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Tumor Markers:- Part 13 – ACTH, HCG, Calcitonin

January 4, 2025Chemical pathologyLab Tests

Adrenocorticotropic hormone(ACTH)

What sample is needed for ACTH?

  1. We need venous blood to prepare the serum.
  2. Ask the patient not to drink or eat after midnight of the sample to be drawn.
  3. Do not use steroids before this test because steroids increase the ACTH.

What are the indications for ACTH?

  1. This test will tell the production of ACTH by the anterior pituitary gland.
  2. It helps to diagnose primary and secondary adrenal gland dysfunction.

What are the precautions for ACTH?

  1. Estrogen, glucocorticoids, and oral contraceptives can decrease the value.
  2. Stress, whether it is mental or physical, can increase the level.
  3. Obesity also increases the level.
  4. Physical activity also increases the level.
  5. Blood glucose levels also interfere with the result.
  6. Radioactive scans can interfere with the result.

How will you define ACTH?

  1. The adrenocorticotropic hormone (ACTH) is a peptide hormone secreted by adenohypophysis.
  2. It acts primarily on the adrenal cortex, stimulating its growth and synthesis of corticosteroids.
  3. This hormone is also known as corticotropin, corticotrophin, adrenocorticotrophin, and adrenocorticotropin.

What is the pathophysiology of ACTH?

  1. ACTH hormone is synthesized by the anterior pituitary glands and stimulates the adrenal cortex.
ACTH and role of CRH

ACTH and the Role of CRH

  1. This is a polypeptide hormone produced by the corticotropic cells of the anterior pituitary gland.
  2. ACTH is a tropic hormone; it binds to the adrenal cortex cells and influences their activities.
  3. ACTH in plasma is highest between 6 to 8 AM and lowest in the evening between 6 to 11 PM.
  4. ACTH secretion is increased during stress.
ACTH functions

ACTH functions

What is the control mechanism of ACTH?

  1. The hypothalamus produces corticotropin-releasing hormone (CRH), which stimulates the anterior pituitary gland and releases ACTH.
  2. A high level of cortisol suppresses the CRH and ACTH.
  3. ACTH follows diurnal rhythem. There is a peak in the morning; then it decreases throughout the day.

What are the functions of ACTH?

  1. It stimulates the adrenal cortex and promotes the production of glucocorticoids (Cortisol), mineralocorticoids (Aldosterone), and adrenal androgens.
  2. During stress, ACTH increases and increases cortisol production, which helps release physical or psychological stress.
  3. ACTH controls glucose metabolism, protein breakdown, and fat mobilization.

What is the normal ACTH level?

  1. AM level = <80 pg/mL (<18 pmol/L).
  2. PM level = <50 pg/mL (<11 pmol/L).

Another reference

  • 9 to 52 pg/mL (2 to 11 pmol/L)

Another source

  • 8 AM = Fasting = Adult, child, and elders = 15 to 100 pg/mL (10 to 80 ng//L).
  • 4 PM = Nonfasting = 10 to 50 pg/mL (10 to 50 ng/L).
  • Newborn = 10 to 185 pg/mL.

What are the causes of raised ACTH levels?

  1.  ACTH may be raised as primary or ectopic production.
  2. Ectopic production from:
    1. Small cell carcinoma of the lung ( >200 ng/L).
    2. Pancreatic carcinoma.
    3. Breast.
    4. Stomach.
    5. Colon.
  3. Benign conditions are:
    1. Chronic obstructive pulmonary disease.
    2. Mental depression.
    3. Obesity.
    4. Hypertension.
    5. Diabetes.
    6. Stress.
  4. In primary adrenal deficiency.
  5. In patients with Cushing’s syndrome.
  6. In patients with ectopic tumors, e.g.
    1. Basophilic neoplasm of the anterior pituitary.
    2. Ectopic carcinoma of the lung.
  7. Addison’s disease.
  8. Cushing’s disease.

What are the causes of decreased ACTH?

  • Secondary adrenal insufficiency is due to pituitary dysfunction, where the cortisol level is low.
  • ACTH in a normal person does not exceed 50 pg/mL at its peak, and the basal level is near 5 pg/mL.

Human Chorionic gonadotropin hormone (HCG)

What sample is needed for HCG?

  • Collect venous blood to prepare serum.

What are the indications for HCG?

  1. This test is advised to diagnose pregnancy or abortion.
  2. This test is also advised for the diagnosis of a hydatidiform mole.
  3. HCG is also advised for some cancers.

What are the precautions for the estimation of HCG?

  1. Avoid hemolysed, icteric, or lipemic serum.
  2. Excessive secretion of luteinizing hormone leads to false positive results.
  3. HCG-producing tumors may cause false positive results in a test conducted for pregnancy.
  4. Anticonvulsants, hypnotics, tranquilizers, and antiparkinsonian drugs may lead to false positive results.
  5. Heparine and phenothiazines may decrease HCG levels.
  6. May see false negative results in early pregnancy, threatened abortion, and ectopic pregnancy.
  7. Proteinuria and hematuria cause false positive results.
  8. Diuretics and promethazine may cause false negative urine tests.

How will you define human chorionic gonadotropin (HCG) hormone?

  1. Chorionic gonadotropin (HCG) is a glycoprotein hormone produced by the placenta’s syncytiotrophoblast cells during pregnancy.
  2. HCG has a vital role in the maintenance of the pregnancy and the development of the fetal parts.
HCG formation in pregnancy

HCG formation in pregnancy

What is the structure of the HCG hormone?

