RESUMEN
INTRODUCTION: Newborn screening is important for early diagnosis and effective treatment of inborn errors of metabolism (IEM). In response to a 2008 coroners' report of a 14-year-old boy who died of an undiagnosed IEM, the OPathPaed service model was proposed. In the present study, we investigated the feasibility of the OPathPaed model for delivering expanded newborn screening in Hong Kong. In addition, health care professionals were surveyed on their knowledge and opinions of newborn screening for IEM. METHODS: The present prospective study involving three regional hospitals was conducted in phases, from 1 October 2012 to 31 August 2014. The 10 steps of the OPathPaed model were evaluated: parental education, consent, sampling, sample dispatch, dried blood spot preparation and testing, reporting, recall and counselling, confirmation test, treatment and monitoring, and cost-benefit analysis. A fully automated online extraction system for dried blood spot analysis was also evaluated. A questionnaire was distributed to 430 health care professionals by convenience sampling. RESULTS: In total, 2440 neonates were recruited for newborn screening; no true-positive cases were found. Completed questionnaires were received from 210 respondents. Health care professionals supported implementation of an expanded newborn screening for IEM. In addition, there is a substantial need of more education for health care professionals. The majority of respondents supported implementing the expanded newborn screening for IEM immediately or within 3 years. CONCLUSION: The feasibility of OPathPaed model has been confirmed. It is significant and timely that when this pilot study was completed, a government-led initiative to study the feasibility of newborn screening for IEM in the public health care system on a larger scale was announced in the Hong Kong Special Administrative Region Chief Executive Policy Address of 2015.
Asunto(s)
Conocimientos, Actitudes y Práctica en Salud , Personal de Salud , Errores Innatos del Metabolismo/diagnóstico , Tamizaje Neonatal/métodos , Diagnóstico Precoz , Femenino , Hong Kong , Humanos , Recién Nacido , Masculino , Errores Innatos del Metabolismo/terapia , Proyectos Piloto , Guías de Práctica Clínica como Asunto , Estudios Prospectivos , Encuestas y CuestionariosRESUMEN
INTRODUCTION: There is a pressing need to identify diagnostic testing for Cushing's syndrome that can be achieved with ease and at low cost. This study aimed to explore the usefulness of late-night and post-overnight 1-mg dexamethasone suppression salivary cortisone, as measured by liquid chromatography-tandem mass spectrometry, for investigation of hypercortisolism. METHODS: Salivary cortisone data of subjects were investigated according to a pre-specified protocol. Subjects were classified as having 'hypercortisolism' or 'eucortisolism' on the basis of histological or biochemical criteria. Receiver operating characteristic curves were drawn to identify the cut-off values and study their performance characteristics. We measured 24-hour urinary free cortisol; late-night salivary cortisol and cortisone; and post-overnight 1-mg dexamethasone suppression serum cortisol, and salivary cortisol and cortisone. Saliva and urine samples were assayed by liquid chromatography-tandem mass spectrometry. RESULTS: In this study, 21 subjects were classified as having hypercortisolism and 78 as having eucortisolism. A late-night salivary cortisone cut-off of 13.50 nmol/L had a sensitivity of 94.7% and a specificity of 87.2%. After taking 1-mg dexamethasone the night before, a salivary cortisol cut-off of 0.85 nmol/L had a sensitivity of 76.2% and a specificity of 96.2%; a salivary cortisone cut-off of 7.45 nmol/L had a sensitivity of 85.7% and a specificity of 94.9%, while a salivary cortisone cut-off of 3.25 nmol/L had a sensitivity of 95.2% and a specificity of 79.5%. Many salivary cortisol samples were below the detection limit of liquid chromatography-tandem mass spectrometry. In comparison with salivary cortisol, salivary cortisone had a better correlation with total serum cortisol and better diagnostic performance following dexamethasone suppression. CONCLUSIONS: Both late-night and post-overnight dexamethasone suppression salivary cortisone levels are of diagnostic value in the investigation of hypercortisolism.
