source: Endocrine Society

year: 2015

authors: Spyridoula Maraka, M Regina Castro, Diana S Dean, Vahab Fatourechi, Pravin Thapa, Rebecca S Bahn, Marius N Stan

Background:
Radioactive iodine (RAI) therapy is the most common method of treating Graves’ disease (GD) in the United States.  The current practice is to reevaluate these patients 2-3 months after RAI.  The majority are hypothyroid by that time with some experiencing related troublesome symptoms and possible development or worsening of Graves’ orbitopathy.  We initiated this randomized controlled trial (RCT) to determine whether early treatment with levothyroxine after RAI therapy for GD will prevent overt hypothyroidism (OH).

Hypothesis:
The aim of this interim analysis of our RCT is to test the safety of early levothyroxine therapy following RAI therapy using our study protocol.

Design and Methods:
Patients (ages 18-70 yr) with GD treated with RAI were randomized 4 weeks later, in double-blinded manner, to start levothyroxine 25 mcg/day or placebo.  The levothyroxine dose was increased to 50 mcg/day, 2 weeks later.  At 8 weeks post RAI, all patients had a face-to-face clinical evaluation.  Patients in both groups had blood drawn for measurement of TSH and free thyroxine (fT4) at 4, 6, and 8 weeks.  Incidence of OH at 8 weeks, defined as TSH > 4.5 mIU/L or fT4 < 0.8 ng/dL, was the primary endpoint.  Hyperthyroidism was defined as fT4 > 1.8 ng/dL.  The hypothyroid-Health Related Quality of Life (H-HRQL) and the Thyroid Specific Questionnaire (TSQ) were completed at 4, 6, and 8 weeks by both groups to assess quality of life.  Data is reported as median and interquartile range.

Results:
This analysis reports on the initial 17 patients enrolled in our trial, in which 60 patients will ultimately be enrolled.  Eleven patients were randomized to levothyroxine and 6 patients to placebo.  There was no difference at baseline between patients in the levothyroxine and placebo arm regarding age (52.7, 27.6-60.6 vs. 55.3, 46.7-66.2 yr), gender (female 72.7 vs. 66.7%), thyroid size (30, 25-40 vs. 30, 15-35 g), and fT4 (2.7, 2.4-4.8 vs. 1.9, 1.3-2.6 ng/dL).  Only one adverse event was reported; a patient in the levothyroxine arm discontinued the study drug due to palpitations.  At 8 weeks, OH was found in 54.5% of patients on levothyroxine compared to 66.7% of patients on placebo.  The levothyroxine group had lower rate of hyperthyroidism (18.2%) than the placebo group (33.3%).  The levothyroxine group had similar TSQ score with the placebo group (12, 12-22 vs. 12, 11-13) but somewhat worse H-HRQL score (46, 39-67 vs. 36, 31.5-42.5).  As expected none of the analyses reached statistical significance given that the sample size is 25% of the planned population.

Conclusions:
It is reassuring that initiating low dose levothyroxine 4 weeks after RAI appears safe, without increased prevalence of hyperthyroidism.  There is an encouraging trend for prevention of OH.  In this small sample we do not see yet congruent improvement in the quality of life.  Accordingly, we plan to continue the trial to completion without protocol modifications.

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