Cortisol Hormone

Sample for Cortisol Hormone

1. It is done on serum (3-5 ml clotted blood).
2. Also, it can use plasma.
   1. Collect the blood at 8 a.m.
   2. Then, collect blood at 4 p.m.
      1. 4 pm value is one-third to two-thirds of the 8 am value.
3. The sample can be stored at 4 °C for 2 days.
4. For a longer period, freeze the sample.
5. Urine sample. This is a 24-hour sample. Add Acetic acid (30%) 20 ml to the container.
   1. Or preserve with 1 gram of boric acid.

Purpose of the test (Indications) for Cortisol Hormone

1. This will measure the serum cortisol level.
2. Cortisol level is estimated to rule out hypo or hyperfunction of the adrenal gland.

What are the precautions for Cortisol Hormone:

1. There is increased value during pregnancy.
2. Emotional and physical stress can increase value.
3. Drugs like amphetamine, estrogen, cortisone, oral contraceptives, and spironolactone can increase value.
4. Drugs like androgens, betamethasone, exogenous steroids, lithium, danazol, Dilantin, and methyldopa can decrease the value.

Pathophysiology of Cortisol Hormone

1. This is a major adrenal gland glucocorticoid synthesized in the zona fasciculate of the adrenal cortex, and this will control the metabolism of:
   1. Glucose (Carbohydrate).
   2. Lipids (fats).
   3. Proteins.
2. While zona fasciculata is the middle zone, and it produces 17-hydroxycortisone, also called cortisol or hydrocortisone.
3. The inner zone is the zona reticularis, which produces androgens or estrogen.

4. The adrenal cortex produces various steroid hormones.

5. This hormone is involved in the metabolism of the body.
   1. Cortisone and its oxidation products cortisone are inactivated in the liver by two separate reduction processes (hydrogenation) into tetrahydro-derivates.
   2. This will conjugate with glucuronic acid in the liver and then be excreted in the urine.
6. Cortisol is a steroid.
   1. Because of its tight bonding with Cortisol-binding-globulin, cortisol is metabolized slowly.

What are the types of Cortisol present in the body:

1. 75% is bound to alpha-1-globulins called transcortin.
2. 15% is bound to albumin.
3. 10% is unbound and is in free form.
   1. The bound form is not physiologically active.
4. The kidney, liver, and thyroid diseases affect the secretion and metabolism of cortisol (adrenal gland steroids).
5. Other factors that affect the cortisol level are our age, stress, nutrition, estrogen therapy, and drugs.
6. Glucocorticoid hormone is secreted 10 to 30 mg/24 hours, influencing carbohydrate metabolism.
   1. Adrenal Cortisol, roughly 25 mg, is produced in 24 hours, while plasma concentration is 5 to 25 µg/dL.
   2. Cortisol takes part in the metabolism of carbohydrates, protein, and fats.
7. Cortisol breaks down the proteins.
   1. There is an amino acid formation.
   2. Amino acids are converted into glucose.
   3. Cortisol is an insulin antagonist.
   4. Cortisol is a glucocorticoid secreted by the adrenal cortex in response to ACTH stimulation.

What is the metabolism of the Cortisol hormone in the body:

The cholesterol forms cortisol in the adrenal zona fasciculata and reticularis of the adrenal cortex.

1. After entering into the blood circulation, it will bind with corticosteroid-binding globulin.
2. Cortisol will be metabolized and conjugated in the liver.
   1. >95% cortisol metabolites conjugated with glucuronic acid and excreted in urine as such.
   2. <2% unmetabolized cortisol is excreted in the urine.

How is Cortisol hormone transported in the body:

1. Freeform.
2. Bound form.
   1. 85% binds the corticosteroid-binding α-globulin (transcortin).
   2. 10% bound to albumin.
   3. Approximately 5% is free.

1. ACTH is controlled by the hypothalamus, the Corticotropin-releasing hormone (CRH).
   1. In case of increased ACTH, after a few minutes, cortisol is excreted.
   2. Decreased ACTH level leads to the atrophy of zona fasciculata (and zone reticularis).
   3. Exogenous glucocorticoids lead to suppression of ACTH and adrenocortical atrophy.

Cortisol production and the role of ACTH on the adrenal cortex

2. Corticotropin-releasing hormone ( CRH ), made in the hypothalamus,  stimulates the anterior pituitary gland to produce ACTH, which stimulates the adrenal cortex to produce cortisol.
3. Cortisol in blood exists in the following forms:
   1. Cortisol free.
   2. Cortisol in total.
   3. <2% cortisol is excreted unchanged in the urine.

What are the functions of the Cortisol hormone:

1. Cortisol controls the glucose level in the blood:
   1. By suppressing the secretion of insulin.
   2. It inhibits the uptake of glucose by the peripheral tissues.
   3. It promotes hepatic glucose synthesis.
2. Cortisol increases glucose levels by increasing gluconeogenesis in the liver (from the glucose store).
3. Cortisol will control the Carbohydrate, fat, and protein metabolism.
4. It has anti-inflammatory properties:
   1. By suppressing the cytokines.
   2. It decreases the eosinophils (inhibitory effect on eosinophils).
   3. It depresses the T-lymphocytes.
5. In case of overproduction of cortisol hormones:
   1. It causes poor wound healing.
   2. There may be bruising.
   3. There is immunosuppression during infection.
6. Cortisol regulates water-electrolyte balance:
   1. Water migrates into extracellular fluids through renal excretion.
   2. Excessive levels of Cortisol cause an accumulation of water in the face and other body areas.

7. Cortisol plays a role in the immune system.
8. It is influenced by heat, cold, infection, trauma, exercise, debilitating diseases, and obesity.

What are the conditions where there are Cortisol level variations:

1. There are diurnal variations in cortisol secretion in the morning and evening or at midnight cortisol levels. So, a random sample is not helpful.
   1. The highest level is between 6 to 8 am.
   2. The lowest level is between 4 to 6 pm. (Gradually false during the day, lower between 4 to 6 pm.)
   3. The lowest level is at midnight.

Cortisol Hormone: Cortisol circadian rhythm

2. Cushing’s syndrome has an average upper level in the morning.
   1. Cushing’s syndrome does not show diurnal change.
   2. There is no decline throughout the day.
3. Addison’s disease has the lowest level.
4. The variation is lost under stress.

Cortisol Hormone: Cortisol inhibitory function

Cortisol control mechanism and negative feedback

Explain Cortisol excretion:

1. Mostly >1% of the total cortisol is synthesized daily and is excreted as such in the urine.
2. 30% to 50% appears as glucuronide conjugates as tetrahydro-derivates of cortisol and cortisone.
3. All these compounds contain the dihydroxyacetone group in the side chain, known as 17-hydroxycorticosteroid (17-OHCS).
4. There is a higher concentration of these compounds in the urine.
5. Chemical estimation of the urinary 17-OHCS  or 17-Ketogenic steroids does not accurately estimate the plasma cortisol concentration or output because they may form other steroids similar in structure.

What is the Normal Total Cortisone hormone

Source 2

1. Serum AM (8 am) = 5 to 23  µg/dL
   1. Serum PM (4 pm) = 3 to 13 µg/dL
2. Urine (free cortisol) = 20 to 90 µg /24 hours
3. Children = 1 to 16 years.
   1. 8 AM = 15 to 25  µg/dL
   2. 4 PM = 5 to 10  µg/dL
4. Newborn = 1 to 24  µg/dL
   • Maternal at birth = 51.2 to 57.4  µg/dL
5. The blood sample was usually taken at 8 am and 4 pm; the 4 pm level is one-third to two-thirds lower than the 8 am level.
6. Urine 24 hours
   • Adult / old people = <100  µg/dL/24 hours (<276 nmol/day).
   • Adolescent = 5 to 55 µg/dL/24 hours
   • Child = 2 to 27 µg/dL/24 hours

 Source 1

Total Cortisol (free and bound by RIA)

• For conversion of µg/dL  into SI unit x 27.6 = nmol/L

Source 4

Cortisol Hormone level

• 0800 AM =5 to 23 µg/dL (138 to 635 nmol/L).
• 4.00 PM = 3 to 16 µg/dL  (83 to 441 nmol/L).
• Midnight = <50% of 0800 AM level.
• Newborn = 2 to 11 µg/dL  (55 to 304 nmol/L).
• Maternal at birth = 52.1 to 57.4 µg/dL   (1413 to 1584 nmol/L).
  • After the first week of life, the cortisol level is like an adult level.

What are the conditions where there is an increased level of cortisol:

1. Cushing syndrome ( Pituitary disease)
2. adrenal adenoma and carcinoma.
3. Pregnancy leads to a raised level.
4. Physical and emotional stress can increase levels.
5. Ectopic ACTH-producing tumors.
6. Hyperthyroidism.
7. Stress.
8. Major depression.
9. Severe anxiety.
10. Obesity. All steroid hormones are increased in obese, which may be due to deposition or synthesis in the fat.

• An extremely high level is seen in Ectopic ACTH syndrome.

What are conditions where there is a decreased level of cortisol:

1. Addison disease.
2. congenital adrenal hyperplasia ( adrenogenital syndrome )
3. Hypopituitarism.
4. Hypothyroidism.

Cushing’s syndrome:

What is the definition of Cushing’s syndrome:

1. Cushing’s syndrome is the result of an increase in serum cortisol production.
2. Basically, this condition is due to excessive body levels of glucocorticoids like cortisol, and this may be:
   1. Primary where there is overproduction due to the adrenal cortex.
   2. The secondary is due to therapeutic therapy.

What are the causes of Cushing’s syndrome:

1. Around 70% of the cases are due to the overproduction of cortisol by the adrenal cortex caused by the pituitary hypersecretion of ACTH, leading to bilateral adrenal cortex hyperplasia.
2. 10% of the cases are due to adrenal cortex gland adenoma.
3. 10% of the cases are due to adrenal cortex carcinoma.
4. Around 28% to 38% of the cases are ectopic production of ACTH, like lung small cell carcinoma.
5. Few cases are caused by thymus carcinoid, pancreatic islet cell tumors, pheochromocytoma, and various adenocarcinomas.

Clinical presentation of Cushing’s syndrome: 

1. Cushing’s syndrome is more common in females, 4 times more than in males.
2. There is truncal obesity.
3. Neuropsychiatric symptoms.
4. There is hypertension.
5. There is an intolerance of carbohydrates.
6. There is hyperglycemia and decreased glucose tolerance.
7. There are polyuria and polyphagia.
8. There are hirsutism and acne.
9. There are proximal myopathy and weakness.
10. The patients are prone to easy bruises.
11. There are sexual dysfunction and menstrual problems.

How you will diagnose Cushing’s syndrome:

1. There is hypokalemic metabolic alkalosis.
2. There is an increase in urinary-free cortisol.
   1.  Single increased serum cortisol level.
   2. Or advise 24 hours urinary 17-OHCS.
3. Measure urine 17-ketosteroids for the diagnosis of Cushing’s syndrome.
   1. It is increased in 50% to 55% of Cushing’s syndrome patients.
4. Diurnal variation is absent in 90% of the cases.
   1. Take two blood samples, one at 89 A.M. and one at 8 P.M.
   2. there will be no diurnal variation.
5. There is a lake of normal suppression by dexamethasone.
   1. Low dose dexamethasone suppression test where cortisol level remains elevated.
6. A high level of cortisol indicates Cushing’s syndrome.
   1. A low level of cortisol indicates Addison’s disease.

Table for differentiation of Adrenal diseases:

Urinary cortisol per/day in various diseases:

What is the function of the cortisol hormone?

1. It regulates the body’s response to stress.
2. Cortisol stimulates the release of glucose from the liver in response to stress.

What happens when the cortisol level is high?

1. High cortisol hormone level leads to:
   1. Weight gain.
   2. Headache.
   3. irritability etc.
   4. It suppresses inflammation.
   5. It regulates blood pressure.
   6. It regulates blood glucose levels.

What is the effect of the cortisol hormone on the behavior?

1. Excessive levels of cortisol, like in Cushing’s syndrome, lead to depression.

Questions and answers: