The child, female, aged 11 years and 6 months, was seen in our outpatient clinic on February 26, 2007.
The parents complained of short stature since childhood.
Medical history
If a child complains of short stature, we should first determine whether the child is really short. If the child’s height is below the 3rd percentile of height for children of the same age and gender, growth hormone and thyroid function should be examined. For female children, chromosomal examination is also required to exclude chromosomal abnormalities that cause short stature. Li Wenjing, Endocrine Genetic Metabolism Center, Beijing Children’s Hospital
(a) Further inquiry content and purpose.
1. Ask the parents if they have any growth records of the child in recent years, so as to determine the growth rate of the child. If the parents cannot provide the above records, they can ask the parents whether the child has bought a suit that is small after one year or can wear it for two years without any problem. Normal child growth and development process, a piece of clothing can rarely wear two years.
2. Ask the child about his or her intellectual development. If the short stature is caused by growth hormone deficiency, the child’s intellectual development is normal. If it is hypothyroidism or congenital ovarian insufficiency syndrome (Turner syndrome, TS), the child can have different degrees of mental retardation.
3. In the case of older female children, attention should be paid to the presence or absence of pubertal development of secondary sex characteristics.
4. The child’s condition at birth, whether it was born prematurely or with low birth weight.
5. Ask if the child has a history of serious heart, liver, kidney and other important organ disease and functional abnormalities.
6. The height of the child’s parents to assist in the diagnosis of familial short stature. Whether there are similar children in the family.
7. Any abnormalities during maternal pregnancy, such as history of early pregnancy, history of pre-eclampsia, history of radiation and other toxic exposure.
(ii) Results (medical history).
The child was born at full term and was not weighed at birth, but had the same appearance as a normal child. 1 year later, the child was found to walk later than his peers, and walked only at 1.5 years. The child’s intellectual development was close to that of the same age, and he could adapt to normal learning. There is no record of the child’s growth rate in recent years, but the child can usually wear a suit for two years. There are no signs of pubertal development.
The child is a first-born, full-term, normal child with an uneventful maternal pregnancy and no history of disease. Her sister, 5 years old, is 110 cm tall.
She has no history of serious cardiopulmonary, hepatic or renal disease. The child’s parents were of normal height.
Analysis of the findings (medical history): ① the child’s growth is backward and her height is lower than the third percentile of height for the same age and sex, which means that the diagnosis of short stature of the child is valid; ② there are no signs of pubertal development, which means that she has no pubertal development, and for girls who are short in puberty, attention should be paid to whether she has congenital ovarian hypoplasia syndrome; ③ there is no history of serious diseases, except for those caused by serious diseases. (3) There is no history of serious diseases, except for those caused by serious diseases; (4) The child’s sister has normal growth and development; (5) The child’s parents have normal height, except for familial short stature. (6) The child was born at full term, and the condition at birth was generally normal, excluding prematurity or low birth weight caused by short stature.
Physical examination
(a) Content and purpose of the preliminary physical examination.
Accurate measurement of height to help evaluate whether the child is short; upper and lower measurements to determine whether the child is proportionate; presence of special facial features and signs, pubertal development, to help diagnose TS or hypothyroidism, etc.
(ii) Physical examination findings.
Height 128,5 cm, sitting height 70 cm, finger spacing 126 cm, weight 36,5 kg, height below the third percentile of height for the same age and sex, clear consciousness, mental response, short and fat body type, no obvious mucus edema face, low hairline, ear position approximately normal, neck webbing (+), barrel-shaped thorax, widened breast distance, strong heart sounds, no murmurs, no palpable abdomen, liver and spleen No enlargement, elbow valgus (+), no abnormalities in neurological examination. Bilateral breast Tanner stage I, external genital pubic hair Tanner stage I.
IV. Outpatient and external examination findings.
Bone age: 11 years old.
Ultrasound of uterus and ovaries showed that the uterus was smaller than that of children of the same age, and the bilateral ovaries were striated.
Growth hormone movement test: 2,2ng/mL anteriorly and 7,6ng/mL posteriorly
Insulin-like growth factor-1 367, 1ng/mL, insulin-like growth factor binding protein-3 3998ng/mL
Sex IV: follicular maturation hormone 59, 2mIU/mL, luteinizing hormone 18, 3mIU/mL, estradiol 19, 6pg/mL, testosterone 27, 6ng/dL
Alpha five: T3 199ng/dL, T4 9, 4ug/dL, TSH 1, 8uIU/mL, FT3 6, 7pmol/L, FT4 21, 7pmol/L.
Analysis of physical and current examination results: ① the child’s height was lower than the 3rd percentile of the height of normal children of the same age and sex, and the diagnosis of short stature was established; ② the peak of growth hormone motor test was <10ng/mL, and there might be a partial deficiency of growth hormone; however, the motor test was only a screening test, and the child's bone age was normal, so whether the diagnosis of growth hormone deficiency was pending the drug-stimulated growth hormone stimulation test. ③ Physical examination showed signs such as low hairline, webbed neck, barrel-shaped thorax, widened breast distance, and elbow ectropion, without signs of secondary sex characteristics development, suggesting whether TS was present; ④ pelvic ultrasound indicated backward uterine development and ovarian dysplasia, which should be considered whether TS was present; ⑤ there was no obvious mucinous edema face, and thyroid function was normal, which could exclude short stature due to hypothyroidism; ⑥ sex hormone examination: gonadotropins were significantly elevated, while none of the peripheral hormones were significantly elevated.
