Clinical practice guidelines for the care of girls and women with Turner syndrome: proceedings from the 2016 Cincinnati International Turner Syndrome Meeting

Abstract

Turner syndrome affects 25-50 per 100,000 females and can involve multiple organs through all stages of life, necessitating multidisciplinary approach to care. Previous guidelines have highlighted this, but numerous important advances have been noted recently. These advances cover all specialty fields involved in the care of girls and women with TS. This paper is based on an international effort that started with exploratory meetings in 2014 in both Europe and the USA, and culminated with a Consensus Meeting held in Cincinnati, Ohio, USA in July 2016. Prior to this meeting, five groups each addressed important areas in TS care: 1) diagnostic and genetic issues, 2) growth and development during childhood and adolescence, 3) congenital and acquired cardiovascular disease, 4) transition and adult care, and 5) other comorbidities and neurocognitive issues. These groups produced proposals for the present guidelines. Additionally, four pertinent questions were submitted for formal GRADE (Grading of Recommendations, Assessment, Development and Evaluation) evaluation with a separate systematic review of the literature. These four questions related to the efficacy and most optimal treatment of short stature, infertility, hypertension, and hormonal replacement therapy. The guidelines project was initiated by the European Society of Endocrinology and the Pediatric Endocrine Society, in collaboration with the European Society for Paediatric Endocrinology, the Endocrine Society, the European Society of Human Reproduction and Embryology, the American Heart Association, the Society for Endocrinology, and the European Society of Cardiology. The guideline has been formally endorsed by the European Society of Endocrinology, the Pediatric Endocrine Society, the European Society for Paediatric Endocrinology, the European Society of Human Reproduction and Embryology and Summary of recommendationsThe recommendations (R) are worded as recommend (strong recommendation) and suggest (weak recommendation). We formally graded only the evidence underlying recommendations for therapeutic choices. The quality of evidence behind the recommendations is classified as very low (⨁◯◯◯), low (⨁⨁◯◯), moderate (⨁⨁⨁◯) and strong (⨁⨁⨁⨁). See further section 'Summary of methods used for guideline development'. Diagnosis and geneticsR 1.1. We recommend considering a diagnosis of TS in phenotypic females with a karyotype containing one X chromosome and complete or partial absence of the second sex chromosome, associated with one or more typical clinical manifestations of TS (⨁⨁⨁⨁). R 1.2. We recommend against considering a diagnosis of TS in females with one X chromosome and a deletion distal to Xq24 on the other X chromosome, and in women over the age of 50 years with less than 5% 45,X mosaicism (⨁⨁◯◯). R 1.3. We suggest that the new general surveillance management guideline applies to TS patients with any karyotype (⨁⨁◯◯). R 1.4. We recommend to consider testing for Turner syndrome (TS) in a female with typical signs (Table 2) (⨁⨁⨁⨁). R 1.5. We ...

Optimal Pubertal Induction in Girls with Turner Syndrome Using Either Oral or Transdermal Estradiol: A Proposed Modern Strategy

“…TSWG agreed that initiation of treatment should normally begin at between 11 and 12 years, consistent with the Cincinnati and UK guidelines [12, 13], to mimic normal puberty and facilitate positive psychosocial and psychosexual adaptation in girls with evidence of POI. A serum FSH cut-off of ≥10 IU/L at 10 or more years of age was considered a reasonable indicator of ovarian impairment requiring pubertal induction in girls with TS.…”

“…Although choice will depend partly on the availability of the recommended transdermal or oral 17β-estradiol preparations, it was felt that clinicians are entitled to request appropriate, guideline-compliant treatment from their hospitals and pharmacies [12, 13]. In the event of a family choosing either of the proposed regimens, written informed consent would be requested by the clinician for data before, during and after pubertal induction to be sent to a designated European centre and entered into an independent ESPE-approved database under the supervision of an ESPE TSWG member trained in Good Clinical Practice.…”

“…Recommended oral progestogens were dydrogesterone (9β,10α-pregna-4,6-diene-3,20-dione) 10 mg; micronised progesterone 100 mg; and medroxyprogesterone acetate 5–10 mg [13]. In keeping with the Cincinnati guidelines [12] a duration of 10 days each calendar month was proposed.…”

“…In contrast to the Cincinnati guidelines [12], advice from gynaecology and reproductive endocrine colleagues indicated that oral progesterone should not be given pre-emptively after 2 years, or automatically at the time of the first breakthrough bleed. Instead, to allow maximum time for uterine and breast development with unopposed estrogen, it was recommended that pubertal staging and where possible pelvic ultrasound examination should be carried out at the time of bleeding so that uterine size and endometrial thickness could be determined.…”

“…The European Society of Human Reproduction and Embryology has developed clinical practice guidelines for the management of women with POI [11]. Clinical practice guidelines for the care of girls and women with TS were published after the International TS Meeting in Cincinnati [12]. Matthews et al [13] from the United Kingdom have described a consensus from the British Society for Paediatric Endocrinology and Diabetes on hormone supplementation for pubertal induction in girls.…”