Adrenocorticotropic hormone (ACTH) is produced by cells of the anterior pituitary gland. The “command” for its synthesis is given by the hypothalamus with the help of corticotropic releasing factor (corticotropic releasing factor). For ACTH, the target organ is the adrenal glands. It stimulates the activity of the cortical layer and the formation of cortisol, cortisone and corticosterone.
With its participation, male sex hormones (androgens) and female sex hormones (progesterone and estrogen) are synthesized and released into the blood. Slightly affects the level of adrenaline, norepinephrine and dopamine, the function of the adrenal medulla.
The rate of ACTH synthesis depends on the concentration of cortisol in the blood. An external factor that can increase the secretion of the hormone is stress - severe pain, hypothermia, emotional and physical overload, hunger or a decrease in blood sugar levels when insulin is administered.
If the hormone is produced in excess (for example, due to a tumor in the pituitary gland), then hypercortisolism occurs - the adrenal cortex produces too much cortisol. The pathology is called Itsenko-Cushing's disease. ACTH deficiency inhibits cortisol production and leads to low adrenal function. Patients' blood pressure drops, their skin darkens, their appetite decreases, weight loss is noted, and a coma may occur.
The main point of application of ACT G is the adrenal glands, namely their zona fasciculata of the cortical layer. With intense exposure the hormone can cause its growth, an increase in the size and weight of the adrenal glands, and increased accumulation of cholesterol, pantothenic and ascorbic acid in them. The release of cortisol into the blood increases.
Extra-adrenal properties:
- removal of fat from subcutaneous tissue;
- ensuring the breakdown of lipids and the use of formed fatty acids for energy production;
- increased secretion of insulin and growth hormone;
- accumulation of glucose reserves in the muscles in the form of glycogen;
- increased pigment coloration of the skin (stimulates melanocytes);
- inhibition of inflammatory processes;
- improvement of memory, learning, emergence of motivation for activity;
- promotes bone restoration in case of fractures;
- stimulates the formation of new blood vessels.
Signs and symptoms for ordering an examination:
- obesity with a moon-shaped face, acne rashes on the skin, stretch marks with a purple tint;
- increased hair growth on the body, face, irregular menstruation;
- muscle weakness, low blood pressure and sudden weight loss without changing your eating style;
- decreased blood glucose, increased calcium and potassium levels;
- premature appearance of menstruation in girls and hair growth on the legs, along the midline of the abdomen, near the nipples;
- rapid sexual development in boys, enlargement of the external genitalia, darkening of the skin of the scrotum.
Low pressure
Preparation for analysis includes:
- complete physical and emotional peace;
- limiting caffeine, avoiding alcohol;
- light dinner 10 hours or more before the test;
- no smoking in three hours.
In a healthy person, the ACTH concentration ranges from 5 to 45 pg per 1 ml. Since the hormone is unstable, if the indicators change, you should retake it in a week.
If the adrenal glands produce little cortisol, then ACTH increases 1.5-2 times . This condition is called Addison's disease. The second reason is a tumor (adenoma) of the anterior pituitary gland, which develops hypercortisolism syndrome, Itsenko-Cushing's disease. Sometimes they provoke an increase in tumors in the uterus, lungs and intestines, as well as some drugs and other diseases in which ACTH is actively produced.
Pathologically low readings occur if:
- long-term treatment with corticosteroids;
- secondary adrenal insufficiency;
- Itsenko-Cushing syndrome;
- adrenal tumors;
- low activity of the pituitary gland (hypopituitarism).
Read more in our article about adrenocorticotropic hormone.
Indications for analysis
A test for hormone levels is prescribed for the diagnosis and treatment of diseases associated with dysfunction of the adrenal cortex. Monitoring indicators is also necessary to assess the effectiveness of therapy for oncological pathologies.
In women, ACTH is performed in case of menstrual irregularities, excessive hair growth, and infertility.
What symptoms and activities may be a reason for getting tested:
- abnormal pigmentation of the epidermis;
- acne in adults;
- early puberty in adolescents;
- Cushing's disease (fat deposition on the face, neck, abdomen, purple stretch marks on the abdomen, thinning limbs, increased blood sugar, high blood pressure);
- diseases of the skeletal system (osteoporosis), as well as muscle weakness and pain;
- causeless weight loss accompanied by high blood pressure;
- regular attacks of hypertension;
- severe fatigue, weakness and lethargy for a long time;
- deviation from the norm of cortisol in the blood;
- monitoring the patient’s rehabilitation after removal of corticotropinoma (tumor in the pituitary gland);
- long-term treatment with medications (for example, glucocorticoids);
- dysfunction of the adrenal cortex;
- monitoring the effectiveness of treatment for cancer patients.
For a doctor, the reason for referring a patient to ACTH may be:
- test with corticotropin-releasing hormone;
- changes in cortisol levels;
- suspected ACTH-producing tumor.
