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Biomedical subjects

G Faglia

Publications and source records attributed to G Faglia.

At least 19 recordsLinked to original sources
PubMed2004

Elite volunteer athletes of different sport disciplines may have elevated baseline GH levels divorced from unaltered levels of both IGF-I and GH-dependent bone and collagen markers: a study on-the-field.

Seventy-seven Italian eliteathletes(42 M, 35 F, mean age +/- SE: 24.4-0.7 yr, age range: 17-47 yr) of different sport disciplines (sprinters, triathletes, middle-distance runners, road-walkers, cyclists, rowing athletes, skiers, roller hockey players, swimmers) were sampled on-the-field (before a training session) for the determination of basal GH, IGF-I, C-terminal cross-linked telopeptide of type I collagen (ICTP) and amino-terminal propeptide of type III procollagen (PIIINP) levels, two GH-dependent peripheral markers of bone and collagen turnover, respectively. Basal GH concentrations were significantly higher (p<0.001) in female (5.8 +/- 1.0 ng/ml) vs male athletes (1.8 +/- 0.5 ng/ml), with a large spread of values in either gender. Mean GH levels of athletes were significantly higher than those recorded in age-matched sedentary controls (females: 2.5 +/- 0.5 ng/ml, p<0.001; males: 0.5 +/- 0.2 ng/ml, p<0.05). Among female athletes, 7/35 had basal GH values higher than the upper limit of control values (>9.5 ng/ml), while among males 7/42 had values higher than the upper limit of male sedentary controls (>3.6 ng/ml). No significant differences in basal GH concentrations were found between females taking oral contraceptives (OC) and those who did not receive this treatment (5.0 +/- 2.1 vs 6.0 +/- 1.2 ng/ml). IGF-I levels (236.4 +/- 7.8 ng/ml) were in the normal range for age in all athletes (except for 1 athlete with slightly increased levels), no significant correlation being found between GH and IGF-I levels (R2=0.0393). Mean ICTP (4.6 +/- 0.2 ng/ml) and PIIINP (4.4-0.1 ng/ml) concentrations of elite athletes were not significantly different from those recorded in age and matched healthy sedentary subjects; 4 athletes showed increased PIIINP levels and 2 had increased ICTP levels. ICTP and PIIINP levels were positively correlated with chronological age (p<0.001), a positive correlation being also found between the two markers (p<0.001). On the contrary, no significant correlation was found between basal GH/IGF-I levels and ICTP/PIIINP levels. In conclusion, the present study demonstrates that: 1) elite athletes (particularly females), which have frequently increased basal GH on-the-field, have actually normal IGF-I levels; 2) ICTP and PIIINP levels of athletes are similar to those recorded in healthy sedentary, being significantly higher in younger subjects of both groups; 3) the presence of increased basal GH levels, being associated with normal IGF-I, ICTP and PIIINP levels, is probably the result of a transient GH peak in this study group. Further additional studies are requested to verify the possible use of these peripheral GH-dependent markers for detecting exogenous chronic administration of recombinant GH in athletes.

Adolescent↗
PubMed2004

Gender-, age-, body composition- and training workload-dependent differences of GH response to a discipline-specific training session in elite athletes: a study on the field.

Ninety-nine Italian elite athletes (61 M, 38 F, mean age +/- SE: 24.1 +/- 0.6 yr, age range: 17-47 yr) of different disciplines volunteered to participate in this investigation. Basal GH concentrations were significantly higher (p<0.0001) in females (6.2 +/- 1.1 ng/ml) vs males (1.9 +/- 0.5 ng/ml). Basal GH values were negatively correlated with age and body mass index (BMI); no significant correlation was found between GH and IGF-I levels. Among female athletes, 8/38 had basal GH values higher than 10 ng/ml [2/8 athletes were taking oral contraceptives (OC)], while among males 6/61 had values higher than 5 ng/ml. In females, training sessions significantly increased (p<0.0001) basal GH concentrations (peak GH: 18.5 +/- 1.9 ng/ml), while in males GH responses were lower than in females (11.8 +/- 1.4 ng/ml, vs F: p<0.005). Six out of 38 female and 6/61 male athletes were considered GH hypo-responders (i.e. negative difference between peak GH and basal GH values), the large majority of them being subjects with elevated basal GH concentrations. In responsive athletes, peak GH values occurred immediately at the end of the training session both in males and in females; GH concentrations rapidly declined during recovery. No significant correlations were found between peak GH and age, body weight and BMI in either gender. GH responses were directly related (p<0.001) to the intensity of the workload during the sessions. In conclusion, the present study demonstrates that: 1) some elite athletes had increased GH concentrations before training, which were however associated with normal IGF-I levels; 2) GH peaks after a discipline-specific training session were significantly higher in females than in males performing the same discipline, gender-related differences disappearing when post-exercise total GH outputs (area under the curve) were compared; 3) peak GH values were directly correlated with training workload; 4) GH concentrations rapidly declined during recovery, values at the end of the post-training GH sampling being generally lower than those found in basal condition.

