HỘI CHỨNG TURNER TRÌNH BÀY:BS.TRẦN HOÀNG MINH CHÂU Lớp CK2 Nội Tiết 2007-2009 ĐẠI CƯƠNG ĐẠI CƯƠNG • Năm 1938, lần Henry Turner mô tả hội chứng Turner, bất thường NST hay gặp • Hơn 95% phụ nữ bị hc Turner có hình dáng thấp vô sinh • Nguyên nhân vắng mặt nhóm gen nhánh ngắn NST X • Ở BN có kiểu 45X, khoảng 2/3 NST X thiếu từ cha • Sự thiếu gen SHOX NST X nguyên nhân ĐẠI CƯƠNG • Bất thường NST người mắc hội chứng Turner đa dạng • Khoảng 50% bệnh nhân có karyotype 45,X đánh giá tế bào lympho máu ngoại vi • Khoảng từ 30% đến 40% dạng khảm, phổ biến 46,XX/45,X, dạng 46,XY/45,X gặp (khoảng 5%) Khoảng 10% đến 20% bệnh nhân có bất thường NST X đoạn phần toàn nhánh ngắn NST X • Sự đa dạng giải thích khác biệt lớn biểu kiểu hình người mắc hội chứng TẦN SUẤT • Ở Mỹ:Tần suất khoảng 1/2000 trẻ sơ sinh nữ.Khoảng 15% sẩy thai tự nhiên có kiểu hình 45X • Thế giới:Tần suất tương tự Mỹ.Không thấy có liên quan đến chủng tộc màu da MORTALITY / MORBIDYTY • TVcó thể tăng lên thời kỳ chu sinh bệnh ĐMC người lớn bệnh tim mạch.Béo phì , kết hợp với ĐTĐ THA góp phần làm TV sớm • Những NC DTH giới hạn cho thấy tuổi thọ trung bình giảm 10 năm • LX thường gặp • Bất thường thận số BN gây NTT tái tái lại THA.Ngay bất thường tim thận, BN có xu hướng bị THA • BN có bệnh lý tim BS ( mitral or aortic disease) dễ bị viêm nội tâm mạc bán cấp GIỚI TÍNH • HC Turner xảy nữ • HC Noonan, gọi cách không xác HC Turner, xảy nam nữ.Đó bất thường gen trội không liên quan đến rối loạn NST không liên quan đến HC Turner TUỔI • Là RL NST, HC Turner diện lúc thụ thai thời kỳ phân chia thứ tồn suốt đời • Gonadotropins, đặc biệt FSH, tăng lúc sanh, không đủ để chẩn đoán, trở lại bình thường khoảng năm tuổi, tăng lên đến mức MK sau 10 tuổi LÂM SÀNG 10 PSYCHOLOGY • Hầu hết BN vấn đề phát triển trí tuệ, BN thường chậm tiếp xúc, học hành chậm hơn đánh giá số thông minh, khả học,kỷ vận động, khả hòa nhập XH trước trẻ đến trường (As with any chronic illness, attention should be paid to fostering healthy socialization and to appropriate career and vocational planning.) GENETICS • HC Turner bệnh di truyền, • Xảy trình thụ thai • Hội chẩn quan trọng chẩn đoán TC HC Turner nghi ngờ xét nghiệm mẫu máu ngoại vi bình thường • BN nên khám phá diện Ychromosomal material using a Y-centromeric probe DIET • Tình trạng thấp bé suy buồng trứng loãng xương bảo đảm cung cấp calci (1-1,5g/ngày) vitaminD (400UI) • Tránh béo phì phòng nguy THA đề kháng insulin • BN thấp bé đòi hỏi calories trẻ bình thường • Luyện tập thể lực khuyến cáo để tránh béo phì loãng xương MEDICATION 51 HUMAN GROWTH HORMONES Drug Name Somatotropin (Nutropin, Genotropin, Humatrope, Norditropin, Saizen, Tevtropin) Taller adult heights are associated with earlier treatment and with the duration of treatment prior to induced or spontaneous puberty With treatment, approximately 50% of patients reach an adult height of 150 cm (59") or more, compared to an untreated mean adult height of 142 cm (56") Adult Dose Not recommended at present for adults after the epiphyses have closed Pediatric Dose Varies with specific product: 0.05 mg/kg/d (as somatropin [Saizen]) SC is one example; individualize according to growth results Contraindications Documented hypersensitivity; hypersensitivity to benzyl alcohol, cresol, or other preservatives used in preparation of liquid injectable; fused (closed) epiphyses; active neoplasia; neonates Interactions Corticosteroids interfere with growth-promoting actions; estrogens can cause epiphyseal fusion, which stops growth; patient must be euthyroid for optimal effects Pregnancy C - Safety for use during pregnancy has not been established Precautions Caution in diabetes mellitus; reconstitute with sterile water for injection if administering to newborns (avoids benzyl alcohol); monitor bone age, thyroid hormones, and blood glucose; intracranial hypertension 52 Anabolic steroids: This is an adjuvant for growth hormone therapy Drug Name Oxandrolone (Oxandrin, Anavar) Of limited use Some endocrinologists recommend use in patients diagnosed in their teens to achieve a maximum adult height quickly When used, it is often combined with growth hormone to allow a lower dose, thus decreasing the potential for adverse effects Adult Dose Not recommended Pediatric Dose 8 years: 0.05 mg/kg/d PO; not to exceed 0.05 mg/kg/d Contraindications Documented hypersensitivity; hypercalcemia Interactions May worsen glucose tolerance; possible increased sensitivity to PO anticoagulants Pregnancy X - Contraindicated in pregnancy Precautions Caution in heart failure, CAD, edema, hypertension, psychiatric disorders, substance abuse, or liver dysfunction; monitor bone growth and blood glucose 53 Estrogen replacement therapies • Almost all individuals require estrogen replacement Usually, this is started at a bone age of 12 years or more because starting earlier may compromise adult height Estrogens usually are started at a chronologic age of 12-15 years Adults usually require cyclic therapy with both estrogens and progestins Transdermal or parenteral estrogens may be useful in limiting some adverse effects of estrogen therapy Drug Name Estrogens Available in many forms, eg, ethinyl estradiol (Estinyl), estradiol (Estrace), and