搜索结果：Journal of pediatric endocrinology & metabolism : JPEM

No AccessJournal of Urology1 Oct 1963Familial Female Pseudohermaphroditism with Hypertension and Penile Urethra Paul O. Madsen Paul O. MadsenPaul O. Madsen Present address: Department of Urology, Veterans Administration Hospital, Madison, Wisc. More articles by this author View All Author Informationhttps://doi.org/10.1016/S0022-5347(17)64439-2AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail © 1963 by The American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetailsCited by Bangalore Krishna K, Houk C, Mohsin F and Lee P (2020) Congenital adrenal hyperplasia as a model to explore gender fluidity in early life; particularly 46,XX patients with male external genitalia The Plasticity of Sex, 10.1016/B978-0-12-815968-2.00013-X, (109-135), . Isaacson D, Shen J, Cao M, Sinclair A, Yue X, Cunha G and Baskin L (2017) Renal Subcapsular xenografing of human fetal external genital tissue – A new model for investigating urethral developmentDifferentiation, 10.1016/j.diff.2017.09.002, VOL. 98, (1-13), Online publication date: 1-Nov-2017. Dessens A, Slijper F and Drop S (2005) Gender Dysphoria and Gender Change in Chromosomal Females with Congenital Adrenal HyperplasiaArchives of Sexual Behavior, 10.1007/s10508-005-4338-5, VOL. 34, NO. 4, (389-397), Online publication date: 1-Aug-2005. Woelfle J, Hoepffner W, Sippell W, Brämswig J, Heidemann P, Deiß D, Bökenkamp A, Roth C, Irle U, Wollmann H, Zachmann M, Kubini K and Albers N (2002) Complete virilization in congenital adrenal hyperplasia: clinical course, medical management and disease-related complicationsClinical Endocrinology, 10.1046/j.0300-0664.2001.01463.x, VOL. 56, NO. 2, (231-238), Online publication date: 1-Feb-2002. Castro-Magana M, Angulo M, Canas J, Mazur B, Sarrantonio M, Vitollo P, Palekar A, Fuentes B and Lee A Characterization of Zona Glomerulosa Function in Patients with Classic and Non-classic Forms of Congenital Adrenal Hyperplasia due to 11ß-Hydroxylase DeficiencyJournal of Pediatric Endocrinology and Metabolism, 10.1515/JPEM.1995.8.1.19, VOL. 8, NO. 1 Chan-Cua S, Freidenberg G and Jones K (1989) Occurrence of male phenotype in genotypic females with congenital virilizing adrenal hyperplasiaAmerican Journal of Medical Genetics, 10.1002/ajmg.1320340317, VOL. 34, NO. 3, (406-412), Online publication date: 1-Nov-1989. NEW M, DUPONT B, PANG S, POLLACK M and LEVINE L (1981) An Update of Congenital Adrenal Hyperplasia Proceedings of the 1980 Laurentian Hormone Conference, 10.1016/B978-0-12-571137-1.50008-6, (105-181), . Kiviat M and Leonard J (1978) True prostatic tissue in 46,xx female with adrenogenital syndromeUrology, 10.1016/0090-4295(78)90375-8, VOL. 12, NO. 1, (75-78), Online publication date: 1-Jul-1978. Gillenwater J, Wyker A, Birdsong M and Thornton W (2018) Adrenogenital Syndrome Producing Female Pseudohermaphroditism with a Phallic UrethraJournal of Urology, VOL. 103, NO. 4, (500-504), Online publication date: 1-Apr-1970. Hardy Hendren W and Crawford J (1969) Adrenogenital syndrome: The anatomy of the anomaly and its repair. Some new conceptsJournal of Pediatric Surgery, 10.1016/0022-3468(69)90183-3, VOL. 4, NO. 1, (49-58), Online publication date: 1-Feb-1969. Rosenberg B, Hendren W and Crawford J (1969) Posterior Urethrovaginal Communication in Apparent Males with Congenital Adrenocortical HyperplasiaNew England Journal of Medicine, 10.1056/NEJM196901162800303, VOL. 280, NO. 3, (131-134), Online publication date: 16-Jan-1969. Maxted W, Baker R, McCrystal H and Fitzgerald E (2018) Complete Masculinization of the External Genitalia in Congenital Adrenocortical Hyperplasia. Presentation of Two CasesJournal of Urology, VOL. 94, NO. 3, (266-270), Online publication date: 1-Sep-1965. Gabrilove J, Sharma D and Dorfman R (1965) Adrenocortical 11β-Hydroxylase Deficiency and Virilism First Manifest in the Adult WomanNew England Journal of Medicine, 10.1056/NEJM196506102722301, VOL. 272, NO. 23, (1189-1194), Online publication date: 10-Jun-1965. Volume 90Issue 4October 1963Page: 466-469 Advertisement Copyright & Permissions© 1963 by The American Urological Association Education and Research, Inc.MetricsAuthor Information Paul O. Madsen Present address: Department of Urology, Veterans Administration Hospital, Madison, Wisc. More articles by this author Expand All Advertisement PDF downloadLoading ...

