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DIABETES INSIPIDUS
- 2. Minh T. Huynh INTRO 7/27/2021 • Diabetes insipidus (DI) is a condition in which the kidneys are unable to concentrate urine. • Central DI: insufficient levels of circulating antidiuretic hormone (ADH); • Nephrogenic DI: defective renal ADH receptors in the kidneys.
- 3. Minh T. Huynh INDEX 7/27/2021 1. PHYSIOLOGY OF ADH 2. ETIOLOGY 3. PATHOPHYSIOLOGY 4. CLINICAL MANIIFESTATIONS 5. DIAGNOSTICS 6. TREATMENT
- 4. Minh T. Huynh 7/27/2021 PHYSIOLOGY OF ADH
- 5. Source: AMBOSS – GENERAL ENDOCRINOLOGY Minh T. Huynh PHYSIOLOGY OF ADH 7/27/2021
- 6. Source: AMBOSS – GENERAL ENDOCRINOLOGY Minh T. Huynh REGULATION OF ADH 7/27/2021 • Plasma osmolality: sensed by hypothalamic osmoreceptors • Hypovolemia: sensed by the atrial stretch receptors • Hypotension: sensed by the peripheral baroreceptors • Angiotensin II: sensed by hypothalamic receptors
- 7. Source: Wondisford F.E. (2020) Posterior Pituitary. In: Essentials of Endocrinology and Metabolism. Springer, Cham. Minh T. Huynh REGULATION OF ADH 7/27/2021
- 8. Source: AMBOSS – GENERAL ENDOCRINOLOGY Minh T. Huynh ADH RECEPTOR 7/27/2021 RECEPTOR MAIN EFFECT ACTION V1 (V1a) Regulation of blood pressure Vasoconstrictive effects at higher levels V2 Regulation of plasma osmolality - Insertion of aquaporin channels in the principal cells of the renal collecting duct and DCT Results in increased water reabsorption V3 (V1b) ACTH release
- 9. Source:AMBOSS – GENERAL ENDOCRINOLOGY, KATZUNG BASIC CLINICAL PHARMACOLOGY 14TH Minh T. Huynh V2 RECEPTOR 7/27/2021
- 10. Source: LECTURIO - ACTIONS OF ADH Minh T. Huynh V2 RECEPTOR 7/27/2021
- 12. Source: AMBOSS – Diabetes insipidus Minh T. Huynh CENTRAL DIABETES INSIPIDUS (CDI) 7/27/2021 Most common form: caused by insufficient or absent hypothalamic synthesis or secretion of antidiuretic hormone (ADH) from the posterior pituitary Primary (∼ ⅓ of cases) • Most cases are idiopathic. • The hereditary form is rare. • Autoimmune etiology of primary CDI has been suggested
- 13. Source: AMBOSS – Diabetes insipidus Minh T. Huynh CENTRAL DIABETES INSIPIDUS (CDI) 7/27/2021 Secondary (∼ ⅔ of cases) • Brain tumors (especially craniopharyngioma) and cerebral metastasis (most common: lung cancer and leukemia/lymphoma) • Neurosurgery: usually after the removal of large adenomas • Traumatic brain injury, pituitary bleeding, subarachnoid hemorrhage • Pituitary ischemia (e.g., Sheehan syndrome, ischemic stroke) • Infection (e.g., meningitis)
- 14. Source: Daniel G Bichet, MD, Clinical manifestations and causes of central diabetes insipidus, UpToDate, last accessed on 7/26/2021 Minh T. Huynh NEUROSURGERY OR TRAUMA 7/27/2021 • Often results in a typical triphasic response 1. Initial polyuric phase, beginning within 24 hours and lasting 4 to 5 days; this phase reflects inhibition of ADH release due to hypothalamic dysfunction 2. On days 6 to 11, by an antidiuretic phase in which stored hormone is slowly released from the degenerating posterior pituitary. During this stage, excessive water intake can lead to hyponatremia because of a transient syndrome of inappropriate ADH secretion 3. Permanent DI may then ensue after the posterior pituitary stores are depleted.
