{"paper_id":"602c299e-e878-4fbd-8ecb-316ee5dfa074","body_text":"Adenomyosis in a patient with mosaic Turner syndrome:\ncase report\nRieko Kojima, Koji Nakagawa, Shirei Ohgi, Takashi Horikawa, Satoshi Kawachiya, Hidekazu Saito\nAbstract\nAdenomyosis has only been reported in one patient with mosaic Turner\nsyndrome. We report a case of mosaic Turner syndrome in a patient who suffered\nfrom hypermenorrhoea and severe anaemia due to adenomyosis. A 40-year-old\nwoman visited us desiring to conceive. The patient had got pregnant twice, but\nthey resulted in spontaneous abortion. After her third miscarriage, chromosomal\nbanding was performed and the patient was found to have a mosaic\nchromosome complement (45,X [9]/46,XX [21]). We report an extremely rare\ncase of a patient with mosaic Turner syndrome who presented with typical\nclinical symptoms of adenomyosis.\nKKeeyy  wwoorrddss:: adenomyosis, dysmenorrhoea, hypermenorrhoea, mosaic Turner \nsyndrome.\nIntroduction\nAdenomyosis has been reported only in one patient with Turner\nsyndrome and, in this case, adenomyosis was confirmed in\nhistopathological examination of a myomectomy specimen [1]. This patient\nshowed hypermenorrhoea and subsequent severe anaemia. However,\nthese symptoms were not due to adenomyosis, but to a uterine fibroid.\nOn the other hand, as for endometriosis, 7 cases of Turner syndrome in\npatients having endometriosis have been reported [2]. Thus, it is extremely\nrare for Turner syndrome patients to present with symptoms typical of\nadenomyosis – namely, an enlarged uterus and secondary dysmenorrhoea.\nNatural pregnancies occur in at least 2% of women with Turner\nsyndrome [3] and, to date, up to 160 spontaneous pregnancies in 74\nwomen have been recorded [4]. Most had a mosaic Turner’s karyotype\ncontaining a 46XX line, although some had non-mosaic Turner syndrome\n[5]. We report here adenomyosis in a patient with mosaic Turner syndrome\nwith a history of severe dysmenorrhoea and three miscarriages.\nCase report\nThe patient, a Japanese woman, presented initially to our hospital at\nthe age of 40 years; her primary complaint was infertility. Pubertal\ndevelopment of pubic and axillary hair, secondary sex characteristics, and\nbreasts were apparently unremarkable. After her menarche at 12 years\nof age, the patient experienced regular menstrual cycles at a frequency\nof 30 days. Her height was 163 cm and body weight was 54 kg. She had\nno abnormal physical findings, including short stature, webbed neck or\nDivision of Reproductive Medicine, Department of Perinatal Medicine and Maternal \nCare, National Center for Child Health and Development, Okura, Setagaya, Tokyo, Japan\nSSuubbmmiitttteedd::  25 July 2007\nAAcccceepptteedd:: 10 October 2007\nArch Med Sci 2008; 4, 1: 85–87\nCopyright © 2008 Termedia & Banach\nCCoorrrreessppoonnddiinngg  aauutthhoorr::\nKoji Nakagawa, MD, PhD\nDivision of Reproductive Medicine\nDepartment of Perinatal \nMedicine and Maternal Care\nNational Center for Child Health\nand Development\n2-10-1 Okura, Setagaya\n157-8538, Tokyo, Japan\nPhone: +81 3 3416 0181\nFax: +81 3 3416 2222\nE-mail: nakagawa-kj@ncchd.go.jp\n\n86 Arch Med Sci 1, March / 2008\nshield chest. She has had a regular menstrual cycle\nsince her menarche. She was nulliparous, as her\nprior pregnancies resulted in spontaneous\nabortions at 6 and 7 weeks of gestation. After \nher third miscarriage, chromosomal banding \nwas performed. The patient was found to \nhave a mosaic chromosome complement\n(45,X [9]/46,XX [21]) and was diagnosed with\nmosaic Turner syndrome.\nGonadotropin levels were normal [follicle-\nstimulating hormone (FSH), 7.16 IU/l luteinizing\nhormone (LH), 3.12 IU/l]. Cancer antigen-125\n(CA-125), which is elevated in association with some\ncancers and other benign conditions, such as\nendometriosis and adenomyosis, was high \n(256 IU/l). Severe iron deficiency anaemia, as\nevidenced by a haemoglobin (Hb) concentration \nof 8.7 g/dl, was present. Transvaginal ultrasound\nexamination revealed an enlarged uterus \n(145 × 99 × 100 mm) with extreme hypertrophy of\nthe anterior and posterior uterine walls. In\nNovember 2004, the patient underwent a magnetic\nresonance imaging (MRI) scan of the pelvic cavity.