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Biomedical subjects

M Maccario

Publications and source records attributed to M Maccario.

At least 19 recordsLinked to original sources
PubMed2000

DHEA-S levels in hypopituitaric patients with severe GH deficiency are strongly reduced across lifespan. Comparison with IGF-I levels before and during rhGH replacement.

Both IGF-I and DHEA-S undergo an age-related decrease and their decrease could be involved in age-related changes in body composition, structure functions and metabolism. On the other hand, it is well known that mean IGF-I levels are clearly reduced in hypopituitaric patients with GH deficiency (GHD) while data about dehydroepiandrosterone sulfate (DHEA-S) levels in hypopituitarism are scanty. We evaluated DHEA-S and IGF-I levels and their relationship in 90 patients with panhypopituitarism (HYPOPIT) with severe GHD [49 women and 41 men; age, mean+/-SE: 47.9+/-1.49 yr, range: 20-80 yr, BMI: 26.4+/-0.6 kg/m2; 21 with childhood-onset (CO) and 69 with adult-onset (AO) HYPOPIT]. DHEA-S and IGF-I levels were also evaluated in 24 HYPOPIT with GHD after 3-month recombinant human GH (rhGH) replacement. Data in HYPOPIT were compared with those in a large group of healthy controls (NS, 233 women and 103 men, aged 20-80 yr; all subjects were within +/-15% of their ideal body weight). In NS both DHEA-S levels and IGF-I were gender-independent while showed a strong, inverse correlation with age (r=-0.6; p<0.001 and r=-0.56; p<0.0001, respectively). Nevertheless, no relationship was found between DHEA-S and IGF-I levels in NS. In HYPOPIT, age-adjusted mean DHEA-S and IGF-I levels were clearly lower than those in NS (2.3+/-0.4 vs 16.0+/-0.7 microg/l, p<0.005; 71.1 +/- 4.5 vs 170+/-4.7 microg/l, p<0.005). IGF-I levels in CO-HYPOPIT were lower (p<0.01) than those in AO-HYPOPIT (49.6+/-4.8 vs 77.0+/-5.4 microg/l), while DHEA-S levels were similar in both subgroups (2.6+/-0.7 vs 2.3+/-0.4 microg/l). In HYPOPIT both DHEA-S and IGF-I were independent of age and gender while there was a trend toward a positive association between each other (r=0.45; p<0.003). Analyzing individual levels in HYPOPIT with respect to age-adjusted normal ranges, IGF-I levels were below normal in 84, 62 and 0% between 20-40, 40-60 and 60-80 yr, respectively. On the other hand, DHEA-S levels were below normal in 84, 86 and 67% between 20-40, 40-60 and 60-80, respectively. In HYPOPIT rhGH treatment strikingly increased IGF-I levels (150+/-3.2 vs 85.3+/-4.1 microg/l, p<0.005) while did not modify DHEA-S levels (1.7+/-0.2 vs 1.6+/-0.2 microg/l). In conclusion, our results demonstrate that DHEA-S and IGF-I are negatively and independently associated to age in physiological conditions but not in hypopituitaric patients in whom both are strikingly reduced. Both DHEA-S and IGF-I levels in HYPOPIT show some overlap with those in normal subjects; thus the assay of these parameters is not diagnostic for hypopituitarism. DHEA-S reduction in HYPOPIT does not depend on IGF-I as indicated also by evidence that GH replacement restores IGF-I but does not modify DHEA-S levels.

Adult↗
PubMed2000

Comparisons among old and new provocative tests of GH secretion in 178 normal adults.

