Adherence to Growth Hormone Treatment in Children During COVID-19 Pandemic

Objective: Treatment adherence is crucial for the success of growth hormone (GH) therapy. Reported nonadherence rates in GH treatment have varied widely. Several factors may have an impact on adherence. Apart from these factors, the global impact of the COVID-19 pandemic, including problems with hospital admission and routine follow-up of patients using GH treatment, may have additionally affected the adherence rate. The primary objective of this study was to investigate adherence to treatment in patients receiving GH. In addition, potential problems with GH treatment during the pandemic were investigated. Materials and Methods: This was a multicenter survey study that was sent to pediatric endocrinologists in pandemic period (June 2021-December 2021). Patient data, diagnosis, history of pituitary surgery, current GH doses, duration of GH therapy, the person administering therapy (either parent/patient), duration of missed doses, reasons for missed doses, as well as problems associated with GH therapy, and missed dose data and the causes in the recent year (after the onset of the pandemic) were queried. Treatment adherence was categorized based on missed dose rates over the past month (0 to 5%, full adherence; 5.1 to 10% moderate adherence; >10% nonadherence). Results: The study cohort consisted of 427 cases (56.2% male) from thirteen centers. Median age of diagnosis was 8.13 (0.13-16) years. Treatment indications were isolated GH deficiency (61.4%), multiple pituitary hormone deficiency (14%), Turner syndrome (7.5%), idiopathic GH deficiency (7.5%), small for gestational age (2.8%), and "others" (6.8%). GH therapy was administered by parents in 70% and by patients in 30%. Mean daily dose was 32.3 mcg/kg, the annual growth rate was 1.15 SDS (min -2.74, max 9.3). Overall GH adherence rate was good in 70.3%, moderate in 14.7%, and poor in 15% of the patients. The reasons for nonadherence were mainly due to forgetfulness, being tired, inability to access medication, and/or pen problems. It was noteworthy that there was a negative effect on adherence during the COVID-19 pandemic reported by 22% of patients and the main reasons given were problems obtaining an appointment, taking the medication, and anxiety about going to hospital. There was no difference between genders in the adherence rate. Nonadherence to GH treatment decreased significantly when the patient: administered the treatment; was older; had longer duration of treatment; and during the pandemic. There was a non-significant decrease in annual growth rate as nonadherence rate increased. Conclusion: During the COVID-19 pandemic, the poor adherence rate was 15%, and duration of GH therapy and older age were important factors. There was a negative effect on adherence during the pandemic period.

The Level of Inflammatory Markers and Their Relationship with Fat Tissue Distribution in Children with Obesity and Type 2 Diabetes Mellitus.

OBJECTIVE: This study aimed to determine the changes in proinflammatory and anti-inflam- matory markers in children aged 10-18, who were not diagnosed with type 2 diabetes mel- litus, were obese/overweight, and children with type 2 diabetes mellitus. In addition, we aimed to investigate whether these markers were associated with clinical and laboratory parame- ters, subcutaneous adipose tissue, preperitoneal adipose tissue, visceral adipose tissue, and hepatosteatosis. MATERIALS AND METHODS: Children between the ages of 10 and 18, obese/overweight, with type 2 diabetes mellitus, and with a normal body mass index were included. Fat tissue thick- ness was measured. Tumor necrosis factor-α, interleukin-1ß, interleukin-6, interleukin-18, and interferon-γ as proinflammatory markers and transforming growth factor-ß and interleukin-10 levels as anti-inflammatory markers were studied. RESULTS: Twenty-eight (31.8%) controls, 44 (50%) obese/overweight, and 16 (18.2%) patients with type 2 diabetes mellitus were included in our study. Age, sex, and puberty were similar between the groups. In the type 2 diabetes mellitus group, the subcutaneous fat tissue thick- ness was higher than that in the obese group, and the preperitoneal and visceral fat tissue thicknesses were similar to those in the obese group. Proinflammatory markers and interleu- kin-10 levels were similar in the obese/overweight, type 2 diabetes mellitus, and control groups. Transforming growth factor-ß levels were significantly lower in the type 2 diabetes mellitus group than in the control group (P = .039). Transforming growth factor-ß levels and other labo- ratory variables did not differ significantly in the type 2 diabetes mellitus group. CONCLUSION: While there was no change in all markers in the obese/overweight group com- pared with the control group, proinflammatory markers in the type 2 diabetes mellitus group were similar to those in the obese/overweight and control groups, and transforming growth factor-ß level, an anti-inflammatory marker, was lower in the type 2 diabetes mellitus group than in the control group.

