ACTH: all you need to know about the corticotropic hormone

ACTH: all you need to know about the corticotropic hormone

ACTH is a hormone secreted by the pituitary gland. It acts on the production of cortisol (stress hormone) by the adrenal glands. Too high or on the contrary too low blood levels of ACTH are symptomatic of certain chronic diseases: pituitary or adrenal tumors and insufficiencies or even certain digestive or pulmonary cancers.

What is ACTH?

The corticotropic hormone or adrenocorticotropic hormone or even adrenocorticotrophin (ACTH, Adreno CorticoTropic Hormone) is a polypeptide hormone of 39 amino acids and a mass of 4500 daltons.

It is secreted by basophil cells in the anterior lobe of the pituitary gland. It acts on the adrenal gland by increasing its production of cortisol (also called stress hormone), aldosterone (hormone contributing to the maintenance of plasma volume, blood pressure and serum potassium) but also steroid sex hormones ( such as DHEA or dehydroepiandrosterone, androstenedione and testosterone).

There are pathologies characterized by deregulation of ACTH secretion, this is particularly the case of Cushing’s syndrome and Addison’s disease.

ACTH in the stress circuit

In a situation of physical or psychological stress (fever, pain, infection, fatigue, activity or intense emotion, etc.), l hypothalamus secretes a greater amount of Corticotropin-Releasing hormone (CRH). This hormone stimulates the cells of the anterior and intermediate pituitary gland that produce ACTH. The latter acts on a membrane receptor of the adrenal cortex. This results in the release of cortisol from the fascicular area of ​​the adrenal cortex. Cortisol will operate a negative feedback on the hypothalamic-pituitary axis.

ACTH dosage

When should an ACTH test be performed?

Usually, a dosage of ACTH is prescribed by the doctor:

  • in the event of clinical signs suggestive of certain endocrine pathologies: Cushing’s syndrome, ectopic production of ACTH, tumor of the adrenal glands, Addison’s disease, pituitary insufficiency, etc. ;
  • when taking certain medications such as corticosteroids, insulin, amphetamines, etc. ;
  • if blood tests show altered cortisol levels.

A blood test morning and evening

ACTH is a hormone with a circadian cycle and a pulsatile secretion. In other words, his blood levels vary depending on the time of day and night. Its concentration is maximum before waking up (around 6 a.m.) and minimal in the evening before going to bed (around 23 p.m.). The ACTH dosage must therefore be carried out in the morning and in the evening.

The assay is performed by puncture of a blood sample at the crease of the elbow. This test simultaneously measures blood levels of cortisol. In fact, blood cortisol regulates the release of ACTH: this increases when cortisol is low, and conversely, decreases when blood cortisol is high.

ACTH and cortisol: which reference values?

ACTH and cortisol should first be measured in the morning, at the time of their peak: between 6 and 9 a.m.

At 8 a.m.:

  • normal ACTH levels are between 10 and 50 pg / ml;
  • normal cortisol levels are between 70 and 130 µg/l.

Between 18 p.m. and midnight, these rates are greatly reduced:

  • ACTH <10 pg / ml;
  • Cortisol < 20 µg/l.

Anomalies, pathologies linked to an abnormal level of ACTH

I have too high an ACTH dosage

  • An increased ACTH level may be a sign of Cushing syndrome, most commonly linked to an ACTH-secreting pituitary tumor. The latter is generally benign, we are talking aboutpituitary adenoma;
  • A high ACTH level can also be a sign of production ectopique d’ACTH(i.e. outside the pituitary gland) due to a benign tumor (eg a bronchial carcinoid) or malignant (such as a small cell lung tumor);
  • Finally, an increase in ACTH levels is symptomatic of Addison’s disease. The latter can be caused by an infection of the adrenal glands (such as tuberculosis), an autoimmune disorder (in particular in the context of autoimmune polyendocrinopathy) or even by mutations of ACTH receptors (this is called resistance to ACTH).

I have a low dosage of ACTH

Collapsed levels of ACTH may bee a sign of pituitary insufficiency (whether or not complicated by adrenal insufficiency) or a tumor of the adrenal glands.

Pathologies

Cortisol

ACTH

Cushing’s disease (ACTH-secreting pituitary tumor)

High

High

Adrenal tumor

High

Weakened

Ectopic production of ACTH, i.e. production by an extra-pituitary tumor (most commonly pulmonary or digestive)

High

High

Addison’s disease (primary adrenal insufficiency)

Weakened

High

Pituitary insufficiency

Weakened

Decreases

Treatment

The treatments depend on the pathology being treated.

PathologiesTreatments
Cushing’s diseaseThe treatment strategy differs depending on the cause and severity of the disease:
  • pituitary surgery;
  • bilateral adrenalectomy;
  • drugs that affect the production of cortisol;
  • drugs acting on pituitary adenoma;
  • drugs that affect the effect of cortisol;
  • pituitary radiotherapy;
  • hydrocortisone ;
  • other hormone replacement.
Adrenal tumor
  • unilateral adrenalectomy;
  • drugs that decrease cortisol production;
  • adrenal replacement therapy.
Production ectopique d’ACTH
  • management of endocrine tumor;
  • bilateral adrenalectomy;
  • drug that decreases the production of cortisol;
  • adrenal replacement therapy.
Addison’s diseaseHormone replacement therapy:
  • hydrocortisone ;
  • fludrocortisone.
Pituitary insufficiencyHormonal supplements such as steroids, growth hormones, cortisols …

Diagnostic

The dosage of ACTH is prescribed:

  • after a dosage of cortisol whose values ​​have collapsed;
  • in case of symptoms suggestive of adrenal or pituitary disease.

(see paragraph “ACTH assay” for ACTH reference values).

In some cases, the results of ACTH assays are not exhaustive.

Dynamic tests which aim to modify the secretions of ACTH and / or cortisol by the effect of drugs, are then necessary to clarify the diagnosis. The most commonly used drugs are tetracosactide (Synacthene®) and dexamethasone. Other drugs are sometimes used: insulin, corticoliberin and Metopyrone.

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