Adrenocorticotropic Hormone

(ACTH)
Definition of ACTH

1. Adrenocorticotropic hormone (ACTH) is a peptide hormone secreted

by the 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.

Pathophysiology Of ACTH

ACTH and the Role of CRH

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

ACTH functions

6. ACTH may be raised as primary or ectopic production.

7. Ectopic production from:
1. Small cell carcinoma of the lung ( >200 ng/L).
2. Pancreatic carcinoma.
3. Breast.
4. Stomach.
5. Colon.
8. Benign conditions are:
1. Chronic obstructive pulmonary disease.
2. Mental depression.
3. Obesity.
4. Hypertension.
5. Diabetes.
6. Stress.
 9. ACTH in a normal person does not exceed 50 pg/mL at its peak, and
the basal level is near 5 pg/mL.
10. Raised ACTH level is seen in:
1. In primary adrenal deficiency.
2. In patients with Cushing’s syndrome.
3. In patients with ectopic tumors e.g.
1. Basophilic neoplasm of the anterior pituitary.
2. Ectopic carcinoma of the lung.
11. Normal
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)

Human Chorionic Gonadotropin

Hormone (HCG)
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.
2. β-HCG.
4. 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.
5. The presence of HCG in seminoma indicates another component of
choriocarcinoma.
6. Also raised in benign conditions like:
1. Cirrhosis.
2. Duodenal ulcer.
3. Inflammatory bowel diseases.
4. Pregnancy.
7. Normal HCG
 1. Male and nonpregnant females = <5 mIU/mL.

HCG in malignancies

Calcitonin
Indications Of 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 and after the surgery to see
complete removal.

Calcitonin Definition:

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 is <0.1 µg /L.
5. There is circadian variation in the calcitonin level, and the peak
level is after lunchtime.

Mechanism Of Calcitonin:

1. Calcitonin acts directly on osteoclasts to decrease bone-resorbing

activity and leads to a decrease in calcium levels.
 2. This is produced in response to increased serum calcium levels.
3. Calcitonin is useful for the monitoring of disease after treatment.
4. It inhibits the release of calcium from the bone and lowers serum
calcium.

Calcitonin Is Useful For Diagnosing:

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 thyroid, but 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 do the provocative test; if the repeat test after 1
to 2 months is abnormal, then advise thyroidectomy.
3. Carcinoid tumor.
4. Lung cancers.
5. Breast cancer.
6. Kidney tumor.
7. Liver tumor.

Calcitonin Levels Also Raised In Nonmalignant Conditions Like:

1. Pulmonary disease.
2. Pancreatitis.
3. Hyperparathyroidism.
4. Paget’s disease of bone.
5. Pregnancy.
6. Pernicious anemia.

Normal (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. Female = ≤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)

Alkaline Phosphatase

Alkaline phosphatase isoenzyme

 Tumor Markers: Alkaline phosphatase distribution in the body

Tumor Markers: Alkaline phosphatase secretion in bile

1. Alkaline phosphatase is present in all the tissue, but the maximum

amount is found in the liver, bone, and placenta.
2. The liver isoenzyme is more stable than the bone isoenzyme.
 Placental isoenzyme is produced by the trophoblastic cells.

1. Placental isoenzyme is also raised in pregnant women.

2. This was discovered by Fishman in 1968.
3. This was the first tumor marker, along with AFP and CEA.

The alkaline phosphatase marker is raised in the following ways:

4. Metastatic tumors of bone or liver.

5. Prostatic cancer with bone metastasis. There is osteoblastic
activity and a markedly raised level.
6. Breast cancer metastasis to the bone with osteolytic activity
and mildly raised level.
7. Leukemia, Lymphoma, and sarcoma with metastases to the
liver.
8. This may be raised in other malignancies like ovarian, lung,
trophoblastic, gestation tumors, seminoma, Hodgkin’s
lymphoma, and GIT tumors.

Normal Alkaline phosphatase

Source 2

1. Adult = 30 to 120 units/L

2. Old people = Higher than the adult’s value.
3. Children/adolescents:
1. <2 years = 85 to 235 units/L.
2. 2 to 8 years = 65 to 210 units/L.
3. 9 to 15 years = 60 to 300 units/L.
4. 16 to 21 years = 30 to 300 units/L.