\nSeveral findings typical of adenomyosis were\nevident as follows: a) enlargement of the uterine\nwall with diffusing foci of hyperintensity on the \nT2 weighted scans, b) small cystically dilated glands,\nc) more acute sites of microhaemorrhages (Figure 1).\nThe pelvic cavity MRI image of the patient shown in\nFigure 1 is characteristic of adenomyosis. Because of\nher severe dysmenorrhoea and anaemia, treatment\nof the adenomyosis with gonadotropin-releasing\nhormone analogue (GnRH-a) was recommended, but\nthe patient refused treatment with GnRH-a because\nof her desire to conceive.\nDiscussion\nTurner syndrome occurs at a frequency of\napproximately 50 per 100 000 females, and is the\nmost frequent common chromosomal aberration\nin females. This syndrome is characterized by the\ncomplete or partial absence of one X chromosome.\nThe most frequent chromosomal constitution is 45X\n[6]. About a half of such patients have a mosaic\nchromosome component. The most common is\n45X/46XX (15%), and 6% of patients have 46XXq or\n46XXp deletions. Thus, the syndrome could be the\nresult of a limited amount of genetic material in\nthese abnormal chromosomes [7].\nTurner syndrome is characterized by the physical\nfinding that often includes congenital lymphedema,\nshort stature, and gonadal dysgenesis [8]. However,\nmost patients with mosaic karyotypes have ovaries\nwith a relatively low number of follicles [9]. There\nare some correlations between karyotype and\nphenotype [8]. Patients with a karyotype of\n45,X/46,XX are the most likely to have spontaneous\nmenarche and fertility, and they are marginally taller\nthan other women with Turner syndrome as\na group. Nonetheless, phenotype is unpredictable\nbased on karyotype only. In our case the patient\nhad a common mosaic chromosomal complement\nin mosaic Turner’s syndrome (45X/46XX). 40% of\nthem have spontaneous menarche and usually early\novarian failure, but she had both ovaries with the\nnormal number of antral follicles by transvaginal\nultrasound examination. She did not show the\ntypical Turner syndrome in clinical symptoms, but\nthe rate of 45X cells was 30% and ruled out\ncommon low-level sex chromosome mosaicism\ndetected in phenotypically normal women.\nOnly one case of adenomyosis in a patient with\nTuner syndrome who was not receiving long-term\nhormone replacement therapy has been reported\n[1]. In that report, the patient was a 31-year-old\nwoman who had been diagnosed with mosaic\nTurner syndrome by cytogenetic examination of her\nlymphocytes. She had received several cycles of\nhormone replacement therapy during adolescence,\nbut had not received GnRH-agonist treatment.\nBecause of the patient’s severe anaemia,\na myomectomy was performed, revealing not only\na uterine leiomyoma, but also adenomyosis in the\npost-operative histological examination.\nIn contrast, the patient described in this case report\nwas a 40-year-old woman who presented with a chief\ncomplaint of infertility. Adenomyosis was not\nconfirmed histopathologically, but clinical features\nand MRI findings, which indicated uterine\nenlargement and diffusing foci of hyperintensity on\nthe T2-weighted scan, were consistent with\nadenomyosis. The patient’s chromosomal pattern \nwas 45X/46XX, which is the most common form \nof mosaic Turner syndrome. Adenomyosis is an\nRieko Kojima, Koji Nakagawa, Shirei Ohgi, Takashi Horikawa, Satoshi Kawachiya, Hidekazu Saito\nFFiigguurree  11..  T2-weighted midline, sagittal magnetic\nresonance image. Findings typical of adenomyosis\nare evident: a) enlargement of the uterine wall with\ndiffusing foci of hyperintensity, b) small cystically\ndilated glands, c) more acute sites of\nmicrohaemorrhages. White arrows show small\ncystically dilated glands\n\nArch Med Sci 1, March / 2008 87\noestrogen-dependent disease. If the oestrogenic\ncondition was maintained, it would cause\noestrogen-dependent disease, such as adenomyosis\nand endometriosis, even in patients with mosaic\nTurner syndrome. The patient did not have any of the\ncharacteristic physical features of Turner syndrome,\nsuch as short stature, webbed neck and shield chest.