Adolescent↗
PubMed2002

Comparison between buserelin and dexamethasone testing in the assessment of hirsutism.

Many hirsute women may present a form of functional ovarian hyperandrogenism (FOH), since they show an exaggerated 17-hydroxyprogesterone (17-OHP) response to GnRH agonists administration. As the failure of dexamethasone to reduce testosterone levels may be indicative of an ovarian source of androgen secretion, we evaluated the usefulness of dexamethasone suppression test, in comparison with buserelin challenge, in the assessment of hirsutism. Twenty-seven hirsute women (aged 15-42 yr) underwent ACTH and buserelin tests: 4 patients were heterozygotes for 21-OH deficiency and 8 patients were affected with FOH: 2 of the patients with hyperresponse to buserelin also had 21-hydroxylase deficiency. The results of the dexamethasone suppression test (2 mg/day for 7 days) were compared to those obtained after buserelin test. Basal T and delta4 levels (mean+/-SE) were higher than in controls (4.2+/-0.5 vs 2.2+/-0.2 nmol/l and 10.9+/-0.9 vs 5.9+/-0.6 nmol/l, p<0.02), while no differences were found in 17-OHP and DHEAS levels. A significant reduction (p<0.001) in T (1.8+/-0.4 nmol/l), delta4 (3.2+/-0.5 nmol/l) and DHEAS levels (2.4+/-0.3 micromol/l) was observed at the 3rd day of dexamethasone administration and no differences between sampling at 3rd, 5th and 7th day were found. Serum T was not suppressed in 6 cases, delta4 and DHEAS levels in 3 and 1 of them, respectively. Buserelin injection caused an excessive 17-OHP response in 8 patients, only 4 of them did not reduce T levels during dexamethasone. The sensitivity and specificity of the dexamethasone suppression test, with respect to the buserelin test, were 50% and 89%, respectively. In conclusion, 37% of hirsute patients had an abnormal responsiveness to buserelin and/or ACTH tests, indicating that hormonal investigations are mandatory. An ovarian origin of hirsutism was identified by buserelin test in 30% of patients and by dexamethasone in 22% of cases; only 4 of 8 patients showed concordant results to both tests. Therefore, buserelin challenge seems a more useful, cost-effective and less time consuming tool than dexamethasone administration in order to recognize the possible ovarian origin of hyperandrogenism.

Adolescent↗
PubMed2002

Prevalence of thyroid diseases in patients with acromegaly: results of an Italian multi-center study.