Asunto(s)
Antiinflamatorios/farmacología , Cortisona/metabolismo , Síndrome de Cushing/diagnóstico , Dexametasona/farmacología , Saliva/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Cromatografía Liquida , Ritmo Circadiano , Cortisona/análisis , Síndrome de Cushing/metabolismo , Femenino , Humanos , Hidrocortisona/análisis , Hidrocortisona/orina , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Curva ROC , Saliva/química , Glándulas Salivales/efectos de los fármacos , Sensibilidad y Especificidad , Adulto JovenRESUMEN
OBJECTIVE: Disorders of sex development are due to congenital defects in chromosomal, gonadal, or anatomical sex development. The objective of this study was to determine the aetiology of this group of disorders in the Hong Kong Chinese population. SETTING: Five public hospitals in Hong Kong. PATIENTS: Patients with 46,XY disorders of sex development under the care of paediatric endocrinologists between July 2009 and June 2011. MAIN OUTCOME MEASURES: Measurement of serum gonadotropins, adrenal and testicular hormones, and urinary steroid profiling. Mutational analysis of genes involved in sexual differentiation by direct DNA sequencing and multiplex ligation-dependent probe amplification. RESULTS: Overall, 64 patients were recruited for the study. Their age at presentation ranged from birth to 17 years. The majority presented with ambiguous external genitalia including micropenis and severe hypospadias. A few presented with delayed puberty and primary amenorrhea. Baseline and post-human chorionic gonadotropin-stimulated testosterone and dihydrotestosterone levels were not discriminatory in patients with or without AR gene mutations. Of the patients, 22 had a confirmed genetic disease, with 11 having 5α-reductase 2 deficiency, seven with androgen insensitivity syndrome, one each with cholesterol side-chain cleavage enzyme deficiency, Frasier syndrome, NR5A1-related sex reversal, and persistent Müllerian duct syndrome. CONCLUSIONS: Our findings suggest that 5α-reductase 2 deficiency and androgen insensitivity syndrome are possibly the two most common causes of 46,XY disorders of sex development in the Hong Kong Chinese population. Since hormonal findings can be unreliable, mutational analysis of the SRD5A2 and AR genes should be considered the first-line tests for these patients.
Asunto(s)
Pueblo Asiatico , Trastorno del Desarrollo Sexual 46,XY/etiología , 3-Oxo-5-alfa-Esteroide 4-Deshidrogenasa/deficiencia , Trastornos del Desarrollo Sexual 46, XX/etiología , Adolescente , Amenorrea/etiología , Síndrome de Resistencia Androgénica/etiología , Niño , Preescolar , Enzima de Desdoblamiento de la Cadena Lateral del Colesterol/deficiencia , Anomalías Congénitas/etiología , Análisis Mutacional de ADN , Dihidrotestosterona/sangre , Trastorno del Desarrollo Sexual 46,XY/sangre , Trastorno del Desarrollo Sexual 46,XY/orina , Femenino , Síndrome de Frasier/etiología , Enfermedades de los Genitales Masculinos/etiología , Gonadotropinas/sangre , Hong Kong , Humanos , Hipospadias/etiología , Lactante , Recién Nacido , Masculino , Conductos Paramesonéfricos/anomalías , Mutación , Pene/anomalías , Pubertad Tardía/etiología , Factor Esteroidogénico 1/genética , Testosterona/sangreRESUMEN
Classical congenital adrenal hyperplasia due to 21-hydroxylase deficiency is a well-known disorder of sexual development (previously known as ambiguous genitalia) in genotypic female neonates. We report on a 66-year-old Chinese, brought up as male, with a simple virilising form of congenital adrenal hyperplasia associated with Turner's syndrome (karyotype 45,X/47,XXX/46,XX). His late presentation was recognised due to his exceptionally short stature and persistent sexual ambiguity. His condition was only brought to medical attention as he developed a huge abdominal mass, which later turned out to be a benign ovarian mucinous cyst. It is therefore important to look out for co-existing congenital adrenal hyperplasia in patients with Turner's syndrome and virilisation, after the presence of Y chromosome material has been excluded.
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Hiperplasia Suprarrenal Congénita/diagnóstico , Síndrome de Turner/diagnóstico , Virilismo/diagnóstico , Hiperplasia Suprarrenal Congénita/fisiopatología , Factores de Edad , Anciano , Estatura , China , Femenino , Humanos , Quistes Ováricos/etiología , Quistes Ováricos/patología , Síndrome de Turner/fisiopatología , Virilismo/etiologíaRESUMEN
Capecitabine is an orally administered pro-drug of 5-fluorouracil that confers superior disease-free survival and presumably has a more favourable side-effect profile. Here we report on a patient who developed acute necrotising pancreatitis and very high triglyceride levels as well as hand-foot syndrome after receiving capecitabine for colonic cancer. Increased awareness of this potential side-effect and close monitoring of lipid levels may be warranted, especially in patients who have other conditions predisposing them to severe secondary hyperlipidaemia when using this drug.
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Antimetabolitos Antineoplásicos/efectos adversos , Desoxicitidina/análogos & derivados , Fluorouracilo/análogos & derivados , Hipertrigliceridemia/complicaciones , Pancreatitis Aguda Necrotizante/etiología , Administración Oral , Adulto , Antimetabolitos Antineoplásicos/administración & dosificación , Antimetabolitos Antineoplásicos/uso terapéutico , Capecitabina , Neoplasias del Colon/tratamiento farmacológico , Desoxicitidina/administración & dosificación , Desoxicitidina/efectos adversos , Desoxicitidina/uso terapéutico , Supervivencia sin Enfermedad , Femenino , Fluorouracilo/administración & dosificación , Fluorouracilo/efectos adversos , Fluorouracilo/uso terapéutico , Síndrome Mano-Pie/etiología , Humanos , Pancreatitis Aguda Necrotizante/patología , Triglicéridos/sangreRESUMEN
We report on an adult patient with citrin deficiency in Hong Kong, in whom a novel mutation was identified. The patient presented with recurrent hyperammonaemic encephalopathy due to impairment of the liver urea cycle enzyme argininosuccinate synthetase. This autosomal recessive condition is also characterised by interesting food preferences, notably aversion to carbohydrates and craving for protein-rich and/or lipid-rich foods, as well as neuropsychiatric symptoms. Plasma amino acid analysis is very useful in revealing urea cycle disorders, and mutational analysis of the SLC25A13 gene can confirm the diagnosis.
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Encefalopatías Metabólicas Innatas/genética , Proteínas de Unión al Calcio/deficiencia , Hiperamonemia/etiología , Proteínas de Transporte de Membrana Mitocondrial/genética , Transportadores de Anión Orgánico/deficiencia , Adulto , Proteínas de Unión al Calcio/genética , Citrulinemia/complicaciones , Confusión/etiología , Dieta , Humanos , Masculino , Mutación , Transportadores de Anión Orgánico/genéticaRESUMEN
Mucopolysaccharidosis VI (Maroteaux-Lamy syndrome) is a very rare inherited lysosomal storage disease. We evaluated the efficacy and safety of weekly infusions of recombinant human arylsulfatase B as enzyme replacement therapy for two patients in whom this condition was advanced. The primary outcome variables were the distance walked in a 6-minute walk test, forced vital capacity, and ejection fraction. The secondary outcome variables were the number of stairs climbed in a 3-minute stair climbing test, joint mobility, urinary glycosaminoglycan excretion, auto-continuous positive airway pressure study and liver size. After 24 weeks of treatment, patient A walked 40 m (36%) and patient B walked 66 m (58%) more in the walk test than at baseline. After 48 weeks, in patient A the corresponding improvements were 142 m (129%) in the walk test and 33 stairs (60%) in the 3-minute stair climbing test, and in patient B the respective improvements were 198 m (174%) and 77 stairs (140%). There was a significant decline in urinary glycosaminoglycan excretion and improvement in range of motion of joints in both patients. The auto-continuous positive airway pressure study revealed improvements in patient A, while other efficacy variables remained static. There were no drug-related adverse events or allergic reactions reported during and after the infusions of recombinant human arylsulfatase B. Recombinant human arylsulfatase B significantly improves endurance and reduces urinary glycosaminoglycan excretion. The drug is generally safe and well tolerated.
Asunto(s)
Terapia de Reemplazo Enzimático , Mucopolisacaridosis VI/tratamiento farmacológico , N-Acetilgalactosamina-4-Sulfatasa/uso terapéutico , Adolescente , Volumen Espiratorio Forzado , Glicosaminoglicanos/orina , Hong Kong , Humanos , Masculino , Mucopolisacaridosis VI/fisiopatología , Estudios Prospectivos , Proteínas Recombinantes/uso terapéutico , Capacidad VitalRESUMEN
Cytochrome P450 oxidoreductase deficiency is a recently established autosomal recessive disease characterised by ambiguous genitalia, impaired steroidogenesis, and skeletal malformations, referred to as Antley-Bixler syndrome. Clinical manifestations in affected patients are highly variable. We report on a girl with P450 oxidoreductase deficiency who presented with virilisation at birth. There was transient maternal virilisation during pregnancy as well. She was initially diagnosed with congenital adrenal hyperplasia caused by 21-hydroxylase deficiency and/or aromatase deficiency. At 1 year of age, skeletal abnormalities suggestive of Antley-Bixler syndrome were detected. Molecular analysis of the fibroblast growth factor receptor 2 (FGFR2) gene was normal but POR gene analysis showed that she was homozygous for an R457H missense mutation. The diagnosis, P450 oxidoreductase deficiency, was confirmed. Results of her endocrine studies and urinary steroid profiling are also presented.
Asunto(s)
Fenotipo del Síndrome de Antley-Bixler/genética , Sistema Enzimático del Citocromo P-450/deficiencia , Esteroides/biosíntesis , Virilismo/genética , Hormona Adrenocorticotrópica/farmacología , Niño , Sistema Enzimático del Citocromo P-450/genética , Femenino , Humanos , Mutación MissenseRESUMEN
Lipoprotein glomerulopathy is a rare kidney disease in which lipoprotein thrombi are seen in the glomerular capillaries. Most of these patients are found in Japan and East Asian countries. The presenting symptoms include proteinuria, an abnormal plasma lipoprotein profile that resembles type III hyperlipoproteinaemia, and a marked increase in serum apolipoprotein E concentration. Previous studies have suggested that lipoprotein glomerulopathy might be related to APOE gene mutation. No effective therapeutic regimen has been established for lipoprotein glomerulopathy. We report the first case of biopsy-proven lipoprotein glomerulopathy in Hong Kong in a patient who presented with nephrotic syndrome and dyslipidaemia. DNA analysis revealed apolipoprotein E Kyoto together with a novel apolipoprotein E mutation, apolipoprotein E (Asp230Tyr) Hong Kong. There was significant improvement in the clinical parameters and resolution of symptoms after the introduction of statins. Further studies will be needed to clarify the role of apolipoprotein E Hong Kong and its interaction with apolipoprotein E Kyoto in the pathogenesis of lipoprotein glomerulopathy.
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Apolipoproteínas E/sangre , Apolipoproteínas E/genética , Nefrosis Lipoidea/diagnóstico , Nefrosis Lipoidea/genética , Adulto , Análisis Mutacional de ADN , Glomerulonefritis/diagnóstico , Glomerulonefritis/tratamiento farmacológico , Hong Kong , Humanos , Hipolipemiantes/administración & dosificación , Lipoproteínas/sangre , Masculino , Mutación , Nefrosis Lipoidea/tratamiento farmacológico , Síndrome Nefrótico , Reacción en Cadena de la Polimerasa , Proteinuria , Simvastatina/administración & dosificaciónRESUMEN
5Alpha-reductase 2 deficiency is an autosomal recessive disorder characterised by lack of masculinisation in XY individuals due to failure to convert testosterone to dihydrotestosterone, the bioactive androgen. Traditionally, the testosterone-to-dihydrotestosterone ratio is used to diagnose this condition but interpreting these results is not always straightforward, thus they may be inconclusive. On the contrary, urinary steroid profiling unambiguously demonstrates a significantly reduced excretion of 5alpha-reduced steroid metabolites compared to their 5beta counterparts. This analytical technique can also simultaneously confirm or rule out other causes of ambiguous genitalia due to steroidogenic defects. Making a DNA-based diagnosis by studying the SRD5A2 gene has become increasingly popular. Here, we report six Chinese patients from different families who were all diagnosed with 5alpha-reductase 2 deficiency based on urinary steroid profile findings and mutational analysis of the SRD5A2 gene. R227Q was the most commonly identified mutation in these patients. Management of sexual development disorders is also discussed.
Asunto(s)
3-Oxo-5-alfa-Esteroide 4-Deshidrogenasa/deficiencia , Trastornos del Desarrollo Sexual/diagnóstico , Esteroides/orina , 3-Oxo-5-alfa-Esteroide 4-Deshidrogenasa/genética , Adolescente , Adulto , Preescolar , Cromosomas Humanos X , Cromosomas Humanos Y , Análisis Mutacional de ADN , Femenino , Genitales/anomalías , Humanos , Masculino , MutaciónRESUMEN
It has been suggested that urinary steroid profiling may be used to provide information aiding the diagnosis and monitoring of adrenocortical carcinoma. Nonetheless, the abnormal patterns suggestive of adrenal malignancy are not well defined. We retrospectively studied the urinary steroid profiles of five patients with adrenocortical carcinoma at presentation and at follow-up, and compared these results with those from 76 patients with benign adrenocortical adenoma and 172 healthy controls. Three abnormal patterns of urinary steroid excretion were identified in patients with adrenocortical carcinoma at presentation and/or follow-up of residual disease: (1) hypersecretion in multiple steroid axes; (2) excretion of unusual metabolites, notably 5-pregnene-3alpha,16alpha,20alpha-triol, 5-pregnene-3beta,16alpha,20alpha-triol, and neonatal steroid metabolites in the post-neonatal period; (3) increase of tetrahydro-11-deoxycortisol relative to total cortisol metabolites. These preliminary findings offer ways in which urinary steroid profiling performed using gas chromatography-mass spectrometry can be helpful in the diagnosis and monitoring of adrenocortical carcinoma.
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Neoplasias de la Corteza Suprarrenal/diagnóstico , Adenoma Corticosuprarrenal/diagnóstico , Carcinoma Corticosuprarrenal/diagnóstico , Esteroides/orina , Neoplasias de la Corteza Suprarrenal/orina , Adenoma Corticosuprarrenal/orina , Carcinoma Corticosuprarrenal/orina , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Cromatografía de Gases y Espectrometría de Masas , Humanos , Lactante , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Adulto JovenRESUMEN
BACKGROUND: Urinary steroid profiling by GC or GC-MS are established clinical tools to complement other biochemical tests in the diagnosis and investigation of a wide range of adrenocortical disorders, but normative data on adults using the more specific GC-MS are lacking. Our objective was to set up the reference intervals of commonly detected urinary steroid metabolites as well as marker metabolites seen in disease states. METHOD: Apparently healthy adult Chinese males and females were recruited by completing health questionnaires. A 24-h urine specimen was collected from all the participants for urinary steroid profiling by GC-MS in cyclic scan mode. The analyzer was calibrated by using authentic steroid standards. Statistical methods recommended by the National Committee for Clinical Laboratory Standards were followed for setting up the reference intervals of various steroid metabolites. After outliers were excluded, the data were tested for the necessity to partition into sex-, menopausal status- and age-specific reference intervals. RESULTS: 83 males and 89 females were recruited for the study. Necessity to partition into sex-specific reference intervals was demonstrated for almost all steroid metabolites. Menopausal status and age also had a significant impact on steroid metabolite excretion, making separate reference intervals necessary. CONCLUSIONS: We have set up the normative data on the levels of urinary steroid metabolite excretion in Chinese adults for future reference in patient management and research in steroid metabolism.
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Cromatografía de Gases y Espectrometría de Masas/métodos , Esteroides/orina , Adulto , Anciano , China , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valores de Referencia , Esteroides/normasRESUMEN
Cryoglobulins are immunoglobulins that precipitate in the serum upon cooling to below core body temperature and re-dissolve at higher temperatures. Cryoglobulinaemia may be life-threatening. The three types of cryoglobulinaemia are associated with a wide spectrum of haematological, autoimmune, and chronic infectious diseases, especially hepatitis C infection. Our laboratory has received 378 requests for cryoglobulin testing over the past 5 years, with a detection rate of 4.8% in the 271 patients involved. Twelve per cent of the specimens were not processed due to being at an inappropriate temperature on arrival at the laboratory. Clinicians should be aware of temperature requirements when requesting cryoglobulin testing in suspected cases, and for all relevant protein tests in patients with cryoglobulinaemia. Handling specimens at inappropriate temperatures in the pre-analytical and analytical phases of the investigation might lead to cryoprecipitation and therefore false-negative results. The potential pitfalls encountered with specimen handling, analysis, and result interpretation are discussed in detail.
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Crioglobulinemia/sangre , Crioglobulinemia/diagnóstico , Manejo de Especímenes/efectos adversos , Electroforesis de las Proteínas Sanguíneas/métodos , Humanos , Masculino , Persona de Mediana EdadRESUMEN
We report on three Chinese neonates with carnitine-acylcarnitine translocase deficiency. They presented within the first 48 hours of life. Two neonates were found in cardiac arrest; one of them survived after resuscitation. The third neonate suddenly developed cardiorespiratory insufficiency and succumbed eventually. The clustering of three cases in 5 years suggests that carnitine-acylcarnitine translocase deficiency is not rare in our Chinese population. We advocate that investigation for metabolic diseases including carnitine-acylcarnitine translocase deficiency should be performed in cases of sudden infant death and unexplained abrupt clinical deterioration in the early neonatal period. Non-ketotic hypoglycaemia is an early clue. The mainstay of initial treatment is glucose infusion at a rate greater than 7 mg/kg/minute, which inhibits beta-oxidation of fatty acids (the defective enzymatic steps in carnitine-acylcarnitine translocase deficiency) and thus prevents the accumulation of toxic long-chain acylcarnitines.
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Carnitina Aciltransferasas/deficiencia , Reanimación Cardiopulmonar , Resultado Fatal , Femenino , Paro Cardíaco/etiología , Paro Cardíaco/terapia , Humanos , Recién Nacido , Masculino , Proteínas de Transporte de Membrana/genética , Mutación , Insuficiencia Respiratoria/etiologíaRESUMEN
OBJECTIVE: To evaluate the relation between chorioamnionitis and hypotension in very low birthweight infants. METHODS: Retrospective cohort study in infants with a birth weight of <1500 g born between January 2002 and September 2004. The placentas were examined for evidence of chorioamnionitis and funisitis. Hypotension was defined by the use of vasopressors. RESULTS: Of 105 infants, 37 (35%) were chorioamnionitis positive. The onset of hypotension had a skewed distribution: day 1 for 30 episodes and scattered from day 2 to day 19 for the remaining 22. Of the 30 infants who developed hypotension on day 1, 17 (57%) were chorioamnionitis positive. The mean maturity of the chorioamnionitis positive group was 27.91 weeks, marginally less than the mean maturity of 29.05 weeks of the chorioamnionitis negative group (p = 0.05). After adjustment of the effects for confounding variables (birth weight, gestation, surfactant therapy, mechanical ventilation on day 1, high frequency oscillatory ventilation, patent ductus arteriosus), chorioamnionitis was the significant factor in line with hypotension developing on day 1 (adjusted odds ratio 5.14, 95% confidence interval 1.51 to 17.50). There was no evidence that hypotension developing after day 1 was associated with chorioamnionitis. CONCLUSIONS: There is a strong association between chorioamnionitis and hypotension developing on day 1 in very low birthweight infants.
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Corioamnionitis/fisiopatología , Hipotensión/etiología , Enfermedades del Prematuro/fisiopatología , Recién Nacido de muy Bajo Peso , Factores de Edad , Peso al Nacer , Corioamnionitis/terapia , Femenino , Edad Gestacional , Humanos , Recién Nacido , Recien Nacido Prematuro , Enfermedades del Prematuro/terapia , Masculino , Embarazo , Estudios Retrospectivos , Factores de RiesgoRESUMEN
We report on the first Chinese patient with triple-A syndrome, who presented at 22 months with status epilepticus secondary to hyponatraemia and hypoglycaemia. Subsequent endocrine investigations confirmed primary adrenal insufficiency and aldosterone deficiency. In the presence of achalasia and alacrima, this patient satisfies the diagnostic criteria of triple-A syndrome. Further molecular testing detected compound heterozygous mutations in the AAAS gene: a c.580C --> T transition in exon 7 and a c.771delG single nucleotide deletion in exon 8. Testing of parents and brother confirmed their heterozygous carrier status.
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Proteínas de Complejo Poro Nuclear/genética , Enfermedades de la Corteza Suprarrenal/complicaciones , Pruebas de Función de la Corteza Suprarrenal , Aldosterona/deficiencia , China , Epilepsia Tónico-Clónica/complicaciones , Epilepsia Tónico-Clónica/genética , Exones/genética , Humanos , Hipoglucemia/complicaciones , Hiponatremia/complicaciones , Recién Nacido , Masculino , Mutación/genética , Proteínas del Tejido Nervioso , Estado Epiléptico/etiología , SíndromeRESUMEN
OBJECTIVES: To evaluate the efficacy and safety of lithium in the treatment of thyrotoxicosis, and to study the dose and serum levels at which therapeutic response occurs. DESIGN: Retrospective study. SETTING: Thyroid clinic of a regional hospital in Hong Kong. PATIENTS: Thirteen patients with thyrotoxicosis pending therapy with radioiodine or surgery, in whom thionamides were contra-indicated due to adverse reactions or failure of treatment. MAIN OUTCOME MEASURES: Free thyroxine levels, time to euthyroidism, and side-effects of lithium. RESULTS: A satisfactory response, defined as a fall by 40% or more in free thyroxine levels and clinical improvement, was achieved in eight patients within 1 to 2 weeks of lithium therapy. In four others, response occurred in 3 to 5 weeks. Response was slow and inadequate in one patient due to 'escape'. The median dosage of lithium was 750 mg daily, with a range of 500 to 1500 mg daily. The median serum lithium level was 0.63 mmol/L. Lithium toxicity was observed in one patient. CONCLUSIONS: A relatively low dose of lithium offers a safe and effective alternative means of controlling thyrotoxicosis in patients who cannot tolerate or do not respond to thionamides.
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Compuestos de Litio/uso terapéutico , Tirotoxicosis/tratamiento farmacológico , Adolescente , Adulto , Femenino , Humanos , Radioisótopos de Yodo/uso terapéutico , Compuestos de Litio/efectos adversos , Compuestos de Litio/sangre , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Tiroxina/sangreRESUMEN
OBJECTIVE: To review the causes of drug-induced hypoglycaemia in patients not taking hypoglycaemic medications. DESIGN: Retrospective study. SETTING: Regional hospitals in Hong Kong. PATIENTS: Patients with suspected drug-induced hypoglycaemia without a known history of exposure to hypoglycaemic agents, referred to the Hospital Authority Toxicology Reference Laboratory from June 2005 to March 2006 inclusive. MAIN OUTCOME MEASURES: Rate of positive cases, laboratory findings, possible causes, age distribution, and final outcomes. RESULTS: A total of 51 such patients were referred, in whom the presence of oral hypoglycaemic agents was detected (or inferred) in 23 (45%). In 12 of the 23 patients, oral hypoglycaemic agents could only be detected by target analysis, not through broad-spectrum screening. Gliclazide and glibenclamide were detected in 14 and eight patients respectively, whereas glimepiride, nateglinide and rosiglitazone were detected in the remaining patient. Possible sources of oral hypoglycaemic agents included drug administration errors in residential care homes for the elderly (n=9), mistakenly taking medication of a family member or employer (n=6), taking stock medication by mistake (n=2), taking Chinese proprietary medicine adulterated with oral hypoglycaemic agents (n=1), taking unknown pills bought from a retail pharmacy (n=1), and unknown (n=4). Regarding these 23 patients, 17 (74%) were aged 70 years or above and 21 (91%) recovered uneventfully. CONCLUSION: Hypoglycaemia due to inadvertent use of oral hypoglycaemic agents is a recognised problem, particularly in cases where family members living in the same household are taking similar medications. Possible drug administration errors in residential care homes for the elderly should be investigated, and procedures rectified if confirmed. Health care providers should be vigilant to such potential errors, especially in cases of unexplained hypoglycaemia.
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Hipoglucemia/inducido químicamente , Adulto , Anciano , Anciano de 80 o más Años , Preescolar , Femenino , Hogares para Ancianos , Humanos , Hipoglucemiantes/análisis , Hipoglucemiantes/toxicidad , Masculino , Errores de Medicación , Persona de Mediana EdadRESUMEN
Many studies showed an increased occurrence of primary hyperparathyroidism during lithium therapy. We studied 53 patients receiving lithium therapy prospectively for 2 yr. Serum PTH levels were unequivocally elevated. The baseline PTH level was 2.8 +/- 1.2 pmol/L and increased progressively to 3.9 +/- 1.5 pmol/L after 2 yr (P < 0.0005). There was no change in serum calcium, alkaline phosphatase, inorganic phosphate concentrations or tubular reabsorption of phosphate in relation to glomerular filtration rate. Fasting urinary reabsorption of calcium increased significantly (P < 0.0005), which was concordant with the PTH change. Fasting and 24-h urinary excretion of calcium decreased significantly (P < 0.0005), suggesting reduced, rather than enhanced, bone resorption as in primary hyperparathyroidism. This may be the main mechanism in maintaining normocalcemia, despite PTH elevation, during lithium therapy.
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Densidad Ósea/efectos de los fármacos , Hiperparatiroidismo/inducido químicamente , Litio/efectos adversos , Psicotrópicos/efectos adversos , Adolescente , Adulto , Análisis de Varianza , Células Cultivadas , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
The effects of fluvastatin treatment on lipid profile and apolipoproteins were assessed in a group of 31 Chinese patients with hypercholesterolemia, maintained on a constant low-fat diet. Some patients had the additional cardiovascular risk factors of hypertension and non-insulin-dependent diabetes mellitus, and 6 patients had familial hypercholesterolemia. Baseline lipid levels were measured after a 4-week placebo period, and these were repeated after 4 weeks of treatment with fluvastatin 20 mg daily, and after 4 weeks of treatment with fluvastatin 40 mg daily. Total cholesterol, low density lipoprotein cholesterol, and apolipoprotein (apo) B were each reduced to the same extent with the 2 doses of fluvastatin (-20%, -26%, and -20%, respectively). Triglycerides and very low density lipoprotein cholesterol were also reduced by about 12% with the 2 doses of fluvastatin. Apo A-I was increased by 7% and high density lipoprotein cholesterol (HDL-C) was increased by 10% with the 40 mg dose. The increase in HDL-C was due to increases in both HDL2-C (18%) and HDL3-C (7%). Lipoprotein(a) levels did not show any significant change with the 2 doses of fluvastatin in this short-term study. One patient developed reversible asymptomatic elevation of liver enzymes with the higher dose of fluvastatin; otherwise the drug was well tolerated and no patients had to be withdrawn from the study.