Adrenal insufficiency

Ammar Aladaileh
Adrenal gland histology
 Hypothalamic-pituitary adrenal axis
• Cortisol secretion is under influence
of ACTH, while mineralocorticoid
secretion is under influence of
RAAS.
• POMC (proopiomelanocortin) is the
precursor for MSH, ACTH and
endorphins.
 Aldosterone
• Secretion is stimulated by hyperkalemia and
decrease renal blood flow.

• Effects on principle cell of DCT:

1. Decrease serum K+
2. Increase serum Na+
3. Secretion of H+ in the urine
4. Maintain intravascular volume.
 Adrenal insufficiency
• Inadequate secretion of adrenal hormones caused by a failure of the
adrenal glands (primary adrenal insufficiency) or pituitary disease
(secondary adrenal insufficiency).
• Primary causes the deficiency of all hormones of the adrenal gland
• Secondary causes the deficiency in cortisol only.
Primary hypoadrenalism causes:

Autoimmune (Addison’s disease) >> most common causes of primary adrenal

insufficiency in developed countries .

1. Infections (Tuberculosis, Fungal infections, CMV, HIV)

2. Metastatic tumor
3. Infiltrations (Amyloid, Hemochromatosis)
4. Intra-adrenal hemorrhage (Waterhouse-Friderichsen syndrome) after meningococcal
septicemia
5. Congenital adrenal hypolasia
6. Bilateral adrenalectomy

Which might be isolated or part of APS

 Autoimmune polyendocrine syndrome type I (Addison's disease, chronic
mucocutaneous candidiasis, hypoparathyroidism, dental enamel hypoplasia, )
 Autoimmune polyendocrine syndrome type II (Schmidt's syndrome) :Addison's disease
+ primary hypothyroidism, or insulin-dependent diabetes .
Secondary adrenal insufficiency causes:
1. Exogenous glucocorticoid therapy >> most common cause of
secondary adrenal insufficiency . Look for patients who recently
discontinued glucocorticoid therapy or did not increase their
glucocorticoid dose in times of stress
2. Hypopituitarism
3. Pituitary apoplexy
4. Granulomatous disease (tuberculosis, sarcoid, eosinophilic
granuloma)
5. Secondary tumor deposits (breast, bronchus)
6. Postpartum pituitary infarction (Sheehan's syndrome)
7. Pituitary irradiation (effect usually delayed for several years)
8. Isolated ACTH deficiency
9. Idiopathic
Clinical manifestations of adrenal insufficiency
1. GI symptoms: nausea, vomiting, diarrhea, weight loss and salt craving.
2. CVS: hypotension, dizziness and weakness
3. Skin & mucous membrane hyperpigmentation: in primary adrenal
insufficiency. (due to increase MSH)
 Investigations
1. CBC: eosinophilia, lymphocytosis
2. Kidney function &electrolytes: hypoglycemia, hyponatremia and hyperkalemia. High
creatinine and urea (prerenal).
3. 8:00 am serum cortisol level , if <3 µg/dL diagnoses cortisol deficiency and values >15 µg/dL
exclude the diagnosis.
4. Cosyntropin stimulation test with baseline cortisol and ACTH.  For nondiagnostic cortisol
values, select stimulation testing with synthetic ACTH (cosyntropin)  A stimulated serum
cortisol >18 µg/dL excludes adrenal insufficiency , values < 18 confirms the diagnosis .
5. Morning ACTH level can help distinguish primary from secondary adrenal deficiency
6. Imaging:
 If morning ACTH is elevated (>20pg/ml)  Primary hypoadrenalism  Adrenal CT
 If morning ACTH is suppressed or normal  Secondary hypoadrenalism Do Pituitary MRI
• 21 hydroxylase antibodies
 Adrenal crisis
Similar symptoms and signs of adrenal insufficiency but are more
severe, including but not limited to:
1. Severe hypotension (<90/50)
2. Fever & decreased level of consciousness.
3. Hyperkalemia & hyponatremia & metabolic acidosis
 Long term replacement therapy
1. Glucocorticoid Replacement
• Hydrocortisone 10 mg on awakening and 5 to 10 mg in early afternoon.
• Monitor clinical symptoms and morning plasma ACTH.
2. Mineralocorticoid Replacement
• Fludrocortisone 0.1 (0.05 to 0.2) mg orally.
• Liberal salt intake.
• Monitor lying and standing blood pressure and pulse, edema, serum
potassium, and plasma renin activity.
 Patient advice
• All patients requiring replacement steroids should:
1. Know how to increase steroid replacement by doubling the dose for
intercurrent illness
2. Carry a ‘steroid card’
3. Wear a MedicAlert bracelet (or similar), which gives details of their
condition so that emergency replacement therapy can be given if found
unconscious
4. Keep an ampoule of hydrocortisone at home in case oral therapy is
impossible, for administration by self, family, ambulance or doctor.