17α-hydroxylase/17,20 lyase deficiency (17OHD) is a rare form of congenital adrenal hyperplasia (CAH), characterized by hypertension and varying degrees of ambiguous genitalia and delayed puberty. The disease is associated with bi-allelic mutations in the CYP17A1 gene located on chromosome 10q24.3. We aimed to present clinical and genetic findings and follow-up and treatment outcomes of 17OHD patients. We evaluated six patients with 17OHD from five families at presentation and at follow up. Standard deviation score of all auxological measurements was calculated according to national data and karyotype status. CYP17A1 gene sequence alterations were investigated in all patients. The mean (±standard deviation) age of patients at presentation and follow-up time was 14.6±4.2 and 5.0±2.7 years respectively. Five patients were referred to us because of delayed puberty and primary amenorrhea and four for hypertension. One novel single nucleotide insertion leading to frame shift and another novel variant occurring at an ultra rare position, leading to a missense change, are reported, both of which caused 17OHD deficiency. Steroid replacement was started. The three patients with 46,XY karyotype who were raised as females underwent gonadectomy. Osteoporosis was detected in five patients. Four patients needed antihypertensive treatment. Improvement in osteoporosis was noted with gonadal steroid replacement and supportive therapy. 17OHD, a rare cause of CAH, should be kept in mind in patients with pubertal delay and/or hypertension. Patients with 46,XY who are raised as females require gonadectomy. Due to late diagnosis, psychological problems, gender selection, hypertension and osteoporosis are important health problems affecting a high proportion of these patients.

Hypophosphatemic rickets (HR) is a rare renal phosphate wasting disorder commonly related to X-linked form, caused by PHEX mutations and its treatment and follow-up is challenging due to imperfect treatment options. Here we presented nationwide data on HR with initial and follow-up data on the patients. From 24 centers, 166 patients were included in the study data. Genetic analysis (n:75) showed PHEX mutation in 80% patients. The mean follow-up period of the patients was 6.7± 2.4 years. During first 3 year treatment (n:91), mild increase in phosphate , decrease in ALP and, elevation in PTH levels had been detected. The height SDS were -2.38, -2.77, -2.72, -2.47 at intitial, 1st, 2nd and 3rd year of treatment, respectively (p>0.05). In follow-up: 36% of the patients showed complete or significant improvement in leg deformities, and, these patients had similar phosphate levels at presentation with better levels in 1st and 2nd years of treatment, even the treatment doses of phosphate were similar. Furthermore, 27 patients developed nephrocalcinosis, the patients showed no difference in biochemical differences in presentation and follow-up, but 3rd year PTH was higher, however, higher treatment dose of phosphate and calcitriol has been detected in nephrocalcinosis group. HR treatment and follow-up is challenging and our results showed higher treatment doses leading nephrocalcinosis without any change in serum levels, suggesting given higher doses lead higher phoshaturia probably through the stimulation FGF23. However, higher calcitriol doses could improve bone deformities. Safer and more efficacious therapies are needed.

To investigate clinical characteristics and response to growth hormone (GH) treatment in patients with Prader-Willi syndrome (PWS) in Turkey. The data of 52 PWS patients from ten centers was retrospectively analyzed. A nation-wide, web-based data system was used for data collection. Demographic, clinical, genetic, and laboratory data and follow-up information of the patients were evaluated. The median age of patients at presentation was 1.5 years, and 50% were females. Genetic analysis showed microdeletion in 69.2%, uniparental disomy in 11.5%, imprinting defect in 1.9% and methylation abnormality in 17.3%. Hypotonia (55.7%), feeding difficulties (36.5%) and obesity (30.7%) were the most common complaints. Cryptorchidism and micropenis were present in 69.2% and 15.3% of males, respectively. At presentation, 25% had short stature, 44.2% were obese, 9.6% were overweight and 17.3% were underweight. Median age of obese patients was significantly higher than underweight patients. Central hypothyroidism and adrenal insufficiency were present in 30.7% and 4.7%, respectively. Hypogonadism was present in 75% at normal age of puberty. Growth hormone treatment was started in 40% at a mean age of 4.7±2.7 years. After two years of GH treatment, a significant increase in height SDS was observed. However, BMI SDS remained unchanged. The most frequent complaints were hypotonia and feeding difficulty at first presentation. Obesity was the initial finding in 44.2%. Growth hormone treatment was started in less than half of the patients. While GH treatment significantly increased height SDS, BMI SDS remained unchanged, possibly due to the relatively older age at GH start.

