Effect of Dosage of 17ß-Estradiol on Uterine Growth in Turner Syndrome-A Randomized Controlled Clinical Pilot Trial.

CONTEXT: Most Turner syndrome (TS) girls need exogenous estrogen treatment to induce puberty and normal uterine growth. After puberty, the optimal estrogen treatment protocol has not been determined. OBJECTIVE: To compare 2 doses of oral 17ß-estradiol on uterine size. DESIGN: A double-blind, 5-year randomized controlled clinical trial. SETTING: Ambulatory care. PARTICIPANTS: Twenty young TS women (19.2 ± 2.5 years, range 16.0-24.9) participated. Sixteen patients completed the study. No patients withdrew due to adverse effects. INTERVENTION: The lower dose (LD) group took 2 mg 17ß-estradiol/d orally and placebo. The higher dose (HD) group took 4 mg 17ß-estradiol/d orally. MAIN OUTCOME MEASURE(S): Uterine volume evaluated by transabdominal ultrasound yearly. RESULTS: Uterine size increased significantly more in the HD group compared with the LD group (P = 0.038), with a gain in uterine volume within the first 3 years of treatment of 19.6 mL (95% confidence interval [CI] = 4.0-19.0) in the HD group compared with 11.5 mL (95% CI = 11.2-27.9) in the LD group. The difference in 3-year gain was 8.1 mL (95% CI = 0.7-15.9). At the last visit, there were no significant differences in uterine volume between the groups. CONCLUSION: HD oral 17ß-estradiol induces a steeper increase in uterine volume within the first years of treatment compared with the LD. However, the uterine growth potential seems to be the same in most young TS women making the duration of treatment equally significant as estrogen dose, although a few TS women did not experience sufficient uterine growth on 2 mg of estradiol. CLINICALTRIALS.GOV: NCT00134745Abbreviations: BMI, body mass index; BSA, body surface area; DHEAS, dihydroepiandrosteronesulfate; HD, higher dose; HRT, hormone replacement therapy; LD, lower dose; TS, Turner syndrome; US, ultrasound.

[Pelvic inflammatory disease is a rare cause of acute abdomen in a child].

Pelvic inflammatory disease (PID) is a frequent cause of acute abdomen among sexually active females, although rarely seen in girls prior to their sexual debut. In this case report, a 12-year-old girl was hospitalised due to abdominal pain. She was virgo and premenarcheal. A laparoscopy showed a normal appendix but revealed pyosalpinx. A follow-up with ultrasound of the genitalia interna showed normal relations. PID should be considered in all females with compatible symptoms, irrespective of their age.

Five-Year Randomized Study Demonstrates Blood Pressure Increases in Young Women With Turner Syndrome Regardless of Estradiol Dose.

We evaluated the development in blood pressure (BP) and heart rate in young women with Turner syndrome (TS) and investigated potential influencing cofactors. Twenty TS women (mean±SD, 22.9±2.3 years of age) were investigated in a 5-year prospective setting. Data were derived from a randomized controlled clinical trial investigating 2 different doses of estradiol treatment (2 mg 17ß-estradiol per day and placebo or 2+2 mg 17ß-estradiol per day). A control group of 12 healthy age-matched young women (mean±SD, 23.11±2.2 years of age) was examined at the end of the study. BP and lipids were monitored yearly. At the end of the study, TS (n=15) and controls were examined by 24-hour ambulatory BP monitoring. Systolic and diastolic BPs increased regardless of estradiol dose ( P=0.005 and P=0.009) in TS patients, whereas heart rate decreased ( P=0.05). Neither body mass index, height, weight, nor lipids contributed significant to the changes. There was no difference in BP, heart rate, or lipids because of treatment. At the end of the study, diastolic BP and heart rate were significantly higher in TS during day, night, and over 24 hours. Systolic BP increased insignificantly. Lipids did not change during the study period, but body mass index determined individual levels. In conclusion, systolic and diastolic BPs increase significantly in late adolescence and early adulthood in TS. It remains an enigma why BP increases early in life in TS. Clinical Trial Registration- URL: http://www.clinicaltrials.gov . Unique identifier: NCT00134745.

[The correlation between motivation, emotions land learning].

This article explores the importance of emotions as conditional for motivation in medical education. The main principles in self-determination theory and in control-value theory are outlined, and practical consequences which may be drawn from these theories are discussed. Based on the literature we hypothesize that human need for autonomy and competence may be violated by strict regulations and detailed plans for medical education, and that constructive feedback may modify these potential negative effects and support feelings of competence and autonomy.

[A rare type of severe obesity in children and adolescents].

A four-year-old girl was referred to a paediatric department with low height, obesity and hypothyroidism. Her paraclinical tests were characteristic with elevated P-parathyroid hormone concentration, hypothyroidism, growth hormone deficiency, abnormal phenotype with brachydactyly, tooth problems and mental retardation, which led to a suspicion of Albright's hereditary osteodystrophy (AHO). The diagnosis was verified by molecular genetic testing. Less than 1% of children with obesity have an endocrine disorder, and AHO is one of them.

Dosage of estradiol, bone and body composition in Turner syndrome: a 5-year randomized controlled clinical trial.

OBJECTIVE: Reduced bone mineral density (BMD) is seen in Turner syndrome (TS) with an increased risk of fractures, and body composition is characterized by increased body fat and decreased lean body mass. To evaluate the effect of two different doses of oral 17B-estradiol in young TS women on bone mineral density (BMD), biochemical markers of bone turnover and body composition with the hypothesis of a positive effect of the higher dose. DESIGN: A double-blind 5-year randomized controlled clinical trial. 20 young TS women participated. Inclusion criteria were diagnosis of TS, age 15-25 years and current treatment with 2 mg oral estradiol daily. METHODS: The low-dose (LD) group was administered 2 mg 17B-estradiol/day orally and placebo, the high-dose (HD) group was administered 2 + 2 mg 17B-estradiol/day orally. Main outcome measures were whole body and regional bone mineral density (BMD), lean body mass (LBM), fat mass (FM) measured yearly by DXA scan and resorptive and formative bone markers in serum. RESULTS: BMD, whole body and regional, increased over time with an attenuation toward the end of the study, and bone turnover markers decreased over time, both with no differences between the treatment groups (P = 0.2-0.9). LBM increased significantly more in the HD group (P = 0.02). FM remained stable in both groups. CONCLUSIONS: A steady increase in BMD over time in TS was found similar to healthy young women. The higher estrogen dose did not differentially affect BMD or bone markers. The positive effect on body composition may have long-ranging health benefits in TS.

Expression profiling and functional analyses of BghPTR2, a peptide transporter from Blumeria graminis f. sp. hordei.

The obligate ascomycete parasitic fungus Blumeria graminis f. sp. hordei (Bgh) has a unique lifestyle as it is completely dependent on living barley leaves as substrate for growth. Genes involved in inorganic nitrogen utilization are notably lacking, and the fungus relies on uptake of host-derived peptides and amino acids. The PTR2 transporter family takes up di- and tri- peptides in a proton coupled process and filamentous fungi typically have two or more di/tri peptide transporters. Here we show that Bgh appear to have one PTR2 that can restore dipeptide uptake in a Saccharomyces cerevisiae PTR2 deletion strain. The Bgh PTR2 gene is expressed in conidia and germinating conidia. During Bgh infection of barley the expression level of the BghPTR2 gene is high in the appressorial germ tube, low in the haustoria and high again during conidiation and secondary infection in the compatible and intermediate resistant interactions. BghPTR2 appears to be important for the initial establishment of fungal infection but not for uptake of di-tri-peptides at the haustorial interface. Based on the expression profile we suggest that BghPTR2 is active in internal transport of nutrient reserves and/or uptake of break down products from the plant surface during the early infection stages.

Ovarian morphology and function during growth hormone therapy of short girls born small for gestational age.

OBJECTIVE: To study the effect of growth hormone (GH) treatment on ovarian and uterine morphology and function in short, prepubertal small-for-gestational-age (SGA) girls. DESIGN: A multinational, randomized controlled trial on safety and efficacy of GH therapy in short, prepubertal children born SGA. SETTING: Not applicable. PATIENT(S): A subgroup of 18 Danish girls born SGA included in North European SGA Study (NESGAS). INTERVENTION(S): One year of GH treatment (67 µg/kg/day) followed by 2 years of randomized GH treatment (67 µg/kg/day, 35 µg/kg/day, or IGF-I titrated). MAIN OUTCOME MEASURE(S): Data on anthropometrics, reproductive hormones, and ultrasonographic examination of the internal genitalia were collected during 36 months of GH treatment. RESULT(S): Uterine and ovarian volume increased significantly during 3 years of treatment (64% and 110%, respectively) but remained low within normal reference ranges. Ovarian follicles became visible in 58% after 1 year compared with 28% before GH therapy. Anti-Müllerian hormone increased significantly during the 3 years of GH therapy but remained within the normal range. Precocious puberty was observed in one girl; another girl developed multicystic ovaries. CONCLUSION(S): GH treatment was associated with statistically significant growth of the internal genitalia, but remained within the normal range. As altered pubertal development and ovarian morphology were found in 2 of 18 girls, monitoring of puberty and ovarian function during GH therapy in SGA girls is prudent. Altogether, the findings are reassuring. However, long-term effects of GH treatment on adult reproductive function remain unknown. CLINICAL TRIAL REGISTRATION NUMBER: EudraCT 2005-001507-19.

[360-degree feedback for medical trainees].

In 360-degree feedback medical colleagues and collaborators give a trainee feedback by answering a questionnaire on behaviour of the trainee. The questionnaire may contain questions answered on a scale or/and they may contain open questions. The result from 360-degree feedback is used for formative feedback and assessment. In order to secure reliability 8-15 respondents are needed. It is a matter of discussion whether the respondents should be chosen by the trainee or by a third part, and if respondents should be anonymous. The process includes a feedback session with a trained supervisor.

[Pituitary apoplexy in a young woman].

Pituitary apoplexy occurs when a preexisting pituitary adenoma undergoes acute haemorrhage, infarct or both. The patho-genesis is not fully understood but macroadenomas and prolactinomas have been reported as being predisposed to apoplexy. Only a few cases are described in the paediatric population. We present a 17-year-old woman with secondary amenorrhoea, headache and blurred vision. An MRI showed a pituitary apoplexy in a preexisting macroadenoma. The majority of milder cases resolve spontaneously. Close monitoring of the pituitary function is important to detect pituitary insufficiency witch may need long-term hormone replacement therapy.

Hospital contacts for endocrine disorders in Adult Life after Childhood Cancer in Scandinavia (ALiCCS): a population-based cohort study.

BACKGROUND: The pattern of endocrine disorders in long-term survivors of childhood cancer has not been investigated comprehensively. Here, we aimed to assess the lifetime risk of these disorders in Nordic survivors of childhood cancer. METHODS: From the national cancer registries of Denmark, Finland, Iceland, Norway, and Sweden, we identified 31,723 1-year survivors of childhood cancer, notified since the start of registration in the 1940s and 1950s. From the national population registries, we randomly selected a comparison cohort of people matched by age, sex, and country. Study participants were linked to the national hospital registries, and observed numbers of first-time hospital contacts for endocrine disorders in survivors of childhood cancer were compared with the expected numbers derived from the population comparison cohort. We calculated the absolute excess risks attributable to status as a childhood cancer survivor and standardised hospitalisation rate ratios (SHRRs). FINDINGS: Of the childhood cancer survivors, 3292 had contact with a hospital for an endocrine disorder, yielding a SHRR of 4·8 (95% CI 4·6-5·0); the highest risks were in survivors of leukaemia (SHRR 7·3 [95% CI 6·7-7·9]), CNS tumours (6·6 [6·2-7·0]), and Hodgkin's lymphoma (6·2 [5·6-7·0]). The absolute excess risk for endocrine disorders was roughly 1000 per 100,000 person-years before 20 years of age, and 400 per 100,000 person-years during the remaining lifetime. For children with cancer diagnosed at 5-9 years of age, the cumulative risk for endocrine disorders was highest, and reached 43% at the age of 60 years. Diagnoses of pituitary hypofunction (SHRR 88·0), hypothyroidism (9·9), and testicular and ovarian dysfunction (42·5 and 4·7, respectively) together constituted 61% (655 of 1078) of all excess disease-induced and treatment-induced endocrine disorders in survivors of childhood cancer. INTERPRETATION: A cumulative risk for endocrine disorders at 60 years of age of above 40% in survivors of childhood cancer emphasises the importance of minimisation of damaging treatment, intensification of secondary prevention, and targeting of survivor follow-up throughout life. Since most long-term childhood cancer survivors are not followed in a specialised late-effect clinic, they are a growing challenge for the primary care physician and medical specialists working outside the late-effect area. FUNDING: The Danish Council for Strategic Research.

[Multiple mini interviews before the occupation of main training posts in paediatrics]. / Multiple miniinterview før besættelse af pædiatriske hoveduddannelsesstillinger er gennemførlige.

Interviews are mandatory in Denmark when selecting doctors for training positions. We used multiple mini interviews (MMI) at four recruitment rounds for the main training posts in paediatrics. In total, 125 candidates were evaluated and assessed by CV and MMI (4-5 stations). Reliability for individual stations in MMI assessed by Cronbach's alpha was adequate (0.63-0.92). The overall reliability assessed by G-theory was lower, suggesting that different skills were tested. The acceptability was high. Our experiences with MMI suggest good feasibility and reliability. An increasing number of stations may improve the overall reliability.

Normal tempo of bone formation in Turner syndrome despite signs of accelerated bone resorption.

AIMS: To evaluate area bone mineral density (aBMD) and volumetric BMD (vBMD) by dual-energy X-ray absorptiometry, and relations to bone markers and hormones in adolescent women with Turner syndrome (TS). METHODS: Cross-sectional study in TS patients (n = 37, 16.7 ± 3.4 years) and control group (n = 49), assessed by dual-energy X-ray absorptiometry, bone markers and hormones. TS patients were divided into a young group receiving ('ongoing') GH (n = 15) and an older group previously receiving ('previous') GH (n = 22). RESULTS: vBMD(spine) was similar in 'ongoing GH' TS, but higher in 'previous GH' TS, compared to controls. vBMD(hip) was lower in 'ongoing GH' TS, but similar in 'previous GH'. z scores for aBMD were uniformly reduced in 'ongoing TS', but near-normalized in 'previous GH' TS. Bone formation and resorption markers were increased in 'ongoing GH' TS, while 'previous GH' TS had elevated bone resorption markers. CONCLUSION: BMD increased in parallel with age in TS patients receiving optimal estradiol replacement therapy and GH according to consensus guidelines, and in controls. Young TS undergoing pubertal induction and still receiving GH have lower z score BMD than older TS patients receiving hormonal replacement therapy, where a near-normalization of BMD was achieved. TS patients previously receiving GH showed signs of increased bone resorption.

[Precocious pseudopuberty in a seven year-old girl due to estrogen treatment of labial adhesion]. / Perifer pubertas praecox som bivirkning i forbindelse med østrogenbehandling af labial adhærens hos en syvårig pige.

Labial adhesions are well-known in prepubertal girls. We present a seven year-old girl treated with estrogen gel due to labial adhesion resulting in precocious pseudopuberty. Endocrine tests and bone age were normal. Symptoms regressed upon cessation of treatment. Labial adhesions often resolve spontaneously in early puberty. Precocious pseudopuberty is a well-known side effect to estrogen gel used in excess which should only be initiated in prepubertal girls with great caution and after careful consideration.

Uterus and ovaries in girls and young women with Turner syndrome evaluated by ultrasound and magnetic resonance imaging.

OBJECTIVE: To determine uterine and ovarian size in Turner syndrome (TS) and to compare uterine and ovarian size evaluated by transabdominal ultrasound (US) and magnetic resonance imaging (MRI) in girls with TS and two groups of controls. DESIGN: A cross-sectional study. PATIENTS: Forty-one girls with TS (17·0 ± 3·3 years, range 11·2-24·9 years), 50 healthy age-matched controls (16·9 ± 3·2 years, range 12·5-25·0 years) and 107 Tanner-stage-matched controls (15·0 ± 3·2 years, range 10·1-24·2). MEASUREMENTS: Uterine and ovarian volume by US and MRI. RESULTS: Ovaries were detected in 37% in TS by US and in 55% in TS by MRI (P = 0·1). Total ovarian volume was lower in TS compared to both groups of controls (TS vs C-US: median 1·1 ml (range 0·1-29·3) vs 11·52 ml (1·9-77·9), P = 0·001, TS vs C-MRI: 1·0 ml (0·1-34·2) vs 13·2 ml (2·4-30·1), P < 0·0005). Mean difference in total ovarian volume measured by MRI and US in patients with TS was 2·3 ± 3·8 ml (P = 0·01). Mean uterine volume by MRI was lower in TS compared to controls (29·5 ± 25·1 vs 54·3 ± 23·3 ml, P < 0·0005). Uterine volume by US was lower in TS at Tanner stage B5 compared to controls (TS vs C: 33·6 ± 18·2 vs 50·2 ± 18·0 ml, P = 0·007). CONCLUSIONS: A larger ovarian volume was detected by MRI in TS compared to US. This finding is important with the advancements of performing ovarian biopsies for cryopreservation and later reimplantation. Mean uterine volumes by MRI and US in fully matured TS were lower compared to controls despite appropriate hormonal replacement therapy in TS.

Serum levels of anti-Müllerian hormone as a marker of ovarian function in 926 healthy females from birth to adulthood and in 172 Turner syndrome patients.

CONTEXT: In adult women, anti-Müllerian hormone (AMH) is related to the ovarian follicle pool. Little is known about AMH in girls. OBJECTIVE: The objective of the study was to provide a reference range for AMH in girls and adolescents and to evaluate AMH as a marker of ovarian function. SETTING: The study was conducted at a tertiary referral center for pediatric endocrinology. MAIN OUTCOME MEASURES: We measured AMH in 926 healthy females (longitudinal values during infancy) as well as in 172 Turner syndrome (TS) patients according to age, karyotype (A: 45,X; B: miscellaneous karyotypes; C: 45,X/46,XX), and ovarian function (1: absent puberty; 2: cessation of ovarian function; 3: ongoing ovarian function). RESULTS: AMH was undetectable in 54% (38 of 71) of cord blood samples (<2; <2-15 pmol/liter) (median; 2.5th to 97.5th percentile) and increased in all (37 of 37) infants from birth to 3 months (15; 4.5-29.5 pmol/liter). From 8 to 25 yr, AMH levels were stable (19.9; 4.7-60.1 pmol/liter), with the lower level of the reference range clearly above the detection limit. AMH levels were associated with TS-karyotype groups (median A vs. B: <2 vs. 3 pmol/liter, P = 0.044; B vs. C: 3 vs. 16 pmol/liter, P < 0.001) as well as with ovarian function (absent puberty vs. cessation of ovarian function: <2 vs. 6 pmol/liter, P = 0.004; cessation of ovarian function vs. ongoing ovarian function: 6 vs. 14 pmol/liter, P = 0.001). As a screening test of premature ovarian failure in TS, the sensitivity and specificity of AMH less than 8 pmol/liter was 96 and 86%, respectively. CONCLUSION: AMH seems to be a promising marker of ovarian function in healthy girls and TS patients.

[Morbus Addison in five-year-old girl]. / Addisons sygdom hos femårig.

This case-report presents a 5-year-old girl with gastrointestinal symptoms, who became increasingly confused over the last day before admission. She was believed to be in septic shock or have meningitis and was treated with normal saline infusion, glucocorticoid and antibiotics intravenously. A few days later she was diagnosed with primary adrenal insufficiency (Morbus Addison), which is a very rare disorder among children. If untreated, the condition is lethal, and should always be considered as a differential diagnosis in severely ill patients.

Aortic dimensions in girls and young women with turner syndrome: a magnetic resonance imaging study.

This study aimed to determine the dimensions of the thoracic aorta and the predictors of aortic dimensions in girls and young women with Turner syndrome (TS). A cross-sectional study was performed at a secondary care center. The study compared 41 TS patients with 50 healthy age-matched control subjects. The mean age of the patients was 17 +/- 3.3 years. Magnetic resonance imaging was performed for all the patients. The thoracic aortic diameters of the patients were measured at nine positions. Adjustment for body surface area (BSA) was performed. The outcome for the patients was measured in terms of absolute and BSA-adjusted aortic dilation. In TS, both the absolute and the BSA-adjusted mean aortic diameters were smaller than or comparable with those of the control subjects. However, individual aortic dilation at one to four positions was found in four TS patients according to the uncorrected data and in five TS patients after BSA-adjustment. The aortic diameters correlated with height, weight, body mass index (BMI), and BSA at all positions (R = 0.34-0.60; all p < 0.04). The diameters of the aortic arch and the descending aorta correlated with a history of aortic coarctation (R = 0.35-0.52; p < 0.03). The presence of bicuspid aortic valves correlated at the descending part of the aorta (R = 0.38; p < 0.03). The mean thoracic aortic dimensions were not enlarged in girls or young TS patients. The BSA predicted aortic size at all positions. The prevalence of aortic dilation and aneurysm was lower in this population of girls and younger women with TS than in older TS populations.

[Bacterial pyomyositis in a 12-year-old girl without fever]. / Pyomyositis uden feber hos 12-årig pige.

Bacterial pyomyositis is generally found in tropical countries. This case report presents pyomyositis in a 12-year-old girl who was admitted without fever to the paediatric department. The only symptom was pain in the left hip. Staphylococcus aureus was cultured from the blood on day 4. Magnetic resonance imaging (MRI) revealed infection in the left m. ileopsoas. Previous ultrasound, computerised tomography, x-ray and bone-scintigraphy were normal. After 11 days of intravenous antibiotic therapy and clinical remission, secondary bone affection was detected by a new MRI. Long-term antibiotic treatment is required in such cases because of the risk of secondary bone affection. This patient was treated for 11 days with intravenous antibiotic therapy and for the subsequent three months with tablets.