Evaluation of Kisspeptin levels in prepubertal obese and overweight children: sexual dimorphism and modulation of antioxidant levels.

OBJECTIVE: Kisspeptin, neuropeptide involved in puberty beginning and regulation of pituitary-gonadal axis, has been shown to stimulate antioxidant defenses in murine models. Its levels are greater in females than males and also in obese prepubertal girls. Therefore, our aim was to evaluate sex-related differences in prepubertal obese patients and the relationships of Kisspeptin with metabolic/hormonal parameters. PATIENTS AND METHODS: We studied Kisspeptin concentrations in 54 children (22 males and 32 females, Tanner stage 1), 5-12 ys, classified according to Cole's criteria into 17 overweight and 37 obese; 25 normal-weight children, aged 6-12 years, were studied as controls. We evaluated metabolic (glucose and insulin levels after oral glucose load, total- LDL- HDL-cholesterol, triglycerides, uric acid) and hormonal (fT3, fT4, TSH, IGF-1, leptin) parameters. Moreover, total antioxidant capacity (TAC) was evaluated by spectrophotometric method, using the system H202-metmyoglobin-ABTS. Kisspeptin levels were measured by RIA. RESULTS: We did not find significant differences between obese and normal-weight children, but obese males presented significantly lower levels than females. Kisspeptin did not correlate with BMI, HOMA-IR, Insulin peak levels and TAC; a significant correlation was found between Kisspeptin and fT3 (r2=0.25; p=0.003) in the obese group; leptin levels, significantly greater in obese vs. overweight and control children, significantly correlated with TAC (r2=0.39; p=0.03). CONCLUSIONS: These data suggest that both hormones could modulate antioxidants, Kisspeptin indirectly via influence on thyroid hormones, and Leptin by a direct effect. This mechanism seems to be sex-related, not attributable to peripheral steroid levels. Further studies can clarify the complex interrelationship between central and peripheral Kisspeptin secretion and oxidative stress in children obesity.

Thyroid hormones modulate irisin concentrations in patients with recently onset hypothyroidism following total thyroidectomy.

PURPOSE: Irisin is a newly discovered adipo-myokine known for having significant effects on body metabolism. Currently, there is a discussion regarding the relation between thyroid function and irisin concentration. This study was designed to evaluate the influential role of levothyroxine replacement therapy on circulating levels of irisin in patients with recently onset hypothyroidism following total thyroidectomy. METHODS: Circulating levels of thyroid hormones, irisin and other metabolic parameters, were assessed in 40 recently thyroidectomized patients (34 females, mean age 50.1 ± 15.2 years) at baseline (5-7 day after surgery) and after 2 months under replacement therapy with levothyroxine. RESULTS: At baseline, circulating levels of thyroid hormones were indicative of hypothyroidism (TSH 12.7 ± 5.0 µU/mL, FT3 1.9 ± 0.7 pg/mL, FT4 8.7 ± 3.6 pg/mL). Mean serum irisin concentrations significantly increased after 2 months under replacement therapy with levothyroxine (from 2.2 ± 0.6 to 2.9 ± 0.6 µg/mL, p < 0.0001). Variations of circulating levels of irisin under levothyroxine replacement therapy were directly correlated with those of FT3 (Rho = 0.454, p = 0.0033) and FT4 (Rho = 0.451, p = 0.0035). Multivariate regression analysis revealed that changes in thyroid hormones concentrations explained up to 10% of the variations of serum irisin levels under levothyroxine replacement therapy (FT3 R2 = 0.098, FT4 R2 = 0.103). CONCLUSION: Our study suggests that levothyroxine replacement therapy mildly influences irisin metabolism in patients with recently onset hypothyroidism following total thyroidectomy.

Lack of association between Vitamin D status and free light chains profile with different chronic HCV-related liver and extrahepatic disorders.

