Management of Secondary Adrenal Insufficiency

Diagnostic Confirmation

The Endocrine Society recommends morning (8 AM) paired measurements of serum cortisol and plasma ACTH to establish the pattern of secondary adrenal insufficiency (low ACTH with low cortisol) 3, 2
A basic metabolic panel is recommended to assess for hyponatremia, which occurs in 90% of newly diagnosed cases, though hyperkalemia is typically absent in secondary adrenal insufficiency 3, 2
An ACTH stimulation test is recommended if morning cortisol falls in the indeterminate range (5-18 mcg/dL or 140-500 nmol/L): administer 0.25 mg cosyntropin IV or IM with cortisol measured at baseline, 30, and 60 minutes—peak cortisol <18 mcg/dL (<500 nmol/L) confirms adrenal insufficiency 3, 2

The American College of Clinical Endocrinologists recommends assessing other pituitary hormones: TSH, free T4, LH, FSH, testosterone (males) or estradiol (premenopausal females) to identify hypopituitarism 4, 1
An MRI of the brain with pituitary/sellar cuts is recommended if multiple endocrine abnormalities are present, or if patient has new severe headaches or vision changes 4, 1
A review of medication history is recommended for exogenous corticosteroids (prednisone, inhaled fluticasone), opioids, or immune checkpoint inhibitors that can cause iatrogenic secondary adrenal insufficiency 4, 3

The Endocrine Society recommends initiating hydrocortisone 10-20 mg orally in the morning and 5-10 mg in early afternoon to mimic physiological cortisol rhythm 4, 1, 2
If concurrent hypothyroidism exists, start corticosteroids several days before initiating levothyroxine to prevent precipitating adrenal crisis 4, 1
For Grade 3-4: Severe Symptoms or Adrenal Crisis, immediate treatment with IV hydrocortisone 100 mg bolus (or dexamethasone 4 mg if diagnosis uncertain and stimulation testing still needed) is recommended 4, 3, 2
Infuse 0.9% normal saline at 1 L/hour (at least 2 liters total) for volume resuscitation 4, 2

The American College of Clinical Endocrinologists recommends stress dosing education: Double or triple usual dose during illness, fever, injury, or significant physical stress 3, 2
An emergency injectable hydrocortisone 100 mg IM kit with self-injection training is recommended for use during vomiting, severe illness, or inability to take oral medications 3, 2
A medical alert bracelet or necklace indicating adrenal insufficiency is recommended to trigger stress-dose corticosteroids by emergency medical services 4, 1, 2

CYP3A4 inducers (anticonvulsants, rifampin, barbiturates) increase cortisol clearance and may require higher replacement doses 3
CYP3A4 inhibitors (grapefruit juice, liquorice) decrease cortisol clearance and may require lower doses—patients should avoid these 3
Hydrocortisone is preferred over long-acting steroids (dexamethasone, betamethasone) because it allows recreation of diurnal cortisol rhythm 3

Annual review with assessment of health, well-being, weight, blood pressure, and serum electrolytes is recommended 3
Periodic screening for new autoimmune disorders, particularly hypothyroidism, as autoimmune conditions frequently coexist 3
Follow free T4 (not TSH) for thyroid hormone replacement titration in patients with concurrent central hypothyroidism, as TSH is unreliable 4, 1