D-penicillamine, a metal antagonist, has been widely used in the treatment of rheumatoid arthritis, Wilson’s disease, systemic sclerosis, and biliary cirrhosis (1).
Possible complications of penicillamine therapy, howev- er, are macromastia and gynecomastia, and several cas- es have been reported (1-7). We describe a case involv- ing a 22-year-old woman who underwent ten months of D-penicillamine therapy for Wilson’s disease and no- ticed gradual enlargement of both breasts.
Case Report
During a two-month period, a 22-year-old woman no- ticed gradual enlargement of both breasts. After Wilson’s disease was diagnosed in 1992, D-penicil- lamine treatment was initiated, but after seven years the medication was withdrawn due to hirsutism. Due to dysarthria and gait disturbance, D-penicillamine treat-
ment (750 mg per day) was restarted, but 10 months lat- er, both breasts had become significantly larger, without mass. Physical examination showed that the breasts were tense, hard, and lumpy (Fig. 1A), and laboratory tests indicated that prolactin levels had risen to 37.9 ng/ml. Levels of both luteinizing and follicule-stimulat- ing hormone were within the normal range, however.
Mammography demonstrated bilaterally enlarged dense breasts (Fig. 1B, C); ultrasonography also demonstrated breast enlargement, together with a benign mass in the left one. Ultrasonography-guided core needle biopsy was performed (Fig. 1D), revealing mild hyperplasia of the myxoid stroma. Three months after discontinuing D-penicillamine, the breasts had reverted to their nor- mal size.
Discussion
Wilson’s disease is a congenital disorder of metal me- tabolism, arising due to a lack of ceruloplasmin. D-peni- cillamine, as a chelating agent of copper, is the drug of choice for the treatment of the condition (2), and is also an effective treatment for rheumatoid arthritis and sys- temic sclerosis. D-penicillamine has numerous adverse effects on bone marrow suppression, obliterating bron-
J Korean Radiol Soc 2004;50:213-215
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Breast Gigantism Induced by D-Penicillamine:
Case Report
1Ji Hyeon Cha, M.D., Hak Hee Kim, M.D., Sun Mi Kim, M.D., Myung Hee Seo, M.D., Hoi Soo Yoon, M.D.
D-penicillamine, a chelating agent of copper, is the drug of choice for the treatment of Wilson’s disease. Breast enlargement is a rare complication arising from its use, and we report a case of breast gigantism which developed after it had been used for ten months to treat this condition. Mammography demonstrated bilaterally enlarged dense breasts; ultrasonography, similarly, demonstrated enlargement, revealing the presence of a mass, shown at biopsy to be benign, in the left one.
Index words :Breast gigantism
D-penicillamine, breast enlargement Breast
1Department of Radiology, Asan Medial Center, University of Ulsan College of Medicine
Received August 6, 2003 ; Accepted December 19, 2003
Address reprint requests to : Hak Hee Kim, M.D., Department of Radiology, Asan Medial Center, University of Ulsan College of Medicine, 388-1 Pungnap-dong, Songpa-gu, Seoul 138-736, Korea.
Tel. 82-2-3010-4400 Fax. 82-2-476-0090 E-mail: [email protected]
chiolitis, nephritic syndrome, thyroiditis, and polyneu- ropathy of both the mouth and skin (3, 4). Breast en- largement is an unusual complication, encountered in both pre- and postmenopausal patients with normal or increased prolactin levels (1). The nature of the relation- ship between D-penicillamine, serum prolactin levels, and breast enlargement has not yet been clearly ex- plained, through a report has indicated that D-penicil- lamine may alter the circulating prolactin level or the re- sponse of the mammary glands to prolactin (5). Only two cases of Breast enlargement and hyperprolactine- mia after treatment with D-penicillamine have been re- posted (6).
Breast tissues are of two major histologic types:
parenchymal tissue, which is dependent upon estrogen and progesterone for growth and development, and stro- mal or connective tissue which, in contrast, is regulated by the pituitary gonadotrophins, prolactin, and growth hormone. Histologic examinations has thus mainly re- vealed rich connective tissues and no changes in glandu- lar tissues (5, 7), while readiography has demonstrated the presence of large nodules with or without distorted internal architecture and external contours (7).
The interval between the start of treatment and the onset of mammary enlargement has ranged from 12 weeks to 18 months (8). In our case, the enlargement of
Ji Hyeon Cha, et al: Breast Gigantism Induced by D-Penicillamine
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A B
C D
Fig. 1. A 22-year-old woman with Wilson’s disease.
A. Both breasts are enlarged on physical examination.
B, C. On mediolateral oblique view (B) and craniocaudal view (C) shows large and dense breasts.
D. On ultrasonography shows a benign-looking nodule in the left breast (arrows) and ultrasonography-guided core biopsy reduced mild hyperplasia of myxoid stroma.
both breasts was apparent after ten months. Reports have stated that when D-penicillamine was replaced by danazole, the symptoms subsided, through surgery was sometimes necessary (1, 7).
Breast gigantism is a rare complication of D-penicil- lamine therapy, and we have described a case in which the condition arose after the drug was used to treat Wilson`s diasease. The radiologic findings were bilater- ally enlarged breasts with extremely dense fibro-glandu- lar tissue at mammography, and a benign mass at ultra- sonography.
References
1. Joseph ZT. Breast enlargement induced by D-penicillamine. Ann
Pharmaco 2002;36:444-445
2. Rose BI, LeMaire WJ, Jeffers LJ. Macromastia in a woman treated with penicillamine and oral contraceptives. J Reprod Med 1990;35:
43-45
3. Passas C, Weinstein A. Breast gigantism with penicillamine thera- py. Arthritis Rheum 1978;21:167-168
4. Desai SN. Sudden gigantism of breasts: drug induced?. Br J Plast Surg 1973;26:371-372
5. Finer N, Emery P, Hicks BH. Mammary gigantism and D-penicil- lamine. Clin Endocrinol 1984;21:219-222
6. Kahl LE, Medsgner TH, Klein I. Massive breast enlargement in a patient receiving D-penicillamine for systemic sclerosis. J Rheumatol 1985;12:990-991
7. Desaultes JE. Breast gigantism due to D-penicillamine. Can Asso Radiol J 1994;45:143-144
8. Sakai Y, Wakamatsu S, Ono K, Kumagai N. Gigantomastia in- duced by bucillamine. Ann Plast Surg 2002;49:193-195
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대한방사선의학회지 2004;50:213-215
D-penicillamine을 사용한 환자에서 유방확대: 증례 보고1
1울산의대 서울아산병원 진단방사선과 차지현・김학희・김선미・서명희・윤회수
D-penicillamine은 구리를 킬레이팅(chelating) 시키는 약물로 윌슨씨 병 치료등에 이용되고, 드문 합병증으로 유방 확대가 나타날 수 있다. 본 증례는 윌슨씨 병 치료를 위해 10개월간 D-penicillamine을 사용한 환자에서 유방확대가 발 생한 경우로 유방 촬영술에서 양측 유방의 확대와 치밀유방의 소견을 보였다. 또한 초음파검사에서 양측 유방의 확대 와 왼쪽 유방에 결절이 관찰되었지만 조직 검사상 악성의 소견은 없었다.
