7 Turner Syndrome

Suggested citation:  Endocrine Society. Endocrine Facts and Figures: Reproduction and Development. First Edition. 2017


Turner Syndrome (TS) occurs in one in 2,500 live-born females and is defined as the loss of all or part of the X sex chromosome 183.

Roughly half of individuals with TS are of the 45,X karyotype, and do not have the full complement of 46 chromosomes. The other half can have other genetic alterations, including ring X-chromosome formations, deletions along the short or long arm of the X chromosome, or mosaic cell lines comprised of 45,X cells and various combinations of 46,XX, 47,XXX, or other karyotypes. Some individuals have cell lines with Y chromosome material 184.

These chromosomal abnormalities are thought to occur because of the nondisjunction of sex chromosomes during the process of meiosis or during early post-zygotic stages of embryonic development 184.

Girls with TS usually experience ovarian failure, which can occur prior to puberty. This results in decreased sex hormone production and can directly affect neurodevelopment 184.


There is higher morbidity and mortality seen in TS versus the non-TS population 183. Some studies suggest that early medical intervention may decrease this higher risk of morbidity and mortality and improve the quality of life of women with TS 185-188. However, other data indicate that current treatments and detection have little impact on the high morbidity and mortality rates associated with TS, leading to controversy regarding how to best manage several aspects of the disease 183.

Women with TS also display a higher susceptibility to hypertension and stroke, autoimmune thyroiditis, ischemic heart disease, renal and gastrointestinal disease, auditory problems, osteoporosis, and fractures 185,186,188.

A multidisciplinary team of physicians with an interest in the disorder should follow up with all women diagnosed with TS following discharge from pediatric care 185,186,188.


Features associated with TS (and to what extent they are visible) relate to an individual’s specific karyotype and can vary among those with TS 184.

However, common features can include: gastrointestinal issues, diabetes, webbed neck, short stature, hearing loss, lymphedema, POF/POI, hypothyroidism, renal abnormalities, orthopedic disorders, and structural cardiac abnormalities 184.

There are many areas of uncertainty regarding the diagnosis and management of TS. However, clinicians routinely use detailed healthcare checklists and screening guidelines to detect known complications associated with TS 183.

 Table 22. Screening at diagnosis in children and adults with Turner syndrome.
All patients
    Hearing evaluation by an audiologist
    Cardiovascular evaluation by specialist
    TS knowledge evaluation; referral to support groups
    Renal ultrasound
    Scoliosis/kyphosis evaluation
    Growth and pubertal development evaluation
Ages 0–4 year
    Hip dislocation evaluation
    Eye exam by pediatric ophthalmologist (if age ≥ 1)
Ages 4–10 year
    Orthodontic evaluation (if age ≥ 7)
    Thyroid function tests (T4, TSH) and celiac screen (TTG Ab)
    Educational/psychosocial evaluations
Age >10
    Orthodontic evaluation
    Thyroid function tests (T4, TSH) and celiac screen (TTG Ab)
    Educational and psychosocial evaluations
    BMD (if age ≥ 18 year)
    Evaluation of ovarian function/estrogen replacement
    LFTs, FBG, lipids, CBC, Cr, BUN
Abbreviations: BUN, Blood urea nitrogen; CBC, complete blood count; Cr, creatinine; FBG, fasting blood glucose; LFTs, liver function tests; T4, thyroxine; TTG Ab, tissue transglutaminase antibody; TSH, thyroid-stimulating hormone.

Source: Bondy et al. 2007 189

Table 23. Ongoing monitoring in Turner syndrome.
All ages
 Blood pressure annually
 Cardiological evaluation as indicated
 ENT and audiology every 1-5 year
Girls <5 year
 Social skills at age 4-5 year
School age
 Celiac screen every 2-5 year
 Liver and thyroid screening annually
 Dental and orthodontic as needed
 Educational and social progress annually
Older girls and adults
 Liver and thyroid screening annually
    Age-appropriate evaluation of pubertal development/psychosexual adjustment
 Fasting lipids and blood sugar annually
 Celiac screen as indicated

Source: Bondy et al. 2007 189

Table 24. Cardiovascular screening and monitoring algorithm for girls and women with Turner syndrome.
Screening: All patients at time of diagnosis
    Comprehensive exam including blood pressure in all extremities
    Evaluation by cardiologist with expertise in congenital heart disease
    Clear imaging of heart, aortic valve, aortic arch, and pulmonary veins
        • Echocardiography is usually adequate for infants and young girls
        • MRI and echo for older girls and adults
Monitoring: Follow-up depends on clinical situation
    For patients with age-appropriate blood pressure and an apparently normal cardiovascular system
        • Reevaluation with imaging at timely occasions (e.g., at transition to adult clinic, before attempting pregnancy, or with appearance of hypertension). Girls that have only had echocardiography should undergo MRI when old enough to cooperate with the procedure
        • Otherwise, imaging about every 5-10 year
For patients with cardiovascular pathology, treatment and monitoring determined by cardiologist
Abbreviations: MRI, magnetic resonance imaging.

