Diagnostic value of urinary luteinizing hormone levels in the monitoring of precocious puberty treatment.

Objective To determine whether first-voided urinary LH (FV-ULH) - level measurement can adequately assess pubertal suppression as much as standard tests can. Subjects and methods The study group included patients with central precocious puberty and rapidly progressing early puberty who received up to 3 - 4 doses of GnRHa therapy monthly and did not have adequate hormonal suppression after GnRH stimulation (90-minute LH level > 4 IU/L). Design: All of the participants underwent an LHRH test just after admission to the study. According to the stimulated peak LH levels, the patients were divided into 2 groups and followed until the end of the first year of treatment. The concordance between FV-ULH and stimulated LH levels was assessed. Results The FV-ULH levels in patients with inadequate hormonal suppression were significantly high compared to patients with adequate hormonal suppression. FV-ULH levels were very strongly correlated with stimulated LH levels (r = 0.91). Its correlation with basal LH levels was significant (r = 0.65). However, this positive correlation was modestly weakened after the first year of treatment. The cutoff value for FV-ULH of 1.01 mIU/mL had the highest sensitivity (92.3%) and specificity (100%). Conclusion FV-ULH levels, using more reliable and sensitive assay methods, can be used to monitor the adequacy of GnRHa therapy.

Diagnostic value of urinary luteinizing hormone levels in the monitoring of precocious puberty treatment

ABSTRACT Objective To determine whether first-voided urinary LH (FV-ULH) - level measurement can adequately assess pubertal suppression as much as standard tests can. Subjects and methods The study group included patients with central precocious puberty and rapidly progressing early puberty who received up to 3 - 4 doses of GnRHa therapy monthly and did not have adequate hormonal suppression after GnRH stimulation (90-minute LH level > 4 IU/L). Design: All of the participants underwent an LHRH test just after admission to the study. According to the stimulated peak LH levels, the patients were divided into 2 groups and followed until the end of the first year of treatment. The concordance between FV-ULH and stimulated LH levels was assessed. Results The FV-ULH levels in patients with inadequate hormonal suppression were significantly high compared to patients with adequate hormonal suppression. FV-ULH levels were very strongly correlated with stimulated LH levels (r = 0.91). Its correlation with basal LH levels was significant (r = 0.65). However, this positive correlation was modestly weakened after the first year of treatment. The cutoff value for FV-ULH of 1.01 mIU/mL had the highest sensitivity (92.3%) and specificity (100%). Conclusion FV-ULH levels, using more reliable and sensitive assay methods, can be used to monitor the adequacy of GnRHa therapy.

Impaired dynamic thiol/disulfide homeostasis in pubertal gynecomastia.

BACKGROUND: The aim of the study was to evaluate the dynamic thiol/disulfide homeostasis (TDH) with a new method in patients with pubertal gynecomastia and also to investigate the relationship between sex hormones. METHODS: Thiol/disulfide homeostasis, involving native thiol (SH), disulfide (SS) and total thiol (SS + SH), was evaluated between 20 adolescent boys with gynecomastia in mid-puberty and 50 healthy adolescents, who were matched for age, body mass index (BMI) and pubertal stage. The correlations of total serum testosterone (TT) and estradiol (E2) levels with the oxidative parameters were also determined. RESULTS: No significant difference was found between the total thiol, native thiol, disulfide/native thiol and disulfide/total thiol ratios of the patient and control groups. The mean disulfide concentrations, disulfide/native thiol and the disulfide/total thiol ratios were statistically significantly higher in the patient group than in the controls. A positive correlation was found between the E2 and native thiol levels, also there was a negative correlation between the E2 and disulfide levels. TT was negatively correlated with both native thiol and disulfide levels. All these did not statistically differ between the patients with unilateral and bilateral gynecomastia. CONCLUSIONS: There was an impaired thiol/disulfide homeostasis in patients with pubertal gynecomastia. According to this result, we can postulate that oxidative stress may be an etiologic factor that contributes to initiation and/or progression of gynecomastia.

Ultrasonographic assessment of pubertal breast development in obese children: compliance with the clinic.

BACKGROUND: The aim of the study was to determine the compliance with the clinical and ultrasonographic staging of pubertal breast development in obese children. METHODS: Fifty-two obese children with Tanner stage 2 and stage 3 breast development accompanied by at least one pubertal clinical finding were included in the study. The staging of breast development was also performed according to the ultrasonographic morphostructural appearance. The subjects were then divided into subgroups according to their clinical and ultrasonographic breast stages. The stages given by both methods were compared for consistency with the hormonal values and other radiological (uterus long diameter, ovary sizes) findings. RESULTS: The correlation between the clinical and ultrasonographic staging of pubertal breast development was determined to be weak (r=0.19). Estradiol levels, uterus long diameter and ovary sizes were significantly increased when the ultrasonographic stage increased among the subjects with clinically similar breast development stage. However, no statistical difference was determined in these parameters among the subjects with ultrasonographically similar but clinically different breast development. CONCLUSIONS: It was shown that the ultrasonographic staging of breast development could provide more accurate and objective data due to the possible mistakes caused in the breast development staging of obese children by their adipose tissue.

Retinal Neural and Vascular Structure in Isolated Growth Hormone Deficiency Children and Evaluation of Growth Hormone Treatment Effect

OBJECTIVE: To evaluate neural and vascular retinal morphology of children with isolated growth hormone deficiency (GHD) and to determine any retinal changes due to GH treatment. METHODS: Twenty-eight children with isolated GHD and 53 age-, gender- and body mass index-matched healthy volunteers were enrolled in this prospective study. The retinal nerve fibre layer (RNFL) and macular thickness (MT) were measured, as well as intraocular pressure (IOP). The number of retinal vascular branching points were calculated. Effect of GH treatment on the retina and IOP was evaluated after one year of treatment. Measurements were also made in the control group at baseline and following the initial examination. Pre- and post-treatment changes were compared. The findings were also compared with those of the controls. The correlation between ocular dimensions and insulin-like growth factor-I (IGF-1) levels were also analysed. RESULTS: The number of branching points was significantly lower in GHD patients as compared with control subjects (15.11±2.67 and 19.70±3.37, respectively, p=0.05 for all comparisons). No statistically significant differences were found in mean RNFL, MT and IOP values between GHD patients and control subjects. GH treatment did not create any significant changes in the retinal vascularization or other retinal neural parameters and IOP either within the patient group or when compared with the control group. No correlations were observed between ocular dimensions and IGF-1 levels. CONCLUSION: Our findings suggest that isolated GHD may lead to decreased retinal vascularization. However, retinal neural growth and differentiation were not affected by GHD. These findings may be related to the fetal development process of pituitary somatotropic cells and the retina. Additionally, GH treatment did not cause any changes in retinal neural and vascular tissues.

Endoglin and obestatin levels, cardiometabolic risk factors and subclinical atherosclerosis in children aged 10-18 years.

BACKGROUND: The aim of this study was to investigate the early signs of atherosclerosis and to evaluate serum endoglin and obestatin levels as predictors of subclinical atherosclerosis in obese children. METHODS: A total of 95 children (60 obese and 35 controls) aged 10-18 years were included in the study. Their endoglin and obestatin levels and biochemical parameters were measured. The carotid intima media thickness (cIMT) and brachial artery flow-mediated dilatation (FMD) responses were evaluated. RESULTS: The cIMT values were higher (p < 0.001) and FMD responses were lower (p = 0.003) in the obese group than in the control group. A logistic regression multivariate analysis revealed that cIMT was independently associated with the body mass index (BMI) Z-score (ß = 0.323, p = 0.003) and low density lipoprotein (LDL) (ß = 0.29, p = 0.008), while FMD % was independently associated with waist circumference (ß = -0.36, p = 0.002). The obese and control groups were similar in endoglin (p = 0.67) and obestatin levels (p = 0.70). The endoglin level was inversely correlated with the cholesterol and LDL levels (r = -0.23, p = 0.032; rho = -0.25, p = 0.019). CONCLUSIONS: The cIMT and brachial artery FMD response in obese children are significantly different compared to healthy controls. Circulating endoglin and obestatin levels are not predictive markers for subclinical atherosclerosis in obese children aged 10-18 years old.

Soluble Endoglin Level Increase Occurs Prior to Development of Subclinical Structural Vascular Alterations in Diabetic Adolescents.

OBJECTIVE: Soluble endoglin (S-endoglin) has been implicated as a potential marker of endothelial dysfunction (ED) and was reported to be elevated in diabetic adults, correlating with the severity of diabetic vasculopathy. However, circulating S-endoglin and its association with other markers of ED have not been formerly analyzed in the first decade of diabetes onset in adolescents with type 1 diabetes mellitus (T1DM). METHODS: Fifty-eight adolescents with moderately/poorly controlled T1DM were included in this study and twenty-nine healthy adolescents served as controls. The diabetic group was divided into two groups based on the presence of microalbuminuria, as the microalbuminuria group (n=15) and the normoalbuminuria group (n=43). Functional vascular alterations were evaluated by measuring serum S-endoglin and plasma nitric oxide (NO) concentrations, the flow-mediated dilatation (FMD) of the brachial artery. Carotid intima media thickness (CIMT) was measured for evaluation of structural vascular alterations. RESULTS: The S-endoglin and NO levels of both microalbuminuria and normoalbuminuria groups were higher than those of the control group (for S-endoglin, p=0.047 and p<0.001; for NO, p=0.004 and p=0.006, respectively). The FMD percent was lower in the microalbuminuria group compared to the normoalbuminuria and control groups (p=0.036 and p=0.020, respectively). There were negative correlations between S-endoglin concentration and FMD percent (r=-0.213, p=0.051) and between serum S-endoglin concentration and albumin excretion rate (r=-0.361, p=0.005). No significant differences were found in CIMT among any of the groups (p=0.443). CONCLUSION: In adolescents with T1DM, S-endoglin concentrations might increase in parallel to the deterioration in endothelial function before subclinical structural vascular alterations become evident.

Abnormal circadian blood pressure regulation in children with nocturnal enuresis.

INTRODUCTION: To investigate autonomic nervous system function in enuretic children by performing ambulatory blood pressure monitor (ABPM) for 24 h. METHODS: Twenty-eight children ranging in age from 6 to 15 years with primary nocturnal enuresis and 27 age-matched healthy controls were enrolled and they get 24 h ABPM. Hypertension was defined as standard deviation score (SDS) > 1.64 (i.e., >95th percentile) adjusted for gender and height. Urinalysis, urine electrolyte levels, urinary culture, and urinary system ultrasound were carried out in all children. They have also requested to have a diary about daily fluid intake and urine volume. RESULTS: Although the mean 24-h and daytime diastolic blood pressure (BP) did not differ between the groups, systolic BP (SBP) was significantly higher in enuretic children (p < 0.05). The mean night-time SBP, DBP values, SDS and BP loads were found to be significantly higher than those in the controls (p < 0.01). A lack of nocturnal decrease was more prevalent in the enuretic children compared with the control subjects, the difference was statistically significant for DBP but not for SBP. Patients with elevated night-time BP load was found to have higher frequency of urinary incontinence per week as well as per night when compared with enuretic children with normal night-time BP load (r = 0.72, r = 0.69, p < 0.01, respectively). CONCLUSION: Subtle abnormalities of circadian BP regulation in enuretic children indicated by a selective elevation of nocturnal SBP, DBP, and MAP, and attenuated nocturnal dipping may reflect sympathetic hyper activation and its possible role in pathogenesis of enuresis.

Gonadoblastoma with Dysgerminoma in a Phenotypically Turner-Like Girl with 45,X/46,XY Karyotype.

Individuals with 45,X/46,XY karyotype are at increased risk for germ cell tumor development. We report a case with a diagnosis of 45,X/46,XY gonadal dysgenesis who presented with short stature, physical stigmata of Turner syndrome. Her pubertal development was at Tanner stage 3. At follow-up, bilateral prophylactic gonadectomy was performed when considering the risk factors. Pathological assessment was consistent with gonadoblastoma in the left gonad, and dysgerminoma and gonadoblastoma in neighboring areas in the right gonad. The karyotype analysis of the right and left gonadal tissues reveled 45,X[97,3]/46,XY[2,7] and 45,X[92,7]/46,XY[4,5]/47,XYY [2,8] mosaic, respectively. The clinical management of such patient should be individualized according to the present risk factors. Additionally, signs of estrogenization like advanced breast development always suggest the possible presence of germ cell tumor.