The hypothalamic control of prolactin secretion is different from other anterior pituitary hormones, in that it is predominantly inhibitory, by means of dopamine from the tuberoinfundibular dopamine neurons. In addition, prolactin does not have an endocrine target tissue, and therefore lacks the classical feedback pathway to regulate its secretion. Instead, it is regulated by short loop feedback, whereby prolactin itself acts in the brain to stimulate production of dopamine and thereby inhibit its own secretion. Finally, despite its relatively simple name, prolactin has a broad range of functions in the body, in addition to its defining role in promoting lactation. As such, the hypothalamo-prolactin axis has many characteristics that are quite distinct from other hypothalamo-pituitary systems. This review will provide a brief overview of our current understanding of the neuroendocrine control of prolactin secretion, in particular focusing on the plasticity evident in this system, which keeps prolactin secretion at low levels most of the time, but enables extended periods of hyperprolactinemia when necessary for lactation. Key prolactin functions beyond milk production will be discussed, particularly focusing on the role of prolactin in inducing adaptive responses in multiple different systems to facilitate lactation, and the consequences if prolactin action is impaired. A feature of this pleiotropic activity is that functions that may be adaptive in the lactating state might be maladaptive if prolactin levels are elevated inappropriately. Overall, my goal is to give a flavour of both the history and current state of the field of prolactin neuroendocrinology, and identify some exciting new areas of research development.

At present, no European recommendations for the management of pediatric thyroid nodules and differentiated thyroid carcinoma (DTC) exist. Differences in clinical, molecular, and pathological characteristics between pediatric and adult DTC emphasize the need for specific recommendations for the pediatric population. An expert panel was instituted by the executive committee of the European Thyroid Association including an international community of experts from a variety of disciplines including pediatric and adult endocrinology, pathology, endocrine surgery, nuclear medicine, clinical genetics, and oncology. The 2015 American Thyroid Association Pediatric Guideline was used as framework for the present guideline. Areas of discordance were identified, and clinical questions were formulated. The expert panel members discussed the evidence and formulated recommendations based on the latest evidence and expert opinion. Children with a thyroid nodule or DTC require expert care in an experienced center. The present guideline provides guidance for healthcare professionals to make well-considered decisions together with patients and parents regarding diagnosis, treatment, and follow-up of pediatric thyroid nodules and DTC.

GnRH analogues (GnRHa) are the treatment of choice for central precocious puberty (CPP), with the main objective to recover the height potential compromised by the premature fusion of growth cartilages. The aim of this review was to analyze long-term effects of GnRHa on height, body weight, reproductive function, and bone mineral density (BMD) in patients with CPP, as well as the potential predictors of outcome. Because randomized controlled trials on the effectiveness and long-term outcomes of treatment are not available, only qualified conclusions about the efficacy of interventions can be drawn. GnRHa treatment appears to improve adult height in girls with CPP, especially if diagnosed before the age of 6, whereas a real benefit in terms of adult height is still controversial in patients with the onset of puberty between 6 and 8 years of age. No height benefit was shown in patients treated after 8 years. Gonadal function is promptly restored in girls after cessation of treatment, and reproductive potential appears normal in young adulthood. Data are conflicting on the long-term risk of polycystic ovarian syndrome in both treated and untreated women. Fat mass is increased at the start of treatment but normalizes thereafter, and GnRHa itself does not seem to have any long-term effect on BMI. Similarly, analogue treatment does not appear to have a negative impact on BMD. Owing to the paucity of data available, no conclusions can be drawn on the repercussions of CPP and/or its treatment on the timing of menopause and on the health of the offspring.