conjugated estrogens (Premarin) Restore estrogen levels to concentrations that induce negative feedback at gonadotrophic regulatory centers, which in turn reduces release of gonadotropins from pituitary Increases synthesis of DNA, RNA, and many proteins in target tissues Adult Dose 35-100 PO mcg/d Pediatric Dose Estrogen should begin at lowest possible dose and not earlier than bone age of 13 y Some endocrinologists start with a low daily dose of ethinyl estradiol 10 mcg/d or less PO, and cycle therapy after several mo of treatment; low-dose transdermal or parenteral treatment may be preferable and is being investigated Contraindications Documented hypersensitivity; breast cancer; undiagnosed abnormal genital bleeding; active thrombophlebitis or thromboembolic disorders; history of thrombophlebitis, thrombosis, or thromboembolic disorders associated with previous estrogen use (except when used in treatment of breast malignancy); Premarin may be rejected by some patients as an animal-rights issue Interactions May reduce hypoprothrombinemic effect of anticoagulants; possible reduced estrogen levels with coadministration of barbiturates, rifampin, and other agents that induce hepatic microsomal enzymes; possible increase in pharmacologic and toxicologic effects of corticosteroids, via inactivation of hepatic P450 enzyme; possible loss of seizure control when administered concurrently with hydantoins Pregnancy X - Contraindicated in pregnancy Precautions May cause some degree of fluid retention and require careful observation; possible undesirable manifestations of excessive estrogenic stimulation 55 ANTIHYPERTENSION AGENTS • These products are used to control hypertension and ultimately prevent complications such as aortic dissection • The most common class of medications used for these purposes in pediatric patients are beta-blockers and ACE inhibitors Propranolol is an example of of the beta-blockers used in pediatrics, while captopril is an example of an ACE inhibitor THYROID REPLACEMENT THERAPIES • These agents are used for treatment of hypothyroidism VITAMINS AND MINERALS • Osteoporosis is common and is a major cause of morbidity in adults • Treatment is the same as for other adult women with osteoporosis Monitor diet and ensure an intake of at least g/d of calcium and 400 IU/d of vitamin D • Treatment with growth hormone and estrogen also are important in the prevention of osteoporosis later in life PROGNOSIS • Overall prognosis is good • Even with growth hormone therapy, most individuals are shorter than average • Turner syndrome is not a cause of mental retardation • Life expectancy is slightly shorter than average but may be improved by attention to associated chronic illnesses, such as obesity and hypertension • Almost all individuals are infertile, but pregnancy with donor embryos is possible SPECIAL CONCERNS • Infertility – Most patients are infertile, although spontaneous unassisted pregnancy has occurred – In spontaneous unassisted pregnancy, the risk of having an infant with Turner syndrome or Down syndrome is increased Risk of miscarriage also is high SPECIAL CONCERNS • Assisted reproduction – Pregnancy has been achieved by means of fresh or frozen embryo transfer Transfer of only one embryo at a time is recommended to avoid additional complications of twin pregnancies – Prior to embryo transfer, a complete renal and cardiovascular evaluation is warranted, including echocardiography Hypertension or other cardiovascular problems may complicate pregnancy, and careful follow-up care during pregnancy is needed Thyroid status should also be assessed because hypothyroidism during pregnancy may be associated with a poorer outcome – Although implantation and clinical pregnancy rates are similar to other women with ovarian failure, the miscarriage rate is high, probably because of uterine factors – Caesarean delivery is usual and is possibly related to small pelvic outlet size KẾT LUẬN • The presentation of Turner syndrome may be subtle Consider ordering a karyotype for any girl with unexplained short stature • Yearly follow-up TSH tests help avoid unrecognized hypothyroidism, which can interfere with growth • Osteoporosis and aortic arch dissection are known complications of Turner syndrome in adulthood Successful treatment requires screening and early treatment, before symptoms occur • Virilization of a patient with Turner syndrome suggests a gonadoblastoma or other tumor In such patients, Y chromosome material should be sought using a Y-centromeric probe and a gonad, adrenal, or midline tumor should be vigorously pursued • GUIDELINE ... TÍNH • HC Turner xảy nữ • HC Noonan, gọi cách không xác HC Turner, xảy nam nữ.Đó bất thường gen trội không liên quan đến rối loạn NST không liên quan đến HC Turner TUỔI • Là RL NST, HC Turner. ..ĐẠI CƯƠNG ĐẠI CƯƠNG • Năm 1938, lần Henry Turner mô tả hội chứng Turner, bất thường NST hay gặp • Hơn 95% phụ nữ bị hc Turner có hình dáng thấp vô sinh • Nguyên nhân vắng mặt nhóm... tương đối đặc hiệu cho HC Turner KHÁM THỰC THỂ • Shield chest: Lồng ngực rộng đầu vú xa nhau.Điều gây phần xương ức ngắn • Lymphedema:Có thể diện tuổi dấu hiệu nghi ngờ HC Turner siêu âm thai.Sự