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Adrenocorticotropic hormone (ACTH)

Adrenocorticotropic Hormone (ACTH)

Definition:

Adrenocorticotropic hormone (ACTH) is a peptide hormone produced by the anterior pituitary gland that stimulates the adrenal cortex to secrete cortisol, a crucial hormone involved in stress response, metabolism, and immune regulation. ACTH plays a central role in the hypothalamic-pituitary-adrenal (HPA) axis, ensuring homeostasis during physiological and pathological conditions.

Symptoms of Dysregulation:

Abnormal ACTH levels can lead to various clinical manifestations depending on whether there is excess or deficiency:

• Cushing’s Syndrome: Excess ACTH results in hypercortisolism, causing symptoms such as weight gain, hypertension, muscle weakness, and central adiposity [3][6].
• Addison’s Disease: Deficient ACTH leads to adrenal insufficiency, characterized by fatigue, weight loss, hypotension, and hyperpigmentation [1][4].
• Mood Disorders: Dysregulated ACTH levels are associated with anxiety, depression, and cognitive impairments due to altered cortisol secretion [5].

Causes of Abnormal Levels:

ACTH dysregulation can result from several factors:

• Pituitary Tumors: Overproduction of ACTH from pituitary adenomas causes Cushing’s disease [6][7].
• Adrenal Disorders: Adrenal insufficiency or hyperplasia affects the feedback regulation of ACTH [2][5].
• Ectopic ACTH Production: Non-pituitary tumors may produce ACTH autonomously, leading to ectopic Cushing’s syndrome [3][7].
• Autoimmune Conditions: Autoimmune destruction of the pituitary gland can result in isolated ACTH deficiency [1].

Clinical Significance:

Monitoring and managing ACTH levels are critical for addressing endocrine disorders:

• Cushing’s Syndrome: Chronic high cortisol due to elevated ACTH can lead to metabolic syndrome and cardiovascular complications [3][6].
• Adrenal Insufficiency: Untreated low ACTH levels can result in life-threatening Addisonian crises [1][4].
• Subclinical Hypercortisolism: Even mild elevations in ACTH can cause long-term health effects such as osteoporosis and diabetes [7].

Diagnosis:

Diagnosing abnormalities in ACTH secretion involves:

• Plasma ACTH Measurement: Evaluating circulating ACTH levels alongside cortisol levels for adrenal function assessment [5][6].
• Dynamic Testing: Tests such as the dexamethasone suppression test or corticotropin-releasing hormone (CRH) stimulation test help identify the source of dysregulation [3][7].
• Imaging Studies: MRI or CT scans are used to detect pituitary or adrenal abnormalities [6].

Treatment:

Management strategies for ACTH-related disorders include:

• Medications: Corticosteroid replacement for adrenal insufficiency or cortisol-lowering drugs like ketoconazole for hypercortisolism [3][6].
• Surgical Interventions: Removal of pituitary adenomas or ectopic ACTH-producing tumors when indicated [3][7].
• Hormonal Therapy: Long-term hormonal balance may require tailored therapies based on individual needs [6].

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References:

1. Isolated Adrenocorticotropic Hormone Deficiency – PubMed. DOI: 10.7759/cureus.9270
2. Role of ACTH in the Interactive/Paracrine Regulation of Adrenal Function – Frontiers in Endocrinology. DOI: 10.3389/fendo.2016.00098
3. Dynamics of ACTH and Cortisol Secretion – Endocrine Reviews. DOI: 10.1210/edrv/bnaa002
4. Subclinical Cushing’s Disease with High-Molecular-Weight Forms – Wiley Online Library. DOI: 10.1155/2024/8721614
5. The Mechanisms Underlying Autonomous Adrenocorticotropic Hormone Secretion – MDPI International Journal of Molecular Sciences. DOI: 10.3390/ijms21239132