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1.
J Clin Endocrinol Metab ; 97(6): 2059-67, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22472563

RESUMO

CONTEXT: Cytotoxic treatment may accelerate depletion of the primordial follicle pool, leading to impaired fertility and premature menopause. Assessment of ovarian damage in prepubertal girls is not currently possible, but Anti-Müllerian Hormone (AMH) is a useful marker of ovarian reserve in adults. OBJECTIVE: The objective of the study was to prospectively evaluate AMH measurement in children as a marker of ovarian toxicity during cancer treatment. DESIGN AND SETTING: This was a prospective, longitudinal study at a University Hospital. PATIENTS: Twenty-two females (17 prepubertal), median age 4.4 yr (range 0.3-15 yr), were recruited before treatment for cancer. MAIN OUTCOME MEASURES: AMH, inhibin B, and FSH at diagnosis, after each chemotherapy course and during follow-up, were measured. Risk of gonadotoxicity was classified as low/medium (n = 13) or high (n = 9) based on chemotherapy agent, cumulative dose, and radiotherapy involving the ovaries. RESULTS: Pretreatment AMH was detectable across the age range studied. AMH decreased progressively during chemotherapy (P < 0.0001) in both prepubertal and pubertal girls, becoming undetectable in 50% of patients, with recovery in the low/medium risk groups after completion of treatment. In the high-risk group, AMH became undetectable in all patients and showed no recovery. Inhibin B was undetectable in most patients before treatment and, with FSH, showed no clear relationship to treatment. CONCLUSION: AMH is detectable in girls of all ages and falls rapidly during cancer treatment in both prepubertal and pubertal girls. Both the fall during treatment and recovery thereafter varied with risk of gonadotoxicity. AMH is therefore a clinically useful marker of damage to the ovarian reserve in girls receiving treatment for cancer.


Assuntos
Hormônio Antimülleriano/sangue , Quimiorradioterapia/efeitos adversos , Infertilidade Feminina/sangue , Neoplasias/terapia , Ovário/efeitos dos fármacos , Ovário/efeitos da radiação , Adolescente , Antineoplásicos/efeitos adversos , Biomarcadores/sangue , Criança , Pré-Escolar , Cisplatino/efeitos adversos , Ciclofosfamida/efeitos adversos , Feminino , Humanos , Lactente , Infertilidade Feminina/epidemiologia , Infertilidade Feminina/etiologia , Inibinas/sangue , Estudos Longitudinais , Neoplasias/epidemiologia , Ovário/fisiologia , Estudos Prospectivos , Puberdade , Fatores de Risco
2.
Clin Endocrinol (Oxf) ; 73(6): 707-14, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20738314

RESUMO

BACKGROUND: The aim of this exploratory study was to establish whether we could improve skeletal health with a physiological regimen of SSR in young women with premature ovarian failure (POF). PATIENTS AND METHODS: In an open-label randomized controlled crossover trial, 34 women with POF were randomized to 4-week cycles of pSSR (transdermal oestradiol, 100 µg daily for week 1, 150 µg for weeks 2-4; vaginal progesterone, 200 mg twice daily for weeks 3-4) or standard hormone replacement treatment (sHRT) (oral ethinyloestradiol 30 µg and 1·5 mg norethisterone daily for weeks 1-3, week 4 'pill-free') for 12 months. Bone mineral density (BMD) was measured by DEXA at study entry and after each 12-month treatment period. Blood samples for hormones and markers of bone formation (bone alkaline phosphatase, BALP and type I collagen N-terminal propeptide, PINP) and bone resorption (CrossLaps) were collected pre-/postwashout and after 3, 6 and 12 months of each treatment. RESULTS: Eighteen women, mean 27 (range 19-39) years, completed the study. Both regimens caused similar suppression of LH and FSH. Mean baseline lumbar spine BMD z-score was -0·89 (95% CI -1·27 to -0·51) and increased by +0·17 (CI +0·07 to +0·27) in response to pSSR (P = 0·003), compared with +0·07 (CI -0·03 to +0·18) during standard HRT (P = 0·2). During pSSR, the increment in lumbar spine BMD z-score was related positively to oestradiol (r = +0·49, P = 0·04) and inversely to FSH (r = -0·65, P = 0·004). Bone formation markers, BALP and P1NP increased in the pSSR arm (anova P < 0·001) but decreased in the sHRT arm (P < 0·01). Both treatments suppressed the bone resorption marker, CrossLaps (P < 0·001). CONCLUSION: We conclude that pSSR over 12 months has a beneficial affect on bone mass acquisition on the lumbar spine in women with POF, mediated by increased bone formation and decreased bone resorption.


Assuntos
Densidade Óssea/efeitos dos fármacos , Terapia de Reposição de Estrogênios , Insuficiência Ovariana Primária/tratamento farmacológico , Insuficiência Ovariana Primária/metabolismo , Adulto , Vias de Administração de Medicamentos , Esquema de Medicação , Estradiol/administração & dosagem , Estradiol/uso terapêutico , Etinilestradiol/administração & dosagem , Etinilestradiol/uso terapêutico , Feminino , Humanos , Noretindrona/administração & dosagem , Noretindrona/uso terapêutico , Progesterona/administração & dosagem , Progesterona/uso terapêutico , Adulto Jovem
3.
Clin Endocrinol (Oxf) ; 73(5): 637-43, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-20681995

RESUMO

OBJECTIVES: Post-traumatic hypopituitarism is well described amongst adult traumatic brain injury (TBI) survivors. We aimed to determine the prevalence and clinical significance of pituitary dysfunction after head injury in childhood. DESIGN: Retrospective exploratory study. PATIENTS: 33 survivors of accidental head injury (27 boys). Mean (range) age at study was 13·4 years (5·4-21·7 years) and median (range) interval since injury 4·3 years (1·4-7·8 years). Functional outcome at study: 15 good recovery, 16 moderate disability, two severe disability. MEASUREMENTS: Early morning urine osmolality and basal hormone evaluation were followed by the gonadotrophin releasing hormone (GnRH) and insulin tolerance (n = 25) or glucagon tests (if previous seizures, n = 8). Subjects were not primed. Head injury details were extracted from patient records. RESULTS: No subject had short stature (mean height SD score +0·50, range -1·57 to +3·00). Suboptimal GH responses (<5 µg/l) occurred in six peri-pubertal boys (one with slow growth on follow-up) and one postpubertal adolescent (peak GH 3·2 µg/l). Median peak cortisol responses to insulin tolerance or glucagon tests were 538 and 562 nm. Nine of twenty-five and two of eight subjects had suboptimal responses, respectively, two with high basal cortisol levels. None required routine glucocorticoid replacement. In three, steroid cover was recommended for moderate/severe illness or injury. One boy was prolactin deficient. Other basal endocrine results and GnRH-stimulated LH and FSH were appropriate for age, sex and pubertal stage. Abnormal endocrine findings were unrelated to the severity or other characteristics of TBI or functional outcome. CONCLUSIONS: No clinically significant endocrinopathy was identified amongst survivors of accidental childhood TBI, although minor pituitary hormone abnormalities were observed.


Assuntos
Lesões Encefálicas/fisiopatologia , Hipófise/fisiopatologia , Hormônios Hipofisários/fisiologia , Adolescente , Criança , Estudos Transversais , Feminino , Glucagon , Hormônio do Crescimento Humano/deficiência , Humanos , Hidrocortisona/deficiência , Sistema Hipotálamo-Hipofisário/fisiopatologia , Insulina , Masculino , Sistema Hipófise-Suprarrenal/fisiopatologia , Estudos Retrospectivos
4.
J Cyst Fibros ; 8(6): 382-5, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19800301

RESUMO

BACKGROUND: CF infants may be at increased risk of sodium depletion which may lead to impaired growth. The objective of this study was to evaluate their sodium supplementation requirements. METHODS: Ten CF infants had serial measurements of weight and plasma/urine sodium and creatinine. Sodium supplementation was adjusted with the aim of maintaining fractional excretion (FENa) between 0.5% and 1.5% and urinary sodium > 10 mmol/L. RESULTS: Urine sodium:creatinine (UNa:Cr) ratio strongly correlated with FENa [UNa:Cr (mmol/mmol)=35.0 x FENa (r=0.99)]. The FENa target range corresponded to UNa:Cr 17-52 mmol/mmol. All infants required sodium supplementation to achieve UNa:Cr > 17 mmol/mmol. Sodium supplement requirements (mean+/-SD) at ages 0-3, 3-6, 6-9 and 9-12 months were 1.9+/-0.5, 1.8+/-0.8, 1.9+/-0.9 and 0.8+/-0.4 mmol/kg/d. No infant required calorie supplementation to achieve expected weight gain. CONCLUSIONS: Using current UK guidelines, many cases of sodium depletion may be overlooked. Some infants require more than the recommended 1-2 mmol/kg/d. UNa:Cr ratio is a useful non-invasive measure to monitor sodium supplementation.


Assuntos
Fibrose Cística/dietoterapia , Hiponatremia/dietoterapia , Doenças do Recém-Nascido/dietoterapia , Cloreto de Sódio na Dieta/administração & dosagem , Adolescente , Peso Corporal , Creatinina/urina , Fibrose Cística/metabolismo , Feminino , Humanos , Hiponatremia/sangue , Hiponatremia/urina , Recém-Nascido , Doenças do Recém-Nascido/metabolismo , Masculino , Cloreto de Sódio na Dieta/farmacocinética
5.
Endocr Dev ; 15: 77-100, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19293605

RESUMO

Children with cancer are exposed to multiple influences that may adversely affect bone health. Some treatments have direct deleterious effects on bone whilst others may have indirect effects mediated through various endocrine abnormalities. Most clinical outcome studies have concentrated on survivors of acute lymphoblastic leukaemia (ALL). There is now good evidence that earlier treatment protocols that included cranial irradiation with doses of 24 Gy or greater may result in growth hormone deficiency and low bone mineral density (BMD) in the lumbar spine and femoral neck. Under current protocols, BMD decreases during intensive chemotherapy and fracture risk increases. Although total body BMD may eventually return to normal after completion of chemotherapy, lumbar spine trabecular BMD may remain low for many years. The implications for long-term fracture risk are unknown. Risk factors for low BMD include high dose methotrexate, higher cumulative doses of glucocorticoids, male gender and low physical activity. BMD outcome in non-ALL childhood cancers has been less well studied but there is evidence that survivors of childhood brain or bone tumours, and survivors of bone marrow transplants for childhood malignancy, all have a high risk of long-term osteopenia. Long-term follow-up is required, with appropriate treatment of any endocrine abnormalities identified.


Assuntos
Remodelação Óssea/fisiologia , Osso e Ossos/fisiologia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Transplante de Medula Óssea/efeitos adversos , Remodelação Óssea/efeitos dos fármacos , Remodelação Óssea/efeitos da radiação , Osso e Ossos/efeitos dos fármacos , Osso e Ossos/efeitos da radiação , Criança , Ensaios Clínicos como Assunto , Gônadas/efeitos dos fármacos , Gônadas/fisiopatologia , Gônadas/efeitos da radiação , Humanos , Monitorização Fisiológica/métodos , Neoplasias/complicações , Neoplasias/terapia , Lesões por Radiação/complicações , Lesões por Radiação/fisiopatologia , Radioterapia/efeitos adversos
6.
Eur J Pediatr ; 167(11): 1313-9, 2008 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18493793

RESUMO

The aim of our study was to evaluate whether specifically designed urine collection pads give reliable results for routine and metabolic biochemistry tests in paediatric urine. Urine collected by bag or clean-catch from infants and children <2 yrs without metabolic disorders was divided into two aliquots, one of which was added to a collection pad, incubated for 15 min at 37 degrees C (simulating in vivo collection conditions), then recovered by aspiration. Urine from adults with phaeochromocytoma and aqueous solutions of catecholamines were similarly treated. Routine, catecholamine, and metabolic analyses were performed on pad/non-pad aliquots. Selected metabolic analyses were also performed on pad/non-pad urine from patients with diagnosed inborn errors and urine containing added metabolites to simulate metabolic disorders. Routine tests (urea, electrolytes, creatinine, osmolality, calcium:creatinine, phosphate:creatinine, magnesium:creatinine, urate:creatinine [n = 32], oxalate:creatinine [n = 10]), and catecholamines (n = 12) showed good or acceptable concordance with no clinically significant pad/non-pad differences. Metabolic tests in infants and children without metabolic disorders all showed good pad/non-pad concordance for amino acids (n = 10), organic acids (n = 12), and glycosaminoglycans (n = 8). In patients with metabolic disorders (phenylketonuria [n = 1], homozygous/heterozygous cystinuria [n = 3], mucopolysaccharidoses II [n = 2] and III [n = 1], organic acid disorders [n = 6]) and urine containing added orotic acid to simulate urea cycle disorders, there was also good pad/non-pad concordance for diagnostic urinary metabolites. No extraneous organic acids were eluted from the pads. Sugar chromatography showed identical staining intensity in pad/non-pad samples. In conclusion, urine collection pads give reliable results for a wide range of routine and metabolic biochemistry tests in urine from paediatric patients.


Assuntos
Absorventes Higiênicos , Catecolaminas/urina , Erros Inatos do Metabolismo/urina , Urina/química , Testes Diagnósticos de Rotina , Humanos , Lactente , Reprodutibilidade dos Testes
7.
Horm Res ; 69(1): 53-9, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18059084

RESUMO

AIM: The aim of this retrospective study was to evaluate the clinical usefulness of the thyrotropin-releasing hormone (TRH) test in children with suspected hypothalamic or pituitary dysfunction. METHODS: We reviewed the case notes of all patients in whom a TRH test had been performed over a 6-year period. Group 1 (n = 85, 34 males, aged 0.9-18.8 years) was the reference group with no evidence of hypothalamic, pituitary or thyroid dysfunction. Group 2 (n = 42, 24 males, 0.1-18.0 years) were being investigated for possible pituitary or hypothalamic insufficiency. RESULTS: In Group 1, thyrotropin (TSH) responses were higher in females than males (p < 0.01). In Group 2, TSH responses were normal for gender in 26 patients, subnormal in 5, and exaggerated/delayed in 11. Four patients with normal TSH responses and 4 with exaggerated/delayed responses had persistently low free thyroxine (FT(4)) or later developed low FT(4) and were treated with thyroxine. All those with subnormal TSH responses had normal FT(4) and were not treated. The TRH test did not reliably discriminate between hypothalamic and pituitary disorders. CONCLUSIONS: The TRH test did not give useful clinical information. Clinical decisions regarding thyroxine treatment were based on FT(4), not the TRH test. The TRH test should be abandoned in paediatric practice.


Assuntos
Técnicas de Diagnóstico Endócrino , Hipopituitarismo/diagnóstico , Doenças Hipotalâmicas/diagnóstico , Hormônio Liberador de Tireotropina , Adolescente , Criança , Pré-Escolar , Diagnóstico Diferencial , Técnicas de Diagnóstico Endócrino/efeitos adversos , Feminino , Humanos , Hipopituitarismo/tratamento farmacológico , Doenças Hipotalâmicas/tratamento farmacológico , Lactente , Masculino , Puberdade , Estudos Retrospectivos , Hormônio Liberador de Tireotropina/sangue , Tiroxina/administração & dosagem , Tiroxina/sangue
9.
Eur J Pediatr ; 164(11): 655-9, 2005 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-16025295

RESUMO

UNLABELLED: Isolated sulphite oxidase deficiency (ISOD) is a rare autosomal recessive inborn error of metabolism, which may present at birth with intractable seizures (often of prenatal onset) and severe neurological abnormalities. In infants who survive, lens dislocation may occur from 8 weeks of age. The neuropathological findings in ISOD are similar to those seen in severe perinatal asphyxia. We describe two siblings with ISOD born to healthy non-consanguineous parents. The first child presented within 48 h of birth with poor feeding and seizures. He died from septicaemia on day 20 of life. The clinical presentation, neuroradiology and autopsy suggested a diagnosis of severe hypoxic ischaemic encephalopathy with a low recurrence risk. The second child presented with seizures within an hour of birth. She lived for 16 months during which time she failed to make developmental progress and continued to experience intractable seizures. Her neuroradiology was similar to her brother's. A diagnosis of ISOD was suggested from high urinary S-sulphocysteine in the second child and confirmed by the absence of sulphite oxidase activity in skin fibroblast culture. The diagnosis has enabled the couple to access prenatal testing in a subsequent pregnancy. CONCLUSION: Isolated sulphite oxidase deficiency is an autosomal recessive condition which may mimic ischaemic encephalophathy. The disorder should be considered in all cases of intrauterine seizures, intractable seizures in the newborn period and infants with clinical and radiological features of ischaemic encephalophathy, especially when no obvious insult can be determined.


Assuntos
Encefalopatias Metabólicas Congênitas/diagnóstico , Hipóxia-Isquemia Encefálica/diagnóstico , Erros Inatos do Metabolismo/diagnóstico , Sulfito Oxidase/deficiência , Encéfalo/patologia , Cisteína/análogos & derivados , Cisteína/sangue , Cisteína/urina , Diagnóstico Diferencial , Evolução Fatal , Feminino , Humanos , Lactente , Recém-Nascido , Imageamento por Ressonância Magnética , Masculino , Erros Inatos do Metabolismo/complicações , Erros Inatos do Metabolismo/metabolismo , Hipotonia Muscular/diagnóstico , Hipotonia Muscular/etiologia , Convulsões/etiologia , Irmãos
10.
Clin Endocrinol (Oxf) ; 62(2): 205-9, 2005 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-15670197

RESUMO

OBJECTIVE: Inhibin B is produced by granulosa cells in small antral follicles, under the influence of FSH, and has a paracrine role in oestradiol synthesis. To test the hypothesis that premature thelarche is associated with increased FSH-driven follicular development, we measured inhibin B and FSH in girls with premature thelarche, girls with central precocious puberty (CPP) and controls matched either for age or breast stage. PATIENTS: Blood samples were collected from 11 girls with premature thelarche (breast stage 2, aged 0.4-5.6 years), 11 prepubertal controls age-matched to the thelarche girls (0.5-5.4 years), 13 girls with CPP (breast stage 2, 3.9-8.2 years) and nine normal pubertal controls (breast stage 2, 9.0-13.2 years). MEASUREMENTS: Dimeric inhibin B was measured in plasma by double-antibody enzyme-linked immunoassay and FSH by immunoradiometric assay. Pelvic ultrasonography was performed on all girls with CPP and 10/11 girls with premature thelarche. RESULTS: Seven of the 13 girls with CPP and three of the eight girls with premature thelarche whose ovaries could be visualized had visibly nonhomogeneous ovarian structure on ultrasonography. Girls with premature thelarche had inhibin B and FSH concentrations higher than those in their age-matched controls (P < 0.01 and P < 0.05, respectively), and similar to those observed in girls with CPP and normal pubertal controls matched for breast stage. In thelarche girls, as in precocious puberty girls and normal pubertal controls, inhibin B and FSH were positively related (rs = 0.54-0.61). CONCLUSIONS: This study provides further evidence that premature thelarche is associated with enhanced follicular development, similar to that which occurs in early puberty, probably under the influence of FSH.


Assuntos
Doenças Mamárias/metabolismo , Hormônio Foliculoestimulante/sangue , Inibinas/sangue , Ovário/metabolismo , Mama/crescimento & desenvolvimento , Mama/fisiopatologia , Doenças Mamárias/fisiopatologia , Estudos de Casos e Controles , Criança , Feminino , Humanos , Puberdade/sangue , Puberdade Precoce/sangue , Estatísticas não Paramétricas
11.
Acta Orthop ; 76(6): 841-7, 2005 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-16470439

RESUMO

BACKGROUND: Abnormalities in distal growth and low levels of insulin-like growth factor (IGF)-I have been reported in children with Perthes' disease. Our aim was to establish whether the acute phase of Perthes' disease is associated with abnormalities of growth, of bone or of collagen turnover. METHODS: We performed a cross-sectional study of 15 children (3-11 years of age, 13 boys) at acute presentation and a longitudinal cohort study of 9 children. We measured (1) the lengths of both lower legs (by knemometry) at weeks 1, 2, 6 and 12, (2) height and weight at presentation and at the second-year follow-up, and (3) levels of IGF-I, IGFBP-3, collagen markers and bone alkaline phosphatase at weeks 1 and 12, and in year 2. RESULTS: Height SD scores were normal at presentation but declined thereafter. Lower leg growth was not impaired at presentation but was asymmetrical, ceased during weeks 2-6, and then resumed symmetrically. Patients had persistently low IGF-I, low soft tissue collagen synthesis and enhanced collagen breakdown compared with age- and sex-related reference data. Markers of bone formation increased during follow-up. INTERPRETATION: Acute changes in lower leg growth reflected differential weight bearing, then immobilization and remobilization. Persistently low IGF-I may have contributed to low soft tissue collagen synthesis and growth. Changes in bone formation markers most likely reflected bone healing.


Assuntos
Biomarcadores/metabolismo , Osso e Ossos/metabolismo , Colágeno/metabolismo , Perna (Membro)/crescimento & desenvolvimento , Doença de Legg-Calve-Perthes/fisiopatologia , Doença Aguda , Fosfatase Alcalina/metabolismo , Estatura , Criança , Pré-Escolar , Estudos Transversais , Seguimentos , Humanos , Fator de Crescimento Insulin-Like I/metabolismo , Doença de Legg-Calve-Perthes/metabolismo , Estudos Longitudinais , Pró-Colágeno/metabolismo , Estudos Prospectivos , Suporte de Carga
13.
Pediatr Res ; 55(2): 224-30, 2004 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-14605245

RESUMO

Children who are treated for malignancy have been shown to have decreased bone mineral density. We investigated the effect of serial courses of chemotherapy on growth and bone turnover in children with solid tumors. We measured height, weight, and lower leg length (LLL; n = 10) and markers of bone formation [bone alkaline phosphatase (BALP) and C-terminal propeptide of type I collagen (P1CP)], bone resorption [C terminal telopeptide of type I collagen (1CTP)], soft tissue collagen turnover [N-terminal propeptide of type III procollagen (P3NP)], and the GH axis [IGF1 and its binding proteins (IGFBP3 and IGFBP2)] before and after each course (n = 25) and on completion of treatment (n = 12). Height SD score decreased during treatment (p < 0.01) and increased to pretreatment levels at 3 mo off treatment (p < 0.05). LLL growth increased off treatment (p < 0.01). At diagnosis, BALP, PICP, and IGF1 SD score were low compared with age- and sex-matched reference groups (p < 0.001, p < 0.001, and p < 0.002, respectively) and IGFBP2 was elevated (p < 0.001). During treatment, P1CP, 1CTP, and P3NP showed a cyclical pattern decreasing after each course (p < 0.001) and increasing before the next course (p < 0.001). Precourse levels of BALP, P1CP, 1CTP, P3NP, IGF1, and IGFBP3 showed an upward trend during treatment. BALP remained suppressed throughout treatment (p < 0.001). Intense courses of treatment for solid tumors have a direct suppressive effect on bone turnover, with an imbalance between collagen synthesis and degradation.


Assuntos
Antieméticos/efeitos adversos , Densidade Óssea/efeitos dos fármacos , Desenvolvimento Ósseo/efeitos dos fármacos , Osso e Ossos/metabolismo , Dexametasona/efeitos adversos , Neoplasias/tratamento farmacológico , Adolescente , Antineoplásicos/efeitos adversos , Biomarcadores , Estatura , Criança , Pré-Escolar , Humanos , Lactente , Vômito/induzido quimicamente , Vômito/tratamento farmacológico
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