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syndrome of inappropriate antidiuretic hormone; SIADH; nephrogenic syndrome of inappropriate antidiuresis; NSIAD

Not diagnosed in patients on diuretics. Volume depletion caused by diuretic induces ADH secretion. [4] Etiology: 1) central nervous system disorders [5] a) meningitis, encephalitis b) brain abscess c) CNS infections d) subarachnoid hemorrhage, subdural hematoma e) ischemic stroke f) neoplasm* g) Guillain-Barre syndrome h) lupus erythematosus i) multiple sclerosis j) Shy-Drager syndrome k) delirium tremens l) acute intermittent porphyria m) trauma, skull fracture* n) hydrocephalus o) cavernous sinus thrombosis 2) psychiatric disorders 3) infections a) Rocky Mountain spotted fever b) HIV1 infection, AIDS c) Legionnaire's disease 4) pharmacologic agents* a) anticonvulsants - carbamazepine - valproate b) cyclophosphamide c) chlorpropamide d) vasopressin, desmopressin, oxytocin (also see drugs that increase vasopressin) e) thiazide diuretics (especially the elderly) f) vincristine, vinblastine g) antidepressants - tricyclic antidepressants - amitriptyline - selective serotonin reuptake inhibitors (SSRI) & - serotonin norepinephrine reuptake inhibitors (SNRI) - mirtazapine h) neuroleptics, antipsychotics - phenothiazines - thioridazine - thiothixene - haloperidol i) bromocryptine j) narcotics (opiates), tramadol k) NSAIDs & COX2 inhibitors l) methylenedioxymethamphetamine (Ecstasy) m) clofibrate n) ifosfamide o) nicotine 5) pulmonary disease [5] a) pneumonia b) tuberculosis c) aspergillosis d) pulmonary abscess, empyema e) asthma f) cystic fibrosis g) positive pressure ventilation 6) neoplasms causing ectopic production of ADH [5] a) small cell carcinoma of the lung b) pancreatic cancer, gastric cancer, duodenal cancer c) non-Hodgkin's lymphoma d) Hodgkin's disease e) thymoma f) mesothelioma g) carcinoma of the genitourinary tract - prostate cancer, bladder cancer endometrial cancer, ureteral cancer h) Ewing's sarcoma i) oropharyngeal cancer (squamous cell carcinoma) - head & neck cancer 7) postoperative state a) nausea b) pain c) anesthesia d) orthopedic surgery, esp. premenopausal women [4] e) hypophysectomy 8) endocrine disorders - hypothyroidism - glucocorticoid insufficiency, adrenal insufficiency 9) stress 10) endurance exercise (marathon) [5] 11) familial disorders - gain of function mutations in vasopressin V2 receptor 12) increase intrathoracic pressure & decreased venous return to the heart increase risk for SIADH 13) idiopathic * most common causes in adults [4] Pathology: - cerebral edema in symptomatic patients [2] Genetics: - gain of function mutations in vasopressin V2 receptor Clinical manifestations: 1) clinical euvolemia 2) initial presentation with non-specific symptoms a) headache b) nausea/vomiting is common c) dysgeusia is common 3) delirium may occur 4) severe hyponatremia a) obtundation b) seizures c) coma d) hypoxia e) respiratory arrest [2] 5) also see hyponatremia Laboratory: 1) serum chemistries a) hypotonic hyponatremia a] serum Na+ low b] serum osmolality low - of secondary importance to hyponatremia [4] b) normal renal function, adrenal function & thyroid function 1] serum creatinine normal 2] serum glucose normal 3] serum K+ normal 4] serum TSH normal c) serum chloride low, corresponding to low serum Na+ d) decreased serum urea nitrogen may be present (< 10 mg/dL) e) decreased serum uric acid may be present (< 4 mg/dL) f) osmolal gap: measured & calculated serum osmols NOT different 2) urine chemistries a) less than maximally dilute urine 1] urine osmolality generally > 100 mosm/kg H20 - elderly may not be able to dilute urine < 150 mOsm/kg H2O [4] 2] urine osmolality > plasma osmolality confirmatory b) elevated urine Na+, generally > 20 meq/L c) fractional excretion of sodium > 1% d) fractional excretion of urea > 50% e) 24 hour urine volume is low Special laboratory: - water load test (rarely used) Differential diagnosis: - polydipsia - 24 hour urine volume is high - urine osmolality may be maximally dilute Management: 1) acute treatment a) indications - symptomatic patients, neurologic symptoms - severe hyponatremia b) 3% saline infusion - increase serum sodium < 0.5 meq/L/hour & - < 10 meq/L/24 hours, < 18 meq/L/48 hrs [2] - target: formerly 4-6 meq/24 hours [2] - 6-10 meq/L/24 hours aligns with guidelines (2023) [10] - central pontine myelinolysis is danger of too rapidly correcting serum sodium - D5W +/- desmopressin for overcorrection of hyponatremia [2] - ref [2] recommends D5W + desmopressin - infusion of normal saline can result in worsening of hyponatremia [2] c) boluses of hypertonic saline may result in more-rapid neurological improvement without serious adverse events [6] d) IV loop diuretic (Bumetanide, Bumex; furosemide, Lasix) may be given for volume overload e) serum Na+ is usually corrected to 120 meq/L f) conivaptan IV or tolvaptan PO for life-threatening euvolemic & hypervolemic hyponatremia in hospitalized patients 2) chronic treatment (asymptomatic patients) a) may not be necessary after recovery from precipitating illness b) water restriction 500 mL to 1 L/day (restriction of all fluids) [8] - no restriction on dietary sodium [2] - increase solute intake (urea 15 g BID mixed with fruit juice) for low plasma osmolality & high urine osmolality not responding to fluid restriction [8,9] c) increased salt & protein intake d) loop diuretic (Lasix, Bumex) e) salt tablets, furosemide, or both no better than fluid restriction alone [7] f) demeclocycline 300-600 mg/day - doses as high as 600-1200 mg/day may be used - do NOT use in patients with cirrhosis 3) unless hyponatremia is indicated as acute, treat a chronic hyponatremia [2]

