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    "textoCompleto" => "<p class="elsevierStylePara"><span class="elsevierStyleBold">To the Editor&#58;</span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">INTRODUCTION</span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">Mammary gland hypertrophy is frequently observed as a side effect of medications such as calcium channel blockers&#44; angiotensin II receptor antagonists&#44; omeprazole or some immunosuppressants such as cyclosporine A&#46;<span class="elsevierStyleSup">1-3 </span>In women with a kidney transplant on treatment with calcineurin inhibitors&#44; mammary gland growth of varying intensity has been described&#44; usually after more than one year&#46; The patient may not always return after the drug is withdrawn and sometimes corrective mammoplasty is required to reduce the large volumes&#46; However&#44; we have not found this adverse effect reported in patients with glomerulonephritis on treatment with cyclosporin A&#46;</p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">CASE STUDY</span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">Our patient is a 48-year-old male who had been referred 9 months previously due to proteinuria&#46; He had high blood pressure for 2 years and had been on treatment with amlodipine&#44; atenolol and irbesartan for several years&#46; The general test displayed&#58; proteinuria of 1200mg&#47;day&#44; 448 red blood cells&#47;&#956;l in sediment&#44; creatinine of 1&#46;05mg&#47;dl and negative immunology&#46; The renal biopsy showed&#58; 5-10 glomeruli without remarkable cellularity&#44; without exudation&#44; 2-4 glomeruli with complete sclerosis&#44; discrete chronic interstitial lymphocyte-monocyte infiltrates&#44; without vascular involvement and without tubular atrophy&#46; In the immunofluorescence&#58; IgM immunoglobulin deposits of focal and segmental distribution in 10 glomeruli&#44; with &#43; and &#43; &#43; intensity in the mesangial region&#46; It was treated as focal segmental glomerulosclerosis with 2&#46;5-5mg&#47;day of ramipril being administered&#44; and proteinuria decreased to &#60;400mg&#47;day&#46; Three years ago&#44; the patient had an increase in proteinuria of 1&#46;6g&#47;day&#44; albuminuria of 895mg&#47;day and 250 red blood cells&#47;&#956;l with normoalbuminaemia and oedemas&#46; We treated him with prednisone and cyclophosphamide&#44; with a decrease in proteinuria being observed after 7 months of treatment to 1&#46;1g&#47;day&#44; but with proximal muscle weakness&#44; which was interpreted as a myopathy due to steroids&#46; Prednisone was discontinued and replaced by 1g&#47;day mycophenolate mofetil and we withdrew amlodipine due to its potential influence on oedema&#44; with 12&#46;5mg of hydrochlorothiazide being administered due to poor blood pressure control&#46; After 2 months we suspended mycophenolate because the patient expressed experiencing significant fatigue&#44; which he attributed to this drug&#46; Cyclosporine A was then administered at a dose of 150mg&#47;day &#40;1&#46;9mg&#47;kg&#47;day&#41; with good initial tolerance &#40;67&#46;8ng&#47;ml&#41;&#46; After 2 months&#44; the patient presented with pain in left breast accompanied by a retroareolar nodule sensitive to touch&#44; which was the size of a chestnut&#46; Cyclosporine A was discontinued and a mammography and ultrasound were performed&#46; We found glandular increase with no evidence of malignancy&#44; and therefore it was interpreted as medication-related glandular hyperplasia&#46; Eight months later we introduced tacrolimus &#40;6mg&#47;day with subsequent reduction to 4-5mg&#47;day with levels &#60;8ng&#47;ml&#41;&#46; Two months later&#44; the patient presented again with left breast pain&#44; and as such tacrolimus was discontinued upon finding proteinuria of &#60;250mg&#47;day&#46; In the last review 5 months later&#44; proteinuria had increased to 650mg&#47;day and glandular growth had stopped&#46; The patient was subsequently treated with doxazosin&#44; atenolol&#44; irbesartan and ramipril&#46;</p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">DISCUSSION</span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">Cyclosporine is occasionally associated with uni- or bilateral breast growth in women&#44; accompanied by variable local inflammatory signs&#44; with significant erythema and considerable pain&#46;<span class="elsevierStyleSup">2</span> The histology usually shows mild to intense mammary glandular epithelial hyperplasia which may even raise suspicion of malignancy&#44; although it is not atypical&#46; In addition to glandular growth&#44; variable growth of the surrounding fibrous tissue is normally observed&#44; which is comparable with the histology of fibroadenomas that may reach a large size and be non-reversible&#44; depending on the degree of fibrosis&#46;<span class="elsevierStyleSup">2</span> This histological profile is similar to that of cyclosporine A-induced gingival hypertrophy&#44; although an association between the two profiles has not been observed and no relationship has been found with drug levels&#46;<span class="elsevierStyleSup">4</span></p><p class="elsevierStylePara">It is unknown what stimulates glandular growth&#44; although it is considered that TGF-beta is involved&#46; Sometimes it occurs with an increase in estradiol and a decrease in the FSH &#40;follicle stimulating hormone&#41;<span class="elsevierStyleSup">4</span> and in one case increased prolactin levels were found and associated with lactation&#44; although in most cases prolactin is normal&#46; In 2 male liver transplant recipients there was an increase in the LH &#40;luteinizing hormone&#41; coinciding with the administration of cyclosporin A&#44; and a decrease in these levels on replacing the immunosuppressive drug with tacrolimus&#46;<span class="elsevierStyleSup">3</span> Cyclosporin A and tacrolimus are able to effectively inhibit estradiol degradation&#44; which would explain the increased levels of estradiol&#44; a mechanism also suggested for spironolactone&#46;<span class="elsevierStyleSup">5</span></p><p class="elsevierStylePara">Some of the antihypertensive drugs taken by the patient have been associated with the appearance of gynaecomastia&#46;<span class="elsevierStyleSup">1 </span>However&#44; there was a clear temporal relationship between the introduction and discontinuation of cyclosporine A and subsequently tacrolimus&#44; and the occurrence of painful breast growth&#44; which stopped when calcineurin inhibitors were introduced&#44; which means that they were most likely the cause of breast growth&#46; The time on treatment it takes for gynaecomastia to appear varies in the literature&#46; In our case&#44; it occurred at an early stage&#46; It is uncommon to observe it in males and most fibroadenomas of the breast described occur in solid organ transplant recipients&#44;<span class="elsevierStyleSup">3</span> unlike with our patient&#44; in whom it was established during treatment for chronic glomerulonephritis&#46;</p><p class="elsevierStylePara">The progression of this breast hyperplasia was benign and growth stopped when cyclosporine A was discontinued&#46; In transplant patients in whom it is replaced with tacrolimus&#44; clinical improvement may occur in up to a third of patients&#44; although it is frequently necessary to replace it with another immunosuppressive drug&#46;<span class="elsevierStyleSup">6</span> We changed the patient to tacrolimus after 8 months without cyclosporine A and he displayed the same symptoms again quickly&#46; As such&#44; we discontinued medication definitively&#46; In cases in which growth is not reversible and causes discomfort&#44; lumpectomy or breast reduction may be considered&#46;<span class="elsevierStyleSup">7</span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Conflicts of interest</span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">The authors declare that they have no conflicts of interest related to the contents of this article&#46;</p>"
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