Case: The Stockbroker Who Collapsed


A 60-year-old man was admitted to the ICU with shock and sepsis (source undetermined). Treated with vasopressors and empirical antibiotics and hydrocortisone. No specific specific source of sepsis was found and the patient improved hemodynamically. Two days into the admission to the ICU, hydrocortisone was stopped due to lack of an indication.

An ACTH stimulation test was performed shortly after stopping steroids and showed the following cortisol levels:

  • Baseline — cortisol not recorded
  • 30 minutes — 430
  • 60 minutes — 640

The following day, the patients blood pressure dropped again. Hydrocortisone was restarted resulting in return of hemodynamic stability.

Ten days later, the ACTH stimulation test was repeated again:

  • Baseline: cortisol 20, ACTH pending
  • 30 min: cortisol 110
  • 60 min: cortisol 130

List 4 differential diagnoses

1. 2. 3. 4.


  • Primary adrenal insufficiency due to sepsis (Waterhouse–Friderichsen syndrome)
  • Secondary adrenal insufficiency due to pituitary disease
  • Physiologic secondary adrenal insufficiency due to suppression with steroids
  • Low albumin state leading to low total and bound cortisol levels with normal free cortisol levels (not measured)

Baseline ACTH level, which was pending, returned showing:

  • Baseline ACTH — undetectable

How does that affect your differential diagnosis?

How might the following differ in cases of primary vs secondary adrenal insufficiency?

Clinical: ACTH: Potassium: Sodium: Glucose:

Primary vs Secondary AI

  • Clinical Features
    • Hyperpigmentation may be seen in primary adrenal insufficiency due to elevated ACTH levels but is not a feature of secondary adrenal insufficiency.
    • Crnial nerve invovlvement due to a pituitary lesion may be seen in secondary adrenal insufficiency (e.g., reduced visual acuity and/or visual field abnormalities, extra-occular eye movements, reduced facial sensations).
  • ACTH
    • In a patient with AI and an intact pituitary gland, ACTH will be elevated.
    • ACTH will be low or “inappropriately normal” in patients with secondary adrenal insufficiency.
  • Potassium
    • Elevated in primary adrenal insufficiency due to mineralocorticoid insufficiency
    • Normal in patients with secondary AI. Mineralocorticoid release is not ACTH dependent and will therefore be intact in patients with secondary AI
  • Sodium
    • Hypocortisolism leads to hyponatraemia, regardless of the cause. Hyponatraemia is not helpful in differentiating primary vs secondary AI.
    • Cortisol inhibits AVP and this inhibition is lost in hypocortisol states. Reduced GFR also contributes to hyponatraemia.
    • In patients with secondary AI, central hypothyroidism may also contribute to hyponatraemia.
  • Glucose
    • Hypoglycaemia is more common in secondary AI. Glucose levels are maintained by the counter-regulatory system which includes: cortisol, growth hormone, and glucagon.
    • In secondary AI, there’s usually loss of GH in addition to ACTH/cortisol, which contributes to favouring hypoglycaemia.

Pituitary Panel

Low ACTH is consistent with secondary adrenal insufficiency.

A pituitary panel is performed and shows the following:

  • TSH 1.99
  • Free T4 10.9
  • FSH 1.0
  • LH 0.7
  • Prolactin 1.5
  • Testosterone undetectable
  • GH < 0.1
  • IGF-1 13

What is your differential diagnosis now?

Differential Revisited

  • Secondary adrenal insufficiency + hypogonadotrophic hypogonadism due to severe illness and/or opiate use
  • Panhypopituitarism (sparing the H-P-thyroid axis)

What would the differential diagnosis be if

  • TSH 0.1
  • Free T4 6

In this case, the differential diagnosis would be:

  • Secondary adrenal insufficiency + nonthyroidal illness + hypogonadotrophic hypogonadism due to severe illness and/or opiate use
  • Panhypopituitarism


  • Adrenal insufficiency should be in the differential diagnosis of patients presenting with shock of unclear ethology (“Endocrine Shock”)
  • Patients with adrenal insufficiency due to acute pituitary conditions may have a “normal” ACTH stimulation test
  • Similar to primary adrenal insufficiency, acute secondary adrenal insufficiency may also present with hyponatremia and hypoglycaemia, but not with hyperkalemia