\nThe patient had normal pubertal development of\npubic and axillary hair, secondary sex characteristics\nand breast development. After spontaneous\nmenarche at 12 years of age, the patient had regular\nand normal ovulatory menstrual cycles. Surprisingly,\nthe patient three times became pregnant – at 38, 39\nand 40 years of age – but, unfortunately, these\npregnancies ended in miscarriages. Conception is very\nrare in patients with mosaic Turner syndrome; among\nwomen with Turner syndrome who become pregnant,\nthe rates of miscarriages (29%), stillbirths (7%) and\nmalformation (20%) also are very high [2, 3].\nThus, it appears that the only symptom of\nmosaic Turner syndrome exhibited by the patient\ndescribed in this report was her miscarriage.\nSpontaneous abortion may result from fetal\nchromosomal aberrations due to maternal\ntranslocation. From this point of view, the patient\ndescribed in this case report would be an ideal\ncandidate for pre-implantation genetic diagnosis\n(PGD). However, in Japan PGD is permitted only for\nDuchenne dystrophy and is prohibited by the Japan\nSociety of Obstetrics and Gynecology for repeated\nspontaneous abortions, even though caused by\nmaternal chromosomal abnormalities. Therefore,\nPGD was not performed for this patient.\nBecause the patient suffered from hyper- and\ndysmenorrhoea, resulting in severe anaemia, several\ntreatment alternatives were recommended,\nincluding a GnRH-agonist, oral contraceptives, or\nhysterectomy. However, because of the patient’s\nstrong desire to conceive none of these treatments\nwas acceptable.\nA strategy for maintaining fecundity in patients\ndiagnosed with Turner syndrome during\nadolescence is needed. For this purpose several\ntypes of assisted reproductive technology, not\noocyte donation and ovarian surrogacy, but, rather,\ncryopreservation of ovarian tissue, in vitro\nmaturation of immature oocytes and ovarian tissue\ntransplantation techniques are indispensable. In the\nnear future it will be possible for more patients with\nTurner syndrome to bear children.\nIn conclusion we report an extremely rare case\nof a patient with mosaic Turner syndrome who\npresented with typical clinical symptoms of\nadenomyosis, such as dysmenorrhoea and uterine\nenlargement. An alternative condition seems \nto be that even though it is extremely rare,\ndysmenorrhoea and anaemia may be symptoms of\nadenomyosis in women with Turner syndrome.\nReferences\n1. Ferrero S, Bentivoglio G. Adenomyosis in a patient with\nmosaic Turner’s syndrome. Arch Gynecol Obstet 2005; 271:\n249-50.\n2. Lazovic G, Spremovic S, Cmiljic I, Vilendacic Z, Milicevic S.\nEndometriosis in a woman with mosaic Turner's syndrome:\ncase report. Int J Fertil Womens Med 2006; 51: 160-2.\n3. Hovatta O. Pregnancies in women with Turner's syndrome.\nAnn Med 1999; 31: 106-10.\n4. Tarani L, Lampariello S, Raguso G, et al. Pregnancy in\npatients with Turner's syndrome: six new cases and review\nof literature. Gynecol Endocrinol 1998; 12: 83-7.\n5. Abir R, Fisch B, Nahum R, Orvieto R, Nitke S, Ben-Rafael Z.\nTurner’s syndrome and fertility: current status and possible\nputative prospects. Hum Reprod Update 2001; 7: 603-10.\n6. Thompson MW, Mclnnes RR, Willard HF . The sex\nchromosomal and their abnormalities. In: Thompson MW,\nMclnnes RR, Willard HF (eds). Genetics in Medicine.\nPhiladelphia: WB Saunders, 1991; 239-43.\n7. Turner C, Dennis NR, Skuse DH, Jacobs PA. Seven ring (X)\nchromosomes lacking the XIST locus, six with an\nunexpectedly mild phenotype. Hum Genet 2001; 106: 93-\n100.\n8. Virginia PS, McCauley E. Turner's syndrome. N Engl J Med\n2004; 351: 1227-38.\n9. Novak AZ, Kokai GK, Popovic VP, Ludoski MD, Jurukovski\nVA. Interphase cytogenetics on paraffin-embedded sections\nof ovary for detection of genomic constitution in a patient\nwith Turner's syndrome and chromosomal mosaicism. Hum\nGenet 1995; 95: 293-8.\nAdenomyosis in a patient with mosaic Turner syndrome: case report","source_license":"CC0","license_restricted":false}