Menstrual Pattern, Reproductive Hormones, and Transabdominal 3D Ultrasound in 317 Adolescent Girls.

CONTEXT: The knowledge of normal variation of reproductive hormones, internal genitalia imaging, and the prevalence of gynecological disorders in adolescent girls is limited. OBJECTIVE: The study aimed to describe reproductive parameters in postmenarchal girls from the general population including the frequency of oligomenorrhea, polycystic ovary syndrome, and use of hormonal contraception. DESIGN: The Copenhagen Mother-Child Cohort is a population-based longitudinal birth cohort of 1210 girls born between 1997 and 2002. SETTING: University hospital. PARTICIPANTS: A total of 317 girls were included, with a median age of 16.1 years and time since menarche of 2.9 years. MAIN OUTCOME MEASURE(S): Tanner stage, height, weight, age at menarche, menstrual cycle length and regularity, ovarian/uterine volume, and number of follicles were recorded. Serum concentrations of FSH, LH, anti-Müllerian hormone (AMH), inhibin B, estradiol, testosterone, SHBG, androstenedione, dehydroepiandrosterone sulfate, 17-OH-progesterone, and IGF-1 were measured. RESULTS: Twenty girls (6.3%) had oligomenorrhea and differed significantly in serum androgens and AMH, age at and time since menarche from girls with regular cycles. Twenty-seven girls were classified with PCOS (8.5%) and had significantly higher 17-OH-progesterone, estradiol, AMH, LH, and age at menarche than the reference group. Girls on oral contraception had significantly higher serum SHBG concentrations and lower serum concentrations of all hormones except AMH and IGF-1. Ovarian follicles 2 to 29.9 mm correlated positively with serum AMH (P < 0.0001). CONCLUSIONS: Most 16-year-old girls had regular menstrual cycles, normal reproductive hormones, and uterine and ovarian ultrasound. Serum AMH reflected ovarian follicle count and may be a useful biomarker of ovarian reserve.

Uterine volume and endometrial thickness in healthy girls evaluated by ultrasound (3-dimensional) and magnetic resonance imaging.

OBJECTIVE: To report normative data on uterine volume and endometrial thickness in girls, according to pubertal stages; to evaluate factors that affect uterine volume; and to compare transabdominal ultrasound (TAUS) and magnetic resonance imaging (MRI). DESIGN: Cross-sectional study of a nested cohort of girls participating in The Copenhagen Mother-Child Cohort. SETTING: General community. PATIENT(S): One hundred twenty-one healthy girls, aged 9.8-14.7 years. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Clinical examination, including pubertal breast stage (Tanner classification: B1-B5). Uterine volume: ellipsoid TAUS (n = 112) and 3-dimensional TAUS (n = 111); ellipsoid MRI (n = 61). Endometrial thickness: TAUS (n = 110) and MRI (n = 60). RESULT(S): Uterine volume and endometrial thickness were positively correlated with pubertal stages; e.g., ellipsoid TAUS: r = 0.753, and endometrium TAUS: 0.648. In multiple regression analyses, uterine volume was associated with the number of large follicles (TAUS >5 mm) (Beta 0.270); estradiol (E2) (Beta 0.504); and height (Beta 0.341). Volumes from ellipsoid vs. 3-dimensional TAUS were strongly correlated (r = 0.931), as were TAUS and MRI: ellipsoid volume (r = 0.891) and endometrial thickness (r = 0.540). Uterine volume was larger in TAUS compared with MRI; mean difference across the measured range: 7.7 (5.2-10.2) cm(3). Agreement was best for small uteri. CONCLUSION(S): Uterine volume and endometrial thickness increased as puberty progressed. Circulating E2 from large follicles was the main contributor to uterine and endometrial growth. The TAUS and MRI assessments of uterus and endometrium were strongly correlated.

Circulating AMH reflects ovarian morphology by magnetic resonance imaging and 3D ultrasound in 121 healthy girls.

CONTEXT: In adult women, Anti-Müllerian hormone (AMH) is produced by small growing follicles, and circulating levels of AMH reflect the number of antral follicles as well as primordial follicles. Whether AMH reflects follicle numbers in healthy girls remains to be elucidated. OBJECTIVE: This study aimed to evaluate whether serum levels of AMH reflects ovarian morphology in healthy girls. DESIGN AND SETTING: This was a population-based cohort study involving the general community. PARTICIPANTS: Included in the study were 121 healthy girls 9.8-14.7 years of age. MAIN OUTCOME MEASURES: Clinical examination, including pubertal breast stage (Tanner's classification B1-5), ovarian volume, as well as the number and size of antral follicles were assessed by two independent modalities: magnetic resonance imaging (MRI), Ellipsoid volume, follicles ≥2 mm; and Transabdominal ultrasound, Ellipsoid and 3D volume, follicles ≥1 mm. Circulating levels of AMH, inhibin B, estradiol, FSH, and LH were assessed by immunoassays; T and androstenedione were assessed by liquid chromatography-tandem mass spectrometry. RESULTS: AMH reflected the number of small (MRI 2-3 mm) and medium (4-6 mm) follicles (Pearson's Rho [r] = 0.531 and r = 0.512, P < .001) but not large follicles (≥7 mm) (r = 0.109, P = .323). In multiple regression analysis, small and medium follicles (MRI ≤ 6 mm) remained the main contributors to circulating AMH (ß, 0.501; P < .001) whereas the correlation between AMH and estradiol was negative (ß, -0.318; P = .005). In early puberty (B1-B3), the number of AMH-producing follicles (2-6 mm) correlated positively with pubertal stages (r = 0.453, P = .001), whereas AMH levels were unaffected (-0.183, P = .118). CONCLUSIONS: Similarly to adult women, small and medium antral follicles (≤6 mm) were the main contributors to circulating levels of AMH in girls.

Antithyroid drug-induced fetal goitrous hypothyroidism.

Maternal overtreatment with antithyroid drugs can induce fetal goitrous hypothyroidism. This condition can have a critical effect on pregnancy outcome, as well as on fetal growth and neurological development. The purpose of this Review is to clarify if and how fetal goitrous hypothyroidism can be prevented, and how to react when prevention has failed. Understanding the importance of pregnancy-related changes in maternal thyroid status when treating a pregnant woman is crucial to preventing fetal goitrous hypothyroidism. Maternal levels of free T(4) are the most consistent indication of maternal and fetal thyroid status. In patients with fetal goitrous hypothyroidism, intra-amniotic levothyroxine injections improve fetal outcome. The best way to avoid maternal overtreatment with antithyroid drugs is to monitor closely the maternal thyroid status, especially estimates of free T(4) levels.

Graves' disease in two pregnancies complicated by fetal goitrous hypothyroidism: successful in utero treatment with levothyroxine.

BACKGROUND: Treatment of Graves' disease during pregnancy with antithyroid drugs (ATDs) poses a risk of inducing hypothyroidism and, thus, development of a goiter to the fetus. PATIENT FINDINGS: We report two patients referred to our department after discovery of a fetal goiter by ultrasound examination in the second trimester of pregnancy. The women receiving 400 mg/day propylthiouracil and 10 mg/day thiamizole, respectively, had thyrotropin and total thyroxine values within the normal reference range but a lowered free thyroxine level. Fetal blood sampling by cordocentesis revealed severe fetal hypothyroidism as the cause of goiter development. Reduction of maternal ATD dose and injection of levothyroxine intra-amniotically quickly reduced the goiter size, and both babies were born euthyroid and without goiters. SUMMARY: Two pregnant women with Graves' disease were overtreated with ATDs inducing iatrogenic goiter in the fetuses. Successful treatment with intra-amniotic levothyroxine injections rendered the babies euthyroid and nongoitrous at birth. CONCLUSIONS: Correct interpretation of thyroid function tests during pregnancy in general--and during ATD therapy of Graves' disease in particular--is difficult. Awareness of pregnancy-related changes in maternal thyroid status, and a close teamwork among endocrinologists, obstetricians, and experts in fetal medicine, is pivotal in ensuring normal growth and development of the unborn child of these patients.

Early pituitary-gonadal activation before clinical signs of puberty in 5- to 8-year-old adopted girls: a study of 99 foreign adopted girls and 93 controls.

CONTEXT: Recent studies have indicated that internationally adopted girls are at high risk of developing precocious puberty. Clinical studies including a contemporary control group are lacking. OBJECTIVE: The objective was to study clinical, biochemical, and ultrasonographic markers of pituitary-gonadal activation in prepubertal adopted girls and a control group in the same age categories. SETTING: The study took place at University Hospital, Copenhagen, Denmark. DESIGN AND PARTICIPANTS: The study included randomly selected internationally adopted girls [(n = 99; mean age, 6.9 (5.1-8.5) yr] and controls of Danish origin [n = 93; mean age, 6.8 (5.2-8.5) yr] who were studied cross-sectionally. METHODS: Height, weight, and pubertal stage were assessed with serum levels of reproductive hormones. Size and morphology of internal genitals were evaluated by ultrasonography. Bone age was evaluated by x-ray of the left hand. RESULTS: Serum values of FSH were significantly higher in prepubertal adopted girls compared with controls [median, 1.4 (95% confidence interval, 0.4-3.6) vs. 1.0 (0.4-2.4) IU/liter; P <0.001]. Serum estradiol was above detection limit (>18 pmol/liter) in 46.5% of prepubertal adopted girls and 20.7% of controls (P = 0.001). In prepubertal adopted girls, the proportion of measurable samples increased significantly with age [odds ratio, 2.5 (95% confidence interval, 1.3-5.0; P = 0.009]. In controls, the odds ratio was 1.0 (0.6-1.7) (P = 0.9). Serum SHBG levels were significantly lower in prepubertal adopted girls compared with controls [99.0 (50.4-153.0) vs. 115.0 (53.1-202.1); P < 0.001]. CONCLUSION: Five- to 8-yr-old adopted girls showed signs of increased pituitary as well as gonadal activity despite prepubertal phenotype in the majority of girls. Our findings suggest that early onset of puberty in adopted girls is centrally driven.