The relationship of carotid intima-media thickness with anthropometric and metabolic parameters in patients with classic congenital adrenal hyperplasia

Background/aim: We aimed to determine the presence of subclinical atherosclerosis using carotid intima-media thickness (CIMT) and biochemical parameters in children and adolescents with congenital adrenal hyperplasia (CAH). Materials and methods: Thirty-four patients with classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency on regular glucocorticoid treatment for ≥3 years and 31 healthy subjects were included in the study. The patients were divided into two groups according to the degree of control of the clinic, laboratory, and radiological parameters as a) "uncontrolled" [n= 22; with increased height velocity (HV) standard deviation score (SDS) (≥2 SDS), advanced bone age, serum 17-OH progesterone <2.0 and ≥10.0 ng/mL or androstenedione <0.3 and ≥ 3.0 ng/mL] or b) "controlled" [n= 12; with HV SDS < 2, bone age (BA)/ chronologic age (CA) ratio < 1.2, serum 17-OH progesterone between 2 and 10 ng/mL and androstenedione between 0.3 and 3.0 ng/mL]. Ultrasonographic examination of carotid artery was performed by the same radiologist using a B-mode ultrasound system. Results: There was no significant difference between the CAH and control groups in terms of median (IQR) CIMT values [0.47 (0.05) mm and 0.47 (0.07) mm, respectively; p > 0.05]. When subgroup comparisons were done in terms of median (IQR) CIMT values, there was no significant difference among the controlled, uncontrolled, and healthy control groups [0.45 (0.03) mm, 0.47 (0.04) mm, 0.47 (0.07) mm, respectively; p> 0.05]. In addition, CIMT levels were similar according to sex and disease control status. Conclusion: In this study, the CIMT values of CAH cases were similar to those of healthy subjects.

Impaired systolic and diastolic left ventricular function in children and adolescents with congenital adrenal hyperplasia receiving corticosteroid therapy.

AimThe present study aimed to evaluate systolic and diastolic myocardial function in children and adolescents with congenital adrenal hyperplasia. METHODS: The study included 44 children with the diagnosis of classic congenital adrenal hyperplasia and 39 healthy children whose age, pubertal status, and gender were similar to those of the patient group. Anthropometric parameters and 17-hydroxyprogesterone levels were measured, and bone age was calculated. The average daily hydrocortisone dose was calculated over the last 1-year file records. Hyperandrogenic state was defined according to bone age SD score (⩾2) and 17-hydroxyprogesterone levels (>10 ng/ml). Echocardiographic examinations were assessed by conventional two-dimensional Doppler echocardiography and tissue Doppler imaging. RESULTS: Patients had higher morphological parameters, such as left ventricular end-systolic diameter, interventricular septal thickness at end diastole, left ventricular posterior wall thickness at end diastole, left ventricular mass and index, than the control group (p<0.05). On pulsed-wave and tissue Doppler echocardiography, significant subclinical alterations were observed in systolic (isovolumic contraction time), diastolic (isovolumic relaxation time), and global left ventricular functional (myocardial performance index) parameters in the congenital adrenal hyperplasia group compared to the control group (p<0.05). In partial correlation analyses, after controlling the effect of hyperandrogenism, the mean hydrocortisone dosage was positively correlated with isovolumic relaxation time in congenital adrenal hyperplasia group (p<0.05). CONCLUSION: This study demonstrated that the patients with congenital adrenal hyperplasia are at risk for left ventricular hypertrophy, systolic and diastolic myocardial subclinical alterations. Overtreatment may be responsible for the increased risk of myocardial dysfunction in patients with congenital adrenal hyperplasia.

The effect of low-level laser therapy on tooth movement during canine distalization.

The aim of the study is to determine the effects of low level laser therapy on tooth movement during canine distalization by evaluating IL-1ß, TGF-ß1 levels in gingival crevicular fluid. Maxillary first premolars of the 15 Angle Class II division I patients (12-19 years old) were extracted. Right maxillary canines were distalized by standard protocol as control group whereas the left maxillary canines distalized by laser application. A gallium-aluminum-arsenide diode laser with an output power of 20 mW was applied as five doses from the buccal and the palatal side on the day 0, and the 3rd, 7th, 14th, 21th 30th, 33st, 37th, 60th, 63th, and 67th days. Gingival crevicular fluid samples were obtained with filtration paper at the initial, 7th, 14th, and 21th days, and the IL-1ß and TGF-ß1 cytokine levels were analyzed. Orthodontic models and periodontal indices were taken initially and on the days 30th, 60th, and 90th of canine distalization period. Tooth movement was assessed by scanning models (3Shape). The amount of tooth movement in the laser group was 40% more than the control group. First day IL-1ß levels were statistically higher than initial and 21st day levels (P= 0.003, P = 0.012). The rise in IL-1ß levels caused the negative correlations between 7th day IL-1ß and 21st day TGF-ß1 levels describes the tissue effects of laser application. Periodontal indices showed no sign of gingival inflammation during canine distalization period. As conclusion, laser does accelerate tooth movement and could shorten the whole treatment duration.