Extensive middle cranial fossa arachnoid cysts and different clinical presentation in two patients.

Arachnoid cysts (ACs), particularly suprasellar cysts, cause a wide spectrum of endocrine disorders. Herein, we report two patients diagnosed with an extensive AC in the middle cranial fossa while being investigated for etiologies of precocious puberty and short stature. One of them required surgery due to his pubertal disorders associated with compression effects of cyst. After surgery, his puberty progression was regressed within one year. On the other hand, surgery was not planned for the second patient considering of his cranial imaging findings and the extremely low incidence of growth hormone (GH) deficiency caused by middle fossa AC (MFAC). We started treatment with recombinant human GH and no complication was found during treatment follow-up. Endocrine disorders associated with MFACs are extremely rare. By presenting with these two cases, we aimed to remain our fellow physcians that ACs can be possibly cause of endocrine disorders. Clinicians should be careful evaluating endocrine disorders because real cause may not be cyst itself but masked by it.

Cardio-facio-cutaneous syndrome with precocious puberty, growth hormone deficiency and hyperprolactinemia.

Cardio-facio-cutaneous (CFC) syndrome is a rare disorder characterized by craniofacial dysmorphia, ectodermal abnormalities, cardiac malformations, as well as growth and developmental delay. Although some endocrine abnormalities have been reported in this syndrome, very little is known about CFC syndrome-related endocrine disorders. A 7.5-year-old boy was admitted to our endocrinology clinic with the complaint of short stature. He had a height of 103 cm [-4 standard deviation (SD)], a weight of 16 kg (<3(th) percentile, -1.7 SD), a facial appearance typical for the CFC syndrome, optic nerve hypoplasia and pulmonary stenosis. Genetic investigation revealed a heterozygous mutation in exon 3 of the MEK1 gene, c.389A>G (p. Y130C). During his long-term follow-up, the patient developed a variety of endocrine disorders including precocious puberty, growth hormone deficiency and hyperprolactinemia.

Preterm ovarian hyperstimulation syndrome presented with vaginal bleeding: a case report.

Preterm ovarian hyperstimulation syndrome (POHS) is an uncommon disorder characterized by prematurity, hypogastric and upper leg swelling of various intensities, high serum estradiol and gonadotropin levels, and ovarian follicular cyst/cysts. In this paper, we present the first case of POHS presenting with vaginal bleeding. A female infant was born via spontaneous vaginal delivery at 25 weeks of gestation with a birth weight of 610 g. At 36 weeks of post-conception age, she developed breast enlargement, swelling of the clitoral hood, labia major and minor, hypogastrium and upper legs. Several weeks later, vaginal bleeding started and lasted 3 days. The vaginal bleeding continued to occur at monthly intervals. The elevated levels of gonadotropins and estrogens, vulvar swelling and cysts in both ovaries confirmed the diagnosis of preterm ovarian hyperstimulation syndrome.

Octreotide-induced long QT syndrome in a child with congenital hyperinsulinemia and a novel missense mutation (p.Met115Val) in the ABCC8 gene.

BACKGROUND/AIMS: Congenital hyperinsulinism (CHI) denotes an inappropriate secretion of insulin from pancreatic ß-cells in the presence of a low blood glucose level due to various genetic causes. Diazoxide is the first-line medical treatment for CHI. In case of failure, a somatostatin analogue called octreotide is used. A prolonged QT interval is an unusual side effect of octreotide which can be lethal if unrecognized. CASE PRESENTATION: We report on a 35-day-old infant who was diagnosed with CHI on the 3rd day of his life and underwent pancreatectomy due to failure of medical treatment at 8 months. His genetic analysis revealed a compound heterozygosity for a novel missense mutation (p.Met115Val) and a nonsense mutation (p.Trp1339X) in the ABCC8 gene. Furthermore, at the 6th month of follow-up, a long QT (0.49 s) was determined by ECG examination, which was normalized following discontinuation of octreotide treatment after pancreatectomy. Thus, the long QT was considered to be secondary to octreotide medication. CONCLUSION: We recommend ECG monitoring before and during octreotide treatment in order to recognize a prolonged QT interval and to prevent related complications in cases with congenital hyperinsulinemia.