Assessment of the Admission and Follow-up Characteristics of Children Diagnosed with Secondary Osteoporosis.

Objective: Secondary osteoporosis is a condition when the underlying disease or its treatment causes the bone mass to decrease and the bone structure to deteriorate, increasing the risk of fracture. The importance of diagnosis and treatment during childhood and adolescence is due to its long-term negative effects. In this study, our objectives were to determine the diagnostic findings, treatment efficacy, and follow-up characteristics of childhood with secondary osteoporosis. Methods: 61 patients diagnosed with secondary osteoporosis between January 2000 and January 2021 were included in the study. The research is a cross-sectional and descriptive study. Study participants had to be under 18 years of age when the primary underlying disease was diagnosed and received treatment for secondary osteoporosis. Patient data were collected from patient files. Patient data were obtained from patient files in hospitals and were interpreted through the IBM SPSS Statistics for Windows version 20.0 (IBM Corp, Armonk, NY, USA). Results: 61 patients (28 women/33 men) were evaluated. The most common underlying primary diseases in patients with secondary osteoporosis were inflammatory diseases (57.7%), neuromuscular diseases (26.2%), immunodeficiency (13.1%), acute lymphoblastic leukemia (8.2%), metabolic diseases (8.2%), and solid organ transplantation. (8.2%), bone marrow transplantation (6.6%) and epilepsy (6.6%). The average chronological age when secondary osteoporosis was diagnosed was 11.89±4.88 years. They were evaluated for osteoporosis 6.39±5.13 years after the onset of the underlying primary chronic diseases. 78.7% of the patients had one or more chronic drug use. Systemic steroid use was 59%, chemotherapeutics 23%, immunomodulatory drugs 19.7%, antiepileptic drugs 8.2%, inhaled steroids 4.9%, IVIG 1.6%, and antituberculosis drugs 1.6%. Additionally, 1.6% of the patients were using testosterone as replacement, 3.3% L-Thyroxine, 1.6% estrogen, and 1.6% growth hormone. Bone pain was detected in 49.2% of the patients. All patients had vertebral fractures before treatment. Bisphosphonate treatment was given to 45 patients with secondary osteoporosis. There was a statistically significant increase in mean bone mineral density (BMD) and bone mineral content values six months after treatment, (p<0.001). There was a significant increase in BMD Z-score values for chronological and height age (p<0.001). The patients' BMD values increased on average by 31.15% with treatment. Following bisphosphonate treatment, there was a significant reduction in both fracture number and bone pain in patients (p<0.01). When patients who received and did not receive steroid treatment were compared, both groups received similar benefits from bisphosphonate treatment. Conclusion: Secondary osteoporosis is a condition that is influenced by many factors, such as the primary disease causing osteoporosis, chronic medication use, especially steroids. If left untreated, osteoporosis leads to important diseases such as bone pain, bone fractures, immobilization, and reduced linear growth of bone. When used to treat childhood secondary osteoporosis, Bisphosphonates significantly improve BMD and reduce fracture risk.

Comprehensive Insights into Pediatric Craniopharyngioma: Endocrine and Metabolic Profiles, Treatment Challenges, and Long-term Outcomes with a Multicenter Approach.

