Update on care of girls with Turner’s syndrome

Issue: February 2007

ByJanet H. Silverstein, MD

Janet Silverstein, MD
Janet Silverstein

The Clinical Practice Guideline for girls with Turner’s syndrome, recently released by the Turner Syndrome Consensus Study Group and published in the Journal of Clinical Endocrinology and Metabolism, has some important differences from the previous guidelines published in 2001. These updated guidelines, based on new data, are considerably more comprehensive and require more intensive management of many of the organ systems affected by TS.

The differences are outlined below.

Growth, puberty induction

As growth hormone has been shown to effectively promote growth in most girls with TS, it is recommended that all girls begin treatment with GH as soon as growth failure is demonstrated. The previous recommendation was use of GH as early as 2 years of age. Newer studies demonstrating safety and efficacy as early as 9 months of age resulted in the modified recommendation that GH treatment be initiated at onset of growth failure, no matter how young the child.

The current FDA approved dose of GH is 0.375 mg/kg/week, slightly higher than the previous recommendation of 0.35 mg/kg/wk. Current recommendations that oxandrolone in a dose of no more than 0.05 mg/kg/d may be given in addition to GH in girls initiating treatment at 9 years of age or older and in girls with extreme short stature. Previous recommendations recommended initiation of oxandrolone treatment in girls 9 to 12 years of age.

A major departure from previous guidelines is the lowering of the age at initiation of estrogen replacement. It had been thought that early initiation of estrogen treatment would result in earlier epiphyseal fusion and ultimately a decrease in final height. As recent studies have demonstrated no adverse effect on final height with initiation of estrogen replacement therapy with physiologic doses at the usual age of puberty, the current recommendation is to initiate treatment with estrogen as early as 12 years rather than at the previous age recommendation of 15 years.

Options for estrogen treatment have expanded, with transdermal and injectable depot estradiol providing physiologic alternatives to oral estrogen. Replacement doses are begun at 1/8 to 1/10 of adult replacement and gradually increased over two to four years. Progestins are begun two years after beginning estrogen treatment or when breakthrough bleeding occurs to optimize breast and uterine development.

Lymphedema

If lymphedema is severe and does not respond to treatment with support stockings and elevation, complete decongestive physiotherapy (skin and nail care, massage for manual lymphatic drainage, compression bandaging, and remedial exercise) may be effective. Long-term treatment with diuretics is not a recommended treatment and vascular surgery should be avoided. This differs from the previous guideline, in which it was stated that vascular surgery may be necessary in some patients, with the caveat that it should be avoided, if possible, because of lack of clear efficacy data.

Cardiovascular system

The section on cardiovascular disease has been expanded considerably because of recent studies indicating that girls with TS have a broader range of cardiovascular disease than previously recognized, including many vascular anomalies (elongated transverse arch, partial anomalous pulmonary connection, and persistent left superior vena cava) and conduction abnormalities (T wave abnormalities, accelerated AV conduction, resting tachycardia and prolonged QTc). Thus, clinicians must be aware of the risk of developing cardiac disease throughout life, even if the patient doesn’t have the classic findings of bicuspid aortic arch, coarctation of the aorta and dilated aortic root. More emphasis is placed on the recognition and aggressive treatment of hypertension in these girls, as this is likely the most important and common treatable risk factor for aortic dilatation and dissection.

The previous recommendation was for a complete physical examination with echocardiogram read by a pediatric cardiologist at the time of diagnosis and, if no congenital heart disease is present, a repeat cardiovascular PE and echocardiogram at age 12 to 15 years to evaluate the diameter of the aortic root.

Because of the broadened spectrum of cardiovascular disease and the recognition that cardiovascular disease may progress over time, the recommendation has been expanded to include an MRI for all girls old enough to cooperate with the procedure without sedation. Imaging and re-evaluation should now be done at regular intervals every five to 10 years and at the time of development of hypertension, pregnancy or at transition to the adult clinic.

Orthodontics

Previously, it was recommended that girls with TS see a dental specialist at 8 to 10 years of age. Because of the recognition that girls with TS have abnormal maxillary and mandibular anatomy resulting in poor dental occlusion, have abnormal tooth development and eruption, and have increased risk of root absorption, the current recommendations include earlier referral to a dental specialist by age 2 years and referral to an orthodontist by age 7 years. GH-treated girls should have regular follow-up by an orthodontist because of the effect of GH on craniofacial proportions.

Psychosocial function

Girls with TS are at significant risk of social isolation, immaturity, and decreased self-esteem, which appears to be related more to their ovarian failure than to their final adult height. They also have a higher risk of specific learning disabilities. The new recommendations, therefore, call for a comprehensive psycho-educational evaluation at the time of school entry or at the time of TS diagnosis, with repeat evaluation any time the child experiences academic difficulties.

Genetic counseling

There is an inordinately high elective abortion rate for fetuses with incidental findings of 45,XO or Turner mosaic karyotypes, despite evidence that these girls generally have normal quality of life. It is recommended that the physicians and genetic counselors who perform prenatal counseling be fully informed about the prognosis and complications of girls with TS, and they should be knowledgeable about advances in current management as well.

There are many other specific recommendations in the updated guidelines; I’ve only highlighted some of those requiring change in the way endocrinologists practice. The care of a girl with TS requires a multidisciplinary team knowledgeable about the state-of-the-art management of girls with the disease.

For more information:
Janet Silverstein, MD, is Chief of the Division of Endocrinology, Department of Pediatrics, at the University of Florida in Gainesville and a member of Endocrine Today’s Editorial Board.
Bondy CA. Care of girls and women with Turner syndrome: a guideline of the Turner syndrome study group. J Clin Endocrinol Metab. 2007;92:10-25.