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Adrenocorticotropin (ACTH) – Hormone & Function

Adrenocorticotropin (ACTH) is a pituitary hormone that stimulates the adrenal cortex to produce cortisol and plays a key role in the body´s stress response system.

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Things worth knowing about "Adrenocorticotropin"

Adrenocorticotropin (ACTH) is a pituitary hormone that stimulates the adrenal cortex to produce cortisol and plays a key role in the body´s stress response system.

What is Adrenocorticotropin?

Adrenocorticotropin (commonly abbreviated as ACTH, also known as corticotropin) is a peptide hormone produced and secreted by the anterior pituitary gland. It is a crucial component of the hypothalamic-pituitary-adrenal (HPA) axis, which governs the body´s response to stress and regulates numerous physiological processes.

Mechanism of Action

ACTH is derived from a precursor protein called proopiomelanocortin (POMC). Its release from the pituitary is triggered by corticotropin-releasing hormone (CRH) from the hypothalamus. Once in the bloodstream, ACTH travels to the adrenal cortex, where it binds to specific receptors (MC2 receptors) and stimulates the synthesis and release of cortisol, as well as smaller amounts of other glucocorticoids and adrenal androgens.

The system is regulated by a negative feedback loop: elevated cortisol levels suppress both CRH secretion from the hypothalamus and ACTH release from the pituitary.

Biological Functions

Stimulation of cortisol production in the adrenal cortex
Activation and regulation of the stress response
Modulation of metabolism, immune function, and inflammation
Influence on blood pressure and electrolyte balance
Trophic (growth-supporting) effect on adrenal cortex tissue

Circadian Rhythm of ACTH

ACTH secretion follows a distinct circadian (daily) rhythm, with peak levels occurring in the early morning hours and declining throughout the day. Stress, sleep deprivation, hypoglycemia, and other physiological challenges can further stimulate ACTH release.

Clinical Significance

Excess ACTH

Abnormally elevated ACTH levels lead to excessive cortisol production. This can result from:

Cushing disease: An ACTH-secreting tumor of the pituitary gland
Ectopic ACTH syndrome: ACTH production by non-pituitary tumors (e.g., small cell lung carcinoma)

ACTH Deficiency

Insufficient ACTH leads to reduced cortisol production, known as secondary adrenal insufficiency. Common causes include:

Pituitary tumors or damage
Long-term corticosteroid therapy (suppression of the HPA axis)
Sheehan syndrome (pituitary infarction following childbirth)

Diagnostic Applications

The ACTH stimulation test (also known as the Synacthen test) is widely used to assess adrenal cortex function. Synthetic ACTH (tetracosactide) is administered, and the cortisol response is measured. This test is essential in diagnosing adrenal insufficiency (Addison disease) and other HPA axis disorders.

Baseline ACTH levels are typically measured in the morning (between 7 and 9 a.m.) to account for circadian variation. Blood samples must be handled carefully -- collected in chilled tubes and processed promptly to ensure accurate results.

Therapeutic Applications

Synthetic ACTH analogues are used clinically in several contexts:

Tetracosactide (Synacthen): Used both diagnostically and therapeutically in certain inflammatory conditions
Management of specific pediatric epilepsy syndromes, such as West syndrome (infantile spasms)

References

Chrousos G.P. - Stress and disorders of the stress system. Nature Reviews Endocrinology, 5(7), 374-381 (2009). PubMed PMID: 19488073
Melmed S. et al. - Williams Textbook of Endocrinology, 14th Edition, Elsevier (2020)
World Health Organization (WHO) - Endocrine Disorders: Adrenal Gland Pathologies. WHO Technical Report Series (updated guidelines)

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