1/10. Delayed closure of epiphyseal cartilages induced by the aromatase inhibitor anastrozole. Would it help short children grow up?estrogens locally generated from androgen precursors due to the action of aromatase play a main role in epiphyseal cartilage fusion. Treatment with an aromatase inhibitor (anastrozole, 1 mg/day for 3 yr) in a boy previously operated on for a hamartoma causing precocious puberty and presenting with advanced bone maturation and nearly fused epiphyseal cartilages, slowed cartilage fusion consenting a higher final stature than expected (164.4 cm vs 158.4 cm). It is suggested that treatment with aromatase inhibitors, alone or in combination with rh-GH, may also be useful in children with constitutional short stature in order to delay epiphyseal closure and improve the final height.- - - - - - - - - - ranking = 1keywords = androgen (Clic here for more details about this article) |
2/10. Abnormalities of GH secretion in a young girl with Floating-Harbor syndrome.We present a 9.1-year-old girl of Calabrian (italy) ancestry, with clinical features (cranio-facial dysmorphism, short stature with delayed bone age and speech delay) suggesting the diagnosis of Floating-Harbor syndrome (FHS). physical examination showed: height 113.9 cm (-2.9 SD), with a parent's target of 156.2 cm ( 1.0 SD), weight 20.7 kg, BMI 16.0 (-0.04 SD), and many phenotypic abnormalities: long eyelashes, large bulbous nose with broad nasal bridge, short philtrum, moderately broad mouth, tooth folding and malocclusion, posteriorly rotated ears, low posterior hair line, short neck, clinodactyly of the 5th finger and hyperextensible finger joints. Diffused hyperpigmentation and hypertrichosis with sporadic pubic terminal hairs, but neither clitoromegaly nor other signs of hyperandrogenism and/or precocious puberty, were observed (T1, P1). Carpal bone evaluation showed a delayed bone age (TW2: 5-5/10, - 3.6 yr) and the statural age/bone age ratio was 1.1. Other dysmorphic syndromes were excluded on the basis of clinical evidence, also evaluated by a computer-assisted search (P.O.S.S.U.M. version 3.5, 1992). Analysis of chromosome 22 by the FISH method, using specific probes Cos29 and Tuple1, excluded microdeletions in the region 22q11.2, typical of Velo-cardio-facial syndrome. In this case, we report the impairment of serum GH responsiveness (GH baseline values: 0.2-1.9 ng/ml) to the administration of oral 150 microg clonidine [peak 4.7 ng/ml, normal values (nv)>10 ng/ml] and oral 4 mg dexamethasone (8.1 ng/ml, nv>10 ng/ml). Moreover, the evaluation of spontaneous 24-h GH secretion (Carmeda AB, Stockholm, sweden) showed low mean GH levels (1.75 ng/ml, nv>3.0 ng/ml), with a maximum sleep-related peak of 2.8 ng/ml. serum IGF-1 values were in the low-normal range (80-176 ng/ml, nv 133-626 ng/ml). While in FHS the cranio-facial features minimize with advancement of age, the impairment of growth velocity is permanent and results in severe dwarfism. In our case, treatment with recombinant GH (0.10 U/kg/day), administered by a needle-free device, induced a dramatic increase of growth velocity, increasing the height from -2.8 to -1.9 SD after 18 months, thus indirectly confirming a role of GH deficiency in the pathogenesis of FHS dwarfism.- - - - - - - - - - ranking = 1keywords = androgen (Clic here for more details about this article) |
3/10. Cortisol and estradiol secretion by a benign virilizing adrenocortical tumor in a prepubertal girl.We report a 5.5 year-old girl with a benign adrenocortical adenoma who presented with virilization and rapid growth. She did not have any clinical features of isosexual precocity or, except for hypertension, Cushing's syndrome. Measurement of hormones in adrenal vein blood obtained at surgery showed high concentrations of testosterone, cortisol, estradiol and intermediary substrates. Elevated levels of hormones detected in the peripheral blood were released directly from the tumor and were not the result of peripheral interconversion. hyperandrogenism can obscure the clinical features of Cushing's syndrome and estrogen hypersecretion in patients with functional adrenal tumors.- - - - - - - - - - ranking = 1keywords = androgen (Clic here for more details about this article) |
