Physiology
The posterior pituitary is responsible for the production and release of these two hormones
What is antidiuretic hormone & oxytocin ?
The most common cause of primary (central) diabetes insipidus
What is idiopathic ?
Note. Primary, or central, DI is characterized by a complete (or partial) absence of anti diuretic hormone. There is lack of production of ADH by the posterior pituitary. There are many etiologies of DI. Some include: head trauma, neoplasms (craniopharyngioma, adenoma, meningioma), granulomatous disease (sarcoid, TB, histocytosis, eosinophilic granuloma), and vascular lesions (sheehan's, CVA, internal carotid artery aneurysm).
Two medications that result in nephrogenic diabetes insidipidus
What is lithium and demeclocycline ?
Note: In nephrogenic DI, ADH is present but the physiologic action of ADH is absent. Nephrogenic DI is due to dysfunction or loss of receptors at the kidney. Medications are a main etiology but genetic forms and acquired forms (sickle cell, sarcoid, amyloid) also exist.
Medical term used to describe excessive fluid intake and thereby reduced plasma osmolarity with subsequent anti diuretic hormone suppression
What is primary polyipsia ?
Lung cancer that is highly associated with the syndrome of inappropriate anti-diuretic hormone secretion
What is small cell lung cancer ?
Note: SIADH has several etiologies. Head trauma, any lung infection, and neurologic pathologies including brain abscess, meningitis, GBS, MS, ALS, and delirium tremens can all result in SIADH.
Oxytocin initiates and facilitates labor by stimulating contraction of the smooth muscle of this organ
What is the uterus ?
Note: Oxytocin acts on the mammary ducts to facilitate milk let-down and initiates and facilitates labor by stimulating contraction of the uterus.
Diagnostic test that differentiates between central and nephrogenic DI
What is the desmopressin challenge ?
Note: In central DI, when desmopressin is administered, the urine will concentrate and patient will be relieved of symptoms. In nephrogenic DI, desmospressin has no effect because the defect is at the level of the ADH receptor in the kidney. In nephrogenic DI, desmopressin DOES NOT result in concentration of the urine which remains dilute.
Two electrolyte abnormalities that inhibit ADH's effect on the kidney resulting in a nephrogenic DI-like syndrome
What is hypercalcemia & hypokalemia ?
Primary polydipsia in the setting of obsessive compulsive disorder, schizophrenia, or bipolar disorder
What is psychogenic polydipsia ?
Chemotherapeutic agent that inhibits microtubule assembly that can cause a sensorimotor peripheral neuropathy as well as SIADH
What is vinca alkaloids ?
Accept: vincristine, vinblastine
Note: Many medications can result in SIADH. Vasopressin, desmompressin, or oxytocin can all result in SIADH. Vinca alkaloids and cyclophosphamide can result in SIADH. Antipsychotics, SSRIs, TCAs can result in SIADH. Carbamazepine can result in SIADH. Some sources say that NSAIDs also can potentiate the action of ADH.
Water channels inserted into the distal tubule & medullary collecting duct due to ADH stimulation which increases water reabsorption & concentrate the urine
What is aquaporins ?
Note: The most important physiologic action of ADH is to reduce water excretion by promoting concentration of urine. ADH results in the insertion of water channels (known as aquaporins) into the luminal surface. ADH acts in the renal tubule and results in the insertion of water channels into the distal tubule and medullary collecting ducts. Permeability of cells that line the distal tubule and medullary collecting ducts is increased dramatically to water and water only. ADH saves waters, which in turn, concentrates the urine.
Test that can distinguish primary polydipsia from both central or nephrogenic DI
What is the water deprivation test ?
Note: under normal circumstances, if fluid is withheld, plasma osmolarity will increase with a resultant increase in ADH. The ADH would then act on the kidney to concentrate the urine. If the urine does not concentrate and remains dilute, there are two possible scenarios: central or nephrogenic DI.
Expected urine osmolality response to desmopressin infusion in nephrogenic DI
What is no change in urine osmolality ?