Related

hyponatremia vasopressin (antidiuretic hormone, ADH)

General

syndrome neuroendocrine disease

Database Correlations

OMIM 300539

References

  1. Manual of Medical Therapeutics, 28th ed, Ewald & McKenzie (eds), Little, Brown & Co, Boston, 1995, pg 47-48
  2. Medical Knowledge Self Assessment Program (MKSAP) 11, 14, 15, 16, 17, 18, 19. American College of Physicians, Philadelphia 1998, 2006, 2009, 2012, 2015. 2018, 2021. - Medical Knowledge Self Assessment Program (MKSAP) 19 Board Basics. An Enhancement to MKSAP19. American College of Physicians, Philadelphia 2022
  3. Harrison's Principles of Internal Medicine, 14th ed. Fauci et al (eds), McGraw-Hill Inc. NY, 1998, pg 2009
  4. Geriatrics Review Syllabus, American Geriatrics Society, 5th edition, 2002-2004; 7th edition 2010 - Geriatric Review Syllabus, 10th edition (GRS10) Harper GM, Lyons WL, Potter JF (eds) American Geriatrics Society, 2019
  5. Ellison DH and Berl T Clinical Practice: The syndrome of inappropriate antidiuresis N Engl J Med 2007, 356:2064 PMID: 17507705
  6. Garrahy A, Dineen R, Hannon AM et al. Continuous versus bolus infusion of hypertonic saline in the treatment of symptomatic hyponatremia caused by SIAD. J Clin Endocrinol Metab 2019 Sep 1; 104:3595. PMID: 30882872 https://academic.oup.com/jcem/article-abstract/104/9/3595/5381922?redirectedFrom=fulltext
  7. Vongsanim S, Pin-On P, Ruengorn C, Noppakun K. Efficacy of furosemide, oral sodium chloride, and fluid restriction for treatment of syndrome of inappropriate antidiuresis (SIAD): An open-label randomized controlled study (the EFFUSE-FLUID trial). Am J Kidney Dis 2020 Aug; 76:203 PMID: 32199708 https://www.ajkd.org/article/S0272-6386(19)31172-2/fulltext
  8. NEJM Knowledge+ Endocrinology
  9. Rondon-Berrios H, Tandukar S, Mor MK et al Urea for the Treatment of Hyponatremia. Clin J Am Soc Nephrol. 2018 Nov 7;13(11):1627-1632. PMID: 30181129 PMCID: PMC6237061 Free PMC article.
  10. Seethapathy H, Zhao S, Ouyang T et al. Severe hyponatremia correction, mortality, and central pontine myelinolysis. NEJM Evid 2023 Sep 26; 2:EVIDoa2300107. PMID: 38320180 https://evidence.nejm.org/doi/10.1056/EVIDoa2300107
  11. Adrogue HJ, Madias NE. The Syndrome of Inappropriate Antidiuresis. N Engl J Med. 2023 Oct 19;389(16):1499-1509. PMID: 37851876 Review. https://www.nejm.org/doi/pdf/10.1056/NEJMcp2210411