Syndrome of inappropriate antidiuretic hormone

SIADH is largely a condition identified by abnormal serum sodium levels on laboratory testing, with variable presentations in terms of history and physical examination.[2]Gross P. Clinical management of SIADH. Ther Adv Endocrinol Metab. 2012 Apr;3(2):61-73. https://www.doi.org/10.1177/2042018812437561 http://www.ncbi.nlm.nih.gov/pubmed/23148195?tool=bestpractice.com Chemistry panels are obtained frequently with any office or emergency department visit and hyponatremia diagnosed accordingly. This prompts further investigation into the etiology of hyponatremia, SIADH being the most common etiology.[16]Ellison DH, Berl T. The syndrome of inappropriate antidiuresis. N Engl J Med. 2007 May 17;356(20):2064-72.

Risk factors

Risk factors strongly associated with SIADH include increasing age (>50 years), nursing home residence, presence of pulmonary conditions (e.g., pneumonia), malignancy, central nervous system (CNS) disease or trauma, medication associated with SIADH induction, postoperative state and a history of endurance exercise.

History

Key points to investigate in the history include symptoms and signs of cerebral edema, such as nausea, vomiting, headache, altered mental status, seizure, and, most alarmingly, coma. These signs can alert the physician to the possibility of hyponatremia-induced CNS dysfunction. It is imperative to elicit the duration of these symptoms, if present.

Physical exam

There are no definitive physical exam findings that support SIADH; however, a patient may demonstrate signs of cerebral edema, including mental status changes, increased somnolence, or coma. The patient appears euvolemic.

Physical signs of hyper- or hypovolemia argue against SIADH.

Signs of hypovolemia include:

• Tachycardia

• Orthostasis

• Dry mucous membranes

• Poor skin turgor.

Signs of hypervolemia may be due to:

• Cirrhosis (e.g., ascites or lower extremity edema)

• Congestive heart failure (e.g., orthopnea, paroxysmal nocturnal dyspnea, or lower extremity edema)

• Nephrosis (e.g., anasarca or lower extremity edema).

There should also be an absence of physical findings consistent with adrenal insufficiency or hypothyroidism.

Investigations

Laboratory tests are used to confirm the following diagnostic criteria:[4]Spasovski G, Vanholder R, Allolio B, et al. Clinical practice guideline on diagnosis and treatment of hyponatraemia. Eur J Endocrinol. 2014 Mar;170(3):G1-47. https://academic.oup.com/ejendo/article/170/3/G1/6668028 http://www.ncbi.nlm.nih.gov/pubmed/24569125?tool=bestpractice.com [5]Ball S, Barth J, Levy M, et al. Society for Endocrinology endocrine emergency guidance: emergency management of severe symptomatic hyponatraemia in adult patients. Endocr Connect. 2016 Sep;5(5):G4-6. https://pmc.ncbi.nlm.nih.gov/articles/PMC5314809 http://www.ncbi.nlm.nih.gov/pubmed/27935814?tool=bestpractice.com ​​

• Hypotonic hyponatremia: low serum sodium and osmolality

• Euvolemic hyponatremia: high urine sodium, fractional excretion of sodium and urea; low BUN and serum uric acid levels

• Relatively concentrated urine: elevated urine osmolality while serum sodium and osmolality are low

• Exclusion of endocrinopathy: serum TSH and cortisol levels to rule out hypothyroidism and Addison disease, both of which cause euvolemic hyponatremia.

Further investigations include a diagnostic trial with normal saline infusion. This is only performed in patients with suspected volume depletion and should not be used in symptomatic hyponatremic patients. In SIADH, serum sodium level does not improve after a normal saline infusion (1-2 L of normal saline) is administered.

Rarely, plasma arginine vasopressin level may be measured. This test may not be readily available and is only indicated in patients with nondiagnostic laboratory results or absence of SIADH etiologies.