Major side effect concern with desmopressin administration in primary polydipsia
What is hyponatremia ?
Also except: water intoxication
Note: Signs of water intoxication might include: headache, weakness, anorexia, nausea, vomiting, lethargy, somnolence, coma, and convulsions.
Acute, potentially fatal neurologic syndrome characterized by quadriparesis, ataxia, & abnormal extraocular movements that can occur when a life-threatening hyponatremia is corrected to quickly
What is central pontine myelinolysis ?
Also accept: the osmotic demyelination syndrome
Note: in severe hyponatremia, the rate of correction should not exceed 0.5 mEq/L/hr with a total increase NOT to exceed 8-12 mEq/L/d in 24 hours
The primary regulator of ADH secretion
What is plasma osmolality ?
Note: osmoreceptors, specialized cells of the hypothalamus, are extremely sensitive to small changes in the plasma concentration of sodium (& some other solutes). The set point of plasma osmolality in humans is ~280 - 295 mosmol/L. If plasma osmolarity increases, ADH rises steeply in direct proportion to plasma osmolarity. In other words, hypernatremia will lead to ADH secretion in an attempt to decrease plasma osmolarity to normal. If plasma osmolarity decreases, ADH is suppressed.
Treatment of central diabetes insidipidus
What is desmopressin ?
Also accept: DDAVP
Note: desmopressin is a synthetic analogue of ADH that acts selectively at V2 receptors to increase urine concentration by increasing the permeability of cells of the distal tubule and medullary collecting ducts via aquaporin placement at the luminal surface of the renal tubular cell.
Expected urine osmolality response to water deprivation in nephrogenic DI
What is no change in urine osmolality ?
Laboratory parameters in primary polydipsia (comment on urine osm, urine sodium, serum osm, urine volume)
What is decreased urine osmolarity, decreased urine sodium, normal/decreased serum osmolality, and increased urine volume ?
Note: in primary polydipsia, when water is withheld, plasma osmolarity will rise, ADH will be released, and the urine will be concentrated.
Initial treatment of asymptomatic, mild hyponatremia suspected to be due to SIADH
What is free water restriction ?
Note: In patients with SIADH and severe signs/symptoms, fluid restriction is probably the best initial step in management. The use of hypertonic 3% saline should be considered on a case-by-case basis and nephrology is usually involved with this decision. In patients with chronic SIADH, demeclocycline, fludrocortisone, or lithium are effective in treating the hyponatremia in SIADH.
The posterior pituitary is formed by axons originating in these two nuclei of the hypothalamus
What is supraoptic and paraventricular nuclei ?
Condition, characterized by mucocutaneous bleeding and an increase in the activated partial thromboplastin time, in which desmopressin has efficacy
What is Von Willebrand deficiency ?
Note: VWF deficiency is a common bleeding disorder characterized by mucocutaneous bleeding. There is often a normal platelet count and typically, the aPTT is prolonged. In some instances (mild-moderate vWF deficiency), the aPTT may not be elevated.
Medication that may have efficacy in the treatment of nephrogenic DI
What is amiloride ?
Also accept: thiazide diuretics, indomethacin
Primary polydipsia as a result of inappropriate thirst due to a reduction in the 'set-point' of the osmoregulatory mechanism; often idiopathic but sometimes seen in neurosarcoid, TB, MS and meningitis
What is dipsogenic polydipsia ?
Also accept: dipsogenic diabetes insipidus
Note: There are three main forms of primary polydipsia - iatrogenic polydipsia, psychogenic polydipsia, and dipsogenic polydipsia.
Aquaretic medications that are approved for treatment of autosomal dominant polycystic kidney disease and short term in hospital treatment of SIADH
What is ADH antagonists ?
Also accept: Conivaptan and tolvaptan
Note: ADH antagonists block the antidiuretic effect of ADH and result in an increase in urinary free water excretion. Body water is reduced and hyponatremia is corrected.