An Unusual Case of SIADH

Case Report

Presentation

A 67-year-old male resident of Florida initially presented to another institution with an 8-week history of fatigue, loss of appetite, abdominal pain, and diarrhea that led to muscle wasting and a more-than-20% weight loss. The patient complained of poor appetite, early satiety, and intermittent right upper quadrant abdominal pain associated with nausea and vomiting, but no hematemesis, hematochezia, or melena. The patient was having multiple daily episodes of loose stools that did not contain mucus or blood. He denied having fevers, chills, night sweats, headaches, visual changes, dysphagia, odynophagia, cough, chest pain, dyspnea, orthopnea, edema, bleeding, or recent exposure to antibiotics. A review of systems was otherwise normal. The patient was not taking any scheduled medications at the time of his presentation. He denied smoking or heavy alcohol or illicit drug use. The patient had traveled to South America several times over the past few years, but he denied having traveled to other destinations, being exposed to animals or ticks, or consuming raw meat or unpasteurized dairy products. The patient worked in a healthcare facility and had a past medical history of hypertension, hypothyroidism, anal squamous carcinoma in situ, and diverticulitis.

Assessment

A physical examination revealed normal vital signs, presence of pallor, and generalized muscle wasting. An abdominal examination revealed mild abdominal tenderness in the right upper quadrant, with no rebound tenderness. Cardiovascular, respiratory, and neurologic examinations were normal.

The patient's laboratory evaluation revealed iron-deficiency anemia: a low hemoglobin level (10.5 g/dL) with microcytosis, a low iron level (10 mcg/dL), and a normal ferritin level (93 mcg/L). Other significant laboratory findings included a normal white blood cell count with peripheral eosinophilia (1,000 cells/uL), hyponatremia (122 mmol/L), hypoalbuminemia (2.3 g/dL), an elevated erythrocyte sedimentation rate (ESR; 55 mm), and an elevated C-reactive protein level (41.6 mg/dL). In addition, the patient's 25-hydroxy vitamin D level was low (16 ng/mL). Other routine laboratory tests, including measurement of serum creatinine, blood urea nitrogen, calcium, magnesium, and phosphorus levels, were within normal limits.

Further work-up of the patient's hyponatremia revealed high-urine osmolality and low-plasma osmolality, which were consistent with the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). Other laboratory findings included negative serologies for celiac disease, antinuclear antibody, antineutrophil cytoplasmic antibodies, acute and chronic hepatitis, HIV, Lyme disease, and syphilis. Other normal tests included measurement of serum protein electrophoresis, complement, vitamin B12, and red blood cell folate levels; stool cultures for enteric pathogens and Clostridium difficile infection; and stool microscopy for ova and parasites. To further evaluate the patient for ongoing diarrhea and SIADH, the following imaging studies were performed: a magnetic resonance imaging scan of the head; a chest radiograph; computed tomography scans of the chest, abdomen, and pelvis; and a positron emission tomography scan. These studies had unremarkable findings except for the presence of sigmoid diverticulitis. A colonoscopy showed no recurrence of the patient's anal carcinoma. The patient continued to have persistent systemic symptoms, laboratory findings revealing eosinophilia, an elevated ESR, and SIADH despite adequate treatment and resolution of diverticulitis with a 2-week course of antibiotics.

Diagnosis

After this unrevealing, extensive work-up and the persistence of the previously mentioned symptoms, the patient presented to our institution. After thoroughly reviewing his history and medical records, we suspected an underlying small-bowel pathology. An esophagogastroduodenoscopy (EGD) was performed to rule out conditions such as celiac sprue, Whipple disease, and small intestinal bacterial overgrowth. Interestingly, the EGD revealed edema, erythema, exudates, and mucosal friability located diffusely throughout the duodenum, which was consistent with extremely severe ulcerative duodenitis (Figure 1). Small-bowel biopsies revealed chronic active duodenitis with lymphocytic and eosinophilic infiltration of the duodenum associated with mucosal erosions and Strongyloides stercoralis parasitic infection invading the duodenal mucosa (Figure 2).

Figure 1.

Endoscopic images of the second (A) and third (B) portions of the duodenum showing diffuse duodenal edema, erythema, and exudates consistent with severe ulcerative duodenitis.

Figure 2.

