Assessment of early atherosclerosis and left ventricular dysfunction in children with 21-hydroxylase deficiency.

AIM: We analysed 25 children with 21-hydroxylase deficiency who received glucocorticoid and/or mineralocorticoid treatment for at least 12 months to determine the effects of the disease and its treatment on vascular structures and ventricular function. METHODS: Twenty-five patients with 21-hydroxylase-deficient congenital adrenal hyperplasia (CAH) and 25 control subjects were enrolled into this observational, cross-sectional study. The patients were investigated in terms of fasting blood glucose and insulin; fasting serum lipid profile; serum 17-hydroxyprogesterone; dehydroepiandrosterone sulphate; androstenedione; and adrenocorticotropic hormone. M-mode tracings of the wall motion of major arteries were obtained to measure carotid intima-media thickness (cIMT), as well as elasticity and distensibility of the aorta and carotid artery. Conventional and relatively new tissue Doppler imaging techniques were employed to assess ventricular systolic and diastolic functions. RESULTS: The median age and weight of patients were 9·4 years (1·5-16·75) and 35·5 kg (7·5-76·3), respectively. The median duration of treatment was 52·2 months. Tissue Doppler imaging measurements revealed left ventricular diastolic impairment in the patient group compared to the controls. Carotid intima-media thickness, stiffness index, elastic modulus of the aorta and carotid artery were significantly higher; meanwhile, aortic distensibility and carotid distensibility were lower in the patient group, all of which indicates the presence of subclinical atherosclerosis. BMI was found to be an independent variable for cIMT (ß: 0·5, P = 0·01) and aortic stiffness index (ß: 0·52, P < 0·001). CONCLUSION: Cardiovascular function and the elastic properties of major arteries are disturbed in children and adolescents with 21-hydroxylase-deficient CAH.

Increased circulating urocortin-3 levels is associated with polycystic ovary syndrome.

This study was aimed to compare serum urocortin-3 (UCN3) levels in women with polycystic ovary syndrome (PCOS) and healthy women, and establish what role UCN3 levels play in PCOS. Fifty-two patients with PCOS and 55 healthy women were included in the study, matched for age and body mass index. Fasting blood glucose (FBG), insulin, hs-CRP, UCN3 and free-testosterone levels of the all participants were measured. HOMA-IR was used to calculate the insulin resistance. Circulating UCN3 levels were significantly increased in women with PCOS than in control subjects (54.49 ± 5.77 versus 51.28 ± 5.86 pmol/l, p = 0.005). Serum insulin, hs-CRP and HOMA-IR levels were higher in women with PCOS than in control group. UCN3 levels positively correlated with hs-CRP in PCOS group (r = 0.391, p = 0.004). Receiver operating characteristic (ROC) curve analysis showed that the area under the ROC curves were 0.732 (95% CI 0.634-0.830, p < 0.001) for UCN3 levels. The optimal cut-off value of UCN3 for detecting PCOS was ≥51.46 pmol/l, at which the sensitivity was 75% and specificity was 68%. Our results suggest that there is a potential link between PCOS and UCN3 levels. The results of this study support the presence of increased UCN3 levels for the association of inflammation with PCOS.

Can mean platelet volume be used as a biomarker for asthma?

INTRODUCTION: Platelets play important roles in airway inflammation and are activated in inflammatory lung diseases, including asthma. AIM: We evaluated the mean platelet volume (MPV), used as a marker of platelet activation, in asthmatic patients during asymptomatic periods and exacerbations compared to healthy controls to determine whether MPV can be used as an indicator of inflammation. MATERIAL AND METHODS: Our patient group consisted of 95 children with exacerbation of asthma who were admitted to our allergy clinic. The control group consisted of 100 healthy children matched for age, gender, and ethnicity. Mean platelet volume values of the patient group obtained during exacerbation of asthma were compared to those of the same group during the asymptomatic period and with the control group. We investigated factors that can affect the MPV values of asthma patients, including infection, atopy, immunotherapy treatment, and severity of asthma exacerbation. RESULTS: The patient group consisted of 50 (52.6%) boys and 45 (47.4%) girls with a mean age of 125 ±38 months old. Mean MPV values in the exacerbation period, the healthy period, and in the control group were 8.1 ±0.8 fl, 8.1 ±1.06 fl, and 8.2 ±0.9 fl, respectively; there were no significant differences between groups (p > 0.05). The severity of asthma, severity of asthma exacerbation, immunotherapy, coinfection, eosinophil count, and IgE level also had no effect on MPV (p > 0.05). CONCLUSIONS: Although platelets play a role in the pathophysiology of asthma, MPV measurement is insufficient to detect inflammation through platelets.