Genotype of congenital adrenal hyperplasia patients with testicular adrenal rest tumor.

Testicular adrenal rest tumor (TART) is one of the important complications that can cause infertility in male patients with congenital adrenal hyperplasia (CAH) and should therefore be diagnosed and treated at an early age. The factors that result in TART in CAH have not been completely understood. The aim of this study is to evaluate the genotype-phenotype correlation in CAH patients with TART. METHOD: Among 230 malepatients with CAH who were followed upwith regular scrotal ultrasonography in 11 different centers in Turkey, 40 patients who developed TARTand whose CAH diagnosis was confirmed by genetic testing were included in this study. Different approaches and methods were used for genotype analysis in this multicenter study. A few centers first screened the patients for the ten most common mutations in CYP21A2 and performed Sanger sequencing for the remaining regions only if these prior results were inconclusive while the majority of the departments adopted Sanger sequencing for the whole coding regions and exon-intron boundaries as the primary molecular diagnostic approach for patients with either CYP21A2 orCYP11B1 deficiency. The age of CAH diagnosis and TART diagnosis, type of CAH, and identified mutations were recorded. RESULTS: TART was detected in 17.4% of the cohort [24 patients with salt-wasting (SW) type, four simple virilizing type, and one with nonclassical type with 21-hydroxylase (CYP21A2) deficiency and 11 patients with 11-beta hydroxylase (CYP11B1) deficiency]. The youngest patients with TART presenting with CYP11B1 and CYP21A2 deficiency were of 2 and 4 years, respectively. Eight different pathogenic variants in CYP21A2were identified. The most common genotypes were c.293-13C>G/c.293-13C>G (31%) followed by c.955C>T/c.955C>T(27.6%) and c.1069C>T/c.1069C>T (17.2%). Seven different pathogenic variants were identified in CYP11B1. The most common mutation in CYP11B1 in our study was c.896T>C (p.Leu299Pro). CONCLUSION: We found that 83% TART patients were affected with SW typeCYP21A2 deficiency,and the frequent mutations detected were c.955C>T (p.Gln319Ter), c.293-13C>G in CYP21A2 and c.896T>C (p.Leu299Pro) inCYP11B1. Patients with CYP11B1 deficiency may develop TART at an earlier age. This study that examined the genotype-phenotype correlation in TART may benefit further investigations in larger series.

A major health problem facing immigrant children: nutritional rickets.

OBJECTIVES: Nutritional rickets (NR) is still an important problem and one which increasing influxes of immigrants are further exacerbating. This study evaluated cases of mostly immigrant children followed up with diagnoses of NR in our pediatric endocrinology clinic. METHODS: Details of 20 cases diagnosed with NR between 2017 and 2020 were retrieved from file records. RESULTS: Twenty (11 male) cases were included in the study. Three (15%) were Turkish nationals and the others (85%) were immigrants. Hypocalcemia and hypophosphatemia were detected in 17 and 13, respectively. Alkaline phosphatase (ALP) values were normal in two cases, while ALP and parathyroid hormone (PTH) values were elevated in all other cases, and PTH levels were very high (473.64 ± 197.05 pg/mL). 25-hydroxyvitamin D levels were below 20 ng/mL in all cases. Patients with NR received high-dose long-term vitamin D or stoss therapy. Six patients failed to attend long-term follow-up, while PTH and ALP levels and clinical findings improved at long-term follow-up in the other 14 cases. CONCLUSIONS: The elevated PTH levels suggest only the most severe cases of NR presented to our clinic. Clinically evident NR is therefore only the tip of the iceberg, and the true burden of subclinical rickets and osteomalacia remains unidentified. Public health policies should therefore focus on universal vitamin D supplementation and adequate dietary calcium provision, their integration into child surveillance programs, adequate advice and support to ensure normal nutrition, exposure to sunlight, and informing families of the increased risk not only for resident populations but also for refugee and immigrant children.

