ACTH Deficiency Syndrome

Glucocorticoid replacement is similar to that described for Addison disease. Each case varies regarding the type and degree of specific hormone deficiencies. Normally, cortisol is secreted maximally in the early morning and minimally at night. Thus, hydrocortisone (identical to cortisol) is given in 2 or 3 divided doses with a typical total daily dose of 15 to 30 mg. One regimen gives half the total in the morning, and the remaining half split between lunchtime and early evening (eg, 10 mg, 5 mg, 5 mg). Others give two-thirds in the morning and one-third in the evening. Doses immediately before bed should generally be avoided because they may cause insomnia. Alternatively, prednisone 4 to 5 mg orally in the morning and possibly an additional 2.5 mg orally in the evening may be used. During acute febrile illness or after trauma, patients receiving corticosteroids for nonendocrine disorders may require supplemental doses to augment their endogenous hydrocortisone production.

Fludrocortisone is not required because the intact adrenals produce aldosterone.

In panhypopituitarism, other pituitary deficiencies should be treated appropriately.

or

Treatment of Chronic Primary Adrenal Insufficiency

1. Glucocorticoid replacement (one of the given regimens):

• Hydrocortisone 15 to 25 mg orally in two or three divided doses (the largest dose is taken early in the  morning; typically 10 mg upon awakening in the morning, 5 mg early afternoon, 2.5 mg late afternoon), or
• Prednisone 5 mg (2.5 to 7.5 mg) orally at bedtime, or
• Dexamethasone 0.75 mg (0.25 to 0.75 mg) orally at bedtime
• Monitor clinical symptoms and morning plasma ACTH as needed.

2. Mineralocorticoid replacement:

• Fludrocortisone 0.1 mg (range: 0.05 to 0.2 mg) orally. Hydrocortisone 20 mg and prednisone 50 mg provide a mineralocorticoid effect that is almost equivalent to 0.1 mg of fludrocortisone. Therefore, fludrocortisone replacement (if needed) must be decreased accordingly. Dexamethasone, however, lacks a mineralocorticoid effect and would require a full dose of fludrocortisone.
• Liberal salt intake.
• Monitor supine and standing blood pressure as well as pulse, edema, serum potassium, and plasma renin activity

3. Androgen replacement:

• Dehydroepiandrosterone (DHEA) initially 25 to 50 mg orally (only in women for psychological well-being, if needed, after optimal glucocorticoid and mineralocorticoid replacement).

4. Patient education:

• Educate the patient about the illness, how to manage stress, and inject dexamethasone or other glucocorticoids intramuscularly or subcutaneously.

5. Emergency precautions:

• Patients should have a medical alert bracelet/necklace, an emergency medical information card on their phone or inside their wallet, and prefilled syringes containing 4 mg of dexamethasone in 1 mL saline.

6. Treatment of minor febrile illness or stress:

• Increase glucocorticoid dose two to three times for the few days of illness. Do not change the mineralocorticoid dose (3×3 rule).
• The patient should contact the clinician if the condition worsens or persists for more than three days.
• No extra dose is required for most uncomplicated, outpatient dental procedures under local anesthesia.
• Glucocorticoid supplement for surgical stress:
• Minor: hydrocortisone 25 mg IV (or equivalent) on the day of the procedure
• Moderate: hydrocortisone 50 to 75 mg IV (or equivalent) on day of surgery and postoperative day 1
• Major: hydrocortisone 100 to 150 mg IV (or equivalent) in two or three divided doses on the day of surgery and postoperative days 1 and 2

7. Emergency treatment of severe stress or trauma:

• Each patient should have an injectable as well as vials of sterile 0.9% normal saline and syringes.

Treatment of Adrenal Crisis

Measures to stabilize the patient:

1. Intravenous access with one or two large-gauge needles
2. Laboratory analysis, including serum electrolytes, glucose, and routine measurement of plasma cortisol and ACTH.
3. Infusion of 2 to 3 liters of isotonic saline or 5% dextrose in isotonic saline as urgently as possible. Periodic hemodynamic monitoring and measurement of serum electrolytes.
4. Give hydrocortisone 100 mg intravenous bolus, followed by 50 mg intravenously every 6 hours (or 200 mg/24 hours as a continuous intravenous infusion for the first 24 hours). If hydrocortisone is unavailable, alternatives include prednisolone, prednisone, and dexamethasone.
5. Correct any ongoing electrolyte abnormalities. Hyponatremia is often corrected by cortisol and volume repletion.

Subacute measures after stabilization of the patient:

1. Intravenous isotonic saline infusion at a slower rate for the next 24 to 48 hours.
2. Diagnosis and treatment of possible infectious precipitating causes of the adrenal crisis.
3. If the patient does not have known adrenal insufficiency, a short ACTH stimulation test should establish the diagnosis and determine its type and cause.
4. Tapering of parenteral glucocorticoid over 1 to 3 days to the oral glucocorticoid maintenance dose, if there are no ongoing contraindications.
5. Initiating mineralocorticoid replacement with fludrocortisone, 0.1 mg by mouth daily after stopping the saline infusion.