Hypothyroidism less common with preemptive levothyroxine after Graves’ treatment

San Diego – Preemptive levothyroxine seems to help prevent hypothyroidism after radioactive iodine treatment for Graves’ disease, according to an interim analysis of an ongoing randomized, placebo-controlled trial at the Mayo Clinic in Rochester, Minn.

Following iodine treatment, the team is randomizing adult patients to levothyroxine 25 mcg/day or placebo at 4 weeks, then increasing the levothyroxine dose to 50 mcg/day at 6 weeks. The enrollment goal is 60 patients; the team presented results for the first 17 at the Endocrine Society annual meeting.

At 8 weeks, six of 11 (54.5%) levothyroxine patients – but four of the six (66.7%) placebo patients – had overt hypothyroidism.

Hyperthyroidism is the main concern with preemptive levothyroxine, but that hasn’t been a problem so far; in fact, the levothyroxine group has had lower rates of hyperthyroidism (18.2%) than the placebo group (33.3%). Quality of life indicators haven’t separated much; at 8 weeks, thyroid Specific Questionnaire scores were about 12 in both groups, and levothyroxine patients did slightly worse on the hypothyroid–Health Related Quality of Life survey (46 vs. 36).

Given the low numbers, you can’t put too much stock in the findings yet, but the prevention trends are moving in the right direction, said lead investigator Dr. Spyridoula Maraka, a Mayo endocrinology fellow.

“As expected, none of the analyses reached statistical significance given that the sample size is 25% of the planned population,” but “it is reassuring that initiating low-dose levothyroxine 4 weeks after [Graves’ treatment] appears safe, without an increased prevalence of hyperthyroidism. There is an encouraging trend for prevention of overt hypothyroidism .... Accordingly, we plan to continue the trial to completion,” she said.

The work is important because, in many places, the first follow-up visit after Graves’ treatment is at 2 or even 3 months. By then, the majority of patients are hypothyroid, and may even have new or worsened Graves’ orbitopathy. The hope is that pre-emptive levothyroxine will counter the problem.

The fact that more than half of the levothyroxine subjects developed hypothryroidism suggests that “maybe we need a higher dose,” Dr. Maraka said.

If nothing else, the findings argue for earlier follow-up after radioactive iodine treatment, when there’s still a chance of catching nascent hypothyroidism before symptoms set in. “Try to see your patients earlier than week 8.” Six weeks might be a good goal, Dr. Maraka said.

There were no significant baseline differences between the placebo and levothyroxine arms of the study. In both, patients were in their mid-50s, on average, with thyroids of about 30 grams; about two-thirds of patients in both arms were women.

There’s been one adverse event so far; a levothyroxine patient with a history of atrial fibrillation had heart palpitations after quitting her beta-blocker, and dropped out of the study.

Pre-emptive levothyroxine has been studied before, but only retrospectively.

Dr. Maraka has no disclosures, and there was no outside funding for the work.

[email protected]

San Diego – Preemptive levothyroxine seems to help prevent hypothyroidism after radioactive iodine treatment for Graves’ disease, according to an interim analysis of an ongoing randomized, placebo-controlled trial at the Mayo Clinic in Rochester, Minn.

Following iodine treatment, the team is randomizing adult patients to levothyroxine 25 mcg/day or placebo at 4 weeks, then increasing the levothyroxine dose to 50 mcg/day at 6 weeks. The enrollment goal is 60 patients; the team presented results for the first 17 at the Endocrine Society annual meeting.

At 8 weeks, six of 11 (54.5%) levothyroxine patients – but four of the six (66.7%) placebo patients – had overt hypothyroidism.

Hyperthyroidism is the main concern with preemptive levothyroxine, but that hasn’t been a problem so far; in fact, the levothyroxine group has had lower rates of hyperthyroidism (18.2%) than the placebo group (33.3%). Quality of life indicators haven’t separated much; at 8 weeks, thyroid Specific Questionnaire scores were about 12 in both groups, and levothyroxine patients did slightly worse on the hypothyroid–Health Related Quality of Life survey (46 vs. 36).

Given the low numbers, you can’t put too much stock in the findings yet, but the prevention trends are moving in the right direction, said lead investigator Dr. Spyridoula Maraka, a Mayo endocrinology fellow.