Acromegaly is frequently associated with the presence of thyroid disorders, however the exact prevalence is still controversial. An Italian multicenter study was performed on 258 patients with active acromegaly (high levels of IGF-I and lack of suppression of serum GH levels below 2 microg/l after an OGTT). The control group was represented by 150 patients affected by non-functioning and PRL-secreting pituitary adenomas. Two hundred and two out of 258 acromegalic patients (78%) were affected by thyroid disorders with a significantly higher prevalence with respect to the control group (27%, p<0.0001). One hundred and three patients presented (39.9%) non-toxic nodular goiter, 46 (17.8%) non-toxic diffuse goiter, 37 (14.3%) toxic nodular goiter, 1 toxic diffuse goiter (0.4%), 12 (4.6%) Hashimoto's thyroiditis, 3 (1.2%) thyroid cancer. Two patients presented a co-secreting TSH pituitary adenoma. Thirty-six patients had been previously treated for various thyroid abnormalities. Among the 222 acromegalic patients never treated for thyroid disorders thyroid ultrasonography was performed on 194 subjects. Thyroid volume in patients with thyroid abnormalities was 28+/-17.5 ml (median 23) while it was 10.8+/-3.6 ml (median 10) in patients without thyroid disorders (p<0.0001). Thyroid volume was correlated with the estimated duration of acromegaly (r=0.7, p<000.1), but not with age or with serum GH, IGF-I and TSH concentrations. Thyroid volume was higher in acromegalic patients than in the above control population (23.5+/-16.9 ml vs 13.9+/-12.8 ml, p<0.0001). In 62 acromegalic patients 101 fine-needle biopsies of thyroid nodules were performed; 7 nodules were suspicious and the patients were submitted to thyroid surgery: papillary thyroid carcinoma was found in 3 patients. In conclusion, in a large series of acromegalic patients an increased prevalence of thyroid disorders (78%), particularly non-toxic nodular goiter, has been observed. Thyroid volume, evaluated by ultrasonography, was correlated to the estimated duration of acromegaly. Finally, the prevalence of thyroid carcinoma was slightly increased than in the general population.

Acromegaly↗
PubMed2002

MEN1 gene mutations are a rare event in patients with sporadic neuroendocrine tumors.

BACKGROUND: Neuroendocrine tumors of the gastroenteropancreatic (GEP) tract are encountered either as a sporadic type or as part of multiple endocrine neoplasia type 1 (MEN-1) syndrome. Inactivating MEN1 gene mutations have been found to be responsible for this syndrome and have also been described in sporadic cases. The aim of the present study was to evaluate the presence of mutations in the MEN1 gene in a series of 10 well-differentiated neuroendocrine tumors: five of the foregut and five of the midgut tract. METHODS: Retrospective screening for MEN1 gene mutations was carried out in 10 archived, paraffin-embedded neuroendocrine tumors. Polymerase chain reaction amplification and automated sequence analysis of the DNA extracted from the tumors were performed. RESULTS: One mutation (359 del 4) in exon 2 of the MEN1 gene was identified in a neuroendocrine tumor of the foregut (VIPoma of the pancreas). No mutation was identified in midgut neuroendocrine tumors. CONCLUSIONS: Our data confirm that retrospective genetic analysis can be used to identify mutations in the MEN1 gene and indicate that somatic MEN1 gene mutations are a rare event in sporadic neuroendocrine GEP tumors. The frequency of these mutations was 10% in our series, which may differ from that in other studies, due to the small number of cases analyzed.

Journal Article↗
PubMed2002

Impaired estrogen-induced negative feedback on gonadotropin secretion in patients with gonadotropin-secreting and nonfunctioning pituitary adenomas.

BACKGROUND: Several in vitro studies suggest that gonadotropin-secreting pituitary adenomas (Gn-omas) and non functioning pituitary adenomas (NFPA) originate from gonadotroph cells. Patients with Gn-oma and NFPA frequently show abnormal gonadotropin response to TRH. The aim of the study was to investigate whether the estrogen-induced negative feedback is operating in either patients with Gn-oma or NFPA. MATERIALS AND METHODS: Serum gonadotropin levels were evaluated at 24 h after ethinylestradiol administration (1 mg per os; EE2 test) in seven patients with a diagnosis of Gn-oma, based on the presence of high follicle-stimulating hormone (FSH) and/or lutenising hormone (LH) levels with normal or high levels of sex steroids, in 22 patients with NFPA with normal or low levels of gonadotropin and sex steroids, and 30 sex- and age-matched healthy subjects. A normal response to EE2 test was arbitrarily defined as a serum LH and FSH decrease of at least 40 and 30% below basal levels. RESULTS: Among patients with Gn-oma, only one had a normal FSH inhibition and another, a normal LH inhibition. Among the 22 patients with NFPA, the EE2 test caused a normal FSH or LH reduction in 10 and 15, respectively, while a normal reduction of both FSH and LH was observed in nine. CONCLUSIONS: The study demonstrates that estrogen-induced negative feedback of gonadotropin secretion is disrupted in almost all patients with Gn-oma and in half of those with NFPA. This defective feedback is reminiscent of the resistance to thyroid hormones and glucocorticoids observed in patients with thyroid-stimulating hormone- (TSH-) and adrenocorticotropic hormone- (ACTH-)secreting adenomas, respectively.

