What ACTH and Prolactin Measure
ACTH (adrenocorticotropic hormone) measures pituitary function and adrenal axis integrity, while prolactin measures lactotroph cell activity and helps identify prolactinomas or other causes of hyperprolactinemia.
ACTH Measurement
ACTH is measured in plasma and serves as a critical diagnostic tool for distinguishing primary from secondary adrenal insufficiency 1:
- In primary adrenal insufficiency (PAI): ACTH is markedly elevated (>2-fold above the upper limit of normal) because the pituitary attempts to stimulate failing adrenal glands
- Diagnostic threshold: ACTH >66 pmol/L (300 ng/L) represents maximum stimulation of glucocorticoid synthesis 1
- Key diagnostic pattern: Low cortisol (<140 nmol/L or 5 µg/dL) combined with elevated ACTH is highly predictive of PAI 1
Clinical Application
Measure plasma ACTH paired with morning cortisol or at baseline during corticotropin stimulation testing 1. The sample timing is flexible as ACTH testing is not significantly affected by diurnal variations for diagnostic purposes, though ACTH does have physiologic circadian rhythm.
Important Caveats
- ACTH assays demonstrate significant analytical bias between different laboratory methods 1
- In early-stage PAI, ACTH may be elevated while cortisol remains in the normal range 1
- ACTH levels help distinguish primary adrenal failure (high ACTH) from secondary/central causes (low or inappropriately normal ACTH)
Prolactin Measurement
Prolactin measures lactotroph function and is straightforward to assess 2:
- Normal values: Generally <25 µg/L (assay-specific; higher in women than men) 2
- Prolactinoma diagnosis: Levels >500 µg/L are diagnostic of macroprolactinoma 2
- Moderate elevation: Levels >250 µg/L usually indicate prolactinoma, though certain drugs (risperidone, metoclopramide) can elevate prolactin >200 µg/L without adenoma 2
Diagnostic Approach
A single serum prolactin measurement above the upper limit of normal confirms hyperprolactinemia, provided the sample was obtained without excessive venipuncture stress 2. Dynamic testing with TRH, L-dopa, or other agents is not recommended as it provides no diagnostic advantage over a single measurement 2.
Testing Technique
- Draw at any time of day (diurnal variation is not clinically significant for diagnosis)
- Avoid excessive venipuncture stress
- Single determination is usually sufficient 2
Macroprolactin Consideration
In patients with asymptomatic hyperprolactinemia, assess for macroprolactin 2. Macroprolactin consists of larger, less bioactive prolactin polymers (including antibody-bound forms) that can cause falsely elevated readings without clinical significance.
Clinical Context
Prolactin elevation indicates:
- Prolactinoma (most common functional pituitary adenoma)
- Medication effects (antipsychotics, antiemetics)
- Stalk compression from other pituitary masses
- Physiologic causes (pregnancy, lactation, stress)