MON-372 - Once Profoundly Hypothyroid Is Not Forever! Reversal of Near-Complete Physiologic Levothyroxine Replacement in Long-Standing Hashimoto'S Thyroiditis with Evolution to Graves' Disease

Hashimoto’s thyroiditis and Graves’ disease represent opposite ends of the autoimmune thyroid disease spectrum, characterized by destructive versus stimulatory immune mechanisms. While progression from Graves’ disease to hypothyroidism is well described, conversion from Hashimoto’s thyroiditis to Graves’ disease is rare, particularly in cases with presumed near-complete thyroid destruction. Previous cases often involve only mild hypothyroidism. We present a unique case of reversal of profound, long-standing hypothyroidism requiring full physiologic levothyroxine replacement, followed by development of Graves’ disease and sustained euthyroidism.

A 13-years old male presented with progressive hypothyroid symptoms and was found to have profound hypothyroidism with TSH >200 mcIU/mL, free T4 < 0.1 ng/dL, and thyroid peroxidase antibody >600 IU/mL. He was started on near-full levothyroxine replacement (137 mcg/day; 2.4 mcg/kg/day, 83 mcg/m2/day), with dose escalation over several years. By age 17 years, he required a full adult replacement dose of 175 mcg/day (2.2 mcg/kg/day, 88mcg/m2/day).

At age 19, while still receiving high-dose levothyroxine, his TSH became suppressed ( < 0.02 mcIU/mL) with normal T4 10.3 mcg/dL. Levothyroxine was gradually reduced and ultimately discontinued over 42 months due to persistent TSH suppression. Further evaluation revealed elevated thyroid-stimulating immunoglobulin 167% (normal < 140%) and an I-123 thyroid uptake scan showed diffusely increased homogeneous uptake of 29.8% at 6 hours (normal 6-18%) and 45.5% at 24 hours (normal 15-30%), with no ectopic activity, consistent with Graves’ disease. Thyroid ultrasound showed a diffusely heterogeneous, hyperemic gland without nodules. Thyroid function normalized off medication, and the patient has remained euthyroid for over five years with persistently elevated TSI levels, most recent at 158%.

This case illustrates that in the setting of presumed near-total thyroid destruction, as supported by extremely elevated TSH and prolonged need for full replacement dosing (2–3 mcg/kg/day), recovery of endogenous thyroid hormone production is possible as the limiting factor for adequate circulating thyroid hormone was not thyroid stimulation, given maximal pituitary reserve, but rather the availability of functional thyroid tissue, which later became responsive to stimulatory antibodies. Potential mechanisms include markedly potent stimulation of minimal residual thyroid tissue by TSI, redifferentiation of thyroid tissue, or long-standing unrecognized blocking TSH receptor antibodies. This case challenges the dogma that chronic, severe Hashimoto’s thyroiditis with essentially complete physiologic levothyroxine replacement invariably leads to irreversible hypothyroidism and supports viewing autoimmune thyroid disease as a dynamic and potentially reversible spectrum.

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