Comparison of serum cystatin C and creatinine levels in determining glomerular filtration rate in children with stage I to III chronic renal disease.

BACKGROUND: Pediatric studies are relatively scarce on the superiority of cystatin C over creatinine in estimation of glomerular filtration rate (GFR). This study measured cystatin C and serum creatinine levels, and compared GFR estimated from these two parameters in patients with chronic renal disease. METHODS: This prospective, observational, controlled study included 166 patients aged 1-18 years diagnosed with stage I to III chronic renal disease, and 29 age- and sex-matched control subjects. In all patients, GFR was estimated via creatinine clearance, Schwartz formula, Zappitelli 1 and Zappitelli 2 formula and the results were compared using Bland-Altman analysis. RESULTS: Patients and controls did not differ with regard to height, body weight, BMI, serum creatinine and serum cystatin levels, and Schwartz formula-based GFR (p > 0.05). There was a significant relationship between creatinine and cystatin C levels. However, although creatinine levels showed a significant association with age, height, and BMI, cystatin C levels showed no such association. ROC analysis showed that cystatin C performed better than creatinine in detecting low GFR. CONCLUSION: Cystatin C is a more sensitive and feasible indicator than creatinine for the diagnosis of stage I to III chronic renal disease.

DRESS syndrome associated with type 2 diabetes in a child.

Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome is an uncommon, life-threatening drug reaction. The basic findings are skin rash, multiorgan involvement, and eosinophilia. Most of the aromatic anticonvulsants, such as phenytoin, phenobarbital and carbamazepine can induce DRESS. Herein we report a 14-year-old patient with DRESS syndrome related to carbamazepine use. The patient presented with signs of involvement of the skin, lungs, liver, and microscopic hematuria. Carbamazepine treatment was discontinued; antihistamines and steroids were started. Hyperglycemia, commencing on the first dose of the steroid given, persisted even after the discontinuation of steroids and improvement of other signs. There were no signs of pancreatitis or type 1 diabetes clinically in laboratory tests. Her blood glucose levels were regulated at first with insulin and later with metformin. Within 1 year of follow-up, still regulated with oral antidiabetics, she has been diagnosed with type 2 diabetes. Formerly, long-term sequelae related to "drug rash with eosinophilia and systemic symptoms syndrome" such as hepatic and renal failure, type 1 diabetes mellitus, Grave's disease, autoimmune hemolytic anemia, and lupus have also been reported. However, up to date, no cases with type 2 diabetes have been reported as long-term sequelae. To our knowledge, this is the first case in the literature presenting with type 2 diabetes as long-term sequelae.

The protective effect of granulocyte colony-stimulating factor on endometrium and ovary in a rat model of diabetes mellitus.

AIMS: To evaluate the effect of granulocyte colony-stimulating factor (G-CSF) on the endometrium and ovaries in an experimental diabetes mellitus (DM) rat model. METHODS: A total of 18 female Sprague-Dawley albino mature rats (8 weeks, 200-220 g) were used in this study. Diabetes was induced by intraperitoneal (i.p.) injection of streptozocin randomly in 12 rats. No drug was administered to the remainder of the rats (control group, group 1, n = 6). The other 12 rats were randomly divided into 2 groups; 1 ml/kg i.p. saline was given as vehicle to group 2 (diabetic nontreated control group, n = 6) and 100 µg/kg/day of i.p. G-CSF was given to group 3 (G-CSF-treated group, n = 6) for 4 weeks. After 4 weeks, blood samples were collected and hysterectomy with bilateral oophorectomy was performed for histopathological examination. RESULTS: The mean endometrial gland degeneration and stromal fibrosis scores were significantly higher in group 2 compared with groups 1 and 3. Ovarian follicle degeneration, stromal degeneration and stromal fibrosis scores were significantly higher in group 2 compared with groups 1 and 3. Plasma TGF-ß and malondialdehyde levels were significantly lower in groups 1 and 3 compared with group 2. Antimüllerian hormone levels were significantly lower in group 2 compared with groups 1 and 3. CONCLUSION: Glucose toxicity occurred severely in the ovaries and endometrium of the DM rats. After G-CSF treatment, ovarian and endometrial injury and fibrosis scores decreased significantly. The effects of G-CSF in rat models give hope to improved treatment of human DM complications such as premature ovarian failure and endometrial dysfunction.

