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secondary adrenal insufficiency (SAI)

Adrenal insufficiency due to pituitary insufficiency. Only glucocorticoid synthesis is affected. The renin-angiotensin- aldosterone axis remains intact. Etiology: 1) suppression of the hypothalamic-pituitary-adrenal axis a) exogenous glucocorticoids (most common) or ACTH b) post surgical treatment for Cushing's disease c) chronic administration of drugs with corticosteroid activity: megestrol (Megace) 2) pituitary or hypothalamic lesion resulting in ACTH deficiency a) tumors 1] pituitary adenoma 2] craniopharyngioma or Rathke cyst 3] hypothalmic tumor 4] sarcoidosis 5] metastatic tumor b) surgery or trauma c) cranial irradiation d) pituitary infarction (Sheehan's syndrome) e) infectious or autoimmune adenohypophysitis Clinical manifestations: 1) signs & symptoms milder than Addison's disease 2) no salt craving or postural dizziness 3) tachycardia, nausea, weakness, dizziness, & hyponatremia [3] 3) pigmentation absent 4) no dehydration, only slight decrease in blood pressure 5) other obnormalities of hypothalamic or pituitary function may be present Laboratory: 1) cosyntropin (Cortrosyn) stimulation test a) generally increased response b) in long-standing disease, repeated daily injections of ACTH may be necessary to prime adrenal gland 2) serum Na+: hyponatremia is often present 3) serum K+: hyperkalemia is NOT a feature 4) serum ACTH: low or inappropriately normal 5) serum cortisol (NOT generally useful) a) useful in the setting of acute pituitary injury b) in the setting of acute stress, a normal serum cortisol is 20-120 ug/dL 6) serum aldosterone: normal 7) plasma renin: normal 8) insulin tolerance test 9) metyrapone stimulation test Radiology: -> MRI of the pituitary & hypothalamus Management: 1) glucocorticoid a) prednisone 5 mg PO qAM & 2.5 mg PO qPM b) hydrocortisone 12-15 mg/m2/day (20-25 mg QD) c) for minor illness, stress, fever > 100 F, influenza - double the oral maintenance dose d) for severe illness or injury 1] hydrocortisone 100-150 mg/day IV divided every 6 hours 2] septic shock: 150-200 mg/day [3] e) do not use dexamethasone for chronic glucocorticoid replacement therapy [3] f) when glucocorticoid therapy is > 3-4 weeks, a taper is necessary to minimize withdrawal & promote recovery of the hypothalamic-pituitary-adrenal axis - a taper is unnecessary when glucocorticoid therapy is < 3-4 weeks, regardless of dose [6] - see glucocorticoid taper 2) mineralocorticoid replacement generally not necessary 3) patient education 4) glucocorticoid coverage at times of stress is indicated in patients who have taken potentially suppressive doses of glucocorticoids for more than 3 weeks the preceding year

Interactions

disease interactions

Related

ACTH deficiency (central adrenal insufficiency) Addison's disease (primary adrenal failure)

General

adrenal insufficiency

References

  1. DeGowin & DeGowin's Diagnostic Examination, 6th edition, RL DeGowin (ed), McGraw Hill, NY 1994, pg 862
  2. Saunders Manual of Medical Practice, Rakel (ed), WB Saunders, Philadelphia, 1996, pg 653-656
  3. Medical Knowledge Self Assessment Program (MKSAP) 11, 14, 15 16, 19. American College of Physicians, Philadelphia 1998, 2006, 2009, 2012, 2023
  4. Toogood AA, Stewart PM. Hypopituitarism: clinical features, diagnosis, and management. Endocrinol Metab Clin North Am. 2008 Mar;37(1):235-61 PMID: 18226739
  5. Leinung MC, Liporace R, Miller CH. Induction of adrenal suppression by megestrol acetate in patients with AIDS. Ann Intern Med. 1995 Jun 1;122(11):843-5. PMID: 7741369
  6. Beuschlein F, Else T, Bancos I et a; European Society of Endocrinology and Endocrine Society Joint Clinical Guideline: Diagnosis and Therapy of Glucocorticoid-induced Adrenal Insufficiency. J Clin Endocrinol Metab. 2024 Jun 17;109(7):1657-1683. PMID: 38724043 PMCID: PMC11180513 Free PMC article.