A significant rise in the number of trans adolescents seeking medical interventions has been reported in recent years. In this study, we aimed to report the clinical features, treatment, and follow-up of adolescents with gender dysphoria (GD) with our increased experience. Twenty-six male-to-female (MTF) and twenty-seven female-to-male (FTM) adolescents who were referred to our GD-outpatient clinic between the years 2016 and 2022 were reviewed. The clinical and laboratory findings of thirty transgender adolescents (15FTM /15 MTF) who received medical intervention were evaluated retrospectively. The vast majority of individuals (60.4%) were admitted between 2020 and 2022, and the remaining (39.6%) were admitted between 2016 and 2019. At the referral time, median age was 16.3 years (IQR,1.53; range, 13.2-19.4) in 26 MTF, and 16.4 years (IQR,1.74; range, 11.7-21.6) in 27 FTM adolescents. The median age of the pubertal blockage with gonadotropin-releasing hormone analog (GnRHa) and androgen receptor blocker was 16.4 years (IQR,1.4; range, 11.7-17.8) in 22 adolescents (9 MTF,13 FTM), and 17.4 years (IQR,1.4; range, 15.5-19.4) in 6 MTF individuals, respectively. The cross-sex hormone therapy (CSH) was commenced in 21 adolescents (12 MTF, 9 FTM) at the median age of 17.7 years (IQR,0.61; range,16-19.5). Fifteen individuals (8 MTF, 7 FTM) have been transferred to the adult endocrinology department in transition clinics. All treatments were well tolerated and effective including bicalutamide, no side effects were observed. Besides, transition clinics play an important role in the better management of gender reassignment processes.

Introduction: Isolated adrenocorticotropic hormone (ACTH) deficiency (IAD) is a rare cause of adrenal insufficiency and T-box pituitary restricted transcription factor (TBX19) mutations are responsible for two-thirds of the neonatal onset form of the disease. IAD presents with hypoglycemia and prolonged jaundice in the neonatal period. TBX19 is important for both pro-opiomelanocortin (POMC) gene transcription and differentiation of POMC-expressing cells. We describe 2 patients, 1 with a reported and 1 with a novel TBX19 mutation, and present information about the long-term follow-up of these patients. Case Presentation: Both patients had critical illnesses, recurrent hypoglycemia, convulsions, and neonatal hyperbilirubinemia. They also had low cortisol and ACTH levels, while other pituitary hormones were within the normal range. Pituitary imaging was normal. After hydrocortisone treatment, there was resolution of the hypoglycemia and the convulsions were controlled. Genetic studies of the patients revealed both had inherited a homozygous mutation of the TBX19 gene. The first patient had an alteration of NM_005149.3:c.856C>T (p.R286*) and the second patient had a novel NM_005149.3:c.584C>T (p.T195I) mutation, analyzed by next-generation sequencing. The noteworthy findings of the patients at follow-up were: short stature, microcephaly, and decreased pubic hair in the first, and dysmorphic features, Chiari type 1 malformation, tall stature, and low bone mineral density (BMD) in the second. Conclusion: Congenital IAD can be life-threatening if it is not recognized and treated early. TBX19 mutations should be considered in the differential diagnosis of IAD. Further cases or functional analyses are needed for genotype-phenotype correlations. Low BMD, dysmorphic features, Chiari type 1 malformation, and sparse pubic hair are some of the important features in these patients.