The boy’s mother told the medical team that the trouble had begun roughly six weeks earlier with gradual swelling of the face and lower limbs that slowly spread across his entire body. Over the same period he grew increasingly lethargic, less interactive, and more irritable than usual, with intermittent constipation. Only in the final four to five days did shortness of breath appear, worsening sharply in the last two. Beyond Down syndrome itself, he had no known medical conditions. That slow, nonspecific buildup of symptoms is precisely what makes severe hypothyroidism so dangerous in children with Down syndrome: developmental delay, reduced cognitive function, decreased activity, constipation, low muscle tone, and behavioral changes are all features that overlap with the syndrome itself, so families and clinicians alike can miss the point at which a treatable hormonal deficiency has tipped into organ-threatening decompensation.

On arrival, the boy was ill-looking and drowsy, though arousable and intermittently irritable during examination. His respiratory rate was 26 breaths per minute with an irregular pattern and visible use of accessory muscles. He had the classic physical features of Down syndrome — a flat nasal bridge, small low-set ears, a short neck, and a single transverse palmar crease — along with generalized non-pitting edema, facial puffiness, and gross abdominal distension. His lungs revealed bilateral basal crepitations with markedly decreased air entry on the left, and cardiac examination showed distant heart sounds with no visible apical impulse, no murmur, and no pericardial rub. Blood tests showed mild anemia, elevated white cell counts with neutrophil predominance, low platelets, elevated liver enzymes with AST of 243 U/L and ALT of 229 U/L, raised alkaline phosphatase, and mild kidney impairment.

The initial working diagnosis was pneumonia with sepsis, and the chest radiograph seemed to support it: a massive left-sided pleural effusion, a smaller right-sided effusion, compressed lung, and — crucially — an enlarged cardiac silhouette. That last finding changed the trajectory of the case. Pleural fluid analysis showed an exudative effusion, but the discovery of cardiomegaly prompted an echocardiogram, which revealed a large pericardial effusion without any evidence of tamponade physiology — the dangerous compression of the heart that would have demanded emergency drainage. A limited diagnostic pericardiocentesis yielded about 20 milliliters of fluid, which was strikingly uninfected: only 10 white cells per cubic millimeter, 95 percent of them lymphocytes, with negative Gram stain and bacterial culture. Point-of-care ultrasound also picked up incidental gallstones and a right-sided kidney stone, but the pivotal clue was the sterile, lymphocyte-rich fluid surrounding an enlarged heart.

Thyroid function tests, ordered because of the combination of pericardial effusion and generalized edema, confirmed the diagnosis. Free T3 was low at 1.02 pg/mL, free T4 was below the detection threshold at less than 0.42 ng/dL, and TSH was extremely elevated at 359.964 μIU/mL. Anti-thyroid peroxidase antibodies were markedly elevated at 1020 IU/mL, pointing to Hashimoto’s thyroiditis — an autoimmune destruction of the thyroid gland — as the underlying cause. Taken together with the generalized edema, the pleural and pericardial effusions, the altered sensorium, the constipation, and the towering TSH, the picture was one of severe decompensated hypothyroidism with features of myxedema crisis: the most extreme, potentially fatal form of long-standing thyroid failure.

Myxedema crisis is well recognized in adults but extremely rare in children and adolescents, and it carries high mortality if not treated early. It is characterized by progressive slowing of physical and mental activity, hypothermia, bradycardia, hypotension, hypoventilation, altered mental status, and sometimes hypoglycemia, and it can progress to multiorgan dysfunction. In this teenager, the presence of massive pericardial effusion, decreased mental status, hypotension, and a precipitating illness — suspected pneumonia — suggested that long-standing, severe hypothyroidism had finally overwhelmed the body’s compensatory mechanisms. The mechanism behind the fluid accumulation is itself instructive: hypothyroidism increases capillary permeability, allowing plasma proteins to leak into the interstitial space, while the compensatory increase in lymphatic drainage fails to keep pace. The result is protein-rich fluid accumulating in serous cavities, including the pericardium, typically over weeks to months — a slow buildup that allows the pericardium to stretch and often avoids the acute hemodynamic collapse seen with rapid effusions.