- 15. Source: Hoorn EJ, Zietse R. Water balance disorders after neurosurgery: the triphasic response revisited. NDT Plus. 2010 Feb;3(1):42-44. Minh T. Huynh NEUROSURGERY OR TRAUMA 7/27/2021
- 16. Source: AMBOSS – Diabetes insipidus Minh T. Huynh NEPHROGENIC DIABETES INSIPIDUS (NDI) 7/27/2021 Rare: caused by defective ADH receptors in the distal tubules and collecting ducts Hereditary • X-linked mutation of AVPR2 gene and AR/AD mutation of aquaporin-2 gene Acquired • Adverse effect of medications (lithium, demeclocycline) • Hypokalemia, hypercalcemia • Renal disease (e.g., autosomal dominant polycystic kidney disease, renal amyloidosis) • Pregnancy
- 17. Source: Minh T. Huynh HEREDITARY CAUSES 7/27/2021 How to differentitate between AVPR2 gene & aquaporin-2 gene ?
- 18. Source: Daniel G Bichet, MD, Clinical manifestations and causes of nephrogenic diabetes insipidus, UpToDate, last accessed 7/26/2021 Minh T. Huynh LITHIUM 7/27/2021 • Dysfunction of the aquaporin-2 water channel
- 19. Source: Daniel G Bichet, MD, Clinical manifestations and causes of nephrogenic diabetes insipidus, UpToDate, last accessed on 7/26/2021 Minh T. Huynh OTHER CAUSE 7/27/2021 • Hypercalcemia: reduces the antidiuretic hormone-induced increase in water permeability • Hypokalemia: both decreased collecting tubule responsiveness to ADH • Pregnancy: vasopressinase
- 21. Source: AMBOSS – Diabetes insipidus Minh T. Huynh PATHOPHYSIOLOGY 7/27/2021 • Either ↓ ADH (central DI) or defective renal ADH receptors (nephrogenic DI) → impaired ability of the kidneys to concentrate urine (hypotonic collecting ducts) → dilute urine (low urine osmolarity) • Urine osmolality changes • Normal: 500–800 mOsmol/kg • Partial DI (300–500 mOsmol/kg) • Complete DI (< 300 mOsmol/kg, often < 100 mOsmol/kg)
- 22. Source: AMBOSS – Diabetes insipidus Minh T. Huynh HYPEROSMOTIC VOLUME CONTRACTION 7/27/2021 • Loss of fluid with urine → increased extracellular fluid osmolarity → passage of fluid from the intracellular to the extracellular space → equalization of the osmolarities of the extracellular and intracellular fluid • Due to the loss of fluid, the osmolarities of intracellular and extracellular compartments are now higher (hyperosmotic) than the initial values. • The fluid volume is redistributed between the two compartments to equalize the osmolarities and remains lower than the initial values in each of them (volume contraction)
- 23. Minh T. Huynh 7/27/2021 CLINICAL MANIFESTATIONS
- 24. Source: AMBOSS – Diabetes insipidus Minh T. Huynh CLINICAL MANIFESTATIONS 7/27/2021 • Polyuria with dilute urine • Nocturia → restless sleep, daytime sleepiness • Polydipsia (excessive thirst) • In cases of low water intake → severe dehydration (altered mental status, lethargy, seizures, coma) and hypotension
- 26. Source: AMBOSS – Diabetes insipidus Minh T. Huynh DIAGNOSTICS 7/27/2021
- 27. Source: AMBOSS – Diabetes insipidus Minh T. Huynh DIFFERENTIAL DIAGNOSIS 7/27/2021 PRIMARY POLYDIPSIA CENTRAL DI NEPHROGENIC DI Cause Psychiatric diseases (e.g. schizophrenia, obsessive-compulsive disorder) Lesions in the hypothalamic thirst center • Primary: idiopathic • Secondary: brain lesions (e.g., tumors, hypoxic injury, surgery, etc.) • ADH receptor mutation • Medications (e.g., lithium, demeclocycline) • Electrolyte disturbances (hypercalcemia, hypokalemia) Mechanism Excessive water intake Decreased ADH release ADH resistance
