Adrenocorticotropin (ACTH)

Updated: June 24, 2024

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Background

The ACTH hormone is a polypeptide hormone. It is produced by anterior pituitary gland. It is used as a drug and a diagnostic tool. ACTH is important in the hypothalamic-pituitary-adrenal axis. The principal effect of CATH are increased level of synthesis and excretion of androgen and cortisol by the medulla and cortex of adrenal gland. ACTH produces and releases adrenal hormones. It also maintains the size, shape, and function of the adrenal glands.

Numerous species have a connection between ACTH and the circadian cycle. There are two pattern by which ACTH secreted. The circadian rhythm at its highest point between 4 am and 7 am and reaches its lowest point between 11 pm and 3 am. Secretory bursts occur around 40 times each day. These are the characteristic of the ultradian pulsatility pattern.

Pre-pro-opiomelanocortin or pre-POMC is the precursor of ACTH. Before the endopeptidases break, post-translations changes occur. This includes glycosylation and phosphorylation. This process leads to the formation of different and various polypeptide fragments. It includes physiological activities like melanotropin alpha (α-MSH), melanotropin gamma (γ-MSH), lipotropin beta (β-LPH), lipotropin gamma (γ-LPH), beta-endorphin, and ACTH.

Corticotropin-releasing hormone released by the hypothalamus. It is inhibited by glucocorticoids. This can lead to reduced level of ACTH in anterior pituitary. These compounds are important for controlling the physiological processes of the organism.

Indications/Applications

Throughout the day, due to changes and irregular secretion patterns the diagnostic usefulness of random plasma ACTH levels is limited. To understand plasma ACTH levels better it is essential to conduct tests involving elements of the HPA axis. When there is ACTH production, stimulatory tests such as CRH or induced hypocortisolism are necessary.

In cases of Cushing’s disease, which involves cortisol due to a tumor producing ACTH (usually benign) serum cortisol analysis is preferred over plasma ACTH for dexamethasone suppression testing because it offers more consistent results.

Nelson syndrome occurs when there are increased plasma ACTH levels due to a lack of cortisol feedback inhibition and uncontrolled activity following bilateral adrenalectomy.

Distinguishing between Pituitary and ectopic Cushing syndrome from Cushing syndrome can be done by observing plasma ACTH levels. Some adrenal adenomas decrease ACTH production leading to Cushing syndrome. Surgical procedures can suppress the HPA axis causing adrenal insufficiency necessitating short term cortisol replacement.

In cases of insufficiency (Addisons disease) damage to the adrenal glands results in reduced cortisol release.

Secondary adrenal insufficiency occurs when there is a decrease, in induced release of cortisol.

The ACTH test is performed when there is an increase level of cortisol and symptoms are present like:

Fatigue

Weight gain

Weakness or low energy

Acne

Extra fat present in shoulder and neck

Thin arms and thin legs

Hyperpigmentation

Pink or purple spots on the body like under the arms, hips, breasts, stomach

The ACTH test is performed when there is a decrease level of cortisol and symptoms are present like:

Abdominal pain

Weight loss

Loss of appetite

Nausea

Vomiting

Diarrhea

Weakness or low energy

Fatigue

Dark spots on the different areas of skin

Assessment of ACTH:

The provocative CRH stimulation test involves inserting an IV line 30 minutes before a test to prevent cortisol levels. Blood samples are taken at intervals before and after CRH administration with doses ranging from 1 µg/Kg to 200 µg/Kg.

To differentiate between Cushing’s disease and an ectopic ACTH secreting tumor petrosal sampling can be combined with the test. The dexamethasone CRH test has shown 100% accuracy, in distinguishing between Cushing’s syndrome and pseudo-Cushing’s states.

Reference Range

Normal range of ACTH in adult and elder:

Male: 7 pg/mL – 69 pg/mL

Female: 6 pg/mL – 58 pg/mL

ACTH level in children whose age is a between 10 to 18 years is 6 pg/mL to 55 pg/mL and whose age is between 1 week to 9 years is 5 pg/mL to 46 pg/mL.

Men and pregnant female have increased level of ACTH.

Each laboratory has a different normal range for ACTH.

