- Adrenocorticotropic hormone (ACTH), also known as corticotropin, is a crucial peptide hormone produced and secreted by the anterior pituitary gland.
- It plays a vital role in the hypothalamic-pituitary-adrenal (HPA) axis, serving as the primary stimulator of the adrenal cortex, particularly the zona fasciculata, to produce and release glucocorticoids, most notably cortisol. Cortisol is essential for a wide range of physiological processes, including stress response, metabolism regulation, immune function, and blood pressure maintenance.
- ACTH is synthesized from a larger precursor protein called pro-opiomelanocortin (POMC). When POMC is cleaved in the anterior pituitary, it gives rise to several biologically active peptides, including ACTH, β-endorphin, and melanocyte-stimulating hormones (MSHs). ACTH is secreted in response to corticotropin-releasing hormone (CRH), which is released by the hypothalamus. CRH travels through the hypophyseal portal system to reach the anterior pituitary, where it stimulates ACTH production.
- Once released into the bloodstream, ACTH travels to the adrenal glands, which sit atop the kidneys. There, it binds to specific melanocortin 2 receptors (MC2R) on adrenal cortical cells. This binding activates a signaling cascade that leads to the production and secretion of cortisol. In turn, cortisol exerts a negative feedback effect on both the hypothalamus and pituitary gland to suppress further CRH and ACTH release, maintaining hormonal balance.
- The secretion of ACTH follows a diurnal (circadian) rhythm, with peak levels in the early morning (typically around 6–8 a.m.) and the lowest levels at night. This rhythm is influenced by light-dark cycles and the suprachiasmatic nucleus of the hypothalamus, which synchronizes the HPA axis with the body’s internal clock. The release of ACTH is also markedly elevated during stress, both physical and psychological, enabling the body to respond with increased cortisol production—enhancing energy availability, blood glucose levels, and anti-inflammatory mechanisms.
- ACTH is also clinically significant. Elevated ACTH levels can be seen in conditions such as Addison’s disease (primary adrenal insufficiency), where the adrenal glands fail to produce adequate cortisol, prompting a compensatory rise in ACTH. High ACTH can also result from Cushing’s disease, a condition caused by a pituitary adenoma that secretes excess ACTH, leading to hypercortisolism. In contrast, low ACTH levels are seen in secondary adrenal insufficiency, where the pituitary fails to produce adequate ACTH, often due to tumors, trauma, or long-term corticosteroid therapy.
- ACTH measurement is used diagnostically in various endocrine evaluations. The ACTH stimulation test is a standard procedure to assess adrenal function by evaluating the cortisol response to synthetic ACTH. Similarly, ACTH levels are monitored in patients with adrenal or pituitary disorders, as well as in those being weaned off chronic steroid therapy to assess recovery of the HPA axis.
