What is the comprehensive evaluation and management of Turner Syndrome (TS)?

From the Guidelines

Turner syndrome patients require a comprehensive management plan that prioritizes cardiovascular health, growth hormone therapy, and estrogen replacement therapy to improve morbidity, mortality, and quality of life. The management of Turner syndrome should start with early diagnosis through karyotype analysis, followed by an initial evaluation that includes cardiac assessment with echocardiography to detect congenital heart defects, particularly coarctation of the aorta and bicuspid aortic valve 1.

Key Recommendations

• Initial cardiac assessment should include TTE and cardiac MRI at the time of diagnosis to evaluate for BAV, aortic root and ascending aortic dilation, aortic coarctation, and other congenital heart defects 1.
• Growth hormone therapy should begin as soon as growth failure is evident, typically at a dose of 0.375 mg/kg/week divided into daily subcutaneous injections, continuing until final height is achieved or epiphyseal fusion occurs.
• Estrogen replacement therapy should start at age 11-12 to induce puberty, beginning with low-dose estradiol (0.25 mg daily) and gradually increasing over 2-3 years, followed by adding progesterone (typically medroxyprogesterone acetate 5-10 mg for 12-14 days monthly) once breakthrough bleeding occurs or after 2 years of estrogen.
• Regular monitoring includes annual thyroid function tests, hearing evaluations, bone density scans, and glucose tolerance tests.
• Renal ultrasound should be performed at diagnosis to detect structural abnormalities.
• Psychological support is essential, as girls with Turner syndrome may face learning difficulties, particularly in spatial-visual organization and mathematics.

Cardiovascular Management

• In patients with Turner syndrome who are ≥15 years old, the use of the ASI (ratio of aortic diameter [cm] to BSA [m2]) is recommended to define the degree of aortic dilation and assess the risk of aortic dissection 1.
• Surveillance imaging with TTE or MRI to evaluate the aorta is recommended every 5 years in children and every 10 years in adults, as well as before planning a pregnancy 1.
• Elective surgery for aneurysms of the aortic root and/or ascending aorta should be considered in women with TS who are ≥15 years of age, have an ascending ASI >23 mm/m2, an AHI >23 mm/m, a z-score >3.5, and have associated risk factors for aortic dissection or are planning pregnancy 1.

Multidisciplinary Approach

Regular follow-up with an endocrinologist, cardiologist, and reproductive specialist is necessary throughout life, with particular attention to cardiovascular health as these patients have increased risk of aortic dissection and hypertension 1. This multidisciplinary approach addresses the various manifestations of Turner syndrome, improving growth outcomes, sexual development, and overall quality of life.

From the Research

Extensive Valuation and Management of Turner Syndrome

• Turner syndrome is a genetic condition that affects females, characterized by partial or complete loss of the second X-chromosome, leading to a range of clinical findings including short stature, primary ovarian failure, and neurocognitive difficulties 2, 3.
• Individuals with Turner syndrome commonly exhibit cardiovascular, endocrine, renal, reproductive, and/or psychosocial abnormalities, among other conditions, requiring a multidisciplinary approach to care 4, 3.
• The optimal estrogen replacement treatment regimen to induce pubertal development is still being determined, with the goals of estrogen replacement being to mimic normal physical and social development for timing and progression of puberty 5, 4.
• Treatment should begin at 11-12 years of age, with dose increases every 6 months over a 2-3 year period, and initiation with low doses of estrogen is crucial to preserve growth potential 5, 4.
• Delaying estrogen replacement may be deleterious to bone and uterine health, and evidence supports the effectiveness of starting pubertal estrogen replacement with low-dose transdermal E2 5, 4.

Hormone Replacement Therapy

• Most girls with Turner syndrome have hypergonadotropic hypogonadism and need hormonal replacement for induction of puberty and then for maintaining secondary sex characteristics, attaining peak bone mass, and uterine growth 5, 4.
• The choice of hormone replacement therapy in the young person with Turner syndrome and in adulthood is still an unanswered question, and further research is needed in relation to hormone replacement therapy in TS 6.
• A systematic and holistic approach to provision of health care in TS is needed, including screening for other comorbidities and addressing psychosocial issues 3, 6.

Management and Care

• A multidisciplinary approach and a well-planned transition to adult follow-up care will improve health care delivery significantly for this population 3.
• The optimal model of care and transition to adult services in TS requires attention, and further research is needed in relation to cardiovascular risk assessment, pregnancy management, and hormone replacement therapy in TS 6.
• Individuals with Turner syndrome have a lifetime increased risk from autoimmune conditions like hypothyroidism, coeliac disease, hearing loss, and aortic dilatation with the potential to lead to aortic dissection, requiring regular monitoring and management 2, 6.