14CanazGokhan_Pituitary Romanian Neurosurgery | Volume XXX | Number 4 | 2016 | October - December Article Pituitary adenoma in monozigotic twins with Cri du Chat syndome: a rare case report Gokhan Canaz, Huseyin Canaz, Ibrahim Alatas TURKEY DOI: 10.1515/romneu-2016-0086 536 | Canaz et al - Pituitary adenoma in monozigotic twins with Cri du Chat syndome DOI: 10.1515/romneu-2016-0086 Pituitary adenoma in monozigotic twins with Cri du Chat syndome: a rare case report Gokhan Canaz1, Huseyin Canaz2, Ibrahim Alatas2 1Bakirkoy Research and Training Hospital for Neurology, Neurosurgery and Psychiatry, Department of Neurosurgery, Istanbul, TURKEY 2Florence Nightingale Hospital, Istanbul Bilim University, Department of Neurosurgery, Istanbul, TURKEY Abstract: Pituitary adenomas are rare tumours of pediatric population. In etiology, genetic factors are more common than they are in adults. Because of the rarity of the cases, there are only a few large case studies in the literature. Pituitary tumours in children are often related with syndromes like MEN type 1, Carney Complex and Mc Cune Albright, but there is no case in the literature associated with Cri Du Chat syndrome. Statisticlly, it has been reported that, pediatric tumours occur more often in twins, in the pediatric population. Main treatment for prolactinomas is medical intervention with dopamine agonists, as in adults. Surgery is prefered when the tumour is resistant to medical treatment or shows mass effects around sellae. In that situation, as in adults, both transcranial and transsphenoidal approach is possible. Key words: pituitary, Cri du Chat, twins, adenoma Introduction Pituitary adenomas are rare tumours in children and adolescents. They comprise approximately 3% of all suprasellar pediatric tumors and 2-6% of them can be surgically treated (3, 13). Pituitary tumours in children are rarely malignant and secretory. ACTH secretory adenomas occur more frequent in early childhood but the most common secretory adenomas in elder children are prolactinomas (5, 9, 17). Although etiology is uncertain, concordance with genetic syndromes, oral contaseptive use in pregnancy, twining and some malignancies are reported (4). The best known genetic syndromes accompanying pituitary adenomas are multiple endocrine neoplasia type 1 (MEN 1), Carney compex, familial isolated pituitary adenoma (FIPA) and McCune Albright syndromes. Case presentation 14 years old monozygotic twin sisters, who had been diagnosed with Cri Du Chat syndorme, were admitted to hospital with premenarcheal galactorrhea complaint. Romanian Neurosurgery (2016) XXX 4: 536 – 539 | 537 Pituitary magnetic resonance imaging (MRI) was performed. Both sisters presented with a pituitary lesion of 5.8mm x 3.3mm and a 33 3.4mm x 2.6mm, respectively, with low contrast enhancement, which was compatible with pituitary microadenoma (figures 1, 2). Figure 1 - MRI study showing a 5.8mm x 3.3mm solid lesion with low contrast enhancement in the right portion of the pituitary gland, suggestive for a microadenoma. A. Coronal view. B. Sagittal view Figure 2 - MRI study showing a 3.4mm x 2.6mm sized cystic lesion with low, peripheral contrast enhancement in theright side of the pituitary gland. A. Coronal view. B. Sagittal view Prolactin levels were respectively 120 μg/L and 70 μg/L (normal range 3.3-26.7 μg/L). Laboratory studies revealed no renal dysfunction or hypothyroidism. Visual examination appeared suboptimal, although the exam was scarcely reliable because of the 538 | Canaz et al - Pituitary adenoma in monozigotic twins with Cri du Chat syndome patient mental retardation. Surgical intervention was suggested for both patients, but family refused the surgery. Patients were directed to the endocrinology department for medical treatment and follow-up. Discussion Cri Du Chat syndrome is a hereditary congenital syndrome, caused by a deletion on short arm of 5th chromosome (7). Incidence is 1/20.000-50.000 birth (11). Microcephaly, round face shape, hypertelorism, micrognathia, low ear line, hypotonia and various psychomotor symptoms and mental retardation are common findings. The main clinical feature is, a high-pitched monochromatic cry, that gives the name to the syndrome (7, 12). 'Some studies demonstrated the association between deletions on 5q and neoplasia like acute myeloid leuchemia, myelodisplastic syndrome and Crohn disease (14). Morphological anormalities of the clivus and sella turcica, but not any pituitary disorders nor increase in the risk of neoplasia has been reported in Cri du Chat syndrome (6). Some studies have reported an increased prevalence of some tumors, i.e. testicular and non-thyroid endocrine cancers - in twins. On the other hand, colorectal cancer and leukemia appear to be less frequent in twins. In a study including 3,200 twin cancer patients, the reported frequency of pituitary tumours was two-fold higher than in the general population, but the etiopathological mechanisms remain to be defined (4). Pediatric pituitary adenomas are extraordinarily rare tumours in early childhood. Frequency is a little bit higher in adolescents but stil very rare relative to adults (9). These tumours in pediatric population are frequently part of a genetic condition. Pituitary tumors often present in the context of MEN type 1, Carney complex, FIPA and McCune Albright syndromes. Mutations to oncogens and tumour supressor genes, like GNAS, PTTG, HMGA2, and FGFR-64, have been also identified in sporadic cases of pituitary adenoma (2, 15). In early childhood, ACTH secretor tumours are the most common functional adenomas although they are very rare. They usually occur as a part of MEN type 1(8). During adolescent period, rate of prolactinomas and growth hormon secretory tumours evaluated relatively higher (1). Beside genetic factors, oral contraseptive use, high parity count and twining also considered among potential risk factors (4). Some authors suggest that pituitary adenomas in children are more aggressive than in adults, although this matter is still largely debated' and add references. 50% of all pituitary tumorus are prolactinomas. They occur more often in late childhood and girls (9). Two main complaints are headache and visual deficites, due to mass effect, but delayed puberty, amenorrhea and galactorrhea are more characterised complaints in girls. 'The first line treatment for prolactinomas in both children and adults is dopamine agonists. Main purpose is to reduce both prolactin levels and tumour size (10). Conditions like acute visual deficit, hydrocephaly, CSF leakage require emergency surgery. Elective surgery should be reserved to cases of resistance to medical treatment (16). Romanian Neurosurgery (2016) XXX 4: 536 – 539 | 539 Conclusion Pediatric pituitary adenomas are extremely rare tumors which relationship with genetic syndromes have been revealed. Beside known syndromes, their concommitance with different syndromes in some cases, shows the importance of genetic studies. Further investigations are necessary to enlight the possible genetic etiology. Correspondence Gokhan Canaz, Bakirkoy Research and Training Hospital for Neurology, Neurosurgery and Psychiatry, Department of Neurosurgery 34147 Bakırkoy/Istanbul. Tel: +90 212 409 15 15 Mobile: +90 536 944 94 39 Email: gokhancanaz@gmail.com References 1. Abe T, Ludecke DK, Saeger W. Clinically nonsecreting pituitary adenomas in childhood and adolescence. Neurosurgery 1998; 42: 744-750; discussion 750-741. 2. Alexander JM, Biller BM, Bikkal H, et al. Clinically nonfunctioning pituitary tumors are monoclonal in origin. 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