The association between plasma thyroxine levels and neurocognitive impairment in early-onset schizophrenia and other psychosis spectrum disorders.

BACKGROUND/AIM: Limited studies have delved into the association between thyroid hormones and neurocognition in schizophrenia. We aimed to evaluate the relationship between thyroid hormone levels and neurocognitive functions in patients with schizophrenia and other psychosis spectrum disorders (SSD). METHOD: A total of 135 patients with early-onset SSD were included in the study. The participants underwent a cognitive assessment. Blood samples were collected to measure serum levels of thyroid-stimulating hormone (TSH), free thyroxine (fT4), and free triiodothyronine (fT3). Subgroup analyses were conducted based on the severity of the psychosis. FINDINGS: The results revealed a significant association between fT4 levels and various cognitive domains, including processing speed, verbal fluency, working memory, verbal learning, verbal memory, and visual memory. However, serum TSH and fT3 levels exhibited no significant association with neurocognitive impairment in adjusted linear regression models. Specifically, the correlation between fT4 levels and global cognition was more pronounced in patients with higher scores. CONCLUSIONS: Serum fT4 levels were associated with the performance across various cognitive domains in cases of early-onset psychotic disorders. This correlation was accentuated among patients with higher illness severity. Future studies could focus on the effects of specific pathways that can affect the course and progression of psychosis.

Does an episode of diabetic ketoacidosis affect thyroid function tests in pediatric patients?

OBJECTIVES: The aim of our study was to investigate the changes in thyroid hormone levels during and after acute metabolic disorder in patients with diabetic ketoacidosis (DKA). METHODS: Eighty five patients diagnosed with DKA were included in the study. Patients with control thyroid function test (TFT) values at admission (the first blood sample) and 1 month later were included in the study. Thyroid function tests obtained during diabetic ketoacidosis and at the first month follow-up were compared. Euthyroidism and euthyroid sick syndrome were defined and grouped according to current guidelines. The mild and moderate groups, according to DKA classification, were combined and compared with the severe group. RESULTS: A significant increase was observed between the first admission and the control TFT values 1 month later. However, there was no significant difference found in TFT between mild/moderate and severe groups taken at the time of DKA. Difference between two groups, euthyroid sick syndrome and euthyroid, was examined and the result that was different from the literature was the difference between TSH levels. We found that low FT4 levels were associated with higher HgbA1c, although the correlation was weak. CONCLUSIONS: Thyroid hormone levels may not reflect a thyroid disease during severe DKA attack. Therefore, it is unnecessary to check thyroid function tests.

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.

Attempted suicide with levothyroxine in an adolescent girl.

Attempted suicide with levothyroxine is very rare and has been described only in a few case reports. Although acute accidental or intentional overdoses of thyroid hormones can lead to marked elevations in serum T4 levels, many children who take as much as 5-10 mg of levothyroxine as a single dose have few or no symptoms of thyrotoxicosis. We report an adolescent girl who attempted suicide by ingesting levothyroxine. She responded well to ß-adrenergic blockade.

Hypoparathyroidism in children and adolescents.

Hypoparathyroidism is characterized by insufficient parathyroid hormone (PTH) release from the parathyroid glands to maintain serum calcium level within normal limits and unresponsiveness of target tissues despite normal serum PTH level. Hypoparathyroidism is defined as low or inappropriately normal serum PTH level. In this narrative review, we discuss the etiology of hypoparathyroidism in children.

Approach to nutritional rickets.

Rickets is the disease of a growing skeleton and results from impaired apoptosis of hypertrophic chondrocytes and mineralization of the growth plate. Nutritionally induced rickets, secondary to vitamin D and/or calcium deficiency, remains a major global problem. In this review, we discuss pathogenesis, clinical signs, investigation and management of nutritional rickets.

The therapeutic effect of oral desmopressin lyophilisate formulation in children with central diabetes insipidus.