Introduction: Craniopharyngiomas (CPG) have complex challenges in treatment due to their proximity to vital structures, surgical and radiotherapeutic complexities, and the tendency for recurrence. This study aims to identify the prevalence of endocrine and metabolic comorbidities observed during initial diagnosis and long-term follow-up in a nationwide cohort of pediatric CPG patients. The study also highlights the associated difficulties in their management. Methods: Sixteen centers entered 152 patients into the ÇEDD NET data system. We evaluated the clinical and laboratory characteristics at presentation, administered treatments, accompanying endocrine, metabolic, and other system involvements, and the patient's follow-up features. Results: Of the evaluated patients, 64 were female, and 88 were male. At presentation, the mean age was 9.1 ± 3.67 (min:1.46-max:16.92) years. The most common complaints at presentation were headache (68.4%), vision problems (42%), short stature (15%), nausea and vomiting (7%). The surgical procedure applied to the patients was gross total resection (GTR) in 97 cases (63.8%) and subtotal resection in 55 cases (36.2%). Radiotherapy was initiated in 11.8% of the patients. In the pathological examination, 92% of the cases were adamantinamatous type, 8% were papillary type. Postoperatively, hormone deficiencies consisted of thyroid-stimulating hormone (92.1%), adrenocorticotropic hormone (81%), antidiuretic hormone (79%), growth hormone (65.1%), and gonadotropin (43.4%) deficiencies. Recombinant growth hormone treatment (rhGH) was initiated on 27 patients. The study showed hesitancy among physicians regarding rhGH. The median survival without relapse was 2.2 years. Median time of relapse was 1.82 years (range: 0.13-10.35 years). Relapse was related to longer follow-ups and reduced GTR rates. The median follow-up time was 3.13 years. Among the last follow-up visits, the prevalence of obesity was 38%, but of these, 46.5% were already obese at diagnosis. However, 20% who were not obese at baseline became obese on follow-up. Permanent visual impairment was observed in 26 patients, neurological deficits in 13 patients, and diabetes mellitus in 5 patients. Conclusion: Recurrence was predominantly due to incomplete resection and the low rate of postoperative radiotherapy. It also emphasized challenges in multidisciplinary regular follow ups and suggested early interventions such as dietary restrictions and increased exercise to prevent obesity.

Variant characterisation and clinical profile in a large cohort of patients with Ellis-van Creveld syndrome and a family with Weyers acrofacial dysostosis.

BACKGROUND: Ellis-van Creveld syndrome (EvC) is a recessive disorder characterised by acromesomelic limb shortening, postaxial polydactyly, nail-teeth dysplasia and congenital cardiac defects, primarily caused by pathogenic variants in EVC or EVC2. Weyers acrofacial dysostosis (WAD) is an ultra-rare dominant condition allelic to EvC. The present work aimed to enhance current knowledge on the clinical manifestations of EvC and WAD and broaden their mutational spectrum. METHODS: We conducted molecular studies in 46 individuals from 43 unrelated families with a preliminary clinical diagnosis of EvC and 3 affected individuals from a family with WAD and retrospectively analysed clinical data. The deleterious effect of selected variants of uncertain significance was evaluated by cellular assays. MAIN RESULTS: We identified pathogenic variants in EVC/EVC2 in affected individuals from 41 of the 43 families with EvC. Patients from each of the two remaining families were found with a homozygous splicing variant in WDR35 and a de novo heterozygous frameshift variant in GLI3, respectively. The phenotype of these patients showed a remarkable overlap with EvC. A novel EVC2 C-terminal truncating variant was identified in the family with WAD. Deep phenotyping of the cohort recapitulated 'classical EvC findings' in the literature and highlighted findings previously undescribed or rarely described as part of EvC. CONCLUSIONS: This study presents the largest cohort of living patients with EvC to date, contributing to better understanding of the full clinical spectrum of EvC. We also provide comprehensive information on the EVC/EVC2 mutational landscape and add GLI3 to the list of genes associated with EvC-like phenotypes.

Exploring Multiple Endocrinological Issues and Dysautonomia in a Rare Case: Hypoparathyroidism in MIRAGE Syndrome.

MIRAGE syndrome is a rare multisystemic disorder characterized by various manifestations, such as myelodysplasia, susceptibility to infections, growth retardation, adrenal hypoplasia, genital anomalies, and enteropathy. In the literature, there have been rare cases of dysautonomia. We present a 6.5-year-old girl, who was first admitted to our department with short stature. On follow up, she exhibited multiple endocrinological issues, including transient hypothyroidism, primary hypoparathyroidism and dysautonomia, along with multisystem involvement. Further investigations revealed recurrent moniliasis, low IgM levels, and transient monosomy 7 in the bone marrow. Whole exome sequencing revealed a heterozygous pathogenic variant of SAMD9 (c.2159del; p.Asn720ThrfsTer35). Additional complications observed during follow-up included medullary nephrocalcinosis, hypomagnesemia, hypermagnesiuria, hypophosphatemia, decreased glomerular filtration rate, and nephrotic proteinuria. The patient also developed hyperglycemia, which was managed with low-dose insulin. This case highlights the diagnostic challenges and the diverse phenotypic presentation observed in MIRAGE syndrome.

