ACTH - Adrenocorticotropic Hormone
How does the hypothalamic-pituitary-adrenal axis work?
ACTH secretion is part of a hormonal cascade finely regulated by a negative feedback mechanism:
| Step | Gland or structure | Secreted hormone | Action |
|---|---|---|---|
| 1 | Hypothalamus | CRH (corticorelin) | Stimulates the release of ACTH by the pituitary gland |
| 2 | Anterior pituitary | ACTH | Stimulates the adrenal glands to produce cortisol |
| 3 | Adrenal glands (cortex) | Cortisol | Exerts its effects in the body (metabolism, immunity, stress) |
| 4 | Negative feedback | Cortisol (in return) | Inhibits the secretion of CRH and ACTH to maintain hormonal balance |
ACTH is secreted in pulses and follows a marked circadian rhythm: its level is highest in the early morning (between 6 a.m. and 8 a.m.) and lowest in the late evening. This rhythm directly influences cortisol secretion, which follows the same diurnal profile. This is why ACTH dosage samples must be taken fasting in the morning.
The ACTH's roles are: * Stimulate the adrenal cortex to produce and secrete glucocorticoids, mineralocorticoids, and adrenal androgens. * Maintain the structure of the adrenal cortex. * Have a trophic effect on the adrenal cortex.
- Stimulation of cortisol synthesis and secretion by the adrenal cortex's zona fasciculata, the principal physiological role of ACTH
- Stimulation of adrenal androgen production (DHEA, androstenedione) by the zona reticularis of the adrenal cortex
- Trophicity of the adrenal cortex: in the absence of ACTH over a long period, the adrenal glands gradually atrophy
- Minor stimulation of aldosterone production by the glomerulosa zone, although the main regulation of aldosterone depends on the renin-angiotensin system.
- Melanotropic effect: at very high levels, ACTH can stimulate skin melanocytes and cause hyperpigmentation, due to its molecular structure shared with MSH (melanocyte-stimulating hormone).
The ACTH dosage is prescribed in the following contexts:
- Suspicion of adrenal insufficiency (Addison's disease or secondary insufficiency of pituitary origin): profound chronic fatigue, orthostatic hypotension, weight loss, nausea, skin hyperpigmentation
- Suspicion of Cushing's syndrome: truncal obesity, purple striae, hypertension, diabetes, proximal muscle weakness, osteoporosis
- Evaluation of unexplained diffuse cutaneous hyperpigmentation
- Exploration of a pituitary mass (corticotroph adenoma) discovered on imaging
- Post-surgical follow-up of an operated adrenal or pituitary tumor
- Evaluation of ectopic ACTH secretion in the workup for neoplasia
- Follow-up of long-term corticosteroid treatment to assess HHS axis suppression
How to interpret the results?
ACTH should never be interpreted alone: it must always be correlated with the cortisol level taken at the same time, and placed in the patient's clinical context. Reference values vary depending on the laboratory and assay methods.
| ACTH test result (morning) | Cortisol related | Probable diagnostic orientation |
|---|---|---|
| Normal (10 to 60 pg/mL) | Normal | Functional HHS Axe, no significant anomalies |
| Elevated (> 60 pg/mL) | Bass | Primary adrenal insufficiency (Addison's disease): the adrenal glands do not respond despite intense pituitary stimulation |
| Low or undetectable | Bass | Secondary (pituitary origin) or tertiary (hypothalamic origin) adrenocortical insufficiency, or suppression by exogenous corticosteroids |
| Elevated (> 60 pg/mL) | Raised | ACTH-dependent Cushing's syndrome: corticotroph pituitary adenoma (Cushing's disease) or ectopic ACTH secretion (lung tumor, carcinoid) |
| Low or undetectable | Raised | Cushing's syndrome ACTH-independent: autonomous adrenal adenoma or carcinoma producing cortisol without ACTH stimulation |
The main diseases associated with an ACTH abnormality are Cushing's disease and Addison's disease.
| Illness | ACTH | Cortisol | Key Features |
|---|---|---|---|
| Addison's disease | Very high | Bass | Autoimmune (80 % of cases) or infectious destruction of the adrenal glands. Profound fatigue, hypotension, skin and mucous membrane hyperpigmentation, hyponatremia, hyperkalemia |
| Secondary adrenal insufficiency | Low | Bass | Pituitary ACTH deficiency (adenoma, surgery, radiotherapy, trauma) or suppression by prolonged exogenous corticosteroids. No hyperpigmentation or major electrolyte disturbance. |
| Cushing's disease | High | Very high | Corticotroph pituitary adenoma secreting excess ACTH. Facio-trunk obesity, purple striae, hypertension, diabetes, osteoporosis, skin fragility |
| Ectopic ACTH secretion | Very high | Very high | ACTH production by a non-pituitary tumor (small cell lung cancer, bronchial carcinoid tumor, thymoma). Often severe and rapidly developing Cushing's syndrome |
| Cortisol-secreting adrenal adenoma | Very low | Raised | Autonomous adrenal tumor producing cortisol independently of ACTH. Negative feedback inhibits pituitary ACTH secretion. |
What are the complementary tests associated with ACTH testing?
- Morning plasma cortisol: measured simultaneously, essential for ACTH interpretation
- Synacthen (tetracosactide) stimulation test: IV or IM injection of synthetic ACTH and measurement of cortisol at 30 and 60 minutes, to assess adrenal reserve and confirm adrenal insufficiency.
- Dexamethasone suppression test: taking dexamethasone the night before and measuring cortisol the next morning to screen for hypercortisolism (Cushing's syndrome)
- 24-hour urinary cortisol: measurement of urinary free cortisol, a reflection of total daily cortisol production
- Pituitary MRI with gadolinium injection: Search for a corticotroph microadenoma in case of suspected Cushing's disease
- Adrenal scan: visualization of the adrenal glands, search for adenoma, hyperplasia, or carcinoma
- Inferior Petrosal Sinus Sampling (IPSS): A reference invasive examination to differentiate pituitary adenoma from ectopic ACTH secretion in difficult cases
Consult at Clinique Omicron
If you are experiencing symptoms suggestive of adrenal or pituitary dysfunction, such as unexplained and persistent fatigue, weight gain centered on the abdomen, skin hyperpigmentation, low blood pressure, or metabolic disorders, Clinique Omicron physicians, at its service points in Quebec, can initiate the appropriate hormonal assessment, interpret the results, and refer you to an endocrinologist based on your clinical presentation.
The content of this page is provided for informational purposes only and is not intended to replace the advice of a qualified healthcare professional. Consult a physician for any symptoms, questions or decisions you may have regarding your health.
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