OBJECTIVES: We aimed to assess the efficacy of oral use of oral desamino-D-arginine-8-vasopressin lyophilisate (OLD) in children with central diabetes insipidus (CDI). METHODS: Clinical, laboratory, and imaging characteristics of twenty-five children with CDI treated with OLD were evaluated. RESULTS: Fourteen boys and eleven girls with a mean age of 52.37 months were evaluated. These children (mean weight and height at admission, 26.81 ± 14.8 kg vs. 92.52 ± 30 cm) presented with failure to thrive, irritability, prolonged fever, polyuria and hypernatremia (mean sodium level, 143.12 ± 8.6 mEq/L). At the time of hypernatremia, mean serum and urine osmolality were 298.2 ± 18 mOsm/kg and 160.20 ± 8.7 mOsm/kg, respectively. ADH levels were undetectable (<0.5 pmol/L) at admission in all cases. Oral administration of desmopressin lyophilisate (120 µg/tablet) was initiated at a dose of 5 µg/kg/day in two divided doses together with controlled water intake to avoid hyponatremia. Serum sodium levels normalised in a mean duration of 15.2 ± 16.4 h with a mean decline rate of 0.12 ± 0.04 mEq/L/h. Nine children needed rehospitalization because of hypernatremia due to non-compliance. Four episode of hyponatremia was observed. Weight gain and growth were normal during the mean follow-up duration of 37.79 ± 48.2 months. CONCLUSIONS: Administration of OLD was practical and safe in the treatment of CDI in children with CNS malformations in this small retrospective series.

Management of Central Diabetes Insipidus in Disabled Children with Diluted Oral Desmopressin Lyophilisate Formulation Administered Through Nasogastric Tube: A Retrospective Case Series.

BACKGROUND: Experience with nasogastric administration of oral DDAVP [desamino-D-arginine-8-vasopressin] lyophilisate (ODL) for central diabetes insipidus (CDI) in disabled children with swallowing coordination difficulties is limited. OBJECTIVE: We aimed to assess the safety and efficacy of nasogastric use of ODL in disabled children with CDI. Time to serum sodium normalisation was compared with that of children with normal intellect and CDI treated with sublingual DDAVP. METHODS: Clinical, laboratory and neuroimaging characteristics were evaluated for 12 disabled children with CDI treated with ODL through nasogastric tube at Dr Behcet Uz Children's Hospital, Turkey, between 2012 and 2022. RESULTS: Six boys and six girls with a mean (±SD) age of 43 (± 40) months were evaluated. These children (mean [±SD] weight standard deviation score [SDS] - 1.2 ± 1.7; mean [±SD] height SDS - 1.3 ± 1.4) presented with failure to thrive, irritability, prolonged fever, polyuria and hypernatraemia (mean serum sodium 162 [±3.6] mEq/L). At diagnosis, mean serum and urine osmolality were 321 (± 14) mOsm/kg and 105 (± 7.8) mOsm/kg, respectively. Arginine vasopressin (AVP) levels were undetectable (< 0.5 pmol/L) at diagnosis in all patients. Nasogastric tube administration of DDAVP lyophilisate (120 µg/tablet) dissolved in water (10 mL) was commenced at a dose of 1-5 µg/kg/day in two divided doses together with controlled water intake to avoid hyponatraemia. The frequency and dose of DDAVP were titrated based on urine output and serum sodium concentration. Serum sodium declined at a rate of 0.11 ± 0.03 mEq/L/h and reached normal range in a mean duration of 174 ± 46.5 h. Serum sodium declined faster in children with normal intellect and CDI treated with sublingual DDAVP (1.28 ± 0.39 mEq/L/h; p = 0.0003). Three disabled children needed rehospitalisation because of hypernatraemia due to unintentional DDAVP omission by caregivers. No episode of hyponatraemia was observed. Weight gain and growth were normal during the median (± interquartile range) follow-up duration of 32 ± 67 months. CONCLUSIONS: Nasogastric administration of oral DDAVP lyophilised formulation was safe and effective in the treatment of CDI in disabled children in this small retrospective series.