  1. This is also called Chorionic gonadotropin.
  2. This is a glycoprotein secreted by the syncytiotrophoblastic cells of the placenta.
  3. This consists of two subunits:
    1. α- HCG:
      1. It is shared with other glycoproteins like LH, FSH, and TSH.
    2. β-HCG:
      1. It is unique to HCG and provides biological properties.
HCG specific for pregnancy

HCG specific for pregnancy

What are the functions of HCG?

  1. It maintains the pregnancy.
  2. It helps in fetal development.
  3. It stimulates the fetal testes to produce testosterone hormone, which will help in male differentiation.
  4. It suppresses the mother’s immune system against the fetal tissue.

What is the normal HCG?

  1. Male and nonpregnant females serum = Negative or <5 mIU/mL.
  2. Urine = Negative in males and nonpregnant females.
  3. Pregnant women:
    1. Serum = 0 to 14 weeks of gestation = 100mIU/mL (rising level).
    2. Urine = First trimester = up to 500,000 IU.
    3. Second trimester = 10,000 to 25,000 IU.
    4. Third trimester = 5,000 to 15,000 IU.

What are the causes of raised HCG levels?

  1. Elevated HCG level is seen in:
    1. Trophoblastic disease (level is usually >one million IU/L).
    2. Germ cell tumors and non-seminomatous tumors of the testis (there is a moderate increase).
    3. Reported in melanoma and carcinoma of the breast, GIT tumors, lung, and ovary.
  2. The presence of HCG in seminoma indicates another component of choriocarcinoma.
  3. Also raised in benign conditions like:
    1. Cirrhosis.
    2. Duodenal ulcer.
    3. Inflammatory bowel diseases.
    4. Pregnancy.

Calcitonin

What sample is needed for the Calcitonin level?

  1. Please get venous blood to prepare the serum.
  2. A fasting sample is needed.
  3. Heparinize and chill the sample immediately.
  4. If the test is not performed immediately, then freeze the sample.

What are the precautions for Calcitonin levels?

  1. Calcitonin is usually raised in pregnancy at term and in the newborn.
  2. Avoid gross lipemia and hemolysis.

What are the indications for Calcitonin?

  1. It is advised for the diagnosis of recurrence of medullary carcinoma.
  2. It is also advised in metastases after the removal of the primary tumor.
  3. Calcitonin is advised with basal value after the surgery to see complete removal.

How will you define Calcitonin?

  1. This is a polypeptide with 32 amino acids.
  2. This is produced by the parafollicular C cells of the thyroid.
  3. The serum half-life is 12 minutes.
  4. In a normal person, it is <0.1 µg /L.
  5. There is circadian variation in the calcitonin level, and the peak level is after lunchtime.

What is the mechanism of calcitonin on bone?

  1. Calcitonin acts directly on osteoclasts to decrease bone-resorbing activity and leads to a decrease in calcium levels.
    1. Calcitonin inhibits bone resorption by regulating the number and activity of the osteoclast.
  2. This is produced in response to increased serum calcium levels. This response is directly related to calcium levels.
  3. Calcitonin helps monitor disease after treatment.
  4. It inhibits the release of calcium from the bone and lowers serum calcium.
Calcitonin role for Calcium regulation

Calcitonin’s role in Calcium regulation

What is the normal Calcitonin level?

Source 2

  1. Basal (plasma)
    1. Male = ≤19 pg/mL  (≤19 ng/L)
    2. Female = ≤14 pg/mL  (≤14 ng/L)
  2. Calcium infusion  (2.4 mg/kg)
    1. Male = ≤190 pg/mL  (≤190 ng/L)
    2. Femal =   ≤130 pg/mL  (≤130 ng/L)
  3. Pentagastrin injection (0.5 µg/kg)
    1. Male = ≤110 pg/mL  (≤110 ng/L)
    2. Female = ≤30 pg/mL   (≤30 ng/L)

Another source

  • Male = <8pg/mL,
  • Female = <6 pg/mL.

What are the causes of increased Calcitonin?

  1. A basal fasting level of calcitonin may be increased in patients with medullary carcinoma of the thyroid, even in the absence of a palpable mass.
  2. Medullary carcinoma of the thyroid. The level is >2000 pg/mL and is always associated with medullary carcinoma.
    1. A level of 500 to 2000 pg/mL generally indicates medullary carcinoma of the thyroid but is also seen in renal failure or ectopic production of calcitonin.
    2. A level of 100 pg/mL to 500 pg/mL should be interpreted carefully, and the provocative test should be performed; if the repeat test after 1 to 2 months is abnormal, thyroidectomy should be advised.
  3. Myeloproliferative disorders.
  4. Carcinoid tumor.
  5. Lung cancers.
  6. Breast cancer.
  7. Kidney tumor.
  8. Liver tumor.

What are the causes of increased Calcitonin levels in nonmalignant conditions?

  1. Zollinger-Ellison syndrome.
  2. Pulmonary disease.
  3. Pancreatitis.
  4. Hyperparathyroidism.
  5. Paget’s disease of bone.
  6. Pregnancy.
  7. Pernicious anemia.
  8. Newborn.
  9. Chronic renal failure.

Questions and answers:

Question 1: What is the value of calcitonin in the diagnosis?
Show answer
Raised calcitonin level is suggestive of medullary carcinoma of the thyroid.
Question 2: In which condition ACTH is raised?
Show answer
ACTH is raised in small cell carcinoma, pancreatic carcinoma, and few other carcinomas.

Possible References Used
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