Management of Turner syndrome
- Philippe Backeljauw, MD
Philippe Backeljauw, MD
- Professor of Clinical Pediatrics
- Director, Pediatric Endocrinology Fellowship Program
- Center for Pediatric & Adult Turner Syndrome Care
- Cincinnati Children’s Hospital Medical Center
- Section Editors
- Peter J Snyder, MD
Peter J Snyder, MD
- Editor-in-Chief — Endocrinology
- Section Editor — Pituitary Disease; Male Reproductive Endocrinology
- Professor of Medicine
- University of Pennsylvania School of Medicine
- Mitchell Geffner, MD
Mitchell Geffner, MD
- Section Editor — Pediatric Endocrinology
- Professor of Pediatrics
- Keck School of Medicine, University of Southern California
- Deputy Editors
- Kathryn A Martin, MD
Kathryn A Martin, MD
- Senior Deputy Editor — UpToDate
- Deputy Editor — Endocrinology and Patient Education
- Assistant Professor of Medicine
- Harvard Medical School
- Alison G Hoppin, MD
Alison G Hoppin, MD
- Deputy Editor — Pediatrics
- Assistant Professor of Pediatrics, part time
- Harvard Medical School
Turner syndrome is an important cause of short stature in girls and primary amenorrhea in adolescents and young women, and is caused by loss of part or all of an X chromosome .
This topic will review the treatment of patients with this disorder. Management varies with the age of the patient and includes therapy for the short stature and estrogen deficiency, as well as identifying and managing the associated congenital anomalies and related complications (table 1) . The clinical manifestations and diagnosis of Turner syndrome are reviewed separately. (See "Clinical manifestations and diagnosis of Turner syndrome".)
Cases of Turner syndrome are sometimes discovered incidentally during chorionic-villus sampling or amniocentesis performed for unrelated reasons, such as advanced maternal age or for suspicion about congenital anomalies noted on fetal ultrasonography. Ultrasonography may show increased nuchal translucency, which is a good marker for fetal chromosomal defects . As an example, if a fetus with hydrops or a large cystic hygroma is found to have a 45,X karyotype, the diagnosis of Turner syndrome can be made with a high degree of certainty. The chance for spontaneous abortion will also be quite high.
The parents should receive detailed genetic counseling. Parents sometimes consider elective termination of the pregnancy, often prompted by their review of information that is available on the internet. However, prenatal counseling is challenging because it is difficult to predict the phenotype of girls with incidentally diagnosed Turner syndrome. Retrospective studies suggest that these girls, and particularly those with 45,X/46,XX mosaicism , may have a milder phenotype than those diagnosed on the basis of clinical suspicion [4,5], but more prospective studies confirming these results are necessary. It is important that some of the counseling be provided by health care professionals with direct experience caring for Turner syndrome patients throughout childhood and adolescence; these are often pediatric endocrinologists. Such physicians are best suited to answer questions about available treatments and prognosis related to the Turner syndrome comorbidities. (See "Sonographic findings associated with fetal aneuploidy", section on 'Turner syndrome'.).
INFANTS AND CHILDREN
Disclosure of diagnosis — Many patients report that their Turner syndrome diagnosis or other important information was inappropriately withheld from them. In a study conducted in the United States, about one third of patients with Turner syndrome reported that their families or health care providers had withheld all or part of the Turner syndrome diagnosis . In addition, several patients were not informed of the infertility associated with the diagnosis. How the diagnosis is shared with the patients may result in a negative disclosure experience. We encourage helping parents disclose diagnostic and other health-related information in a timely, caring, and age-appropriate manner. This is of great importance to the overall mental and physical health of the patient.
- Saenger P. Turner's syndrome. N Engl J Med 1996; 335:1749.
- Ostberg JE, Conway GS. Adulthood in women with Turner syndrome. Horm Res 2003; 59:211.
- Taipale P, Hiilesmaa V, Salonen R, Ylöstalo P. Increased nuchal translucency as a marker for fetal chromosomal defects. N Engl J Med 1997; 337:1654.
- Koeberl DD, McGillivray B, Sybert VP. Prenatal diagnosis of 45,X/46,XX mosaicism and 45,X: implications for postnatal outcome. Am J Hum Genet 1995; 57:661.
