Oscillating Hypo-Hyperthyroidism; a Rare Type of Autoimmune Thyroiditis in Adolescence

Abstract

Background: Spontaneous conversion of hypothyroidism to hyperthyroidism and vice versa is a unique autoimmune entity characterized by the oscillating activity of thyrotropin blocking inhibiting immunoglobulin (TBII) and thyroid-stimulating immunoglobulin (TSI). The simultaneous presence of both antibodies is a rare phenomenon in children. Clinical Case: At 11 years of age a female with Trisomy 21 and mild developmental delay had elevated TSH 5.4uIU/mL (0.4-4.5), normal thyroxine (T4), negative thyroglobulin peroxide antibody (anti-TPO), and thyroglobulin antibody (Anti-Tg). Levothyroxine (LT4) 1.2mcg/kg/day was started. At 12 years of age, she relocated, and the same treatment was continued. About 7 months later, she was referred for weight loss of 8lbs, tachycardia, high BP, suppressed TSH <0.015uIU/mL, high total T4 15.9ng/dL (4.5-12.0), and anti-TPO 38 IU/mL (<9). She was diagnosed with hyperthyroidism and LT4 was discontinued. Repeat lab showed persistently undetectable TSH, high T4, TBII 70 (normal <16%), and TSI 698 (<140 %). Methimazole (MMI) 0.38mg/kg/day and Atenolol 25mg daily was started for Grave’s disease.At 15 years of age, she presented with symptoms of hypothyroidism; 10lb weight gain in 2months, high TSH >150mIU/L, low FreeT4 0.12ng/dl (0.8-2), anti-TPO 95 IU/mL, and TSI 2.1 IU/L (0.0 - 0.55). MMI was discontinued and she was started on LT4 0.9mcg/kg/day. Repeat TFT’s 5weeks later showed a normal TSH and Free T4. Thyroid ultrasound showed a diffusely enlarged gland; right lobe - 3.9 x 2.0 x 2.0 cm (volume of: 7.6 mL) and left lobe 4.5 x 1.6 x 2.4 cm (volume: 8.6 mL) with increased vascularity on color Doppler consistent with diffuse thyroiditis. A year later, she developed hyperthyroid symptoms for the second time with 6lb weight loss, tachycardia, suppressed TSH <0.015uIU/mL, elevated free T4 >6.9ng/dl, TBII 8.6 U/L (<1.0), and TSI 12 IU/L. However, this time her TSI level was significantly higher than when she was hypothyroid. She was treated with MMI 0.15mg/kg/day which was increased to 0.3mg/kg/day, and 3months later she reverted to hypothyroidism; TSH 17.5uIU/mL, Low free T4 0.54ng/dl, normal total T3, with 15lb weight gain. Her MMI dose was lowered to 0.15mg/kg/day, however more definitive treatment options including thyroidectomy and radioactive iodine ablation was discussed with the family. Conclusion: The spectrum of autoimmune thyroid disorders span between extremes of Hashimoto’s thyroiditis and Graves’ disease, but rarely in adolescents, these conditions can co-exist, and management can be challenging and tedious to the patient, family, and physician. Since autoantibody status/titer may not always predict the clinical course, it is important for clinicians to keep a high index of suspicion of this process when the clinical course is atypical. Definitive therapy with thyroidectomy or radioactive iodine ablation may be a suitable option in these cases.