Source: Bondy et al. 2007 189

7.3.2. Treatment

Clinicians should treat growth failure as early as possible. However, puberty should not be delayed to promote statural growth 183,189.

Clinicians should also collect baseline cardiac and serial magnetic resonance imaging data to identify any findings that are unique to TS and that might point to an increased risk of aortic dissection 183,189.

Clinicians should advise patients with defined cardiovascular defects in regards to pregnancy and exercise 189.

Clinicians should start administering hormone replacement therapy at the normal age of puberty and counsel patients regarding long-term health risks associated with TS (Table 25). After 1-2 years, clinicians should add progesterone compounds in order to prevent unopposed estrogen stimulation of the uterus 183.

Clinicians should evaluate TS individuals in early childhood to identify potential learning disorders. Caregivers should discuss POF/POI and advise on the importance of estrogen treatment for both feminization and bone health during teen and adult years. Clinicians should also advise TS patients of the broad phenotypic spectrum regarding the disease and that TS individuals have experienced good quality of life in recent years 189.

All TS patients should be regularly monitored for hearing aortic enlargement, hypertension, dyslipidemia, diabetes, and thyroid function 189.

There are no recommendations for preserving fertility in TS patients due to the reduced follicle pool. Thus, TS women might consider egg donation, gestational surrogacy, or adoption 190.

Future research might make it possible for TS women to conceive with their own oocytes. However there is still a high risk of maternal and fetal morbidity and mortality associated with TS and pregnancy 191.

Clinicians should provide counseling and screening for all TS women who are considering pregnancy 191.

Table 25. Ovarian hormone replacement treatment in patients with Turner syndrome.
Age (years) Age-specific suggestions Comments
10-11 Clinicians should monitor for spontaneous puberty by Tanner staging and FSH levels. Low-dose estrogen treatment may not inhibit GH-enhanced growth in stature.
12-13 If no spontaneous development and FSH elevated, clinicians should begin low-dose E2. Equivalent initial E2 doses include: 0.2-0.4 mg/month, depot (IM); 6.25 μg daily, transdermal; 0.25 mg daily, by mouth.
12.5-15 Clinicians should gradually increase E2 dose over about 2 year (e.g., 14, 25, 37, 50, 75, 100, 200 μg daily via patch) to adult dose. Usual adult daily doses include: 100-200 μg transdermal E2, 2-4 mg oral E2, 1.25-2.5 mg CEE.
14-16 Clinicians should begin cyclic progesterone treatment after 2 year of estrogen or when breakthrough bleeding occurs. Oral micronized progesterone is the best option at present; the usual adult dose is 200 mg/d on d 16-25 of monthly cycle or  100 mg on a daily of 3-month cycle.
14-35 Clinicians should continue full doses at least until age 30 because normally estrogen levels are highest between age 15-30 years. Some women may prefer using oral or transdermal contraceptive for HRT; Clinicians should monitor endometrial thickness.
35-50 Clinicians should administer the lowest estrogen dose that provides full protection against osteoporosis or vasomotor instability—0.625 mg CEE, 1 mg E2, or equivalent. Clinicians should monitor osteoporosis risk factors, diet, exercise; obtain BMD and begin regular screening mammography by age 45 years.
>50 Clinicians should make decisions on estrogen use based on same considerations as for other postmenopausal women. New HRT options are appearing, and these recommendations may need updating in near future.
Abbreviations: CEE, conjugated equine estrogens; d, day; E2, estradiol; EE2, ethinyl estradiol; HRT, hormone replacement treatment; BMD, bone-mineral density; GH, growth hormone.

