The effect of GnRH stimulation on AMH regulation in central precocious puberty and isolated premature thelarche.

OBJECTIVES: There is a complex interaction between the anti-müllerian hormone (AMH) and hypothalamic-pituitary-gonadal axis. However, the effect of gonadotropin-releasing hormone (GnRH) stimulation on AMH levels is not clearly known. In the study, we aimed to evaluate the effect of GnRH stimulation on AMH levels in central precocious puberty (CPP) and isolated premature thelarche (PT) groups. METHODS: Sixty-three girls with breast development before the age of 8 were enrolled in the study. GnRH test was performed on all subjects. Blood samples for follicle-stimulating hormone (FSH), luteinizing hormone (LH), and AMH levels were taken at basal, 40th, and 90th minute of GnRH test. Subjects were grouped as CPP and PT group. RESULTS: After GnRH stimulation, AMH levels increased significantly at the 40th minute and the stimulating effect of GnRH on AMH continued till the 90th minute (p: 0.0001). There was a positive correlation between basal and 90th-minute AMH levels (r: 479, p: 0.0001). The highest FSH, LH, and AMH times were significantly different after the GnRH stimulation (p: 0.001, p: 0.001, and p: 0.007). Although the CPP group had a lower basal AMH level than the PT group's basal AMH level; AMH response to GnRH stimulation was not different (p>0.05). CONCLUSIONS: In our study, which examined the effect of GnRH stimulation on AMH levels in early pubertal development disorders for the first time, GnRH stimulated AMH secretion rapidly, correlated with basal AMH. Basal AMH levels were lower in patients with CPP than in those with PT; however, the effect of GnRH stimulation on AMH levels was similar in both groups.

Anterior Segment Findings in Patients With Osteogenesis Imperfecta: A Case-Control Study.

PURPOSE: To evaluate the anterior segment parameters in patients with osteogenesis imperfecta (OI) compared with healthy control subjects. METHODS: Seventeen patients with OI and 19 age-matched healthy controls were included into this cross-sectional case-control study. Corneal topographic, topometric and Belin-Ambrósio Enhanced Ectasia Display III analysis, corneal densitometry (12-mm corneal diameter), and lens densitometry measurements were obtained by using the Pentacam HR-Scheimpflug imaging system (Oculus, Wetzlar, Germany). The corneal endothelial cell properties were determined by specular microscopy. RESULTS: In comparison to the control group, patients with OI had significantly higher front astigmatism (0.8 ± 0.4 vs. 1.4 ± 1.1 mm, P = 0.026), thinner thinnest corneal thickness (556.4 ± 32.7 µm vs. 482.5 ± 66.9 µm, P = 0.002), smaller corneal volume (62.4 ± 3.5 mm vs. 53.7 ± 6.4 mm, P < 0.001), lower anterior chamber depth (3.2 ± 0.3 mm vs. 3.0 ± 0.2 mm, P = 0.009), higher index of vertical asymmetry (0.1 ± 0.04 vs. 0.2 ± 0.11, P < 0.001), higher posterior elevation (6.0 ± 2.7 µm vs. 11.9 ± 7.8 µm, P = 0.002), lower maximum Ambrósio relational thickness indice (456.6 ± 67.5 vs. 365.6 ± 115.7, P = 0.009), and higher final "D" value (0.7 ± 0.4 vs. 2.0 ± 1.6, P = 0.002). The corneal and lens densitometry values were similar in all concentric zones and layers in both groups except that 6 to 10 mm in the center. Corneal densitometry was higher in eyes with OI than that in the control group (9.8 ± 1.7 and 8.8 ± 1.0, P = 0.010). There was no difference in endothelial cell morphology between the groups (P > 0.05). CONCLUSIONS: The morphologic parameters determined on the corneal analysis are in general agreement with the known pathophysiology of OI. Corneal analysis may prove useful in monitoring patients with OI in clinical practice.

Early Ophthalmic Artery Blood Flow Parameter Changes in Patients with Type 1 Diabetes Mellitus.

OBJECTIVES: The aim of this study was to assess initial changes in blood flow parameters of the ophthalmic artery (OA) in pediatric patients with type 1 diabetes mellitus (DM). METHODS: Sixty-three subjects were included in this prospective, cross-sectional, observational study. Thirty-one (49.2%) patients with type 1 DM without diabetic retinopathy formed the DM group. The control group comprised 32 (50.8%) healthy subjects. The OA of all of the patients was examined with Doppler ultrasonography. The main outcomes were peak systolic velocity (PSV), end diastolic velocity (EDV), pulsatility index (PI), and resistivity index (RI) measurements. RESULTS: The mean age at onset of type 1 DM was 10.7±2.0 years and the mean duration was 11.4±11.0 months. The mean PSV and EDV outcomes in both eyes were significantly higher in the control group than in the DM group, whereas, the mean PI and RI outcomes in both eyes were significantly higher in the DM group (p<0.05). A mean RI of ≥0.75 indicated vascular hemodynamic changes associated with type 1 DM with a sensitivity of 72% and a specificity of 65% (area under the curve: 0.702; p=0.007). A mean PI of ≥1.69 predicted vascular hemodynamic changes associated with type 1 DM with a sensitivity of 79% and a specificity of 71% (area under the curve: 0.742; p=0.001). CONCLUSION: The results of this study revealed that disturbances in ocular hemodynamics might be present as early as the first year after a type 1 DM diagnosis. Changes in ocular hemodynamic parameters could be used to predict or screen for the development of vascular changes.

How does thiol/disulfide homeostasis change in children with type 1 diabetes mellitus?

AIMS: An increase in reactive oxygen species leads to formation of covalent bonds between sulfur atoms, thus thiol/disulfide homeostasis shifts towards the disulfide direction and oxidative damage occurs. We aimed to determine thiol/disulfide homeostasis in children with T1DM. METHODS: Thiol/disulfide homeostasis was evaluated in 30 patients with T1DM and 30 age, gender matched healthy controls. Thiol/disulfide homeostasis parameters were measured using a novel automated measurement method and correlation between demographic data and parameters was measured. RESULTS: There weren't any significant differences in age or gender between the T1DM and control groups. T1DM group, findings were as follows: native thiol: 388.3 ±â€¯76.7 µmol/L, total thiol: 426.2 ±â€¯87 µmol/L, disulfide: 18.9 ±â€¯7 µmol/L, control group findings were as follows: native thiol: 423.1 ±â€¯45.2 µmol/L, total thiol: 455.7 ±â€¯49.9 µmol/L, disulfide: 16.2 ±â€¯5.6 µmol/L. The disulfide/native thiol and disulfide/total thiol ratios were significantly higher in the T1DM group (p = 0.005 and p = 0.004, respectively), whereas the native thiol level and the native thiol/total thiol ratio were significantly lower in the T1DM group than in the control group (p = 0.036 and p = 0.015, respectively). There wasn't significant correlation between demographic data and thiol/disulfide homeostasis parameters. DISCUSSION: This study shows that dynamic thiol/disulfide homeostasis in children with T1DM shifts towards the disulfide direction. We think that this shift is caused by oxidative damage in ß-cells. Additional research on thiol/disulfide homeostasis in children with T1DM might provide techniques for early detection of oxidative damage in ß-cells.

Vaginal bleeding and a giant ovarian cyst in an infant with 21-hydroxylase deficiency.

BACKGROUND: Increased adrenal androgen hormones in congenital adrenal hyperplasia (CAH) can rarely cause giant ovarian cysts in the neonatal period. Although the exact mechanism of the development of ovarian cysts is unknown, it is thought that increased androgen levels stimulate folicle development by increasing follicle stimulating hormone (FSH) levels. CASE PRESENTATION: A 16-day-old newborn with ambiguous genitalia was presented to our clinic. Laboratory test results were as follows: sodium: 126 mEq/L, potassium: 5.4 mEq/L, renin: 132 pg/mL, adrenocorticotropic hormone (ACTH): 207 pg/mL, cortisole: 7.8 µg/dL, basal 17OH progesterone: 21 ng/mL, androstenedione: 5.1 ng/mL, testosterone: 1188 ng/dL and dehydroepiandrosterone sulfate (DHEAS)>1500 µg/dL. Karyotype analysis resulted in 46,XX. A homozygous mutation of R356W was detected in the CYP21A2 gene. The classical severe form of salt wasting 21 hydroxylase deficiency was diagnosed and treatment was started with hydrocortisone and fludrocortisone. Good metabolic control was ensured by monthly visits but the baby presented with vaginal bleeding as soiling at 4 months. The cystic lesion which extended to the epigastric area from the pelvis in the midline abdomen, had a size of 90×80×60 mm and medially, thin ovarian parenchyma was detected in ultrasonography. CONCLUSIONS: The findings in our patient suggest that a decline in adrenal androgens after glucocorticoid treatment resulted in an increase in gonadotropin levels and the giant cyst is developed by activation of gonadotropin cascade and increased gonadotropin receptors, instead of androgens.

