CoChat
Sign Up
Cited by 224Genetic and Clinical Aspects of Sex Determination and Chromosomal AbnormalitiesSexual Differentiation and DisordersAdolescent and Pediatric Healthcare

The DOI matches its Crossref record; 919 of the 996 references it cites were found in a registry or an index; none of the 1,081 sources its claims cite is checked for support yet.

Clinical practice guidelines for the care of girls and women with Turner syndrome.

Open access
Gravholt, Claus H, Andersen, Niels H, Christin-Maitre, Sophie, Davis, Shanlee M, Duijnhouwer, Anthonie, Gawlik, Aneta, Maciel-Guerra, Andrea T, Gutmark-Little, Iris, Fleischer, Kathrin, Hong, David, Klein, Karen O, Prakash, Siddharth K, Shankar, Roopa Kanakatti, Sandberg, David E, Sas, Theo C J, Skakkebæk, Anne, Stochholm, Kirstine, van der Velden, Janielle A, The International Turner Syndrome Consensus Group, Alvarez-Nava, Francisco, Avdic, Hanna Bjorlin, Balle, Camilla M, Bamba, Vaneeta, Bedei, Ivonne, Bonnard, Åsa, Brickman, Wendy J, Brown, Nicole M, Chernausek, Steven, Cobbold, Jeremy, Corathers, Sarah D, Corpechot, Christophe, Crenshaw, Melissa L, Davies, Melanie, Deeb, Asma, Dessens, Arianne, Dowlut-McElroy, Tazim, Elliott, Victoria, Fadoju, Doris, Fechner, Patricia Y, Geffner, Mitchell, Gitomer, Sarah, de Groote, Katya, Hewitt, Jacky, Ho, Cindy, Hutaff-Lee, Christa, Isojima, Tsuyoshi, Johannsen, Emma B, Kawai, Masanobu, Keselman, Ana, Knickmeyer, Rebecca Christine, Kremen, Jessica, Kristrøm, Berit, Kruszka, Paul, Law, Jennifer, Lin, Angela E, Loechner, Karen, Mauras, Nelly, Matthews, Deborah, Mikkelborg, Trine, Mortensen, Kristian Havmand, Nahata, Leena, Norman, Mackenzie, Patel, Sheetal R, Quigley, Charmian, Ridder, Lukas O, Santen, Richard J, Sheanon, Nicole, Smyth, Arlene, Turner, Helen, Verlinde, Franciska, Viuff, Mette Hansen, Wasniewska, Malgorzata, van der Weijde, Berber, Woelfle, Joachim, Wolstencroft, Jeanne, Backeljauw, Philippe F·2024·European Journal of Endocrinology
DOI 10.1093/ejendo/lvae050PMC PMC11759048
Open this paper in CoChat — free account

Abstract

Turner syndrome (TS) affects 50 per 100 000 females. TS affects multiple organs through all stages of life, necessitating multidisciplinary care. This guideline extends previous ones and includes important new advances, within diagnostics and genetics, estrogen treatment, fertility, co-morbidities, and neurocognition and neuropsychology. Exploratory meetings were held in 2021 in Europe and United States culminating with a consensus meeting in Aarhus, Denmark in June 2023. Prior to this, eight groups addressed important areas in TS care: (1) diagnosis and genetics, (2) growth, (3) puberty and estrogen treatment, (4) cardiovascular health, (5) transition, (6) fertility assessment, monitoring, and counselling, (7) health surveillance for comorbidities throughout the lifespan, and (8) neurocognition and its implications for mental health and well-being. Each group produced proposals for the present guidelines, which were meticulously discussed by the entire group. Four pertinent questions were submitted for formal GRADE (Grading of Recommendations, Assessment, Development and Evaluation) evaluation with systematic review of the literature. The guidelines project was initiated by the European Society for Endocrinology and the Pediatric Endocrine Society, in collaboration with members from the European Society for Pediatric Endocrinology, the European Society of Human Reproduction and Embryology, the European Reference Network on Rare Endocrine Conditions, the Society for Endocrinology, and the European Society of Cardiology, Japanese Society for Pediatric Endocrinology, Australia and New Zealand Society for Pediatric Endocrinology and Diabetes, Latin American Society for Pediatric Endocrinology, Arab Society for Pediatric Endocrinology and Diabetes, and the Asia Pacific Pediatric Endocrine Society. Advocacy groups appointed representatives for pre-meeting discussions and the consensus meeting.

Overview

AI snapshot

Written from a shortened version of the paper’s full text (it is longer than we read).

TL;DR

This 2024 international clinical practice guideline updates care for girls and women with Turner syndrome across diagnosis/genetics, growth, puberty and estrogen treatment, cardiovascular health, transition, fertility, comorbidities, and neurocognition. It provides graded recommendations, but only four clinical questions were formally GRADE-evaluated, with many recommendations based on expert consensus.

Key findings

  • Turner syndrome affects 50 per 100 000 females (abstract; the introduction says 25-50 per 100 000) and requires multidisciplinary care across the lifespan; the guideline covers eight domains and includes new advances in diagnostics/genetics, estrogen treatment, fertility, comorbidities, and neurocognition/neuropsychology.
  • For growth, the guideline recommends GH starting at 45-50 µg kg−1 day−1 (1.3-1.5 mg m−2 day−1), increasing to a maximum of 68 µg kg−1 day−1 (2.0 mg m−2 day−1) if response is suboptimal; it reports adult height gains of approximately 5-8 cm, a meta-analysis mean gain of 7.2 cm, and normal adult height in 40%-50% of treated vs 4%-16% of non-GH-treated individuals in long-term controlled trials.
  • Cardiovascular findings include CHD prevalence of 40%-60%, BAV in more than 25%, and aortic dissection incidence of approximately 164 per 100 000 person-years vs 6 per 100 000 person-years in the general population; the guideline recommends lifelong surveillance, aortic size indexing (AHI, ASI, Z-score), blood pressure control, and pregnancy-specific cardiovascular management.
  • For puberty and fertility, the guideline recommends measuring LH, FSH, and AMH at 8-9 years and yearly until 11-12 years, initiating low-dose estrogen at 11-12 years if FSH is elevated on at least two measurements, preferring transdermal E2, adding cyclic progesterone after breakthrough bleeding, and offering oocyte cryopreservation as the primary fertility preservation option for post-menarche individuals of appropriate maturity; ovarian tissue cryopreservation should only be offered under ethics board approval.

Methods

  • The guideline was developed by an international working group initiated by the European Society of Endocrinology and the Pediatric Endocrine Society, with eight groups addressing diagnosis/genetics, growth, puberty/estrogen, cardiovascular health, transition, fertility, comorbidities, and neurocognition; exploratory meetings were held in 2021 and a consensus meeting in Aarhus, Denmark in June 2023.
  • Four clinical questions—growth-promoting treatment, probability of viable pregnancy after oocyte donation, effects of blood pressure treatment, and optimal estrogen replacement—underwent formal GRADE evaluation with systematic literature searches in PubMed, Embase, and the Cochrane Library; other recommendations were derived from majority consensus or expert opinion and graded with the same evidence symbols.
  • Recommendations are worded as “recommend” (strong) or “suggest” (weak), with evidence quality classified from very low to strong.

Limitations

  • The paper states that formal evidence syntheses and grading were performed only for four GRADE questions; all other recommendations were based on majority consensus or expert opinion, and some GRADE questions had insufficient evidence—for example, no comparative studies of antihypertensive treatments or blood pressure targets in Turner syndrome were identified.
  • The paper notes that many areas lack rigorous long-term prospective studies, including optimal estrogen route/dose, progesterone regimens, fertility preservation outcomes, and transition outcomes; recommendations often rely on limited data and extrapolation from non-Turner populations.
  • Evident from the text: this is a clinical practice guideline, not a primary empirical study, and several recommendations are ungraded Good Practice Statements.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1093/ejendo/lvae050

Cites

919 of 919 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Verification

Claims the paper makes

0 of 1081 cited sources checked · 0 supported · 0 flagged

Show all 348 claims

  • It may state two separate claims as one. 245
  • Probably not a substantial claim. 77
  • The quote only partly states this claim. 2
304 of 304

  • The paper relies on this without support.

    TS affects multiple organs through all stages of life, necessitating multidisciplinary care.

    “TS affects multiple organs through all stages of life, necessitating multidisciplinary care.”

  • The paper relies on this without support.

    TS is usually accompanied by infertility due to premature ovarian insufficiency.

    “TS is usually accompanied by infertility due to premature ovarian insufficiency.”

  • The paper relies on this without support.

    TS is often accompanied by hypertension, which has been linked to the development of aortic dilation or dissection, both observed with strikingly increased frequency in TS.

    “TS is often accompanied by hypertension, which has been linked to the development of aortic dilation or dissection, both observed with strikingly increased frequency in TS.”

  • The paper relies on this without support.

    TS is usually accompanied by hypergonadotropic hypogonadism and primary or secondary amenorrhea.

    “TS is usually accompanied by hypergonadotropic hypogonadism and primary or secondary amenorrhea.”

  • The paper relies on this without support.

    Individuals with a deletion distal to Xq24 frequently have primary or secondary amenorrhea without short stature or other TS features and should be referred to as having premature ovarian insufficiency.

    “Those who have a deletion distal to Xq24 frequently have primary or secondary amenorrhea without short stature or other TS features and should be referred to as having premature ovarian insufficiency.”

  • The paper relies on this without support.

    Karyotyping is the gold standard test to diagnose TS.

    “Karyotyping is the gold standard test to diagnose TS.”

  • The paper relies on this without support.

    TS is associated with significant phenotypic variability ranging from individuals with classic traits to individuals without apparent observable traits.

    “TS is associated with significant phenotypic variability ranging from individuals with classic traits to individuals without apparent observable traits.”

  • The paper relies on this without support.

    Constitutional karyotype of individuals with prenatally diagnosed TS are uncertain, especially in patients with mosaicism.

    “Because constitutional karyotype of individuals with prenatally diagnosed TS are uncertain, especially in patients with mosaicism, postnatal confirmation by standard chromosome analysis performed on a peripheral blood sample is indicated, irrespective of prenatal ascertainment.”

  • The paper relies on this without support.

    A sufficient ovarian reserve to obtain sufficient embryos for testing is a prerequisite for applying pre-implantation genetic testing.

    “However, a sufficient ovarian reserve to obtain sufficient embryos for testing is a prerequisite for applying pre-implantation genetic testing.”

  • The paper relies on this without support.

    Missed and delayed diagnoses of TS continue to be a challenge.

    “Although there seems to be a tendency towards earlier diagnosis, missed and delayed diagnoses of TS continues to be a challenge.”

  • The paper relies on this without support.

    NIPT does not routinely include screening for sex chromosome abnormalities.

    “Despite the widespread use of NIPT, this does not routinely include screening for sex chromosome abnormalities necessitating postnatal recognition and testing.”

  • The paper relies on this without support.

    The later GH therapy is initiated, the larger the growth deficit and the lower the likelihood of normal adult stature.

    “In general, the later GH therapy is initiated, the larger the growth deficit and the lower the likelihood of normal adult stature.”

  • The paper relies on this without support.

    Karyotyping is the gold-standard technique for diagnosing TS.

    “While karyotyping is the gold-standard technique for diagnosing TS, it has major limitations as a screening tool.”

  • The paper relies on this without support.

    Karyotyping has major limitations as a screening tool, requiring specialized personnel, long processing time, and greater expense.

    “This requires specialized personnel and entails a long processing time and greater expense.”

  • The paper relies on this without support.

    Most girls with TS will require estrogen therapy to initiate or complete puberty prior to completion of linear growth.

    “Furthermore, as most girls with TS will require estrogen therapy to either initiate or complete puberty prior to completion of linear growth,”

  • The paper relies on this without support.

    Estrogen route, dose, and tempo of dose escalation impact pubertal growth and adult height.

    “the estrogen route, dose, and tempo of dose escalation will have an impact on pubertal growth and, therefore, on AH.”

  • The paper relies on this without support.

    Growth response to rhGH varies significantly across individuals.

    “as the growth response varies significantly across individuals.”

  • The paper relies on this without support.

    Short stature is a common feature and often the presenting concern leading to the diagnosis of TS.

    “Short stature is a common feature and often the presenting concern leading to the diagnosis of TS.”

  • The paper relies on this without support.

    The formulation, route, and dosing of childhood estrogen have not been optimized.

    “The formulation, route, and dosing of childhood estrogen have not been optimized.”

  • The paper relies on this without support.

    Height is only one of many factors that affect QoL in TS.

    “Height is only one of many factors that affect QoL in TS.”

  • The paper relies on this without support.

    Very low concentrations of serum E2 in healthy prepubertal girls have minimal impact on uterine growth.

    “Because very low concentrations of serum E2 in healthy prepubertal girls seem to have minimal impact on uterine growth”

  • The paper relies on this without support.

    Using physiological age as a guide to the initiation of hormone replacement therapy supports normal bone mineral accrual.

    “using physiological age as a guide to the initiation of HRT supports normal bone mineral accrual”

  • The paper relies on this without support.

    17β-estradiol is the natural physiological form of estrogen.

    “17β-estradiol (E2) is the natural physiological form of estrogen”

  • The paper relies on this without support.

    Ethinyl estradiol is a potent synthetic E2 analogue, widely used in the combined oral contraceptive pill and historically used as hormone replacement therapy in women with premature ovarian insufficiency including those with Turner syndrome.

    “Ethinyl estradiol is a potent synthetic E2 analogue, widely used in the combined oral contraceptive pill and, historically, has been used as HRT in women with premature ovarian insufficiency including those with TS.”

  • The paper relies on this without support.

    Ethinyl estradiol is long-acting; therefore, it cannot mimic the typical diurnal variation seen in early puberty, and serum concentration of E2 cannot be measured meaningfully while on ethinyl estradiol.

    “It is long-acting; therefore, it cannot mimic the typical diurnal variation seen in early puberty, and serum concentration of E2 cannot be measured meaningfully while on ethinyl estradiol.”

  • The paper relies on this without support.

    Transdermal patches may fail to adhere well in girls with skin conditions such as eczema and may also cause skin irritation, both limiting their use.

    “However, TD patches may fail to adhere well in girls with skin conditions such as eczema and they may also cause skin irritation, both limiting their use.”

  • The paper relies on this without support.

    Tablets are available in fixed doses, and it is difficult to divide into smaller doses.

    “However, a drawback is that tablets are available in fixed doses, and it is difficult to divide into smaller doses.”

  • The paper relies on this without support.

    The lowest dose available is 0.5 mg but is only available in a few countries.

    “The lowest dose available is 0.5 mg but is only available in a few countries.”

  • The paper relies on this without support.

    It has not been shown scientifically whether any route is superior to the other in a lifelong replacement situation in Turner syndrome or in any other hypogonadal group.

    “Even though the transdermal route is theoretically attractive, it has not been shown scientifically whether any route is superior to the other in a lifelong replacement situation in TS or in any other hypogonadal group.”

  • The paper relies on this without support.

    In early puberty there is a diurnal variation with E2 serum concentrations increasing first during night-time and very early morning; in mid-puberty, the diurnal variation ceases, and serum E2 concentrations increase until menarche followed by the estradiol–progesterone cyclic variation of the adult fertile woman.

    “In early puberty there is a diurnal variation with E2 serum concentrations increasing first during night-time and very early morning. In mid-puberty, the diurnal variation ceases, and serum E2 concentrations increase until menarche followed by the estradiol–progesterone cyclic variation of the adult fertile woman.”

  • The paper relies on this without support.

    Estrogen has a dual effect on the growth plate: initially stimulatory but also leading to physeal fusion at higher concentrations.

    “estrogen has a dual effect on the growth plate: initially stimulatory but also leading to physeal fusion at higher concentrations.”

  • The paper relies on this without support.

    Ethinyl estradiol has been shown to be inferior to E2 for bone health after attainment of pubertal induction.

    “For estrogen replacement after attainment of pubertal induction, ethinyl estradiol has been shown to be inferior to E2 for bone health”

  • The paper relies on this without support.

    A standard oral contraceptive pill is taken for 21/28 days and a woman with Turner syndrome will therefore be hypoestrogenic during the pause.

    “It is useful to remember that a standard oral contraceptive pill is taken for 21/28 days and that a woman with TS will therefore be hypoestrogenic during the pause.”

  • The paper relies on this without support.

    The addition of progesterone administered in a cyclic regimen with estrogen allows regular, controlled, predictable episodes of withdrawal bleeding or “periods”.

    “Secondly, the addition of progesterone administered in a cyclic regimen with estrogen allows regular, controlled, predictable episodes of withdrawal bleeding or “periods”.”

  • The paper relies on this without support.

    Medroxyprogesterone acetate is effective at providing endometrial protection.

    “It is effective at providing endometrial protection.”

  • The paper relies on this without support.

    Medroxyprogesterone acetate also acts on the glucocorticoid receptor giving rise to potential glucocorticoid-like adverse effects, including an increased risk for breast cancer in non-Turner syndrome populations and stroke in postmenopausal women.

    “However, although it primarily acts on the PR, it also acts on the GR giving rise to potential glucocorticoid-like adverse effects, not shared with natural progesterone, including an increased risk for breast cancer in non-TS populations and stroke in postmenopausal women.”

  • The paper relies on this without support.

    The levonorgestrel intra-uterine device (LNG-IUS 52) is licensed for endometrial protection and contraception, has minimal side effects, and lasts for 5 years.

    “The levonorgestrel intra-uterine device (LNG-IUS 52) is licensed for endometrial protection and contraception. It has minimal side effects and lasts for 5 years.”

  • The paper relies on this without support.

    A continuous combined regimen is designed to avoid withdrawal bleeding which may not be attractive to young women and may also give rise to erratic vaginal bleeding, especially in those women using transdermal preparations.

    “However, such a regimen is designed to avoid withdrawal bleeding which may not be attractive to young women and may also give rise to erratic vaginal bleeding, especially in those women using TD preparations.”

  • The paper relies on this without support.

    A continuous combined regimen gives rise to an atrophic endometrium, and it is unclear whether this is a disadvantage in the short- or medium-term in women planning an oocyte-donated pregnancy.

    “A continuous combined regimen gives rise to an atrophic endometrium, and it is unclear whether this is a disadvantage in the short- or medium-term in women planning an oocyte-donated pregnancy.”

  • The paper relies on this without support.

    It is important not to underdose progesterone as that leads to more abnormal uterine bleeding.

    “It is important not to underdose progesterone as that leads to more abnormal uterine bleeding.”

  • The paper relies on this without support.

    Progesterone is unnecessary until uterine growth and development is approaching maturity.

    “Progesterone is unnecessary until uterine growth and development is approaching maturity.”

  • The paper relies on this without support.

    In girls undergoing pubertal induction, progesterone will likely be needed after about 1.5-3 years of unopposed estrogen administration or after the first episode of vaginal bleeding.

    “In girls undergoing pubertal induction, it is likely that progesterone will be needed after about 1.5-3 years of unopposed estrogen administration or after the first episode of vaginal bleeding.”

  • The paper relies on this without support.

    This ensures maximum time for uterine and breast development with unopposed estrogen.

    “This ensures maximum time for uterine and breast development with unopposed estrogen.”

  • The paper relies on this without support.

    Initial vaginal bleeding may be spotting only from an immature endometrium and does not necessarily indicate timing to start progesterone.

    “Initial vaginal bleeding may be spotting only from an immature endometrium and does not necessarily indicate timing to start progesterone.”

  • The paper relies on this without support.

    There are very few good quality studies of progesterone/progestins in pubertal induction or hormone replacement therapy in adolescents and women with Turner syndrome.

    “There are very few good quality studies of progesterone/progestins in pubertal induction or HRT in adolescents and women with TS.”

  • The paper relies on this without support.

    Studies of premature ovarian insufficiency tend to include many subjects with Turner syndrome and so this approach has some credence.

    “In practice, studies of premature ovarian insufficiency tend to include many subjects with TS and so this approach has some credence.”

  • The paper relies on this without support.

    Studies and trials describing the adverse effects of hormone replacement therapy invariably involve post-menopausal women, and extrapolation of results to young women with Turner syndrome is much more dubious and results should be regarded with great caution.

    “Studies and trials describing the adverse effects of HRT invariably involve post-menopausal women. In these cases, extrapolation of results to young women with TS is much more dubious and results should be regarded with great caution.”

  • The paper relies on this without support.

    There are also very few studies addressing compliance with and acceptability of hormone replacement therapy medication.

    “There are also very few studies addressing compliance with and acceptability of HRT medication.”

  • The paper relies on this without support.

    Social deprivation was a key influence on the availability of hormone replacement therapy treatment options but the reasons for this inequity are not understood.

    “Social deprivation was a key influence on the availability of HRT treatment options but the reasons for this inequity are not understood.”

  • The paper relies on this without support.