OBJECTIVE: A still uncertain association between vitamin D levels and HCV chronic liver diseases has been reported. Increased levels of serum-free light chains (FLCs) and an altered k/λ FLC ratio correlate with Mixed Cryoglobulinemia (MC) vasculitis and/or B-cell non-Hodgkin's lymphoma in HCV-positive patients. We aimed to investigate the possible role of vitamin D, vitamin D Binding Protein (DBP), and FLCs levels as a tool for discriminating different stages of HCV- related MC and chronic liver diseases. PATIENTS AND METHODS: Sixty-five untreated patients were retrospectively enrolled and 21 healthy blood donors (HBD) were used as controls. Vitamin D, DBP, FLCs, and cryoglobulins levels were measured. Based on cryoglobulins, patients were divided in three subgroups (without cryoglobulins, type II, and type III). RESULTS: We didn't find any significant differences in vitamin D and DBP levels between HCV patients' main groups and HBD. Serum FLCs levels were significantly higher in HCV patients than in HBD. FLCs ratio among patients' subgroups did not reveal differences. CONCLUSIONS: Our results confirm the presence of an increased serum level of FLCs in HCV patients and suggest that nor vitamin D and DBP or FLC levels can be considered reliable biomarkers for discriminating different stages of HCV-associated chronic liver diseases and/or HCV-associated extrahepatic manifestation. We confirm that serological FLCs levels are significantly higher in patients than in HBD as a signature of B cell activation in course of HCV infection.

Replacement therapy with levothyroxine modulates platelet activation in recent-onset post-thyroidectomy subclinical hypothyroidism.

BACKGROUND AND AIM: Subclinical hypothyroidism has been linked to increased risk of atherosclerotic disease. Soluble CD40 ligand (sCD40L), mainly derived from activated platelets, and the lipid peroxidation product 8-iso-prostaglandin F2α (8-iso-PGF2α) are known to play a relevant pathophysiological role in atherogenesis. In this study, we analyzed the relationship between thyroid hormones and circulating levels of sCD40L and 8-iso-PGF2α in patient with recent-onset post-thyroidectomy subclinical hypothyroidism under replacement therapy. METHODS AND RESULTS: Circulating levels of thyroid hormones, sCD40L, and 8-iso-PGF2α were assessed in 40 recently thyroidectomized patients (33 females, mean age 52.0 ± 11.7 years) at baseline (5-7 day after surgery) and after 2 months under replacement therapy with levothyroxine (LT-4). At baseline, circulating levels of thyroid hormones were indicative of a subclinical hypothyroidism (TSH 7.7 ± 3.9 µU/mL, FT3 1.8 ± 0.6 pg/mL, and FT3 8.9 ± 3.0 pg/mL). Circulating levels of sCD40L and 8-iso-PGF2α were directly correlated with each other (r = 0.360, p = 0.023) and with TSH levels (r = 0.322, p = 0.043 and r = 0.329 p = 0.038, respectively). After 2 months under the replacement therapy with LT-4 circulating levels of TSH (from 7.7 ± 3.9 to 2.7 ± 2.8 µU/mL, p < 0.0001), sCD40L (from 6.11 ± 2.41 to 2.43 ± 2.00 ng/mL, p < 0.0001) and 8-iso-PGF2α (from 45.33 ± 6.94 to 40.36 ± 6.20, p < 0.0001) significantly decreased. Changes in circulating levels of sCD40L and 8-iso-PGF2α were directly correlated with each other (r = 0.349 p = 0.028) and with changes in TSH levels (r = 0.367 p = 0.020 and r = 0.339 p = 0.032, respectively). CONCLUSION: Our study suggests an influential role of TSH on proatherogenic activation of platelets, probably through enhanced lipid peroxidation. These findings could partially explain the increased susceptibility of patients with subclinical hypothyroidism to develop atherosclerotic disease.

Serum γ - glutamyltransferase activity as an indicator of chronic liver injury in cattle with no clinical signs / γ - glutamiltransferase como indicador de lesão hepática crônica em bovinos sem sinais clínicos

This study aimed to determine the power of the serum aspartate aminotransferase (AST) and gamma-glutamyltransferasase (GGT) activities and of the albumin and cholesterol dosages for detecting hepatic histopathological injuries. A total of 220 healthy male Nelore cattle that had been extensively bred were evaluated. Blood and liver samples were collected on the day of slaughter for biochemical and histopathological tests. The results showed that the sensitivity to AST, GGT, albumin, and cholesterol tests were respectively 22.4%, 22.4%, 36%, and 37.2%.

