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ACTH – Adrenocorticotropic Hormone Explained

ACTH (Adrenocorticotropic Hormone) 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 "ACTH"

ACTH (Adrenocorticotropic Hormone) 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 ACTH?

ACTH stands for Adrenocorticotropic Hormone (also known as corticotropin or adrenocorticotrophin). It is a peptide hormone produced and secreted by the anterior pituitary gland, a small gland located at the base of the brain. ACTH is a central component of the hypothalamic-pituitary-adrenal (HPA) axis, which governs the body's response to stress.

Mechanism of Action

ACTH secretion is triggered by corticotropin-releasing hormone (CRH) from the hypothalamus. Once released into the bloodstream, ACTH binds to specific receptors on the adrenal cortex (the outer layer of the adrenal glands, located above the kidneys) and stimulates the production and release of cortisol – the body's primary stress hormone. Cortisol in turn suppresses further ACTH release through a negative feedback loop, keeping hormone levels in balance.

Biological Functions

Regulation of cortisol production in the adrenal cortex
Control of the physiological stress response
Modulation of immune system activity
Influence on metabolism of carbohydrates, fats, and proteins
Contribution to blood pressure regulation
Stimulation of skin pigmentation (due to structural similarity to melanocyte-stimulating hormone, MSH)

ACTH Levels and Circadian Rhythm

ACTH secretion follows a natural circadian (daily) rhythm: levels peak in the early morning (approximately 6–8 a.m.) and are lowest in the late evening. Physical or psychological stress, sleep deprivation, pain, and illness can all cause additional spikes in ACTH secretion.

Conditions Associated with ACTH

Elevated ACTH Levels

Addison's Disease (primary adrenal insufficiency): The adrenal glands fail to produce enough cortisol; without the negative feedback signal, ACTH levels rise significantly
Cushing's Disease (pituitary Cushing's): An ACTH-secreting tumor of the pituitary gland leads to excessive cortisol production
Ectopic ACTH Syndrome: Certain tumors outside the pituitary (e.g., small cell lung cancer) produce ACTH autonomously

Low ACTH Levels

Secondary adrenal insufficiency: Damage to or dysfunction of the pituitary gland reduces ACTH production
Long-term corticosteroid therapy: Exogenous corticosteroids suppress ACTH secretion through negative feedback

Diagnosis: The ACTH Test

In clinical practice, the ACTH stimulation test (also called the Synacthen test or cosyntropin test) is frequently used. Synthetic ACTH is injected, and the subsequent cortisol response of the adrenal glands is measured. This helps determine whether the adrenal cortex responds adequately to ACTH stimulation. Baseline plasma ACTH levels are also measured to distinguish between primary (adrenal) and secondary (pituitary) adrenal insufficiency.

ACTH as a Medication

Synthetic ACTH preparations (e.g., tetracosactide) are used therapeutically in medicine, for example in certain forms of childhood epilepsy (West syndrome / infantile spasms), and diagnostically in adrenal function testing.

References

Boron, W. F. & Boulpaep, E. L. (2017). Medical Physiology (3rd edition). Elsevier.
Chrousos, G. P. (2009). Stress and disorders of the stress system. Nature Reviews Endocrinology, 5(7), 374–381.
Nieman, L. K. & Chanco Turner, M. L. (2006). Addison's disease. Clinics in Dermatology, 24(4), 276–280.

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