washout time 1, 7
• Endocrinology consultation is recommended for a safe weaning protocol using hydrocortisone 7

If Your Secondary Adrenal Insufficiency Is From Pituitary Disease:

• This is typically permanent and requires lifelong replacement therapy 7, 4