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

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.

A Case for Lithium Pretreatment Prior to Radioactive Iodine Ablation in Grave’s Disease

Radioactive iodine ablation (RAIA) therapy with Iodine-131 (I-131) is an established treatment for grave’s thyrotoxicosis. However, there is 10 to 20% chance of treatment failure. Lithium, a drug used to treat bipolar disorder, has significant effects on thyroid function. The most clinically relevant is the inhibition of thyroid hormone release. It is also known to inhibit colloid formation, and is involved in blocking organic iodine as well as thyroid hormone release from the thyroid gland without an effect on radioiodine uptake. This leads to increased radioiodine retention in the thyroid gland. Here, we present a case which exemplifies this action of lithium. A 46 year old male with a history of atrial fibrillation and grave’s disease presented to the endocrine clinic. TSH was <0.01 and FT4 was 36. RAI uptake (RAIU) scan showed diffusely increased uptakes with 4 and 24 hour values of 61.2 and 54.6 %. He subsequently underwent RAI ablation with 18 mCi of I 131. He then presented three years later with persistent hyperthyroid symptoms. TSH <0.01 and FT4 4.3. RAIU showed 24-h thyroid uptake of 41%. Patient opted for a second treatment with RAIA and was treated with 30 millicuries of I 131. He however continued to have clinical and biochemical evidence of thyrotoxicosis and was started on methimazole (MMI). Although he was biochemically euthyroid on MMI, he continued to complain of hyperthyroid symptoms such as palpitations, tremors and weight loss. When methimazole was briefly held six months after initiation, TSH was undetectable and FT4 had increased from 0.83 to 1.42. He subsequently underwent a third RAIU off MMI which showed normal 4 and 24 hour uptake, measuring 15.7% and 28% respectively. Patient subsequently opted for third trial of RAI ablation with lithium pretreatment. He declined surgery. He was started on lithium 900mg/day for 6 days, starting on the day of RAI ablation. He underwent RAI ablation with 45 mCi I-131. Patient tolerated the procedure well with subsequent tests indicating hypothyroidism requiring levothyroxine supplementation. Patient’s hyperthyroid symptoms resolved. Several factors affect the efficacy of radioiodide therapy for hyperthyroidism including the short persistence of radioiodide in the thyroid gland. In hyperthyroid Graves’ patients, radioactive iodide uptake is enhanced due to presence of TSH receptor antibody, however, radioiodide is also rapidly discharged because of its increased turnover. Lithium can significantly reduce the release of iodine from the thyroid gland and thus increase iodine retention. There is evidence to suggest that adjuvant lithium can increase thyroidal radioiodine uptake in patients with a low baseline RAIU (< 30%). This case demonstrate that lithium can be used safely prior to RAI therapy in cases of RAI ablation failure even with low baseline RAIU.

Surgery for Grave’s Disease

Graves’ disease (GD) is the commonest cause of hyperthyroidism followed by toxic nodular goitre. Patients presenting as goitre with clinical features of hyperthyroidism are to be carefully evaluated with biochemically with thyroid stimulating hormone (TSH), free thyroxine (fT4) and radionuclide scan (Technitium-99/Iodine-123). Those with GD also have raised thyroid receptor stimulating antibody levels. Patients are simultaneously evaluated for eye disease and managed accordingly. Initial treatment is rendering patient euthyroid using anti thyroid drugs (ATD) and if remission does not occur either continue medical therapy or proceed for definitive therapy by radioactive iodine ablation (RAI) or surgery. In last decades there is ample literature preferring surgery as preferred definitive therapy. Surgery in thyroid disease has become safer with development of many intra-operative adjuncts but it should be performed by high volume thyroid surgeon. The procedure of choice is near total or total thyroidectomy as it avoids recurrences. Patients who are not eligible or willing for surgery can be managed with RAI.

Manifestation of Marine Lenhart Syndrome after failed Radioactive Iodine therapy

Marine Lenhart Syndrome (MLS) is caused by a coexistence of active thyroid nodules and Graves’ disease1. Here, we present a case of hyperthyroidism characterized by the presence of stimulating TSH receptor antibodies, unsuccessful radioactive iodine ablation, ultimately requiring Methimazole followed by thyroidectomy. We review the current literature.

Preablation Diagnostic Whole-Body Scan vs Empiric Radioactive Iodine Ablation in Differentiated Thyroid Cancer: Cost-effectiveness Analysis

Objective To perform a comparative analysis of postthyroidectomy radioactive iodine ablation dosing with or without the implementation of a diagnostic whole-body scan in patients with well-differentiated thyroid cancer. Study Design Decision analysis model. Setting Hospital or ambulatory center. Methods A decision tree model was created to determine the cost-effectiveness of radioactive iodine ablation dosed with diagnostic whole-body scans versus empiric radioactive iodine ablation in patients with differentiated thyroid cancer undergoing postthyroidectomy ablation. The decision tree was populated with values from the published literature. Costs were represented by 2020 Medicare reimbursement rates (US dollars), and morbidity and survival data were used to calculate quality-adjusted life-years. The incremental cost-effectiveness ratio was the primary outcome. Results Empiric radioactive iodine dosing was the dominant economic strategy, producing 0.94 more quality-adjusted life-years while costing $1250.07 less than management with a diagnostic whole-body scan. Sensitivity analyses upheld these results except in cases involving a large discrepancy in successful ablation rates between the diagnostic and empiric treatment arms. Conclusion For patients with differentiated thyroid cancer requiring postthyroidectomy ablation, it is more cost-effective to administer radioactive iodine empirically.