Endocrine Abstracts

Graves’ disease (GD) and Hashimoto’s thyroiditis (HT) are both autoimmune thyroid diseases. While transition from GD to hypothyroidism has been more frequently reported, conversion of hypothyroidism to GD is uncommon. We describe a series of 3 patients diagnosed with HT and hypothyroidism, treated with L-thyroxine (LT4), who developed persistent hyperthyroidism with increased thyrotropin receptor antibodies (TRAb) levels and, in two of the patients, Graves’ ophtalmopathy.

Case 1: A 46 year-old woman with primary hypothyroidism (TSH 169 mIU/l, normal values 0.5–4.5) treated for 3 years with LT4 50 μg/day, develops hyperthyroidism (TSH 0.013 mIU/l, FT4 2.69 pmol/l (0.6–1.76), TPOAb 260 U/ml (0–35), TRAb 27 IU/ml (< 1.75). Although LT4 was reduced and eventually discontinued, the patient developed mild unilateral exophthalmos and diplopia, with a normal-sized highly vascularized thyroid. She was treated with methimazole and i.v. methylprednisolone pulse-therapy. Her TSH level is still suppressed after 5 months.

Case 2: A 54 year-old woman with chronic hepatitis C, treated with pegylated interferon for 3 months, developed overt hypothyroidism with a small diffuse goiter 3 months after IFNα withdrawal (TSH 63.7 mIU/l, FT4 5.38 pmol/ml (10–28.2), TPOAb 3815 U/ml. LT4 was gradually increased up to 100 μg/day. Two months later, despite progressive LT4 withdrawal, the patient developed hyperthyroidism with mild bilateral exophthalmia (TSH < 0.005 mIU/l, FT4 39.6 pmol/l, TPOAb =434 IU/ml, TRAb 15.5 IU/ml), increased homogenous uptake of ⁹⁹Tc pertechnetate at thyroid scintigraphy. On methimazole she had rapid oscillations of TSH levels and was treated with radioactive iodine 1 year later.

Case 3: A 39 year-old man with HT, hypothyroidism and intermittent mildly increased calcitonin levels (TSH 12.9 mIU/l, FT4 0.71 ng/dl (0.7–1.48), TPOAb >1000 U/ml, calcitonin 9.01 pg/ml (1–8.4), with a small micronodular goiter, has been treated with LT4 50 μg/day for 14 months, when he developed progressive hyperthyroidism with increased ¹³¹I uptake and TRAb 1.87 IU/ml (<1.75). He was started on methimazole which normalized TSH levels in 5 months.

Conclusion: Conversion of LT4-treated hypothyroidism to GD is very rare (i.e. three cases in a 20 year- experience of a single clinician). Conversion of blocking- to stimulating- TRAb or distinct immune paradigms for GD and HT may account for this switch, while interferon treatment may be a trigger in some cases.