Thanks to Jess for presenting the fascinating case of a middle-aged woman with family history of autoimmune disease who presented with acute onset of fatigue and abdominal pain, found to have vitiligo on exam.  Work up revealed hyponatremia due to a secondary adrenal insufficiency, pancytopenia, and panhypopituitarism possibly due to a yet to be diagnosed autoimmune disorder!

Clinical pearls

• Remember that hyponatremia is a problem of water regulation that can be compounded by low solute intake.
• Primary adrenal insufficiency is disorder at the level of the adrenal glands and manifests with low sodium and high serum potassium levels.
• Secondary adrenal insufficiency is disorder at the level of the pituitary and manifests with low/normal sodium and normal potassium levels (because low cortisol leads to high ADH levels and hyponatremia).
  • Make sure to do work up to rule out panhypopituitarism.  Keep in mind that the most sensitive test for HPA access integrity is LH/FSH.
• Tertiary adrenal insufficiency is disorder at the level of the hypothalamus and presents similarly to secondary AI.
• Test for adrenal insufficiency with a cort-stim test and/or AM cortisol and ACTH levels.

Hyponatremia

Remember these three steps to working up hyponatremia:

1. Is there a sodium problem? check serum osm
2. Are the kidneys responding appropriately? check urine osm
3. Is ADH revved up for a hemodynamic reason? check urine Na 

Adrenal insufficiency

Primary AI:

• Failure of adrenal glands
• Causes: Addison’s (most common in the US), infiltrative processes (TB, sarcoid), hemorrhage, toxins
• Labs would show ↓Na and ↑potassium (b/c aldosterone is gone)

Secondary AI:

• Failure of pituitary (low ACTH)
• Causes: pituitary lesions, surgeries, TBI, drugs
• Clinically may present with loss of other anterior pituitary hormones
• Labs would show ↓Na (because low cortisol leads to high ADH levels) but normal potassium levels (b/c aldosterone is active)

Tertiary AI:

• Failure of hypothalamus (low CRH)
• Causes: more commonly iatrogenic (cessation of high dose glucocorticoid therapy without taper) or post surgical interventions.

Hypopituitarism

Hypophysitis:

• Inflammation of the pituitary
• Four categories based on histologic findings:
  • Lymphocytic
    • Most common form
    • Seen in late pregnancy and post-partum period
    • Also associated with CTLA4 inhibitors like ipilimumab
  • Granulomatous
    • Idiopathic or secondary to GPA, sarcoid, TB
  • Plasmacytic (IgG4-related)
  • Xanthomatous (most rare)
• Clinical presentation
  • Headache out of proportion to exam findings
  • Preferential decrease in ACTH and TSH ⇒ adrenal insufficiency and hypothyroidism
• Prognosis:
  • Pituitary size eventually normalizes but pituitary loss of function is often permanent.