Lymphocytic and eosinophilic infiltrates in the lamina propria consistent with chronic active duodenitis (hematoxylin and eosin stain; 200× magnification; A). Strongyloides stercoralis parasitic infection (hematoxylin and eosin stain; 200× magnification; B). Images courtesy of Tsung-Teh Wu, MD, PhD, Department of Anatomic Pathology, Mayo Clinic College of Medicine, Rochester, Minnesota.

Management

Treatment options for Strongyloides infection in immunocompetent hosts include albendazole (Albenza, Glaxo SmithKline) and ivermectin (Stromectol, Merck). Due to the presence of systemic symptoms, we chose to initially treat the patient with 1 course of ivermectin 200 mcg/kg/day for 2 days, which resulted in an interim improvement in symptoms. Three weeks later, he experienced a recurrence of abdominal pain and diarrhea. A 2-day course of ivermectin was repeated, resulting in complete resolution of symptoms and laboratory findings of hyponatremia and peripheral eosinophilia. Six weeks after his initial treatment, a repeat EGD showed complete endoscopic resolution. Duodenal biopsies revealed the presence of mild eosinophilic infiltration in the duodenal wall but no signs of active duodenitis or parasitic infection.

Discussion

S. stercoralis is an intestinal nematode that is endemic to tropical regions, occurring sporadically in temperate areas and primarily affecting travelers, immigrants, and military personnel in nonendemic areas. The highest rates of S. stercoralis infection in the United States are found in the Southeast.^1,2 Our patient resided within this endemic area and had traveled several times to various parts of South America.

S. stercoralis is unique among infectious parasites because it completes its life cycle entirely within the human host, causing autoinfection and potentially hyper-infection. Filariform larvae are found in soil and feces; they penetrate human skin, migrate to the lungs, and are later swallowed. These larvae mature into adult worms in the gastrointestinal tract and reside in the duodenal and jejunal mucosa. Infected patients experience gastrointestinal symptoms (anorexia, nausea, abdominal pain, diarrhea, and weight loss) as well as pulmonary symptoms (cough, dyspnea, wheezing, and hemoptysis). Adult worms may live up to 5 years without causing symptoms, and the only finding may be peripheral eosinophilia. Thus, individuals infected with Strongyloides may have a dormant parasitic infection for several years until they experience an immunosuppressed state, such as malnutrition; hypogammaglobulinemia; drug therapy with corticosteroids or anticancer medications; hematologic malignancies; solid-organ or bone marrow transplantation; or HIV infection.

Severe disseminated Strongyloides hyperinfection may develop in immunocompromised patients, leading to sepsis, respiratory failure, and death. Within the intestinal tract of immunocompromised hosts, rhabditiform larvae tend to transform into invasive filariform larvae that invade the gut wall and migrate to various organs, including the lungs and central nervous system (CNS), resulting in hyperinfection. Clinical features of Strongyloides hyperinfection include severe abdominal pain, nausea, vomiting, protein-losing enteropathy, and ileus associated with diffuse rash, pulmonary infiltration, gram-negative bacteremia, and sepsis.^3,4 The mechanism of sepsis in these patients is bloodstream penetration of intestinal flora secondary to weakening of the gut-blood barrier. Therefore, patients with suspicious symptoms should be routinely screened for Strongyloides infection via a complete blood cell count (to detect eosinophilia), stool specimen examination (to detect ova and parasites), and serologic testing before initiating systemic steroids or antineoplastic agents in order to prevent a dormant infection from becoming a hyperinfection.

SIADH has been associated with systemic strongyloidiasis; the mechanism is unknown, although it has been attributed to CNS or pulmonary involvement.^5–9 However, our patient did not have CNS features or pulmonary infiltration by the parasite, and the mechanism through which Strongyloides caused SIADH remains a mystery.

Conclusion

Strongyloides infection should be considered in patients with a clinical presentation of chronic abdominal pain, diarrhea, and failure to thrive (with or without skin rash) and laboratory findings of eosinophilia, elevated inflammatory markers, and SIADH in the setting of epidemiologic exposure.¹⁰ This infection is usually seen in immunocompromised patients, but it can be found in immunocompetent hosts. The failure to consider strongyloidiasis may lead to a missed or delayed diagnosis and a complicated clinical course.