- 28. Source: AMBOSS – Diabetes insipidus Minh T. Huynh DIFFERENTIAL DIAGNOSIS 7/27/2021 PRIMARY POLYDIPSIA CENTRAL DI NEPHROGENIC DI Lab findings Sodium Hyponatremia (< 137 meq/L) Mild hypernatremia (> 150 mEq/L) ADH level Normal or decreased Decreased Normal or increased Plasmia osmolality Low-normal (255–280 mOsmol/kg) High-normal or slightly elevated (280–290 mOsmol/kg) Urine osmolality Very low (< 250 mOsmol/kg) • Low • Partial DI: 300–500 mOsmol/kg • Complete DI: < 300 mOsmol/kg • Urine specific gravity < 1.006
- 29. Source: AMBOSS – Diabetes insipidus Minh T. Huynh DIFFERENTIAL DIAGNOSIS 7/27/2021 PRIMARY POLYDIPSIA CENTRAL DI NEPHROGENIC DI Water deprivation test results • Plasma osmolality: does not raise above normal level (275–290 mOsmol/kg) • Urine osmolality: rises, reaches normal value (> 600 mOsmol/kg) • Plasma osmolality: rises (> 290 mOsmol/kg) • Urine osmolality: remains low Desmopressin administration test result Water deprivation test results confirm diagnosis; no need to administer desmopressin Plasma osmolality: normalizes (275–290 mOsmol/kg) Urine osmolality rises In partial CDI: ∼ 10% In complete CDI: by > 50% Plasma osmolality remains elevated Urine osmolality remains low In partial NDI: ∼ 10% In complete NDI: no change
- 31. Source: AMBOSS – Diabetes Insipidus Minh T. Huynh CENTRAL DIABETES INSIPIDUS 7/27/2021 • Desmopressin: synthetic vasopressin without vasoconstrictive effects • Administration: intranasal, subcutaneous, or oral • Important side effect: hyponatremia (→ see syndrome of inappropriate antidiuretic hormone secretion) • Other indications besides central diabetes insipidus include: • Hemophilia A • Von Willebrand disease • Sleep enuresis • Alternative medication: chlorpropamide
- 32. Source: AMBOSS – Diabetes Insipidus Minh T. Huynh NEPHROGENIC DIABETES INSIPIDUS 7/27/2021 • Discontinuation of the causative agent (e.g., lithium, demeclocycline) in medication-induced NDI • Thiazide diuretics • NSAIDs (e.g., indomethacin) • Amiloride : Indicated in patients with lithium-induced NDI; amiloride blocks lithium entry through the sodium channel.
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- 37. Source: Daniel G Bichet, MD, Clinical manifestations and causes of nephrogenic diabetes insipidus, UpToDate, last accessed 7/26/2021 Minh T. Huynh SOURCE 7/27/2021 • Wondisford F.E. (2020) Posterior Pituitary. In: Essentials of Endocrinology and Metabolism. Springer, Cham. • AMBOSS – General Endocrinology • AMBOSS – Diabetes Insipidus • KATZUNG BASIC CLINICAL PHARMACOLOGY 14TH • Daniel G Bichet, MD, Clinical manifestations and causes of nephrogenic diabetes insipidus, UpToDate, last accessed 7/26/2021 • Hoorn EJ, Zietse R. Water balance disorders after neurosurgery: the triphasic response revisited. NDT Plus. 2010 Feb;3(1):42-44. • Daniel G Bichet, MD, Clinical manifestations and causes of central diabetes insipidus, UpToDate, last accessed on 7/26/2021
Editor's Notes
- - ĐTN trung ương: V NT 6-12 l/ngày; khởi phát đột ngột, khát suốt ngày và đêm, Na+ HTh bình thường cao. - ĐTN thận: khởi phát từ từ hơn.
- hoạt tính chống lợi niệu cao hơn 2000 so với LAVP Desmopressin: thuốc duy nhất được chọn. - Có 2 – 25% hoạt tính oxytocin so với LAVP chỉ ảnh hưởng ít lên co bóp tử cung. - Desmopressin không bị phá hủy bởi oxytocinase và an toàn cho cả mẹ và thai.