- Gunther DF, Eugster E, Zagar AJ, et al. Ascertainment bias in Turner syndrome: new insights from girls who were diagnosed incidentally in prenatal life. Pediatrics 2004; 114:640.
- Sutton EJ, Young J, McInerney-Leo A, et al. Truth-telling and Turner Syndrome: the importance of diagnostic disclosure. J Pediatr 2006; 148:102.
- Bondy CA, Turner Syndrome Study Group. Care of girls and women with Turner syndrome: a guideline of the Turner Syndrome Study Group. J Clin Endocrinol Metab 2007; 92:10.
- Naeraa RW, Gravholt CH, Hansen J, et al. Mortality in Turner syndrome. In: Turner syndrome in a life span perspective: Research and clinical aspects, Albertsson-Wikland K, Ranke MB (Eds), Elsevier, Amsterdam 1995. p.323.
- Wilson W, Taubert KA, Gewitz M, et al. Prevention of infective endocarditis: guidelines from the American Heart Association: a guideline from the American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee, Council on Cardiovascular Disease in the Young, and the Council on Clinical Cardiology, Council on Cardiovascular Surgery and Anesthesia, and the Quality of Care and Outcomes Research Interdisciplinary Working Group. Circulation 2007; 116:1736.
- De Groote K, Demulier L, De Backer J, et al. Arterial hypertension in Turner syndrome: a review of the literature and a practical approach for diagnosis and treatment. J Hypertens 2015; 33:1342.
- Bender B, Puck M, Salbenblatt J, Robinson A. Cognitive development of unselected girls with complete and partial X monosomy. Pediatrics 1984; 73:175.
- Davenport ML, Roush J, Liu C, et al. Growth hormone treatment does not affect incidences of middle ear disease or hearing loss in infants and toddlers with Turner syndrome. Horm Res Paediatr 2010; 74:23.
- Binder G, Koch A, Wajs E, Ranke MB. Nested polymerase chain reaction study of 53 cases with Turner's syndrome: is cytogenetically undetected Y mosaicism common? J Clin Endocrinol Metab 1995; 80:3532.
- Navot D, Laufer N, Kopolovic J, et al. Artificially induced endometrial cycles and establishment of pregnancies in the absence of ovaries. N Engl J Med 1986; 314:806.
- Elsheikh M, Wass JA, Conway GS. Autoimmune thyroid syndrome in women with Turner's syndrome--the association with karyotype. Clin Endocrinol (Oxf) 2001; 55:223.
- Ranke MB, Pflüger H, Rosendahl W, et al. Turner syndrome: spontaneous growth in 150 cases and review of the literature. Eur J Pediatr 1983; 141:81.
- Brook CG, Mürset G, Zachmann M, Prader A. Growth in children with 45,XO Turner's syndrome. Arch Dis Child 1974; 49:789.
- Davenport ML, Crowe BJ, Travers SH, et al. Growth hormone treatment of early growth failure in toddlers with Turner syndrome: a randomized, controlled, multicenter trial. J Clin Endocrinol Metab 2007; 92:3406.
- Schrier L, de Kam ML, McKinnon R, et al. Comparison of body surface area versus weight-based growth hormone dosing for girls with Turner syndrome. Horm Res Paediatr 2014; 81:319.
- Sas TC, de Muinck Keizer-Schrama SM, Stijnen T, et al. Normalization of height in girls with Turner syndrome after long-term growth hormone treatment: results of a randomized dose-response trial. J Clin Endocrinol Metab 1999; 84:4607.
- van Pareren YK, de Muinck Keizer-Schrama SM, Stijnen T, et al. Final height in girls with turner syndrome after long-term growth hormone treatment in three dosages and low dose estrogens. J Clin Endocrinol Metab 2003; 88:1119.
- Reiter EO, Blethen SL, Baptista J, Price L. Early initiation of growth hormone treatment allows age-appropriate estrogen use in Turner's syndrome. J Clin Endocrinol Metab 2001; 86:1936.
- Ross JL, Quigley CA, Cao D, et al. Growth hormone plus childhood low-dose estrogen in Turner's syndrome. N Engl J Med 2011; 364:1230.
- Saenger P. Growth-promoting strategies in Turner's syndrome. J Clin Endocrinol Metab 1999; 84:4345.
