MON-346 - Misdiagnosis of Refractory Severe Hypothyroidism Due to Nephrotic Syndrome

Hypothyroidism affects approximately 5-10% of the global population and standard treatment is weight-based synthetic levothyroxine (LT4). The bioavailability of oral LT4 is approximately 70%; but when taken appropriately, most patients are able to maintain a clinical and biochemical euthyroid state. There is a subgroup of patients who have refractory hypothyroidism, defined as persistently elevated thyroid stimulating hormone (TSH) in spite of escalating doses of LT4 (>1.9 microgram/kilogram). We present a case of a patient with history of hypothyroidism who developed persistently elevated TSH that was misdiagnosed as medication non-adherence, but was ultimately found to have nephrotic syndrome due to new diagnosis of AL amyloidosis.

A 65-year-old female with medical history of postsurgical hypothyroidism, hypertension, prediabetes, nephrotic syndrome and recently diagnosed AL amyloidosis who presented to the hospital with chief complaints of fatigue, constipation and rectal bleeding. On triage, she was afebrile with blood pressure 89/48 mmHg, pulse 104 bpm and weight 74 kg on admission. Initial labs showed TSH of 70.86 IU/mL (normal 0.50-5.00 IU/mL), free T4 1.12 ng/dL (range 0.60-1.15 ng/dL), Total T4 3.90 g/dL (normal 4.50-12.00 g/dL). and undetectable free T3 and total T3 levels < 1.8 pg/mL (normal 2.5-3.9 pg/mL) and < 42 ng/dL (normal 71-180 ng/dL), respectively. A 24- hour urine protein was 14,900 grams and thyroid binding globulin was 6 ug/mL (normal 13-24 ug/mL). On chart review, the patient was admitted to another hospital one month prior for hypothyroidism which the endocrinology team attributed to medication non-adherence. Urinalysis during that admission revealed 4+ proteinuria which prompted renal biopsy consistent with AL amyloidosis. During present admission, the patient was started on intravenous levothyroxine and liothyronine. Her Free T4 and T3 levels remained intermittently low, but her TSH normalized after multiple dose escalations. The patient was discharged on oral LT4 200 mcg daily.

It is important to consider rare causes of refractory hypothyroidism in patients presenting with unexplained rise in TSH in spite of medication adherence. Refractory hypothyroidism can be due to poor adherence, drug and food interactions, malabsorption, and severe proteinuria. In our patient, nephrotic syndrome likely resulted in severe urinary loss of thyroid hormone and thyroid hormone-binding proteins, along with impaired reabsorption of free thyroid hormone. The most common approach is to treat with escalating doses of thyroid hormone until the TSH normalizes, as measurement of T4 and T3 levels can be challenging in these patients.

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