POU6F2 mutation in humans with pubertal failure alters GnRH transcript expression.

Idiopathic hypogonadotropic hypogonadism (IHH) is characterized by the absence of pubertal development and subsequent impaired fertility often due to gonadotropin-releasing hormone (GnRH) deficits. Exome sequencing of two independent cohorts of IHH patients identified 12 rare missense variants in POU6F2 in 15 patients. POU6F2 encodes two distinct isoforms. In the adult mouse, expression of both isoform1 and isoform2 was detected in the brain, pituitary, and gonads. However, only isoform1 was detected in mouse primary GnRH cells and three immortalized GnRH cell lines, two mouse and one human. To date, the function of isoform2 has been verified as a transcription factor, while the function of isoform1 has been unknown. In the present report, bioinformatics and cell assays on a human-derived GnRH cell line reveal a novel function for isoform1, demonstrating it can act as a transcriptional regulator, decreasing GNRH1 expression. In addition, the impact of the two most prevalent POU6F2 variants, identified in five IHH patients, that were located at/or close to the DNA-binding domain was examined. Notably, one of these mutations prevented the repression of GnRH transcripts by isoform1. Normally, GnRH transcription increases as GnRH cells mature as they near migrate into the brain. Augmentation earlier during development can disrupt normal GnRH cell migration, consistent with some POU6F2 variants contributing to the IHH pathogenesis.

Hyperprolactinemia in children: clinical features and long-term results.

Hyperprolactinemia is a rare endocrine disorder in childhood, which may result from hypophyseal adenoma. We aimed to review the etiologic reasons and clinical features in hyperprolactinemia patients retrospectively. The mean age of 11 female patients at diagnosis was 14.2 ± 1.3 years. Five patients had microadenoma, four patients had macroadenoma, and two patients were diagnosed with idiopathic hyperprolactinemia. The most frequent symptoms were menstrual disorders, headache, and galactorrhea, and one-third of the patients had obesity at diagnosis. There was no anterior pituitary hormone deficiency. All patients received bromocriptine as initial therapy; only two patients with macroadenoma and one patient with microadenoma were switched to cabergoline. Transsphenoidal surgery was performed for a patient with macroadenoma, who had cavernous sinus invasion and visual field defect. Medical treatment should be the first-line treatment option in both microadenoma and macroadenoma cases without any neurological signs. Surgery should be employed with limited indications.

A novel DAX1 gene mutation in a Turkish infant with X-linked adrenal hypoplasia congenita.

Adrenal hypoplasia congenita (AHC) is a rare inherited disorder of the adrenal cortex commonly manifested as an early onset adrenal insufficiency syndrome. A novel DAX1 (NR0B1) gene mutation was detected in a Turkish newborn boy presenting with primary adrenal insufficiency. He was from a family with a history of unexplained death of three male siblings in the neonatal period. This report highlights the value of mutational analysis of the DAX1 gene for definitive diagnosis of AHC as well as for genetic counselling because this disorder shows an X-linked genetic pattern of transmission, providing the possibility of finding new cases even in presymptomatic individuals.

Adult height in Turkish patients with Turner syndrome without growth hormone treatment.

Spontaneous adult height (AH) in Turner syndrome (TS) varies among populations. Population-specific AH data is essential to assess the efficacy of growth-promoting therapies in TS. A multicenter study was performed to establish AH of nongrowth hormone (GH)-treated Turkish patients with TS. One hundred ten patients with TS (diagnosed by karyotype) who reached AH (no growth in the previous year, or bone age > 15 years) without receiving GH treatment were included in the study. The average AH was found to be 141.6 +/- 7.0 cm at the age of 22.9 +/- 6.2 years, which is 18.4 cm below the population average and 16.4 cm below the patients' mid-parental heights. Bone age at start of estrogen replacement was 12.3 +/- 1.3 year. Karyotype distribution of the patients was 45X (43%), 45X/46XX (16%), 45X/46Xi (12%), 45XiXq (10%) and others (19%). When the patients were evaluated according to their karyotype as 45X and non-45X, no significant difference in AH was observed (142.4 +/- 6.9 cm vs 140.9 +/- 7.1 cm, respectively). Adult height of non-GH-treated Turkish TS patients obtained in this study was comparable to that of other Mediterranean populations, but shorter than that of Northern European patients. Karyotype does not seem to affect AH in TS.