Creatine Kinase (CK)

1. Creatine kinase is the enzyme that activates creatine in the
muscles by transferring a high-energy phosphate group in the
reaction. This reaction is reversible.
1. Creatine + ATP ↔ Creatine phosphate + ADP
2. CK is found in high concentrations in the heart muscles,
skeletal muscles, and the brain.
2. Creatine kinase is a dimer consisting of two subunits (polypeptide
chains):
1. CK – M
 2. CK – B
3. There are three isoenzymes:
1. CK-1 (BB). is present in the brain, prostate, GIT, bladder,
lungs, uterus, and placenta.
2. CK-2 (MB) is present in high concentrations in the cardiac
muscles.
3. CK-3 (MM) is present in the cardiac and skeletal muscles.

Creatine kinase isoenzyme

3. This is raised in:

1. Prostatic cancer.
2. Small cell carcinoma of the lung.
3. Maybe elevated in breast, ovary, stomach, and colon cancers.

Normal Total CPK (Source 2):

1. Adult/elderly
1. Male = 55 to 170 units/L
 2. Female = 30 to 135 units/L
1. Values are higher after the exercise.
3. Newborn = 68 to 580 units/L

Lactate Dehydrogenase (LDH)

1. This is an enzyme in the action of the glycolytic pathway, and it is
released when there is cell membrane damage.

Lactate dehydrogenase (LDH) enzyme role in a chemical reaction

2. LDH is found in the cells of Herat, RBCs, kidneys, liver, brain, lungs,
and skeletal muscles.
3. When there is an injury to cells then, LDH enters the blood.
4. This is not a good indicator of cell injury because of its presence in
most of the tissue.
5. Its level correlates with the tumor mass and gives a prognostic
indicator of the progress of the disease.

LDH iso-enzymes are:

LDH isoenzyme Tumor Markers: Organ

  LDH-1  17% to 27%  The main source is the heart

 LDH-2  27% to 37%  It is present in the Reticuloendothelial system

 LDH-3  18% to 25%  Mainly present in the lung

 LDH-4  3% to 8% It is present in:

1. Kidneys
2. Pancreas
3. Placenta

 LDH-5  0 to 5% It is present in:

1. Liver
2. Skeletal muscles

1. Isoenzyme LD-5 is associated with liver metastasis.

2. LDH is a nonspecific tumor marker and is raised in:
1. Liver cell carcinoma.
2. Lymphomas.
3. Acute leukemias.
4. Germ cell testicular tumors.
5. Breast cancer.
6. Colon cancer.
7. Stomach cancer.
8. Lung cancer.
3. An elevated level of LDH in the urine indicates neoplasm or injury to
the urogenital system.
4. LD-5 positive in the spinal fluid indicates metastasis to the central
nervous system.

Normal LDH level (Source 2):

1.
1. Adult/elderly = 100 to 190 units/L at 37 °C
Neuron-specific Enolase (NSE)
1. Neuron-specific enolase (NSE) is the isoenzyme in the glycolytic
pathway identified by the immunoassay and found mostly in neuron
and neuroendocrine cells.
2. This is a glycolytic pathway.
3. Indication:
1. It monitors treatment and predicts relapse in small-cell lung
cancer.
4. Raised level of NSE:
5. It is raised neuroendocrine tumors:
1. Small cell carcinoma of the lung.
1. It is found in 68% of limited diseases.
2. 87% is found in the extensive disease.
6. Use for monitoring the following:
1. Neuroblastoma.
2. Pheochromocytoma.
3. Carcinoid.
4. Medullary carcinoma of the thyroid.
5. Melanoma.
6. Pancreatic endocrine tumors.

Prostatic acid phosphatase

1. Acid phosphatase is found in many tissues, including the liver, blood
vessels, red blood cells, platelets, and bone marrow.
1. The maximum concentration is found in the prostate gland.
2. The estimation of acid phosphatase is advised for:
1. The diagnosis of prostatic carcinoma.
2. Staging of the prostatic carcinoma.
3. To monitor the efficacy of the treatment of prostatic
carcinoma.
3. The level is raised when the prostatic carcinoma has
metastasized beyond the capsules to the other parts of the
body, especially to the bone.
4. In the case of complete curative surgery for prostatic cancer,
the acid phosphatase decreases to normal in several days.
1. When the patient is treated with estrogen therapy, it
returns to normal in several weeks.
5. Prostatic acid phosphatase (PAP) is a better indicator and
most clinically significant.
 1. PAP is more accurate than total acid phosphatase.
2. This is produced primarily by the prostate and raised in:
1. Prostatic cancer.
2. Osteogenic sarcoma.
3. Multiple myelomas.
4. Metastasis to the bone.

