Group 6: Describe the Pathophysiology of Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH).
What is SIADH? The brain’s hypothalamus produces ADH, a hormone which is stored in and released by the pituitary gland. ADH helps the body correct abnormal fluid loss, retain water, and preserve healthy blood pressure. Problems occur when the pituitary releases too much ADH. SIADH makes it harder for your kidneys to release water and causes the levels of electrolytes, like sodium, to fall due to water retention. Moreover, overproduction of ADH can occur in places other than the pituitary gland (Pietrangelo, 2022).
Per our text, Rogers et al. (2023), Syndrome of inappropriate antidiuretic hormone (SIADH) secretion is characterized by high levels of ADH in the absence of normal physiologic stimuli for its release. A common cause of SIADH is the ectopic production of ADH by tumors, such as small cell carcinoma of the duodenum, stomach, and pancreas; cancers of the bladder, prostate, and endometrium; lymphomas; and sarcomas. Pulmonary disorders associated with SIADH include pneumonia (e.g., tuberculosis), small cell carcinoma, asthma, cystic fibrosis, and respiratory failure requiring mechanical ventilation. Central nervous system disorders that may cause SIADH include encephalitis, meningitis, intracranial hemorrhage, tumors, and trauma including neurosurgery. A nephrogenic form of SIADH involves an X-linked mutation in arginine vasopressin (AVP) genes leading to chronic activation of tubular V2 receptor and resulting in excessive free water reabsorption and concentrated urine. (Yasir, 2023) noted, any surgery can result in an increased ADH secretion for as long as 5 to 7 days. The precise mechanism is uncertain but is likely related to fluid and volume changes following surgery, the amount and type of intravenous fluids given, and the use of narcotic analgesics. Transient SIADH is especially common after pituitary surgery because stored ADH is released in an unregulated fashion.
Medications are an important cause of SIADH, especially in the elderly. These include hypoglycemic medications (e.g., chlorpropamide), antidepressants, antipsychotics, narcotics, general anesthetics, chemotherapeutic agents, nonsteroidal anti-inflammatory drugs, and synthetic ADH. These drugs either stimulate ADH release, enhance the physiologic effects of ADH, or have a biologic action similar to that of ADH (Rogers et al., 2023).
Furthermore, the pathophysiologic features of SIADH are the result of enhanced renal water retention. ADH increases renal collecting duct permeability to water by inducing the insertion of aquaporin-2, a water channel protein, into the tubular luminal membrane, which increases water reabsorption by the kidneys. This results in an expansion of extracellular fluid volume that leads to dilutional hyponatremia (low serum sodium concentration), hypoosmolarity, and urine that is inappropriately concentrated with respect to serum osmolarity, because water is reabsorbed that normally would be excreted (Rogers et al., 2023).
The symptoms of SIADH result from hypotonic (dilutional) hyponatremia and are associated with hypervolemia and weight gain. The severity and rapidity of onset determine the extent of the symptoms. Thirst, impaired taste, anorexia, dyspnea on exertion, fatigue, and dulled sensorium occur when the serum sodium level decreases rapidly from 140 to 130 mEq/L. Peripheral edema is usually absent. Gastrointestinal symptoms, including vomiting and abdominal cramps, occur with a drop in sodium concentration from 130 to 120 mEq/L. There is weight gain from water retention, even with nausea and vomiting. Even if hyponatremia develops slowly, serum sodium levels less than 110 to 115 mEq/L cause confusion, lethargy, muscle twitching, and seizures; severe and sometimes irreversible neurologic damage may occur. Symptoms resolve with correction of hyponatremia (Rogers et al., 2023).
Moreover, a diagnosis of SIADH includes the following manifestations: (1) serum hypoosmolality (<280 mOsm/kg) and hyponatremia (serum sodium level <135 mEq/L); (2) urine hyperosmolarity (i.e., the osmolality of the urine is always higher than the concurrent serum osmolality); (3) urine sodium excretion that matches sodium intake; (4) normal renal, adrenal, and thyroid function; and (5) absence of conditions that can alter volume status (e.g., recent diuretic use, heart or liver failure, hypervolemia from any cause, or renal insufficiency). ADH is difficult to measure in the serum. Copeptin, an ADH precursor molecule, may be used as a surrogate marker. Individuals with neurologic injury also may develop hyponatremia caused by cerebral salt wasting syndrome. This can be differentiated from SIADH because cerebral salt wasting is characterized by hyponatremia, hypovolemia, and weight loss. In addition, urine sodium levels are elevated (Rogers et al., 2023). Treatment of SIADH involves the correction of any underlying causal problems and fluid restriction (when feasible) with careful monitoring of sodium level status and neurologic symptoms. In severe SIADH, emergency correction of severe hyponatremia involves careful administration of hypertonic saline and, most importantly, fluid restriction to 800 to 1000 mL/day. Resolution usually occurs within 3 days, with a 2- to 3-kg weight loss resulting from enhanced free water clearance and correction of hyponatremia and salt wasting. If hyponatremia is corrected too rapidly, a severe neurologic syndrome called central pontine myelinolysis can ensue. Demeclocycline, which causes the renal tubules to develop resistance to ADH, may be used to treat resistant or chronic SIADH. Vasopressin receptor antagonists, known as vaptans, are effective in treating SIADH (Rogers et al., 2023). In summary, SIADH “ectopic ADH secretion”, is a frequent cause of hyponatremia in the clinical setting, with a wide spectrum of clinical manifestations, from asymptomatic forms to life-threatening conditions. Therefore, the correct diagnosis is mandatory and an accurate assessment of comorbidities, patient volume status and laboratory findings are required. Traditional treatment options for SIADH include fluid restriction, saline infusion, furosemide, demeclocycline and urea, but all have their limitations. In addition, the risk of hyponatremia overcorrection should be avoided, closely monitoring the response to treatment and, using DDAVP (Desmopressin is used to control the amount of urine your kidneys make) infusion as a preventive strategy (Esposito et al., 2021). References Esposito, P., Piotti, G., Bianzina, S., Malul, Y., & Dal Canton, A. (2021, June 15). The syndrome of inappropriate antidiuresis: Pathophysiology, clinical management and new therapeutic options. Karger Publishers. Pietrangelo, A. (2022, December 23). Syndrome of inappropriate antidiuretic hormone. Healthline. Rogers, J. L., Brashers, V. L., Rogers, J., McCance, K. L., & Huether, S. E. (2023). McCance & Huether’s pathophysiology: The biologic basis for disease in adults and children. Elsevier. Yasir, M. (2023, March 6). Syndrome of inappropriate antidiuretic hormone secretion. StatPearls [Internet]. [order_button_a]
