1. Adrenal insufficiency

2. The adrenal gland..
Nussey SS, Whitehead SA; The adrenal gland. Endocrinology: An integrated approach.

3. Medulla – sympathetic functions
Cortex (Remember GFR)
Glomerulosa – (mineralocorticoids)
Fasiculata – (glucocorticoids)
Reticularis – (androgens)
Medulla – sympathetic functions

4. Adrenal products

5. Adrenal products
Nussey SS, Whitehead SA; The adrenal gland. Endocrinology: An
integrated approach.

6. Answer: Feedback control.
Gordon H. Williams, Robert G. Dluhy.
“Disorders of the Adrenal Cortex.”
Harrison's Principles of Internal Medicine –
17th Ed. (2008)

7. Synthesis of adrenocorticotrophic hormone (ACTH)
Nussey SS, Whitehead SA; The adrenal gland. Endocrinology: An
integrated approach.

8. Cortisol secretion is circadian
Cortisol Androgens
Nussey SS, Whitehead SA; The adrenal gland. Endocrinology: An
intergrated approach.

9. Cortisol actions
Stewart, PM; The adrenal cortex. Kronenberg: Williams Textbook of
Endocrinology, 11th ed.

10. Classification of adrenal disorders
Insufficiency
Primary adrenal insufficiency (Addison’s)
due to adrenal insufficiency (marked skin pigmentation due to high ACTH levels)
Secondary adrenal insufficiency
Pituitary or hypothalamic Insufficiency (no skin pigmentation)
Excess
Cushing's disease/syndrome
Stewart, PM; The adrenal cortex. Kronenberg: Williams Textbook of
Endocrinology, 11th ed.

11. Adrenal insufficiency
chronic primary adrenal insufficiency
prevalence: 39 to 60 per million
mean age at diagnosis: 40 years (17-72)

12. Primary adrenal insufficiency Causes
Autoimmune (Sporadic, Autoimmune polyendocrine syndrome types I & II) 70%
Infections (TB, Fungal [histo, crypto], CMV, HIV)
Infiltrations (Metastases, amyloid, hemochromatosis)
Drugs (ketoconazole, rifampin)
Intra-adrenal hemorrhage (Waterhouse-Friderichsen syndrome) after meningococcal (or other) septicemia
Adrenoleukodystrophies
Congenital adrenal hypoplasia (DAX-1, SF-1 mutations)
ACTH resistance syndromes (Mutations in MC2-R, Triple A syndrome)
Bilateral adrenalectomy
Stewart, PM; The adrenal cortex. Kronenberg: Williams Textbook of
Endocrinology, 11th ed.

13. Primary adrenal insufficiency Associated endocrine disease
None %
Thyroid disease
Hypothyroidism %
Nontoxic goiter %
Thyrotoxicosis %
Gonadal failure
Ovarian %
Testicular %
Insulin-dependent diabetes mellitus 11%
Hypoparathyroidism 10%
Pernicious anemia %
Stewart, PM; The adrenal cortex. Kronenberg: Williams Textbook of
Endocrinology, 11th ed.

14. Secondary adrenal insufficiency Causes
Exogenous glucocorticoid therapy
Hypopituitarism
Selective removal of ACTH-secreting pituitary adenoma
Pituitary tumors and pituitary surgery, craniopharyngiomas
Pituitary apoplexy
Granulomatous disease (tuberculosis, sarcoid, eosinophilic granuloma)
Secondary tumor deposits (breast, bronchus)
Postpartum pituitary infarction (Sheehan's syndrome)
Pituitary irradiation (effect usually delayed for several years)
Isolated ACTH deficiency
Idiopathic (Lymphocytic hypophysitis, TRIT gene mutations, POMC processing defect, POMC gene mutations)
Stewart, PM; The adrenal cortex. Kronenberg: Williams Textbook of
Endocrinology, 11th ed.

