Cabergoline and Mitral Regurgitation
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《新英格兰医药杂志》
To the Editor: Pinero et al. (Nov. 3 issue)1 describe a 74-year-old man with Parkinson's disease in whom severe mitral regurgitation developed after a relatively short course of treatment with cabergoline, an ergot dopamine agonist. Cabergoline is used in different settings at different doses. In patients with Parkinson's disease, the usual daily dose ranges from 2 to 6 mg,2 whereas in hyperprolactinemia, the weekly dose ranges from 0.25 to 3.5 mg.3 So far, fibrotic reactions and valvular heart disease due to the use of ergot dopamine agonists have been reported almost exclusively in patients with Parkinson's disease and thus could be related to age, dosage, or both. I would be very interested to know the dose of cabergoline used for the patient described by Pinero et al., and I wonder whether young patients receiving low-dose cabergoline therapy for hyperprolactinemia should be aware of the potential risk of fibrotic side effects.
Etienne Delgrange, M.D.
Université Catholique de Louvain
5530 Mont-sur-Meuse, Belgium
etienne.delgrange@mint.ucl.ac.be
References
Pinero A, Marcos-Alberca P, Fortes J. Cabergoline-related severe restrictive mitral regurgitation. N Engl J Med 2005;353:1976-1977.
Lang AE, Lozano AM. Parkinson's disease. N Engl J Med 1998;339:1130-1143.
Colao A, Di Sarno A, Cappabianca P, Di Somma C, Pivonello R, Lombardi G. Withdrawal of long-term cabergoline therapy for tumoral and nontumoral hyperprolactinemia. N Engl J Med 2003;349:2023-2033.
The authors reply: We are grateful to Dr. Delgrange for the interest in our letter. Our patient was treated initially with 2 mg of cabergoline daily; he subsequently received an additional 2 mg daily, starting at the beginning of the second month. The serious adverse effect was observed at the end of the fourth month of treatment.
The incidence of valvular damage due to cabergoline is not established. Horvath et al.1 reported polyvalvular regurgitation in a patient taking cabergoline for 20 months, with stepwise increases in the dosage from 2 mg to 4 mg per day. The cumulative dose was greater than in our patient, but the lesions were mild and reversible.1 In clinical trials of cabergoline, the absence of valvular lesions could be due to short follow-up.2
It is true that the doses of cabergoline used in hyperprolactinemia are considerably lower than those used in Parkinson's disease,3 so it would be reasonable to assume a lower risk of valvular lesions. However, higher doses of cabergoline, similar to those used in patients with Parkinson's disease, have been used in treating resistant hyperprolactinemia associated with giant prolactinomas.4 In such cases, the risk of valvular disease may be greater.
Antonio Pinero, M.D.
Pedro Marcos-Alberca, M.D.
José Fortes, M.D.
Fundación Jiménez Díaz
28040 Madrid, Spain
pmarcos@fjd.es
References
Horvath J, Fross RD, Kleiner-Fisman G, et al. Severe multivalvular heart disease: a new complication of the ergot derivative dopamine agonists. Mov Disord 2004;19:656-662.
Clarke CE, Deane KH. Cabergoline for levodopa-induced complications in Parkinson's disease. Cochrane Database Syst Rev 2001;1:CD001518-CD001518.
Colao A, Di Sarno A, Cappabianca P, Di Somma C, Pivonello R, Lombardi G. Withdrawal of long-term cabergoline therapy for tumoral and nontumoral hyperprolactinemia. N Engl J Med 2003;349:2023-2033.
Gillam MP, Middler S, Freed DJ, Molitch ME. The novel use of very high doses of cabergoline and a combination of testosterone and an aromatase inhibitor in the treatment of a giant prolactinoma. J Clin Endocrinol Metab 2002;87:4447-4451.
Etienne Delgrange, M.D.
Université Catholique de Louvain
5530 Mont-sur-Meuse, Belgium
etienne.delgrange@mint.ucl.ac.be
References
Pinero A, Marcos-Alberca P, Fortes J. Cabergoline-related severe restrictive mitral regurgitation. N Engl J Med 2005;353:1976-1977.
Lang AE, Lozano AM. Parkinson's disease. N Engl J Med 1998;339:1130-1143.
Colao A, Di Sarno A, Cappabianca P, Di Somma C, Pivonello R, Lombardi G. Withdrawal of long-term cabergoline therapy for tumoral and nontumoral hyperprolactinemia. N Engl J Med 2003;349:2023-2033.
The authors reply: We are grateful to Dr. Delgrange for the interest in our letter. Our patient was treated initially with 2 mg of cabergoline daily; he subsequently received an additional 2 mg daily, starting at the beginning of the second month. The serious adverse effect was observed at the end of the fourth month of treatment.
The incidence of valvular damage due to cabergoline is not established. Horvath et al.1 reported polyvalvular regurgitation in a patient taking cabergoline for 20 months, with stepwise increases in the dosage from 2 mg to 4 mg per day. The cumulative dose was greater than in our patient, but the lesions were mild and reversible.1 In clinical trials of cabergoline, the absence of valvular lesions could be due to short follow-up.2
It is true that the doses of cabergoline used in hyperprolactinemia are considerably lower than those used in Parkinson's disease,3 so it would be reasonable to assume a lower risk of valvular lesions. However, higher doses of cabergoline, similar to those used in patients with Parkinson's disease, have been used in treating resistant hyperprolactinemia associated with giant prolactinomas.4 In such cases, the risk of valvular disease may be greater.
Antonio Pinero, M.D.
Pedro Marcos-Alberca, M.D.
José Fortes, M.D.
Fundación Jiménez Díaz
28040 Madrid, Spain
pmarcos@fjd.es
References
Horvath J, Fross RD, Kleiner-Fisman G, et al. Severe multivalvular heart disease: a new complication of the ergot derivative dopamine agonists. Mov Disord 2004;19:656-662.
Clarke CE, Deane KH. Cabergoline for levodopa-induced complications in Parkinson's disease. Cochrane Database Syst Rev 2001;1:CD001518-CD001518.
Colao A, Di Sarno A, Cappabianca P, Di Somma C, Pivonello R, Lombardi G. Withdrawal of long-term cabergoline therapy for tumoral and nontumoral hyperprolactinemia. N Engl J Med 2003;349:2023-2033.
Gillam MP, Middler S, Freed DJ, Molitch ME. The novel use of very high doses of cabergoline and a combination of testosterone and an aromatase inhibitor in the treatment of a giant prolactinoma. J Clin Endocrinol Metab 2002;87:4447-4451.