OBJECTIVE: Laron syndrome (LS) is a rare, autosomal recessive disorder in humans caused by loss-of-function mutations of the growth hormone receptor (GHR) gene. To establish a large animal model for LS, pigs with GHR knockout (KO) mutations were generated and characterized. METHODS: CRISPR/Cas9 technology was applied to mutate exon 3 of the GHR gene in porcine zygotes. Two heterozygous founder sows with a 1-bp or 7-bp insertion in GHR exon 3 were obtained, and their heterozygous F1 offspring were intercrossed to produce GHR-KO, heterozygous GHR mutant, and wild-type pigs. Since the latter two groups were not significantly different in any parameter investigated, they were pooled as the GHR expressing control group. The characterization program included body and organ growth, body composition, endocrine and clinical-chemical parameters, as well as signaling studies in liver tissue. RESULTS: GHR-KO pigs lacked GHR and had markedly reduced serum insulin-like growth factor 1 (IGF1) levels and reduced IGF-binding protein 3 (IGFBP3) activity but increased IGFBP2 levels. Serum GH concentrations were significantly elevated compared with control pigs. GHR-KO pigs had a normal birth weight. Growth retardation became significant at the age of five weeks. At the age of six months, the body weight of GHR-KO pigs was reduced by 60% compared with controls. Most organ weights of GHR-KO pigs were reduced proportionally to body weight. However, the weights of liver, kidneys, and heart were disproportionately reduced, while the relative brain weight was almost doubled. GHR-KO pigs had a markedly increased percentage of total body fat relative to body weight and displayed transient juvenile hypoglycemia along with decreased serum triglyceride and cholesterol levels. Analysis of insulin receptor related signaling in the liver of adult fasted pigs revealed increased phosphorylation of IRS1 and PI3K. In agreement with the loss of GHR, phosphorylation of STAT5 was significantly reduced. In contrast, phosphorylation of JAK2 was significantly increased, possibly due to the increased serum leptin levels and increased hepatic leptin receptor expression and activation in GHR-KO pigs. In addition, increased mTOR phosphorylation was observed in GHR-KO liver samples, and phosphorylation studies of downstream substrates suggested the activation of mainly mTOR complex 2. CONCLUSION: GHR-KO pigs resemble the pathophysiology of LS and are an interesting model for mechanistic studies and treatment trials.

In children, hypophosphatemic rickets (HR) is revealed by delayed walking, waddling gait, leg bowing, enlarged cartilages, bone pain, craniostenosis, spontaneous dental abscesses, and growth failure. If undiagnosed during childhood, patients with hypophosphatemia present with bone and/or joint pain, fractures, mineralization defects such as osteomalacia, entesopathy, severe dental anomalies, hearing loss, and fatigue. Healing rickets is the initial endpoint of treatment in children. Therapy aims at counteracting consequences of FGF23 excess, i.e. oral phosphorus supplementation with multiple daily intakes to compensate for renal phosphate wasting and active vitamin D analogs (alfacalcidol or calcitriol) to counter the 1,25-diOH-vitamin D deficiency. Corrective surgeries for residual leg bowing at the end of growth are occasionally performed. In absence of consensus regarding indications of the treatment in adults, it is generally accepted that medical treatment should be reinitiated (or maintained) in symptomatic patients to reduce pain, which may be due to bone microfractures and/or osteomalacia. In addition to the conventional treatment, optimal care of symptomatic patients requires pharmacological and non-pharmacological management of pain and joint stiffness, through appropriated rehabilitation. Much attention should be given to the dental and periodontal manifestations of HR. Besides vitamin D analogs and phosphate supplements that improve tooth mineralization, rigorous oral hygiene, active endodontic treatment of root abscesses and preventive protection of teeth surfaces are recommended. Current outcomes of this therapy are still not optimal, and therapies targeting the pathophysiology of the disease, i.e. FGF23 excess, are desirable. In this review, medical, dental, surgical, and contributions of various expertises to the treatment of HR are described, with an effort to highlight the importance of coordinated care.