Prostatic specific antigen (PSA)

Prostatic specific antigen (PSA) mode of action

1. PSA is a glycoprotein normally found in the cytoplasm of the

prostatic epithelial cells.
2. This antigen is detected in all males, but its level is markedly
increased in prostatic carcinoma.
3. Its level is related to the size of the tumor.

1. The use of PSA:

1. This is specific for the diagnosis of prostatic cancer.
2. It is used to detect, stage, and monitor the treatment of
prostatic carcinoma.
3. Its use is more specific for monitoring the treatment.
2. The sensitivity of PSA is 70% at the cut-off value of 4.0 µg/L.
3. Specificity is more than 90% if the cut-off value is raised to 8 µg/L.
4. The level of PSA correlates with the stage of the disease.
5. Measure PSA for the follow-up of prostatic carcinoma:
1. Every 3 months after the surgery during the first year.
2. After 4 months in the second year.
3. After 6 months every year.
 Prolactin
Indications

 Prolactin levels are primarily used to diagnose and monitor:

o Hyperprolactinemia: This is a condition characterized by abnormally high
levels of prolactin in the blood.
o Causes of infertility: In both men and women, high prolactin can affect
fertility.
o Pituitary tumors: Prolactinomas are benign tumors of the pituitary gland
that produce prolactin.

Definition

 Prolactin (PRL) is a polypeptide hormone.

 It is produced by the lactotroph cells of the anterior pituitary gland.
 Prolactin has a short half-life in the bloodstream, typically around 40-60 minutes.
 Normal prolactin levels vary depending on sex, age, and physiological state.
o In non-pregnant and non-lactating adults:
 Males: < 18 ng/mL
 Females: < 25 ng/mL
o Prolactin levels are naturally higher in pregnant and breastfeeding women.

Mechanism

 Prolactin has various functions, including:

o Stimulating milk production: Prolactin plays a crucial role in lactation by
promoting milk production in the mammary glands.
o Breast development: Prolactin works alongside other hormones like
estrogen and progesterone to stimulate breast development during
pregnancy.
o Regulation of reproductive function: Prolactin can influence sex
hormone production and function in both males and females.

Prolactin Levels and Conditions

 Increased prolactin levels:

o Can be caused by:
 Pituitary tumors (prolactinomas)
 Medications
 Certain medical conditions (hypothyroidism, polycystic ovary
syndrome)
 Stress, exercise, and sleep disturbances (can cause temporary
elevations)
o Symptoms of high prolactin may include:
  Irregular periods or amenorrhea (absence of periods) in women
 Breast milk production (galactorrhea) outside of pregnancy or
breastfeeding
 Decreased sex drive and erectile dysfunction in men
 Decreased prolactin levels:
o Less common than elevated levels.
o May be associated with:
 Pituitary gland dysfunction
 Certain medications

Normal Prolactin Levels (reference ranges may vary slightly depending on the lab)

 Non-pregnant and non-lactating adults:

o Males: < 18 ng/mL
o Females: < 25 ng/mL
 Pregnant women: Levels progressively increase throughout pregnancy.
 Breastfeeding women: Levels vary depending on breastfeeding frequency.

Diagnosis of Pituitary adenoma:

1. Imaging like CT or MRI is advised.

2. Patients with >150 ng/mL have PRL-secreting tumors.
1. Many patients have >1000 ng/mL of PRL.
2. PRL level >200 ng/mL is enough evidence for PRL-secreting
pituitary tumors.

NORMAL Prolactin (PRL)

Source 1

Age ng/mL

Coed blood 45 to 539

Newborn 1 to 7 30 to 495
days

Children Tanner Male Female

stage
1 <10 3.6 to 12

2 to 3 <6.1 2.6 to 18

4 to 5 2.8 to 11.0 3.2 to 20

Adult

3.0 to 14.7 3.8 to 23.2

Pregnancy

3rd trimester= 95
to 473

 To convert into SI unit x 1.0 = µg/L

 The Tanner stage is the physical scale of the development of
primary and secondary sex characteristics.

Source 2

 Adult male = 0 to 20 ng/mL

 Adult female = 0 to 25 ng/mL
 Pregnant female = 20 to 400 ng/mL

Source 4

Nonpregnant women 0 to 23 ng/mL

Pregnant women 34 to 386

ng/mL

Pregnancy 1st <80 ng/mL

trimester
Pregnancy 2nd <169 ng/mL
trimester

Pregnancy 3rd <400 ng/mL

trimester

Men 0 to 20 ng/mL

Children 3.2 to 20 ng/mL