Olfactory dysfunction in children with Kallmann syndrome: relation of smell tests with brain magnetic resonance imaging.

OBJECTIVE: Kallmann syndrome (KS) is a genetic disorder with the distinctive features of hyposmia or anosmia and hypogonadotropic hypogonadism. Though hyposmia/anosmia can be evaluated by both objective and subjective smell tests, there is no study comparing these two methods in KS. The aim of the present case series was to discuss the results of objective and subjective smell tests and compare them to volumetric magnetic resonance imaging (MRI). METHODS: A total of six adolescent males (aged between 14-18 years) with KS were examined by objective and subjective olfactometry to test smell function and by specific MRI sequences to measure the olfactory bulbs. RESULTS: The objective smell test showed anosmia in all six of the patients. However, the subjective test revealed anosmia in five patients and hyposmia in one patient. Brain MRI showed olfactory bulb aplasia in all six cases. CONCLUSION: MRI provides robust evaluation of the olfactory bulb volume. Our data show excellent compatibility between the results obtained via objective olfactometry and those obtained by measuring olfactory bulb volume as determined by MRI and therefore demonstrate that objective olfactometry remains a highly reliable test. Furthermore, although the number of subjects studied was small, these data also suggest that cheaper and more easily available subjective tests could be used in preference to the more expensive as well as labor-intensive and time-consuming objective smell tests. In the event of doubts as to the validity of the subjective tests, the objective olfactometry tests can confirm the diagnosis. The bulb volumetric MRI may be also used in difficult cases.

Current practice in diagnosis and treatment of growth hormone deficiency in childhood: a survey from Turkey.

OBJECTIVE: Approaches to diagnosis and treatment of growth hormone deficiency (GHD) in children vary among countries and even among centers in the same country. This survey, aiming to facilitate the process of preparing the new consensus on GHD by the Turkish Pediatric Endocrinology and Diabetes Society, was designed to evaluate the current practices in diagnosis and treatment of GHD in different centers in Turkey. METHODS: A questionnaire covering relevant items for diagnosis and treatment of GHD was sent out to all pediatric endocrinology centers. RESULTS: Twenty-four centers returned the questionnaire. The most frequently used GH stimulation test was L-dopa, followed by clonidine. Eighteen centers used a GH cut-off value of 10 ng/mL for the diagnosis of GHD; this value was 7 ng/mL in 4 centers and 5 ng/mL in 2 centers. The most frequently used assay was immunochemiluminescence for determination of GH, insulin-like growth factor-1 and insulin-like growth factor binding protein-3 concentrations. Sex steroid priming in both sexes was used by 19 centers. The most frequently used starting dose of recombinant human GH (rhGH) in prepubertal children was 0.025-0.030 mg/kg/day and 0.030-0.035 mg/kg/day in pubertal children. Growth velocity was used in the evaluation for growth response to rhGH therapy in all centers. Anthropometric measurements of patients every 3-6 months, fasting blood glucose, bone age and thyroid panel evaluation were used by all centers at follow-up. Main indications for cessation of therapy were decreased height velocity and advanced bone age. Fourteen centers used combined treatment (rhGH and gonadotropin-releasing analogues) to increase final height. CONCLUSION: Although conformity was found among centers in Turkey in current practice, it is very important to update guideline statements and to modify, if needed, the approach to GHD over time in accordance with new evidence-based clinical studies.

Carnitine metabolism in diabetes mellitus.

In diabetes mellitus (DM), increased fatty acids have negative effects on pancreatic beta-cell functions, in addition to enhanced mitochondrial transportation of fatty acids related to decreased insulin levels. The aim of this study was to evaluate lipid metabolism in children with DM by measuring plasma fatty acids and carnitine fractions to reveal relationships between carnitine status and increased fatty acid oxidation. Increased plasma fatty acids (except for arachidonic acid, there were no significant differences in the ratio of each specific fatty acid to total fatty acids), lipoprotein (a), acyl carnitine levels and urinary total and free acyl carnitine excretion, and decreased plasma free carnitine levels, were found in children with DM. There were no correlations between the duration of DM or HbA1c and study parameters. It is recommended that plasma free carnitine determinations should be made even if the patient has good metabolic control.