Comparison of Optical Coherence Tomography Angiography Findings between Healthy Children and Children with Type 1 Diabetes Mellitus and Autoimmune Thyroiditis

Objective: The aim of this study was to compare the development of early diabetic retinopathy (DR) findings, a microvascular complication, between patients with isolated type 1 diabetes mellitus (T1DM) (Group 1), concurrent T1DM and autoimmune thyroiditis (AT) (Group 2), and healthy controls (Group 3), who were matched for age, sex, number, and body mass index for comparison. Methods: This was a prospective observational study that included individuals aged 10-20 years, and patients in Groups 1 and 2 had been followed up for ≥5 years. None of them developed clinical DR during the follow-up period. Optical coherence tomography angiography (OCTA) was used to evaluate the foveal avascular zone (FAZ) and parafoveal vascular density (PVD) for the development of early DR. OCTA findings were compared between patients and healthy controls. Results: Thirty-five individuals were included in each of the groups. The mean FAZ and PVD differed significantly between the three groups (FAZ, p=0.016; PVD, p=0.006). The mean FAZ was higher in Groups 1 and 2 than in Group 3 (p=0.013 and p=0.119, respectively). The mean PVD was lower in Groups 1 and 2 than in Group 3 (p=0.007, respectively). No significant difference was found between Groups 1 and 2 in terms of the mean FAZ and PVD (p=0.832 and p=0.653, respectively). The mean glycated hemoglobin (HbA1c) level was significantly correlated with FAZ and PVD (FAZ: r=0.496, p<0.001; PVD: r=-0.36, p=0.001). Conclusion: In patients with T1DM who did not develop clinical DR, OCTA findings revealed an increase in FAZ, which was associated with higher HbA1c levels. The mean PVD was significantly lower in the group with coexisting AT and T1DM than in the control group. These results suggest that the coexistence of AT and T1DM can contribute to the development of microvascular complications. However, studies with larger patient series are required.

The Association between Vitamin D deficiency and Hepatosteatosis in Children and Adolescents with Obesity.

INTRODUCTION: Increasingly, research groups have been studying the association of serum vitamin D and metabolic health indicators, especially in patients with obesity. We compared the serum 25-hydroxy Vitamin D [25(OH)D] concentrations in children and adolescents who had obesity and hepatosteatosis with children and adolescents who had obesity without hepatosteatosis, and investigate the relationship between serum 25(OH)D concentrations and severity of hepatosteatosis. We also aimed to assess the effect of vitamin D treatment after 6 months on hepatosteatosis and liver biochemistry. METHODS: One hundred thirty-three patients with obesity (body mass index (BMI) > +2 standard deviations (SD) for their age and gender) and vitamin D deficiency [serum 25(OH)D < 12 ng/ml] were recruited. Anthropometric measurements, biochemical parameters [serum calcium, phosphate, alkaline phosphatase, parathyroid hormone, 25(OH)D, glucose and insulin concentrations] and ultrasonographic findings of hepatosteatosis were recorded before and six months after Vitamin D treatment. Chi-square, Student's t tests and multivariate analysis were performed. RESULTS: Grade 1, 2 and 3 hepatosteatosis at baseline was present in 51 (38.4%) , 43 (32.3%) and 10 (7.5%) subjects respectively. Mean (± SD) serum 25(OH)D concentrations were significantly lower in those with hepatosteatosis (8.4 ± 2.4 ng/ml) compared with those without hepatosteatosis (9.9 ± 2.4 ng/ml, P < 0.005). Multivariable logistic regression analysis showed serum 25(OH)D concentration was the independent predictor for hepatosteatosis (P < 0.005), whereas age, sex, weight SD, BMI SD and HOMA-IR were not (P > 0.05). There was no significant difference in BMI SD, HOMA-IR and liver enzymes between subjects with and without hepatosteatosis (P > 0.05). Despite improvement in serum 25(OH)D concentrations at 6 months post-treatment (34.7 ± 10.6 ng/ml vs. 8.7 ± 2.4 ng/ml; p < 0.0001), there was no significant difference in the proportion of patients with different severity of hepatosteatosis as compared to before treatment (p = 0.88). CONCLUSION: Serum 25(OH)D concentrations were lower in children and adolescents with obesity and hepatic steatosis as compared to those without hepatic steatosis, with an inverse association between the severity of hepatosteatosis and serum 25(OH)D concentrations. Vitamin D treatment in children and adolescents with obesity and hypovitaminosis D did not improve severity of hepatic steatosis on ultrasonography at 6 months.