Classical provocative stimuli of GH secretion such as insulin-induced hypoglycaemia, arginine, clonidine, glucagon and levodopa have been widely used in clinical practice for approximately 30 years. On the other hand, in the last 10 years new potent stimuli of GH secretion have been proposed, but an extensive comparison with the classical ones has rarely been performed, at least in adults. In order to compare the GH-releasing activity of old and new provocative stimuli of GH secretion, and to define the normative values of the GH response, in 178 normal adults (95 males, 83 females; age range: 20-50 years, all within +/-15% of their ideal body weight), we studied the GH response to: insulin-induced hypoglycaemia (ITT, 0.1IU/kg i.v.), arginine (ARG, 0.5g/kg i.v.), clonidine (CLO, 300 microg/kg p.o.), glucagon (GLU, 1mg i.m.), pyridostigmine (PD, 120mg p.o.), galanin (GAL, 80pmol/kg per min), GH-releasing hormone (GHRH, 1 microg/kg i.v.), GHRH+ARG, GHRH+PD, hexarelin, a GH-releasing protein (HEX, 2 microg/kg i.v.) and GHRH+HEX (0.25 microg/kg i.v.). The mean (+/-s.e.m.) peak GH response to ITT (21.8+/-2.8, range: 3.0-84.0 microg/l) was similar to those to ARG (18.0+/-1.6, range: 2.9-39.5 microg/l) or GLU (20. 5+/-2.2, range: 10.6-36.9 microg/l) which, in turn, were higher (P<0. 001) than those to CLO (8.2+/-1.6, range: 0.3-21.5 microg/l), PD (9. 6+/-1.1, range: 2.2-33.0 microg/l) and GAL (9.3+/-1.1, range: 3.9-18. 3 microg/l). The GH response to GHRH (19.1+/-1.5, range: 2.7-55.0 microg/l) was similar to those after ITT, ARG or GLU but clearly lower than those after GHRH+ARG (65.9+/-5.5, range: 13.8-171.0 microg/l) and GHRH+PD (50.2+/-4.6, range: 17.7-134.5 microg/l) which, in turn, were similar. The GH response to HEX (55.3+/-5.5, range: 13.9-163.5 microg/l) was similar to those after GHRH+ARG and GHRH+PD but lower (P<0.001) than that after GHRH+HEX (86.0+/-4.3, range: 49. 0-125.0 microg/l) which was the most potent stimulus of GH secretion. In this adult population the third centile limits of peak GH response to various stimuli were the following: ITT: 5.3; ARG: 2.9; CLO: 1.5; GLU: 7.6; PD: 2.2; GAL: 4.0; GHRH: 5.0; GHRH+ARG: 17.8; GHRH+PD: 17.9; HEX: 21.6; GHRH+HEX: 57.1. These results confirm that, among classical provocative tests of GH secretion, ITT followed by ARG and GLU are the most potent ones and possess clear limits of normality. GHRH+ARG or PD and HEX are strong stimuli of GH secretion which, however, is maximally stimulated by a combination of GHRH and a low dose of HEX. It is recommended that each test is used with appropriate cut-off limits.

Adult↗
PubMed1999

Assessment of GH/IGF-I axis in obesity by evaluation of IGF-I levels and the GH response to GHRH+arginine test.

The GH response to provocative stimuli in obese is often as low as in panhypopituitaric patients with severe GHD; however, IGF-I levels are normal or slightly reduced. In 53 patients with simple obesity (11 M and 42 F, age: 40.3+/-1.6 yr, BMI: 39.1+/-1.0 Kg/m2), we evaluated the GH response to GHRH (1 microg/kg iv)+arginine (ARG, 0.5 g/kg iv), and total IGF-I levels. The mean (+/-SE) GH peak after GHRH+ARG was markedly lower (74% reduction, p<0.0001) in obese (16.8+/-2.0 microg/l) than in normal subjects (62.7+/-4.3 microg/l). IGF-I levels in obese patients (134.0+/-7.6 microg/l) were lower (33% reduction, p<0.001) than in normal subjects (200.8+/-5.7 microg/l). Taking into account the 3rd centile limit of normal response, the GH response to GHRH+ARG was reduced in 62.3% (33/53) of the obese patients, and 21.2% (7/33) of them had low IGF-I levels. Assuming the 1st centile limit, it was reduced in 33.9% (18/53) obese subjects, and 22% (4/18) of them had low IGF-I levels. Considering 3.0 microg/L as arbitrary cut-off, the GH response was reduced in 5.7% (3/53) of the obese patients, and still one of them had low IGF-I levels. Our findings: a) confirm that the secretory capacity of somatotroph cells is often deeply impaired in obesity; b) demonstrate that IGF-I assay generally rules out severe impairment of GH/IGF-I axis in obese patients with marked reduction of the GH secretion; c) indicate that the percentage of obese patients with concomitant reduction of GH secretion and IGF-I levels is not negligible. Thus, IGF-I assay should be routinely performed in obese patients; those presenting with low IGF-I levels should undergo further evaluation of their hypothalamo-pituitary function and morphology, particularly in the presence of empty sella.

Adult↗
PubMed1999

Dehydroepiandrosterone sulfate levels in women. Relationships with age, body mass index and insulin levels.

Sex and age are the major determinants of serum levels of dehydroepiandrosterone sulfate (DHEA-S): they are about twice in men than in women and show a progressive reduction from the end of the puberty to aging in both sexes. It has been reported that DHEA-S levels are also negatively influenced by insulin. Moreover, DHEA-S levels reduction has been associated to increased risk for cardiovascular disease, which connotes hyperinsulinemic states, such as obesity. We have evaluated serum levels of DHEA-S and insulin as function of age and body mass index (BMI) in 376 adult women (age 18.1-89.6 yrs, median 42.2; BMI 15.7-57.8 kg/m2, median 32.7) by multiple regression and piecewise regression analysis. Insulin levels positively associated to BMI (p=0.000002) and DHEA-S levels negatively associated with age (p=0.000001). Considering the whole population, DHEA-S levels were related positively with BMI (p=0.0013) independently of age. DHEA-S were also directly related to insulin levels independently of age (p=0.042), but this association disappeared after correction for BMI. Piecewise regression analysis did not reveal a threshold level for the increase of BMI (p=0.0004). Interestingly, DHEA-S levels and BMI were positively associated before but not after menopause. Taking into account only obese population, (no.=143, age 18.7-67.3 yrs, mean 39.0, median 39.4) DHEA-S levels were again related negatively with age and positively with BMI, while were unrelated with waist to hip ratio (p=0.391). Our data show that increasing body mass and insulin secretion is not associated to DHEA-S reduction in women. This evidence suggests that DHEA-S is unlikely implicated in the pathogenesis of cardiovascular disease in obese women.

Adolescent↗
PubMed1999

Three-month treatment with metformin or dexfenfluramine does not modify the effects of diet on anthropometric and endocrine-metabolic parameters in abdominal obesity.

Abdominal obesity is connoted by hyperinsulinism and insulin insensitivity, a trend toward glucose intolerance, hypoactivity of GH/IGF-I axis and alterations of hypothalamo-pituitary-adrenal (HPA) axis. It has been hypothesized that treatment with metformin (MET) and dexfenfluramine (DEX) could counteract those endocrine-metabolic alterations. Thus, we studied the effects of 3-month treatment with MET or DEX on anthropometric (BMI, WHR, FM and FFM), metabolic (basal and OGTT-induced glucose) and hormonal variables (IGF-I, DHEA-S, androstendione, testosterone, fT3, fT4, TSH, basal and OGTT-induced insulin) as well as on blood pressure in 28 normotensive patients with abdominal obesity (OB, 3 M, 25 F; 47.5+/-1.5 yr [mean+/-SE], BMI 35.4+/-1.1 kg/m2, WHR 0.98+/-0.04 and 0.86+/-0.07, in M and F, respectively). All patients were on balanced hypocaloric diet (1400 Kcal/day). Patients were randomly assigned to treatment with MET (no.=10, 500 mg twice daily po) or DEX (no.=10, 15 mg thrice daily po) or placebo (no.=8). Before treatment all groups had similar anthropometric, metabolic and hormonal values. After 3-month treatment with MET, DEX or placebo, weight, BMI and WHR reductions were similar in all groups (p<0.05 vs baseline in either group). In each group FFM/FM ratio showed non significant trend toward increase. No significant variations in metabolic and endocrine variables were recorded in each group after 1 and 3-month treatment. However, glucose tolerance, OGTT-induced insulin response, glucose/insulin ratio showed a similar trend toward improvement in all groups, while IGF-I, 24 h urinary cortisol, DHEA-S, androstendione, testosterone, thyroid hormone and TSH levels did not show any variation. Significant (p<0.02) and similar reductions of DBP, but not of SBP, levels were found in all groups. In conclusion, our findings demonstrate that, at least after 3-month treatment, metformin and dexfenfluramine do not modify the effects of diet on anthropometric, metabolic and hormonal parameters as well as on blood pressure in patients with abdominal obesity.

Abdomen↗
PubMed1999

Clinical and prognostic value of serial renal biopsies in lupus nephritis.

Little information is available about the role of repeated renal biopsies in lupus nephritis. We analyzed retrospectively the prognostic significance of serial renal biopsies in patients with lupus nephritis. Thirty-one patients with lupus nephritis underwent two or more renal biopsies during follow-up. The indications for repeated biopsy were as follows: improvement of renal disease but persistence of nonnephrotic proteinuria (group A, 7 patients); persistent or relapsing nephrotic syndrome (group B, 12 patients); and worsening of renal function (group C, 19 patients). After a median follow-up of 10.5 years, 17 patients reached the end point (persistent doubling of plasma creatinine level). At repeated renal biopsy, there was a correlation between improved clinical and histological features for group A. In these patients, treatment was reduced or stopped successfully. Histological features remained almost unchanged in group B. All patients showed an improvement of proteinuria after reinforcement of therapy. In group C, the worsening of renal function was associated with a variable and clinically unpredictable combination of active and chronic lesions. Only the few patients with an elevated activity index and moderate chronicity index showed a favorable and persistent improvement of renal disease after reinforcement of therapy. At multivariate analysis of clinical and histological data at presentation, only male sex was predictive of an adverse outcome (P = 0.015). At repeated renal biopsy, crescents in more than 30% of glomeruli (P = 0.0009) and chronicity index of 5 or greater (P = 0.00006) were associated with the probability of reaching the end point at multivariate analysis. Repeated renal biopsy may be helpful for establishing the prognosis in patients with lupus nephritis, particularly in the presence of worsening of renal function.

Adolescent↗
PubMed1999

Relationships between IGF-I and age, gender, body mass, fat distribution, metabolic and hormonal variables in obese patients.

OBJECTIVE: To compare insulin-like growth factor-I (IGF-I) concentrations in obese and normal subjects, and evaluate the possible relationships between IGF-I concentrations and demographic, anthropometric, metabolic and hormonal variables in obese patients. SUBJECTS AND METHODS: 286 obese outpatients (OB, 234 female and 52 male; age 18-71 y, body mass index (BMI) > 27 kg/m2) were recruited. MEASUREMENTS: BMI, waist-to-hip ratio (WHR), serum basal and oral glucose tolerance test (OGTT)-stimulated glucose and insulin concentrations, IGF-I, basal growth hormone (GH), prolactin (PRL), androgens, thyrotropin (TSH), free triiodothyronine (fT3), free thyroxine (fT4), free fatty acids (FFA), triglycerides, total and high density lipoprotein (HDL)-cholesterol, 24h-urinary cortisol levels and blood pressure (BP) values were measured. IGF-I concentrations were also evaluated in a large population of 326 age-matched controls (controls, 228 women, 98 men; age 20-86 y, BMI < 25 kg/m2). RESULTS: IGF-I concentrations were lower in OB than in controls (age-adjusted mean: 21.6 vs 23.6 nmol/L, P < 0.03). However, individual IGF-I concentrations in OB were within the age-adjusted normal range. In both groups, IGF-I concentrations were gender-independent, and showed a simple negative correlation with age (r = -0.47). In OB, univariate analysis also shows that IGF-I concentrations were negatively correlated with BMI (r = -0.33), but not WHR, with both basal (r = -0.16) and OGTT-stimulated glucose levels (r = -0.17), as well as FFA levels (r = -0.19), and with both diastolic and systolic BP (both r = -0.17). In OB women, IGF-I concentrations positively correlated with PRL (r = 0.31), testosterone (r = 0.30), androstenedione (r = 0.30), and dehydroepiandrosterone-sulfate (DHEAS) concentrations (r = 0.41). No correlation was found with other variables. The multiple regression analysis showed that IGF-I concentrations were inversely and independently related to age and BMI only. CONCLUSIONS: In obesity, IGF-I concentrations are slightly reduced, but generally within the age-adjusted normal range. IGF-I concentrations in obesity show independent and negative relationships with age and BMI, but are not associated with fat distribution, insulin secretion, glucose tolerance, BP or risk indices for cardiovascular disease (CVD).

Adipose Tissue↗
PubMed1999

Relationships between dehydroepiandrosterone-sulphate and anthropometric, metabolic and hormonal variables in a large cohort of obese women.

OBJECTIVE: The aim of the present study was to measure dehydroepiandrosterone-sulphate (DHEA-S) levels in obesity and assess the relationships between DHEA-S and anthropometric, metabolic and hormonal variables. SUBJECTS AND METHODS: We evaluated the serum DHEA-S levels in 217 obese but otherwise normal female subjects (age (mean +/- SEM): 39.4 +/- 0.9, range 18-67 years, body mass index (BMI) = 36.1 +/- 0.4, range 27.1-57.1 kg/m2). RESULTS: DHEA-S levels showed an age-dependent fall similar to that observed in normal women (n = 156, age 46.2 +/- 1.2, range 22-69 years, BMI < 25 kg/m2). Adjusting for age, obese women had mean DHEA-S levels higher than the control group (P < 0.02). In obese patients, DHEA-S levels were directly associated with serum testosterone, androstendione, IGF-I, fT3 levels and 24 h-urinary cortisol. On the other hand, DHEA-S levels were negatively associated with age, total cholesterol, triglycerides levels and systolic blood pressure. No correlation was found with BMI, waist:hip ratio, basal and post-OGTT insulin and glucose, free fatty acids, GH, PRL, fT4, TSH, SHBG levels or diastolic blood pressure. Multiple regression analysis indicated that in obese women, DHEA-S levels were associated negatively to age and positively to testosterone, androstendione and IGF-I levels and daily urinary cortisol. In a subgroup of 20 obese women, DHEA-S levels significantly (P < 0.001) fell after OGTT without any correlation with the insulin response. CONCLUSIONS: The present results show that dehydroepiandrosterone-sulphate levels are not reduced in obesity, being slightly increased, particularly in young adulthood. Dehydroepiandrosterone-sulphate levels are positively and independently associated with androgen, 24-h urinary cortisol and IGF-I levels but do not seem associated with insulin levels or cardiovascular risk indices.

Adolescent↗
PubMed1999

Dose-response study of GH effects on circulating IGF-I and IGFBP-3 levels in healthy young men and women.

The aim of our study was to define the dose-response effect of a short-term treatment with different recombinant human growth hormone (rhGH) doses (1.25, 2.5, 5.0, 10.0, and 20.0 micrograms . kg-1. day-1 for 4 days) on insulin-like growth factor I (IGF-I) and insulin-like growth factor-binding protein (IGFBP)-3 levels in 21 normal young adults of both sexes. The dose of 1.25 microgram/kg rhGH did not modify IGF-I levels. The dose of 2.5 micrograms/kg rhGH significantly increased IGF-I levels in men (P < 0.05) but not in women, whereas the higher doses increased IGF-I levels in both sexes (P < 0.002). IGFBP-3 levels were not modified by 1.25 or 2.5 micrograms/kg rhGH in either sex. On the other hand, 5.0 micrograms/kg increased IGFBP-3 levels in men (P < 0.05) but not in women, whereas the higher doses increased IGFBP-3 levels similarly in both sexes (P < 0.02). In conclusion, our results demonstrate that IGF-I and IGFBP-3 responses to rhGH are dose and sex dependent. However, IGFBP-3 is less sensitive than IGF-I to rhGH stimulation.

Adult↗
PubMed1998

Effects of 3-month nifedipine treatment on endocrine-metabolic parameters in patients with abdominal obesity and mild hypertension.

It is widely accepted that abdominal obesity presents with exaggerated insulin secretion, insulin resistance and a trend toward glucose intolerance. Hypertension is frequently associated to abdominal obesity, and hyperinsulinism could play a role in its pathogenesis. Some studies reported that Ca-antagonists positively influence insulin sensitivity and glucose tolerance in obese patients with normal or elevated blood pressure. However, other studies reported worsening of metabolic balance during treatment with Ca-antagonists in hypertensive non-insulin-dependent diabetes mellitus (NIDDM) patients and in normal subjects. We studied 19 patients with abdominal obesity, mild hypertension and insulin resistance on balanced, mild hypocaloric diet (1400 Kcal), to verify the effects of the Ca-antagonist nifedipine on both basal and oral glucose tolerance test (OGTT)-induced glucose and insulin levels as well as on IGF-I basal and DHEA-S levels and fat mass (FM). To achieve this goal, 10 hypertensive obese subjects (HOB-NIFE, 3 males, 7 females, mean age +/- SD 44.6 +/- 1.7 yr; body mass index (BMI) 37.1 +/- 2.5 Kg/m2, WHR 0.95 +/- 0.02) received 3-month treatment with nifedipine (Adalat Crono 30 Bayer, 1 tab daily) while other 9 hypertensive obese (HOB, 3 males, 6 females, 42 +/- 2.4 yr, BMI 35.8 +/- 1.8 Kg/m2, WHR 0.91 +/- 0.03) were studied during diet only. The same parameters were studied also in 8 normotensive obese patients (OB: 3 males, 5 females, 48.1 +/- 2.1 yr, BMI 35.8 +/- 2.4 Kg/m2, WHR 0.90 +/- 0.03) on the same balanced hypocaloric diet. Basal systolic (SBP) and diastolic (DBP) blood pressure levels in HOB-NIFE and HOB were similar. At baseline, all groups had similar basal and OGTT-induced glucose, insulin and glucose insulin ratio (GIR) levels as well as IGF-I and DHEA-S levels. After 3 months BMI fell to the same extent in all groups (p < 0.05 vs baseline) while WHR and FFM/FM ratio did not change. SBP and DBP decreased HOB-NIFE (p < 0.02) but also during diet alone in both HOB and OB, though to a lesser extent (p < 0.05). Both basal and OGTT-stimulated glucose and insulin levels as well as IGF-I and DHEA-S levels were not modified in HOB-NIFE as well as in HOB and OB. In conclusion, our data indicate that nifedipine treatment does not modify glucose tolerance as well as insulin secretion and sensitivity, IGF-I and DHEA-S levels in hypertensive abdominal obese patients. Thus, nifedipine treatment has no detrimental effects on endocrine-metabolic balance in hypertensive obese patients.

Adult↗
PubMed1998

Campylobacter jejuni bacteremia and Guillain-Barré syndrome in a renal transplant recipient.

In patients who have not undergone transplantation, Guillain-Barré syndrome (GBS) is typically preceded by an acute infection often sustained by Campylobacter jejuni. Thus far, in renal transplant recipients, only eight cases of GBS have been reported. In seven patients GBS was attributed to cytomegalovirus infection and in the eighth patient to cyclosporin A neurotoxicity. We report here the case of a GBS in a renal transplant recipient following C. jejuni bacteremia. The infection quickly disappeared after erythromycin and methronidazole therapy. GBS progressively evolved into a paraparesis within 1 week. After reaching a plateau phase, the clinical status improved and the patient was able to walk unassisted after 3 weeks. At this last check-up, 54 months later, the patient was doing well with a functioning graft and only minimal weakness of the lower limbs.

Bacteremia↗
PubMed1998

Peritoneal dialysis in nondiabetic patients older than 70 years: comparison with patients aged 40 to 60 years.

In all industrial countries, the number of elderly patients who need dialysis has increased in recent years. In the present study, we retrospectively analyzed two different age groups of nondiabetic peritoneal dialysis patients treated at the same unit by the same team of physicians and nurses with the same protocols. However, our purpose was to study possible differences in technique and survival rates, causes of dropout, complications, hospitalization rate, and everyday needs between the two groups. The results of 63 consecutive nondiabetic patients older than 70 years treated with continuous ambulatory peritoneal dialysis (CAPD) were compared with those of 86 nondiabetic patients aged 40 to 60 years treated during the same period. Patient survival was significantly worse in the elderly patients, but the observed to expected survival ratio with respect to age was similar. Technique survival was comparable in the two groups. Total hospitalization was 5,501 days (32 d/yr) in the elderly patients and 4,511 days (18 d/yr; P < 0.05) in the younger group. The peritonitis rate was 0.52 episodes/patient-year in the elderly patients and 0.37 episodes/patient-year in the younger patients (P < 0.002). The exit site infection rate was similar in the two groups (0.30 episodes/yr v0.29 episodes/yr). Other complications related to CAPD did not differ between the elderly and younger patients. Rehabilitation and biochemical data after 1 year of CAPD were similar in the two groups of patients. After 1 year of treatment, 12% of the younger patients and 43% of the elderly patients (P < 0.005) needed a partner for dialysis. Twenty-nine of 39 (74%) of the elderly patients and 30 of 53 (57%) of the younger patients considered their lifestyle acceptable after 1 year of dialysis. Thirty-four of 39 (87%) of the elderly patients and 32 of 53 (60%) of the younger patients (P < 0.02) rated their physical and social state after rehabilitation as better or comparable to that they had before terminal uremia.

Adult↗
PubMed1998

Treatment of membranous lupus nephritis.

In this study, we retrospectively analyzed the effects of treatment in 19 patients with membranous lupus nephritis (MLN) and nephrotic syndrome. Eight patients were treated with corticosteroids alone, and the other 11 patients received methylprednisolone and chlorambucil alternated every other month for 6 months. At presentation, sex, age, duration of renal disease before renal biopsy, plasma creatinine, and arterial hypertension were similar in the two study groups. Of the eight patients treated with corticosteroids alone, three showed complete remission and one partial remission of the nephrotic syndrome. During the follow-up (mean, 114+/-63 months), seven of these eight patients developed one or more renal flare-ups. Of the 11 patients treated with methylprednisolone and chlorambucil, seven had complete remission, and the other four had partial remission of the nephrotic syndrome. During the follow-up (mean, 83+/-59 months), only one patient had renal flare-up. At the end of the follow-up, all patients were alive, but three patients in the group treated with corticosteroids alone had developed a doubling of plasma creatinine, and another patient had persistent nephrotic syndrome. Two other patients were in complete remission, one patient was in partial remission, and the last patient had nonnephrotic proteinuria. In the group of patients treated with methylprednisolone and chlorambucil, one patient developed extracapillary glomerulonephritis and eventually entered end-stage renal failure 24 years after the clinical onset of renal disease. Seven patients were in complete remission, and three patients were in partial remission at the last follow-up visit. This retrospective study suggests that methylprednisolone and chlorambucil may induce a more stable remission of nephrotic syndrome and may better protect renal function in the long term in comparison with corticosteroids alone. However, these results must be confirmed by a prospective controlled trial.

Adolescent↗
PubMed1998

GH response to GHRH combined with pyridostigmine or arginine in different conditions of low somatotrope secretion in adulthood: obesity and Cushing's syndrome in comparison with hypopituitarism.

BACKGROUND: Diagnosing GH deficiency in adults is difficult due to the age-related variations of GH/IGF-I axis and the influence of nutrition. Nowadays, GH replacement is allowed for patients with GH peak to provocative stimuli < 3 micrograms/L. Somatotrope insufficiency is present in hypopituitarism but also in obesity and hypercortisolism. However, to evaluate GH insufficiency in adults is difficult due to variations of GH and IGF-I levels as function of age and nutrition status. METHODS: We aimed to verify the GH response to GHRH (1 microgram/kg i.v.) combined with pyridostigmine (PD, 120 mg p.o.) or arginine (ARG, 0.5 g/kg i.v.), in 26 hypopituitaric patients (GHD), in 11 obese women (OB), in 8 women with Cushing's syndrome (CS), and in 72 control subjects (NS). RESULTS: IGF-l levels in GHD were lower than those in OB (p < 0.01) and in CS (p < 0.01) which, in turn, were lower to those in NS (p < 0.02). In NS, the GH peak responses to GHRH + PD and GHRH + ARG were similar and the minimum normal GH peak was 16.5 micrograms/L. GHD had GH responses similar, lower than those in NS (p < 0.01) and always below the normal limit. However, only 12/20 and 8/14 had peaks < 3 micrograms/L; conventionally, below this limit severe GH deficiency is shown and rhGH replacement is allowed. In OB, the GH responses to GHRH + PD and GHRH + ARG were similar, lower (p < 0.01) and higher (p < 0.01) than those in NS and GHD, respectively. Six out of 11 OB had GH peaks below the normal limits but nobody < 3 micrograms/L. In CS the GH response to GHRH + PD was lower than that to GHRH + ARG (p < 0.01); both these responses were lower than those in NS (p < 0.01) and even in OB (p < 0.01) but higher than those in GHD (p < 0.01). All and 7/8 CS had GH peaks lower than normal limits after PD + GHRH and ARG + GHRH, respectively while 6/8 showed GH peak < 3 micrograms/L after PD + GHRH but only 1 after ARG + GHRH. CONCLUSIONS: Present data demonstrate that the maximal somatotrope secretory capacity is reduced in OB and even more in CS. From a diagnostic point of view, PD + GHRH and ARG + GHRH tests distinguish OB from severe GHD. As hypercortisolism impairs the activity of cholinesterase inhibitors, only ARG + GHRH, but not PD + GHRH is a reliable test to explore the maximal somatotrope secretory capacity in CS. Notably, even with the ARG + GHRH test, in CS the maximal somatotrope secretory capacity is sometimes so reduced as to overlap with that of severe GHD.

Adult↗
PubMed1998

IGF-I levels in different conditions of low somatotrope secretion in adulthood: obesity in comparison with GH deficiency.

BACKGROUND: It is widely accepted that IGF-I synthesis and release depend on GH secretion as well as on the nutritional status and vary with age. Based on these premises, after the definition of normal IGF-I levels during lifespan, in a large population of normal subjects of both sexes, our aim was to verify IGF-I levels in large groups of adult patients with GH deficiency or obesity, a condition in which a reduced somatotrope secretion is well known. METHODS: To this goal, IGF-I levels were assayed after acidethanol extraction, in 326 normal subjects (NS, 98 men and 228 women, age 20-80 yrs, BMI 17.9-26.1 kg/m2), 54 patients with GH deficiency (GHD), 24 men and 30 women, age 20-80 yrs, BMI 18.2-27.1 kg/m2), and 195 patients with obesity (OB, 33 men and 162 women, age 17-71 yrs, BMI 27.7-64.9 kg/m2). In NS, IGF-I levels were similar in both sexes and showed a progressive decrease with age. No correlation was present between IGF-I and BMI in NS. Median IGF-I levels and the 3rd centile in NS when considered per decade were: III) 230 and 108.6; IV) 220 and 129.8; V) 150.5 and 72.4; VI) 163.0 and 62.4; VII) 110 and 41.6; VIII) 82 and 24.7 microgram/l. In GHD, IGF-I levels were independent on sex and did not show reduction during lifespan. Mean IGF-I levels in GHD were lower than that in NS (64 +/- 5.9 vs 171.3 +/- 4.8 microgram/l, p < 0.01) and did not correlate with age or BMI. Analyzing individual IGF-I levels, in GHD, in the III and IV decade 21/24 patients had IGF-I levels lower than 3rd centile while, up to the VIII decade, only 10/30 had IGF-I levels below normal limits. In OB, IGF-I levels were independent on sex but, like in NS, showed a progressive decrease with age and were independently, negatively correlated with BMI but not with WHR. Analyzing individual IGF-I levels, in OB, IGF-I levels were below 3rd centile in 10/77 patients in the III and IV decade and in only 8/108 patients up to the VIII decade. Mean IGF-I levels in the whole OB population (179.6 +/- 5.9 microgram/l) were higher (p < 0.01) than those in GHD (64.5 +/- 5.9 microgram/l) while only in the IV decade IGF-I levels in OB group were lower (p < 0.02) than those in NS (184.7 +/- 12.6 microgram/l vs 224.0 +/- 9.2 microgram/l). CONCLUSIONS: In conclusion, present data confirm that IGF-I levels depends on GH secretion as well as on nutritional status, being negatively and independently correlated with age and BMI. IGF-I assay is not a reliable test for the diagnosis of GH deficiency in adulthood though it gives good discrimination between GHD and normal subjects up to 40 yrs of age. In spite of low GH secretion, IGF-I levels are only slightly reduced in obesity, probably as consequence of hyperinsulinism.

Adolescent↗
PubMed1997

The inhibitory effect of glucose on growth hormone secretion is lost in obesity but not in hypertension.

In obesity there is a clear reduction of both spontaneous and stimulated GH secretion. Furthermore, in obese patients the somatotrope responsiveness to provocative stimulation is selectively refractory to the inhibitory effect of glucose load. It has been hypothesized that hyperinsulinism of obese patients could play a role in the pathogenesis of these alterations. Aim of the present study was to verify the GH response to GHRH and the ability of glucose load to inhibit it in patients with essential hypertension in whom hyperinsulinism and insulin resistance are frequently present. To this goal, 7 patients with essential hypertension (HP, age, mean +/- SE: 29.6 +/- 2.4 yr, 3 females and 4 males, BMI: 21.7 +/- 1.2 kg/m2), 7 obese (OB, 4 females and 3 males, 31.9 +/- 4.1 yr, 35.6 +/- 2.0 kg/m2) and 7 normal subjects (NS, 4 females and 3 males, 28.3 +/- 3.9 yr, 21.0 +/- 1.6 kg/m2) underwent the following tests: GHRH (1 microgram/kg i.v. at time 0) alone and preceded by oral glucose load (OGTT, 100 g po at -45 min). Basal insulin levels were similar in HP and OB (11.3 +/- 0.5 and 12.7 +/- 2.2 microU/ml, respectively); these, in turn, were higher (p < 0.005) than those in NS (6.8 +/- 0.8 microU/ml). Basal plasma glucose levels in HP were similar to those in OB and NS (80.3 +/- 3.6, 86.9 +/- 6.7 and 84.4 +/- 1.7 mg/dl, respectively). In HP and OB and NS basal GH (1.0 +/- 0.5, 1.0 +/- 0.6 and 0.3 +/- 0.1 micrograms/l, respectively) and IGF-I levels (132.6 +/- 14.8, 137.3 +/- 13.2 and 138.8 +/- 12.2 micrograms/l, respectively) were similar. In HP the GH response to GHRH (AUC: 1058.8 +/- 347.8 micrograms/l/min) was similar to that observed in NS (959.0 +/- 167.8 micrograms/l/min) and higher than that in OB (344.8 +/- 67.2 micrograms/l/min, p < 0.01). OGTT clearly blunted (p < 0.01) the GHRH-induced GH response in HP as well as in NS (401.8 +/- 104.4 and 521.6 +/- 76.6 (g/l/min, respectively) but not in OB (387.4 +/- 78.8 (g/l/min). The OGTT-induced insulin levels in HP did not differ from those of OB, both being higher (p < 0.05) than those recorded in NS. Glucose levels after OGTT were similar in the three groups. In conclusion, this study demonstrates that, like in normal subjects but differently from in obese patients the GH response to GHRH is normal in patients with essential hypertension and it is normally inhibited by oral glucose load even when these patients show high insulin levels. Thus, it is unlikely that the low somatotrope secretion and its refractoriness to inhibition by glucose load in obesity is due to hyperinsulinism.

Adult↗
PubMed1997

Effects of cholinergic blockade by pirenzepine on insulin and glucose response to oral and intravenous glucose and to arginine load in obesity.

Parasympathetic nervous system is known to affect insulin secretion in animal and man and there is evidence that it is involved in the outcome of spontaneous and stimulated insulin hypersecretion observed in animal obesity. In human obesity, there are contradictory data. We studied the effect of 150 mg orally administered pirenzepine (PNZ), a muscarinic receptor antagonist, on the insulin response to glucose (75 g p.o. or 0.33 g/kg i.b.w. i.v.) or arginine (0.5 g/kg infused in 30 min) in 18 obese subjects normotolerant to glucose. PNZ did not modify basal serum insulin and the hormone response to either intravenous glucose (AUC: 5221.6 +/- 1177:6 vs 5309.8 +/- 1534.8 mU/L.min) or arginine load (4257.9 +/- 832.7 vs 3952.8 +/- 549.3 mU/L.min). Calculated as AUC the insulin response to oral glucose load was unaffected by PNZ (6601.5 +/- 1218.6 vs 8614.3 +/- 1095.2 mU/L.min). Actually, the insulin rises at +30 min after oral glucose load was significantly blunted by PNZ (37.0 +/- 3.4 vs 81.6 +/- 16.9 mU/L; p < 0.03). However, after statistical evaluation by ANCOVA assuming basal insulin and +30 min glucose levels as covariates, this significant disappeared. Our present data do not agree with the hypothesis that the cholinergic system plays a role in the exaggerated insulin secretion of obesity. Nevertheless, these findings confirm that acetylcholine positively influences insulin secretion in humans, likely via indirect mechanisms.

Adult↗