Adrenocorticotropic Hormone (ACTH)
Composed By Muhammad Aqeel Khan
Date 16/1/2026
Composed By Muhammad Aqeel Khan
Date 16/1/2026
Introduction to Adrenocorticotropic Hormone (ACTH)
Adrenocorticotropic hormone (ACTH) is a vital hormone that plays a central role in the body’s response to stress, metabolism, immune regulation, and overall hormonal balance. It is a key component of the endocrine system, acting as a messenger between the brain and the adrenal glands. ACTH regulates the production of cortisol, a hormone essential for survival, particularly during physical and psychological stress.
Because abnormalities in ACTH secretion can lead to serious disorders such as Cushing’s disease and adrenal insufficiency, understanding how ACTH works is essential for students, healthcare professionals, and anyone interested in human physiology. This article provides a detailed explanation of what ACTH is, how it is regulated, its functions, related disorders, diagnostic testing, and its broader health significance.
What Is Adrenocorticotropic Hormone?
Structure and Origin in the Pituitary Gland
ACTH is derived from a larger precursor molecule called proopiomelanocortin (POMC). When POMC is broken down, it produces ACTH along with other biologically active peptides. This molecular origin explains why ACTH is linked to several physiological processes beyond cortisol regulation.
Relationship with the Hypothalamus
The release of ACTH is tightly controlled by the hypothalamus, a region of the brain that links the nervous system to the endocrine system. The hypothalamus secretes corticotropin-releasing hormone (CRH), which stimulates the pituitary gland to release ACTH. This close relationship ensures precise hormonal control in response to stress and internal balance.
Production and Regulation of ACTH
Role of Corticotropin-Releasing Hormone (CRH)
ACTH secretion begins in the hypothalamus with the release of CRH. When the body experiences stress such as illness, injury, emotional strain, or low blood sugar CRH levels rise. CRH then signals the anterior pituitary to increase ACTH secretion into the bloodstream.
This process allows the body to respond quickly to changing conditions and maintain homeostasis.
Feedback Regulation via Cortisol
ACTH regulation operates through a negative feedback mechanism involving cortisol. Once ACTH stimulates the adrenal glands to release cortisol, rising cortisol levels signal both the hypothalamus and pituitary gland to reduce CRH and ACTH secretion. This feedback loop prevents excessive hormone production and maintains hormonal balance.
ACTH in the Hypothalamic–Pituitary–Adrenal (HPA) Axis
ACTH is a central component of the hypothalamic–pituitary–adrenal (HPA) axis, one of the body’s most important regulatory systems. The HPA axis controls stress response, immune function, energy metabolism, and circadian rhythms. Disruption of this axis can lead to hormonal disorders, mental health conditions, and metabolic disease.
Functions of ACTH
Stimulation of Cortisol Secretion
The primary ACTH function is to stimulate the adrenal cortex to produce and release cortisol. Cortisol helps regulate:
-
Blood glucose levels
-
Blood pressure
-
Fat, protein, and carbohydrate metabolism
-
Inflammatory and immune responses
Without adequate ACTH, cortisol production decreases, leading to serious health consequences.
Effects on Metabolism, Stress Response, and Immune Function
ACTH indirectly influences many physiological systems through cortisol. During stress, ACTH-driven cortisol release provides the body with energy by increasing glucose availability. It also suppresses excessive immune reactions, preventing harmful inflammation.
In this way, ACTH is essential for both short-term survival and long-term physiological stability.
ACTH and Cortisol Balance
How ACTH Controls Adrenal Hormones
ACTH primarily targets the zona fasciculata of the adrenal cortex, where cortisol is produced. While ACTH has minor effects on other adrenal hormones, its strongest influence is on cortisol synthesis and release.
Balanced ACTH secretion ensures appropriate cortisol levels throughout the day, following a circadian rhythm with peak levels in the early morning and lowest levels at night.
Normal vs. Abnormal Hormone Levels
Normal ACTH levels vary depending on the time of day and individual physiology. Abnormal levels may indicate pituitary or adrenal disorders. Persistently high or low ACTH levels disrupt cortisol balance and contribute to disease development.
Disorders Related to ACTH Imbalance
ACTH Excess and Cushing’s Disease
ACTH excess is most commonly associated with Cushing’s disease, a condition caused by an ACTH-secreting pituitary tumor. Excess ACTH leads to excessive cortisol production, resulting in symptoms such as:
-
Weight gain, especially in the face and trunk
-
High blood pressure
-
Muscle weakness
-
Osteoporosis
-
Diabetes
-
Mood changes
Another cause of ACTH excess is ectopic ACTH syndrome, where ACTH is produced by non-pituitary tumors, often in the lungs.
ACTH Deficiency and Adrenal Insufficiency
ACTH deficiency occurs when the pituitary gland fails to produce sufficient ACTH. This leads to secondary adrenal insufficiency, characterized by low cortisol levels. Symptoms may include:
-
Chronic fatigue
-
Weight loss
-
Low blood pressure
-
Hypoglycemia
-
Weakness
In contrast, Addison’s disease is a primary adrenal disorder where the adrenal glands themselves fail, often resulting in elevated ACTH levels due to lack of cortisol feedback.
ACTH Testing and Diagnosis
ACTH Blood Test and Normal Ranges
The ACTH test measures the concentration of ACTH in the blood and is usually performed in the morning when levels are highest. Results are interpreted alongside cortisol levels to identify the underlying cause of hormonal imbalance.
Normal ACTH levels vary by laboratory but typically fall within a defined reference range when measured under standardized conditions.
Role in Diagnosing Endocrine Disorders
ACTH testing is essential in diagnosing:
-
Cushing’s disease
-
Ectopic ACTH syndrome
-
Addison’s disease
-
Secondary adrenal insufficiency
Dynamic tests, such as the ACTH stimulation test and dexamethasone suppression test, provide further insight into HPA axis function.
Clinical and Health Significance of ACTH
Importance in Stress Response and Chronic Illness
ACTH plays a crucial role in the body’s ability to respond to stress. Chronic stress can dysregulate ACTH secretion, contributing to fatigue, immune dysfunction, and metabolic disorders. Abnormal ACTH activity has also been linked to depression, anxiety, and inflammatory diseases.
Relevance in Endocrinology and Medicine
In clinical medicine, ACTH is fundamental to endocrinology. It guides diagnosis, treatment decisions, and long-term management of hormonal disorders. Synthetic ACTH is also used in diagnostic testing and certain therapeutic applications.
Conclusion
Adrenocorticotropic hormone (ACTH) is a cornerstone of endocrine regulation, linking the brain to the adrenal glands through the HPA axis. By controlling cortisol secretion, ACTH influences metabolism, immune response, stress adaptation, and overall health. Disorders of ACTH excess or deficiency can lead to serious conditions such as Cushing’s disease and adrenal insufficiency.
Understanding ACTH function, regulation, testing, and clinical significance is essential for early diagnosis and effective treatment of endocrine disorders. Continued research and clinical awareness remain critical to maintaining hormonal balance and long-term health.
References
-
Guyton, A. C., & Hall, J. E. Textbook of Medical Physiology. Elsevier.
-
Melmed, S. et al. Williams Textbook of Endocrinology. Elsevier.
-
National Institutes of Health (NIH). Adrenocorticotropic Hormone (ACTH).
-
Endocrine Society. Clinical Practice Guidelines on Cushing’s Syndrome.
-
Mayo Clinic. ACTH Test and Adrenal Disorders.
-
StatPearls Publishing. Physiology, Adrenocorticotropic Hormone.