Determinou-se a capacidade da dosagem das atividades séricas da aspartato aminotransferase (AST) e gama-glutamiltransferase (GGT) e das dosagens de albumina e de colesterol para a detecção de lesões histopatológicas hepáticas. Foram avaliados 220 bovinos, machos da raça Nelore, criados de forma extensiva. Amostras de sangue e de fígado foram coletadas para a realização dos testes histopatológicos e bioquímicos no dia do abate. Os resultados mostraram que a sensibilidade dos testes de AST, GGT, albumina e colesterol foram, respectivamente, de 22,4%, 22,4%, 36%, e 37,2%. A especificidade dos testes AST, GGT, albumina e colesterol foram, respectivamente, de 78,8%, 90,4%, 75,6% e 68,3%.

Bone mineral density in survivors of childhood brain tumours.

BACKGROUND: Osteopenia has been reported in children surviving acute lymphoblastic leukaemia, apparently as consequence of therapy. Few studies have been published on bone mineral density (BMD) evaluation in children surviving from brain tumours. The endocrine system in these patients is frequently affected as consequence of therapeutic interventions such as cranial irradiation and anti-neoplastic agents: growth hormone deficiency is the most common adverse sequel. The pathogenesis of osteopenia in brain cancer survivors is multi-factorial but still uncertain. OBJECTIVE: The aim of this study is to examine bone mass in 12 brain cancer survivors and its relationship with their hormonal status. RESULTS AND DISCUSSION: We observed that most of the patients had a BMD that was lower than normal in both the lumbar column and in the femoral neck. Bone mass loss was higher in the lumbar region rather than in the femoral neck, due to spinal radiation therapy and to the effect of hormonal deficiencies. Particularly hypogonadism, but also multiple hormonal deficiencies, are associated with lower BMD values. Experience in clinical care of these patients suggests the importance of periodic evaluations of BMD, especially in those with secondary hormone deficiencies. Moreover, the periodic assessment of the hypothalamus-pituitary function is essential for an early diagnosis of hormonal insufficiency, primarily hypogonadism, to precociously detect bone mineral loss and to prevent pathological fractures, thus improving the quality of life.

Superalimentação e desenvolvimento do esqueleto de cães da raça Dogue Alemão: aspectos clínicos e radiográficos / Overfeeding and skeletal development in Great Dane puppies: clinical and radiographic aspects

Estudou-se o efeito da superalimentação no desenvolvimento do esqueleto de 14 cães da raça Dogue Alemão, utilizando dieta hipercalórica (ração super-premium) associada ao método de alimentação à vontade. Os animais foram distribuídos em dois tratamentos, sendo a ração fornecida à vontade ou restrita. O consumo de alimento foi registrado diariamente e realizaram-se, mensalmente, radiografias do cotovelo e, bimestralmente, do ombro, do quadril e do carpo, visando acompanhar alterações do esqueleto, especificamente quanto ao aparecimento da osteocondrose do ombro e da metáfise distal da ulna, da osteodistrofia hipertrófica e da displasia coxofemoral (DCF). Ao final do experimento, seis cães do grupo que recebeu alimentação à vontade apresentaram-se gordos (87,7 por cento) e um animal obeso (14,3 por cento). Do grupo de alimentação restrita, três filhotes mostraram condição corporal ideal (42,8 por cento), e quatro apresentaram-se magros (57,2 por cento). O exame radiológico revelou alterações compatíveis com o diagnóstico de DCF nos dois grupos; nos alimentados à vontade, a prevalência foi de 51,1 por cento e nos restritos, de 28,6 por cento. A osteocondrose na metáfise distal da ulna, conhecida como retenção do núcleo cartilaginoso, foi observada apenas nos cães alimentados à vontade (57,1 por cento). A superalimentação provocada pelo método de alimentação à vontade, associada com dieta de alta palatabilidade e alta densidade energética em filhotes da raça Dogue Alemão, induziu ao aparecimento de osteocondrose na metáfise distal da ulna e de displasia coxofemoral.

The effects of overfeeding on growing Great Dane puppies were examined by ad libitum feeding of a hypercaloric diet (super premium ration). Fourteen puppies from six litters were divided into two groups, with representation from each litter in each group. The dogs in the overfed group were provided ad libitum access to the diet from 8 AM to 6 PM daily, while the restricted group received the same feed but in amounts recommended by the manufacturer at 7 AM, 12:30 PM and 5 PM. Daily intake was individually recorded. To monitor skeletal changes due to osteochondrosis, hypertrophic osteodystrophy and hip dysplasia, elbow radiographs were taken monthly and shoulder, pelvis and corpus radiographs were taken bi-monthly. Weekly feed consumption and weight gain were greater in ad libitum than in restricted puppies (P<0.01). At the end of the experiment, 85.7 percent of the ad libitum group was over weight and 14.3 percent was obese, whereas 57.2 percent of restricted puppies were slim and 42.8 percent had ideal body weight. None of the dogs had hypertrophic osteodystrophy. Radiographic examination showed alterations compatible with hip dysplasia in both groups, but such observations were more frequent and more severe in the ad libitum group. Osteochondrosis of metaphisis distal ulna, known by the retention of cartiloginous nucleus, was observed only in the ad libitum group, at a rate of 57.1 percent. The thickness of the cortical and diameter of the ulna were greater (P<0.01) in ad libitum dogs than in those fed a restricted amount of the same diet. In summary, overfeeding caused by ad libitum access to a highly palatable and high energy food caused osteochondrosis and hip dysplasia in Great Dane puppies.

Does autonomic neuropathy play a role in erythropoietin regulation in non-proteinuric Type 2 diabetic patients?

AIMS: Erythropoietin (EPO)-deficient anaemia has been described in Type 1 diabetic patients with both severe autonomic neuropathy (AN) and proteinuria. This study was aimed at distinguishing between the effects of AN and nephropathy on haemoglobin and EPO levels in Type 2 diabetic patients at an early stage of diabetic nephropathy. METHODS: In 64 Type 2 diabetic patients (age 52 +/- 10 years, duration 10 +/- 9 years) without overt nephropathy and other causes of anaemia or EPO deficit, we assessed cardiovascular tests of AN, 24-h blood pressure (BP) monitoring, urinary albumin excretion rate (UAE), a full blood count, and serum EPO. RESULTS: Although the Type 2 diabetic patients with AN did not show differences in haemoglobin and EPO when compared with patients without AN, the presence of haemoglobin < 13 g/dl was associated with the presence of AN (chi(2)= 3.9, P < 0.05) and of postural hypotension (chi(2)= 7.8, P < 0.05). In a multiple regression analysis including as independent variables gender, body mass index, duration of diabetes, smoking, creatinine, 24-h UAE, 24-h diastolic BP, ferritin, erythrocyte sedimentation rate, and autonomic score, we found that the only variables independently related to haematocrit were autonomic score, ferritin and erythrocyte sedimentation rate. Finally, the physiological inverse relationship between EPO and haemoglobin present in a control group of 42 non-diabetic non-anaemic subjects was completely lost in Type 2 diabetic patients. The slopes of the regression lines between EPO and haemoglobin of the control subjects and the Type 2 diabetic patients were significantly different (t = 14.4, P < 0.0001). CONCLUSIONS: This study documents an early abnormality of EPO regulation in Type 2 diabetes before clinical nephropathy and points to a contributory role of AN in EPO dysregulation.

Which treatment options should be used in adolescents with polycystic ovary syndrome?

Several studies have hypothesized a peripubertal onset of polycystic ovary syndrome (PCOS). This syndrome affects different pathogenetic pathways and includes endocrine-metabolic abnormalities such as hyperandrogenism, hyperinsulinism and insulin resistance. The therapeutic approaches must be addressed to individualization of therapy, considering the major clinical manifestations of the syndrome during adolescence. While the treatment of hyperandrogenism makes use of different drugs already studied, the debate about the use of insulin sensitizing drugs is still open. It will be more and more necessary to define the phenotypic and genotypic milieu in which all treatments will be as safe and effective as possible.

Young stroke and basal plasma and post-methionine load homocysteine and cysteine levels 1 year after the acute event: do plasma folates make the difference?

We conducted a case-control study to evaluate the relationship between ischemic stroke in young adults (<45 years of age) and plasma homocysteine (Hcy), plasma folate and vitamin B(12), after a methionine load. We studied 42 patients with a history of ischemic stroke and 29 controls with a negative clinical history of cardio- or cerebrovascular diseases, venous thrombosis and renal disease. A fasting blood sample was drawn from each participant; the second and third samples were collected, respectively, 120 and 240 min after the methionine load. Whilst there was no difference between controls and patients in basal total homocysteine (tHcy), we found a statistically significant difference in both the 120- and 240-min samples. We compared the basal and 240-min tHcy in patients and controls. We obtained a median value of 17.8 and 11.6 micromol/l in patients and controls, respectively. The difference between these two values was highly significant. The methionine loading test (MLT) reveals Hcy metabolism abnormalities that were not revealed by the basal sample. MLT may help identify and treat this new risk factor, which seems to be both atherogenic and prothrombotic, and is hypothesized to operate through various mechanisms.

Insulin and GH secretion in adolescent girls with irregular cycles: polycystic vs multifollicular ovaries.

In the present study insulin (I) and GH secretion was studied in a group of twenty-five young adolescent girls (mean age: 15 +/- 0.23 yr) with cycle irregularity associated to clinical signs of hyperandrogenism in comparison with that observed in eleven normal matched subjects with regular menses. All patients underwent basal hormone measurements and, on two consecutive days, an oral glucose tolerance test (OGTT) and a GHRH iv test. Therefore, all subjects had a transabdominal US scan for the measurement of ovarian volume and the characterization of ovarian morphology. On the basis of the US examination we found patients with polycystic ovaries (PCO-like group) and subjects with multifollicular ovaries (MFO group). PCO-like group exhibited T (p<0.01) and LH (p<0.05) plasma levels higher than control group and the highest free androgen index (FAI) values (13 +/- 0.87). All patients with irregular menses showed plasma concentrations of AUC for I (AUC-I) significantly higher in respect to control group (7359.4 +/- 709 vs 5447 +/- 431 microIU/ml x 180 min, p<0.01) as well as both PCO-like group and MFO group did (p<0.001 and p<0.01) respectively. MFO group showed higher values of the AUC for GH (AUC-GH) (2809 +/- 432 ng/ml x 120 min) in respect to controls (1708 +/- 208 ng/ml x 120 min, p<0.05) and PCO-like subjects (p<0.001), who on the contrary showed the lowest AUC-GH values (618 +/- 119 ng/ml x 120 min). In conclusion, PCO-like patients associated hyperinsulinemia with a blunted GH secretion while MFO patients had higher GH secretion associated with higher AUC-I values in a way suggesting an immature and still developing reproductive system.

ACTH, cortisol and prolactin in active rheumatoid arthritis.

Prolactin (PRL) and glucocorticoids are hormones involved in the regulation of the immune system. Rheumatoid arthritis (RA) is an inflammatory condition that presents a diurnal rhythm of disease activity. ACTH, PRL, cortisol, IL-1 beta and TNF-alpha circadian rhythms have been studied in active RA (aRA) to evaluate a possible relationship between the neuroendocrine system and immunological activity in rheumatoid patients. ACTH, PRL, cortisol, PRL/cortisol ratio and IL-1 beta and TNF-alpha levels were determined in aRA patients and in control subjects at 6.00, 10.00, 14.00, 18.00, 22.00 and 02.00 h. In aRA patients we observed lower ACTH and cortisol levels at 22.00 h and 2.00 h, respectively and higher PRL and PRL/cortisol ratio at 2.00 h when compared to controls. IL-1 beta and TNF-alpha reached their highest serum levels in aRA patients at 2.00 and 6.00 h. This study provides evidence that in aRA there could be a temporary and probably causal relationship between diurnal disease activity, hormonal disequilibrium and cytokine secretion. An imbalance in favour of proinflammatory hormones (PRL and cytokines) as opposed to levels of anti-inflammatory hormones could be responsible for the diurnal rhythm of activity disease observed in aRA patients.

Systemic acute-phase response after laparoscopic and open cholecystectomy.

BACKGROUND: Cytokines are the main mediators of inflammation and the response to trauma. The purpose of this study was to compare variations in cytokine levels following laparoscopic cholecystectomy (LC) and mini-laparotomy cholecystectomy (OC), since these two types of operations were considered to be a unique model for examining the role of local tissue injury in postoperative inflammatory reactions. METHODS: A total of 40 patients were studied. Eighteen of them underwent LC; the remaining 22 were operated on using the open technique. Systemic concentrations of interleukin-6 (IL-6), interleukin-1 (IL-1), tumor necrosis factor (TNF), and C-reactive protein (CRP) were measured before and after the operation. In addition, we compared pre- and postoperative white blood cell (WBC) counts, postoperative body temperature, and length of postoperative hospitalization. RESULTS: There was no difference between the two groups in IL-1 and TNF response. The rise in plasma IL-6 levels (18.86 +/- 9.61 vs 5.00 +/- 0.0 pg/ml, p < 0.0001) and CRP (8.40 +/- 5.81 vs 1.43 +/- 1.30 mg/dl, p < 0.001) were more marked after open cholecystectomy than after the laparoscopic procedure. There was no correlation between serum CRP concentrations and the other postoperative parameters. CONCLUSION: The magnitude of the acute-phase response was less pronounced following laparoscopic cholecystectomy, consistent with a reduction in tissue trauma.

Conditional risk factors in men with previous myocardial infarction: relevance of C3 and homocysteine.

OBJECTIVE: To establish which traditional and conditional risk factors were effectively treated, and which remained active, in patients with previous myocardial infarction (PMI). METHODS AND RESULTS: In 47 PMI patients recently submitted to cardiological assessment and in 42 controls (50-70 years old men), traditional risk factors (total cholesterol, high-density lipoprotein cholesterol, blood glucose, blood pressure, cigarette smoking and body mass index) and the following variables were measured: fibrinogen, plasminogen activator inhibitor-1 (PAI-1), lipoprotein(a) [Lp(a)], total homocysteine, plasma folates, vitamin B12, high sensitivity C-reactive protein and C3 complement. Most patients were taking beta-blockers, ACE inhibitors and statins. Accordingly, patients had lower blood pressure and cholesterol values than controls. Moreover, they consumed less alcohol and coffee and did not differ from controls in cigarette smoking and body mass index. Conversely, patients had higher levels of homocysteine, fibrinogen, C3 complement and Lp(a), although of these factors only C3 and homocysteine remained significantly associated with PMI in multivariate analysis. C-reactive protein, PAI-1 and especially C3 often correlated with traditional risk factors in controls, but these correlations tended to disappear or reverse in PMI patients. Fibrinogen inversely correlated with alcohol consumption. Homocysteine correlated (inversely) with plasma folates only. Lp(a) did not correlate with any variable. CONCLUSIONS: Forty-seven patients with previous myocardial infarction displayed an excellent control of traditional risk factors, but they had higher mean C3 and homocysteine levels than the control group.

Factors determining the 24-h blood pressure profile in normotensive patients with type 1 and type 2 diabetes.

Some controversy still exists about factors involved in the abnormal circadian pattern of blood pressure (BP) in diabetes, while prognostic value of non-dipping condition is being increasingly recognised. This study was aimed at evaluating the relative influence of autonomic neuropathy (AN) and albumin excretion on 24-h BP profile in type 1 and type 2 diabetes. We measured AN cardiovascular tests, 24-h ambulatory BP, and urinary albumin excretion rate (UAE) in 47 type 1 and 34 type 2 normotensive non-proteinuric diabetic patients. In type 1 diabetic patients day-night differences (Delta) in systolic and diastolic BP were lower in those with AN than in those without (3 +/- 9 vs 10 +/- 6%, P < 0.01, and 8 +/- 9 vs 16 +/- 6%, P < 0.001), and in univariate regression analysis they were inversely related to both autonomic score, index of degree of AN (r = -0.61, P < 0.001 and r = -0.65, P < 0.001), and to 24-h UAE (r = -0.39, P < 0.01 and r = -0.46, P < 0.001). In type 1 diabetic patients AN was also associated with lower nocturnal decrease in UAE (patients with AN vs without AN: -37 +/- 214 vs 49 +/- 37%, P < 0.05), and with a stronger relationship between simultaneous 24-h UAE and 24-h BP (for systolic BP patients with AN vs without AN: r = 0.62, P < 0.01 vs r = 0.28, NS). In type 2 diabetic patients Delta systolic BP was reduced in patients with AN compared to those without (4 +/- 7 vs 10 +/- 4%, P < 0.01), and it was related only to autonomic score (r = -0.42, P < 0.01). Using a stepwise regression analysis, in type 1 diabetic patients autonomic score was the variable of primary importance for Delta BP, while in type 2 diabetic patients it was the unique determinant not only of Delta systolic BP but also of 24-h systolic BP. In conclusion, AN is the pivotal factor of blunted nocturnal fall in BP in both type 1 and type 2 diabetic patients. In type 1 diabetic patients AN is associated with attenuated circadian pattern of albuminuria and with a steeper relationship between albuminuria and BP, in type 2 diabetic patients AN is the only factor related to elevated 24-h BP levels. Longitudinal studies are needed to establish the potential role of autonomic dysfunction as a progression promoter for nephropathy and hypertension in type 1 and type 2 diabetes respectively.

Hypothalamic-pituitary-adrenal axis sensitivity to opioids in women with polycystic ovary syndrome.

OBJECTIVE: To evaluate the influence of the opioid system on the hypothalamic-pituitary-adrenal axis in women with polycystic ovary syndrome (PCOS). DESIGN: Controlled clinical study. SETTING: Academic research environment. PATIENT(S): Eight lean and 12 obese women with PCOS, and seven lean and 5 obese control subjects. INTERVENTION(S): Each patient received an i.v. bolus of naloxone at a dose of 125 microgram per kilogram of body weight; 48 hours later, each patient received 16 mg of loperamide p.o. MAIN OUTCOME MEASURE(S): Samples were collected for 2 hours for the naloxone test and for 3 hours for the loperamide test. Levels of adrenocorticotropic hormone (ACTH) and cortisol were measured in all plasma samples. RESULT(S): The obese women with PCOS had a greater ACTH and cortisol response to opiate blockade than either the lean women with PCOS or the control subjects, but there was no difference between the lean or obese control subjects and the lean women with PCOS. There was no difference in the responsiveness of the hypothalamic-pituitary-adrenal axis to loperamide between the PCOS and control groups. CONCLUSION(S): The data indicate that the sensitivity of the hypothalamic-pituitary-adrenal axis to opioids cannot be altered in women with PCOS. However, abnormalities of the hypothalamic-pituitary-adrenal axis in women with PCOS could be central in origin, as suggested by the effects of naloxone administration, and probably are related to the anthropometric characteristics of these hyperandrogenic patients.

Differential effect of transdermal estrogen plus progestagen replacement therapy on insulin metabolism in postmenopausal women: relation to their insulinemic secretion.

OBJECTIVE: To evaluate the impact on glucose and insulin metabolism of transdermal estrogen patches before and after the addition of cyclic dydrogesterone in postmenopausal women. DESIGN: We studied 21 postmenopausal women seeking treatment for symptomatic menopause. All patients received transdermal 50 micrograms/day estradiol for 24 weeks. After 12 weeks of treatment, 10 mg/day dydrogesterone were added. METHODS: During both regimens, insulin and C-peptide plasma concentrations were evaluated after an oral glucose tolerance test (OGTT); insulin sensitivity was evaluated by a hyperinsulinemic euglycemic clamp technique. Insulin and C-peptide response to OGTT were expressed as area under the curve (AUC) and as incremental AUC; insulin sensitivity was expressed as mg/kg body weight. Fractional hepatic insulin extraction (FHIE) was estimated by the difference between the incremental AUC of the C-peptide and insulin divided by the incremental AUC of the C-peptide. Plasma hormone and lipid concentrations were assessed at baseline and at 12 and 24 weeks of treatment. RESULTS: Nine patients proved to be hyperinsulinemic and 12 were normoinsulinemic. Transdermal estrogen treatment significantly decreased the insulin AUC (P < 0.05) and the insulin incremental AUC in hyperinsulinemic patients; addition of dydrogesterone further decreased both the AUC and incremental AUC of insulin. Estrogen alone and combined with dydrogesterone evoked a significant increase in C-peptide AUC in hyperinsulinemic (79.2%) and normoinsulinemic (113%) patients. The treatment increased the values for FHIE and insulin sensitivity in all patients (P < 0.04) and in the hyperinsulinemic group (P < 0.01), whereas it did not affect such parameters in normoinsulinemic patients. CONCLUSIONS: Transdermal estrogen substitution alone and combined with cyclical dydrogesterone may ameliorate hyperinsulinemia in a selected population of postmenopausal women.

Influence of body mass on the hypothalamic-pituitary-adrenal-axis response to naloxone in patients with polycystic ovary syndrome.

OBJECTIVE: To evaluate the influence of body mass on the hypothalamic-pituitary-adrenal (HPA)-axis response to naloxone in polycystic ovary syndrome (PCOS). DESIGN: Controlled clinical study. SETTING: Academic research environment. PATIENT(S): Ten lean and 10 obese women with PCOS compared with 7 lean and 8 obese control subjects matched for body mass index. INTERVENTION(S): Each patient received an IV bolus of naloxone at a dosage of 125 microg/kg. MAIN OUTCOME MEASURE(S): Samples were collected 30 minutes before and 0, 15, 30, 60, 90, and 120 minutes after injection: ACTH and cortisol levels were measured in all plasma samples. RESULT(S): No significant differences were found in the ACTH and cortisol responses to opioid blockade between lean women with PCOS and lean as well as obese control subjects; conversely, obese patients with PCOS showed a higher ACTH and cortisol responses to naloxone compared with all other groups. CONCLUSION(S): Hypothalamic-pituitary-adrenal-axis abnormalities of PCOS may be central in origin and abdominal obesity seems to play a key role in the HPA-axis hyperactivity of women with PCOS when naloxone is administered.

Effect of acute and chronic administration of tamoxifen on GH response to GHRH and on IGF-I serum levels in women with breast cancer.

Tamoxifen, an estrogen antagonist, is usually employed in the treatment of breast cancer. Its mechanism of action is not well known because an antiproliferative effect of the drug has been shown also in estrogen receptor negative tumors, most likely mediated by the inhibition of local growth factors and particularly IGF-I. However, the action of tamoxifen on the GH-IGF-I axis is still open to investigation. We have investigated the influence of acute and chronic treatment with tamoxifen on GH response to GHRH and IGF-I serum levels in six postmenopausal women with metastatic breast cancer. A GHRH test (50 microg i.v. at time 0, GH determinations at 0, 15, 30, 60, 90 and 120 min) was performed (a) basally, (b) 3 h after 40 mg oral administration of tamoxifen and (c) after 8 weeks of 20 mg twice a day oral tamoxifen treatment. IGF-I was measured basally and after chronic tamoxifen therapy. No significant modifications in GH response to GHRH were observed after acute or chronic treatment with tamoxifen vs the basal test. On the contrary, chronic tamoxifen treatment induced a significant decrease in serum IGF-I levels. Basal pretreatment levels of 123+/-18 microg/l were suppressed to 65+/-11 microg/l (mean suppression 47%, P < 0.001). These preliminary data confirm the inhibitory effect of tamoxifen on IGF-I production but seem to exclude the possibility that this effect may be due to an inhibition of GH secretion.