RESUMO
We have studied a group of young adult women of mean age 23.8 +/- 6.5 (SD) years with only acne (A, n = 46), only hirsutism (H, n = 10), and acne plus hirsutism (A + H, n = 19) who sought dermatologic care. We measured the androgens, total and free testosterone (T), free 17 beta-hydroxysteroids (17-beta), dehydroepiandrosterone sulfate (DS), and the androgen precursors 17 alpha-hydroxypregnenolone (17-Preg) and 17 alpha-hydroxyprogesterone (17-Prog), as well as testosterone-estrogen binding globulin in all patients. Plasma hormone levels of the patients were compared to those of 23 controls of mean age 25.6 +/- 6.6 years who had neither acne nor hirsutism. Mean levels of all hormones measured, except 17-Preg, were elevated in the women with acne. Fifty-two percent of Group A, 60% of Group H, and 63% of Group A + H patients had at least one abnormal hormone level. The most frequently elevated plasma androgens in all the women with acne were: free T 25%, free 17-beta 23%, and DS 19%. Total T was high in only 12%. Elevations of plasma androgens were present in some women who did not have hirsutism or irregular menses. Identification of endocrine abnormalities in women with acne may potentially offer an opportunity for hormonal therapy.
Assuntos
Acne Vulgar/sangue , Androgênios/sangue , 17-alfa-Hidroxipregnenolona/análogos & derivados , 17-alfa-Hidroxipregnenolona/sangue , 17-alfa-Hidroxiprogesterona , Adolescente , Adulto , Desidroepiandrosterona/sangue , Feminino , Hirsutismo/sangue , Humanos , Hidroxiprogesteronas/sangue , Hidroxiesteroides/sangue , Distúrbios Menstruais/sangue , Globulina de Ligação a Hormônio Sexual/análise , Testosterona/sangueRESUMO
We undertook a pilot study to determine whether infusion of gonadotropin-releasing hormone (GnRH) might improve the distinction of hypogonadotropinism from the normal state and might permit gonadotropin deficiency to be diagnosed in the prepubertal child. Normal prepubertal and pubertal boys had a greater luteinizing hormone (LH) reaction (delta LH 54 +/- 15 [SD] ng/ml and 165 +/- 23 ng/ml, respectively) to a 4-hour infusion (100 microgram/hour) than to a 100-microgram bolus of GnRH (19 +/- 9 and 52 +/- 35 ng/ml). These augmented responses were observed in boys with delayed puberty, but not in apparently hypogonadotropic males greater than or equal to 12 years old. LH (delta LH 445 to 1602 ng/ml) and FSH (delta FSH 718 to 2112 ng/ml) surges were induced consistently by GnRH infusion only in normal, postmenarchial females. In all, of 13 hypopituitary cases classified as hypogonadotropic on the basis of a subnormal response to GnRH infusion, 31% had a normal response to the GnRH bolus (P = 0.05). Thus, GnRH infusion testing seems to improve the distinction of hypogonadotropic patients from normal individuals, including boys with delayed puberty.
Assuntos
Hormônio Foliculoestimulante/sangue , Hipopituitarismo/sangue , Hormônio Luteinizante/sangue , Adolescente , Adulto , Criança , Feminino , Gonadotropinas/deficiência , Hormônio do Crescimento/deficiência , Humanos , Masculino , Menopausa , Pessoa de Meia-Idade , Hormônios Liberadores de Hormônios Hipofisários/farmacologia , PuberdadeAssuntos
17-Cetosteroides/sangue , Córtex Suprarrenal/crescimento & desenvolvimento , Hormônio Adrenocorticotrópico , Maturidade Sexual , 17-alfa-Hidroxipregnenolona/sangue , Adolescente , Adulto , Androstenodiona/sangue , Criança , Pré-Escolar , Desidroepiandrosterona/análogos & derivados , Desidroepiandrosterona/sangue , Sulfato de Desidroepiandrosterona , Dexametasona , Feminino , Humanos , Hidroxiprogesteronas/sangue , MasculinoAssuntos
3-Hidroxiesteroide Desidrogenases/deficiência , Acne Vulgar/etiologia , Hiperplasia Suprarrenal Congênita/sangue , Amenorreia/etiologia , Progesterona Redutase/deficiência , Puberdade , Esteroides/sangue , Adolescente , Hiperplasia Suprarrenal Congênita/complicações , Hormônio Adrenocorticotrópico , Androgênios/sangue , Dexametasona , Estrogênios/sangue , Feminino , Hirsutismo/etiologia , Humanos , Masculino , Menstruação , Progestinas/sangueRESUMO
We found elevations of plasma dehydroepiandrosterone-sulfate (DHAS) in five boys, 5.5 to 10.3 years of age (group A), with premature pubarche (pubic hair development) or acne as an isolated phenomenon. Four boys (group B) with seemingly idiopathic premature pubarche (DHAS normal for age) were discovered to have above-average dehydroepiandrosterone levels. All of these boys with premature pubarche had some evidence of cerebral dysfunction or were obese. Plasma testosterone values and bone age were not markedly increased in either group. In each case studied, the patterns of plasma steroid intermediates before and after administration of adenocorticotropin were typical of adrenarche rather than of congenital adrenal hyperplasia or Cushing syndrome. In addition, DHAS was dexamethasone suppressible, and in those patients in whom nocturnal testosterone sampling or gonadotropin-releasing hormone testing was performed, no evidence of true puberty could be found. Fifteen percent of our normal male volunteers over 10 years of age developed pubarche with plasma DHAS levels over 120 micrograms/dl without evidence of true puberty. Thus pubarche as an isolated phenomenon does not necessarily indicate a virilizing disorder or true puberty. In the majority of cases, isolated pubarche appears to be the result of isolated adrenarche, the maturational increase in adrenal production of 17-ketosteroids.
Assuntos
Puberdade Precoce/etiologia , Maturidade Sexual , Glândulas Suprarrenais/fisiologia , Criança , Pré-Escolar , Desidroepiandrosterona/análogos & derivados , Desidroepiandrosterona/sangue , Sulfato de Desidroepiandrosterona , Humanos , Masculino , Puberdade Precoce/sangue , Testosterona/sangueRESUMO
We have measured bioactive LH in the plasma of 60 normal boys and 45 normal girls throughout puberty because the rise in immunoreactive LH has seemed too small to account for the profound changes in sexual maturation during adolescence. Bioactive LH was determined using an in vitro bioassay (rat interstitial cell testosterone production); I-LH was measured by radioimmunoassay using the same LH standard, LER 907. Bioactive LH was measurable in all 270 plasma samples; I-LH in 218. In both boys and girls, B-LH rose more than I-LH when compared to chronological age, bone age, and pubertal stage. In boys, B-LH increased 8.2-fold (P < 0.001) from prepuberty to late puberty, whereas I-LH rose 3.0-fold (P < 0.001). Similarly, in girls B-LH increased 23.1-fold (P < 0.001) while I-LH increased 4.9-fold (P < 0.001). Between pubertal stages there was less overlap of individual values of B-LH, in comparison to those of I-LH. We conclude that B-LH increases more than I-LH during normal puberty and is a more discriminating measure of maturation. One implication of these findings is that a qualitative change in gonadotropin secretion may occur during puberty.
Assuntos
Hormônio Luteinizante/sangue , Puberdade , Adolescente , Bioensaio , Criança , Feminino , Humanos , Masculino , RadioimunoensaioRESUMO
Since luteinizing hormone levels by radioimmunoassay (I-LH) have rarely been useful in distinguishing true isosexual precocity from other less serious disorders of puberty, we have studied bioassayable B-LH in 17 prepubertal girls, seven girls with premature adrenarche, 12 girls with premature thelarche, and six girls with true isosexual precocity. The I-LH levels were three times higher in the girls with true precocious puberty than in the other groups but there was overlap between those with premature thelarche and true precocious puberty. The B-LH levels were 16 times higher in the girls with isosexual precocity than in the others, and there was no overlap. We conclude that B-LH better discriminates between true isosexual precocity and other disorders of puberty and may be a very useful laboratory test for the early diagnosis of true precocious puberty.