    HRT may improve quality of life and avoid the effects of estrogen deprivation, including vasomotor symptoms, urogenital effects, low BMD with increased fracture risk, cardiovascular disease with increased ischemic heart disease and stroke risk, and possible neurocognitive effects.

    “HRT may also help to improve QoL and to avoid the effects of estrogen deprivation including vasomotor symptoms, urogenital effects, low BMD with increased risk of fracture, cardiovascular disease with increased risk of ischemic heart disease and stroke and, finally, possible neurocognitive effects.”

  • The paper relies on this without support.

    Patient involvement in decisions about care improves adherence.

    “The need for individualized HRT, taking full account of patient preference is crucially important and patient involvement in decisions about care are known to improve adherence.”

  • The paper relies on this without support.

    Fear of side effects and financial constraints are among the reasons women stop HRT, even when evidence is given regarding poorer outcome for those without treatment.

    “Fear of side effects and financial constraints are among the reasons, even when evidence is given regarding poorer outcome for those without treatment.”

  • The paper relies on this without support.

    Prenatal or neonatal TTE may not definitively exclude BAV, anomalous pulmonary venous return, or variant aortic arch anatomy.

    “Even in the most experienced hands, prenatal or neonatal TTE may not definitively exclude BAV, anomalous pulmonary venous return, or variant aortic arch anatomy.”

  • The paper relies on this without support.

    Ultrasound image resolution is insufficient to distinguish small fetal cardiac structures such as the morphology of the aortic valve.

    “Ultrasound image resolution is insufficient to distinguish small fetal cardiac structures such as the morphology of the aortic valve.”

  • The paper relies on this without support.

    Unique features of the fetal circulation due to fetal shunts make prenatal detection of aortic coarctation difficult on the fetal echocardiogram.

    “In addition, there are unique features of the fetal circulation due to fetal shunts, such as patent foramen ovale and ductus arteriosus, that make prenatal detection of aortic coarctation difficult on the fetal echocardiogram.”

  • The paper relies on this without support.

    Postnatal development of aortic coarctation can only be completely ruled out once ductal closure is completed, which typically happens by 2 to 3 days of age.

    “Postnatal development of aortic coarctation can only be completely ruled out once ductal closure is completed, which typically happens by 2 to 3 days of age.”

  • The paper relies on this without support.

    Many individuals with TS are significantly smaller than age and sex matched controls in the general population.

    “Many individuals with TS are significantly smaller than age and sex matched controls in the general population.”

  • The paper relies on this without support.

    Acoustic shadowing tends to be more pronounced in TS and may significantly limit the sensitivity of TTE to detect potentially outcome-determining lesions.

    “Acoustic shadowing tends to be more pronounced in TS and may significantly limit the sensitivity of TTE to detect potentially outcome-determining lesions.”

  • The paper relies on this without support.

    CMR is less widely available compared to TTE and requires more extensive patient cooperation.

    “However, CMR is less widely available compared to TTE and requires more extensive patient cooperation.”

  • The paper relies on this without support.

    CT provides anatomical information of comparable quality to CMR during a much more rapid acquisition.

    “CT provides anatomical information of comparable quality to CMR during a much more rapid acquisition.”

  • The paper relies on this without support.

    CT involves radiation exposure, which is increased when ECG gating is used to obtain accurate aortic measurements.

    “However, CT involves radiation exposure, which is increased when ECG gating is used to obtain accurate aortic measurements.”

  • The paper relies on this without support.

    Hypertension can persist after coarctation repair, even in those without residual descending aortic pressure gradients.

    “Hypertension can persist after coarctation repair, even in those without residual descending aortic pressure gradients.”

  • The paper relies on this without support.

    Diagnosis of nocturnal hypertension can only be made by ambulatory blood pressure monitoring.

    “Diagnosis of nocturnal hypertension can only be made by ABPM.”

  • The paper relies on this without support.

    Outcome data about venous thrombosis are rare in TS, and a common underlying cause of thrombotic events has not yet been identified.

    “Outcome data about venous thrombosis are rare in TS, and a common underlying cause of thrombotic events has not yet been identified.”

  • The paper relies on this without support.

    There is no international consensus on when to begin lipid monitoring in individuals with TS.

    “There is no international consensus on when to begin lipid monitoring in individuals with TS.”

  • The paper relies on this without support.

    Newer research suggests that QTc prolongation may not be more prevalent among individuals with TS compared to the general population when defining prolongation as QTc >450 ms in girls and >460 ms in women using Hodges formula.

    “Newer research that was published after the 2016 guidelines suggests that QTc prolongation may not be more prevalent among individuals with TS compared to the general population when defining prolongation as QTc >450 ms in girls and >460 ms in women using Hodges formula.”

  • The paper relies on this without support.

    The risk of aortic dissection in TS is about 40:100 000 patient–years.

    “the low risk of aortic dissection in TS (about 40:100 000 patient–years)”

  • The paper relies on this without support.

    Cardiovascular demands of pregnancy are high due to increased cardiac output, stroke volume, heart rate, and plasma volume.

    “Cardiovascular demands of pregnancy are high due to increased cardiac output, stroke volume, heart rate, and plasma volume.”

  • The paper relies on this without support.

    After proximal aortic repair, women with TS are still considered to be at high risk for aortic dissections.

    “After proximal aortic repair, women with TS are still considered to be at high risk for aortic dissections.”

  • The paper relies on this without support.

    Beta-blockers do not cause fetal abnormalities.

    “Beta-blockers may be considered during pregnancy for women with aortic dilation (extrapolated from data for women with Marfan syndrome) and do not cause fetal abnormalities.”

  • The paper relies on this without support.

    Aortic dissection during pregnancy is a life-threatening complication that requires emergent cardiovascular specialist care.

    “Aortic dissection during pregnancy is a life-threatening complication that requires emergent cardiovascular specialist care.”

  • The paper relies on this without support.

    The maternal deaths reported in TS have been in oocyte donation pregnancies when IVF practitioners were unaware of TS implications.

    “The maternal deaths reported in TS have been in oocyte donation pregnancies when IVF practitioners were unaware of TS implications.”

  • The paper relies on this without support.

    There is a higher risk of complications, particularly cardiovascular complications, during pregnancy in individuals with TS.

    “Single embryo transfer is strongly recommended because of the higher risk of complications, particularly cardio-vascular complications during pregnancy.”
73 of 73

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Tenfold discrepancy in starting oral estradiol dose

    Major

    Table 4 gives the first-year oral E2 dose as 0.025 mg daily, while the practical guidelines summary recommends 0.25 mg daily as the starting dose.

  • Conflicting annual aortic dissection rates

    Major

    The cardiovascular section reports approximately 164 aortic dissections per 100,000 person-years in TS, but later describes the risk as about 40 per 100,000 patient-years. These are fourfold different rates for essentially the same time denominator.

  • Aortic size index has conflicting units

    Minor

    Table 13 labels ASI in cm per metre, whereas Table 12 defines it as aortic diameter in centimetres divided by body surface area in square metres.

  • Same cited guidelines assigned different years

    Minor

    The paper calls reference 1 the 2017 TS guidelines in one passage but the 2007 TS guidelines in another.

4 of 4

Citations

Cites

Items 801–919 of 919

Flagged first, then by citations

77 of the 996 references couldn’t be matched to a known paper.

Research works printed but not linked: 1

  1. Kollmann, 2016, Turner Syndrome: Growth Promoting Therapies, 201

Cited by

Sorted by citations

See all 224

Related

See all

Metadata

Authors
Gravholt, C. H., Andersen, N. H., Christin-Maitre, S., Davis, S. M., Duijnhouwer, A., Gawlik, A., Maciel-Guerra, A. T., Gutmark-Little, I., Fleischer, K., Hong, D., Klein, K. O., Prakash, S. K., Shankar, R. K., Sandberg, D. E., Sas, T. C. J., Skakkebæk, A., Stochholm, K., van der Velden, J. A., The International Turner Syndrome Consensus Group, Alvarez-Nava, F., Avdic, H. B., Balle, C. M., Bamba, V., Bedei, I., Bonnard, Å., Brickman, W. J., Brown, N. M., Chernausek, S., Cobbold, J., Corathers, S. D., Corpechot, C., Crenshaw, M. L., Davies, M., Deeb, A., Dessens, A., Dowlut-McElroy, T., Elliott, V., Fadoju, D., Fechner, P. Y., Geffner, M., Gitomer, S., de Groote, K., Hewitt, J., Ho, C., Hutaff-Lee, C., Isojima, T., Johannsen, E. B., Kawai, M., Keselman, A., Knickmeyer, R. C., Kremen, J., Kristrøm, B., Kruszka, P., Law, J., Lin, A. E., Loechner, K., Mauras, N., Matthews, D., Mikkelborg, T., Mortensen, K. H., Nahata, L., Norman, M., Patel, S. R., Quigley, C., Ridder, L. O., Santen, R. J., Sheanon, N., Smyth, A., Turner, H., Verlinde, F., Viuff, M. H., Wasniewska, M., van der Weijde, B., Woelfle, J., Wolstencroft, J., & Backeljauw, P. F.
Affiliations
  • Aarhus University (DK)
  • Aalborg University Hospital (DK)
  • Endocrine and Reproductive Medicine Unit, Center of Rare Endocrine Diseases of Growth and Development (CMERCD), FIRENDO, Endo ERN Hôpital Saint-Antoine, Sorbonne University, Assistance Publique-Hôpitaux de Paris , 75012 Paris , France
  • Children's Hospital Colorado (US)
  • Radboud University Medical Center (NL)
  • Medical University of Silesia (PL)
  • Area of Medical Genetics, Department of Translational Medicine, School of Medical Sciences, State University of Campinas , 13083-888 São Paulo , Brazil
  • Cincinnati Children's Hospital Medical Center, University of Cincinnati , Cincinnati, Ohio 45229 , United States
  • Department of Reproductive Medicine, Nij Geertgen Center for Fertility , Ripseweg 9, 5424 SM Elsendorp , The Netherlands
  • Stanford Medicine (US)
  • University of California San Diego (US)
  • The University of Texas Health Science Center at Houston (US)
  • Children's National (US)
  • University of Michigan (US)
  • Erasmus MC - Sophia Children’s Hospital (NL)
  • Department of Molecular Medicine, Aarhus University Hospital , 8200 Aarhus N , Denmark
  • Aarhus University Hospital (DK)
  • Department of Pediatric Endocrinology, Radboud University Medical Center, Amalia Children's Hospital , Nijmegen 6500 HB , The Netherlands
  • Central University of Ecuador (EC)
  • Cincinnati Children's Hospital Medical Center (US)
  • Khalifa University of Science and Technology (AE)
  • Children's Hospital of Philadelphia (US)
Corresponding author
  • Gravholt, Claus H
  • Backeljauw, Philippe F
ORCID
Venue
European Journal of Endocrinology
Publisher
Oxford University Press (OUP)
Published
2024-05-15
Volume
190
Issue
6
Pages
G53-G151
ISSN
  • 0804-4643 (ISSN-L)
  • 1479-683X
DOI
10.1093/ejendo/lvae050
PMC
PMC11759048
OpenAlex
W4396917273
Semantic Scholar
e69326a3dc0e3e1921efaf0f59e074d22ba2fc21
Cited by
224
References
996
Citations by year
2026: 87 · 2025: 111 · 2024: 25
FWCI
59.18
Type
journal article
Language
en
Open access
Licence
Locations
  • European Journal of Endocrinology (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • EUR Research Repository (Erasmus University Rotterdam) (publishedVersion, cc-by-nc)
  • HAL (submittedVersion, cc-by-nc)
  • Ghent University Academic Bibliography (Ghent University) (submittedVersion, cc-by-nc)
  • Radboud Repository (Radboud University) (submittedVersion)
  • Digital Commons-TMC (Texas Medical Center) (submittedVersion)
  • VBN Forskningsportal (Aalborg Universitet) (submittedVersion, cc-by-nc)
Funders
  • Novo Nordisk Foundation (NNF15OC0016474, NNF20OC0060610, 2022–0189)
  • Independent Research Fund Denmark (0134-00406, 0134-00130B)
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01 HD093450)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Sexual Differentiation and Disorders
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Adolescent and Pediatric Healthcare
Keywords
Turner syndrome, women and girls, multidisciplinary care, growth, puberty, estrogen therapy, cardiovascular health, transition to adult care, fertility assessment, comorbidities, health surveillance, neurocognitive function, neuropsychology, mental health, well-being
MeSH terms
Adolescent, Adult, Child, Europe, Female, Humans, Puberty, Turner Syndrome, Practice Guidelines as Topic

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

A language model drew the claims from the paper on 2026-10-07, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).

A second model labelled each claim on 2026-10-07 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review