1. Disorders of ADH secretion Dr. Eman El Eter

2. Deficiency: Diabetes Insipidus. Excess secretion: Syndrome of inappropriate ADH secretion (SIADH)

3. Diabetes insipidus Causes/types: Central DI Nephrogenic DI Despogenic DI

4. Manifestations: Polyuria Polydepsia Low fixed specific gravity urine (diluted urine). Thirst. Dehydration can occur if patients don’t drink enough amount of water. How differs from DM? DM: Polyuria, polydepsia, hyperglycemia, urine is concentrated.

5. Central DI Causes: Central DI, results from damage to the pituitary gland, which disrupts the normal storage and release of ADH. Damage to the pituitary gland can be caused: Head injuries, Neuro­ surgery, or Genetic disorders. Treatment: a synthetic hormone called desmopressin can be taken by an injection, a nasal spray, or a pill. While taking desmopressin, a person should drink fluids only when thirsty and not at other times.

6. Nephrogenic DI Nephrogenic DI results when the kidneys are unable to respond to ADH. The kidneys’ ability to respond to ADH can be impaired by: drugs—like lithium, chronic disorders including polycystic kidney disease, sickle cell disease, kidney failure, partial blockage of the ureters, and inherited genetic disorders. Treatment: Desmopressin will not work for this form of DI. Moduretic. With this drug, one should drink fluids only when thirsty and

7. Dispodenic DI Cause: Dipsogenic DI is caused by a defect in or damage to the thirst mechanism, which is located in the hypothalamus. This defect results in an abnormal increase in thirst and fluid intake that suppresses ADH secretion and increases urine output. Desmopressin or other drugs should not be used to treat dipsogenic DI because they may decrease urine output but not thirst and fluid intake. This fluid overload can lead to water intoxication, a condition that lowers the con­ centration of sodium in the blood and can seriously damage the brain cells. Scientists have not yet found an effective treatment for dipsogenic DI.

8. Diagnosis A fluid deprivation test helps determine whether DI is caused by one of the following: excessive intake of fluid a defect in ADH production a defect in the kidneys’ response to ADH. Measuring ADH

9. SIADH

10. SIADH is characterized by the non-physiological release of ADH, resulting in impaired water excretion with normal sodium excretion SIADH is characterized by: – fluid retention – serum hypo-osmolarity – dilutional hyponatraemia – hypchloremia – concentrated urine in the presence of normal or increased intravascular volume – normal renal function

11. Causes: Increased hypothalamic production – Infections Meningitis, encephalitis, abscess, HIV – Vascular subarachnoid or subdural hemorrhage – Neoplasm – post–pituitary surgery, multiple sclerosis, psychosis, BMT or Stem Cell Transplants – Drugs Chemotherapeutic - Cyclophosphamide, vincristine, vinblastine Antipsychotic - Thiothixene, thioridazine, haloperidol Antidepressants - Monoamine oxidase inhibitors, tricyclic antidepressants, serotonin reuptake inhibitors Miscellaneous – Bromocriptine – Pulmonary diseases Pneumonia, Tuberculosis, Acute respiratory failure,Positive pressure venTILATION – Idiopathic

12. Signs & symptoms Decreased / Low urine output Symptoms of hyponatraemia – Lethargy, apathy, disorientation, muscle cramps, anorexia, agitation Symptoms of water toxicity – nausea, vomiting, personality changes, confusion If Na < 110 mEq/L – seizures, bulbar palsies, hypothermia, stupor, coma