4/10. Duplication of Xq26.2-q27.1, including SOX3, in a mother and daughter with short stature and dyslalia.Duplications of the distal long arm of the x chromosome are rare and carrier females are usually phenotypically normal. We report on a 14-year-old short statured (height and weight <3rd centile) girl with dup(X)(q26.2q27.1) inherited from a short mother. The proband has minor dysmorphic features, lordosis, lack of menarche, late signs of puberty, low prepuberal levels of gonadotrophins and steroids, but borderline low IGF-1 and normal IGF-Bp3 serum levels. Both the proposita and her mother have severe speech problems with stuttering and dyslalia. The 44-year-old mother with a strikingly aged face and a prominent nose, had menarche at 15 years. Both maternal sisters and the grandmother of the proposita are also short. karyotyping revealed an additional band at Xq26 in all metaphases from the proband, her mother, and two maternal aunts. Molecular cytogenetic investigations revealed an Xq26.2-q27.1 direct duplication of approximately 7.5 Mb that encompasses or disrupts the SOX3 gene, which maps at the distal border of the duplicated segment. A similar chromosomal duplication was reported recently in five families and in each was associated with an abnormal phenotype in males with short stature [Hol et al., 2000; Solomon et al., 2002, 2004]. Using an androgen-receptor (HUMARA) gene methylation assay and FISH, we show that despite preferential inactivation of the dup(Xq) chromosome a significant proportion of lymphocytes in both mother and daughter carry an active duplicated x chromosome. Our findings further suggest that a dosage effect of SOX3 may to be responsible for a speech disorder in addition to short stature secondary to hypopituitarism.- - - - - - - - - - ranking = 1keywords = androgen (Clic here for more details about this article) |
5/10. Alternate day prednisone therapy in congenital adrenal hyperplasia: adrenal androgen suppression and normal growth.Daily glucocorticoid therapy of children with congenital adrenal hyperplasia (CAH) frequently results in a suboptimal mature height. In contrast, pharmacological doses of prednisone given on alternate days generally allow normal growth in children with autoimmune, hematological, and renal disorders. Moreover, alternate day prednisone therapy suppresses adrenal androgen secretion on both the day on and the day off therapy in patients with systemic lupus erythematosus. We hypothesized that alternate day prednisone therapy might be efficacious in the treatment of CAH. To evaluate this hypothesis, we studied an 11-yr-old girl with salt-losing 21-hydroxylase deficiency and severe asthma treated with alternate day prednisone therapy (20 mg every other day) for over 3 yr. During this period her linear growth was along the 65th percentile, and her bone age paralleled her chronological age. Pubertal development was normal, and she had no signs of androgen or glucocorticoid excess. In keeping with her clinical picture, basal (24-h samples drawn every 60 min) and ovine CRH-stimulated plasma adrenal androgen (dehydroepiandrosterone sulfate and delta 4-androstenedione) concentrations and 24-h urinary 17-ketosteroid excretion were low on both the day on and the day off prednisone. However, her plasma ACTH and 17-hydroxyprogesterone levels were markedly elevated on both days. The adrenal androgen suppression, therefore, appeared independent of the level of ACTH, suggesting different regulation of the zona fasciculata and the zona reticularis. GH secretion, assessed by measurement of plasma GH every 20 min for 48 h, was normal on both the on and off days of prednisone therapy. Therefore, in this girl pharmacological doses of prednisone given on alternate days caused sustained adrenal androgen suppression and allowed normal growth and pubertal development, despite persistently elevated plasma ACTH and 17-hydroxyprogesterone levels.- - - - - - - - - - ranking = 9keywords = androgen (Clic here for more details about this article) |
6/10. Possible abnormalities of steroid secretion in children with smith-lemli-opitz syndrome and their parents.In early infancy, two unrelated children with smith-lemli-opitz syndrome were found to have elevated levels of androgen sulfates. When the steroid conjugates in the serum of normal infants were hydrolyzed and chromatographed on Sephadex LH-20, 4 androgen containing peaks (I, II, III, IV) were found. In the serum from these two infants with smith-lemli-opitz syndrome, Peaks I and III were increased, but Peaks II and IV were absent. The parents of the two children, and of three additional unrelated children with smith-lemli-opitz syndrome, had exaggerated 17-hydroxyprogesterone responses to an intravenous bolus of ACTH. These findings suggest that a defect in steroid metabolism may be linked to the smith-lemli-opitz syndrome.- - - - - - - - - - ranking = 2keywords = androgen (Clic here for more details about this article) |
