CorticotropinEdit

Corticotropin is a hormone central to the body’s stress response and metabolic regulation. In medical terminology it is most commonly referred to as adrenocorticotropic hormone (ACTH). It is produced by the anterior pituitary and acts on the adrenal cortex to stimulate the production and release of glucocorticoids, primarily cortisol, along with androgens to a lesser extent. ACTH operates within the hypothalamic-pituitary-adrenal axis (Hypothalamic-pituitary-adrenal axis), where corticotropin-releasing hormone (CRH) from the hypothalamus prompts its release, and circulating cortisol exerts negative feedback to modulate further secretion. Clinically, corticotropin can be used as a drug in two broad forms: natural ACTH derived from animal tissue and synthetic fragments used for diagnostic testing, with a long history of applications in endocrinology and immunology. In practice, the pharmacologic use of corticotropin intersects with debates about cost, access, and the best evidence for a given indication.

From a biological standpoint, corticotropin exerts its effects by binding to the melanocortin receptor MC2R on adrenal cortical cells, triggering a cascade that culminates in cortisol synthesis. This mechanism links stress, inflammation, and metabolic regulation through a single hormonal pathway. Because cortisol has wide-reaching effects on glucose metabolism, immune function, blood pressure, and mood, ventricular fluctuations in corticotropin activity can have broad clinical consequences. The therapeutic relevance of corticotropin rests not only in its ability to raise cortisol levels quickly but also in the downstream anti-inflammatory and immunomodulatory actions associated with glucocorticoids. For readers who want to trace the signaling pathway in depth, see Melanocortin receptors and Cortisol.

Biology and mechanism

Anatomy and production: ACTH is produced by the corticotrope cells of the anterior pituitary. Its release is driven by CRH and monitored by feedback from circulating cortisol.
Receptors and signaling: ACTH primarily activates MC2R on adrenal cortex cells to stimulate steroidogenesis and cortisol release.
Hormonal ecology: As a peptide hormone, ACTH acts in a short-acting manner to adjust adrenal output in response to stress, diurnal variation, and inflammatory signals.
Related hormones and tests: Cosyntropin, a synthetic fragment (ACTH 1-24), is used primarily in diagnostic testing to assess adrenal reserve and the integrity of the adrenal cortex Cosyntropin; this contrasts with natural porcine or human ACTH used therapeutically in some settings.

Clinical uses

Diagnostic testing: The cosyntropin stimulation test is used to evaluate suspected adrenal insufficiency by measuring cortisol response after synthetic ACTH exposure.
Therapeutic uses: Historically, ACTH preparations were used to treat severe inflammatory and autoimmune conditions. In contemporary practice, ACTH remains indicated for certain pediatric conditions, notably infantile spasms (West syndrome) when other therapies fail or are unsuitable. ACTH therapy has also been employed in selected acute exacerbations of autoimmune diseases and inflammatory illnesses, but many guidelines favor other first-line treatments due to differential efficacy, safety, and cost considerations.
Historical and modern context: ACTH therapies have evolved alongside the use of other glucocorticoids, such as high-dose steroids, with decisions guided by clinical trial data, patient-specific risk profiles, and cost-benefit analyses. For discussions of specific disease contexts, see Infantile spasms and Multiple sclerosis.

Forms, administration, and pharmacology

Therapeutic corticotropin products: Historically, some ACTH preparations were derived from porcine pituitary tissue and used in a broad range of indications. Modern diagnostic practice frequently employs synthetic fragments such as cosyntropin for stimulation testing.
Dosing and routes: Diagnostic cosyntropin typically involves a fixed dose given intramuscularly or intravenously, with cortisol levels measured to assess adrenal reserve. Therapeutic ACTH products are administered according to condition-specific regimens and patient weight, sometimes via intramuscular or intravenous routes.
Pharmacokinetics and dynamics: The pharmacodynamic response is mediated by the adrenal cortex’s capacity to produce glucocorticoids, with systemic effects reflecting cortisol levels rather than the peptide itself. Side effects largely track glucocorticoid exposure rather than direct ACTH action.

Safety, side effects, and patient considerations

Common adverse effects: Long-term or high-dose exposure to corticotropin therapies can produce Cushingoid features, hyperglycemia, edema, hypertension, osteoporosis, and increased susceptibility to infection due to immunosuppressive effects of glucocorticoids.
Special populations: Pediatric patients receiving ACTH for infantile spasms require careful dosing and monitoring for growth, bone health, and metabolic effects, while adults must be mindful of metabolic and psychiatric consequences.
Drug interactions and care: When corticotropin therapy is used, clinicians monitor for interactions with antidiabetic agents, antihypertensives, and drugs that affect immune function. See Adrenal cortex and Glucocorticoids for broader context on related pharmacology.

Controversies and policy considerations

Evidence base and competing therapies: A central debate concerns when ACTH offers advantages over high-dose glucocorticoids or other immunomodulatory therapies, particularly in infantile spasms and autoimmune flares. Critics emphasize that, in many conditions, similar clinical outcomes can be achieved with less-expensive or safer alternatives, challenging the routine use of expensive corticotropin formulations.
Cost, access, and incentives: ACTH products, especially the natural preparations, have faced critical scrutiny for cost and supply stability. From a policy and market perspective, debates focus on whether patent protections, manufacturing incentives, and market competition adequately balance patient access with encouraging innovation.
Public health and equity: The translational question—do all patient groups have equitable access to ACTH therapies and the diagnostic tests that depend on cosyntropin—remains a topic of discussion in health-system planning and reimbursement decisions.
Skeptical viewpoints and counterpoints: Proponents argue that ACTH’s unique pharmacology can offer advantages in select patients or refractory cases where glucocorticoids have limited efficacy or tolerability. Detractors contend that, where evidence is lacking or cost is prohibitive, clinicians should prioritize safer, cheaper, or more thoroughly studied alternatives. The practical stance tends to emphasize rigorous patient selection, dosing prudence, and adherence to the best available evidence.