Recommendations for Clinical Decision-making in Children with Type 1 Diabetes and Celiac Disease: Type 1 Diabetes and Celiac Disease Joint Working Group Report

It is well-known that in children with type 1 diabetes (T1D), the frequency of Celiac disease (CD) is increased due to mechanisms which are not fully elucidated but include autoimmune injury as well as shared genetic predisposition. Although histopathologic examination is the gold standard for diagnosis, avoiding unnecessary endoscopy is crucial. Therefore, for both clinicians and patients' families, the diagnosis of CD remains challenging. In light of this, a joint working group, the Type 1 Diabetes and Celiac Disease Joint Working Group, was convened, with the aim of reporting institutional data and reviewing current international guidelines, in order to provide a framework for clinicians. Several controversial issues were discussed: For CD screening in children with T1D, regardless of age, it is recommended to measure tissue transglutaminase-immunoglobulin A (tTG-IgA) and/or endomysial-IgA antibody due to their high sensitivity and specificity. However, the decision-making process based on tTG-IgA titer in children with T1D is still debated, since tTG-IgA titers may fluctuate in children with T1D. Moreover, seronegativity may occur spontaneously. The authors' own data showed that most of the cases who have biopsy-proven CD had tTG-IgA levels 7-10 times above the upper limit. The decision for endoscopy based solely on tTG-IgA levels should be avoided, except in cases where tTG-IgA levels are seven times and above the upper limit. A closer collaboration should be built between divisions of pediatric endocrinology and gastroenterology in terms of screening, diagnosis and follow-up of children with T1D and suspicious CD.

Evaluation of the pathophysiological role of Fetuin A levels in adolescents with polycystic ovary syndrome.

OBJECTIVES: Polycystic ovary syndrome (PCOS) is an endocrinopathy, in which hyperandrogenism and hyperinsulinism have both occurred. Fetuin-A, a natural inhibitor of tyrosine kinase, leads to insulin resistance. The aim was to evaluate the relationship between fetuin-A and hyperandrogenism and hyperinsulinism and the role of fetuin-A in the pathophysiology of PCOS. METHODS: Thirty-eight cases with PCOS and 40 healthy adolescents were included in the study. PCOS and controls were divided into obese/non-obese subgroups. LH, FSH, total and free testosterone (TT, FT), SHBG, androstenedione, DHEAS were measured in patients with PCOS. Fasting glucose, insulin, lipid profile, AST, ALT, HsCRP, and fetuin levels of PCOS patients and healthy controls were also measured. RESULTS: Fetuin-A levels were higher in PCOS patients than in controls. In the obese-PCOS group, when compared to non-obese PCOS patients; the levels of SHBG and HDL were low while cholesterol, LDL, triglyceride, HOMA-IR, FT, FAI, and HSCRP levels were high, but Fetuin-A levels were similar. In the obese-PCOS group, fetuin-A levels were higher than in obese-controls. HOMA-IR and fetuin-A levels were higher in non-obese PCOS patients than in non-obese controls. In the PCOS group, fetuin-A was positively correlated with TT, FT, FAI and androstenedione and negatively correlated with SHBG. Regression analysis demonstrated that FT, SHBG, and androstenedione significantly predicted fetuin-A levels (R2=54%). In non-obese PCOS patients and controls, fetuin-A was positively correlated with insulin and HOMA-IR. CONCLUSIONS: These results suggest a relationship between androgen levels and fetuin-A in PCOS cases, independent of insulin resistance, and may shed light on further studies.