Assuntos
Hormônio Luteinizante/sangue , Puberdade Precoce/sangue , Córtex Suprarrenal/fisiologia , Bioensaio , Mama/crescimento & desenvolvimento , Criança , Pré-Escolar , Diagnóstico Diferencial , Feminino , HumanosRESUMO
The cardiac status of 18 hyperthyroid (HT) children (9 black and 9 white) was evaluated by echocardiography. Mitral regurgitation (MR) was diagnosed clinically in 33% (6 of the 9 blacks). None of the 9 white children had MR. Left ventricular end-diastolic diameter (LVEDD) and volume (LVEDV) did not differ from the predicted normal (PN) based on body surface area and heart rate, except in those with MR where increased LVEDD and LVEDV were noted (p less than 0.02). LV mass was +1.75 standard deviations (sigma) of the PN (p less than 0.01), due to increased wall thickness of LVEDV. Left ventricular output (LVO) was +0.35 sigma PN (p = ns); however, when compared to that of normal children, LVO of HT was higher (p less than 0.001) due to the increased heart rate. Enhanced left ventricular contractility was suggested by increased rate of dimensional change during ejection (peak dD/dt-syst), with a mean value of -11.39 cm/sec as compared to the normal of -9.54 cm/sec (p less than 0.01). A linear multivariate regression equation differentiated the cardiac status of HT from that of normal children. Following treatment to euthyroid state, MR disappeared in 2 and became less in 4 patients. LVO, LV mass, and peak dD/dt-syst also became less. Significant cardiac changes occur in children with hyperthyroidism, which may be reversible in part after euthyroidism is restored.
Assuntos
Hipertireoidismo/complicações , Insuficiência da Valva Mitral/complicações , Adolescente , Débito Cardíaco , Volume Cardíaco , Cardiomegalia/fisiopatologia , Criança , Pré-Escolar , Ecocardiografia , Feminino , Ventrículos do Coração/fisiopatologia , Humanos , Masculino , Estudos Prospectivos , Volume SistólicoRESUMO
Eight cases of the fetal alcohol syndrome are presented with emphasis on their frequent orthopedic anomalies, i.e. hypoplastic toenails (100%), shortened fingers, usually the fifth (75%), radioulnar synostosis, camptodactyly of fingers, clinodactyly of toes, and flexion contractures of the elbow (all 50%). These are in addition to 7 other orthopedic anomalies observed less frequently and some 18 general characteristics had an extensive endocrine, biochemical and genetic work-up and no abnormalities were found to explain the snydrome other than the teratogenicity of the maternal alcohol abuse. Since the orthopedist may be the first physician to see these patients, diagnosis of these musculoskeletal anomalies should include a social history and investigation for fetal alcohol syndrome.
Assuntos
Transtornos do Espectro Alcoólico Fetal/diagnóstico , Pré-Escolar , Doenças do Sistema Endócrino/complicações , Feminino , Transtornos do Espectro Alcoólico Fetal/etiologia , Transtornos do Espectro Alcoólico Fetal/patologia , Humanos , Masculino , Síndrome de Noonan/diagnóstico , Gravidez , Sinostose/complicaçõesRESUMO
Two patients who presented at birth with neonatal diabetes mellitus (NDM) are described: one with paternal uniparental disomy for chromosome 6 and one with normal, biparental inheritance. The first child presented with low birth weight, macroglossia, hypertelorism, and club foot in addition to NDM. In this patient hyperglycemia was transient, and insulin treatment was discontinued at 4 months of age. The second child also presented with low birth weight but was normal in appearance, and insulin dependence continues after 5 years. Genetic analysis with polymorphic DNA markers for chromosome 6 indicated the presence of paternal uniparental disomy (UPD) in the first case and normal, biparental inheritance in the second case. Paternal UPD 6 has been reported in 8 previous cases of which 6 showed NDM. Three cases with paternal UPD 6 also included additional anomalies, such as macroglossia, not usually associated with NDM. Therefore the simultaneous finding of NDM and macroglossia should be a strong indicator for genetic testing. The genetic finding of paternal UPD 6 allows prediction of a transient, rather than permanent, form of diabetes mellitus and no increased recurrence risk of transient NDM in subsequent pregnancies.
Assuntos
Aneuploidia , Cromossomos Humanos Par 6 , Diabetes Mellitus/genética , Diabetes Mellitus/tratamento farmacológico , Pai , Feminino , Testes Genéticos , Humanos , Recém-Nascido , Insulina/administração & dosagem , Masculino , Repetições de Microssatélites , Polimorfismo GenéticoRESUMO
Mutations in the gene encoding the Pit-1 transcriptional activator interfere with the embryologic determination and ultimate functions of anterior pituitary cells that produce growth hormone (GH), prolactin (Prl) and thyroid-stimulating hormone (TSH). Central hypothyroidism is often the presenting feature of combined pituitary hormone deficiency (CPHD), but it is not detected in screening programs that rely upon elevation of TSH. We report a child whose hypothyroidism was recognized clinically at age 6 weeks, and subsequently found to have GH and Prl as well as TSH deficiency. With thyroxine and GH replacement he has reached the 70th percentile for height and has normal intelligence. Molecular analysis of genomic DNA for Pit-1 revealed the presence of compound heterozygous recessive mutations: a nonsense mutation in codon 172 and a novel missense mutation substituting glycine for glutamate at codon 174. This case is the first demonstration of CPHD due to compound heterozygous Pit-1 point mutations, as most reported cases of the CPHD phenotype involve either the dominant negative R271W allele or homozygosity for recessive Pit-1 mutations. Therefore, in cases of CPHD, the possibilities of compound heterozygosity for two different Pit-1 mutations, or homozygosity for mutations in the epigenetic gene, Prop-1, should be considered.
Assuntos
Proteínas de Ligação a DNA/genética , Hipotireoidismo/genética , Mutação/fisiologia , Fatores de Transcrição/genética , Alelos , Éxons , Hormônio do Crescimento/uso terapêutico , Heterozigoto , Humanos , Lactente , Masculino , Fenótipo , Reação em Cadeia da Polimerase , Tiroxina/uso terapêutico , Fator de Transcrição Pit-1RESUMO
BACKGROUND: A new form of congenital hyperinsulinism characterized by hypoglycemia and hyperammonemia was described recently. We hypothesized that this syndrome of hyperinsulinism and hyperammonemia was caused by excessive activity of glutamate dehydrogenase, which oxidizes glutamate to alpha-ketoglutarate and which is a potential regulator of insulin secretion in pancreatic beta cells and of ureagenesis in the liver. METHODS: We measured glutamate dehydrogenase activity in lymphoblasts from eight unrelated children with the hyperinsulinism-hyperammonemia syndrome: six with sporadic cases and two with familial cases. We identified mutations in the glutamate dehydrogenase gene by sequencing glutamate dehydrogenase complementary DNA prepared from lymphoblast messenger RNA. Site-directed mutagenesis was used to express the mutations in COS-7 cells. RESULTS: The sensitivity of glutamate dehydrogenase to inhibition by guanosine 5'-triphosphate was a quarter of the normal level in the patients with sporadic hyperinsulinism-hyperammonemia syndrome and half the normal level in patients with familial cases and their affected relatives, findings consistent with overactivity of the enzyme. These differences in enzyme insensitivity correlated with differences in the severity of hypoglycemia in the two groups. All eight children were heterozygous for the wild-type allele and had a mutation in the proposed allosteric domain of the enzyme. Four different mutations were identified in the six patients with sporadic cases; the two patients with familial cases shared a fifth mutation. In two clones of COS-7 cells transfected with the mutant sequence from one patient, the sensitivity of the enzyme to guanosine 5'-triphosphate was reduced, findings similar to those in the child's lymphoblasts. CONCLUSIONS: The hyperinsulinism-hyperammonemia syndrome is caused by mutations in the glutamate dehydrogenase gene that impair the control of enzyme activity.
Assuntos
Amônia/sangue , Glutamato Desidrogenase/genética , Hiperinsulinismo/congênito , Erros Inatos do Metabolismo/genética , Mutação Puntual , Amônia/metabolismo , Criança , Pré-Escolar , Análise Mutacional de DNA , Feminino , Glutamato Desidrogenase/metabolismo , Humanos , Hiperinsulinismo/enzimologia , Hiperinsulinismo/genética , Lactente , Insulina/metabolismo , Secreção de Insulina , Masculino , Mitocôndrias/enzimologia , Síndrome , Ureia/metabolismoRESUMO
Severe neonatal hypoglycemia with pathologic findings of diffuse nesidoblastosis of the pancreas is described in five children of both sexes from two families with unaffected parents. This appears to represent an autosomal recessive disorder of pancreatic development. Despite extensive testing, the diagnosis of hyperinsulinism was difficult in the index case of each family and delayed definitive treatment. Medical therapy with steroids and diazoxide was unsuccessful; pancreatectomy was required to treat persistent hypoglycemia. An abnormality of circulating glucagon found in one child with this disorder suggested that hyperinsulinism may not be the sole hormonal imbalance present, but rather that this disease is one of generalized disturbance of islet cell function. The history of severe, persistent neonatal hypoglycemia in an older sibling should lead the physician to investigate subsequent children for the presence of asymptomatic hypoglycemia.