V. Preliminary diagnosis.
The causes of short stature are to be investigated: (1) congenital ovarian hypoplasia syndrome (TS); (2) growth hormone deficiency?
VI. Further laboratory
(A) Further examination content and purpose
1. Chromosomal examination to determine whether the short stature is due to chromosomal abnormalities.
2. Hospitalization for drug-stimulated growth hormone stimulation test.
3. Cranial MRI examination to exclude short stature due to central nervous system lesions.
(B) Examination results.
1. karyotype: 45, X/46, X, r(X).
2. no abnormalities on MRI examination of the head.
3. Growth hormone stimulation test was not done temporarily because the parents refused to be hospitalized for examination.
Analysis of laboratory findings: abnormal karyotype. The karyotype was chimeric, 45,X with 46,X,,r(X), chimeric.
According to the test results, further diseases that were clarified or excluded: (1) karyotype abnormalities, which could be diagnosed as congenital ovarian hypoplasia syndrome; (2) the child’s growth hormone motor stimulation test peak did not reach 10ng/mL, but the child’s bone age was consistent with the chronological age, which did not support the diagnosis of short stature due to growth hormone deficiency, so further confirmatory stimulation tests were needed to assist the diagnosis, excluding growth hormone deficiency.
VII. Contents and purpose of the next examination.
Children with TS may have congenital heart disease, congenital malformation of kidney development, and other abnormalities including metabolic, immune, digestive, neuropsychiatric and other system abnormalities, such as obesity, idiopathic hypertension, abnormal glucose tolerance thyroid disease, osteoporosis, otitis media, conductive deafness, colitis, etc. The obese body shape of this child may be related to TS. To determine the presence of comorbidities in the child, a glucose tolerance test is needed to exclude abnormal glucose tolerance, a skeletal X-ray to exclude osteoporosis, and an examination of the child’s hearing and other five sensory conditions to exclude deafness and other conditions. If parents agree, hospitalization is required for growth hormone stimulation test to exclude growth hormone deficiency.
Diagnosis: congenital ovarian hypoplasia syndrome
Based on the clinical signs and chromosomal findings of this child, the diagnosis of TS was established.
Treatment
The treatment of TS is aimed at improving the final height of the child in adulthood, correcting somatoform deformities, inducing and maintaining secondary sexual characteristics, and simulating artificial cycles. Growth promotion is treated with high doses of growth hormone. The current recommended dose is 0, 15 U/(kg, d). Estrogen replacement therapy can be started when the child reaches the age of 13 years and the bone age exceeds 11 years.
After the diagnosis of this child was clear, growth hormone 5U/day was added and injected subcutaneously every night at bedtime. She has not yet started estrogen replacement therapy.
X. About Turner syndrome
TS is also known as congenital ovarian hypoplasia syndrome, which is caused by the complete or partial absence of one X chromosome in all or part of the somatic cells; the most typical manifestation of TS is short stature, lack of secondary sex characteristics, special physical features, and sometimes accompanied by varying degrees of mental retardation.
(A) Clinical manifestations
1, short stature, some patients with varying degrees of mental retardation. The degree of growth retardation varies in children with chimeric type.
2. Female phenotype with hypogonadism. It is usually manifested as infantile to vulva; no expression of secondary sexual development at pubertal development age, no breast development, no pubic and axillary hair, and no primary menstruation.
3. The disease has characteristic somatic deformities, including webbed neck, shield chest, widened breast spacing, nipple hypoplasia, elbow ectropion, short and curved fourth and fifth metacarpals and/or metatarsals, narrow maxillary and palatal arches, small mandible, inner canthus, low ear position, and low posterior hairline.
4. Endocrine metabolic, immune, digestive and neurological signs and symptoms may be combined, such as diabetes mellitus, thyroid disease, obesity; occasionally idiopathic hypertension, rheumatoid, etc.
5. Other malformations: congenital heart disease, mainly mitral valve, aortic valve and aortic constriction; congenital urinary system malformations, such as horseshoe kidney, etc.; lymphedema of the dorsum of the hands and feet in the neonatal period; narrow upper jaw (palate), relatively small lower jaw, inner canthus, low ear position, ear malformation, low posterior hairline, skin pigmentation nevus, etc.
(II) Auxiliary examination
1. Chromosomal karyotype analysis is a confirmatory test and can have a variety of karyotypic manifestations.
(1) 45,XO is the most common; (2) 45,XO/46,XX; (3) 45,XO/46,XY; 45,XO/47XXX, etc.; (4) equal-arm X chromosome or partially missing X chromosome. Oral mucosal smear for X chromatin (Barr vesicles, X vesicles) can be used as a screening, which has been rarely used.
2.Serum LH and FSH are significantly increased during puberty, while E2 level is low
3, pelvic ultrasound: ovaries are striped or cystic, and the uterus is infantile or dysplastic.
4. Other abnormal related tests such as cardiac ultrasound, renal ultrasound, thyroid function, glucose tolerance, thyroid function and hearing if necessary.
Treatment is growth promotion and estrogen replacement therapy to maintain female sexual characteristics.
The prevalence of TS in live births is 1 in 2000-2500, and short stature is the most common complaint in pediatric endocrinology clinics, so it is important to pay sufficient attention to whether a female child with short stature has TS and to routinely test for karyotype. Improvement of the phenotype is the main therapeutic goal.