enda-acth-measurement-pai

name	enda-acth-measurement-pai
description	Recommends measurement of plasma ACTH to establish primary adrenal insufficiency (PAI) diagnosis in patients with confirmed cortisol deficiency; a plasma ACTH concentration ≥2-fold the upper limit of the reference range supports PAI. Use when evaluating plasma ACTH in a patient with low morning cortisol or abnormal corticotropin stimulation test.

Measure Plasma ACTH to Establish PAI Diagnosis

STEP 1 — Gather Information

Confirm cortisol deficiency via low morning cortisol (<140 nmol/L) or subnormal response to corticotropin stimulation test; obtain paired plasma ACTH sample (preferably with morning cortisol or baseline ACTH stimulation sample) using EDTA-plasma kept on ice and processed promptly.

STEP 2 — Rule In / Rule Out

Calculate whether plasma ACTH is ≥2-fold the assay-specific upper limit of reference range; if yes, rule in primary adrenal insufficiency; if no, rule out PAI and consider secondary adrenal insufficiency or other causes.

STEP 3 — Classify or Stratify

Classify as primary adrenal insufficiency when ACTH ≥2-fold ULN with confirmed cortisol deficiency; classify as secondary/tertiary adrenal insufficiency when ACTH is low or inappropriately normal despite cortisol deficiency.

STEP 4 — Decide

If PAI confirmed, proceed to etiologic workup (e.g., 21-hydroxylase autoantibodies) and initiate glucocorticoid and mineralocorticoid replacement; if secondary adrenal insufficiency suspected, evaluate pituitary/hypothalamic function and consider glucocorticoid replacement alone.

Clinical Guardrails / Mimics / Pitfalls

ACTH assays are subject to pre-analytical variability (hemolysis, delayed processing) and inter-assay differences; always use cold EDTA plasma and refer to assay-specific reference ranges. Do not rely on ACTH alone without confirming cortisol deficiency, and avoid using ACTH levels to adjust glucocorticoid replacement due to loss of negative feedback. Pitfalls include falsely elevated ACTH from stress, illness, or heterophilic antibodies, and falsely normal ACTH in secondary AI.

Concrete Clinical Example

A 48-year-old man presents with weight loss, hypotension, and morning cortisol 90 nmol/L (<140 nmol/L). Plasma ACTH measured at 110 pmol/L (assay ULN 45 pmol/L) is >2-fold ULN (90 pmol/L), supporting PAI; 21-hydroxylase antibodies are positive, and glucocorticoid/mineralocorticoid replacement is started.

Source: Diagnosis and Treatment of Primary Adrenal Insufficiency: An Endocrine Society Clinical Practice Guideline, Endocrine Society, 2016, DOI:10.1210/jc.2015-1710

TODO: consider adding scripts/calc.py for the enda-acth-measurement-pai calculator