Adenoma↗
PubMed2001

Effects of 12-month GH treatment on bone metabolism and bone mineral density in adults with adult-onset GH deficiency.

Serum bone-Gla protein (BGP), bone alkaline phosphatase (B-AP), and C-terminal cross-linked telopeptide of type I collagen (ICTP) levels were evaluated in 18 adults with acquired GH deficiency (GHD, 14 males and 4 females, age range: 25-59 yr) before, at 3, 6, 9 and 12 months of rec-GH treatment (0.125 IU/kg/week for the first month, followed by 0.25 IU/kg/week for 11 months) and 6 months after the withdrawal of therapy. Total body bone mineral density (BMD, g/cm2) was measured with dual energy X-ray absorptiometry (Hologic QDR 1000/W) before, at 12 months of GH treatment and 6 months after its withdrawal. Before treatment, BGP (mean+/-SE: 5.1+/-0.4 ng/ml), B-AP (59.4+/-6.5 IU/l), ICTP (3.1+/-0.3 ng/ml) levels of patients were similar to in healthy controls (BGP: 5.4+/-0.1 ng/ml; B-AP: 58.2+/-2.0 IU/l; ICTP: 4.1+/-0.3 ng/ml). GH treatment caused a significant increase of BGP, B-AP, ICTP levels, the maximal stimulation of bone resorption, occurring after 3 months of GH treatment, while the maximal effect on bone formation being evident later (at 6th month). A slight decline in BGP, B-AP, T-AP and ICTP levels occurred at 9-12 months of therapy, although the values remained significantly higher than in basal conditions and with respect to healthy controls. Before treatment, mean total body BMD of patients (1.110+/-0.027 g/cm2, range: 0.944-1.350 g/cm2) was not significantly different (z-score: +0.47+/-0.31, NS) from that observed in healthy controls (1.065+/-0.008 g/cm2, range: 1.008-1.121 g/cm2). GH therapy was associated with a significant reduction of mean total body BMD values (6th month: -1.8+/-0.5%, p<0.01; 12th month: -2.1+/-1.0%, p<0.05 vs baseline), particularly evident in the first six months of treatment. Six months after the withdrawal of GH therapy, BGP (5.9+/-0.5 ng/ml), B-AP (57.3+/-7.0 IU/l) and ICTP (3.2+/-0.1 ng/ml) levels returned similar to those recorded before treatment, while total BMD increased (+1.5+/-0.7, p<0.05), remaining however slightly lower than in basal conditions (-0.6+/-1.2, NS). In conclusion, our study shows that: a) acquired GHD in adulthood is associated with both normal bone formation/resorption indexes and normal total body BMD; b) GH therapy causes a significant rise of bone formation/resorption markers (earlier and greater for bone resorption); c) one-year GH therapy is associated with a reduction of total body BMD values, particularly evident in the first 6 months of treatment; d) the effects of GH therapy on bone turnover are transient, being completely reverted six months after the withdrawal of GH therapy; e) the increase of total body BMD (up to baseline values) after GH withdrawal might be explained as consequence of persisting effects of previous GH stimulation on bone remodeling.

Absorptiometry, Photon↗
PubMed2001

Effects of a 16-week progressive high-intensity strength training (HIST) on indexes of bone turnover in men over 65 years: a randomized controlled study.

