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LETTER TO THE EDITOR
Year : 2019  |  Volume : 16  |  Issue : 3  |  Page : 145-146

Trend toward early euthyroxinemia in admitted patients of Graves' disease on carbimazole therapy


Department of Endocrinology, PGIMER and Dr. RML Hospital, Delhi, India

Date of Submission01-Jul-2019
Date of Acceptance12-Jul-2019
Date of Web Publication18-Nov-2019

Correspondence Address:
Dr. Bindu Kulshreshtha
Department of Endocrinology PGIMER and Dr. RML Hospital, Delhi
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/trp.trp_30_19

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How to cite this article:
Roy A, Gupta R, Aggarwal A, Kulshreshtha B. Trend toward early euthyroxinemia in admitted patients of Graves' disease on carbimazole therapy. Thyroid Res Pract 2019;16:145-6

How to cite this URL:
Roy A, Gupta R, Aggarwal A, Kulshreshtha B. Trend toward early euthyroxinemia in admitted patients of Graves' disease on carbimazole therapy. Thyroid Res Pract [serial online] 2019 [cited 2019 Dec 12];16:145-6. Available from: http://www.thetrp.net/text.asp?2019/16/3/145/271153



Sir,

Thyroid function tests (TFTs) in patients with Graves' disease are usually advocated after 4–6 weeks of initiation of antithyroid drugs (ATDs).[1],[2] However, a wide variation in the initial response to ATD has been reported in different studies. While a large randomized studies from Japan involving 303 Graves' disease patients reported 3-month duration to become euthyroid, a multicenter trial from Europe reported euthyroxinemia within 3 weeks of ATD.[3],[4] Azizi tried to explain this discrepancy by comparing patients from an iodine deficient area (Tehran) versus those from an iodine sufficient area (Boston).[5] He observed that patients from Tehran became euthyroid/hypothyroid within 4 weeks of ATD, while those from Boston required 12 weeks of therapy to become euthyroid. They attributed this early response of the former group to iodine deficient state and speculated that low thyroid hormone stores in iodine deficient individuals may be the explanation for such findings. He suggested evaluation of TFT as early as 2 weeks to avoid hypothyroxinemia at a later stage. We, hereby, present our experience with TFTs within the first 2 weeks of carbimazole therapy in patients with Graves' disease admitted in our ward over the past 6 months.

There were 12 patients (age ranging: 18–62 years), 8 males and 4 females [Table 1]. Six patients presented with the impending storm (Burch-Wartofsky-Score [BWS] score: >25), three had atrial fibrillation, one had active ophthalmopathy requiring steroids, one patient presented with associated hypokalemic periodic paralysis, and the other two were admitted for poorly controlled thyrotoxicosis in spite of ATD. All patients had a Grade 3 diffuse goiter except one who had a Grade 2 goiter and seven had associated proptosis. Eight of 12 patients had been on previous ATD (for periods ranging from 1 month to 2 years) that had been discontinued for various durations. After admission, carbimazole was started in the doses of 30–60 mg. [Table 1] presents the TFT at initial presentation and within 1–2 weeks after initiation of carbimazole therapy.
Table 1: Thyroid function tests in patients at the baseline and within 1-2 weeks of carbimazole therapy

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We observed that within 1–2 weeks, there was a trend toward early normalization of T4 in all patients. At this time point, T3 levels had also come down but were still not in the normal range. Three of 12 patients developed hypothyroxinemia within the first 3–6 weeks of initiation of antithyroid therapy. The first patient developed hypothyroxinemia within 18 days, the second within 5 weeks, and the third within 6 weeks of initiation with ATDs. All these three patients had initially presented with an impending thyroid storm with very high T4 and T3 levels (4–50 times' normal values) and large goiters (requiring surgery). All these parameters (high initial T4 levels, large goiters, and clinical severity) have been considered as poor prognostic factors for early normalization of TFT.[3] In spite of this, we observed a trend toward early euthyroxinemia as early as 2 weeks of ATD. It is possible that a low iodine status of our patients may have contributed to early euthyroxinemia/hypothyroxinemia in our patients.

There are very scant data on TFT within 1–2 weeks of initiation of ATD. Azizi demonstrated that FT4 index became normal in 66% of Graves' disease patients from an iodine deficient area of Tehran within 8 days of ATD and in 86% of patients within 14 days of ATD. FT4 index became subnormal in 46% of patients within 4 weeks of antithyroid therapy in their cohort. We also observed a similar trend toward early euthyroxinemia in almost all of our patients within 1–2 weeks of ATD. Three of 12 patients (25%) became hypothyroid within 4–6 weeks of ATD. While we cannot say that euthyroidism was achieved within 2 weeks, since T3 levels were still high. However, it is suggested that early TFTs within 3 weeks are performed to avoid hypothyroxinemia at 4–6 weeks. This time period could be employed for a definitive therapy such as radioablation in poorly compliant patients with a poor follow-up.

In conclusion, there was a trend toward early euthyroxinemia in almost all our patients within 1–2 weeks of ATDs. It is possible that low iodine status of our patients may have contributed to early response to ATD. Large longitudinal studies with respect to iodine status and timed clinical response are needed to assess the duration as to when TFT should be performed after initiation of antithyroid therapy to avoid hypothyroxinemia at a later stage.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Ross DS, Burch HB, Cooper DS, Greenlee MC, Laurberg P, Maia AL, et al. 2016 American thyroid association guidelines for diagnosis and management of hyperthyroidism and other causes of thyrotoxicosis. Thyroid 2016;26:1343-421.  Back to cited text no. 1
    
2.
Kahaly GJ, Bartalena L, Hegedüs L, Leenhardt L, Poppe K, Pearce SH, et al. 2018 European thyroid association guideline for the management of graves' hyperthyroidism. Eur Thyroid J 2018;7:167-86.  Back to cited text no. 2
    
3.
Reinwein D, Benker G, Lazarus JH, Alexander WD. A prospective randomized trial of antithyroid drug dose in graves' disease therapy. European multicenter study group on antithyroid drug treatment. J Clin Endocrinol Metab 1993;76:1516-21.  Back to cited text no. 3
    
4.
Nakamura H, Noh JY, Itoh K, Fukata S, Miyauchi A, Hamada N. Comparison of methimazole and propylthiouracil in patients with hyperthyroidism caused by graves' disease. J Clin Endocrinol Metab 2007;92:2157-62.  Back to cited text no. 4
    
5.
Azizi F. Environmental iodine intake affects the response to methimazole in patients with diffuse toxic goiter. J Clin Endocrinol Metab 1985;61:374-7  Back to cited text no. 5
    



 
 
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