Familial Clinical Heterogeneity of Medullary Thyroid Cancer with Germline RET S891A Protooncogene Mutation: 7-Year Follow-up with Successful Sorafenib Treatment.

Hereditary forms of Medullary thyroid carcinoma (MTC) are rare. Different phenotypes with the same mutation may be due to differences in the timing of RET activation steps, additional mutations in other regions of the gene, or the co-occurrence of germline and somatic mutations, which is an infrequent possibility. Here, we aim to present the different features and difficulties in the follow-up of three family members with the same germline mutation. A 4-year-old male patient with respiratory distress was diagnosed with MTC and found to have a heterozygous germline mutation C.2671T>G(S891A) in the RET gene (classified as intermediate risk according to ATA). As the tumor was inoperable, treatment with a tyrosine kinase inhibitor (sorafenib) was initiated. Sorafenib has prevented tumor progression for seven years. Whole exome sequencing (WES) did not identify additional mutations. Segregation analysis showed the same mutation in the asymptomatic mother and sister. In our case, thyroid tissues were examined for somatic mutations, and SDHA c.1223C>T (p.S408L) was found. The clinical presentation of rare mutations such as RET p.S891A differed among family members carrying the same germline mutation. Our index case's more severe clinical presentation may be due to an additional somatic mutation. Sorafenib treatment can be an option for advanced MTC and may prevent disease progression.

A Challenging Case of Ectopic ACTH Syndrome with Bronchial Carcinoid and Literature Review.

Here we report an adolescent boy diagnosed with ectopic ACTH (Adrenocorticotropin hormone) syndrome (EAS) caused by atypical bronchial carcinoid. The patient was evaluated multidisciplinaryly: he had surgery and took chemotherapy and radiotherapy treatments afterward. The patient is still under our follow-up. Until today eighteen pediatric and adolescent patients with EAS because of bronchial carcinoid tumors were reported in 13 case reports and literature reviews. Ectopic ACTH syndrome caused by bronchial carcinoids is very rare in children and adolescents. Careful diagnostic evaluation and rapid treatment should be started immediately. Although complete remission is possible in bronchial carcinoids, atypical carcinoids have a more aggressive nature. A multidisciplinary approach and follow-up will improve quality of life and survival.

Evaluation of Abnormal Uterine Bleeding in Adolescents: Single Center Experience

Objective: Abnormal uterine bleeding (AUB) is the most common gynecologic complaint in adolescent girls. The aim of this study was to identify the diagnostic and management differences between those with/without heavy menstrual bleeding. Methods: Retrospective data was collected from adolescents aged 10-19 years, diagnosed with AUB. Adolescents with known bleeding disorders at admission were excluded. All girls were classified according to the degree of anemia; group 1 had heavy bleeding [hemoglobin (Hb) <10 g/dL] and group 2 had moderate or mild bleeding (Hb >10 g/dL). Admission and follow-up characteristics were compared between the two groups. Results: The cohort consisted of 79 girls with a mean age of 14.3±1.8 years and mean age of menarche of 11.9±1.4 years, with 85% experiencing menstrual irregularity in the two years after menarche, rising to 95.3% in group 1 (p<0.01). Anovulation was evident in 80% of the cohort. Of these 79 girls, 13 (16.5%) had polycystic ovary syndrome and two (2.5%) had structural anomalies (uterus didelphys). Three girls (group 1, n=2) had previously undiagnosed clotting factor VII deficiency; no other clotting deficiencies were diagnosed. Nineteen of 34 (56%) with personal (n=2)/family history of thrombosis had MTHFR mutation. None had venous thromboembolism during follow-up of >6 months. Conclusion: The majority of AUB (85%) occurred in the first two years after menarche. A small proportion (3.8%) had undiagnosed clotting factor deficiency. The frequency of MTHFR mutation was 50% in girls with history of thrombosis; however this did not increase the risk of bleeding/thrombosis and so routine evaluation does not appear to be justified.

Clinical Profile of Parathyroid Adenoma in Children and Adolescents: A Single-Center Experience.