Impact of Obesity on Bone Metabolism in Children.

Obesity is an epidemic disease that can increase the incidence of type 2 diabetes, cardiovascular disease, malignancy, hypertension, and other health problems that affect the musculoskeletal system. There is a complex interaction between obesity and bone metabolism. In children with obesity, the peroxisome proliferator-activated receptor gamma pathway causes the differentiation of mesenchymal stem cells into adipocytes via osteoblasts, in which results in low bone mass and osteoporosis. Systemic inflammation in obesity has negative effects on bone metabolism. An increase in the number and size of adipose tissue and adipocytokines secreted from adipocytes affect the bone mass of the whole body with hormonal and biochemical effects. The skeletal effects of obesity are mediated by higher oxidative stress and increased production of proinflammatory cytokines. Osteoporosis due to obesity has increased morbidity and mortality in recent years, resulting in important health problems in developed and developing countries.

Central Diabetes Insipidus in Children and Adolescents: Twenty-Six Year Experience from a Single Centre.

Introduction: Paediatric cohorts of central diabetes insipidus (CDI) have shown varying prevalence for different causes of CDI. The objective of this study was to determine the causes of CDI and long-term outcome in children and adolescents from a Tertiary Paediatric Endocrinology unit. Methods: The clinic database was searched to identify patients with CDI managed between 1993 and 2019. Relevant clinical information was collected from patient records. Results: A total of 138 CDI patients, median age 6 years (range <1-18) at presentation, were identified. Principal CDI aetiologies were craniopharyngioma (n = 44), acute central nervous system (CNS) insult (n = 33), germinoma (n = 15), postneurosurgery (indication other than craniopharyngioma and germinoma, n = 20), midline CNS malformation (n = 14), Langerhans cell histiocytosis (n = 5), and familial (n = 2). Idiopathic CDI in this cohort was infrequent (n = 5). Patients with CNS malformations/infections presented with CDI at a younger age compared to patients with CNS tumours (p < 0.0001). Five patients, initially presenting as idiopathic CDI, were subsequently diagnosed with germinoma after a median interval of 3.3 years. All patients with CDI related to craniopharyngioma and nearly all (87%) patients with CDI related to germinoma had concomitant GH, ACTH, and TSH deficiency. The majority of patients who manifested CDI due to acute CNS insult either deceased (30%) or had transient CDI (33.3%). Conclusion: Surgery for craniopharyngioma was the most common underlying aetiology of CDI with ubiquitous occurrence of panhypopituitarism in these patients. Manifestation of CDI in patients with acute CNS insult carries poor prognosis. We affirm that neuroimaging assessment in idiopathic CDI should be continued beyond 3 years from diagnosis as a significant number of patients exhibited progression of infundibular thickening 3 years post-CDI diagnosis.

Detection of SHOX Gene Variations in Patients with Skeletal Abnormalities with or without Short Stature

Objective: SHOX gene mutations constitute one of the genetic causes of short stature. The clinical phenotype includes variable degrees of growth impairment, such as Langer mesomelic dysplasia (LMD), Léri-Weill dyschondrosteosis (LWD) or idiopathic short stature (ISS). The aim of this study was to describe the clinical features and molecular results of SHOX deficiency in a group of Turkish patients who had skeletal findings with and without short stature. Methods: Forty-six patients with ISS, disproportionate short stature or skeletal findings without short stature from 35 different families were included. SHOX gene analysis was performed using Sanger sequencing and multiplex ligation-dependent probe amplification analysis. Results: Three different point mutations (two nonsense, one frameshift) and one whole SHOX gene deletion were detected in 15 patients from four different families. While 4/15 patients had LMD, the remaining patients had clinical features compatible with LWD. Madelung's deformity, cubitus valgus, muscular hypertrophy and short forearm were the most common phenotypic features, as well as short stature. Additionally, hearing loss was detected in two patients with LMD. Conclusion: This study has presented the clinical spectrum and molecular findings of 15 patients with SHOX gene mutations or deletions. SHOX deficiency should be especially considered in patients who have disproportionate short stature or forearm anomalies with or without short stature. Although most of the patients had partial or whole gene deletions, SHOX gene sequencing should be performed in suspected cases. Furthermore, conductive hearing loss may rarely accompany these clinical manifestations.