Unit Converter
Adrenocorticotropic hormone (ACTH)
Synonyms
- ACTH
- Corticotropin
- Adrenocorticotropin
- Hypophyseal ACTH
- Polypeptide hormone (POMC derivative)
Units of Measurement
pmol/L, pg/mL, pg/dL, pg/100 mL, pg%, pg/L, ng/L
(Most modern labs use pg/mL or pmol/L.)
Description
Adrenocorticotropic hormone (ACTH) is a 39–amino acid peptide secreted by the anterior pituitary.
It is derived from pro-opiomelanocortin (POMC).
ACTH stimulates the adrenal cortex (zona fasciculata) to produce cortisol. Its secretion follows a circadian rhythm, peaking around 6–8 AM and lowest near midnight.
ACTH measurement is essential in evaluating:
- Adrenal insufficiency
- Cushing syndrome
- Ectopic ACTH production
- Pituitary vs adrenal causes of cortisol abnormalities
Physiological Role
ACTH regulates:
1) Cortisol Secretion
Binds to adrenal MC2R receptor → activates cAMP → stimulates cortisol synthesis.
2) Adrenal Growth & Maintenance
Chronic high ACTH → adrenal hyperplasia
Low ACTH → adrenal atrophy
3) Stress Response
ACTH increases during:
- Stress
- Illness
- Hypoglycemia
- Surgery
- Trauma
Clinical Significance
Elevated ACTH
Seen in:
1. Primary Adrenal Insufficiency (Addison Disease)
- High ACTH
- Low cortisol
- Hyperpigmentation (↑MSH via POMC)
2. Secondary Conditions
- Congenital adrenal hyperplasia
- Adrenal destruction
- Adrenal enzyme defects
3. Cushing Disease
- ACTH-secreting pituitary adenoma
4. Ectopic ACTH Syndrome
- Small-cell lung carcinoma
- Neuroendocrine tumors
- Pancreatic or thymic tumors
(Usually very high ACTH)
5. Stress States
- Severe illness
- Febrile conditions
- Hypoglycemia
- Major surgery
Low ACTH
Occurs in:
1. Exogenous glucocorticoid use
Most common cause.
2. Cushing Syndrome (Adrenal type)
- High cortisol
- Low ACTH (suppressed)
3. Secondary Adrenal Insufficiency
- Pituitary failure
- Hypothalamic failure
4. Chronic steroid use → HPA axis suppression
Reference Intervals
Morning (6–10 AM)
- 7 – 63 pg/mL
- 1.6 – 14 pmol/L
Evening (10 PM)
- < 20 pg/mL
ACTH Interpretation
| Condition | Typical ACTH |
| Primary adrenal insufficiency | High |
| Secondary adrenal insufficiency | Low |
| Pituitary Cushing disease | High/Normal-High |
| Ectopic ACTH syndrome | Very high (>200 pg/mL) |
| Adrenal tumor/Cushing syndrome | Very low |
Sample Collection Requirements (CRITICAL)
ACTH is highly unstable.
- Collect in pre-chilled EDTA tube
- Keep on ice immediately
- Centrifuge within 1 hour
- Freeze plasma at –20°C or lower if delayed
- Avoid hemolysis and heat exposure
Failure to follow proper handling → falsely low ACTH.
Unit Meanings
| Unit | Meaning |
| pg/mL | picogram per milliliter |
| pmol/L | picomole per liter |
| pg/dL | picogram per deciliter |
| pg/100mL | equivalent to pg% |
| pg% | picogram per 100 mL |
| pg/L | picogram per liter |
| ng/L | nanogram per liter (= pg/mL × 1000) |
Use in ACTH Stimulation Test
Used to differentiate adrenal from pituitary causes.
1. High ACTH + low cortisol
→ Primary adrenal insufficiency
2. Low ACTH + low cortisol
→ Secondary adrenal insufficiency (pituitary)
3. Normal ACTH + subnormal cortisol after stimulation
→ Adrenal insufficiency (chronic)
Clinical Pearls
- Always draw ACTH early morning unless assessing nocturnal secretion.
- In suspected ectopic ACTH, levels are usually >200 pg/mL.
- ACTH and cortisol must be interpreted together, never alone.
- Poor sample handling is the most common cause of falsely low ACTH.
- In hyperpigmentation: ACTH is markedly elevated (MSH effect).
Interesting Fact
ACTH was discovered in 1933 and was one of the first pituitary hormones to be sequenced. Its measurement revolutionized understanding of adrenal disorders long before cortisol assays became widely available.
References
- Tietz Clinical Chemistry and Molecular Diagnostics, 8th Edition — Pituitary Hormone Analysis.
- ESAP 2024 — ACTH Reference Intervals.
- Mayo Clinic Laboratories — ACTH, Plasma Test Catalog.
- ARUP Consult — Adrenal Insufficiency & Cushing Syndrome Evaluation.
- Endocrine Society Guidelines — Primary & Secondary Adrenal Insufficiency.
- MedlinePlus / NIH — ACTH Test Overview.
- Raff H, Findling J. Endocrine Reviews: ACTH physiology and interpretation.