OBJECTIVE: Parathyroid adenoma is less common than in adulthood, but its morbidity is higher in children. We aimed to evaluate the clinical characteristics of parathyroid adenoma and our clinical experience since the early disease is often asymptomatic and late diagnosed. MATERIALS AND METHODS: From 2010 to 2020, all children diagnosed with parathyroid adenoma at our institution were reviewed. We evaluated clinical, biochemical, and radiological aspects and follow-up characteristics. RESULTS: Eight subjects (F/M = 6/2) ranged in age from 10 to 17 years. Three were symptomatic. The symptoms and findings were stomachache (n = 3), myalgia (n = 2), weakness (n = 2), pancreatitis (n = 1), constipation (n = 1), nausea (n = 1), bone ache (n = 1), and anorexia (n = 1). Laboratory findings on admission were as follows: the mean calcium was 12.59 ± 1.28 (11.2-15.3) mg/dL and the mean parathyroid hormone was 244.81 ± 173.61 (74.9-645.4) pg/mL. The most common localization was the lower part of the left parathyroid gland. Parathyroid adenoma could not be demonstrated by ultrasonography in 2 patients. Tc-99m-Sestamibi scintigraphy revealed the presence of parathyroid adenoma in only 7 of 8 patients. All underwent parathyroidectomy. In our follow-up, 2 subjects needed reoperation. A molecular analysis of 6 cases could be done. One was MEN1 positive. RET sequence analysis of 2, and Casr, GNA11, and AP2S1 sequence analysis of 3 were normal. CONCLUSION: Parathyroid adenoma should be considered in children older than the first decade with hypercalcemia. Suspected cases should undergo both ultrasonography and scintigraphy. Early diagnosis prevents the patients from serious complications of hypercalcemia such as nephrocalcinosis, diabetes insipid, and arrhythmia. It is significant to perform surgery in centers experienced in parathyroidectomy to minimize postoperative complications.

Mitotically Active Follicular Nodule in Early Childhood: A Case Report with A Novel Mutation in the Thyroglobulin Gene.

Dyshormonogenesis is the failure of thyroid hormone production due to a defect in thyroid hormonogenesis. Loss-of-function mutations in the thyroglobulin(TG) gene are a cause of dyshormonogenesis, leading to gland stimulation by thyroid-stimulating hormone (TSH), resulting in goiter. We report a mitotically active follicular nodule in an 11-year-old female with a novel mutation in the TG gene. The patient had been under follow-up due to congenital hypothyroidism since the neonatal period, and she had normal TSH levels. Genetic test revealed a novel compound heterogeneous mutation [c.2149C>T (p.R717*) (P.Arg717Ter) / c.5361_5362delCCinsG (p.H1787Qfs*3) (p.His1787GlnfsTer3)] in TG gene. She underwent total thyroidectomy for a thyroid nodule that was reported as Bethesda IV on FNAB and noted as suspicious for noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). Pathological examination revealed a 16 mm well-demarcated follicular nodule with a solid/insular pattern. Mitotic activity and Ki67 proliferation index were unusually high (10 mitoses/2mm2 and 10% respectively). Marked cellular pleomorphism and nuclear atypia are well-known diagnostic pitfalls in patients with dyshormonogenetic goiter. However, high mitotic activity is a feature that is less emphasized in dyshormonogenetic goiter and may raise suspicion of poorly differentiated carcinoma when observed together with a solid pattern. The absence of signs of invasion, history of congenital hypothyroidism, and awareness of the presence of mutations compatible with dyshormonogenetic goiter can prevent the overinterpretation of such lesions. The risk of cancer development in the dyshormonogenetic thyroid gland is possible in childhood. The close follow-up is life-saving and prevents morbidities and mortalities.

Hyperprolactinemia in children and adolescents and longterm follow-up results of prolactinoma cases: a single-centre experience.