Interpretation

In the HPA axis, adrenal cortisol and hypothalamic CRH are also present. This affects the ACTH level. Apart from these, stress, diurnal fluctuations, and cortisol feedback inhibition also affect the plasma level of ACTH.

The ACTH level can be increased because of diseases like:

Pseudo-cushing disease which include alcoholism, depression, and anorexia nervosa

Cushing disease which includes ACTH-producing pituitary adenoma

Ectopic CRH-producing (nonpituitary) tumor

Ectopic ACTH-producing (nonpituitary) tumor

The ACTH level can be increased because of the conditions like deficiency in 17-α-hydroxylase, 21-hydroxylase, 11-β-hydroxylase (CYP11B1), 3-β-hydroxysteroid dehydrogenase, 3-β-hydroxysteroid dehydrogenase and cholesterol side-chain cleavage enzyme. Apart from this, addition disease, nelson disease, congenital adrenal hyperplasia can also increase the ACTH level.

The ACTH level can be decreased because of diseases like:

Pituitary adenoma

Pituitary corticotrophin disease

Pituitary radiotherapy

Pituitary stalk or hypothalamic structural abnormalities like craniopharyngioma

Hypothalamic CRH deficiency

Infiltrative diseases of the hypothalamus like fungal infections, sarcoid, tuberculosis, histiocytosis X

Drug-induced hypophysitis (ipilimumab [Yervoy])

Autoimmune hypophysitis

Hemorrhage, infection, or damaging injuries on the sella turcica

Traumatic brain injury

Congenital ACTH deficiency

The ACTH level can be suppressed by the conditions like cortisolnproducing adrenal adenoma and chronic glucocorticoid therapy.

Collection And Panels

Collection:

Sample type: Whole blood

Container: Lavender top tube (EDTA tube) or Siliconized glass

Sample preparation: Serum is separated from cells and transfer in a transport tube.

Storage instructions: Sample is stored for 14 days in frozen state.

Rejected samples: Hemolyzed specimen

Considerations: The ACTH test requires no preparation. The preferred time for the ACTH test is 6 am to 9 am.

Panel:

Along with the ACTH test, other tests which include are CRH stimulation test, Metyrapone stimulation test, Insulin-induced hypoglycemia test, ACTH stimulation test.

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Adrenocorticotropin (ACTH)


The ACTH hormone is a polypeptide hormone. It is produced by anterior pituitary gland. It is used as a drug and a diagnostic tool. ACTH is important in the hypothalamic-pituitary-adrenal axis. The principal effect of CATH are increased level of synthesis and excretion of androgen and cortisol by the medulla and cortex of adrenal gland. ACTH produces and releases adrenal hormones. It also maintains the size, shape, and function of the adrenal glands.

Numerous species have a connection between ACTH and the circadian cycle. There are two pattern by which ACTH secreted. The circadian rhythm at its highest point between 4 am and 7 am and reaches its lowest point between 11 pm and 3 am. Secretory bursts occur around 40 times each day. These are the characteristic of the ultradian pulsatility pattern.

Pre-pro-opiomelanocortin or pre-POMC is the precursor of ACTH. Before the endopeptidases break, post-translations changes occur. This includes glycosylation and phosphorylation. This process leads to the formation of different and various polypeptide fragments. It includes physiological activities like melanotropin alpha (α-MSH), melanotropin gamma (γ-MSH), lipotropin beta (β-LPH), lipotropin gamma (γ-LPH), beta-endorphin, and ACTH.

Corticotropin-releasing hormone released by the hypothalamus. It is inhibited by glucocorticoids. This can lead to reduced level of ACTH in anterior pituitary. These compounds are important for controlling the physiological processes of the organism.

Throughout the day, due to changes and irregular secretion patterns the diagnostic usefulness of random plasma ACTH levels is limited. To understand plasma ACTH levels better it is essential to conduct tests involving elements of the HPA axis. When there is ACTH production, stimulatory tests such as CRH or induced hypocortisolism are necessary.

In cases of Cushing’s disease, which involves cortisol due to a tumor producing ACTH (usually benign) serum cortisol analysis is preferred over plasma ACTH for dexamethasone suppression testing because it offers more consistent results.

Nelson syndrome occurs when there are increased plasma ACTH levels due to a lack of cortisol feedback inhibition and uncontrolled activity following bilateral adrenalectomy.