Who needs to undergo the study
Your doctor may recommend an ACTH test if you have the following symptoms:
- obesity with a moon-shaped face, acne rashes on the skin, stretch marks with a purple tint;
- increased hair growth on the body, limbs, face and irregular menstruation;
- muscle weakness, low blood pressure and sudden weight loss without changing your eating style;
- decreased blood glucose, increased calcium and potassium levels;
- premature appearance of menstruation in girls and hair growth on the legs, along the midline of the abdomen, near the nipples;
- rapid sexual development in boys, enlargement of the external genitalia, darkening of the skin of the scrotum.
Corticotropin releasing hormone test
In rare cases, ACTH can be produced not only by the pituitary gland, but also by a malignant tumor in any organ. Tests show high levels of ACTH and cortisol. To diagnose the pathology, a test with corticotropin-releasing hormone is prescribed. After it, the ACTH level either increases (indicating Itsenko-Cushing's disease) or remains at the same level (ectopic production syndrome).
To carry out the test, venous blood is taken in the morning on an empty stomach and ACTH is measured. Then 100 mcg of corticotropin-releasing hormone is injected into a vein and blood is drawn after 30, 45 minutes and 1 hour, determining the ACTH level for each time.
What consequences might there be?
With elevated hormone levels, every person who has undergone treatment can return to a full life. In exceptional cases, patients need to take hormonal medications constantly, but, nevertheless, this will not affect their ability to work.
However, when carrying a baby, everything is a little different. If hormone levels increase in the early stages of pregnancy, a spontaneous miscarriage is likely to occur. Help in this situation can only be provided with medications. If the increased level of hormones is not corrected in any way in the later stages, then, most likely, the fetus will be born with pathologies, including intrauterine growth retardation. A complication that always occurs during pregnancy is that the placenta detaches prematurely, and preeclampsia occurs in the later stages.
It should be noted that if treatment is carried out in a timely manner, patients will be able to avoid many negative consequences. That is why expectant mothers should be extremely careful about their health.
ACTH norms
Standard reference values
The norm for the ACTH test is an absolute value of 9-52 pg/ml.
Reference values of the Invitro laboratory Invitro values are somewhat different from the standard ones, since the more modern equipment of this laboratory allows measurements to be taken with greater accuracy.
- <46pg/ml
Factors influencing the result
- failure by the patient or medical staff to comply with the rules of preparation for the procedure;
- taking medications;
- recent injury or surgery;
- inappropriate phase of the menstrual cycle;
- the patient has a high temperature;
- pregnancy and lactation;
- unstable mental state;
- time zone change;
- sleep disorder;
- hemolysis (destruction) of red blood cells.
Important! The interpretation of the results is always carried out comprehensively. It is impossible to make an accurate diagnosis based on only one analysis.
Factors affecting ACTH analysis
- Secretion may increase in stressful situations and during pregnancy and is physiologically higher in men than in women; however, in women, concentrations may increase during menstruation.
- High values may be found if the examination is carried out after a serious injury or even only during an overnight rest.
- The values change significantly throughout the day.
- Increased hormone levels can be caused by taking several drugs, such as: amphetamines
- insulin
- levodopa
- metoclopramide
ACTH is elevated
Pathology is indicated by a 1.5-fold increase in hormone levels:
- Itsenko-Cushing's disease. It occurs against the background of various pathologies (the most common is pituitary adenoma). Increased iron volume produces more hormone, which means it stimulates excess cortisol production - ACTH increases up to 2 times;
- Addison's disease (cortisol deficiency), as well as congenital adrenal hyperplasia. In these pathologies, the adrenal cortex does not produce cortisol, shifting the function to the pituitary gland. In this regard, the level of ACTH rises sharply; — 2-2.5 times (> 1000 pg/ml);
- paraneoplastic syndrome. It is a consequence of the reaction of the pituitary gland to an oncological formation in any organ;
- Nelson's syndrome. Develops in patients with Cushing's disease, in the presence of a pituitary tumor, after amputation of the adrenal glands. The patient experiences secondary adrenal insufficiency and ACTH levels increase;
- syndrome of ectopic production of adrenocorticotropic hormone - 1.5 times the norm. In rare cases, ACTH can be produced not only by the pituitary gland, but also by a malignant tumor in any organ. Tests show high levels of ACTH and cortisol. To diagnose the pathology, a test with corticotropin-releasing hormone is prescribed. After it, the ACTH level either increases (indicates Itsenko-Cushing's disease) or remains at the level (ectopic production syndrome);
- taking medications. Lithium-based drugs, insulin, ethanol, calcium gluconate, amphetamines, aminoglutethimide, levodopa, metoclopramide, metyrapone, pyrogens, vasopressin can artificially increase ACTH levels.
What hormone level should be normal?
It should be noted that the level of the hormone in the body is different for women and men. That is why it would be inappropriate to provide specific figures. If you are wondering what exactly your hormone levels should be, visit a medical facility. In a healthy person, the level of the hormone changes several times a day, with the highest levels observed in the morning. When planning a pregnancy, this parameter is important. If hormones are higher than normal, you need to first adjust them, and only then think about pregnancy.
ACTH is low
Insufficient production of the hormone is associated with the following processes:
- secondary hypocortisolism. If the functioning of the pituitary gland is disrupted (insufficient production of ACTH), atrophy of the adrenal cortex occurs (lack of cortisol synthesis). Functional failure of other glands of the endocrine system may also occur;
- Itsenko-Cushing syndrome. The level of adrenocorticotropic hormone falls in the presence of a malignant tumor in the adrenal glands. It differs from Cushing's disease in that there is excessive production of cortisol and, as a result, a reduction in the production of ACTH by the pituitary gland;
- benign formations in the adrenal glands. The tumors in this case perform the function of the organ and produce additional cortisol, which reduces ACTH levels;
- taking medications from the glucocorticoid group, cryptoheptadine.
Brief description of the substance
Experts were able to reliably establish that there is a relationship between the pituitary gland, hypothalamus and the work of the adrenal glands. Moderate production of the valuable hormone adrenocorticotropin is continuously controlled by the brain. ACTH is responsible for the stable functioning of the adrenal glands and their secretion of other hormones in the body. The multifunctional adrenocorticotropic component affects the intensity of the production of biologically active substances necessary for humans. Thanks to this, doctors were able to determine the level of ACTH in women and the degree of its impact on various functions of the body. Their list:
- stable functioning of the reproductive system;
- increasing the protective function of the immune system;
- improvement of psychological state;
- minimizing the development of allergic reactions;
- rapid adaptation of the body to external changes;
- restrained reaction to stimuli.
Multifunctional ACTH affects the production of adrenaline, as it perfectly stimulates the secretion of adrenocorticosteroid. Without this substance, the normal production of human sex hormones, which affect the functioning of the glands, is simply impossible.
To correctly decipher the diagnostic results, you need to have a good understanding of the main functions of the ACTH hormone:
- The substance affects the formation of multifunctional nucleic acids and proteins in the adrenal glands. Due to this, the secretion of progesterone, cortisol, male testosterone, and female estrogen increases.
- Impact on brain cells. With an acute lack of the hormone, memory problems, frequent depression, and increased aggressiveness occur.
- A slight increase in total cortisol concentration helps a person cope much better with stressful situations.
- Helps the body produce the optimal amount of cholesterol needed to protect red blood cells, synthesize vitamin D, and form strong and durable cell walls.
ACTH levels affect the volume and weight of a person’s muscle mass.
Biosynthesis of adrenocorticotropic hormone and its transformation in the body
The biosynthesis of adrenocorticotropic hormone in the pituitary gland, as well as the biosynthesis of other proteins, is carried out with the participation of ribosomes and is suppressed by specific inhibitors of protein synthesis: puromycin and cycloheximide, as well as ribonuclease, but is not suppressed by actinomycin D and deoxyribonuclease. Below is the chemical structure of adrenocortitropic hormone molecules in humans and some animals (each of them includes 39 amino acid residues). The molecules of adrenocorticotropic syndrome in humans and different animal species differ only in the sequence of amino acid residues in the peptide chain region 25-33 (see diagram). The biological properties of adrenocorticotropic hormone are entirely determined by the structure of the N-terminal region (1-24) of the peptide chain, which is the same in different animal species and humans. The cleavage of one or two amino acids from the N-terminal region, as well as the blocking or cleavage of the N-terminal amino group (NH2), lead to a significant decrease in hormonal activity. However, the presence of N-terminal serine is not required, and replacing it with glycine does not cause noticeable inactivation of the hormone. The species specificity of adrenocorticotropic syndrome determines its immunological properties.
A peptide consisting of 24 amino acid residues and corresponding in structure to the N-terminal region of adrenocorticotropic hormone was obtained synthetically. It has all the biological properties of adrenocorticotropic syndrome, but lacks antigenic properties. Shortening of this peptide from the carboxyl end (in the region of the peptide chain 24-18) leads to a gradual decrease in its activity, which is still found in a peptide consisting of 17 amino acid residues.
Adrenocorticotropic hormone is stable in an acidic environment and is quickly inactivated in an alkaline environment. It is easily adsorbed on glass, which leads to significant losses when working with dilute solutions. Under the influence of oxidizing agents (hydrogen peroxide), adrenocorticotropic hormone is reversibly inactivated due to the oxidation of the 4th amino acid residue of methionine to methionine sulfoxide. Deeper oxidation with the formation of methionine sulfone leads to irreversible loss of hormonal activity. At the same time, methionine cannot be considered the “active center” of the molecule, since replacing it with α-aminobutyric acid or norleucine residues does not lead to a change in the biological properties of adrenocorticotropic hormone.
The C-terminal region of the adrenocorticotropic hormone molecule (39 - 25), which differs in structure in different animals, determines the immunological properties of the hormone, and the cleavage of several amino acids from the C-terminal region leads to a significant decrease in its antigenic properties.
