Adrenocorticotropic Hormone: Physiology and What Research Reports

What Adrenocorticotropic Hormone Is

Adrenocorticotropic hormone (ACTH), also called corticotropin, is a 39-amino-acid peptide hormone produced by corticotroph cells of the anterior pituitary gland. A physiology review described ACTH as a cleavage product of the larger precursor proopiomelanocortin (POMC), and reported that it acts on the adrenal cortex to stimulate glucocorticoid synthesis and release (PMID 29763207). Because POMC is also processed into melanocyte-stimulating hormone and beta-endorphin, ACTH shares sequence features with peptides that influence pigmentation — one reason sustained ACTH excess has been associated with skin darkening in the clinical literature.

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Where It Is Produced and What It Does

ACTH sits in the middle of the hypothalamic–pituitary–adrenal (HPA) axis. The same physiology review reported that hypothalamic corticotropin-releasing hormone stimulates pituitary release of ACTH, that ACTH binds melanocortin-2 receptors in the adrenal cortex to drive cortisol production, and that circulating cortisol feeds back negatively on both the hypothalamus and the pituitary (PMID 29763207). That review also described a diurnal pattern, with ACTH and cortisol typically highest in the early morning and lowest late in the evening (PMID 29763207).

Downstream, cortisol influences gluconeogenesis, immune signalling, vascular tone and the stress response. ACTH also has a trophic effect: the review noted that chronic stimulation supports adrenal cortical mass, while prolonged absence of ACTH is associated with adrenal atrophy (PMID 29763207).

Beyond mammals

ACTH signalling is evolutionarily old. A photochemistry study reported that ACTH and cyclic adenosine monophosphate were involved in the control of luminescence in shark photophores, implicating melanocortin signalling in a non-adrenal function (PMID 31441051). In horses and other equids, a veterinary study reported that plasma ACTH concentrations varied by month and by breed, describing a seasonal rise relevant to how reference intervals are interpreted in that species (PMID 35798232).

How ACTH Is Measured and Studied

Plasma measurement and sample handling

ACTH is measured in plasma, and the peptide has long been considered fragile. A clinical laboratory analysis argued that current requirements for ACTH and renin/aldosterone sample handling were unnecessarily restrictive, reporting that conventional constraints on transport and processing were stricter than the measured stability of the analytes required (PMID 28148573). A later stability study examined ACTH in whole blood samples and reported on the effects of storage conditions on measured concentrations (PMID 39171091). Together these papers illustrate why pre-analytical handling — tube type, temperature, time to centrifugation — is a recurring theme whenever ACTH results are compared across laboratories.

Stimulation testing

Rather than measuring ACTH alone, clinicians often test the adrenal response to it. A review of the ACTH (cosyntropin) stimulation test described the use of synthetic ACTH_1-24 to assess adrenal reserve, with cortisol sampled before and after administration to distinguish adequate from inadequate adrenal responses (PMID 32310400). That review also discussed the distinction between primary adrenal insufficiency and central (secondary) causes, where the pituitary rather than the adrenal gland is the limiting step (PMID 32310400).

Why ACTH Matters to Peptide Readers

ACTH is one of the clearest worked examples of a peptide hormone whose fragment is used as a pharmaceutical: the diagnostic agent cosyntropin is a synthetic 1–24 fragment of the natural 39-amino-acid sequence, and the stimulation-test review described its use for probing adrenal function (PMID 32310400). Readers who encounter melanocortin peptides, POMC biology or HPA-axis discussion will meet ACTH as the reference point for all of them.

It is also a reminder that the HPA axis can be measured indirectly in disease states. A study of patients with mucocutaneous pemphigus measured ACTH levels and assessed adrenal deficiency in that population, reporting on the relationship between the hormone and adrenal insufficiency in these patients (PMID 35514250).

Therapeutic and Ectopic ACTH: What Studies Report

Ectopic secretion

Some tumours secrete ACTH outside the pituitary. Researchers described ectopic ACTH syndrome in patients with olfactory neuroblastoma, characterising the presentation and course of this rare cause of ACTH excess (PMID 38981513). A separate case report described hypokalemia arising from ectopic ACTH, illustrating the electrolyte disturbance that can accompany marked cortisol excess (PMID 38718244). Skin hyperpigmentation, glucose intolerance and muscle weakness are features discussed in the broader physiology literature on ACTH excess (PMID 29763207).

ACTH preparations in clinical case reports

Several small reports describe ACTH-based products used therapeutically. A case report described ACTH therapy that improved spasms and sleep disturbance in a child with Smith-Magenis syndrome (PMID 33114276). Another report described ACTH analog use for podocytopathies, a group of proteinuric kidney diseases (PMID 27418857). In ophthalmology, a case series reported on ACTH gel used in patients with non-infectious uveitis (PMID 31297467). These are case-level reports rather than large controlled trials, and the authors of such reports typically frame their findings as hypothesis-generating.

Interpreting the evidence

Most of what is confidently known about ACTH concerns its physiology and its diagnostic use. Findings from single cases — such as the spasm and sleep observations reported in Smith-Magenis syndrome (PMID 33114276) — cannot be generalised. Similarly, assay results depend heavily on collection conditions, which is why the stability literature matters when comparing ACTH values (PMID 39171091).

References

• Physiology, Adrenocorticotropic Hormone (ACTH) (StatPearls, 2026)
• Adrenocorticotropic Hormone (Cosyntropin) Stimulation Test (StatPearls, 2026)
• Adrenocorticotropic hormone (ACTH) level and adrenal deficiency in patients with mucocutaneous pemphigus (Hormone Molecular Biology and Clinical Investigation, 2022)
• Ectopic adrenocorticotropic hormone syndrome in patients with olfactory neuroblastoma (Endocrine-Related Cancer, 2024)
• The effect of month and breed on plasma adrenocorticotropic hormone concentrations in equids (The Veterinary Journal, 2022)
• Adrenocorticotropic hormone analog use for podocytopathies (International Medical Case Reports Journal, 2016)
• Current laboratory requirements for adrenocorticotropic hormone and renin/aldosterone sample handling are unnecessarily restrictive (Clinical Medicine, 2017)
• Adrenocorticotropic Hormone and Cyclic Adenosine Monophosphate are Involved in the Control of Shark Bioluminescence (Photochemistry and Photobiology, 2020)
• Adrenocorticotropic Hormone Therapy Improved Spasms and Sleep Disturbance in Smith-Magenis Syndrome: A Case Report (Pediatric Reports, 2020)
• Hypokalemia Due to Ectopic Adrenocorticotropic Hormone (WMJ, 2024)
• Adrenocorticotropic hormone gel for patients with non-infectious uveitis (American Journal of Ophthalmology Case Reports, 2019)
• Stability of adrenocorticotropic hormone in whole blood samples: effects of storage conditions (Biochemia Medica, 2024)