OBJECTIVE: Recombinant human growth hormone (rhGH) replacement therapy in children generally requires daily subcutaneous (sc) injections, which may be inconvenient for patients. Jintrolong® is a PEGylated rhGH with the purpose of weekly sc injections. The aim of the current study was to examine the pharmacokinetics, pharmacodynamics, safety, and tolerability of multiple sc doses of Jintrolong® vs daily doses of rhGH. DESIGN AND METHODS: Twelve children with growth hormone deficiency participated in this single-center, open-label, crossover Phase I trial. All subjects received daily sc injections of rhGH at 0.0286 mg/kg/d for 7 days, followed by a 4-week washout period and six weekly doses of Jintrolong® at 0.2 mg/kg/w. RESULTS: In comparison with rhGH, sc injection of Jintrolong® produced a noticeably higher C max, significantly longer half-life (t 1/2), and slower plasma clearance, signifying a profile suitable for long-term treatment. The ratio of the area under the concentration vs time curve (AUC) after the seventh and first injections (AUC(0-∞)7th/AUC(0-∞)1st) of rhGH was 1.02, while the AUC(0-∞)6th/AUC(0-∞)1st of Jintrolong ® was 1.03, indicating no accumulation of circulating growth hormone. There was no significant difference in the change in insulin-like growth factor-1 expression produced by 7 days of sc rhGH and weekly Jintrolong® injections. There were no severe adverse events during the trial. CONCLUSION: The elimination rate of Jintrolong® was slower than that of sc rhGH. No progressive serum accumulation of Jintrolong® was found. The changes in insulin-like growth factor-1 expression produced by rhGH and Jintrolong® were comparable, indicating similar pharmacodynamics. Our results demonstrate that Jintrolong® is suitable for long-term growth hormone treatment in children with growth hormone deficiency.

BACKGROUND: Brain development in fetal life and early infancy is critical to determine lifelong performance in various neuropsychological domains. Metabolic pathologies such as overweight, obesity, and gestational diabetes in pregnant women are prevalent and increasing risk factors that may adversely affect long-term brain development in their offspring. OBJECTIVE: The objective of this research was to investigate the influence of maternal metabolic pathologies on the neurodevelopment of the offspring at 6 and 18 months of life. DESIGN: This was a prospective case-control study of 331 mother- and child pairs from Granada, Spain. The mothers were included during pregnancy into four groups according to their pre-gestational body mass index and their gestational diabetes status; overweight (n:56), obese (n:64), gestational diabetic (n:79), and healthy normal weight controls (n:132). At 6 months and 18 months we assessed the children with the Bayley III scales of neurodevelopment. RESULTS: At 6 months (n=215), we found significant group differences in cognition composite language, and expressive language. Post hoc test revealed unexpectedly higher scores in the obese group compared to the normal weight group and a similar trend in overweight and diabetic group. The effects on language remained significant after adjusting for confounders with an adjusted odds ratio for a value above median in composite language score of 3.3 (95% CI: 1.1, 10.0; p=0.035) for children of obese mothers. At 18 month (n=197), the offspring born to obese mothers had lost five points in language composite scores and the previous differences in language and cognition was replaced by a suggestive trend of lower gross motor scores in the overweight, obese, and diabetic groups. CONCLUSIONS: Infants of obese mothers had a temporary accelerated development of cognition and language, followed by a rapid deceleration until 18 months of age, particularly of language scores. This novel observation prompts further confirmative studies to explore possible placental and neurodevelopmental mechanisms involved.

It is paramount that any child or adolescent with a suspected disorder of sex development (DSD) is assessed by an experienced clinician with adequate knowledge about the range of conditions associated with DSD. If there is any doubt, the case should be discussed with the regional DSD team. In most cases, particularly in the case of the newborn, the paediatric endocrinologist within the regional team acts commonly as the first point of contact. This clinician should be part of a multidisciplinary team experienced in management of DSD and should ensure that the affected person and parents have access to specialist psychological support and that their information needs are comprehensively addressed. The underlying pathophysiology of DSD and the strengths and weaknesses of the tests that can be performed should be discussed with the parents and affected young person and tests undertaken in a timely fashion. Finally, in the field of rare conditions, it is imperative that the clinician shares the experience with others through national and international clinical and research collaboration.

BACKGROUNDS: During the Coronavirus-19 disease (Covid-19) pandemic it was observed that the number of girls presenting with early puberty had increased. The aim of this study was to carry out a retrospective evaluation of the characteristics of girls who had been referred for evaluation of precocious puberty in five different pediatric endocrinology units, before and during the pandemic. METHODS: The study participants comprised 359 girls who were assigned into 2 groups a pre-pandemic group (n:214) and a pandemic group (n:145). Those participants (n:99) who had medical records in the follow-up period were classified into 3 subgroups according to the time of presentation and follow-up visits (group-1: first admission and follow-up visit before the pandemic, group-2: first admission before the pandemic, the follow-up visit during the pandemic, group-3: first admission and follow-up visit during the pandemic). RESULTS: The age at presentation and age at pubertal onset were both significantly lower in the pandemic group than those in the pre-pandemic group(8.1 vs 8.6, p: < 0.001,7.7 vs 7.9,p:0.013, respectively). There was no significant difference between the body mass index standard deviation scores (BMI-SDS) values of the groups (0.57 vs 0.51, p:0.430). The initiation rate of pubertal suppression therapy at the time of presentation was significantly higher in the pandemic group compared to that of the pre-pandemic group (7.7%vs 27.5%), and in groups-2 & 3 compared to group-1, during follow-up (20%&44%vs 8%). CONCLUSION: Our research showed that the onset of puberty occurred earlier in the pandemic period compared to the previous year, and the need for pubertal suppression therapy increased during the pandemic.

INTRODUCTION: Insulin analog glargine (GLA) has been available as one of the therapeutic options for patients with type 1 diabetes mellitus to enhance glycemic control. Studies have shown that a decrease in the frequency of hypoglycemic episodes improves the quality of life (QoL) of diabetic patients. However, there are appreciable acquisition cost differences between different insulins. Consequently, there is a need to assess their impact on QoL to provide future guidance to health authorities. METHOD: A systematic review of multiple databases including Medline, LILACS, Cochrane, and EMBASE databases with several combinations of agreed terms involving randomized controlled trials and cohorts, as well as manual searches and gray literature, was undertaken. The primary outcome measure was a change in QoL. The quality of the studies and the risk of bias was also assessed. RESULTS: Eight studies were eventually included in the systematic review out of 634 publications. Eight different QoL instruments were used (two generic, two mixed, and four specific), in which the Diabetes Treatment Satisfaction Questionnaire (DTSQ) was the most used. The systematic review did not consistently show any significant difference overall in QoL scores, whether as part of subsets or combined into a single score, with the use of GLA versus neutral protamine Hagedorn (NPH) insulin. Only in patient satisfaction measured by DTSQ was a better result consistently seen with GLA versus NPH insulin, but not using the Well-being Inquiry for Diabetics (WED) scale. However, none of the cohort studies scored a maximum on the Newcastle-Ottawa scale for quality, and they generally were of moderate quality with bias in the studies. CONCLUSION: There was no consistent difference in QoL or patient-reported outcomes when the findings from the eight studies were collated. In view of this, we believe the current price differential between GLA and NPH insulin in Brazil cannot be justified by these findings.

Ultrasonography is the best available tool for the initial work-up of thyroid nodules. Substantial interobserver variability has been documented in the recognition and reporting of some of the lesion characteristics. A number of classification systems have been developed to estimate the likelihood of malignancy: several of them have been endorsed by scientific societies, but their reproducibility is yet to be assessed. We evaluated the interobserver variability of the AACE/ACE/AME, ACR, ATA, EU-TIRADS and K-TIRADS classification systems and the interobserver concordance in the indication to FNA biopsy. Two raters independently evaluated 1055 ultrasound images of thyroid nodules identified in 265 patients at multiple time points, in two separate sets (501 and 554 images). After the first set of nodules, a joint reading was performed to reach a consensus in the feature definitions. The interobserver agreement (Krippendorff alpha) in the first set of nodules was 0.47, 0.49, 0.49, 0.61 and 0.53, for AACE/ACE/AME, ACR, ATA, EU-TIRADS and K-TIRADS systems, respectively. The agreement for the indication to biopsy was substantial to near-perfect, being 0.73, 0.61, 0.75, 0.68 and 0.82, respectively (Cohen's kappa). For all systems, agreement on the nodules of the second set increased. Despite the wide variability in the description of single ultrasonographic features, the classification systems may improve the interobserver agreement that further ameliorates after a specific training. When selecting nodules to be submitted to FNA biopsy, that is main purpose of these classifications, the interobserver agreement is substantial to almost perfect.

BACKGROUND: Overweight and obesity can be defined as excessive and abnormal fat depositions in our body. They have become one of the emerging and serious public health concerns of the twenty-first century in low income countries like Ethiopia. Hence, the aim of this study was to determine the pooled prevalence and review associated risk factors of overweight/obesity among children and adolescents in Ethiopia. METHOD: tests were used. Since the included studies exhibited considerable heterogeneity, a random effect model was used to estimate the pooled prevalence of overweight/obesity. Moreover, the risk factors of overweight/obesity were reviewed. RESULTS: The combined pooled prevalence of overweight and obesity among children and adolescents in Ethiopia was 11.30% (95% CI: 8.71, 13.88%). Also, the separate pooled prevalence of overweight and obesity were 8.92 and 2.39%, respectively. Subgroup analysis revealed that the highest overweight/obesity prevalence among children and adolescents was observed in Addis Ababa, 11.94 (95% CI: 9.39, 14.50). Female gender of the children: 3.23 (95% CI 2.03,5.13), high family socioeconomic status: 3.16 (95% CI 1.87,5.34), learning in private school: 3.22 (95% CI 2.36,4.40), physical inactivity: 3.36 (95% CI 1.68,6.72), sweet nutriments preference: 2.78 (95% CI 1.97,3.93) and less use of fruits/vegetables: 1.39 (95% CI 1.10,1.75) have shown a positive association with the development of overweight/obesity among children and adolescents. CONCLUSION: The pooled prevalence of overweight/obesity among children and adolescents in Ethiopia is substantially high, and has become an emerging nutrition linked problem. Female gender, high family socioeconomic status, learning in private school, physical inactivity, sweet nutriments preference and less use of fruits/vegetables were found to be significantly associated with overweight/obesity.

An increasing number of food-based recommendations promote a plant-based diet to address health concerns and environmental sustainability in global food systems. As the main sources of iodine in many countries are fish, eggs and dairy products, it is unclear whether plant-based diets, such as the EAT-Lancet reference diet, would provide sufficient iodine. This is important as iodine, through the thyroid hormones, is required for growth and brain development; adequate iodine intake is especially important before, and during, pregnancy. In this narrative review, we evaluated the current literature and estimated iodine provision from the EAT-Lancet reference diet. There is evidence that those following a strict plant-based diet, such as vegans, cannot reach the recommended iodine intake from food alone and are reliant on iodine supplements. Using the EAT-Lancet reference diet intake recommendations in combination with iodine values from UK food tables, we calculated that the diet would provide 128 μg/d (85 % of the adult recommendation of 150 μg/d and 51–64 % of the pregnancy recommendation of 200–250 μg/d). However, if milk is replaced with unfortified plant-based alternatives, total iodine provision would be just 54 μg/d (34 % and 22–27 % of the recommendations for adults and pregnancy, respectively). Plant-based dietary recommendations might place consumers at risk of iodine deficiency in countries without a fortification programme and where animal products provide the majority of iodine intake, such as the UK and Norway. It is essential that those following a predominantly plant-based diet are given appropriate dietary advice to ensure adequate iodine intake.

Gonadal dysgenesis, a condition in which gonadal development is interrupted leading to gonadal dysfunction, is a unique subset of disorders of sexual development (DSD) that encompasses a wide spectrum of phenotypes ranging from normally virilized males to slightly undervirilized males, ambiguous phenotype, and normal phenotypic females. It presents specific challenges in diagnostic work-up and management. In XY gonadal dysgenesis, the presence of a Y chromosome or Y-chromosome material renders the patient at increased risk for developing gonadal malignancy. No universally accepted guidelines exist for identifying the risk of developing a malignancy or for determining either the timing or necessity of performing a gonadectomy in patients with XY gonadal dysgenesis. Our goal was to evaluate the literature and develop evidence-based medicine guidelines with respect to the diagnostic work-up and management of patients with XY gonadal dysgenesis. We reviewed the published literature and used the Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) system when appropriate to grade the evidence and to provide recommendations for the diagnostic work-up, malignancy risk stratification, timing or necessity of gonadectomy, role of gonadal biopsy, and ethical considerations for performing a gonadectomy. Individualized health care is needed for patients with XY gonadal dysgenesis, and the decisions regarding gonadectomy should be tailored to each patient based on the underlying diagnosis and risk of malignancy. Our recommendations, based on the evidence available, add an important component to the diagnostic and management armament of physicians who treat patients with these conditions.

