RESUMO
PURPOSE: Hypercortisolism is associated with a high prevalence of depression and impaired health-related quality of life (QoL). According to the available literature, studies examining the depression risk in patients with adrenal incidentalomas (AI), nonfunctioning and the ones with (possible) autonomous cortisol secretion ((P)ACS) are scarce. The aim of this observational, case-control study was to screen patients with nonfunctioning adrenal incidentalomas (NAI) and the ones with (P)ACS for depression and to assess their QoL. METHODS: The total studied group consisted of 92 subjects-26 with NAI, 34 with (P)ACS and 32 age-matched healthy controls (HC). To screen for depression, we used the Beck Depression Inventory-II (BDI-II) and to assess the QoL, we used the Short-Form 36 Health Survey (SF-36). RESULTS: Patients with (P)ACS had significantly higher BDI-II scores and substantially lower QoL than patients with NAI or HC. Midnight cortisol level was the most significant predictor of BDI-II and SF-36 score. The receiver operating characteristic curve analysis demonstrated that a midnight cortisol value of 86.95 nmol/l had a high sensitivity (82.8%) and high specificity (80%) for detection of mild depression in patients with (P)ACS. CONCLUSION: Screening for depression and QoL assessment should become an integral part of clinical evaluation in patients with (P)ACS.
Assuntos
Neoplasias do Córtex Suprarrenal/complicações , Neoplasias das Glândulas Suprarrenais/complicações , Depressão/complicações , Depressão/etiologia , Hidrocortisona/metabolismo , Neoplasias do Córtex Suprarrenal/metabolismo , Neoplasias das Glândulas Suprarrenais/psicologia , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Nível de Saúde , Humanos , Achados Incidentais , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Prevalência , Escalas de Graduação Psiquiátrica , Qualidade de Vida , Curva ROC , Sensibilidade e Especificidade , Tomografia Computadorizada por Raios XRESUMO
Controversial data were reported concerning fasting ghrelin (decreased, normal or elevated) in polycystic ovary syndrome (PCOS). The aim of our study was to clarify ghrelin levels in non-obese, overweight, and obese PCOS patients; to investigate the effect of acute insulin infusion on ghrelin in PCOS as a chronic insulin-resistant state, with and without the impact of obesity, and to examine ghrelin-androgen interaction. In that order, we evaluated 1) ghrelin levels among 8 nonobese patients with PCOS [body mass index (BMI): 20.52+/-1.31 kg/m2], 8 overweight and obese patients with PCOS (BMI: 34.36+/-6.53 kg/m2) and their respective controls, 2) ghrelin suppression during euglycemic hyperinsulinemic clamp, and 3) ghrelin-androgen interrelationship. After overnight fast, 2-h euglycemic hyperinsulinemic clamp, was performed in all investigated women. Fasting ghrelin was significantly lower in non-obese PCOS than in controls (64.74+/-25.69 vs 108.36+/-52.60; p<0.05) as well as in overweight and obese PCOS in comparison with controls (38.71+/-14.18 vs 98.77+/-40.49; p<0.05). Insulin infusion significantly suppressed ghrelin in all subgroups of investigated women. Analysis of variance for repeatable measures confirmed that there was no significant difference in pattern of response between PCOS and controls. In conclusion, women with PCOS had lower fasting ghrelin and decreased insulin sensitivity independently of their BMI, compared to the controls. In addition, there were no differences between fasting ghrelin levels among non-obese, overweight, and obese women with PCOS. During euglycemic hyperinsulinemic clamp, ghrelin decreased in all studied groups to a similar extent, implying that, compared to chronic hyperinsulinemia, acute hyperinsulinemia reduces ghrelin levels independently of the degree of insulin resistance.
Assuntos
Grelina/sangue , Hiperinsulinismo/sangue , Hipoglicemiantes/administração & dosagem , Insulina/administração & dosagem , Síndrome do Ovário Policístico/sangue , Doença Aguda , Adulto , Índice de Massa Corporal , Jejum , Feminino , Técnica Clamp de Glucose , Humanos , Resistência à Insulina , Obesidade/sangue , Sobrepeso/sangue , Globulina de Ligação a Hormônio Sexual/metabolismo , Testosterona/sangueRESUMO
Previous studies demonstrated insulin resistance and increased prevalence of impaired glucose tolerance and type 2 diabetes mellitus in patients with primary hyperparathyroidism (PHPT). The effect of curative parathyroidectomy on insulin sensitivity was associated with conflicting results depending on which method for measuring the insulin sensitivity has been used. There was no improvement using HOMA and QUICKI while minimal model demonstrated significant improvement in insulin sensitivity. The aim of our study was to evaluate the insulin sensitivity before and after parathyroidectomy in patients with PHPT using a euglycemic clamp. 44 patients with PHPT and 11 age and body mass index matched healthy controls participated in study protocol. Before surgery M values and HOMA IR suggest insulin resistance in patients with PHPT. There was no difference in M index (3.74±1.89 vs. 4.62±2.27, p>0.05), HOMA IR (2.94±1.39 vs. 3.29±0.81, p>0.05), AUC glucose (863.0±261.3 vs. 842.3±165.5, p>0.05), AUC insulin (7068.7±4159.0 vs. 7229.6±2581.7, p>0.05), ISI (4.73±2.77 vs. 4.25±2.94, p>0.05) and AIR (47.89±32.05 vs. 38.96±21.20, p>0.05) between patients with PHPT and HC. There was significant improvement in insulin sensitivity after parathyroidectomy but both preoperative and postoperative M values were not significantly different in comparison to HC. There were no significant changes in HOMA IR, AUC glucose, AUC insulin, ISI and AIR before and after therapy. In conclusion, we observed significant improvement in insulin sensitivity after parathyroidectomy in patients with PHPT. There was no difference in parameters of insulin secretion before and after parathyroidectomy in patients with PHPT.
