ABSTRACT
BACKGROUND: Endogenous sex steroids influence the pubertal growth spurt and adult height. However, the impact of puberty suppression and sex steroids on growth in transgender adolescents is sparsely studied. AIM: We investigated pubertal growth, serum IGF-I and IGFBP-3, and adult height of transgender adolescents receiving hormone therapy. METHODS: Observational study of a national cohort (2016-2023) comprising 219 transgender adolescents <18 years of age. Treatment consisted of gonadotropin-releasing hormone agonist (GnRHa) combined with estradiol or testosterone (adjusted to serum concentrations between 0 and +2 standard deviations (SDs) corresponding to the gender identity). RESULTS: Adult height was within ±2 SD for sex assigned at birth.Most trans girls reached adult height within references of girls. For trans girls (bone age ≤15 years before treatment), a growth spurt was observed during estradiol therapy. IGF-I and height SDS declined during oral estradiol administration (-0.13 SDS per month, p=0.059, and -0.02 SDS, p=0.001, respectively). We observed significantly lower adult height compared to target height for trans girls (-2.7 cm, p=0.01), and significant differences between height SDS before treatment and at adult height (-0.35 SDS, p<0.001).Half of the trans boys remained short (<-2 SD) compared to references for boys, and most completed growth spurt before initiation of treatment. IGFBP-3 declined following testosterone treatment. There was a significant difference between height SDS before treatment and at adult height (-0.17 SDS, p<0.001). DISCUSSION AND CONCLUSION: The minor reduction in adult height of trans girls after hormone treatment may be beneficial to some, whereas trans boys did not experience height gain.
ABSTRACT
CONTEXT: Nonprogressive premature thelarche (PT) is a self-limiting variant of early puberty, while idiopathic central precocious puberty (ICPP) is a disorder that causes progressive development of secondary sexual characteristics and often requires treatment. The diagnostic differentiation between these conditions is important but can be challenging since they often both initially present clinically with isolated breast development. OBJECTIVE: To describe relevant clinical variables in a large cohort of girls referred for early puberty, and to evaluate clinical and biochemical parameters to distinguish between girls with ICPP and PT. METHODS: This retrospective study included 1361 girls referred with signs of early puberty to a single, tertiary center from 2009 to 2019. We evaluated clinical presentation, medical history, growth velocity, bone age, hormonal serum concentrations, and gonadotropin-releasing hormone (GnRH) test results. RESULTS: Central precocious puberty was diagnosed in 11% (ICPP: n = 143, organic CPP: n = 11) girls, whereas 8% (n = 91 girls) presented with PT. Receiver operating characteristic (ROC) analysis showed several biochemical and anthropometric markers as potential parameters to differentiate between ICPP and PT; however, none were individually adequate. Principal component analysis (PCA)-derived clinical and hormone profiles could predict girls with ICPP from girls with PT with a specificity of 90% and sensitivity of 84%, outperforming any single marker. CONCLUSION: Differentiation of girls with ICPP and PT can be supported by individual clinical and biochemical parameters. However, dimension reduction of clinical and hormonal profiles by PCA improved the diagnostic value, which in the future may support the diagnostic process as a supplement to the GnRH test in evaluation of pubertal disorders.
Subject(s)
Puberty, Precocious , Female , Humans , Puberty, Precocious/diagnosis , Retrospective Studies , Principal Component Analysis , ROC Curve , Gonadotropin-Releasing HormoneABSTRACT
Turner syndrome (TS) is a chromosomal disorder that affects about 1 in 2500 female births and is characterized by the partial or complete absence of the second X chromosome. Depending on karyotype, TS is associated with primary ovarian insufficiency (POI). Approximately 50% of girls with a mosaic 45, X/46, XX karyotype may enter puberty spontaneously, but only 5-10% of women with TS achieve pregnancy without egg donation. In this review, we will evaluate the clinical use of markers of ovarian function in TS patients. Based on longitudinal studies of serum concentrations of reproductive hormones as well as ovarian morphology in healthy females and patients with TS, we will evaluate how they can be applied in a clinical setting. This is important when counseling patients and their families about future ovarian function essential for pubertal development and fertility. Furthermore, we will report on 20 years of experience of transition from pediatric to gynecological and adult endocrinological care in our center at Rigshospitalet, Copenhagen, Denmark.
Subject(s)
Turner Syndrome , Adult , Pregnancy , Child , Female , Humans , Follow-Up Studies , Ovary , Longitudinal Studies , PubertyABSTRACT
Adult patients with Klinefelter syndrome (KS) are characterized by a highly variable phenotype, including tall stature, obesity, and hypergonadotropic hypogonadism, as well as an increased risk of developing insulin resistance, metabolic syndrome, and osteoporosis. Most adults need testosterone replacement therapy (TRT), whereas the use of TRT during puberty has been debated. In this retrospective, observational study, reproductive hormones and whole-body dual-energy x-ray absorptiometry-derived body composition and bone mineral content were standardized to age-related standard deviation scores in 62 patients with KS aged 5.9-20.6 years. Serum concentrations of total testosterone and inhibin B were low, whereas luteinizing hormone and follicle-stimulating hormone were high in patients before TRT. Despite normal body mass index, body fat percentage and the ratio between android fat percentage and gynoid fat percentage were significantly higher in the entire group irrespective of treatment status. In patients evaluated before and during TRT, a tendency toward a more beneficial body composition with a significant reduction in the ratio between android fat percentage and gynoid fat percentage during TRT was found. Bone mineral content (BMC) did not differ from the reference, but BMC corrected for bone area was significantly lower when compared to the reference. This study confirms that patients with KS have an unfavorable body composition and an impaired bone mineral status already during childhood and adolescence. Systematic studies are needed to evaluate whether TRT during puberty will improve these parameters.
ABSTRACT
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.
Subject(s)
Estradiol/administration & dosage , Estrogen Replacement Therapy/methods , Estrogens/administration & dosage , Puberty/drug effects , Turner Syndrome/drug therapy , Uterus/growth & development , Adolescent , Adult , Double-Blind Method , Female , Follow-Up Studies , Humans , Pilot Projects , Prognosis , Prospective Studies , Turner Syndrome/pathology , Ultrasonography , Uterus/diagnostic imaging , Uterus/drug effects , Young AdultABSTRACT
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.
Subject(s)
Blood Pressure/drug effects , Estradiol , Turner Syndrome , Adolescent , Adult , Blood Pressure Monitoring, Ambulatory/methods , Dose-Response Relationship, Drug , Drug Monitoring/methods , Estradiol/administration & dosage , Estradiol/adverse effects , Estrogens/administration & dosage , Estrogens/adverse effects , Female , Heart Rate/drug effects , Humans , Treatment Outcome , Turner Syndrome/diagnosis , Turner Syndrome/drug therapy , Turner Syndrome/physiopathologyABSTRACT
In this case report, a pregnant woman chose non-invasive prenatal testing (NIPT) following a combined first-trimester screening showing a risk of trisomy 21 at 1:200. The NIPT was normal, and the sex of the fetus was predicted to be male. At 20 gestational weeks, an ultrasound examination predicted the fetus to be female. Because of these discordant results, an amniocentesis was offered but declined. The child was postnatally tested with a karyotype: 46,XY and found heterozygous for a pathogenic variant in the androgen receptor gene, which may cause partial or complete androgen insensitivity syndrome.
Subject(s)
Androgen-Insensitivity Syndrome , Down Syndrome , Pregnancy Complications , Amniocentesis , Androgen-Insensitivity Syndrome/diagnosis , Child , Female , Humans , Male , Pregnancy , Pregnancy Complications/diagnosis , Prenatal Diagnosis , TrisomyABSTRACT
Hypogonadism may be suspected if puberty is delayed. Pubertal delay may be caused by a normal physiological variant, by primary ovarian insufficiency (Turner syndrome), or reflect congenital hypogonadotropic hypogonadism (HH; genetic) or acquired HH (brain lesions). Any underlying chronic disease like inflammatory bowel disease, celiac disease, malnutrition (anorexia or orthorexia), or excessive physical activity may also result in functional HH. Thus, girls with delayed puberty should be evaluated for an underlying pathology before any treatment, including oral contraception, is initiated. Estrogen replacement is important and natural 17ß-estradiol, preferably transdermally, is the preferred choice, whereas the oral route can be used as an alternative depending on patient preference and compliance. Sexual activity is often delayed in the hypogonadal adolescent girl. In the adolescent hypogonadal girl, hormone replacement therapy (HRT) most likely has been initiated at the time she becomes sexually active. If a risk of unwanted pregnancy cannot be ruled out, there is a need to consider contraception. This consideration does not contradict the principles of HRT but can be included as a part of the substitution, e.g. oral contraceptives containing 17ß-estradiol or a progestogen intrauterine device combined with continuous 17ß-estradiol (transdermal or oral).
Subject(s)
Contraception/methods , Estrogen Replacement Therapy , Hypogonadism/physiopathology , Hypogonadism/therapy , Sexual Maturation/physiology , Transition to Adult Care , Adolescent , Adult , Child , Estradiol/therapeutic use , Female , Hormone Replacement Therapy , Humans , Hypogonadism/congenital , Pregnancy , Puberty, Delayed/etiology , Puberty, Delayed/physiopathology , Puberty, Delayed/therapy , Transition to Adult Care/organization & administration , Turner Syndrome/physiopathology , Turner Syndrome/therapy , Young AdultABSTRACT
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.
Subject(s)
Estradiol/administration & dosage , Turner Syndrome/drug therapy , Turner Syndrome/physiopathology , Absorptiometry, Photon , Adolescent , Adult , Body Composition/drug effects , Bone Density/drug effects , Double-Blind Method , Estradiol/therapeutic use , Female , Humans , Turner Syndrome/pathology , Young AdultABSTRACT
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.
Subject(s)
Adenoma/complications , Pituitary Apoplexy/etiology , Pituitary Neoplasms/complications , Adenoma/diagnostic imaging , Adenoma/drug therapy , Adolescent , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/therapeutic use , Cabergoline , Ergolines/administration & dosage , Ergolines/therapeutic use , Female , Humans , Magnetic Resonance Imaging , Pituitary Neoplasms/diagnostic imaging , Pituitary Neoplasms/drug therapyABSTRACT
OBJECTIVE: To describe the outcome of adult granulosa cell tumor (AGCT) with respect to initial clinical findings, methods of surgery, and perioperative treatment. STUDY DESIGN: Retrospective follow-up study. SETTING: All hospitals in Jutland. SAMPLE: 163 women diagnosed with AGCT. METHODS: Follow-up by hospital data files, general practitioner, death certificate, and autopsy report. Revision of histopathology by a single pathologist. MAIN OUTCOME MEASURES: Survival and relapse by clinical data, stage, and type of surgery. RESULTS: The incidence of AGCT was 1.37 per year per 100,000 women (95% CI: 1.08, 1.68). The median follow-up time was 15 years and for the 79 surviving women 22 years. Stage I was found in 94% of cases. Relapse occurred in 24% of women in stage I and 100% of the other stages. Survival in stage I was 95%, 89% and 84% after 5, 10 and 20 years respectively. Increased survival of stage I in postmenopausal women was associated with surgery including hysterectomy and bilateral oophorectomy (p<0.001). In women younger than 40 years no difference in survival was found due to type of surgery. Endometrial carcinoma was found 138 times (95% CI: 48, 275) more prevalent than the expected rate. CONCLUSION: The survival of women was better in AGCT than in epithelial ovarian tumor. Age and type of surgery, besides stage, influenced survival. Total abdominal hysterectomy and bilateral salpingo-oophorectomy is the recommended treatment with advancing age. At younger age less extensive surgery was associated with similar survival compared to extensive surgery, but with advancing age conservative surgery increased the risk of relapse and death.
Subject(s)
Granulosa Cell Tumor/surgery , Neoplasm Recurrence, Local/surgery , Ovarian Neoplasms/surgery , Adolescent , Adult , Age Distribution , Age Factors , Aged , Aged, 80 and over , Child , Child, Preschool , Denmark/epidemiology , Female , Follow-Up Studies , Granulosa Cell Tumor/epidemiology , Granulosa Cell Tumor/pathology , Humans , Hysterectomy , Incidence , Infant , Infant, Newborn , Menopause , Middle Aged , Neoplasm Recurrence, Local/mortality , Neoplasm Staging , Ovarian Neoplasms/epidemiology , Ovarian Neoplasms/pathology , Ovariectomy , Retrospective Studies , Salpingectomy , Survival Rate , Young AdultABSTRACT
Turner syndrome (TS) is characterized by numerous medical challenges during adolescence and adulthood. Puberty has to be induced in most cases, and female sex hormone replacement therapy (HRT) should continue during adult years. These issues are normally dealt with by the paediatrician, but once a TS female enters adulthood it is less clear who should be the primary care giver. Morbidity and mortality is increased, especially due to the risk of dissection of the aorta and other cardiovascular diseases, as well as the risk of type 2 diabetes, hypertension, osteoporosis, thyroid disease and other diseases. The proper dose of HRT with female sex steroids has not been established, and, likewise, benefits and/or drawbacks from HRT have not been thoroughly evaluated. The transition period from paediatric to adult care seems to be especially vulnerable and the proper framework for transition has not yet been established. Likewise, no framework is in place for continuous follow-up during adult years in many countries. Today, most treatment recommendations are based on expert opinion and are unfortunately not evidence based, although more areas, such as growth hormone and oxandrolone treatment for increasing height, are becoming well founded. Osteoporosis, diabetes, both type 1 and 2, hypothyroidism, obesity and a host of other endocrine diseases and conditions are seen more frequently in TS. Prevention, intervention and proper treatment is only just being recognized. Hypertension is frequent and can be a forerunner of cardiovascular disease. The description of adult life with TS has been broadened and medical, social and psychological aspects are being added at a compelling pace. Proper care during adulthood should be studied and a framework for care should be in place, since most morbidity potentially is amenable to intervention. In summary, TS is a condition associated with a number of diseases and conditions which need the attention of a multi-disciplinary team during adulthood.
Subject(s)
Cardiovascular Diseases/etiology , Transition to Adult Care , Turner Syndrome/complications , Turner Syndrome/therapy , Adult , Cardiovascular Diseases/therapy , Diabetes Mellitus/therapy , Female , Humans , Liver Diseases/etiology , Liver Diseases/therapy , Osteoporosis/etiology , Osteoporosis/therapy , Primary Ovarian Insufficiency/etiology , Primary Ovarian Insufficiency/therapy , Thyroid Diseases/etiology , Thyroid Diseases/therapyABSTRACT
The cardinal features of Turner syndrome (TS) are short stature, congenital abnormalities, infertility due to gonadal dysgenesis, with sex hormone insufficiency ensuing from premature ovarian failure, which is involved in lack of proper development of secondary sex characteristics and the frequent osteoporosis seen in Turner syndrome. But sex hormone insufficiency is also involved in the increased cardiovascular risk, state of physical fitness, insulin resistance, body composition, and may play a role in the increased incidence of autoimmunity. Severe morbidity and mortality affects females with Turner syndrome. Recent research emphasizes the need for proper sex hormone replacement therapy (HRT) during the entire lifespan of females with TS and new hypotheses concerning estrogen receptors, genetics and the timing of HRT offers valuable new information. In this review, we will discuss the effects of estrogen and androgen insufficiency as well as the effects of sex HRT on morbidity and mortality with special emphasis on evidence based research and areas needing further studies.
Subject(s)
Androgens/therapeutic use , Estrogens/therapeutic use , Hormone Replacement Therapy , Turner Syndrome/drug therapy , Adolescent , Adolescent Development/drug effects , Adult , Androgens/adverse effects , Animals , Body Height/drug effects , Cardiovascular Diseases/etiology , Cardiovascular Diseases/prevention & control , Cognition Disorders/etiology , Cognition Disorders/prevention & control , Estrogens/adverse effects , Female , Hormone Replacement Therapy/adverse effects , Human Growth Hormone/adverse effects , Human Growth Hormone/therapeutic use , Humans , Osteoporosis/etiology , Osteoporosis/prevention & control , Primary Ovarian Insufficiency/etiology , Primary Ovarian Insufficiency/prevention & control , Quality of Life , Recombinant Proteins/adverse effects , Recombinant Proteins/therapeutic use , Sexual Maturation/drug effects , Turner Syndrome/genetics , Turner Syndrome/physiopathology , Turner Syndrome/psychology , Young AdultABSTRACT
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.
Subject(s)
Biological Clocks/physiology , Bone Resorption/complications , Bone Resorption/diagnosis , Osteogenesis/physiology , Turner Syndrome/physiopathology , Absorptiometry, Photon , Adolescent , Adolescent Development/physiology , Adult , Age Determination by Skeleton , Bone Density , Bone Resorption/epidemiology , Child , Cross-Sectional Studies , Female , Fractures, Bone/epidemiology , Fractures, Bone/etiology , Humans , Time Factors , Turner Syndrome/complications , Turner Syndrome/epidemiology , Young AdultABSTRACT
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.
Subject(s)
Estradiol/adverse effects , Estrogens/adverse effects , Tissue Adhesions/drug therapy , Vulva/pathology , Child , Estradiol/administration & dosage , Estrogens/administration & dosage , Female , Gels , Humans , Puberty, Precocious/chemically inducedABSTRACT
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.
Subject(s)
Magnetic Resonance Imaging/methods , Ovary/pathology , Turner Syndrome/pathology , Ultrasonography/methods , Uterus/pathology , Adolescent , Adult , Child , Cross-Sectional Studies , Female , Humans , Karyotyping , Ovary/diagnostic imaging , Radiography , Turner Syndrome/genetics , Uterus/diagnostic imaging , Young AdultABSTRACT
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.
Subject(s)
Anti-Mullerian Hormone/blood , Ovary/physiology , Turner Syndrome/blood , Adolescent , Adult , Age Factors , Aged , Biomarkers/blood , Child , Female , Humans , Infant , Infant, Newborn , Inhibins/blood , Middle Aged , ROC Curve , Reference Values , Statistics, Nonparametric , Turner Syndrome/physiopathologyABSTRACT
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.
Subject(s)
Aorta, Thoracic/pathology , Aortography , Image Processing, Computer-Assisted , Imaging, Three-Dimensional , Magnetic Resonance Angiography , Magnetic Resonance Imaging , Turner Syndrome/diagnosis , Adolescent , Age Factors , Aortic Coarctation/diagnosis , Aortic Valve/abnormalities , Aortic Valve/pathology , Body Height , Body Mass Index , Body Surface Area , Body Weight , Child , Cross-Sectional Studies , Dilatation, Pathologic , Female , Humans , Organ Size/physiology , Reference Values , Young AdultABSTRACT
CONTEXT: Reduced bone mineral density (BMD) and increased risk of fractures are present in many women with Turner syndrome (TS). OBJECTIVE: Examine longitudinal changes in BMD in TS and relate changes to biochemical parameters. DESIGN: Prospective, pragmatic, and observational study. Examinations at baseline and follow-up (5.9+/-0.7 years). SETTING: Tertiary hospital. PARTICIPANTS: Fifty-four women with TS (43.0+/-9.95 years). Interventions Hormone replacement therapy (HRT) and calcium and vitamin D supplementation. Main outcome measures BMD (g/cm(2)) measured at lumbar spine, hip, and the non-dominant forearm. Bone formation and resorption markers, sex hormones, IGF1, and maximal oxygen uptake. RESULTS: At follow-up, forearm BMD, radius ultradistal BMD, and hip BMD remained unchanged, radius 1/3 BMD declined (0.601+/-0.059 vs 0.592+/-0.059, P=0.03), while spine BMD increased (0.972+/-0.139 vs 1.010+/-0.144, P<0.0005). Bone formation markers did not change over time in TS. Bone resorption markers decreased over time in TS. Testosterone, IGF1, and maximal oxygen uptake was significantly reduced in TS. CONCLUSION: Longitudinal changes in BMD in TS were slight. BMD can be maintained at most sites in well-informed women with TS, being encouraged to maintain a healthy lifestyle, including HRT and intake of calcium and vitamin D.