Diabetic ketoacidosis presenting with pseudonormoglycemia in a 15-year-old girl with type 1 diabetes mellitus.

Pseudonormoglycemic diabetic ketoacidosis (DKA) is a rare condition and has been reported only in a few adult patients. We present a 15-year-old girl with a 9-year history of type 1 diabetes who presented with euglycemic and extreme hypertriglyceridemia. The acidosis and hypertriglyceridemia resolved with intravenous insulin therapy and rehydration. Hyperlipidemia was the apparent cause of pseudonormoglycemia in this patient. The findings in the present case demonstrate that also in children, DKA can rarely occur without abnormal blood glucose levels. Assessment of the acid-base status, urinary glucose, and ketone readings is therefore important in all diabetic patients who are unwell at admission and have normal glucose levels. In such patients, hyperlipidemia may cause pseudonormoglycemia. An awareness of this rare treatable life-threatening condition is important.

Gastric emptying of solids and its relationship with microalbuminuria in children and adolescents with type 1 diabetes mellitus.

BACKGROUND: The aims of the present study were to determine the frequency of delayed gastric emptying in children and adolescents with type 1 diabetes mellitus (T1DM) and to investigate the relationship between gastric emptying rate and other contributing factors (e.g. serum HbA1c, duration of diabetes and microalbuminuria) in these patients. METHODS: This was a clinical trial evaluating the rate of gastric emptying of solid meals in 33 children and adolescents with T1DM and in 26 healthy peers using a radionuclide method. Three consecutive overnight urine collections were used to calculate the albumin excretion rate. RESULTS: There was no significant difference in the gastric half-emptying time (GE t½ ) between patients and controls (151.7 ± 154.5 vs 109.8 ± 60.5 min, respectively; P=0.885) or the frequency of delayed gastric emptying (36.4% vs 30.8%, respectively; P=0.433). There was a moderately positive correlation between GE t½ and the duration of diabetes (r=0.380; P=0.029). There was no correlation between GE t½ and microalbumin levels in T1DM patients. In these patients, the body mass index standard deviation scores were significantly lower than in patients with normal gastric emptying (-0.13 ± 0.87 vs 0.7 ± 1.23, respectively; P=0.044). CONCLUSION: Progression of delayed gastric emptying is more likely to be related to a longer duration of diabetes than glycemic control in children and adolescents with T1DM. Patients with delayed gastric emptying are thinner compared with patients with a normal rate of gastric emptying; they may also be asymptomatic.

Low density lipoprotein apheresis in pediatric patients with homozygous familial hypercholesterolemia.

The aim of the present study is to clarify the low density lipoprotein apheresis procedure for pediatric patients with homozygous familial hypercholesterolemia (FH) in terms of efficacy, adverse effects and difficulties. The follow-up was carried out using an open, prospective uncontrolled clinical design. Data were collected from 10 patients (with an average age of 8.4 +/- 4.7 years) with FH treated with double filtration plasmapheresis. The total time span of follow-up covered five years (30.2 +/- 17.8 months [range 9-60 months]) and more than 600 sessions (62.1 +/- 35.5 sessions per patient [range 18-120 sessions]) were evaluated. The mean low density lipoprotein cholesterol (LDL-C) pre-treatment value was 375.5 +/- 127.5 mg/dL, and the post-treatment value was 147.5 +/- 73.9 mg/dL. This corresponded to a 62.8 +/- 10.3% (43-73%) acute reduction of LDL-C, while the mean high density lipoprotein cholesterol losses amounted to 41%. The chronic reduction in LDL-C ranged from 18 to 52%, with a mean level of 36.4 +/- 11.7%. The most frequently occurring technical problems were related to blood lines: puncture difficulties (4.5%), insufficient blood flow (3.5%), and obturation of the blood lines (2.4%). The main clinical adverse effects were hypotension (0.2%), chills/feeling cold (0.1%), and nausea and vomiting (0.2%). We observed that the low pediatric patient tolerance is the main problem in compliance with treatment. In conclusion, LDL apheresis, started under the age of eight years, combined with lipid-lowering drugs, provides a safe and effective lowering of the mean LDL-C levels in pediatric homozygous FH; and there are more problems with compliance for pediatric LDL apheresis than in the adult population.