Assuntos
Hiperparatireoidismo/sangue , Hiperparatireoidismo/cirurgia , Resistência à Insulina , Insulina/metabolismo , Paratireoidectomia , Idoso , Feminino , Humanos , Secreção de Insulina , Masculino , Pessoa de Meia-IdadeRESUMO
The growth hormone (GH) response to GH-releasing hormone (GHRH) in patients with non-insulin-dependent diabetes mellitus (NIDDM) was found to be either decreased or normal. The recent introduction of a new and potent GH stimulus, GH-releasing peptide-6 (GHRP-6), allowed further investigation of the functional properties of somatotropes in a variety of metabolic diseases. The aim of the present study was to investigate the response of GH to GHRP-6, GHRH, and GHRP-6 + GHRH in NIDDM patients. Twenty-one patients with NIDDM were divided into two groups: group A, normal weight (body mass index [BMI], 23.31+/-0.62 kg/m2); and group B, overweight (BMI, 27.62+/-0.72 kg/m2). Eight normal-weight control subjects (group C) were studied. Each subject received GHRP-6 (90 microg intravenously [i.v.]), GHRH (100 microg i.v.), and GHRP-6 + GHRH on three separate occasions. There was no difference between the GH response after GHRP-6 in groups A, B, and C in terms of the GH peak (50.95+/-11.55, 51.96+/-7.71, and 70.07+/-15.59 mU/L, P>.05) and the area under the curve (AUC) for GH (2,340.06+/-617.36, 2,684.54+/-560.57, 3,462.78+/-1,223.53 mU/L/120 min, P>.05). A decreased GH response to GHRH was found in group B in comparison to group A (B v A: peak GH response, 8.25+/-1.90 v 22.19+/-8.81, P<.05; AUC GH, 479.62+/-84.0 v 1,443.21+/-743.76, P<.05). There was no difference in the GH response between group A and group C (peak GH response, 22.19+/-8.81 v 26.42+/-6.71, P>.05; AUC, 1,443.21+/-743.76 v 1,476.51+/-386.56, P>.05). There was a significant difference between the same parameters in group B versus group C (8.25+/-1.90 v 26.42+/-6.71, P<.05; AUC, 479.62+/-84.0 v 1,476.51+/-386.56, P<.05). The combined administration of GHRP-6 + GHRH elicited a synergistic GH response in NIDDM patients and controls. There was a significant difference between groups A and B for the GH peak (96.49+/-9.80 v 68.38+/-8.25, P<.05), whereas there was no difference for the AUC (5,111.13+/-703.77 v 3,425.95+/-459.67, P>.05). There was no difference in the peak GH after the combined test between group A and group C (96.49+/-9.80 v 139.82+/-24.16, P>.05), whereas the peak GH in the same test was significantly decreased in group B in comparison to group C (68.38+/-8.25 v 139.82+/-24.16, P<.05). The AUC for GH after combined GHRP-6 + GHRH in group A versus group C was not significantly different (5,111.13+/-703.77 v 9,274.71+/-1,541.46, P>.05), whereas there was a significant difference for the same test between group B and group C (3,425.95+/-459.67 v 9,274.71+/-1,541.46, P<.05). Our results demonstrate that normal-weight NIDDM patients have a preserved GH response to GHRP-6, GHRH, and GHRP-6 + GHRH, and overweight NIDDM patients have a blunted response to GHRH and GHRP-6 + GHRH. The preserved GH response to GHRP-6 in both diabetic groups suggests that the secretory potential of somatotropes is preserved in NIDDM patients. The impairment of the GH response to GHRH in overweight NIDDM patients could be a functional defect due to the obesity, since it could be overridden by administration of GHRP-6.