- Quigley CA, Wan X, Garg S, et al. Effects of low-dose estrogen replacement during childhood on pubertal development and gonadotropin concentrations in patients with Turner syndrome: results of a randomized, double-blind, placebo-controlled clinical trial. J Clin Endocrinol Metab 2014; 99:E1754.
- Ari M, Bakalov VK, Hill S, Bondy CA. The effects of growth hormone treatment on bone mineral density and body composition in girls with turner syndrome. J Clin Endocrinol Metab 2006; 91:4302.
- Sas TC, Cromme-Dijkhuis AH, de Muinck Keizer-Schrama SM, et al. The effects of long-term growth hormone treatment on cardiac left ventricular dimensions and blood pressure in girls with Turner's syndrome. Dutch Working Group on Growth Hormone. J Pediatr 1999; 135:470.
- Bondy CA, Van PL, Bakalov VK, Ho VB. Growth hormone treatment and aortic dimensions in Turner syndrome. J Clin Endocrinol Metab 2006; 91:1785.
- Matura LA, Sachdev V, Bakalov VK, et al. Growth hormone treatment and left ventricular dimensions in Turner syndrome. J Pediatr 2007; 150:587.
- Bolar K, Hoffman AR, Maneatis T, Lippe B. Long-term safety of recombinant human growth hormone in turner syndrome. J Clin Endocrinol Metab 2008; 93:344.
- Gault EJ, Perry RJ, Cole TJ, et al. Effect of oxandrolone and timing of pubertal induction on final height in Turner's syndrome: randomised, double blind, placebo controlled trial. BMJ 2011; 342:d1980.
- Nilsson KO, Albertsson-Wikland K, Alm J, et al. Improved final height in girls with Turner's syndrome treated with growth hormone and oxandrolone. J Clin Endocrinol Metab 1996; 81:635.
- Rosenfeld RG, Attie KM, Frane J, et al. Growth hormone therapy of Turner's syndrome: beneficial effect on adult height. J Pediatr 1998; 132:319.
- Sheanon NM, Backeljauw PF. Effect of oxandrolone therapy on adult height in Turner syndrome patients treated with growth hormone: a meta-analysis. Int J Pediatr Endocrinol 2015; 2015:18.
- Lunding SA, Aksglaede L, Anderson RA, et al. AMH as Predictor of Premature Ovarian Insufficiency: A Longitudinal Study of 120 Turner Syndrome Patients. J Clin Endocrinol Metab 2015; 100:E1030.
- Visser JA, Hokken-Koelega AC, Zandwijken GR, et al. Anti-Müllerian hormone levels in girls and adolescents with Turner syndrome are related to karyotype, pubertal development and growth hormone treatment. Hum Reprod 2013; 28:1899.
- Fechner PY, Davenport ML, Qualy RL, et al. Differences in follicle-stimulating hormone secretion between 45,X monosomy Turner syndrome and 45,X/46,XX mosaicism are evident at an early age. J Clin Endocrinol Metab 2006; 91:4896.
- Hagen CP, Main KM, Kjaergaard S, Juul A. FSH, LH, inhibin B and estradiol levels in Turner syndrome depend on age and karyotype: longitudinal study of 70 Turner girls with or without spontaneous puberty. Hum Reprod 2010; 25:3134.
- Pasquino AM, Passeri F, Pucarelli I, et al. Spontaneous pubertal development in Turner's syndrome. Italian Study Group for Turner's Syndrome. J Clin Endocrinol Metab 1997; 82:1810.
- Torres-Santiago L, Mericq V, Taboada M, et al. Metabolic effects of oral versus transdermal 17β-estradiol (E₂): a randomized clinical trial in girls with Turner syndrome. J Clin Endocrinol Metab 2013; 98:2716.
- Mauras N, Torres-Santiago L, Taboada M, Santen R. Estrogen therapy in Turner syndrome: does the type, dose and mode of delivery matter? Pediatr Endocrinol Rev 2012; 9 Suppl 2:718.
- Neely EK, Marcus R, Rosenfeld RG, Bachrach LK. Turner syndrome adolescents receiving growth hormone are not osteopenic. J Clin Endocrinol Metab 1993; 76:861.