BACKGROUND: Hyperprolactinaemia refers to increased circulating prolactin and is divided into functional and pathological hyperprolactinaemia. Prolactinoma is the most common cause of severe hyperprolactinaemia. Prolactinomas are rare in children. Treatment outcomes and long-term follow-up data in children are insufficient. Dopamine agonists are the first step in the treatment of prolactinomas. There are no recommendations supported by a high level of evidence regarding the dose and duration of cabergoline treatment. METHODS: Patients with hyperprolactinaemia were evaluated for etiological, clinical, and follow-up characteristics. The case files of patients with high prolactin levels who were followed up in our clinic between 2001 and 2019 were reviewed retrospectively. RESULTS: 27 cases (20 female, 7 male) with hyperprolactinemia were detected. The median age of the cases was 15 years (0.3-17.4). Prolactinoma was detected in 40.7% of the cases (n=11). Among these cases, six were macroadenomas. The median prolactin level was 118 ng/mL (34-4340) in those with prolactinoma and 60 ng/mL (22-200) in the hyperprolactinaemia group (p=0.007). In the prolactinoma group, the median age at presentation in macroadenoma cases (13.8 years) was lower than in microadenoma cases (17 years) (p=0.06). There was a negative correlation between prolactin level and height SDS (r=-0.770, p=0.06). In all cases, the median initial cabergoline dose was 0.5 mg/week, and prolactin levels returned to normal within an average of 2.6±2.4 months. Cabergoline treatment achieved a 50% reduction in adenoma size in the first year of treatment without high doses. CONCLUSIONS: Prolactinoma consists of an important group among hyperplolactinemia in children. In our study, prolactinoma was detected in 40.7% of children with hyperplolactinemia, and children with prolonged use (over 4 years) tolerated cabergoline well and prolactin levels normalized without high doses. Follow-up is required for relapse after discontinuing the treatment.

Evaluation of the etiological and clinical characteristics of pediatric central diabetes insipidus.

OBJECTIVES: Central diabetes insipidus (CDI) is a rare but important disease of varying etiology that poses challenges in diagnosis and follow-up. Identifying diagnostic difficulties in patients with CDI will help ensure an optimal approach to their management and follow-up. This study aimed to characterize the clinical and etiological characteristics of CDI in pediatric patients. METHODS: We analyzed the admission and follow-up data of CDI patients aged 0-18 years who were followed in our center between 2010 and 2019. RESULTS: The study included 56 patients with a mean age at diagnosis of 7.92 ± 5.11 years and symptom duration of 8.65 ± 21.3 months. The patients were grouped by etiology into those with organic causes, such as structural anomalies, tumors, and trauma (group 1, n=41) and other causes (group 2, n=15). The prevalence of idiopathic CDI was 16%. At least one pituitary hormone deficiency was detected in 60.7%, the most common being thyroid stimulating hormone deficiency. Patients in group 1 had a higher mean age at diagnosis, shorter symptom duration, and higher frequency of other pituitary hormone deficiencies compared to group 2. Additionally, germinoma was detected 1 year subsequent to normal MRI findings at diagnosis and another patient was diagnosed with Langerhans cell histiocytosis (LCH) 5 years after diagnosis. All patients responded well to replacement therapies, but two patients with germinoma died during follow-up. CONCLUSIONS: In the pediatric age group, intracranial organic pathologies are an important etiology of CDI, and despite a short symptomatic period, determining the cause may be challenging and prolonged. Patients presenting at a young age with a long history of symptoms and no other pituitary hormone deficiency are unlikely to have organic CDI. However, organic causes such as LCH should be evaluated at all ages. Patients with idiopathic disease are candidates for further etiological studies, and repeated cranial imaging is important during follow-up.

Clinical Characteristics of 46,XX Males with Congenital Adrenal Hyperplasia

Objective: To retrospectively evaluate the follow-up data in patients with 46,XX congenital adrenal hyperplasia (CAH) who were raised male. Methods: A national database was created. The data of patients were asked to be recorded in the data form. Results: The median (range) age of diagnosis was three (0.1-18.3) years in 44 patients. Twenty nine cases were diagnosed after the age of two years. Most (95.4%) cases were stage 4-5 virilized. Hysterectomy and bilateral salpingoopherectomy, at a median age of 7.25 (2.4-25.3) years, was performed in 35 cases. Testicular prostheses were placed in 11 (25%) cases at a median age of 11.2 (2.8-17) years. The median final height was 149.2 (132.8-172) cms in 38 patients, including simple virilizing (n=18), salt-wasting (n=6), and 11-beta hydroxylase (n=12). Of the 16 patients above the age of eighteen, university education was completed in 25%. Conclusion: It was seen that most (65.9%) of the 46,XX CAH cases raised male were diagnosed after two years of age. In these cases, hysterectomy and bilateral salpingoopherectomy, genital corrective surgeries and testicular prosthesis operations were performed in a very wide age rage.

A Rare Cause of Sleep-Disordered Breathing: ROHHAD Syndrome.

Rapid-onset obesity with hypoventilation, hypothalamic dysfunction, and autonomic dysregulation (ROHHAD) syndrome; is a rare but crucial disorder. Sleep-disordered breathing can occur at the beginning or after of obesity. A disease-specific test for diagnosis is not yet available. Neural crest tumors (ganglioneuroma, ganglioneuroblastoma) have been reported in 40% of patients. In our study, three patients diagnosed as having ROHHAD syndrome are presented from our hospital. In the evaluation of the hypothalamic functions of the patients, one of them had growth hormone deficiency and hyperprolactinemia; recurrent hypernatremia reflecting irregular water balance was detected in another. One of the patients had abnormal pupil reflex and heart rate irregularity while another had excessive sweating as autonomic dysfunction. One of the patients was diagnosed with paravertebral ganglioma accompanying ROHHAD syndrome. Non-invasive ventilation treatment was started in all patients because there was a sleep-disorder breathing clinic diagnosis. ROHHAD syndrome deserves a multidisciplinary team approach as it can affect more than one organ system. In these patients, should be sleep-disorder breathing determined early and appropriate treatment should be initiated immediately to reduce morbidity and mortality.

Recombinant GH treatment in a case of Costello syndrome with a 5-year follow-up.

Costello syndrome (CS) is a rare member of the group of neuro-cardio-facio-cutaneous diseases known as RASopathies. CS involves characteristic dysmorphic craniofacial features, cardiac defects, and increased cancer susceptibility, depending on the heterozygous activating germline mutations in HRAS. Polyhydramnios and high birth weight are the most common presentations in the perinatal and neonatal periods; while poor postnatal growth, short stature, and failure to thrive are significant issues in infancy. Possible mechanisms of short stature in CS include GH deficiency and feeding difficulties. Only a few reported cases of CS with GH deficiency exist in literature. Here, we describe the 5-yr follow-up of a CS patient with complete GH deficiency treated with recombinant human GH (rhGH) from the age of four years. No significant adverse events regarding progression of hypertrophic cardiomyopathy and tumor development were observed. She has been responsive to treatment with improved growth velocity and height standard deviation scores. She is still under continuous monitoring for concerns on the possible development of cardiac events and malignancies. This case indicated that rhGH therapy is effective for improving the height and growth velocity of CS patients with GH deficiency under close cardiac and oncological monitoring.

Obese boys with low concentrations of high-density lipoprotein cholesterol are at greater risk of hepatosteatosis.

PURPOSE: Non-alcoholic fatty liver disease (NAFLD) and associated morbidities have become a major public health problem, with a global three-fold increase in incidence among obese children over the last three decades. Although the gold standard for diagnosis of NAFLD is liver biopsy, it is not widely used in children. Imaging techniques, including magnetic resonance imaging (MRI) and ultrasound (US), can provide information on liver fat deposition, however, with variable sensitivity. A number of other predictors are therefore being investigated for pediatric screening and diagnostic purposes. The aim of this study was to assess easily measured parameters to prompt further investigation into NAFLD in obese children. METHODS: Obese children/adolescents with a body mass index (BMI) percentile > 95 were enrolled in the study (n = 353). After a 12-hour fast, venous glucose, insulin, cholesterol, triglycerides (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and uric acid were measured and a full blood count was performed in all subjects. TG/LDL ratio, AST/platelet ratio index (APRI score), and homeostatic model of assessment for insulin resistance (HOMA-IR) were calculated. All patients underwent an abdominal US examination to assess hepatosteatosis. RESULTS: Of 353 patients, median age 12.5 (range, 6-17.9) years, 210 patients (59%) had US-proven hepatosteatosis. Female gender reduced the risk of steatosis 2.08-fold (p = 0.005), a one-unit increase in HDL reduced the risk of steatosis 1.02-fold (p = 0.042), and a one-unit increase in BMI led to a 1.11-fold (p = 0.002) increase in the risk of steatosis. CONCLUSION: Gender, BMI, and HDL were found to be predictors of steatosis. Male patients with low HDL and high BMI are at greater risk of steatosis and should be carefully examined for the presence of NAFLD.

A case of Riley Ruvalcaba syndrome with a novel PTEN mutation accompanied by diffuse testicular microlithiasis and precocious puberty.

BACKGROUND: Bannayan Riley Ruvalcaba syndrome (BRRS) is exceedingly rare, with only about 50 reported cases to date. CASE PRESENTATION: We report a patient with hypoglycemia, precocious puberty and diffuse testicular microlithiasis accompanying BRRS, and think that this case is important in the light of a newly identified mutation in the PTEN gene. CONCLUSIONS: Close attention must be paid in terms of PTEN mutations in cases of macrocephaly and accompanying neurological and dermatological findings.

McCune Albright syndrome in association with excessive GH secretion: case report.

McCune-Albright Syndrome is a rare syndrome characterized with excessive function of peripheral endocrine organs and activating mutations of the stimulatory G protein alpha subunit are involved in the pathogenesis. The three main findings of the disease include hyperpigmented café au lait spots, fibrous dysplasia and increased endocrine functions and excessive secretion of growth hormone is observed in 21% of the patients. Clinical signs may be missed in these patients because of precocious puberty and craniofacial fibrous dysplasia. Since radiotherapy causes to sarcomatous changes and transsphenoidal surgery may cause to severe thickening in the cranial bones, they are not appropriate treatment options and medical treatment is recommended. Bromocriptine, cabergoline and octreotide or different combinations of these drugs are used in treatment and pegvisomant has also been used in recent years. Here, we present a male patient aged 12 years and 7 months to show gigantism as a rare clinical reflection of McCune-Albright Syndrome with an excessive height (197 cm), café au lait spots, growht hormone levels which could not be supressed with oral glucose tolerance test and increased prolactin levels.

Is Hyperpigmentation on the First Day of Life Always Associated with IMAGe Syndrome?

IMAGe syndrome is an exceedingly rare condition first described in 1999. Components of the syndrome are intrauterine growth retardation (IUGR), metaphyseal dysplasia, congenital adrenal hypoplasia and genital anomalies. Cases generally present with life-threatening adrenal insufficiency in the neonatal period. Herein, we describe a patient with pronounced IUGR diagnosed with severe hyperpigmentation and adrenal insufficiency in the neonatal term in order to attract the attention to this rare entity.

Ovotesticular disorder of sexual development and a rare 46,XX/47,XXY karyotype.

Ovotesticular disorder of sexual development (DSD) is characterized by the presence of both ovarian and testicular tissues in the same individual. The most common karyotype is 46,XX. Here, we report the case of a boy with a 46,XX/47,XXY karyotype diagnosed as ovotesticular DSD by gonadal biopsy. A 5-month-old boy presented with hypospadias, unilateral cryptorchidism, and a micropenis. Pelvic magnetic resonance imaging revealed a suspicious gonad tissue that is solid in structure in the right scrotum and a suspicious gonad that is cystic in structure in the left inguinal canal. He underwent a diagnostic laparoscopy. Cytogenetic analysis of peripheral blood revealed a 46,XX/47,XXY karyotype. Histopathologic examination of the left gonad showed ovarian tissue containing primordial follicles with ipsilateral undifferentiated tuba uterina. The right gonad showed immature testis tissue. He underwent left gonadectomy and hypospadias repair, and was raised as a male. Through this rare case, we highlight the importance of histological and cytogenetic investigation in DSD.

Spondyloenchondrodysplasia: a rare cause of short stature.

Skeletal dysplasias (osteochondrodysplasias) are a group of diseases that must be included in the differential diagnosis of disproportionate short stature. History, clinical and radiologic findings and consanguinity are important features to be considered when a specific diagnosis is investigated. Spondyloenchondrodysplasia is a very rare skeletal dysplasia characterized with enchondromas in the long bones and platyspondyly. Manifestation of the disorder may include neurological involvement (spasticity, intracranial calcifications and mental retardation) and immune dysfunction. Herein, we report a 12-year-old boy who admitted to our clinic with short stature, who was born to consanguineous parents. He presented clinical (significant widening of wrists, ankles and knees) and radiologic (enchondromatous lesions in the metaphysis of long bones) features of spondyloenchondrodysplasia but did not yet have neurologic or immunologic involvement.