NDT Advance Access originally published online on May 15, 2006
Nephrology Dialysis Transplantation 2006 21(8):2318-2319; doi:10.1093/ndt/gfl231
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Carbimazole therapy in the setting of end-stage renal disease and haemodialysis
1 Department of Endocrinology and 2 Department of Medicines Information, University Hospital of North Staffordshire, Stoke-on-Trent ST4 6QG, UK
Correspondence and offprint requests to: Dr George I. Varughese MRCPI, MRCP (UK), Specialist Registrar, Department of Endocrinology, C/o Ward 61, The Metabolic Unit, North Buildings, University Hospital of North Staffordshire, Stoke-on-Trent ST4 6QG, UK. Email: georgeiv{at}doctors.org.uk
Keywords: acidosis; carbimazole; haemodialyisis; methimazole; renal failure
Thyrotoxicosis in the setting of end-stage renal disease (ESRD) is rare, and more commonly seen in females [1]. Indeed, hypothyroidism is observed in up to 9.5% of the ESRD population, as compared with 1.1% of that observed in the general population [1]. The effect of acute renal failure on free thyroid hormone levels in the setting of thyrotoxicosis is also recognized (euthyroid picture), i.e. this important beneficial adaptation to severe illness could explain the virtual absence of hyperthyroidism in renal failure patients [2,3]. Regular haemodialysis has also been reported to unmask thyrotoxicosis [4]. Propylthiouracil (PTU: 6-propyl-2-thiouracil) and methimazole (1-methyl-2-mercaptoimidazole, Tapazole) are the antithyroid drugs used in the US. Methimazole is used in most of Europe and Asia, and carbimazole, a methimazole analogue, is used in the UK and parts of the former British Commonwealth [5].
A 19-year-old male with ESRD on regular haemodialysis (thrice a week), was found to have hyperthyroidism (Table 1) with no signs of Grave's disease. Antithyroid peroxidase antibodies were negative. Carbimazole treatment was initiated at a dose of 20 mg/day (October 2005). There was no improvement in his thyroid function tests (TFTs), and he subsequently presented with an episode of paroxysmal atrial fibrillation. The dose of carbimazole was thus increased to 40 mg/day (November 2005). He was very compliant with his medications and took his tablets regularly in the morning, prior to going into hospital for his dialysis sessions. Repeat TFTs after a month again failed to show any progress (December 2005). The patient was advised to take carbimazole at a dose of 60 mg/day after his haemodialyisis. His TFTs promptly showed marked improvement (January 2006), and the dose of carbimazole has since been titrated back to 40 mg/day. He remains clinically euthyroid.
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Methimazole (of which carbimazole is the pro-drug) is not protein-bound and is therefore recommended for administration after haemodialyisis [6]. Interestingly, in the same context, it would be worth noting that carbimazole is more stable in an acidic pH and there is a likelihood that it may not be entirely converted to methimazole (the active form of the drug) in the setting of acidosis [7]. This case highlights some interesting aspects of the management of hyperthyroidism in the setting of ESRD and may also thereby demonstrate the possible impact of acidosis (potentially reduced conversion of carbimazole to methimazole) and dialysis treatment (methimazole is not protein bound and therefore more likely to be dialysed, unlike PTU which is protein bound) on the efficacy of carbimazole (the only available thionamide in the UK) in ESRD.
Timing of treatment in ESRD patients with thyroid disease on haemodialysis is extremely important and should be explored in detail, when TFTs fail to improve despite optimal therapy. The patient described above was not on any other medication that would have interfered with the bioavailability or pharmacokinetics of carbimazole treatment. We suggest that an alternative cause should be considered in such patients, as it is often the case that these factors affecting the management of thyroid dysfunction are less commonly perceived in clinical practice, and patient compliance is usually suspected in these circumstances.
Conflict of interest statement. None declared.
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Accepted in revised form: 27. 3.06
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