Article Reply: Evaluation of hypothalamic-pituitary-adrenal axis (ΗΡΑ) suppression by low-dose (0.5 μg) and standard-dose (250 μg) adrenocorticotropic hormone (ACTH) tests in asthmatic children treated with inhaled corticosteroid (JPEM 2006; 19: 1015-1023) was published on February 1, 2007 in the journal Journal of Pediatric Endocrinology and Metabolism (volume 20, issue 2).

BACKGROUND: Up to now, only limited data on long-term medical treatment in congenital hyperinsulinism (CHI) is available. Moreover, most of the drugs used in CHI are therefore not approved. We aimed to assemble more objective information on medical treatment in CHI with regard to type and duration, dosage as well as side effects. METHODS: We searched MEDLINE (from 1947) and EMBASE (from 1988) using the OVID interface for relevant data to evaluate medical treatment in a large cohort of patients with CHI from different clinical centers. Randomized, controlled trials were not available. We evaluated case reports and case series. No language restrictions were made. RESULTS: A total number of 619 patients were medically treated and information regarding conservative treatment was available. Drugs used were diazoxide (in 84% of patients), somatostatin analogues (16%), calcium channel antagonists (4%) and glucagon (1%). Mean dose of diazoxide was 12.5 (±4.3) mg/kg ⋅ d (range 2-60 mg/kg ⋅ d), mean duration of diazoxide treatment until remission was 57 months. Side effects of diazoxide were usually not severe. The causal relation between diazoxide and severe side effects, e.g. heart failure (3.7%) remains doubtful. Mean dose of octreotide was 14.9 (±7.5) μg/kg ⋅ d (range 2.3-50 μg/kg ⋅ d), of lanreotide 67.3 (±39.8) mg ⋅ month (range 10-120 mg ⋅ month). Mean duration of treatment with somatostatin analogues until remission was 49 months. Frequent side effects included tachyphylaxis and mild gastrointestinal symptoms. The risk of persistent growth deceleration was low (<5%). CONCLUSIONS: Severe side effects are rare and a causal relation remains disputable. We conclude that long-term conservative treatment of CHI is feasible.

Article Re: Evaluation of hypothalamic-pituitary-adrenal axis (ΗΡΑ) suppression by low-dose (0.5 μg) and standard-dose (250 μg) adrenocorticotropic hormone (ACTH) tests in asthmatic children treated with inhaled corticosteroid (JPEM 2006; 19: 1015-1023) was published on February 1, 2007 in the journal Journal of Pediatric Endocrinology and Metabolism (volume 20, issue 2).

BACKGROUND: To review the possible mechanisms proposed to explain the etiology of 46, XX sex reversal by investigating the clinical characteristics and their relationships with chromosomal karyotype and the SRY(sex-determining region Y)gene. METHODS: Five untreated 46, XX patients with SRY-positive were referred for infertility. Clinical data were collected, and Karyotype analysis of G-banding in lymphocytes and Fluorescence in situ hybridization (FISH) were performed. Genomic DNA from peripheral blood of the patients using QIAamp DNA Blood Kits was extracted. The three discrete regions, AZFa, AZFb and AZFc, located on the long arm of the Y chromosome, were performed by multiplex PCRs(Polymerase Chain Reaction) amplification. The set of PCR primers for the diagnosis of microdeletion of the AZFa, AZFb and AZFc region included: sY84, sY86, sY127, sY134, sY254, sY255, SRY and ZFX/ZFY. RESULTS: Our five patients had a lower body height. Physical examination revealed that their testes were small in volume, soft in texture and normal penis. Semen analyses showed azoospermia. All patients had a higher follicle-stimulating hormone(FSH), Luteinizing Hormone(LH) level, lower free testosterone, testosterone level and normal Estradiol, Prolactin level. Karyotype analysis of all patients confirmed 46, XX karyotype, and FISH analysis showed that SRY gene were positive and translocated to Xp. Molecular analysis revealed that the SRY gene were present, and the AZFa, AZFb and AZFc region were absent. CONCLUSIONS: This study adds cases on the five new 46, XX male individuals with SRY-positive and further verifies the view that the presence of SRY gene and the absence of major regions in Y chromosome should lead to the expectance of a completely masculinised phenotype, abnormal hormone levels and infertility.