AMH levels at central precocious puberty and premature thelarche: is it a parameter?

BACKGROUND: The possible difference of antimüllerian hormone (AMH) levels at central precocious puberty (CPP) and premature thelarche (PT) has not been properly evaluated. OBJECTIVE/HYPOTHESIS: By evaluating AMH levels in girls with diagnosed CPP and PT, we aim to show the change of AMH levels at the pubertal onset. SUBJECTS: Sixty-five girls who have breast development before the age of 8 years and 25 healthy girls were enrolled in the study. METHODS: The subjects were divided into two groups as CPP and PT, according to results of GnRH test. AMH levels were determined in the two groups. RESULTS: The mean AMH levels of the CPP group were significantly lower than those in the PT group (13.57±9.85 pmol/L and 58.42±12.78 pmol/L, respectively, p=0.022). CONCLUSION: These results suggest that the AMH levels decrease in the duration of the hypothalamus-pituitary-ovarian axis activation. We thought that AMH might/may be a marker for distinguishing between CPP and PT.

Congenital hyperinsulinism in a newborn with a novel homozygous mutation (p.Q392H) in the ABCC8 gene.

Congenital hyperinsulinism is the most frequent cause of persistent hypoglycemia in infancy. We present the case of a preterm, large-for-gestation-age infant with congenital hyperinsulinism who was found to have a novel p.Q392H homozygous mutation in the ABCC8 gene. The patient had severe brain damage, despite early diagnosis and appropriate management. The new mutations may provide an understanding of the prognosis and treatment of the disease. In addition, the data will help the family make informed decisions about future pregnancies.

Cushing syndrome related to leukemic infiltration of the central nervous system: a case report and a possible role of LIF.

BACKGROUND: Adrenocorticotropic hormone (ACTH)-dependent Cushing syndrome (CS) in the presence of leukemic central nervous system infiltration is very rare. CASE: A 3.8-year-old girl who had been treated for B-cell acute lymphoblastic leukemia (ALL) for 1.5 years was admitted to our hospital with excessive weight gain and depression for the last 2 months. Prior to her admission, she was on maintenance with the ALL-BFM95 study protocol for 10 months that does not contain corticosteroids. On physical examination, central obesity and moon face appearance were determined. Laboratory tests revealed high morning ACTH, cortisol level, and 24-h urinary free cortisol level. Morning cortisol level was 33.94 nmol/L after a 2-day (4 × 0.5 mg) dexamethasone suppression test. A lumbar puncture revealed leukemic cells in the cerebrospinal fluid. No pituitary adenoma was detected on magnetic resonance imaging. We diagnosed the patient with ACTH-dependent CS related to leukemic infiltration of the central nervous system. CONCLUSION: Central nervous system infiltration should be considered in leukemic patients who have developed CS. We believe increased leukemia inhibitory factor levels may be a factor for CS in our patient with ALL.

OGTT results in obese adolescents with normal HOMA-IR values.

OBJECTIVE: To investigate insulin resistance (IR) with OGTT in obese adolescents who have normal fasting insulin and homeostasis model assessment for insulin resistance (HOMA-IR). SUBJECTS: A total of 97 obese adolescents who had values of HOMA-IR <3.16 and insulin levels <18 µU/mL (125 pmol/L) were included in the study. METHODS: Oral glucose tolerance test (OGTT) was performed on all cases. Subjects were divided into two groups: subjects with and without IR using an insulin peak of ≥150 µU/mL (1041.8 pmol/L) and/or ≥75 µU/mL (520.9 pmol/L) 120 min after glucose charge and the sum of insulin levels >2083.5 pmol/L (300 µU/mL) in OGTT. IR risk factors were defined as family history of diabetes mellitus, acanthosis nigricans (AN), and hepatic steatosis. RESULTS: IR was detected in 61 (62.9%) patients. The IR group had significantly more frequent AN (p=0.0001). As the number of risk factors increased, the frequency of IR also increased (p=0.01). CONCLUSION: We advise to perform OGTT in obese adolescents with normal HOMA-IR, if they have risk factors for IR.