7/10. Incomplete testicular feminization with multiple congenital abnormalities.A female infant presented with absent vagina and uterus, absent left kidney, absent right gonad, growth failure, mental retardation, seizure disorder, and facial, limb, and hand anomalies. The chromosome karyotype was 46, XY in her blood and cultured cells, including cells from the sites of both gonads. Her H-Y antigen was positive. Specific dihydrotestosterone binding was reduced in cells from a labial skin biopsy. The case might be due to a minute deletion of the short arm of the x chromosome, resulting in loss of a gene for androgen receptors and of adjacent chromosomal material responsible for the growth failure and the somatic and neurologic anomalies.- - - - - - - - - - ranking = 1keywords = androgen (Clic here for more details about this article) |
8/10. Gonadal function in two siblings with Fanconi's anemia.2 siblings with Fanconi's anemia, 1 male and 1 female, aged 22 and 24 years, respectively, were evaluated at the Johns Hopkins Hospital because of short stature and hypogonadism. plasma levels of somatomedin-C were normal in both patients, suggesting that the production of biologically active growth hormone was normal in these subjects. In addition, measurements of serum gonadotropins and plasma androgens in our patients, along with data accumulated from previous studies in the literature, show that abnormal sexual development in patients with Fanconi's anemia is due to hypergonadotropic hypogonadism.- - - - - - - - - - ranking = 1keywords = androgen (Clic here for more details about this article) |
9/10. "De novo" duplication Xq23-->Xq26 of paternal origin in a girl with a mildly affected phenotype.We report a de novo dup(X)(q23-->q26) in a 3-year-old girl with growth retardation, developmental delay, and minor anomalies. X-inactivation in lymphocytes by BRDU labeling showed the abnormal X was late replicating. The androgen receptor assay (HAR) demonstrated a skewed methylation (88.8%) of the paternal allele and a 11.2% methylation of the maternal allele. These data, which suggest the duplication was paternally inherited, are the first parental-origin identification of a duplication Xq. The mild phenotype of the patient may be related to the size and region of the duplication, the low percentage of a dup(X) active detected by the HAR assay, or a combination of these mechanisms.- - - - - - - - - - ranking = 1keywords = androgen (Clic here for more details about this article) |
10/10. Clinical and molecular characterization of a Brazilian patient with Pit-1 deficiency.We studied a 14 year-old girl with extreme short stature (-9.5 SDS), normal psychomotor development and signs of progressive hypothyroidism. Basal IGF-I and T4 were low. serum GH was low after insulin-induced hypoglycemia and GH-releasing hormone administration. Both TSH and prolactin were low and did not rise after TRH administration. gonadotropins were normal and cortisol levels were elevated. In contrast, DHEA-S levels were low and she did not develop pubic hair until 26 years of age, compatible with deficiency of a putative pituitary adrenal androgen stimulating hormone. Pituitary size was reduced on magnetic resonance imaging. Sequencing of the Pit-1 gene revealed a heterozygous C to T transition in codon 271 resulting in substitution of tryptophane for a highly conserved arginine. Her parents were homozygous normal for this locus indicating a de novo mutation with dominant expression. Genetic and phenotypic heterogeneity of patients with Pit-1 gene mutations, particularly the R271W mutation, may reveal further information about the nature of genetic silencing, imprinting, and epigenetic inheritance. The relationship of Pit-1 deficiency to abnormal adrenal secretion remains to be elucidated.- - - - - - - - - - ranking = 1keywords = androgen (Clic here for more details about this article) |
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