Evaluation of Children and Adolescents with Thyroid Nodules: A Single Center Experience

Objective: We aimed to evaluate the clinical, radiological and pathological findings of children and adolescents with thyroid nodules. Methods: Data of 121 children and adolescent with thyroid nodules and had fine needle aspiration (FNA) were examined retrospectively. Concomitant thyroid disease, ultrasonography (US) features of the nodule, FNA and histopathological results were recorded. FNA results were assessed according to The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC). Results: Median (range) age of the cases was 14 (3-18) years and 81% were female. FNA results of patients were: insufficient in 1 (0.8%); benign in 68 (56.2%); indeterminate in 44 (36.4%); and malignant in 8 (6.6%) patients. Among 39 patients who underwent surgery, 10 (25.6%) had differentiated thyroid cancer (DTC) and the overall malignancy rate was 10.0% (10/100). Follow-up FNA results showed progress based on TBSRTC in 18.7% of benign results and 4/75 patients had DTC on surgical excision. Two of 22 patients with atypia of undetermined significance (AUS) who continued follow-up was diagnosed with DTC. Male gender, presence of Hashimoto thyroiditis and US findings of uninodularity, hypoechogenicity, increased blood flow, irregular margins, solid structure, microcalcification and presence of abnormal cervical lymph nodes were associated with malignancy. Conclusion: In this study 10% of thyroid nodules were malignant in children and adolescents. Patients with AUS have a 9% potential for malignancy. Patients with initially benign FNA result may have changes on repeat FNA when assessed with TBSTRC indicating a 5.3% false negative rate.

Clinical Characteristics of 46,XX Males with Congenital Adrenal Hyperplasia

Objective: To retrospectively evaluate the follow-up data in patients with 46,XX congenital adrenal hyperplasia (CAH) who were raised male. Methods: A national database was created. The data of patients were asked to be recorded in the data form. Results: The median (range) age of diagnosis was three (0.1-18.3) years in 44 patients. Twenty nine cases were diagnosed after the age of two years. Most (95.4%) cases were stage 4-5 virilized. Hysterectomy and bilateral salpingoopherectomy, at a median age of 7.25 (2.4-25.3) years, was performed in 35 cases. Testicular prostheses were placed in 11 (25%) cases at a median age of 11.2 (2.8-17) years. The median final height was 149.2 (132.8-172) cms in 38 patients, including simple virilizing (n=18), salt-wasting (n=6), and 11-beta hydroxylase (n=12). Of the 16 patients above the age of eighteen, university education was completed in 25%. Conclusion: It was seen that most (65.9%) of the 46,XX CAH cases raised male were diagnosed after two years of age. In these cases, hysterectomy and bilateral salpingoopherectomy, genital corrective surgeries and testicular prosthesis operations were performed in a very wide age rage.

The alteration of IGF-1 levels and relationship between IGF-1 levels and growth velocity during GnRH analogue therapy.

