Recurrent ascites with severe hypoproteinemia in 4-year-old child: A diagnostic dilemma - An atypical presentation of hypothyroidism.

Hypothyroidism is frequently encountered condition to a pediatrician. Passive effusions into serous cavities, sometimes to considerable amount are frequently noted. However, the significant ascites caused by this is rare in a child and in no instance, it is too excessive. So diagnosis is frequently delayed and patient frequently receive unnecessary procedures such as liver, even gastrointestinal biopsies. Analysis of ascitic fluid shows exudative nature with high protein. The case we present here is a 4-year-old female child with recurrent ascites, developmental delay and hypoproteinemia. High index of suspicion can lead to diagnosis. Over all prognosis is excellent after stating replacement therapy with L-thyroxine.

INTRODUCTION

The development of significant ascites in hypothyroidism is well-known in adults. But its occurrence in pediatric patients is rare, especially associated with moderate to severe hypoproteinemia. It was first described in 1886 and occurs in 4% of total and less than 1% of newly diagnosed cases in adults.[12] Its exact incidence in pediatric patients is not clear. Most of these patients undergo unnecessary procedures such as multiple paracentesis, gastrointestinal (GI) and liver biopsies before the actual diagnosis is made[3] often leading to unnecessary delay in diagnosis.[4] Therefore in patients presenting as ascites of unknown etiology with physical and developmental delay, hypothyroidism should be kept as differential, as treatment leads to fast recovery.[5]

CASE REPORT

We report a case of 4-year-old female child, who presented to us with history of progressively increasing abdominal distension and minimal pedal edema for 2 months. There was no preceding history of fever, oliguria, orthopnea, jaundice, bleeding, any cough, h/o Koch's contact or recurrent diarrhea suggestive of malabsorption syndrome. She had these symptoms intermittently for past 2 years for which she was treated with diuretics. She was first live issue born at term by vaginal delivery following uncomplicated pregnancy and was immunized for age. She had a history of developmental delay, with developmental age corresponding to 2 years. She was documented to have hypoproteinemia without proteinuria on multiple occasions and had undergone liver and even cardiac biopsy for possibility of some restrictive cardiomyopathy, both of which reported as normal. Her weight and height were both below 3rd centiles. On examination, she was afebrile with pulse rate 64/min, respiratory rate 34/min and blood pressure of 80/60 mm of Hg. She had coarse facies with depressed nasal bridge but no obvious facial dysmorphism. There was mild periorbital puffiness, minimal pedal edema, pallor and normal jugular venous pressure. Her skin was dry and coarse. Abdominal examination revealed grossly distended abdomen with liver palpable 3 cm below right costal margin, non-tender with smooth surface and sharp margins. There was shifting dullness suggestive of free fluid in abdomen. Cardiovascular examination revealed faint and distant heart sounds and no murmur. Central nervous system examination revealed delayed relaxation of ankle jerks. Her complete blood count revealed hemoglobin of 10.2, white blood cells (WBC) 12,700 (P56, L40, M3, E1), platelets 4.13 lakhs/cmm with macrocytosis on peripheral blood smear. Total serum protein was 3.1 mg/dl with 2.2 mg/dl of albumin and normal liver function tests. Her renal functions, electrolytes, calcium, urine for albumin and chest X-ray were normal. Electrocardiogram showed low voltage complexes. echocardiogram (ECHO) revealed intrinsically normal heart with normal ejection fraction and minimal pericardial effusion. Ultrasonography (USG) revealed mild hepatomegaly and moderate ascites [Figure 1]. GI endoscopic biopsy done to rule out protein losing enteropathy was normal. Work-up for Wilson's disease, tuberculosis and celiac serology was normal. Bone age corresponded to age of 2 years. Diagnostic paracentesis revealed 58 cells/μl, with 82% lymphocytes, 68 mg% sugar, 148 mg% cholesterol and 2.8 mg/dl of total proteins, 1.9 mg/dl of albumin with serum-ascites-albumin gradient (SAAG) of 0.3 mg/dl. Thyroid profile was suggestive of hypothyroidism with total serum T3 = 0.84 nmol/L, T4 = 48 nmol/L and thyroid-stimulating hormone (TSH) = 30 mIU/L. Her antithyroid peroxidase antibodies were negative and USG revealed mild enlargement of thyroid glands. On treating with thyroxine replacement at 4 μg/kg/day, ascites started decreasing 3 weeks following treatment [Figure 2]. Her thyroid profile repeated after 3 months normalized to T3 = 3.3 nmol/L, T4 = 79 nmol/L and TSH = 4.3 mIU/L. Repeat serum albumin increased to 3.2 mg/dl. On repeat ECHO, pericardial effusion resolved.

Figure 1

Ultrasonography abdomen showing ascitic fluid

Figure 2

Ultrasonography abdomen after treatment, showing disappearance of ascitic fluid

DISCUSSION

Hypothyroidism is a relatively rare cause of ascites especially in pediatric patients. The exact incidence is not clear but there is slight female preponderance.[6] This is potentially curable with thyroxin replacement unlike chronic hepatic and renal diseases where little can be offered to patients. In evaluation of new cases of ascites, the study of ascitic fluid, especially total protein and SAAG may curtail the list of different invasive and expensive investigations. SAAG differentiates between transudative and exudative processes. SAAG more than 1.1 g/dl indicates transudate.[7] Chronic liver disease, congestive cardiac failure, chronic renal disease, nephrotic syndrome, malnutrition or hypoalbuminemia of any other cause produces transudate. SAAG less than 1.1 g/dl usually indicates an exudative process.[7] Of various causes, tubercular peritonitis, pyogenic peritonitis, peritoneal malignancies and pancreatic causes can all lead to high protein ascites. However, hypothyroidism is a rare possibility that should be kept considered in evaluation of exudative ascites. Ascitic fluid in case of hypothyroidism reveals high protein (>2.5 g/dl) and SAAG value is usually low although it may vary. Review of literature revealed 52 documented cases of myxedema ascites in adults.[4589] A very consistent finding was high total protein level (>2.5 g/dl) in almost all cases with mean SAAG of 1.5 g/dl with a range of 0.8-2.3 g/dl.[1] WBC counts were rather low, usually with a lymphocytic predominance with a mean of 60 cells/μl and 81% lymphocytes. In our patient, WBC count was 58 cells/μl with lymphocyte 82%. The mechanism of ascitic fluid formation in hypothyroidism is unclear. Two hypotheses have been postulated. One is that low levels of circulating thyroid hormones cause increased extravasations of plasma proteins because of abnormal capillary permeability with a lack of a compensatory increase in lymph flow and protein return rate[10] which also accounts for hypoproteinemia in the case of hypothyroidism. The second hypothesis is that hyaluronic acid accumulated in the skin produces edema by direct hygroscopic effect. However, hyaluronic acid has only been found in minute quantities in patients with myxedema ascites, not large enough to exert a direct hygroscopic effect. But it could interact with albumin to form complexes that prevent the lymphatic drainage of extravasated albumin. Prompt recognition of hypothyroid ascites prevents the inappropriate use of diuretics and unnecessary procedures, including repeated paracenteses and liver biopsies.[8]

CONCLUSION

Hypothyroid ascites is rare but easy to treat. Treatment with thyroxine leads to complete regression of the ascites. A very prominent feature is the high total protein level in the ascitic fluid. Once routine evaluation of ascites excludes common causes, thyroid function tests should be performed on patients with clinical features suggestive of hypothyroidism and high protein levels in the ascitic fluid.