Assuntos
Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus/sangue , Hormônio Liberador de Hormônio do Crescimento/farmacologia , Hormônio do Crescimento Humano/sangue , Obesidade , Oligopeptídeos/farmacologia , Área Sob a Curva , Glicemia/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
A 55-year-old gentleman, after being treated for a short time with a diet and with Chlorpropamide, was switched to purified porcine insulin due to ketonuria and ketoacidosis. After a year the patient developed immunological insulin resistance (mean daily insulin dose: 3.72 U/kg body weight; anti-insulin antibodies 78%). In order to lower anti-insulin antibodies human recombinant DNA insulin was introduced into further therapy. Contrary to expectations, the patient did not reduce whatsoever his anti-insulin antibodies and his daily insulin dose increased up to 5.63 U/kg body weight. Introduction of combined immunosuppressive therapy (prednisone plus azathioprine) together with plasmapheresis resulted in rapid lowering of daily insulin requirement and reduction in anti-insulin antibodies. Immunosuppressive therapy was continued with 10 mg of prednisone and a year later the patients insulin daily requirement was 0.66 U/kg BW while his antibodies were 18%. The possible causes of insulin resistance to human recombinant DNA insulin are discussed as well as the advantage of combined immunosuppressive therapy together with plasmapheresis that was used for rapid lowering of insulin daily requirement and anti-insulin antibodies titer.
Assuntos
Imunossupressores/uso terapêutico , Resistência à Insulina/imunologia , Insulina/farmacologia , Plasmaferese , Proteínas Recombinantes/farmacologia , Azatioprina/uso terapêutico , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 1/terapia , Humanos , Insulina/imunologia , Insulina/uso terapêutico , Anticorpos Anti-Insulina/biossíntese , Anticorpos Anti-Insulina/farmacologia , Masculino , Pessoa de Meia-Idade , Prednisona/uso terapêutico , Proteínas Recombinantes/imunologia , Proteínas Recombinantes/uso terapêuticoRESUMO
Women with polycystic ovary syndrome (PCOS) could have associated risk for cardiovascular disease. The aim of the present study was to investigate the relationship between age and metabolic factors on cardiovascular risk in obese women with PCOS. Obese patients with PCOS were divided into an adolescent group (n=11; age 16.90 +/- 0.45 yr; BMI 35.04 +/- 1.70 kg/m2), and an adult group (n=18; age 29.66 +/- 1.31; BMI 34.57 +/- 1.46). We determined basal values of glucose, insulin, lipid and fibrinolytic parameters from blood samples taken in all patients and matched controls. Significantly different concentrations between the groups with PCOS were obtained for glucose, total cholesterol, triglycerides, LDL-cholesterol and Apo-B. Elevated concentrations of insulin (20.63 mU/l), both insulin sensitivity indexes--G:I ratio (7.52 mg/10(-4) U) and HOMA model (4.11 mmol/l x U/l(2))--and PAI-1 (5.49 U/ml) were obtained in the adolescent group with PCOS compared to controls, with further increase in the adult group with PCOS. It seems that the youngest obese population with PCOS represents a cohort with potential cardiovascular disease in adulthood.
Assuntos
Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Obesidade/complicações , Síndrome do Ovário Policístico/complicações , Adolescente , Adulto , Glicemia/metabolismo , Doenças Cardiovasculares/sangue , Estudos de Coortes , Feminino , Hemodinâmica/fisiologia , Hormônios/sangue , Humanos , Lipídeos/sangue , Obesidade/sangue , Síndrome do Ovário Policístico/sangue , Fatores de RiscoRESUMO
OBJECTIVE: This study examined the efficacy and safety of biphasic insulin aspart 30 (BIAsp 30) monotherapy in insulin-naive patients with Type 2 diabetes mellitus. RESEARCH DESIGN AND METHODS: In this 12-week, open-labelled, uncontrolled, clinical-experience study involving 71 patients with secondary oral antidiabetic agent failure, patients received BIAsp 30 after discontinuing oral antidiabetic drugs (OADs). Glucose and lipid concentrations, hypoglycaemic episodes and adverse events were assessed before and after treatment. Patient data were categorised according to previous OADs into the biguanides (BI) plus sulfonylureas/meglitinides (SU/MEG) and SU-only groups. RESULTS: After treatment, glucose and lipid control was significantly improved in both groups, with a greater improvement in the SU-only group. Mean glycated haemoglobin, fasting blood glucose and postprandial blood glucose excursion improved by 2.15 +/- 1.24%, 3.70 +/- 3.18 mmol/l and 1.26 +/- 2.65 mmol/l in the BI plus SU/MEG group, and by 3.09 +/- 1.62%, 6.11 +/- 5.02 mmol/l and 2.06 +/- 2.33 mmol/l in the SU-only group, respectively. Mean high-density lipoprotein cholesterol and triglycerides improved by 0.09 +/- 0.18 mmol/l and 0.94 +/- 1.17 mmol/l in the BI plus SU/MEG group and by 0.09 +/- 0.18 mmol/l and 1.04 +/- 2.72 mmol/l in the SU-only group, respectively. No major hypoglycaemic episodes or serious treatment-related adverse events were reported. CONCLUSIONS: Our study showed that BIAsp 30 treatment safely improved glucose and lipid control in insulin-naive patients with Type 2 diabetes poorly controlled on BI plus SU/MEG and SU-only. Key limitations were the lack of a comparator group and the short study duration.
Assuntos
Glicemia/efeitos dos fármacos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Metabolismo dos Lipídeos/efeitos dos fármacos , Lipídeos/sangue , Idoso , HDL-Colesterol/sangue , Preparações de Ação Retardada , Diabetes Mellitus Tipo 2/sangue , Feminino , Hemoglobinas Glicadas/metabolismo , Humanos , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/efeitos adversos , Injeções Subcutâneas , Insulina/administração & dosagem , Insulina/efeitos adversos , Insulina/análogos & derivados , Masculino , Pessoa de Meia-Idade , Montenegro , Projetos de Pesquisa , Fatores de Tempo , Resultado do Tratamento , Triglicerídeos/sangue , IugosláviaRESUMO
BACKGROUND: Preoperative localization of pancreatic neuroendocrine tumours (NET) is usually very difficult. Noninvasive, imaging tests, such as abdominal ultrasound, CT or MRI are not sensitive enough as well as selective angiography. The aim of the study was to clarify the usefulness of the EUS in preoperative localization of the pancreatic NET. METHODS: From September 1998 March 2005, EUS was performed in 1600 patients. Among them, in 10 (0.7%), this examination was carried out due to previous biochemical tests, which diagnosed the pancreatic NET. We studied the location, the size and echo-pattern of the neoplasm. The results were compared with operation and histology or EUS- FNA guided pancreatic biopsy in 9/10 patients. All EUS examinations were performed using Olympus GIF-130 videoecho-endoscope with 7,5 /12MHz switchable radial probe. RESULTS: EUS correctly localized the pancreatic NET in 7/8 cases, (sensitivity:87.5%). In 2 patients, EUS accurately exclouded pancreatic NET. There were no false positive findings (specificity 100%). Six tumours were benign (75%), and two were malign (25%). We localized 6 insulinomas and single pancreatic carcinoid tumour. The median tumour size detected by EUS was 21mm. CONCLUSION: EUS is highly accurate in preoperative localization of the pancreatic NET-s and We confirmed it in our study. EUS presents the method of choice for preoperative localization of the pancreatic NET.
Assuntos
Endossonografia , Tumores Neuroendócrinos/diagnóstico por imagem , Neoplasias Pancreáticas/diagnóstico por imagem , Humanos , Tumores Neuroendócrinos/patologia , Tumores Neuroendócrinos/cirurgia , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , Sensibilidade e EspecificidadeRESUMO
In the past years remarkable increase in knowledge of the mechanisms of insulin resistance has been made. Interest for the insulin resistance has been heightened by it's prevalence, and by the fact that it has a key role in pathogenesis of obesity, diabetes mellitus, arterial hypertension, polycystic ovary disease. In this review we discuss current concepts of the mechanisms of insulin resistance, methods for the assessment as well as its implications for a variety of disorders in human beings.
Assuntos
Resistência à Insulina , Técnica Clamp de Glucose , Humanos , Resistência à Insulina/fisiologiaRESUMO
The aim of our study was to compare the effectiveness of bromocriptine vs. long acting somatostatin analogue (SMS 201-995) on growth hormone suppression in active acromegaly. A twenty year old female, student of law, was previously treated with Parlodel LA 50 mg i.m. injection and then with bromocriptine 30 mg orally for 2.5 years because of active acromegaly and very large intrasellar and suprasellar pituitary adenoma. She was partial bromocriptine responder with mean growth hormone levels prior the treatment 30 mU/L and after bromocriptine 13.7 mU/L and with gross tumor shrinkage. Since she failed to restore menstrual cycles, had clinical signs of the disease, she was taken off bromocriptine and treated with somatostatin analogue (SMS 201-995) 300 mcg s.c. daily and 400 mcg s.c. daily with mean growth hormone levels 10 mU/L. She was also treated with combined treatment (400 mcg s.c. SMS 201-995 plus 30 mg bromocriptine orally) and mean growth hormone levels were 11 mU/L. SMS 201-995 had a long lasting inhibitory effect on growth hormone secretion in acromegaly (p less than 0.01) but in comparison to daily growth hormone levels during bromocriptine treatment no difference was found (p greater than 0.01). Combined treatment with SMS 201-995 and bromocriptine did not achieve greater suppression of daily growth hormone levels than those achieved with SMS 201-995 alone (p greater than 0.1) or with bromocriptine alone (p greater than 0.05). No significant tumor shrinkage during chronic SMS treatment was seen. Severe clinical and biochemical signs of hypoglycaemia were registered on one occasion only during the first month of treatment with SMS 201-995.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Acromegalia/metabolismo , Bromocriptina/farmacologia , Hormônio do Crescimento/antagonistas & inibidores , Octreotida/farmacologia , Adulto , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Feminino , Humanos , Hipoglicemia/induzido quimicamente , Octreotida/efeitos adversos , Neoplasias Hipofisárias/tratamento farmacológico , Somatostatina/metabolismoRESUMO
OBJECTIVE: GH deficiency, either in children or in adults, is a clinically relevant problem. The diagnosis is based on dynamic tests of GH secretion, which are clear cut on a group basis but highly problematic for individual diagnosis. The controversy surrounding the diagnosis of GH deficiency reflects the absence of a gold standard dynamic test. The synthetic hexapeptide hexarelin and GHRH stimulate GH secretion using different mechanisms. A sequential test has been devised using the administration of GHRH as first stimulus followed 120 minutes later by hexarelin. The two aims of the study were (a) to evaluate the interaction of GHRH and hexarelin, and (b) to devise a sequential test of GH reserve. DESIGN: The GH stimuli used were GHRH (1 microgram/kg i.v.) as a pituitary stimulus, and hexarelin (1 microgram/kg i.v.) as a GH stimulus whose main action is hypothalamic. Each subject was tested twice in order to serve as his own control. Three different studies, each with two duplicate tests, were performed on separate groups of individuals: (a) GHRH followed 120 minutes later by hexarelin and on the second day hexarelin followed 120 minutes later by GHRH; (b) GHRH followed 120 minutes later by GHRH and on the other day hexarelin followed 120 minutes later by hexarelin; (c) GH 0.5 IU i.v. followed 120 minutes later by GHRH and on the other day, the same dose of GH followed 120 minutes later by hexarelin. PATIENTS: Eighteen normal volunteers (12 women, 6 men) after giving informed consent. MEASUREMENTS: Plasma GH levels were measured by time-resolved fluoroimmunoassay; each value shown is the mean +/- SEM of n = 6. RESULTS: GHRH followed 120 minutes later by hexarelin induced two episodes of GH secretion (expressed as mean GH peak, mU/l). The GHRH-mediated GH release showed a mean GH peak of 38.2 +/- 13.6 mU/l and after hexarelin 120 minutes later of 56.7 +/- 18.0 mU/l. The contrary sequence blocked the second stimulus, i.e. the hexarelin-stimulated GH mean peak was 54.7 +/- 18.4, and the GH release 120 minutes later after GHRH was 4.8 +/- 1.9 (P < 0.05 vs GHRH used as first stimulus). In the two sequential tests using the same stimulus, the second GH peak was reduced. In fact, GHRH induced a GH mean peak of 63.8 +/- 21.1 mU/l as first stimulus, greater (P < 0.05) than when GHRH was administered again 120 minutes later (22.0 +/- 5.9 mU/l). Similar results were obtained with hexarelin, with a first mean peak of 70.6 +/- 10.3 mU/l, and a second one 120 minutes later of 13.4 +/- 4.6 mU/l (P < 0.05). The blockade of the second stimulus was not due to the feed-back action of the GH released by the first stimulus. In fact, the i.v. administration of exogenous GH induced a mean GH peak of 168.0 +/- 89.7 and reduced the action of GHRH administered 120 minutes later (26.1 +/- 8.1). The previous administration of GH (mean peak 115.5 +/- 42.0) did not alter the action of hexarelin injected 120 minutes later, showing a mean peak of 71.9 +/- 11.2. The large variability in the stimulatory action of GHRH contrasted vividly with the reproducibility of hexarelin. Furthermore, individually analysed, only one of the 12 subjects tested first with hexarelin, compared to 4 out of 12 tested with GHRH as first stimulus, presented a blunted response (< 13 mU/l). After the sequential stimulus there were no false negatives. CONCLUSION: The sequential administration of GHRH in normal subjects and of hexarelin 120 minutes later provides separate information regarding pituitary GH reserve, of both secretagogues without mutual interference. There were not false negative results to the combined test. This sequentially delayed test may be of some value in the clinical setting for assessing pituitary GH reserve.
Assuntos
Hormônio Liberador de Hormônio do Crescimento , Hormônio do Crescimento/metabolismo , Oligopeptídeos , Hipófise/metabolismo , Adulto , Feminino , Hormônio do Crescimento/sangue , Hormônios , Humanos , Masculino , Hipófise/efeitos dos fármacos , Reprodutibilidade dos Testes , Estimulação QuímicaRESUMO
BACKGROUND: Controversial results have been obtained in measuring insulin sensitivity (S(I)) during recombinant human growth hormone (rhGH) treatment in adult growth hormone deficient (GH-deficient) patients. AIMS: The aim of our study was to estimate S(I) before and during treatment using three different methods for quantifying insulin sensitivity in GH-deficient adults treated with rhGH. SETTINGS AND DESIGN: Twenty-one GH-deficient adults were treated with rhGH during 12 months. S(I) was estimated using Minimal model analysis, Homeostatic Model of Assessment (HOMA) and Quantitative Insulin Sensitivity Check Index (QUICKI) before and after 3, 6, 9 and 12 months of rhGH therapy. MATERIAL AND METHODS: Oral Glucose Tolerance Test (OGTT) and Frequently Sampled Intravenous Glucose Tolerance Test (FSIGT) were performed in each patient at respective time intervals. QUICKI and HOMA were calculated using basal values of glucose and insulin from FSIGT. Minimal model computer analysis was calculated from glucose and insulin data obtained during FSIGT. STATISTICAL ANALYSIS: Area under the curve for glucose, insulin and C-peptide were calculated using trapezoidal rule from OGTT data. Differences and correlations were tested using ANOVA for repeated measures, Wilcoxon's matched-paired test, paired t-test, Pearson's correlation and Bland Altman plot. RESULTS: There were no significant changes in S(I) using Minimal model analysis and QUICKI during rhGH treatment. On the contrary, HOMA analysis indicated significant deterioration in S(I) after 12 months of therapy. CONCLUSION: Our study did not demonstrate any changes in S(I) using Minimal model and QUICKI analysis, while there was significant increase in insulin resistance using HOMA model. We suggest that the choice of method for the determination of S(I) may influence the interpretation of results concerning the effect of rhGH therapy on S(I) in GH-deficient adults.
Assuntos
Transtornos do Crescimento/fisiopatologia , Hormônio do Crescimento/farmacologia , Resistência à Insulina/fisiologia , Adulto , Feminino , Teste de Tolerância a Glucose , Transtornos do Crescimento/tratamento farmacológico , Humanos , Masculino , RadioimunoensaioRESUMO
OBJECTIVE: Growth hormone (GH) secretion in middle and late adulthood declines with age. However, the precise mechanisms causing this impairment in GH release are unknown. His-D-Trp-Ala-Trp-D-Phe-Lys-NH2 (GHRP-6) is a synthetic compound that releases GH in a dose related and specific manner in several species, including man. In order to gain a further insight into disrupted GH secretion in late adulthood, we evaluated GH responses to GHRP-6 or GHRH, administered either alone or in combination, in healthy young and late adulthood groups of subjects. DESIGN: All subjects underwent three different tests carried out in random order and separated by at least one week. Tests were performed at 0900 h after an overnight fast. GHRH (100 micrograms), GHRP-6 (90 micrograms) either alone or in combination were administered as an i.v. bolus. SUBJECTS: Groups of healthy young (mean +/- SEM 22 +/- 1.1 years, n = 9) and older adult subjects (59.5 +/- 1.7 years, n = 9) were studied. MEASUREMENTS: Serum GH levels were measured by radioimmunoassay. RESULTS: In the group of young adult subjects the combined administration of GHRH and GHRP-6 elicited a greater GH increase than GHRH alone (F = 21.9, P < 0.001) or GHRP-6 alone (F = 6.2, P = 0.01). Similarly, the response to the combined stimuli was also greater than with GHRH alone (F = 21.8, P < 0.001) or GHRP-6 alone (F = 23.9, P < 0.001) in the late adulthood group of subjects. GH responses to GHRH were greater in younger than in older subjects (F = 3.45, P = 0.03). In contrast, GH responses to either GHRP-6 (F = 0.71, P = NS) or combined GHRH plus GHRP-6 administration (F = 0.68, P = NS) were not significantly different between the two groups. CONCLUSIONS: These data show that GH responses to GHRP-6 are much greater than to GHRH in late adulthood. The marked increase of plasma GH levels observed after administration of GHRP-6 alone or in combination with GHRH indicates that impaired GH secretion in late adulthood is a functional and potentially reversible state.
Assuntos
Hormônio Liberador de Hormônio do Crescimento/farmacologia , Hormônio do Crescimento/sangue , Oligopeptídeos/farmacologia , Adulto , Envelhecimento/fisiologia , Feminino , Hormônios/farmacologia , Humanos , Masculino , Pessoa de Meia-Idade , Estimulação Química , Fatores de TempoRESUMO
A patient with an FSH secreting pituitary adenoma is reported. Elevated FSH and serum free alpha-subunit (SU) with low levels of LH and testosterone (T) were found. Immunostaining showed the presence of alpha-SU, FSH-beta and LH-beta subunits. LHRH analogue (buserelin) was administered in a pulsatile manner, by portable computerized infusion pump sc for ten days. During the first 24 h of treatment FSH, LH (p less than 0.001) and T (p less than 0.01) rose significantly. Ten days later, the expected desensitization phenomenon did not occur, but further increases of T (8.4 +/- 2.6, mean +/- SD, vs 17.4 +/- 4.1 nmol/l, p less than 0.001) and FSH (58.9 +/- 9.6 vs 70.7 +/- 3.8 mlU/ml, p less than 0.001) were registered. LH decreased (12.5 +/- 2.4 vs 7.1 +/- 0.6 mlU/ml, p less than 0.001) at day 10, but remained higher than basal level (5.0 +/- 0.6, p less than 0.001). Free alpha-SU also rose (2.8 +/- 0.4 vs 4.4 +/- 1.7 mlU/ml, p less than 0.001) after ten days of treatment. The chronic stimulatory effect of analogue on LH with a lack of desensitization suggests tumorous secretion despite a partially preserved negative feedback of testosterone. Low basal LH levels, in some patients with FSH secreting tumors may not be due to tumor mass effect, but rather may be the consequence of altered LH production and/or secretion by the tumor. Although buserelin may not have a therapeutic effect, it is of use in differential diagnosis of hypergonadotropinemia.
Assuntos
Adenoma Cromófobo/sangue , Adenoma Cromófobo/tratamento farmacológico , Busserrelina/uso terapêutico , Hormônio Foliculoestimulante/sangue , Neoplasias Hipofisárias/sangue , Neoplasias Hipofisárias/tratamento farmacológico , Adulto , Subunidade alfa de Hormônios Glicoproteicos/sangue , Humanos , Hormônio Luteinizante/sangue , Masculino , Testosterona/sangueRESUMO
Hypothalamo-hypophyseal metastases are still a relatively unfamiliar entity. Mostly they are confirmed by autopsy. Rear clinical manifestations are presented by diabetes insipidus. In general, patients with endocrine breast carcinoma metastases are young, premenopausal women, with great tumour burden and widely disseminated tumor. We report 54-year-old woman with diabetes insipidus caused by solitary breast carcinoma metastasis, eight years after primary tumour was diagnosed. The operative and radiation therapy were effective.
Assuntos
Neoplasias da Mama/patologia , Diabetes Insípido/etiologia , Neoplasias Hipofisárias/secundário , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Hipofisárias/complicaçõesRESUMO
Inhibition of C-Peptide secretion by exogenous insulin was studied during euglycemic clamp in 13 patients with histologically verified causes of organic hyperinsulinaemia (10 with beta cell adenoma; 2 with beta cell carcinoma and 1 with beta cell hyperplasia) and in 10 healthy controls. Euglycemic clamps were performed using artificial endocrine pancreas (Clamp Mode 9:1) while insulin infusion (Humulin Normal-Lilly) rate was 0.1 U/kg BW/h. Blood samples for serum insulin (RIA INEP) and C-Peptide (RIA-Biodata) were taken at 0; 30; 60; 90 and 120 min. Statistical analysis was done using SPSS on IBM-PC with Wilcoxon sum rank test and one way ANOVA. All the patients were studied before the operation and in four of them clamp studies were repeated after the operation. Statistically significant suppression of C-Peptide values in 120 min was established in the control group (p less than 0.05) while there was no significant suppression in insulinoma group (p greater than 0.05), except in one patient with beta cell hyperplasia. Various types of responses (suppression, no change, paradoxical increase) were observed after the operation in the insulinoma group. Possible mechanisms and the meanings of the absence of insulin induced C-Peptide suppression in insulinoma group are discussed. It is concluded that euglycemic hyperinsulinemic clamp study could be useful and a complementary test to other established tests for the confirmation of the diagnosis of insulinoma. Further work on beta cell response after the operation in patients with insulinoma is necessary.
Assuntos
Adenoma de Células das Ilhotas Pancreáticas/complicações , Técnica Clamp de Glucose , Hiperinsulinismo/diagnóstico , Insulinoma/complicações , Neoplasias Pancreáticas/complicações , Adenoma/complicações , Adenoma/diagnóstico , Adenoma/metabolismo , Adulto , Idoso , Análise de Variância , Índice de Massa Corporal , Peptídeo C/metabolismo , Carcinoma/complicações , Carcinoma/diagnóstico , Carcinoma/metabolismo , Feminino , Humanos , Hiperinsulinismo/etiologia , Hiperplasia/complicações , Hiperplasia/diagnóstico , Hiperplasia/metabolismo , Insulina/metabolismo , Secreção de Insulina , Masculino , Pessoa de Meia-IdadeRESUMO
The response of TSH, PRL, LH and FSH to combined test with LHRH (Relefact LH-RH, HOECHST; 0.1 mg) and TRH (Relefact TRH, HOECHST; 0.2 mg) was examined before (day I) and after naloxone (Narcanti, DUPONT) bolus of 0.8 mg (day III) in 8 patients with polycystic ovary syndrome (POC) diagnosed by established criteria (hirsutism, oligoamenorrhoea, ultrasound appearance of polycystic ovary and serum LH/FSH greater than 2.0). TSH (RIA-INEP), PRL (MAIA-SERONO), LH (MAIA-SERONO) and FSH (MAIA-SERONO) were determined at -15, 0, 10, 20, 30, 45, 60, 90 and 120 min. The hormone responses were calculated as the areas under hormone curves and tested with Wilcoxon sum rank test. No significant difference was found in the hormone responses before and after naloxone injection. In terms of absolute values lower TSH level was found at 30 min after naloxone administration (14.7 +/- 12.0 vs. 9.73 +/- 7.61; P less than 0.05). In conclusion, our data based on short term naloxone application argue against the significant alteration of the opioid activity in patients with POC.
Assuntos
Hormônio Liberador de Gonadotropina , Naloxona/farmacologia , Hipófise/metabolismo , Síndrome do Ovário Policístico/metabolismo , Hormônio Liberador de Tireotropina , Adulto , Feminino , Hormônio Foliculoestimulante/metabolismo , Humanos , Hormônio Luteinizante/metabolismo , Hipófise/efeitos dos fármacos , Prolactina/metabolismo , Tireotropina/metabolismoRESUMO
In order to test whether prolactin response to challenge with TRH and domperidone, dopamine receptor antagonist, is diagnostic for idiopathic hypothalamic hypogonadism (IHH) we studied 8 normal controls, 9 subjects with delayed sexual development and 6 patients with IHH. TRH test (200 micrograms i.v. bolus) and domperidone (10 mg i.v. bolus) were given on two different days. Prolactin (RIA-Biodata) was determined in blood samples during the test. The basal value of prolactin in subjects with delayed puberty and healthy controls did not differ from basal values of prolactin in patients with IHH. The peak elevation of prolactin after TRH in subjects with delayed puberty and healthy controls did not differ from that in patients with IHH. After successful treatment of one patient with IHH (Kallmann's syndrome) with pulsatile s.c. LHRH we did not find any change in the response of prolactin to TRH challenge after 1, 3 and 6 months of treatment, while prolactin response to domperidone increased. Prolactin responses to TRH and domperidone are not differential for the early diagnosis of IHH. Successful treatment of a patient with IHH did not change the response of prolactin to TRH, but increased prolactin response to domperidone possibly due to altered steroid milieu.
Assuntos
Domperidona , Hipogonadismo/diagnóstico , Prolactina/sangue , Puberdade Tardia/diagnóstico , Hormônio Liberador de Tireotropina , Adolescente , Adulto , Diagnóstico Diferencial , Hormônio Liberador de Gonadotropina/uso terapêutico , Humanos , Hipogonadismo/sangue , Doenças Hipotalâmicas/sangue , Doenças Hipotalâmicas/diagnóstico , Masculino , Puberdade Tardia/sangueRESUMO
Assessment of peripheral insulin sensitivity using artificial endocrine pancreas was done in 15 diabetics (6 with insulin dependent diabetes mellitus and 9 with non-insulin dependent diabetes mellitus) and in 10 healthy controls, matched for sex, age and body mass index. Insulin sensitivity-RC was expressed in mg of utilised glucose/kg body weight in minute. Significantly lower insulin sensitivity was found in non-insulin dependent diabetes mellitus (RC = 2.30 +/- 1.37) compared to insulin dependent group (RC = 5.88 +/- 2.89) and control group (RC = 4.93 +/- 1.96). There was no significant change in insulin sensitivity between insulin dependent diabetics and controls (p greater than 0.05). It is concluded that investigations of this kind could be used in search for pathogenetic mechanism of insulin resistance in some types of diabetes mellitus on one side, and on the other side that euglycemic clamp technique could be used for the assessment of the effects of some therapeutical measures on peripheral insulin sensitivity.
Assuntos
Diabetes Mellitus/metabolismo , Técnica Clamp de Glucose , Resistência à Insulina , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
The study was conducted to assess leptin levels and insulin sensitivity in obese and non-obese patients with polycystic ovary syndrome (PCOS). Twenty-two women with PCOS and 19 control healthy women were included in the study, divided into obese and non-obese groups. Leptin was determined using Linco Research radio-immunoassay while insulin sensitivity was calculated from intravenous glucose tolerance tests with frequent blood sampling using MINMOD analysis. Significantly higher basal leptin levels were found in obese compared to non-obese PCOS (31.76 +/- 3.06 vs. 10.42 +/- 2.31 ng/ml; p < 0.05) as well as in obese in comparison to non-obese controls (29.16 +/- 5.06 vs 8.51 +/- 0.88 ng/ml; p < 0.05). A negative correlation was found between insulin sensitivity and leptin levels in both obese (r = -0.2480; p > 0.05) and non-obese PCOS groups (r = -0.4620; p > 0.05). In conclusion, high serum leptin, insulin and testosterone levels together with reduced insulin sensitivity were found in obese PCOS women, suggesting that high leptin levels could be a characteristic of the obese PCOS phenotype.