Background Some studies have examined the effect of gonadal suppression on insulin-like growth factor-1 (IGF-1) levels and the growth velocity (GV) with conflicting results. Methods Forty-four girls treated with gonadotropin-releasing hormone analogue (GnRHa) for central precocious puberty (CPP) were included in the study. IGF-1 levels were examined at the beginning and after 12 months of treatment. Results IGF-1 and IGF-1 standard deviation score (SDS) according to chronological age (CA-IGF-1 SDS) at diagnosis were positively correlated with chronological age (CA), anthropometric measurements, stage of puberty, bone age (BA), BA-CA, follicle-stimulating hormone (FSH), luteinising hormone (LH), oestradiol, uterus length, endometrium thickness and ovarian volume (OV) at diagnosis (p < 0.05). There was no significant difference in IGF-1 levels after treatment. However, there was a negative correlation between ΔIGF-1 SDS and IGF-1 level, CA-IGF-1 SDS and BA-IGF-1 SDS at diagnosis (p < 0.05). There was no correlation between GV and IGF-1, ΔIGF-1. GV was negatively correlated with basal LH level at diagnosis (p = 0.008, r = -0.397). Peak LH levels of the patients who had GV-SDS < 0 were more suppressive than those of the patients who had GV-SDS > 0 after 12 months of treatment. Conclusions It was determined that the IGF-1 level and CA-IGF-1 SDS at baseline were correlated with more advanced pubertal stage prior to treatment. Initiation of treatment with a relatively high level of IGF-1 increased the risk of a decrease in the IGF-1 level. Likewise, the initiation of treatment with a relatively high LH level may increase the risk of low GV, but low GV was not related to the IGF-1 level. Increased sex steroid suppression may increase the risk of low GV.

Contribution of functionally assessed GHRHR mutations to idiopathic isolated growth hormone deficiency in patients without GH1 mutations.

Isolated growth hormone deficiency (IGHD) is a rare condition mainly caused by mutations in GH1. The aim of this study was to assess the contribution of GHRHR mutations to IGHD in an unusually large group of patients. All GHRHR coding exons and flanking intronic regions were sequenced in 312 unrelated patients with nonsyndromic IGHD. Functional consequences of all newly identified missense variants were assessed in vitro (i.e., study of the expression of recombinant GHRHRs and their ability to activate the cyclic adenosine monophosphate (cAMP) signaling pathway). Genotype-phenotype correlation analyses were performed according to the nature of the identified mutation. We identified 20 different disease-causing GHRHR mutations (truncating and missense loss-of-function mutations), among which 15 are novel, in 24 unrelated patients. Of note, about half (13/24) of those patients represent sporadic cases. The clinical phenotype of patients with at least one missense GHRHR mutation was found to be indistinguishable from that of patients with bi-allelic truncating mutations. This study, which unveils disease-causing GHRHR mutations in 8% (24/312) of IGHD cases, identifies GHRHR as the second IGHD gene most frequently involved after GH1. The finding that 8% of IGHD cases without GH1 mutations are explained by GHRHR molecular defects (including missense mutations), together with the high proportion of sporadic cases among those patients, has important implications for genetic counseling.

Detection of the SRY gene in patients with Turner Syndrome.

BACKGROUND: If turner syndrome (TS) patients have a Y-containing cell line, they have an increased risk for gonadal tumors. TS patients are therefore screened for Y-chromosome and Y-specific sequences, such as SRY, DYZ1, DYZ3, DYS132, ZFY, TSPY, etc. In addition, since the dysgenetic gonad may include the stroma and granulosa/sertoli cells, which produce androgens, virilization can seen in girls with Y-chromosomal material. Prophylactic gonadectomy may therefore be required for optimal management in such patients. Our aim is to discuss our observations in the follow-up of TS patients. METHODS: SRY was investigated in 71 out of 85 TS cases (aged 3 months-27 years) between 2005 and 2017. Fluorescent in situ hybridization (FISH) was used until 2014, after which SRY analysis was performed using the polymerase chain reaction (PCR) method. SRY analysis was performed a second time using PCR in 25 cases previously investigated with FISH. RESULTS: We identified no positive cases. No pathological findings in terms of virilization, clitoromegaly, or posterior labial adhesions were also determined in our TS cases. Further studies were not required since no pathological findings also were detected at ultrasonography. CONCLUSION: If Y-chromosome material has not been detected by conventional cytogenetic methods in TS patients with masculine features, further techniques should be applied to prevent the risk of invasive tumors, such as multiple sequences beside the Y centromere. This approach will prevent overtreatment.

