Hematuria as an adverse outcome following provocative growth hormone stimulation testing in children.

BACKGROUND: Provocative growth hormone (GH) stimulation testing is used to evaluate short stature and growth failure in children. Agents commonly used for testing include clonidine, arginine and glucagon. While stimulation testing is generally considered safe, gross hematuria has been described as a rare idiopathic complication of GH stimulation testing. This study was designed to estimate the incidence of both microscopic and macroscopic hematuria following GH testing with different provocative agents. METHODS: Subjects undergoing GH stimulation testing were invited to participate in the study. Prior to testing, vital signs were measured and baseline point-of-care (POC) urinalysis was done. The subjects performed urine testing at home on days 1, 2, 3 and 7 following GH stimulation studies. Families notified the study team with any positive findings and returned the data collection tool by mail. RESULTS: In total, 34 subjects aged 11.14±2.71 years (91.2% male) completed the study. Agents used in provocative testing included arginine (73.5%), clonidine (94.1%) and glucagon (32.4%). Three subjects developed hematuria after GH stimulation testing (clonidine/arginine). The hematuria resolved by 7 days after testing. Additional adverse effects included nausea, vomiting and hypotension. CONCLUSIONS: In this study of children undergoing GH testing, hematuria was identified in three subjects. This study demonstrates that side effects to agents used for GH testing are self-limited, yet not rare, and should be discussed with patients and families prior to stimulation testing.

[Adrenocortical carcinoma and pregnancy]. / Corticosurrénalome et grossesse.

Adrenocortical carcinoma is a rare cancer with a poor but heterogeneous prognosis. These tumours are more frequently encountered in women, sometimes very young and may be diagnosed in women in their child bearing years or already pregnant. Several clinical data have indicated that the secretion and or proliferation of adrenocortical tumors may be affected by the hormonal context of pregnancy. In this review, we will examine the link between ACC and pregnancy in two main aspects. We will first consider the situation of a pregnant woman with a clinical suspicion of adrenocortical carcinoma: which diagnostic procedures will be useful and safe for the foetus? What are the therapeutic options? What is the prognosis if the diagnosis is confirmed? In a second part, we will examine the possible risk of mothering a child in a patient previously treated for an ACC. The data shown here were obtained from studies carried out in a tertiary reference medical centre in Paris (Hôpital Cochin) and from the European Network for the Study of Adrenal Tumor (ENS@T) database of adrenocortical carcinoma.

Diagnostic value of a ghrelin test for the diagnosis of GH deficiency after subarachnoid hemorrhage.

OBJECTIVE: To determine the diagnostic value of a ghrelin test in the diagnosis of GH deficiency (GHD) shortly after aneurysmal subarachnoid hemorrhage (SAH). DESIGN: Prospective single-center observational cohort study. METHODS: A ghrelin test was assessed after the acute phase of SAH and a GH-releasing hormone (GHRH)-arginine test 6 months post SAH. Primary outcome was the diagnostic value of a ghrelin test compared with the GHRH-arginine test in the diagnosis of GHD. The secondary outcome was to assess the safety of the ghrelin test, including patients' comfort, adverse events, and idiosyncratic reactions. RESULTS: Forty-three survivors of SAH were included (15 males, 35%, mean age 56. 6 ± 11.7). Six out of 43 (14%) SAH survivors were diagnosed with GHD by GHRH-arginine test. In GHD subjects, median GH peak during ghrelin test was significantly lower than that of non-GHD subjects (5.4 vs 16.6, P=0.002). Receiver operating characteristics analysis showed an area under the curve of 0.869. A cutoff limit of a GH peak of 15 µg/l corresponded with a sensitivity of 100% and a false-positive rate of 40%. No adverse events or idiosyncratic reactions were observed in subjects undergoing a ghrelin test, except for one subject who reported flushing shortly after ghrelin infusion. CONCLUSION: Owing to its convenience, validity, and safety, the ghrelin test might be a valuable GH provocative test, especially in the early phase of SAH.

Are current diagnostic guidelines delaying early detection of dysglycemic states? Time for new approaches.

Diagnosis of dysglycemic states is likely delayed as current diagnostic criteria apply absolute threshold values to a process that is continuous. The importance of this relates to forestalling opportunities for earlier diagnosis when prevention and reversibility are more likely to occur by preventing further ß cell dysfunction. Although the optimal method for earlier identification of individuals at risk remains uncertain, the paper suggests novel approaches.

Self-limiting hematuria following growth hormone provocative testing with arginine hydrochloride.

Evaluation of growth hormone (GH) deficiency often involves use of agents that stimulate GH secretion, such as clonidine, glucagon, insulin, levo-dopa or arginine hydrochloride. We present three pediatric cases of benign, macroscopic hematuria in children without pre-existing renal disease following GH stimulation testing with clonidine and arginine hydrochloride. In all cases hematuria resolved spontaneously within 3-4 days without any intervention. This suggests that careful observation in such cases is sufficient and additional costly evaluation may be avoided. Other than six anecdotal cases registered via on-line adverse event reporting system (AERS), this is the first published report to date of painless, macroscopic, self-limiting hematuria after arginine hydrochloride infusion.

Risks and benefits of parathyroid fine-needle aspiration with parathyroid hormone washout.

OBJECTIVE: To describe the experience with parathyroid fine-needle aspiration (FNA) and parathyroid hormone (PTH) washout at Mayo Clinic Rochester, Rochester, Minnesota. METHODS: We retrospectively reviewed all parathyroid FNA procedures performed at Mayo Clinic Rochester between January 2000 and December 2007. Clinical, biochemical, and imaging information, parathyroid FNA procedure, and cytology, surgical, and pathology reports were reviewed, and descriptive statistics, sensitivity, specificity, and positive predictive values are presented. RESULTS: During the study period, 75 parathyroid FNAs were performed on 74 patients. Cytology results were available for 74 of 75 procedures, with only 31% interpreted as parathyroid cells. PTH washout was performed in 67 patients (91%). Parathyroid FNA with PTH washout had a sensitivity of 84%, specificity of 100%, positive predictive value of 100%, and accuracy of 84%. At the time of surgical treatment, 2 patients were noted to have an inflammatory response from the parathyroid FNA biopsy, 1 had a parathyroid abscess, and 2 had a hematoma. In 3 of these 5 patients, the necessary conversion of a minimally invasive surgical procedure to the standard surgical approach prolonged the surgical time. CONCLUSION: Parathyroid FNA with PTH washout had a superior performance in comparison with parathyroid scanning or ultrasonography alone. The main limitations of parathyroid FNA with PTH washout are (1) the need for initial identification of a potential parathyroid adenoma by ultrasonography and (2) the number of false-negative results. Parathyroid FNA resulted in complications affecting the surgical procedure in 3 patients.

Caracterización clínica y epidemiológica de los pacientes menores de 15 años de edad con diabetes mellitus tipo 1 / Clinical-epidemiologic characterization of patients aged under 15 presenting with type 1 diabetes mellitus

Objetivo: identificar las características clínico epidemiológicas de los pacientes menores de 15 años de edad, diagnosticados con diabetes mellitus tipo 1 durante el período comprendido entre el 1º de enero de 2000 y el 31 de diciembre de 2008 de la provincia Ciudad de La Habana. Métodos: se realizó un estudio descriptivo-retrospectivo con los pacientes menores de 15 años de edad, diagnosticados con diabetes mellitus tipo 1 durante el período ya mencionado. El grupo de estudio estuvo constituido por 293 pacientes, a los que se realizó la revisión de la historia clínica. Las variables estudiadas fueron: sexo, edad al diagnóstico, color de la piel, duración de lactancia materna exclusiva, forma clínica al diagnóstico y factores ambientales. Se realizó el análisis estadístico mediante cálculo de por cientos y de tasas de incidencia por grupo de edad y sexo durante el período estudiado. Resultados: los resultados más importantes mostraron un predominio de los pacientes que recibieron lactancia materna exclusiva por un tiempo menor de 3 meses. Las formas clínicas menos graves al diagnóstico de la enfermedad fueron las más frecuentes. Entre los factores ambientales predominaron las enfermedades respiratorias agudas. La tasa de incidencia media del período fue de 8,4 x 100 000 habitantes. Conclusiones: la incidencia de la enfermedad durante el período fue más alta en relación con los estudios previos realizados en el país, con un desplazamiento hacia edades tempranas(AU)

Objective: to identify the clinical-epidemiologic features of the patients aged under 15, diagnosed with type 1 diabetes mellitus from January 1, 2000 to December 31, 2008 from Ciudad de La Habana province. Methods: a descriptive-retrospective study was conducted in patients aged under 15 diagnosed with type 1 diabetes mellitus over above mentioned period. The study group included 293 patients and the review of medical record. Study variables were: sex, age at diagnosis, skin color, length of exclusive breast feeding, clinical way at diagnosis and environmental factors. A statistic analysis was carried out by means of percentage calculation and the incidence rates by age group and sex over the study period. Results: the more important results showed predominance of patients received exclusive breastfeeding over a period less than three months. The less severe clinical ways at disease's diagnosis were the more frequent ones. Among the environmental factors there was predominance of acute respiratory diseases. The mean incidence rate of the period was of 8.4 x 100 000 inhabitants. Conclusions: the disease's incidence over the period was higher in relation to the previous studies conducted in our country with a displacement towards early ages(AU)

Quantifying the risk of hypoglycaemia in children undergoing the glucagon stimulation test.

OBJECTIVE: The low-dose (15-30 µg/kg) glucagon stimulation test (GST) is assumed to be associated with fewer episodes of low blood glucose (BG). We aimed to quantify the risk of hypoglycaemia in children undergoing the low-dose GST to evaluate their growth hormone status. DESIGN AND PATIENTS: Blood glucose fluctuations during the GST in 80 children (median age 8·7 years, 45 boys, 66 prepubertal) who received a median 20·5 µg/kg of intramuscular glucagon were reviewed. MEASUREMENTS: The rate of (i) hypoglycaemia (BG < 3·3 mm), (ii) falling BG trend at the end of the GST (lower BG at 180 min than at 120 min), (iii) hypoglycaemia and falling BG trend at the end of the GST, and (iv) at-risk patients (those with at least one of the three risks measures). RESULTS: Twenty-seven of the 80 children had hypoglycaemia during the GST. Twenty-six children showed a falling BG trend at the end of the GST and were significantly younger than the other 54 children with a rising BG trend [5·1 (3·1-10·4) years vs 9·6 (5·4-11·8) years, P = 0·02]. Eight children had both a falling BG trend and hypoglycaemia at end of the test. Forty-four children were at-risk patients, and the odds ratio of being an at-risk patient in those <8 years old was 2·63 (95% CI 1·06-6·57, P = 0·04). CONCLUSIONS: Hypoglycaemia is not uncommon during the low-dose GST. Young children, especially those <8 years old, are particularly at risk. BG monitoring should be considered essential from a safety perspective.

An evaluation of the thyrotrophin-releasing hormone stimulation test in paediatric clinical practice.

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.

A simple diagnostic test using GH-releasing peptide-2 in adult GH deficiency.

OBJECTIVE: The international, first-line diagnostic test for adult GH deficiency is the insulin tolerance test (ITT), which is contraindicated in some patients due to severe adverse events. Alternatives such as GH-releasing hormone combined with arginine or GH-releasing peptides (GHRP) have been proposed. We validated the use of GHRP-2 for diagnosing adult GH deficiency (GHD). METHODS: Seventy-seven healthy subjects and 58 patients with peak GH<3 microg/l by ITT were enrolled. After overnight fasting, a 100 microg dose of GHRP-2 was administered intravenously; blood samples were taken during the subsequent 2 h and GH measured by immunoradiometric assay. RESULTS: Serum GH peak occurred within 60 min after GHRP-2 administration in all subjects. GH responses to GHRP-2 were not affected by gender, but were slightly lower in elderly subjects and those with adiposity, although these did not influence diagnosis of GHD. Repeated tests showed favourable reproducibility. Peak GH concentrations after GHRP-2 were significantly (P<0.001) lower in patients (1.36+/-2.60 microg/l) than the healthy group (84.6+/-60.9 microg/l) with no difference between hypothalamic and pituitary diseases. Serum GH concentration at the point where sensitivity of response crossed with specificity ranged from 15 to 20 microg/l. A cut-off value of 15 microg/l for diagnosing GHD with GHRP-2 corresponded to the diagnostic value of 3 microg/l in the ITT. CONCLUSIONS: The GHRP-2 provocative test showed favourable reproducibility and was mildly influenced by age and adiposity. Severe GH deficiency could be diagnosed with high reliability using a 15 microg/l (9 microg/l when GH calibrated with recombinant World Health Organization 98/574 standard) cut-off for peak GH concentration.

Evaluación crítica del sistema de diagnóstico de la diabetes mellitus, propuesto por la Asociación Americana de Diabetes / Critical evaluation of the diagnostic system of diabetes mellitus proposed by the American Diabetes Association

Se realizó un estudio retrospectivo en 370 sujetos con trastornos de tolerancia a la glucosa, para evaluar la metodología de diagnóstico de la diabetes mellitus tipo 2, que prescinde de la prueba de tolerancia a la glucosa oral (PTG), propuesto por la ADA. Se encontró que la glucemia en ayunas permitió diagnosticar el 27(por ciento) de los diabéticos y el 56(por ciento) de los sujetos con trastornos de la regulación de la glucemia, que se hubieran diagnosticado siguiendo los criterios de la OMS que incluyen la PTG; la tercera parte de los casos clasificados como normales según la glucemia en ayunas solamente, presentó algún tipo de trastorno de la tolerancia a la glucosa. Se comprobó que los diabéticos detectados mediante la hiperglucemia a la segunda hora de la PTG, presentan niveles superiores de glucosa circulante durante la prueba, evaluados por el área total bajo la curva de glucosa. El patrón de respuesta insulínica de estos casos se caracterizó por una respuesta inicial disminuida que se incrementó hasta alcanzar valores máximos a la segunda hora; la frecuencia de casos con baja respuesta insulínica y/o resistencia a la insulina fue alta. Se concluyó que la glucemia en ayunas, como única prueba, no tiene sensibilidad suficiente para detectar trastornos de la tolerancia a la glucosa y diabetes mellitus y los casos con hiperglucemia posprandial únicamente, y que por ello solo pueden ser detectados por la PTG, presentan trastornos metabólicos importantes que requieren su detección y tratamiento precoz por lo cual es recomendable el uso sistemático de la PTG en el diagnóstico de la diabetes mellitus(AU)

A retrospective study was carried out in 370 subjects with glucose tolerance disorders aimed at evaluating the methodology for diagnosing type 2 diabetes mellitus that leaves out the oral glucose tolerance test (GTT) proposed by the ADA, It was found that fasting glycaemia allowed to diagnose 27 percent of the diabetics and 56 percent of the individuals with glycaemia regulation disorders that would have been diagnosed according to the WHO criteria that include the GTT. The third part of those cases classified as normal based only in glycaemia during fasting presented some type of glucose tolerance disorder. It was proved that the diabetics detected by hyperglycemia at the second hour had higher levels of circulating glucose during the test evaluated by the total area under the glucose curve. The pattern of insulinic response of these cases was characterized by a diminished initial response that increased up to reaching maximum values at the second hour. The frequency of cases with low insulinic response and/or insulin resistance was high. It was concluded that the fasting glycaemia test by itself was not sensitive enough to detect glucose tolerance disorders, diabetes mellitus and those cases with postprandial hyperglycaemia, and that's why they can only be detected by GTT. As these patients present important metabolic disorders that require an early detection and treatment, it is recommended the systematic use of GTT in the diagnosis of diabetes mellitus(AU)

Is the short insulin tolerance test safe and reproducible?

The short insulin tolerance test (SITT) is described as a simple method to measure insulin sensitivity. To investigate the safety and reproducibility of the SITT, 16 healthy volunteers underwent two SITTs within 1 week. Intravenous insulin (0.05 U kg(-1) body weight) was injected into an antecubital vein. Blood samples were collected from the contralateral antecubital vein. The insulin-induced glucose disposal rate (Kitt) was calculated from the slope of the regression line of the logarithm of blood glucose against time during the first 3-15 min. Plasma glucose concentrations fell below 2.8 mmol l(-1) in 4 of the 32 tests and below 2.2 mmol I(-1) in 1 of these 4. Five subjects had mild hypoglycaemic symptoms, three of whom had plasma glucose concentrations below 2.8 mmol l(-1) in at least one SITT. The mean Kitt was 4.2% min(-1) (range 0.8-8.4) for the first test and 3.4% min(-1) (range 0.1-6.8) for the second test. The mean within-subject coefficient of variation was 30.7%. We conclude that SITT should be applied with caution especially on insulin sensitive subjects and has poor reproducibility using 0.05 U kg(-1) body weight of insulin injection, venous sampling, uncontrolled physical activity and uncontrolled dietary composition. Whether 0.1 U kg(-1) body weight of insulin injection and arterialized venous blood sampling as in the original description of this test can improve the reproducibility of the SITT needs further investigation.