The aim of the present study was to evaluate the effects of a 16-week progressive high-intensity strength training (HIST) program on peripheral markers of bone turnover (bone Gla protein, BGP; bone alkaline phosphatase, B-AP; N-terminal propeptide of type I procollagen, PINP; C-terminal cross-linked telopeptide of type I collagen, ICTP) in healthy, elderly men over 65 yr of age. Thirty healthy men (aged 65-81 yr), performing light to moderate daily physical activity, were randomly divided into two groups. Group 1 (no.=16) followed a supervised 16-week progressive HIST program, while subjects of group 2 (no.=14), used as controls, were requested to maintain their habitual level of physical activity for 16 weeks. HIST program consisted of 6 different sets of exercise (2 involving the major muscle groups of the lower limb and 4 involving those of the upper limb). Three sessions/ week, during which 10 repetitions of each exercise set were completed, were performed. Lower limb exercises shifted from 50 to 80% of the one maximal repetition (1 MR) during the first month of the protocol and were thereafter maintained at an intensity of 80% 1 MR throughout the training. Upper limb exercises shifted from 40 to 65% of 1 MR with a similar pattern. All sessions were preceded by 15 min of cycloergometer exercise at 50% of maximal oxygen uptake and by a warm-up of 15 repetitions at 20% of 1 MR of each exercise set. The HIST program did not significantly change BGP (mean SE, before: 15.6 +/- 1.2 microg/l vs after: 16.0 +/- 1.2 microg/l, NS) and PINP levels (before: 44.6 +/- 6.7 microg/l vs after: 43.1 +/- 6.0 microg/l, NS). On the contrary, serum B-AP significantly increased (before: 50.2 +/- 6.1 IU/l vs after: 62.3 +/- 7.0 lU/l, p<0.001) and serum ICTP slightly reduced (before: 4.0 +/- 0.3 microg/l vs after: 3.8 +/- 0.3 microg/l, p<0.05). When bone turnover was expressed as the ratio between bone formation to bone resorption (B-AP/ICTP ratio), a significant improvement in this ratio was found in all subjects of group 1 (before: 12.9 +/- 1.3 lU/microg vs after: 17.3 +/- 1.5 IU/microg, p<0.0001), while no significant changes were observed in Group 2. No significant changes of IGF-I levels were observed after the HIST program (before: 94.9 +/- 9.4 microg/l vs after: 89.9 +/- 9.7 microg/l). No significant changes of BGP, PINP, B-AP, ICTP, B-AP-ICTP ratio and IGF-I levels were observed in controls (group 2) during the 16 weeks of observation. Although the positive effects of a progressive HIST program on B-AP levels and B-AP-ICTP ratio seem promising, the support of bone mass measurement and the determination of other bone markers are requested to better identify exercise protocol (duration, intensity) for elderly people.

Aged↗
PubMed2001

Changes in motor control and muscle performance after a short-term body mass reduction program in obese subjects.

Two hundred and thirty obese subjects (age: 18-77 yr, BMI: 31.1-65.8 kg/m2) were studied before and after a 3-week body mass reduction (BMR) program, coupling restricted energy diet (1200-1500 kcal/day) with low intensity exercise prescription. It involved 5 days per week (consisting of one-hour dynamic aerobic standing and floor exercise plus 30 min of cycloergometer exercise at 60 W or, alternatively, 4 km outdoor leisure walking on flat terrain) and psychological counseling. One-leg standing balance test (OLSB) and stair climbing test (SCT) were employed to assess motor control and maximal lower limb muscle power, respectively. The BMR program induced a significant weight loss (4.1%; p<0.001), a higher reduction of body mass index (BMI) being observed in males than in females (p<0.001). OLSB performance time increased by 20.5% (p<0.001) after treatment, the improvement being evident in both genders. A 20.8% reduction in SCT time (p<0.05) was also observed and corresponded to a 13.2% increase (p<0.001) in average absolute muscle power and 15.0% increase (p<0.001) in specific muscle power (i.e. the power output per kg of body mass), with no differences between genders. In conclusion, in spite of the moderate reduction of body mass after restricted energy diet and low intensity physical conditioning, significant improvements in motor control and performance, likely to ameliorate the execution of simple daily activities, were observed in obese subjects.

Adolescent↗
PubMed2001

Genesis of pituitary adenomas: state of the art.

In recent years, remarkable progress has been made in the understanding of the pathogenesis of pituitary tumors. Pituitary tumors originate from the uncontrolled proliferation of a single transformed cell in which an initiating event has caused a gain of proliferative function. After the initiation, promoting factors cooperate in the clonal expansion. Common oncogenes, such as ras, are only exceptionally involved. The only activating mutations identified so far are gsp mutations causing the constitutive activation of cAMP pathway. However, gsp-positive adenomas are not associated to a more aggressive tumoral phenotype. The oncogenic potential of gsp mutations is limited by a more rapid degradation of the mutant Gs(alpha) with respect to the wild-type protein, and by a faster removal of cAMP due to increased phosphodiesterase activity. Estrogen-inducible gene sequences with transforming properties (pituitary tumor-transforming gene (PTTG)) have been identified in human pituitary tumors. Human pituitary tumor-transforming gene (hPTTG) is involved both in early pituitary tumorigenesis, as it causes in vitro and in vivo transformation acting as a transcription activator, and in tumor progression, as it regulates the production of basic fibroblast growth factor (bFGF), a potent activator of angiogenesis and mitogenesis. Moreover, a role of cyclin D1 in pituitary tumorigenesis is emerging. The allelic loss of loci for unknown oncosuppressor genes are currently under investigation, while an exceedingly limited role for menin gene and RB1 has been demonstrated for sporadic pituitary tumors. Abnormal methylation that predisposing toward genetic instability may favor the allelic loss or the reduced expression of oncosuppressor genes, is also an emerging field of investigation. Several promoting factors, including the excessive action of physiological stimulators, the defective action of inhibitors, the susceptibility to respond to inappropriate stimuli and the locally produced growth factors, help in tumor progression. The study of homeobox genes that intervene in pituitary cell differentiation may help in expanding our knowledge in pituitary tumor cell genealogy.

Adenoma↗
PubMed2001

Efficacy of radiotherapy in normalizing serum IGF-I, acid-labile subunit (ALS) and IGFBP-3 levels in acromegaly.

OBJECTIVE: Radiotherapy (RT) has been used for many years in order to complete the cure of unsuccessfully operated acromegalic patients. Several studies have shown its efficacy in normalizing GH levels, while reports about IGF-I normalization are conflicting. Moreover, data regarding other markers of disease activity, such as IGFBP-3 and acid-labile subunit (ALS), i.e. the other two components of the circulating 150 kDa complex, are lacking. DESIGN: Retrospective study. PATIENTS AND MEASUREMENTS: Sixty-seven acromegalic patients (20 males and 47 females, aged 40 +/- 6 years) who underwent postoperative RT (in fractionated doses for a total of 40-75 Gy) were followed-up for 11 +/- 6 years (range: 1-26 years, median: 10 years). Serum GH and IGF-I levels off medical therapy were measured in all patients; ALS and IGFBP-3 were measured in 11 patients with normalization of IGF-I concentrations. Computed tomography or nuclear magnetic resonance imaging periodically assessed possible development of pituitary deficiency along with imaging of the hypothalamic-pituitary region. RESULTS: Forty-one out of 67 patients (58%) achieved GH levels < 2.5 microg/l by 1-15 years after RT (mean 8 +/- 6) and 37/67 patients (55%) had normal or low IGF-I levels 1-26 years after RT (mean: 12 +/- 6), a normalization of both parameters being seen in 37 patients. GH < 2.5 microg/l and normal IGF-I levels were achieved in 17/26 (65%) patients followed-up for at least 15 years. ALS and IGFBP-3 concentrations paralleled IGF-I levels in all patients studied. With respect to secondary pituitary insufficiency, acquired ACTH deficiency was found in 25 patients, TSH deficiency in 20, gonadotropin deficiency in 23 and GH deficiency in seven. In total, two cases of meningioma and one pineal tumour, possibly related to RT, were seen 9-22 years after RT. CONCLUSIONS: RT is an effective, although slow-acting, therapeutic tool for acromegaly, with 'safe' GH levels and normal IGF-I concentrations being achieved in 65% of patients after 15 years. IGF-I levels normalize more slowly than GH levels. Radiotherapy is able to normalize the concentration of all three components of the circulating 150 kDa complex. Checks for loss of pituitary function and appearance of second brain tumours must be carried out life-long.

Acromegaly↗
PubMed2001

Diagnostic value of the acid-labile subunit in acromegaly: evaluation in comparison with insulin-like growth factor (IGF) I, and IGF-binding protein-1, -2, and -3.

In normal subjects the main form of circulating insulin-like growth factor (IGF) is the 150-kDa complex. This complex is formed by the IGF peptide, the acid-stable IGF-binding protein-3 (IGFBP-3), and the acid-labile subunit (ALS). Experimental and clinical data have demonstrated that ALS is primarily under the control of GH and plays a critical role in maintaining constant levels of circulating IGF-I. In this study we evaluated ALS, IGF-I, and IGFBP-1, -2, and -3 in 45 acromegalic patients in basal conditions and, in 37 of these, twice after surgical therapy compared with 100 age- and sex-matched control subjects to estimate their value as parameter of GH secretory state. The results demonstrated that in acromegaly before treatment all parameters (ALS, 523 +/- 26; IGF-I, 129 +/- 6; IGFBP-1, 0.7 +/- 0.1; IGFBP-3, 234 +/- 21; nmol/L; mean +/- SEM) but IGFBP-2 were significantly different (P<0.0001) from those in healthy subjects (ALS, 281 +/- 4; IGF-I, 22 +/- 1; IGFBP-1, 1.6 +/- 0.1; IGFBP-3, 91 +/- 3). IGF-I was more sensitive (100%) than ALS (89%), and both were more predictive of disease status than IGFBP-3, in that 27% of the patients had IGFBP-3 levels within the normal range. Considering the ALS/IGFBP-3 molar ratio, almost 55% of ALS circulated in a free form in active acromegaly. Before treatment, the IGF-I/IGFBPs (-1 + -2 + -3) molar ratio, which can be regarded as free, biologically active, IGF-I, was greatly increased (0.77 +/- 0.06; P<0.0001) compared with that in control subjects (0.23 +/- 0.01). After surgery, all 10 patients with controlled disease showed normalization of ALS (100% sensitivity), whereas 9 of them had normal IGFBP-3; reevaluation after varying lengths of time showed all these parameters within the normal range. In the 27 patients with active disease, IGF-I and ALS were more predictive of disease status (91% and 83% negative predictive values, respectively) than IGFBP-3 (53%). The basal ALS concentration correlated only with IGFBP-3 (r = 0.70; P<0.001). In postsurgery samples (first control) a statistically significant (P<0.001) correlation was found between mean GH values as well as minimum GH after oral glucose tolerance test and ALS (r = 0.72 and 0.83, respectively), IGF-I (r = 0.69 and 0.77), IGFBP-3 (r = 0.50 and 0.72), and IGFBP-2 (r = -0.36 and -0.63). Similarly, IGF-I, IGFBP-3, and ALS were positively correlated among themselves and negatively correlated with IGFBP-2 (P<0.001). In conclusion, in the diagnosis of acromegaly, the measurement of total IGF-I appears to be the most sensitive parameter among the subunits of the 150K complex, and IGFBP-3 the least sensitive. For ALS, this subunit is quite sensitive and appears to be a useful parameter in reassessment after surgical treatment.

Acromegaly↗
PubMed2001

Mutation of somatostatin receptor type 5 in an acromegalic patient resistant to somatostatin analog treatment.

Introduction of somatostatin analogs has greatly contributed to improving the prognosis of acromegaly. Although the majority of patients are effectively treated by these agents, resistance occurs in a subset of patients. So far, resistance to somatostatin has never been associated with mutations of the somatostatin receptor subtypes (sst2 and sst5) that inhibit GH secretion. Molecular analysis of genomic DNA from pituitary tumor and peripheral blood obtained from an acromegalic resistant to octreotide showed a somatic activating mutation of Gsalpha (Arg201Cys), no mutation in sst2, and one polymorphism (Pro109Ser) and one germ line mutation (Arg240Trp) in sst5. Wild-type (WT) and mutant sst5 PCR products were cloned and transfected into Chinese hamster ovary K1 cells. In Chinese hamster ovary K1 cells stably expressing mutant sst5, somatostatin-28 was less potent in inhibiting cyclic AMP levels than in WT cells. Proliferation of mutant cells exceeded that of WT by 50%. Moreover, somatostatin reduced cell growth and MAPK activity in WT but not in mutant cells in which the peptide even increased MAPK activity. We suggest that this mutation that abrogates the antiproliferative action of somatostatin and activates mitogenic pathways may be involved in the resistance to somatostatin treatment.

Acromegaly↗
PubMed2001

Aerobic and anaerobic performance before and after a short-term body mass reduction program in obese subjects.

The cardiovascular response to an aerobic cycloergometer exercise test (ACET, 15 min at 60 W, 60 rpm) and the maximally attainable muscle power output, assessed by a stair climbing test (SCT), were evaluated in 60 obese patients (41 females and 19 males; age: 18-68 yr; body mass index, BMI: 40.8+/-4.8 kg/m2) before and after a 3-week body mass reduction (BMR) program, entailing integrated energy-restricted diet (1200-1500 kcal/day), low-grade aerobic exercise conditioning and individual and/or group psychological therapy. The daily conditioning protocol (5 days/week) consisted of: 1) 30 min of indoor jogging and dynamic aerobic standing and floor exercises performed with arms and legs, under the guidance of a therapist; 2) 30 min of cycloergometer exercise at 60 W; and/or 3) 4-km outdoor leisure walking on flat terrain. Three weeks of BMR program induced a significant weight loss (-4.5 %; p<0.001), a reduction of systolic (-11+/-14 mmHg, -7.3%,p<0.001) and diastolic (-7+/-9 mmHg, -7.3%,p<0.001) resting arterial blood pressure, as well as a reduction of heart rate at rest (-18.6%,p<0.001), during ACET (-11.3%,p<0.001) and 5 min thereafter (-14.8%,p<0.001). The subjective rating of perceived exertion in terms of breathlessness and general fatigue during ACET, scored on a 0-100 visual analogic scale, was significantly reduced (p<0.001) after BMR program. A 11.2% decrease in SCT time (p<0.001) was also observed, corresponding to a 9.6% increase (p<0.001) in average muscle power (W) and 14.6% increase (p<0.001) in specific muscle power (W.kg(-1)). In conclusion, a combination of energy restricted diet, low intensity aerobic exercise and psychological counselling appears to significantly improve both aerobic and anaerobic performance in morbidly obese subjects. Different factors (ie, reduction of body mass, shift in the balance between parasympathetic and sympathetic activity, a weight-loss dependent shift toward a more favourable region of the muscle power-velocity curve, acquisition of a certain degree of motor skillfulness during the conditioning program, improvement of self-esteem and motivation) might be responsible, alone or in combination, for these short-term positive effects of BMR program.

Adolescent↗
PubMed2001

A comparative evaluation of effectiveness of medical and surgical therapy in patients with macroprolactinoma.

BACKGROUND: The surgical success rate in macroprolactinomas is quite low, while medical treatment is more effective in reducing PRL levels and tumour mass. In this study the effectiveness of surgical, medical and radiant approaches on clinical symptoms, PRL levels and tumour size were compared in a large series of patients with macroprolactinomas. METHODS: One hundred and thirty-two patients (63 males and 69 females) were followed-up. Eighty-three patients were operated by trans-sphenoidal (TSS) approach: 18 underwent only TSS, 10 were operated and then irradiated; 30 patients underwent TSS and dopamine agonists, 25 were treated by TSS, radiotherapy and dopamine agonists. One hundred and four patients were treated by medical therapy: 49 patients were only administered dopamine agonists and 55 were given dopamine agonists after unsuccessful surgery and/or radiotherapy. RESULTS: In 83 patients serum PRL levels decreased from 1873+/-319.9 ng/ml to 831.6+/-297.8 ng/ml after trans-sphenoidal surgery: a significant PRL reduction was obtained in 18 cases (22%) and a full PRL normalization was found in 15 patients (18%). The pituitary adenoma was completely removed in the 15 cases, in whom serum PRL normalized. Sexual function was restored in 57 percent; of women and in 29 percent; of men. In contrast, dopaminergic drugs normalized PRL levels (from 1590.5+/-232.7 to 19.2+/-4.8 ng/ml) in 93/104 patients (89 percent;). Sexual function was restored in 74 percent; of women and in 75 percent; of men. Radiotherapy, performed after unsuccessful TSS, was ineffective in normalizing PRL levels. CONCLUSIONS: Medical therapy should be considered the first choice treatment in macroprolactinomas, while the surgical approach is recommended when neurological compressive symptoms are present and in patients resistant or intolerant to dopamine agonists. Radiotherapy may be indicated only in the patients in whom medical and surgical therapy have not been successful.

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