Question 8 from the second paper of 2004 was the only question to ask directly about adrenal insufficiency. Beyond that, it pops up now and then among a list of differentials. Oh's Manual divides adrenal insufficiency into primary, secondary, or relative.
Primary adrenal insufficiency is the state of adrenal malfunction due to genuinely disorderly adrenal glands. Secondary hypoadrenalism is the state of being adreno-suppressed, for whatever reason (be it drugs, critical illness or hypothalamic-pituitary malfunction)- but in the presence of normal adrenal glands. Lastly, one might have completely normal hypothalamic-pituitary-adrenal axis, and it might be secreting normally, but one might have a "relative adrenal insufficiency" if this volume of secretions happens to be inadequate to sustain the magnitude of the stress response which is required.
Apart from Oh's Manual, another resource worth reading in the lead-up to the exams is an article by Marik and Zaloga (2002).
The following table is an adaptation of an entry in Oh's Manual - Box 61.1 on page 661 is a comprehensive source for causes of primary hypoadrenalism. It is an answer to the question, which aetiologies are responsible for the destruction of adrenal glands?
Causes of adrenal insufficiency
Marik and Zaloga (2002) offer a table of causes, which I have reorganised and adapted here:
Infiltrative systemic disease
This can be further separated into primary, secondary and tertiary causes.
Primary causes include anything which attacks the adrenal gland directly. The vascular, autoimmune and neoplastic causes fit here.
Secondary causes feature a structurally and functionally normal adrenal gland, but in the absence of appropriate stimulus. Such situations arise when the adrenal gland function is suppressed by drugs, or dysregulated by a damaged pituitary. An interesting case of traumatic pituitary injury is presented in Question 12.1 from the second paper of 2014.
Tertiary causes are those which result in hypoadrenalism with an intact hypothalamic-pituitary-adrenal axis, such as the cessation of corticosteroids, or the "relative adrenal insufficiency" of septic shock.
Consequences of adrenal insufficiency in critical illness
The stereotypical adreally suppressed patient in the ICU will have a tanned apparance of their skin, be hypoglycaemic, and will likely be suffereing from shock of some sort, with high vasopressor requirements. Hyperkalemia and hyponatremia with a normal anion gap metabolic acidosis will be a feature of mineralocorticid deficiency, and will resemble the wanton use of spironolactone.
Investigation of adrenal insufficiency
- Serum cortisol level
- In normal subjects, a good morning cortisol level is 275 to 555 nmol/L
- High dose ACTH test:
- 250 μg of synacthen is administered
- Cortisol levels are taken 30-60 minutes later
- A normal cortisol level 60 minutes after the synacthen should be >500 nmol/L
- An abnormal response establishes the daignosis of hypoadrenalism
- A normal response rules out primary hypadrenalism
- An abnormal response does not exclude the diagnosis of secondary hypadrenalism
- Metyrapone test:
- Metyrapone blocks the final step in cortisol biosynthesis
- This should decrease the serum cortisol level and stimulate ACTH secretion
- Serum 11-deoxycortisol and cortisol are measured on the next morning
- A normal response consists of a high 11-deoxycortisol level and a low cortisol level
- ACTH can also be measured: a normal response is 10 to 200 pg/mL.
- Insulin-hypoglycaemia test
- Hypoglycaemia is a more potent stimulus for ACTH secretion than metyrapone
- 0.15 units/kg of insulin is given
- A hypoglycaemia of ~ 1.9mmol/L is aimed for (under supervision)
- Cortisol levels are taken at 0, 30 and 45 minutes
- A normal response is a cortisol level around 500 to 600 nmol/L
- ACTH level
- MRI of the adrenal glands