Hypothyroidism Converting to Hyperthyroidism: An Autoimmune Phenomenon?

It is well known that Graves’ disease can convert to hypothyroidism. On the contrary, here we present a case series of 2 patients with hypothyroidism who converted to hyperthyroidism.

Case Description:

Case 1: An 84-year-old female with history of hypothyroidism presented to the emergency department with complaint of fatigue worsening over few weeks. She also endorsed unintentional weight loss of 10 pounds in the last two weeks. Patient reported initially being diagnosed with hypothyroidism by an endocrinologist about 25 years ago, and since had been on levothyroxine therapy. She reported strict compliance with levothyroxine 75 mcg/day for many years. Her last documented TSH level prior to the presentation was 0.79 mIU/ml. Physical exam included normal vitals, skin, and thyroid exam. While in the ER, she was found to have a suppressed TSH of < 0.005 uIU/ml with an elevated Free T4 of 2.5 ng/dL and an elevated Free T3 of 8.7 pg/ml. TPO antibodies were unremarkable. TRAB was elevated at 8.43 IU/L and TSI was elevated at 2.23 IU/L. Thyroid ultrasound revealed a relatively unremarkable thyroid tissue with no prominent heterogeneity. The diagnosis of autoimmune hyperthyroidism was made, and the patient’s levothyroxine therapy was discontinued.

Case 2: A 57-year-old female with history of hypothyroidism presented to the endocrinologist with left neck swelling, palpitations, visual changes, and heat intolerance for the past 6 months. She was diagnosed with hypothyroidism 10 years ago and had been well controlled on levothyroxine. Physical exam revealed tachycardia, large non-tender goiter, exophthalmos, and lid lag. Workup revealed suppressed TSH of < 0.005 uIU/ml, elevated free T4 of 1.6 ng/dL, elevated free T3 of 10.3 pg/ml, elevated TRAB at 108 IU/L , elevated TSI at 90.10 IU/L and elevated TPO antibodies at >1,300 u/ml. Thyroid ultrasound showed an enlarged, diffusely heterogeneous thyroid gland without nodules. The patient was started on atenolol 25 mg daily and levothyroxine was discontinued. RAI uptake and scan demonstrated thyromegaly with elevated 4-hour uptake at 53% and 24-hour uptake at 71% consistent with hyperthyroidism. The patient was started on methimazole 10 mg daily.

Discussion:

The patients had timely diagnosis of conversion from hypothyroidism to hyperthyroidism. Increasing number of such cases have been reported since first being described in 1959 [1]. Underlying mechanism of such conversions have not been proven, but one of the proposed mechanisms is the presence of both blocking and stimulating antibodies causing a pull-push effect shifting to either hypothyroidism or hyperthyroidism respectively [2]. We need to consider testing for Graves’ disease in stable hypothyroidism patients who developed hyperthyroidism.