15. Clinical features of primary adrenal insufficiency: Symptoms
Weakness, tiredness, fatigue 100%
Anorexia %
Gastrointestinal symptoms %
Nausea %
Vomiting %
Constipation %
Abdominal pain %
Diarrhea %
Salt craving %
Postural dizziness %
Muscle or joint pains %
Stewart, PM; The adrenal cortex. Kronenberg: Williams Textbook of
Endocrinology, 11th ed.

16. Clinical features of primary adrenal insufficiency: Signs
Weight loss %
Hyperpigmentation %
Hypotension (<110 mm Hg systolic) 88-94%
Vitiligo %
Auricular calcification %
Hypoglycemia (in adults) ~ <1%
Stewart, PM; The adrenal cortex. Kronenberg: Williams Textbook of
Endocrinology, 11th ed.

17. Nussey SS, Whitehead SA; The adrenal gland. Endocrinology: An
integrated approach.

18. Signs
Stewart, PM; The adrenal cortex. Kronenberg: Williams Textbook of
Endocrinology, 11th ed.

19. Why hyperpigmentation?

20. Clinical features of primary adrenal insufficiency: laboratory
Electrolyte disturbances 92%
Hyponatremia 88%
Hyperkalemia 64%
Hypercalcemia 6%
Azotemia %
Anemia %
Eosinophilia 17%
Stewart, PM; The adrenal cortex. Kronenberg: Williams Textbook of
Endocrinology, 11th ed.

21. Adrenal crisis
Dehydration, hypotension, or shock out of proportion to severity of current illness
Nausea and vomiting with a history of weight loss and anorexia
Abdominal pain, so-called acute abdomen
Unexplained hypoglycemia
Unexplained fever
Hyponatremia, hyperkalemia, azotemia, hypercalcemia, or eosinophilia
Hyperpigmentation or vitiligo
Other autoimmune endocrine deficiencies, such as hypothyroidism or gonadal failure
Stewart, PM; The adrenal cortex. Kronenberg: Williams Textbook of
Endocrinology, 11th ed.

22. Diagnosis 1. Screening test
Early morning basal total/free serum cortisol and plasma corticotropin
Plasma aldosterone and renin activity
(salivary cortisol)
(Urinary free cortisol excretion)

23. Diagnosis 2. Stimulation test
Stimulation of adrenal function
administer 1 or 250 μg corticotropin(1-24)
measure cortisol after 30 and 60 minutes
increase in serum cortisol level to peak > 18 µg/dL indicates normal response
Stimulation of pituitary-adrenal axis
insulin-induced hypoglycemia
Regular insulin (0.1 U) administered intravenously
Basal and minutes after start of insulin tolerance test of cortisol and corticotropin (and growth hormone in case of suspected multiple pituitary hormone deficiency)
Stimulation with CRH
differentiate between hypothalamic and pituitary etiologies

24. Treatment glucocorticoid replacement acute adrenal crisis
two or three daily doses (total 15 to 30 mg of hydrocortisone)
one half to two thirds of the daily dose is given in the morning, in line with the physiologic cortisol-secretion pattern.
Prednisone 5 mg daily
Mineralocorticoid replacement (0.05 to 0.2 mg of fludrocortisone daily as a morning dose) required only with primary adrenal insufficiency
dehydroepiandrosterone replacement (25 to 50 mg) optional treatment
acute adrenal crisis
immediate intravenous administration of 100 mg of hydrocortisone, then
100 to 200 mg of hydrocortisone every 24 hours
continuous infusion of larger volumes of physiologic saline solution (initially 1 liter per hour) under continuous cardiac monitoring
Bornstein SR; Predisposing Factors for Adrenal Insufficiency; NEJM 2009:
Volume 360:

25. Treatment Minor febrile illness or stress
Increase glucocorticoid dose twofold to threefold for the few days of illness; do not change mineralocorticoid dose.
Contact physician if illness worsens or persists for more than 3 days or if vomiting develops.
Emergency treatment of severe stress or trauma
Inject contents of prefilled dexamethasone (4-mg) syringe intramuscularly.
Get to physician as quickly as possible.

26. Treatment: Inpatients
Cooper MS and Stewart PM, Corticosteroid insufficiency in acutely ill patients, NEJM 2003; 348: