Antidiuretic Hormone (ADH)

Sample

1. This test is done on the venous blood sample (Tube is prechilled).
2. Plasma with EDTA is needed.
3. Take the blood when a patient is in a sitting position and calm.
4. Put the sample on ice.
5. Or collect the sample in prechilled vials.
6. Separate plasma immediately in the refrigerated centrifuge and freeze at -20 °C.

Purpose of the test (Indications) for Antidiuretic Hormone (ADH)

1. ADH is done in patients with diabetes insipidus.
2. Advised in a patient with polyuria or polydipsia.
3. This is also advised in hyponatremia.
4. For the diagnosis of ectopic ADH production.
5. This is advised in SIADH (syndrome of inappropriate antidiuretic hormone secretion).
6. This is also advised in psychogenic water intoxication.

Precautions for Antidiuretic Hormone (ADH)

1. Avoid glass syringe or collection tube which causes degradation of the ADH.
2. Avoid dehydration, hypovolemia, and stress, which may lead to increased ADH levels.
3. Avoid overhydration and hypervolemia, which may decrease the ADH level.
4. The use of a glass syringe or collection tube causes degradation of the ADH.
5. Drugs like acetaminophen, cholinergic drugs, barbiturates, nicotine, estrogen, oral hypoglycemic agents, diuretics (thiazide), narcotics, and tricyclic antidepressants will increase the ADH.
6. Drugs like alcohol, morphine antagonists, Dilantin, and beta-adrenergic agents will decrease the ADH level.
7. The recent history of radioisotopes gives the wrong result.

Definition of Antidiuretic Hormone (ADH):

1. ADH also called Vasopressin (or arginine Vasopressin) produced under the influence of the center in the anterior hypothalamus and stored in the posterior pituitary gland is excreted into the blood circulation.
   1. ADH is considered one of the plasma volume regulators, by its ability to concentrate the urine via its action on the renal distal and collecting tubules by water reabsorption.

2. The osmolarity of the extracellular fluid control ADH release.
   1. Increased osmolarity stimulates the osmoreceptors in the hypothalamus, which stimulates the ADH  release.

The major function of Antidiuretic hormone (ADH) and its control:

1. When ADH activity is present, then a small volume of concentrated urine is excreted.
   1. When ADH is absent, then a large volume of dilute urine is excreted.
2. ADH Maintains water homeostasis.
3. There is water reabsorption by the kidney and urine concentrated.
4. ADH in sufficient quantity induces generalized vasoconstriction that leads to an increase in arterial blood pressure.
5. ADH increases the release of more water reabsorbed from the distal and collecting tubule; it increases water reabsorption and leads to concentrated urine and more water in the blood circulation.
6. ADH decreased level, and less water was reabsorbed (water was allowed to be excreted), leading to dilute urine and hemoconcentration.

Antidiuretic hormone (ADH) release is stimulated by:

1. The increase in serum osmolality.
   1. Blood osmotic changes like concentration and dilution, act on osmoreceptors in the hypothalamus.
2. The decrease in intravascular blood volume (blood volume changes).
3. Higher secretion at night and with erect posture and exercise.
4. Physical Stress, surgery, and even anxiety.
5. Neural influences like pain.
6. Certain drugs like morphine and alcohol.

The most important syndromes associated with ADH are:

1. Diabetes inspidus.
2. Inappropriate ADH syndrome.

Syndrome of inappropriate ADH secretion (SIADH):

1. It is associated with high serum ADH levels.
2. There is water retention due to secretion of ADH when not secreted in normal conditions.
3. Criteria for SIADH is that there is the secretion of the ADH in spite of the hemodilution, decreased serum osmolality, or both.
4. Mostly these patients have no edema.

Diagnosis of SIADH, and its characteristic features:

1. Hyponatremia.
2.  Continued renal excretion of the Na⁺ despite the hyponatremia.
3. Serum hypoosmolarity.
4. Urine osmolality shows a significant degree of concentration, instead of what one would expect to have dilute urine.
5. No evidence of blood volume depletion.
6. There is a normal renal and adrenal function that will differentiate from other causes.
   1. These criteria will demonstrate that ADH secreted despite the hemodilution, decreased serum osmolality, or both.
7. Most of these patients do not have edema, because interstitial fluid expansion is usually moderate in degree.
8. The water load test means ADH suppression is used to differentiate the SIADH from the other causes of hyponatremia and or edematous conditions.
   1. Measure urine and serum osmolarity.
      1. Patients with SIADH secrete very little or none of the water overload.
      2. Urine osmolarity will be never <100 mmol/kg
      3. Urine/serum ratio is >100.
9. Treatment of the choice for SIADH is the restriction of the fluid intake and it may provide some evidence of this syndrome.

Paraneoplastic syndrome:

1. It is seen in ectopic production of the ADH like carcinoma of the lung, thymus, lymphoma, carcinoma of the pancreas, leukemia, urinary system, and intestine.
2. This condition may also be seen in pulmonary tuberculosis and pneumonia.
3. Other conditions are CNS tumors, infection, and trauma.

Diabetes Insipidus

Definition of diabetes inspidus:

1. This is a syndrome characterized by hypotonic polyuria.
2. Diabetes insipidus is a chronic condition accompanied by a large volume of hypotonic urine caused by an inability to concentrate the urine due to a lake of ADH secretion or production.
3. Diabetes insipidus is characterized by:
   1. Abnormally increased urine output.
   2. Increased fluid intake.
   3. Often accompanied by thirst.
   4. This is because of the absence of the ADH effect either due to
      1. Impaired or failed secretion from the pituitary gland (neurogenic).
      2. Or no response by the end organ, kidneys (nephrogenic).
   5. This may be seen in a person with psychogenic polydipsia, or compulsive water intake may present as diabetes insipidus patients.
4. This is called diabetes but it has no relation to diabetes mellitus where the polyuria is hypertonic due to overexcretion of the glucose in the urine.

Classification of diabetes insipidus:

1. The possible etiological classification is:
2. Neurogenic where the hypothalamus is unable to produce ADH from the pituitary gland.
3. Renal where the end-organ inability to respond normally to ADH.
4. Primary polydipsia may be psychogenic or abnormal thirst mechanism.
   1. Temporary overpowering of vasopressin system. There is ingestion of a large quantity of water, sometimes called primary diabetes inspidus.
5. Gestational Diabetes inspidus where there is increased metabolism of ADH.
6. High-set osmoreceptors.
7. ADH is inadequate OR
8. When kidneys are not responsive to ADH stimulation.
   1. The patient excretes a large volume of water in the urine.
   2. There is hemoconcentration, and patients feel thirsty.

4. Another Classification of Diabetes Insipidus:
5. Neurogenic Diabetes insipidus. It is caused by:
   1. Trauma, tumor, or inflammation of the brain (Hypothalamus).
   2. ADH level is low.
   3. Surgical ablation of the pituitary gland or mass lesion.
   4. X-linked recessive familial form.
6. Nephrogenic diabetes insipidus. It is caused by:
   1. Renal collecting system unresponsiveness to ADH.
      1. ADH level is raised.
      2. Hypercalcemia.
      3. Hypokalemia.
      4. A very low protein diet.
      5. Lithium therapy.
      6. The release of long-standing obstruction.
      7. Aging may be associated with partial nephrogenic diabetes inspidus.

Diabetes insipidus criteria are:

1. There are polyuria and polydipsia.
2. Low urine osmolarity.
3. Hypernatremia.

Diagnosis of Diabetes inspidus:

1. Before starting the test for the diabetes insipidus, advise the following tests with unrestricted diet and water intake:
   1. Urine output >2000 mL/day.
   2. Urine is hypotonic with osmolality <300 mosm/kg body weight/day (range is 200 to 300 mosm/kg).
   3. The above findings favor the diagnosis of diabetes insipidus.
   4. In that case measure solute contents /day.
   5. If the solute excretion is <20 mosm/kg/day, indicates definitely diabetes insipidus.
   6. The D/D of polyuria excludes:
      1. osmotic diuresis like glucose, mannitol, and sodium chloride.
      2. Diuretics therapy.
      3. Severe chronic renal disease.
         1. After acute tubular necrosis.
         2. After renal transplantation.
      4. Pregnancy-induced.
      5. Hypercalcemia.
      6. Hypokalemia.
      7. Drugs like lithium, chlorpromazine, and thiazide.
      8. Sickle cell disease.
2. Water deprivation or dehydration test:
3. Before starting the test to find the etiology, it is recommended that note:
   1. 24 hours urine volume.
   2. The osmolality of urine.
   3. Amount of solute excreted in the urine.
   4. Serum sodium, potassium, calcium, and osmolality without any restriction of the diet or water are recorded.
   5. When Results show the following value, then think about Diabetes Inspidus:
      1. Excess urine output.
      2. Urine is hypotonic.
4. Stop all medications which can influence the release of ADH, before 24 hours and during the test like:
   1. Alcohol.
   2. Tobacco.
   3. All caffeine-containing drinks.
5. This test is done by overnight deprivation of water.
6. Record the serum osmolality and sodium level before and after the administration of vasopressin.
7. It is followed by the ADH (vasopressin) administration. Inject subcutaneously either 1 µg of desmopressin ( a synthetic analog of ADH), or 5 IU of ADH (vasopressin).
8. Collect urine samples for 30, 60, and 120 minutes.
9. Result:
   1.  Urine osmolality after the injection of ADH is less than 50% higher than the baseline urine osmolality favors diabetes insipidus (nephrogenic type).
   2. If there is an increase equal to or greater than 50%, favor diabetes insipidus, neurogenic type.
10. In a healthy person, urine osmolarity increases during water deprivation.
11. Administration of vasopressin has to additional effect on urine concentration.
12. In the case of neurogenic diabetes inspidus:
    1.  No urine concentration in response to water deprivation.
    2. When vasopressin is given, then urine osmolarity increases.
    3. The Serum ADH level is low.
13. While in the case of nephrogenic diabetes inspidus:
    1. Urine cannot be concentrated in either case.
    2. There is no rise in the urine osmolality after water deprivation or after vasopressin administration.
    3. The Serum ADH level is high.
14. The standard diagnostic test for Diabetes Insipidus is the water deprivation test.
15. ADH presence leads to a small volume of concentrated urine.
    1. ADH absence leads to a large volume of diluted urine.

ADH release is stimulated by:

1. Increase in serum osmolality.
2. A decrease in intravascular blood volume.
3. Sleep
4. At night.
5. In erect position.
6. With pain.
7. In surgery.
8. Physical Stress.
9. High level of anxiety.
10. Exercise.
11. Chemical agents like catecholamine, opiates, nicotine, anesthesia drugs, barbiturates, and angiotensin ii.

ADH release is inhibited by:

1. The increase in plasma volume.
2. The decrease in plasma osmolality.
3. Alcohol.
4. Phenytoin.
5. Glucocorticoids

Normal ADH:

Source 2

• 1 to 5 pg/ mL or <1.5 ng/L.
• Or < 2.5 pg/mL.

ADH suppression test (water load test):

1. 65% of the water load is excreted in 4 hours.
2. 80% of the water load is excreted in 5 hours.
3. Urine osmolality in the second hour = ≤100 mmol/kg
4. Urine to serum  (U/S) osmolality ratio = >100
5. Urine specific gravity = <1.003

Another source

• 2 to 8 pg/mL

Source 4

• <2.5 pg/mL or <2.3 mmol/L

Increased ADH level is seen in:

1. Hyperfunction of ADH state gives rise to Syndrome of inappropriate antidiuretic hormone secretion (SIADH).
2. There is sustained release of ADH in the absence of a known cause.
3. Central nervous system diseases like tumors or infection.
4. Pulmonary tuberculosis or pneumonia.
5. Lung cancer (ectopic ADH).
6. Nephrogenic diabetes insipidus due to renal diseases.
7. Myxedema.
8. Physical stress like pain, and trauma.
9. Hypovolemia.
10. Dehydration.
11. Acute and intermittent porphyria.
12. Guillain-barre syndrome.

Decreased ADH level is seen in:

1. Hypofunction ADH gives rise to a polyuric state.
   1. Urine output is more than 2.5 L/day.
2. Nephrogenic diabetes insipidus.
3. Nephrotic syndrome.
4. Water intoxication (psychogenic polydipsia).
5. Surgical ablation of the pituitary gland.
6. Hypervolemia.
7. Decreased serum osmolality.
8. This polyuric state is divided into:
   1. Hypothalamic diabetes inspidus.
   2. Nephrogenic diabetes inspidus.
   3. Psychogenic polydipsia.

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