Turner's syndrome
Turner's syndrome is characterised by gonadal dysgenesis and short stature. The diagnosis is confirmed by the karyotype 45 XO.
Karyotype analysis
Adult patients with absent puberty require karyotype analysis to confirm the clinical suspicion of Turner’s syndrome.
Genetic counselling
This should be offered to all patients at, or soon after, diagnosis.
Review baseline pituitary function
If there is any doubt that hypogonadotropic hypogonadism may not be isolated, consider dynamic function testing.
MRI pituitary
If karyotype is apparently normal, then other causes of hypogonadotropic hypogonadism are possible. Thorough investigation should therefore be performed.
Consider assessing bone age
Delayed bone age supports the diagnosis of absent puberty. Growth hormone treatment should be considered in those with short stature and delayed bone age. This decision should be undertaken in conjunction with an experienced paediatric endocrinologist.
Discuss fertility issues at, or soon after, diagnosis
If appropriate, fertility should be discussed early with the patient and their family.
Patients need to understand that successful pubertal induction will not affect or restore fertility, although appropriate uterine development is necessary prior to possible future pregnancies.
Screening required at diagnosis
At confirmation of diagnosis or transition to adult care arrange the following tests in all cases: karyotype analysis (if not performed already), echocardiogram, renal ultrasound scan, pelvic ultrasound scan, bone densitometry scan, thyroid stimulating hormone, free thyroxine, thyroid and coeliac antibody screen, urea and electrolytes, liver function test, bone profile, fasting lipid profile, fasting glucose and HbA1c.
Annual follow up
All patients should be offered life long annual follow up. The following tests should be arranged prior to every review: thyroid stimulating hormone, free thyroxine, urea and electrolytes, liver function test, fasting lipid profile, fasting glucose and HbA1c.
Three to five yearly follow up
Every three to five years, consider repeating the following tests: echo three to five yearly; thyroid/coeliac antibodies five yearly; hearing test five yearly; and, bone densitometry scan recommended five yearly.
Pre-pregnancy
Cardiac magnetic resonance imaging and uterine ultrasound scan should be performed prior to considering pregnancy.
Patients will require referral to a specialist fertility unit. In vitro fertilisation, using a donor egg, may be necessary.
Hormone replacement therapy
Discuss treatment aims, timescales and outcomes
Treatment aims to replicate the natural process of puberty and should occur over approximately the same timescale - approximately two to three years. Breast development and secondary sexual hair should occur. Some bleeding may occur during pubertal induction, at which point, cyclical progesterone should be added.
Patients need to understand that accelerating the treatment may have adverse psychological and physical consequences, for example poor breast development.
Initiate treatment
Initiate very low dose estrogen replacement therapy.
Typical starting dose in an estrogen naive patient is 1.25mcg ethinylestradiol. Increase dose to 2.5mcg, then by 2.5mcg increments every six months to 10mcg. The dose may then increase to 15mcg.
Dose titration
Consider pelvic ultrasound scan to assess uterine size at this stage.
Once the patient experiences vaginal bleeding or if the patient has tolerated 15mcg, consider adding cyclical progesterone, for example norethisterone 5mg on the first five days of the month.
Alternative treatment regimens
The combined oral contraceptive pill is a convenient preparation and may be more socially acceptable in young patients, for example Loestrin 20.
However, these do not provide sufficient bony protection unless used continuously and HRT is more appropriate long term.
Topical, depot and oral preparations should be offered and treatment tailored according to the individual.
Duration of treatment
Continue sex hormone replacement therapy until the time of the natural menopause - typically to age 50.
Vaginal gels
Topical estrogen may be beneficial to help vaginal dryness.