“As expected, none of the analyses reached statistical significance given that the sample size is 25% of the planned population,” but “it is reassuring that initiating low-dose levothyroxine 4 weeks after [Graves’ treatment] appears safe, without an increased prevalence of hyperthyroidism. There is an encouraging trend for prevention of overt hypothyroidism .... Accordingly, we plan to continue the trial to completion,” she said.

The work is important because, in many places, the first follow-up visit after Graves’ treatment is at 2 or even 3 months. By then, the majority of patients are hypothyroid, and may even have new or worsened Graves’ orbitopathy. The hope is that pre-emptive levothyroxine will counter the problem.

The fact that more than half of the levothyroxine subjects developed hypothryroidism suggests that “maybe we need a higher dose,” Dr. Maraka said.

If nothing else, the findings argue for earlier follow-up after radioactive iodine treatment, when there’s still a chance of catching nascent hypothyroidism before symptoms set in. “Try to see your patients earlier than week 8.” Six weeks might be a good goal, Dr. Maraka said.

There were no significant baseline differences between the placebo and levothyroxine arms of the study. In both, patients were in their mid-50s, on average, with thyroids of about 30 grams; about two-thirds of patients in both arms were women.

There’s been one adverse event so far; a levothyroxine patient with a history of atrial fibrillation had heart palpitations after quitting her beta-blocker, and dropped out of the study.

Pre-emptive levothyroxine has been studied before, but only retrospectively.

Dr. Maraka has no disclosures, and there was no outside funding for the work.

[email protected]

San Diego – Preemptive levothyroxine seems to help prevent hypothyroidism after radioactive iodine treatment for Graves’ disease, according to an interim analysis of an ongoing randomized, placebo-controlled trial at the Mayo Clinic in Rochester, Minn.

Following iodine treatment, the team is randomizing adult patients to levothyroxine 25 mcg/day or placebo at 4 weeks, then increasing the levothyroxine dose to 50 mcg/day at 6 weeks. The enrollment goal is 60 patients; the team presented results for the first 17 at the Endocrine Society annual meeting.

At 8 weeks, six of 11 (54.5%) levothyroxine patients – but four of the six (66.7%) placebo patients – had overt hypothyroidism.

Hyperthyroidism is the main concern with preemptive levothyroxine, but that hasn’t been a problem so far; in fact, the levothyroxine group has had lower rates of hyperthyroidism (18.2%) than the placebo group (33.3%). Quality of life indicators haven’t separated much; at 8 weeks, thyroid Specific Questionnaire scores were about 12 in both groups, and levothyroxine patients did slightly worse on the hypothyroid–Health Related Quality of Life survey (46 vs. 36).

Given the low numbers, you can’t put too much stock in the findings yet, but the prevention trends are moving in the right direction, said lead investigator Dr. Spyridoula Maraka, a Mayo endocrinology fellow.

“As expected, none of the analyses reached statistical significance given that the sample size is 25% of the planned population,” but “it is reassuring that initiating low-dose levothyroxine 4 weeks after [Graves’ treatment] appears safe, without an increased prevalence of hyperthyroidism. There is an encouraging trend for prevention of overt hypothyroidism .... Accordingly, we plan to continue the trial to completion,” she said.

The work is important because, in many places, the first follow-up visit after Graves’ treatment is at 2 or even 3 months. By then, the majority of patients are hypothyroid, and may even have new or worsened Graves’ orbitopathy. The hope is that pre-emptive levothyroxine will counter the problem.

The fact that more than half of the levothyroxine subjects developed hypothryroidism suggests that “maybe we need a higher dose,” Dr. Maraka said.

If nothing else, the findings argue for earlier follow-up after radioactive iodine treatment, when there’s still a chance of catching nascent hypothyroidism before symptoms set in. “Try to see your patients earlier than week 8.” Six weeks might be a good goal, Dr. Maraka said.

There were no significant baseline differences between the placebo and levothyroxine arms of the study. In both, patients were in their mid-50s, on average, with thyroids of about 30 grams; about two-thirds of patients in both arms were women.

There’s been one adverse event so far; a levothyroxine patient with a history of atrial fibrillation had heart palpitations after quitting her beta-blocker, and dropped out of the study.

Pre-emptive levothyroxine has been studied before, but only retrospectively.

Dr. Maraka has no disclosures, and there was no outside funding for the work.

[email protected]