Distinguishing between Pituitary and ectopic Cushing syndrome from Cushing syndrome can be done by observing plasma ACTH levels. Some adrenal adenomas decrease ACTH production leading to Cushing syndrome. Surgical procedures can suppress the HPA axis causing adrenal insufficiency necessitating short term cortisol replacement.

In cases of insufficiency (Addisons disease) damage to the adrenal glands results in reduced cortisol release.

Secondary adrenal insufficiency occurs when there is a decrease, in induced release of cortisol.

The ACTH test is performed when there is an increase level of cortisol and symptoms are present like:

Fatigue

Weight gain

Weakness or low energy

Acne

Extra fat present in shoulder and neck

Thin arms and thin legs

Hyperpigmentation

Pink or purple spots on the body like under the arms, hips, breasts, stomach

The ACTH test is performed when there is a decrease level of cortisol and symptoms are present like:

Abdominal pain

Weight loss

Loss of appetite

Nausea

Vomiting

Diarrhea

Weakness or low energy

Fatigue

Dark spots on the different areas of skin

Assessment of ACTH:

The provocative CRH stimulation test involves inserting an IV line 30 minutes before a test to prevent cortisol levels. Blood samples are taken at intervals before and after CRH administration with doses ranging from 1 µg/Kg to 200 µg/Kg.

To differentiate between Cushing’s disease and an ectopic ACTH secreting tumor petrosal sampling can be combined with the test. The dexamethasone CRH test has shown 100% accuracy, in distinguishing between Cushing’s syndrome and pseudo-Cushing’s states.

Normal range of ACTH in adult and elder:

Male: 7 pg/mL – 69 pg/mL

Female: 6 pg/mL – 58 pg/mL

ACTH level in children whose age is a between 10 to 18 years is 6 pg/mL to 55 pg/mL and whose age is between 1 week to 9 years is 5 pg/mL to 46 pg/mL.

Men and pregnant female have increased level of ACTH.

Each laboratory has a different normal range for ACTH.

In the HPA axis, adrenal cortisol and hypothalamic CRH are also present. This affects the ACTH level. Apart from these, stress, diurnal fluctuations, and cortisol feedback inhibition also affect the plasma level of ACTH.

The ACTH level can be increased because of diseases like:

Pseudo-cushing disease which include alcoholism, depression, and anorexia nervosa

Cushing disease which includes ACTH-producing pituitary adenoma

Ectopic CRH-producing (nonpituitary) tumor

Ectopic ACTH-producing (nonpituitary) tumor

The ACTH level can be increased because of the conditions like deficiency in 17-α-hydroxylase, 21-hydroxylase, 11-β-hydroxylase (CYP11B1), 3-β-hydroxysteroid dehydrogenase, 3-β-hydroxysteroid dehydrogenase and cholesterol side-chain cleavage enzyme. Apart from this, addition disease, nelson disease, congenital adrenal hyperplasia can also increase the ACTH level.

The ACTH level can be decreased because of diseases like:

Pituitary adenoma

Pituitary corticotrophin disease

Pituitary radiotherapy

Pituitary stalk or hypothalamic structural abnormalities like craniopharyngioma

Hypothalamic CRH deficiency

Infiltrative diseases of the hypothalamus like fungal infections, sarcoid, tuberculosis, histiocytosis X

Drug-induced hypophysitis (ipilimumab [Yervoy])

Autoimmune hypophysitis

Hemorrhage, infection, or damaging injuries on the sella turcica

Traumatic brain injury

Congenital ACTH deficiency

The ACTH level can be suppressed by the conditions like cortisolnproducing adrenal adenoma and chronic glucocorticoid therapy.

Collection:

Sample type: Whole blood

Container: Lavender top tube (EDTA tube) or Siliconized glass

Sample preparation: Serum is separated from cells and transfer in a transport tube.

Storage instructions: Sample is stored for 14 days in frozen state.

Rejected samples: Hemolyzed specimen

Considerations: The ACTH test requires no preparation. The preferred time for the ACTH test is 6 am to 9 am.

Panel:

Along with the ACTH test, other tests which include are CRH stimulation test, Metyrapone stimulation test, Insulin-induced hypoglycemia test, ACTH stimulation test.

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