Source: Bondy et al. 2007 189

Table 26. Studies on growth hormone treatments and adult height in Turner syndrome.
Reference hGH-treated patients Initial hGH dose (mg/kg/wk) Mean treatment duration (y)

(mean +/- SD/mean)

Mean age of start (y) (mean +/- SD) height SDS at baseline (mean +/- SD) Height SDS gain (from baseline to adult height)
Ross et al. 2011 192 382 0.357 g 4.54 8.62 +/- 4.03 -2.58 +/-0.9 (0.43. 0.89, 0.92) h
Linglart et al.  2011 193 43 b

18 c





2.6 +/- 0.6

2.6 +/- 1.3

-2.6 +/- 0.6

-1.6 +/- 0.4

0.98 d

0.98 d

Stephure et al. 2005 194 a 61 0.30 f 5.7 +/- 1.6 10.3 +/- 1.8 -.02 +/- 0.9 1.6 +/- 0.6 e
Davenport et al. 2007 195 45 0.35 2.0 1.98 +/-1.01 -1.42 +/-1.0 1.1 +/- .06
Blum et al. 2009 196 158 0.31 +/- 0.09 5.6 +/- 2.3 10.9 +/-3.1 -2.9 +/-0.8 1.2 +/- .08
Abbreviations: SDS, standard deviation score; SD, standard deviation; hGH, human growth hormone; y, years.
Notes: a, The Canadian Growth Hormone Advisory Committee; b, standard-dose group (0.035 mg/kg/d); c, low-dose group (0.05 mg/kg/d); d, height SDS at start of GH treatment – 2.33 +/- 0.73 and height SDS at end of study – 1.35 +/- 0.86; e, age-specific TS; f, GH dose was given 6 days per week; g, 
GH dose 0.051 +/- 0.0098, h, duration of hGH therapy: 1 year, <3 years, and >3 years, respectively.

Source: Table adapted from Chacko et al. 2012

Table 27. Studies on combined estrogen and growth hormone therapy and adult height gain in Turner syndrome.
Oral estrogen treatment
Chronological age) baseline (y) (mean  +/- SD)
Adult height attained in SD (average gain over projected height, cm)
Ross et al. 2011198
Ultralow dose E2: Age 5-8 y; 25 ng/kg/d
Age 8 y: 50 ng/kg/d
Age >12 y: escalating doses of 100 ng/kg/d – 800 ng/kg/d
A; 33
B: 37
C: 34
D: 33
A: Double PL
B: E2 + PL
C: hGH (.01 mg/kg x 3/wk) + PL
D: E2+ hGH
A: 7.5 +/- 2.3
B: 8.5 +/- 2.7
C: 8.2 +/- 2.6
D: 9.3 +/- 2.5
A: -2.81 +/- 0.85
B: -3.39 +/- 0.74
C: -2.29 +/- 1.10
D: -2.10 +/- 1.02
Quigley et al. 2002 199
Childhood low dose E2:
Age 8 – <10 y: 25-50 ng/kg/d
Age 10 – <12 y: 67-100 ng/kg/d
Age >12 y: 160-200 ng/kg/d
A: 15
B: 24
C: 38
D: 22
A: hGh (0.27 mg/kg/wk) + PL
B: hGH (0.27 mg/kg/wk) + E2
C: hGH (0.36 mg/kg/wk) + PL
D: hGH (0.36 mg/kg/wk)  + E2
E: Double PL
A: 9.7 +/- 2.7
B: 9.6 +/- 2.7
C: 9.8 +/- 2.9
D: 9.9 +/- 2.9
A: -2.2 +/- 1.0
B: -2.7 +/- 1.0
C: -1.9 +/- 1.0
D: -2.2 +/- 1.0
Van Pareren et al. 2003 200
Childhood low dose E2:
5 μg of 17b-E2 (roughly 0.05 μg/kg/d) in 1st 2 y, 7.5 μg/kg/d in 3rd y, 10 μg/kg/d thereafter
A: 19
B: 20
C: 21
A: hGH (4 IUm2 )
B: hGH (1st y 4 IUm2; thereafter 6 IUm2)
C: hGH (1st y 4 IUm2, 2nd y 6 IUm2, thereafter 6 IUm2)
(E2 treatment in each group [A-B] was started after the subject reached age 12 y)
A: 6.5 +/- 1.9
B: 6.9 +/- 2.3
C: 6.5 +/- 2.4
A: -1.6 +/- 1.0
B: -0.7 +/- 1.0
C: -0.6 +/- 1.0
Chernausek et al. 2000 201
Conjugated E2:
.03 mg/d x 6 mo, then increased to 0.625 mg/d
A: 26
B: 29
hGH (0.375 mg/kg/wk)
A: E2 starts at 15 y
B: E2 starts at 12 y
A: 9.54 +/- 0.9
B: 9.6 +/- 1.0
A: (8.4 +/- 4.3 cm)
B: (5.1 +/- 3.6 cm)
Abbreviations: d, day; E2, estradiol; mo, month; N, number; SD, standard deviation; TS, turner syndrome; PL, placebo; y, year

Source: Table adapted from Chacko et al. 2012



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