Cases Referred from the Turkish National Screening Program: Frequency of Congenital Hypothyroidism and Etiological Distribution

Objective: The aim of this study was to evaluate cases referred from the congenital hypothyroidism (CH) newborn screening program. Methods: Infants referred to Pediatric Endocrinology between 30.09.2015 - 01.04.2018 because of suspected CH identified by National Neonatal Screening Program were prospectively evaluated. Results: Of the 109 newborns referred to our clinic, 60 (55%) were diagnosed with elevated neonatal thyroid stimulating hormone (TSH). The diagnosis of elevated neonatal TSH was made in 52 (47.7%) and eight (7.3%) infants at initial evaluation and after follow up, respectively of all referrals with 86.7% (52/60) diagnosed at initial visit. The median first and second heel prick times were 1.8 (0-7) and 8.72 (4-30) days. The median age at starting treatment of the infants diagnosed as a result of initial evaluation was 22.13 (7-53) days. Clinical findings associated with CH were present in 19 (36%) of patients. Etiology in patients diagnosed with elevated neonatal TSH on admission was: agenesis in one (2.08%); ectopia in one (2.08%); hypoplasia in 14 (29.16%); normal gland in situ 16 (33.3%); and hyperplasia in 16 (33.3%). The median time to normalization of TSH and free thyroxine concentrations after treatment initiation was 11.02 (4-30) and 9.03 (3-30) days, respectively. Conclusion: The rate of diagnosis in the first month was found to be 87%. The etiological incidence of both dysgenesis and dyshormonogenesis was equal at 33.3%. The majority of cases with normal thyroid gland will be diagnosed with transient hypothyroidism but some of them may be diagnosed with thyroid dyshormonogenesis so the rate of dyshormonogenesis will increase later after final diagnosis.

SHOX gene deletion screening by FISH in children with short stature and Madelung deformity and their characteristics.

Background The short stature homeobox-containing (SHOX) gene strongly affects height. Therefore, a better understanding of SHOX haploinsufficiency could be advantageous to early diagnosis and treatment. We investigated the rate of SHOX haploinsufficiency in patients of short stature and documented their anthropometric measurements. Methods Between 2010 and 2017, we evaluated 86 patients (70 females, 16 males; age 4.3-18 years) with clinical diagnoses of short stature and Madelung deformity (MD). Clinical abnormalities are presented for patients with MD with and without SHOX haploinsufficiency as determined by fluorescence in situ hybridisation (FISH). Results According to our inclusion criteria, 78 of 86 patients (70 females, 16 males) had short stature (height <-2.5 standard deviation [SD]) and a family history suggestive of short stature. Eight patients had short stature, a family history suggestive of short stature and MD. MD was obvious in eight children in radiographic examinations. Although five of these had no deletion of SHOX, three had deletion of this gene. The deletion detection rate was 37.5% in the individuals with short stature and MD, i.e. Leri-Weill dyschondrosteosis syndrome (LWS), whilst no deletions were detected in the individuals with only short stature. One individual responded well to growth hormone (GH) treatment for the first 2 years but then developed an intolerance with persistently elevated insulin-like growth factor-1 (IGF-1) levels. Conclusions As we likely missed cases due to our methodology, the routine analysis for SHOX screening should be firstly multiplex ligation-dependent probe amplification (MLPA). The incidence of MD may have been higher in the cohort if X-rays were performed in all individuals. GH treatment was not well tolerated in one case due to persistently elevated IGF-1 levels, and long-term evaluations of patients with SHOX deficiency are required.

AMH levels in girls with various pubertal problems.

BACKGROUND: Anti-Müllerian hormone (AMH) is produced by granulosa cells surrounding follicles that have undergone recruitment from the primordial follicle pool but have not been selected for dominance (preantral and early antral follicles). In healthy girls, serum levels of AMH vary considerably between individuals. We aimed to evaluate the AMH level in girls with premature thelarche (PT) and central precocious puberty (CPP). METHODS: Girls with CPP (n=21), PT (n=24) and a control prepubertal group (n=22) were included in the study. RESULTS: AMH levels were significantly higher in the PT group than the prepubertal control group and similar to the CPP group. AMH levels in the CPP group were similar to the prepubertal control group. AMH levels showed a significant negative correlation with luteinizing hormone (LH), free testosterone and dehydroepiandrosterone sulphate (DHEAS) levels in the PT group. AMH levels were negatively correlated with height standard deviation score (HSDS), body mass index (BMI) SDS values and positively correlated with sex hormone binding globulin (SHBG) levels in the CPP group. These levels were positively correlated with SHBG levels in the control prepubertal group. CONCLUSIONS: Serum AMH levels in girls with PT was found to be higher than in prepubertal girls. AMH levels in the CPP group were not different compared with the PT and control groups.

Do the Anti-Müllerian Hormone Levels of Adolescents with Polycystic Ovary Syndrome, Those Who Are at Risk for Developing Polycystic Ovary Syndrome, and Those Who Exhibit Isolated Oligomenorrhea Differ from Those of Adolescents with Normal Menstrual Cycles?

BACKGROUND/AIMS: We aimed to investigate whether the anti-Müllerian hormone (AMH) levels in adolescents with polycystic ovary syndrome (PCOS), PCOS risk, and isolated oligomenorrhea (OM) were different than in adolescents with a normal/regular menstrual cycle (NMC). METHODS: The diagnosis of PCOS was based on the 2012 Amsterdam [European Society of Human Reproduction and Embryology/American Society for Reproductive Medicine (ESHRE/ASRM)] criteria. The PCOS group consisted of cases meeting 3 diagnostic criteria (n = 21), and the PCOS risk group was the 'at risk' group meeting 2 diagnostic criteria (n = 20). Cases with isolated OM that did not satisfy other PCOS diagnostic criteria made up the OM group (n = 21). Thirty adolescent girls with NMCs (21-45 days) were recruited in this study. RESULTS: The AMH levels in the PCOS group were similar to those in the PCOS risk group but significantly higher than those in the OM and NMC groups. The AMH levels in the PCOS risk group were similar to those in the OM group and significantly higher than those in the NMC group. They were also significantly higher in the OM group compared to the NMC group. The specificity for PCOS and PCOS risk with a cutoff value of 7.25 ng/ml for AMH was 72.5% and the sensitivity was 58%. CONCLUSION: An AMH cutoff value of 7.25 ng/ml can be used for the diagnosis of PCOS in the adolescent period.

Co-Existence of Thyroid Nodule and Thyroid Cancer in Children and Adolescents with Hashimoto Thyroiditis: A Single-Center Study.

BACKGROUND: Currently, there is an inadequate number of studies on nodule and malignancy development in children and adolescents with Hashimoto thyroiditis (HT). MATERIAL AND METHODS: Patients who were diagnosed with HT between 2004 and 2013 were included in the study. The HT diagnosis was made with a heterogeneous appearance on thyroid ultrasonography and the elevation of antithyroid peroxidase and/or anti-thyroglobulin antibodies. Fine-needle aspiration biopsy (FNAB) was performed in cases with a nodule size >1 cm or who had ultrasonography findings indicating malignancy. RESULTS: A total of 39 (13%) thyroid nodules were detected in 300 patients with a diagnosis of HT. Papillary thyroid carcinoma (PTC) was diagnosed in 2 of the 12 cases in whom FNAB was performed. The thyroid nodule was detected at the same time as HT in the 2 cases with malignancy. The PTC diagnosis was made 2 years after the HT diagnosis in the first case and 3 years later in the second case. The largest diameter of the thyroid nodule was 5 mm in both cases. CONCLUSION: The thyroid nodule rate on an HT background was found to be 13%, and the thyroid malignancy rate was 0.67% in our study.

Gonadotropin-Releasing Hormone Analogue Treatment in Females with Moderately Early Puberty: No Effect on Final Height.

OBJECTIVE: To investigate the effects of treatment with gonadotropin-releasing hormone analog (GnRHa) on final height in girls who experienced moderately early puberty with symptoms beginning at 7-8.5 years of age. METHODS: Female cases diagnosed with moderately early puberty which had started between ages 7 to 8.5 years were included in the study. In the treatment groups, all cases with a bone age ≤10.5 years constituted group 1 (n=18) and those with a bone age >10.5 years constituted group 2 (n=23). The 8 patients for which treatment approval could not be obtained constituted group 3. The 49 cases in all three groups were observed until they reached their final height. RESULTS: Target height, target height standard deviation score (SDS), final height, and final height SDS values were similar in all 3 groups. Final height showed a significant positive correlation with target height (p=0.000, r=0.54) and height at diagnosis (p=0.003, r=0.467) in all groups. Linear regression analysis revealed that a 1 cm longer height at diagnosis increased the final height 0.213 fold, and a 1 cm longer target height at diagnosis increased the final height 0.459 fold. CONCLUSION: We found that GnRHa did not make a positive contribution to final height in cases of moderately early puberty.

Gonadoblastoma in a patient with 46, XY complete gonadal dysgenesis.

46, XY complete gonadal dysgenesis (Swyer syndrome) is a rare cause of 46, XY sexual development disorder. The patient presented to our clinic with absence of breast development and lack of periods at the age of 17 years. Her history and familial history involved no relevant conditions. She had Tanner stage 1 thelarche, and Tanner stage 2 pubic hair development with no axillary hair development. External genital structure appearance was consistent with female phenotype and the patient had no palpable gonad. The patient diagnosed as 46, XY complete gonadal dysgenesis after evaluation of laboratory analyses, radiological methods and karyotype. The Sexual Orientation and Gender Identity Committee concluded that gonadectomy should be performed. Histopathologic analysis demonstrated gonadoblastoma. Gonad structures should be sought laparoscopically and once diagnosed, streak gonads should be removed prophylactically in patients with 46, XY complete gonadal dysgenesis.

Complete androgen insensitivity syndrome associated with bilateral sertoli cell adenomas and unilateral paratesticular leiomyoma: A case report.

Complete androgen insensitivity syndrome (CAIS) disorder of sex development due to mutations that cause function loss in androgen receptors in 46, XY individuals. The risk of malignancy in CAIS is 5-10% until the age of 25 years. A 17-year-old patient raised as a female presented to our clinic complaining of amenorrhea. She had a history of surgery for inguinal hernia at the age of 2 years. The patient's niece of the same age had been diagnosed with CAIS at our department and gonadectomy had been performed six months ago. She had four other nieces with the same diagnosis. Her external genital appeared phenotypically female. On physical examination, breast development was Tanner stage 5 and pubic hair Tanner stage 2 with scarce axillary hair. The gonad was palpated in the left inguinal region. Chromosome analysis revealed 46, XY and sex determining region Y (SRY) was positive. The patient was diagnosed as CAIS with laboratory and radiology results. The Sexual Orientation and Gender Identity Committee decided on gonadectomy. Histopathological evaluation of the gonad revealed bilateral Sertoli cell tumor and right paratesticular leiomyoma.

A case with atrophic autoimmune thyroiditis-related hypothyroidism causing multisystem involvement in early childhood.

The most common reason of acquired hypothyroidism is autoimmune (Hashimoto) thyroiditis. Autoimmune thyroiditis can be atrophic or goitrogenic. Atrophic autoimmune thyroiditis (ATT) related acquired hypothyroidism causes interruption of growth, obesity, and bone age retardation in early ages while goitrogenic thyroiditis has a higher incidence rate and mostly presents with diffuse goiter. We discuss the effects of hypothyroidism on various systems through a case found to have pericardial effusion during the echocardiography performed after cardiac murmur was detected and later diagnosed with ATT related hypothyroidism.