The boy was admitted to the intensive care unit and managed with non-invasive ventilation, inotropic support for his hypotension, and empirical broad-spectrum antibiotics for the suspected respiratory infection. Because intravenous levothyroxine was unavailable in their setting, the team started oral levothyroxine at 100 micrograms daily, later increased to 125 micrograms, along with intravenous hydrocortisone 50 milligrams four times daily during the acute phase. A therapeutic pleural drainage removed one liter of fluid. Serial thyroid testing documented a steady biochemical recovery: TSH fell from 359.964 to 100 by day three, then to 90.97, 69.14, and 57.151 μIU/mL by day twelve, while free T4 climbed from undetectable to 1.01 ng/dL and free T3 rose to 1.56 pg/mL.

The recovery was as striking as the presentation. The patient remained on non-invasive ventilation for nine days, was weaned to Venturi mask oxygen and then to room air, and his hemodynamic status improved enough to discontinue inotropic support. He transferred out of the ICU on day ten and was discharged on the sixteenth hospital day in stable condition, by which point both the pericardial and pleural effusions had completely resolved on serial chest radiographs. Notably, no therapeutic pericardiocentesis was ever needed: because echocardiography showed no tamponade physiology, the team adopted a conservative strategy, betting — correctly, as it turned out — that thyroid hormone replacement alone would drain the fluid. At one-week follow-up he remained clinically stable, though he was subsequently lost to follow-up, so long-term biochemical and echocardiographic outcomes could not be assessed.

The case gains broader significance from its context. Pericardial effusion occurs in an estimated 10 to 30 percent of adults with hypothyroidism but is rare in children and adolescents, and most reported pediatric cases have occurred in patients with Down syndrome. In the authors’ review of 15 previously reported cases of hypothyroidism-associated pericardial effusion, 12 — 80 percent — involved patients with Down syndrome, and all 15 achieved complete resolution with levothyroxine therapy. Cardiac tamponade developed in only two of those cases, about 13 percent, and therapeutic pericardiocentesis was performed in four. The authors also cite a study by Fort and colleagues in which thyroid dysfunction was found in roughly 1 percent of 1,130 infants with Down syndrome, compared with about 0.03 percent of the general newborn population — a risk difference that underpins the American Academy of Pediatrics recommendation to verify newborn thyroid screening results and then check TSH at 6 months, 12 months, and annually thereafter in children with Down syndrome.

That is where the resource dimension of this case becomes central. In Nepal, as in many low- and middle-income countries, no such consensus screening guidelines exist, and the authors argue that this gap allowed a teenager to reach an advanced, life-threatening stage before diagnosis. The clinical lesson they draw is specific: thyroid function testing should be considered early in any patient with Down syndrome who presents with unexplained edema, altered mental status, respiratory distress, or pericardial effusion, because even massive effusions and full-blown myxedema crisis can reverse with timely hormone replacement and supportive care. Their experience also suggests that invasive pericardiocentesis can be safely reserved for patients with hemodynamic compromise directly attributable to tamponade, and that careful echocardiographic assessment is what guides that decision. The authors acknowledge their limitations — no intravenous levothyroxine was available, long-term follow-up was lost, and the autoimmune diagnosis rested on clinical findings and anti-TPO antibodies rather than histopathology. But the trajectory from an oxygen saturation of 78 percent to complete radiological resolution in sixteen days, driven largely by a daily thyroid pill, is a vivid demonstration of why early recognition matters, and of how easily the signs can hide in plain sight within a syndrome that so often masks them.

Subject of Research: Severe autoimmune hypothyroidism presenting as myxedema crisis and massive pericardial effusion in an adolescent with Down syndrome

Article Title: Massive Pericardial Effusion as a Manifestation of Severe Autoimmune Hypothyroidism in an Adolescent With Down Syndrome: Importance of Early Recognition and Thyroid Hormone Replacement

Article References: Mishra, B., Pokharel, P., Karki, A., Rimal, O., Bakhrel, A., Koirala, D., & Sapkota, R. (2026). Massive Pericardial Effusion as a Manifestation of Severe Autoimmune Hypothyroidism in an Adolescent With Down Syndrome: Importance of Early Recognition and Thyroid Hormone Replacement. Clinical Case Reports, 14(11), Article e73795. https://doi.org/10.1002/ccr3.73795

Image Credits: AI Generated

DOI: 10.1002/ccr3.73795

Keywords: hypothyroidism, myxedema crisis, Down syndrome, pericardial effusion, Hashimoto's thyroiditis, levothyroxine, pediatrics, thyroid screening, case report, Nepal, echocardiography, autoimmune disease