- Conway GS, et al. Adult Turner follow-up: The middlesex experience. In: Optimizing health care for Turner patients in the 21st century, Saenger P, Parquino AM (Eds), Elsevier, Amsterdam 2000. p.295.
- Ostberg JE, Donald AE, Halcox JP, et al. Vasculopathy in Turner syndrome: arterial dilatation and intimal thickening without endothelial dysfunction. J Clin Endocrinol Metab 2005; 90:5161.
- Gravholt CH, Naeraa RW, Nyholm B, et al. Glucose metabolism, lipid metabolism, and cardiovascular risk factors in adult Turner's syndrome. The impact of sex hormone replacement. Diabetes Care 1998; 21:1062.
- Elsheikh M, Hodgson HJ, Wass JA, Conway GS. Hormone replacement therapy may improve hepatic function in women with Turner's syndrome. Clin Endocrinol (Oxf) 2001; 55:227.
- Ross JL, Reiss A, Freund L, et al. Estrogen effects on cognition and social function in Turner syndrome. In: Basic and clinical approach to Turner syndrome, Hibi I, Takano K (Eds), Excerpta Medica, Amsterdam 1993. p.215.
- Ross JL, Roeltgen D, Feuillan P, et al. Use of estrogen in young girls with Turner syndrome: effects on memory. Neurology 2000; 54:164.
- Ross JL, Roeltgen D, Feuillan P, et al. Effects of estrogen on nonverbal processing speed and motor function in girls with Turner's syndrome. J Clin Endocrinol Metab 1998; 83:3198.
- Ross JL, Roeltgen D, Stefanatos GA, et al. Androgen-responsive aspects of cognition in girls with Turner syndrome. J Clin Endocrinol Metab 2003; 88:292.
- Ross JL, Mazzocco MM, Kushner H, et al. Effects of treatment with oxandrolone for 4 years on the frequency of severe arithmetic learning disability in girls with Turner syndrome. J Pediatr 2009; 155:714.
- Oktay K, Bedoschi G. Oocyte cryopreservation for fertility preservation in postpubertal female children at risk for premature ovarian failure due to accelerated follicle loss in Turner syndrome or cancer treatments. J Pediatr Adolesc Gynecol 2014; 27:342.
- Hreinsson JG, Otala M, Fridström M, et al. Follicles are found in the ovaries of adolescent girls with Turner's syndrome. J Clin Endocrinol Metab 2002; 87:3618.
- Devernay M, Ecosse E, Coste J, Carel JC. Determinants of medical care for young women with Turner syndrome. J Clin Endocrinol Metab 2009; 94:3408.
- Gawlik A, Kaczor B, Kaminska H, et al. Quality of medical follow-up of young women with Turner syndrome treated in one clinical center. Horm Res Paediatr 2012; 77:222.
- Lucaccioni L, Wong SC, Smyth A, et al. Turner syndrome--issues to consider for transition to adulthood. Br Med Bull 2015; 113:45.
- Endocrine Society Transitions of Care for Turner syndrome. Available at: http://www.endocrinetransitions.org/turner-syndrome/ (Accessed on August 29, 2016).
- Trolle C, Mortensen KH, Hjerrild BE, et al. Clinical care of adult Turner syndrome--new aspects. Pediatr Endocrinol Rev 2012; 9 Suppl 2:739.
- Saenger P, Wikland KA, Conway GS, et al. Recommendations for the diagnosis and management of Turner syndrome. J Clin Endocrinol Metab 2001; 86:3061.
- Ranke MB, Saenger P. Turner's syndrome. Lancet 2001; 358:309.
- Hiratzka LF, Bakris GL, Beckman JA, et al. 2010 ACCF/AHA/AATS/ACR/ASA/SCA/SCAI/SIR/STS/SVM guidelines for the diagnosis and management of patients with Thoracic Aortic Disease: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, American Association for Thoracic Surgery, American College of Radiology, American Stroke Association, Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, Society of Interventional Radiology, Society of Thoracic Surgeons, and Society for Vascular Medicine. Circulation 2010; 121:e266.
- Wilson W, Taubert KA, Gewitz M, et al. Prevention of Infective Endocarditis. Guidelines From the American Heart Association. A Guideline From the American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee, Council on Cardiovascular Disease in the Young, and the Council on Clinical Cardiology, Council on Cardiovascular Surgery and Anesthesia, and the Quality of Care and Outcomes Research Interdisciplinary Working Group. Circulation 2007; 115 published online April 19, 2007. www.circ.ahajournals.org/cgi/reprint/CIRCULATIONAHA.106.183095v1 (Accessed on May 04, 2007).
- Hultcrantz M, Sylvén L. Turner's syndrome and hearing disorders in women aged 16-34. Hear Res 1997; 103:69.
- Lage AZ, Brandão CA, Mendes JR, et al. High degree of discordance between three-dimensional and two-dimensional lumbar spine bone mineral density in Turner's syndrome. J Clin Densitom 2005; 8:461.
- Bakalov VK, Bondy CA. Fracture risk and bone mineral density in Turner syndrome. Rev Endocr Metab Disord 2008; 9:145.
- Bösze P, Tóth A, Török M. Hormone replacement and the risk of breast cancer in Turner's syndrome. N Engl J Med 2006; 355:2599.
- Kaneko N, Kawagoe S, Hiroi M. Turner's syndrome--review of the literature with reference to a successful pregnancy outcome. Gynecol Obstet Invest 1990; 29:81.
- Bernard V, Donadille B, Zenaty D, et al. Spontaneous fertility and pregnancy outcomes amongst 480 women with Turner syndrome. Hum Reprod 2016; 31:782.
- Press F, Shapiro HM, Cowell CA, Oliver GD. Outcome of ovum donation in Turner's syndrome patients. Fertil Steril 1995; 64:995.
- Yaron Y, Ochshorn Y, Amit A, et al. Patients with Turner's syndrome may have an inherent endometrial abnormality affecting receptivity in oocyte donation. Fertil Steril 1996; 65:1249.
- Foudila T, Söderström-Anttila V, Hovatta O. Turner's syndrome and pregnancies after oocyte donation. Hum Reprod 1999; 14:532.
- Bodri D, Vernaeve V, Figueras F, et al. Oocyte donation in patients with Turner's syndrome: a successful technique but with an accompanying high risk of hypertensive disorders during pregnancy. Hum Reprod 2006; 21:829.
- Karnis MF, Zimon AE, Lalwani SI, et al. Risk of death in pregnancy achieved through oocyte donation in patients with Turner syndrome: a national survey. Fertil Steril 2003; 80:498.
- Practice Committee of the American Society for Reproductive Medicine. Increased maternal cardiovascular mortality associated with pregnancy in women with Turner syndrome. Fertil Steril 2006; 86:S127.
- Practice Committee of American Society For Reproductive Medicine. Increased maternal cardiovascular mortality associated with pregnancy in women with Turner syndrome. Fertil Steril 2012; 97:282.
- Stochholm K, Juul S, Juel K, et al. Prevalence, incidence, diagnostic delay, and mortality in Turner syndrome. J Clin Endocrinol Metab 2006; 91:3897.
- Schoemaker MJ, Swerdlow AJ, Higgins CD, et al. Mortality in women with turner syndrome in Great Britain: a national cohort study. J Clin Endocrinol Metab 2008; 93:4735.
- Hanton L, Axelrod L, Bakalov V, Bondy CA. The importance of estrogen replacement in young women with Turner syndrome. J Womens Health (Larchmt) 2003; 12:971.
- PRENATAL MANAGEMENT
- INFANTS AND CHILDREN
- Disclosure of diagnosis
- Monitoring and managing comorbidities
- - Cardiovascular anomalies
- - Hypertension
- - Cognitive function and learning disabilities
- - Tympanometry and audiology
- - Scoliosis and kyphosis
- - Cancer risk
- - Other issues
- Management of short stature
- - Growth hormone therapy
- - Growth hormone therapy plus oxandrolone
- Management of ovarian failure
- - Estrogen therapy
- Dose and timing
- Route of administration
- Adjunctive progestins
- Benefits of hormonal therapy
- - Cryopreservation of ovarian tissue
- Transition to adult care
- Ongoing monitoring
- - Cardiovascular monitoring
- - Audiology testing
- - Bone densitometry
- - Routine laboratory testing
- Estrogen therapy in adulthood
- - Duration
- - Safety
- Management of fertility and pregnancy
- - IVF with donor oocytes
- Aortic dissection
- RESOURCES AND INFORMATION
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS