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Giovanni Vitale

Publications and source records attributed to Giovanni Vitale.

At least 19 recordsLinked to original sources
PubMed2025

Proteomic profiling identifies miR-423-5p as a modulator of oncogenic metabolism in HCC.

BACKGROUND: Hepatocellular carcinoma (HCC) remains a significant clinical challenge due to limited diagnostic and therapeutic options. Non-coding RNAs (ncRNAs), such as microRNAs (miRNAs), play key roles in cancer biology. Our previous findings showed that miR-423-5p enhances anti-cancer effects on HCC patients treated with sorafenib by promoting autophagy. Here, we investigated the molecular mechanisms underlying miR-423-5p function through a comprehensive proteomic approach. METHODS: We generated an HCC cell line stably overexpressing miR-423-5p via lentiviral transduction. Total proteins were extracted from SNU-387 cells, enzymatically digested into peptides, and subsequently analysed by liquid chromatography-tandem mass spectrometry (LC-MS/M). Raw spectral data were processed and quantified using MaxQuant. Differentially expressed proteins (DEPs) were defined based on fold-change (|log2FC| &#x2265; 1) and false discovery rate (FDR < 0.05). The full proteomic dataset is available via the ProteomeXchange repository (identifier: PXD064869). Functional enrichment analysis of DEPs were performed using DAVID and Reactome. To assess clinical relevance, predicted and validated miR-423-5p targets were integrated with The Cancer Genome Atlas (TCGA) Liver Hepatocellular Carcinoma (LIHC) dataset using GEPIA platform. Survival analyses were performed using the Kaplan-Meier method. RESULTS: Proteomic profiling identified 698 DEPs in miR-423-5p-overexpressing cells compared to controls with significant enrichment in metabolic pathways, related to purine/pyrimidine metabolism and gluconeogenesis. Integration with bioinformatic predictions and miRTarBase validation identified 43 DEPs as potential direct targets of miR-423-5p. Among these, seven proteins (ACACA, ANKRD52, DVL3, MCM5, MCM7, RRM2, SPNS1, and SRM) were significantly associated with patient prognosis in the TCGA-LIHC cohort. These targets were downregulated in miR-423-5p-overexpressing cells but upregulated in advanced-stage HCC tissues, suggesting a potential role for miR-423-5p in the regulation of HCC pathogenesis. Stage-specific expression analysis showed increased levels from stage I to III, followed by a decline at stage IV. Notably, we experimentally confirmed miR-423-5p-mediated suppression of MCM7, DVL3, IMPDH1, and SRM (SPEE), supporting their functional involvement in HCC progression. CONCLUSION: Overall, our findings support a tumour-suppressive role for miR-423-5p in HCC, mediated by modulation of metabolic pathways and suppression of oncogenic proteins. These results suggest that miR-423-5p and its downstream effectors may serve as promising biomarkers and potential therapeutic targets in HCC. HIGHLIGHTS: miR-423-5p acts as a tumor suppressor in HCC by targeting key nodes of pro-tumorigenic signalling. miR-423-5p significantly altered metabolic pathways, including purine/pyrimidine metabolism and gluconeogenesis. Seven miR-423-5p targets correlate with poor prognosis in TCGA-LIHC patients and are downregulated in miR-423-5p overexpressing HCC cells. miR-423-5p over-expression induces a significant downregulation of MCM7, DVL3, IMPDH1, SPEE in HCC cell models. miR-423-5p limits tumor metabolic plasticity, suggesting therapeutic potential.

MicroRNAs↗
PubMed2025

Exploring the tumor suppressor role of RIN1 in familial thyroid carcinoma.

The genetic component is thought to play an important role in the development of familial non-medullary thyroid carcinoma (fNMTC), but the involved molecular mechanisms and genes are poorly understood. The MAPK kinase cascade, particularly involving RAS and BRAF, is crucial in cancer development, with RIN1 emerging as a notable gene due to its differential expression across various tumor types. We identified a frameshift mutation (c.798delC: p.V267Sfs*83) in the RIN1 gene in a family with non-medullary thyroid cancer (NMTC) through whole-exome sequencing. Paraffin-embedded tumor tissues were analyzed to investigate the mutation's characteristics and its potential implications within the thyroid cellular context. Functional assays and RNA sequencing using CRISPR/Cas9-edited Nthy-ori 3-1 thyroid cell line and xenograft zebrafish models confirmed the mutation effect and the putative RIN1 tumor suppressor role. The study revealed significant alterations in cellular behavior upon RIN1 knockout, including increased cell viability, proliferation and colony formation, alongside morphological changes indicative of epithelial-mesenchymal transition. Enhanced phosphorylation of ERK and AKT suggested MAPK pathway dysregulation following RIN1 depletion, supporting its potential tumor suppressive role. Phenotypic rescue experiments confirmed that reintroduction of wild-type RIN1 restored normal cellular behavior. RNA sequencing demonstrated differential gene expression between RIN1-/- and control cells, particularly affecting pathways associated with cancer progression, closely resembled signatures specific to NMTC. This study provides compelling evidence supporting RIN1 as a tumor suppressor gene within thyroid cells. In addition, the findings highlight its potential significance as novel gene involved in FNMTC pathogenesis.

Humans↗
PubMed2006

Potent inhibitory effects of type I interferons on human adrenocortical carcinoma cell growth.

CONTEXT: Adrenocortical carcinoma (ACC) is a rare tumor with a poor prognosis. Despite efforts to develop new therapeutic regimens for metastatic ACC, surgery remains the mainstay of treatment. Interferons are known to exert tumor-suppressive effects in several types of human cancer. DESIGN: We evaluated the tumor-suppressive effects of type I interferons (IFN)-alpha2b and IFNbeta on the H295 and SW13 human ACC cell lines. RESULTS: As determined by quantitative RT-PCR analysis and immunocytochemistry, H295 and SW13 cells expressed the active type I IFN receptor (IFNAR) mRNA and protein (IFNAR-1 and IFNAR-2c subunits). Both IFNalpha2b and IFNbeta1a significantly inhibited ACC cell growth in a dose-dependent manner, but the effect of IFNbeta1a (IC50 5 IU/ml, maximal inhibition 96% in H295; IC50 18 IU/ml, maximal inhibition 85% in SW13) was significantly more potent, compared with that of IFNalpha2b (IC50 57 IU/ml, maximal inhibition 35% in H295; IC50 221 IU/ml, maximal inhibition 60% in SW13). Whereas in H295 cells both IFNs induced apoptosis and accumulation of the cells in S phase, the antitumor mechanism in SW13 cells involved cell cycle arrest only. Inhibitors of caspase-3, caspase-8, and caspase-9 counteracted the apoptosis-inducing effect by IFNbeta1a in H295 cells. In H295 cells, IFNbeta1a, but not IFNalpha2b, also strongly suppressed the IGF-II mRNA expression, an important growth factor and hallmark in ACC. CONCLUSIONS: IFNbeta1a is much more potent than IFNalpha2b to suppress ACC cell proliferation in vitro by induction of apoptosis and cell cycle arrest. Further studies are required to evaluate the potency of IFNbeta1a to inhibit tumor growth in vivo.

Adrenal Cortex Neoplasms↗
PubMed2006

Anxiolytic-like effects of nociceptin/orphanin FQ in the elevated plus maze and in the conditioned defensive burying test in rats.

Different reports suggest that nociceptin/orphanin FQ (N/OFQ) may have either anxiolytic- or anxiogenic-like effect in rodents. Since N/OFQ elicits hypolocomotion, which undergoes rapid tolerance, and hypolocomotion may be associated to emotional consequences, the present study was designed to investigate the effect of N/OFQ on anxiety after development of tolerance to its hypolocomotor effect. The effect of single or double intracerebroventricular (i.c.v.) injection of N/OFQ was evaluated on anxiety-related behaviors in rats, in the elevated plus maze (EPM) and conditioned defensive burying (CDB) tests. After single administration, N/OFQ displayed an anxiogenic-like pattern of response on the elevated plus maze but hypolocomotion was also observed. Conversely, in the CDB test, N/OFQ induced a clear-cut anxiolytic pattern. To produce tolerance to N/OFQ-induced hypolocomotion the peptide was administered by two i.c.v. injections separated by 120 min; in these conditions it decreased the expression of anxiety-related behaviors in both tests without affecting locomotor activity. The nociceptin/orphanin FQ peptide (NOP) receptor antagonist UFP-101 significantly reduced the effects of N/OFQ to control values in either tests. Corticosterone levels were significantly increased after a single N/OFQ administration (not in a dose-dependent manner) but this increase did not reach significance after double administration (1 nmol/rat). Our results support the idea that N/OFQ may act as an anxiolytic-like agent in the rat; the apparent anxiogenic-like effect observed following its single administration in the EPM may be consequent to its effect on locomotion.

Animals↗
PubMed2006

IFN-beta is a highly potent inhibitor of gastroenteropancreatic neuroendocrine tumor cell growth in vitro.

IFN-alpha controls hormone secretion and symptoms in human gastroenteropancreatic neuroendocrine tumors (GEP-NET) but it rarely induces a measurable tumor size reduction. The effect of other type I IFNs, e.g., IFN-beta, has not been evaluated. We compared the antitumor effects of IFN-alpha and IFN-beta in BON cells, a functioning human GEP-NET cell line. As determined by quantitative reverse transcription-PCR analysis and immunocytochemistry, BON cells expressed the active type I IFN receptor mRNA and protein (IFNAR-1 and IFNAR-2c subunits). After 3 and 6 days of treatment, IFN-beta significantly inhibited BON cell growth in a time- and dose-dependent manner. IC50 and maximal inhibitory effect on day 6 were 8 IU/mL and 98%, respectively. In contrast, the effect of IFN-alpha resulted significantly in a less potent effect (IC50: 44 IU/mL, maximal inhibition: 26%). IFN-alpha induced only cell cycle arrest, with an accumulation of the cells in S phase. IFN-beta, apart from a more potent delay in S-G2-M phase transit of the cell cycle, also induced a strong stimulation of apoptosis, evaluated by flow cytometry (Annexin V and 7-AAD) and measurement of the DNA fragmentation. Besides, only IFN-beta severely suppressed chromogranin A levels in the medium from BON cells after 6 days of treatment. In conclusion, IFN-beta is much more potent, compared with IFN-alpha, in its inhibitory effect on GEP-NET cell proliferation in vitro through the induction of apoptosis and cell cycle arrest. Further studies are required to establish whether IFN-beta has comparable potent tumor growth inhibitory effects in vivo.

Apoptosis↗
PubMed2006

Pulsed tissue Doppler identifies subclinical myocardial biventricular dysfunction in active acromegaly.

OBJECTIVE: The aim of this study was to assess the role of pulsed tissue Doppler (TD) to identify left (LV) and right ventricular (RV) myocardial regional involvement in acromegaly. PATIENTS AND MEASUREMENTS: Thirty active acromegaly patients, free of diabetes mellitus, thyroid dysfunction, valvular and coronary heart disease, clinically overt heart failure, and 30 sex- and age-matched healthy controls underwent standard Doppler echocardiography and pulsed TD, by placing the sample volume at the level of basal posterior septum, LV lateral mitral annulus and RV lateral tricuspid annulus. Myocardial systolic (S(m)) and diastolic velocities (E(m)/A(m) ratio) and time-intervals of relaxation (RT(m)), precontraction (PCT(m)) and contraction (CT(m)) and the PCT(m)/CT(m) ratio were measured at each level. RESULTS: The two groups had similar heart rate, whereas acromegaly patients had higher body mass index, systolic and diastolic blood pressure, LV mass and impaired Doppler indexes of LV and RV diastolic function, without any difference in the global systolic function. At TD, acromegaly patients showed significantly delayed RT(m) and PCT(m,) reduced E(m)/A(m), S(m) and increased PCT(m)/CT(m) of posterior septum, mitral annulus and tricuspid annulus in comparison with controls. By separate multilinear regression analyses, after adjusting for body mass index, heart rate, diastolic blood pressure and LV mass index, age was the main independent determinant of tissue Doppler diastolic but not of systolic indexes. CONCLUSIONS: In active acromegaly, pulsed TD confirms LV and RV diastolic abnormalities detectable by standard Doppler, additionally identifying subclinical biventricular impairment of systolic function.

Acromegaly↗
PubMed2005

Acute noise stress analgesia in relation to 5-HT2 and mu-opioid receptor changes in the frontal cortex of young mice.

A number of studies have reported that exposure to stress provoked behavioural changes, including analgesia, in rodents. Differences have been observed in these responses to different types of stress and a link between hormones and neurotransmitters proposed. We studied the effect of acute noise stress on nociception and the possible changes in the serotonergic and opioidergic systems in young mice of both sexes. Naloxone pre-treatment was also investigated. Noise stress was produced by a sound source, nociception was measured by the hot-plate test and binding characteristics were evaluated by a radioligand binding technique using membrane preparation from the total frontal cortex. Acute noise stress provoked an antinociceptive effect, associated with an increase in plasma corticosterone levels, a decrease in the number of 5-HT2 receptors in stressed male and female mice and a decrease in the number of mu receptors in both sexes. The behavioural and biochemical effects were antagonized by 1 mg/kg of naloxone. Acute noise stress behaves like other types of stress on nociception. The opioidergic system seems to be involved in this behaviour but also the serotonergic system may play a role. Sex differences were detected in the number of 5-HT2 and mu receptors between male and female mice not subjected to stress, while the percentage decrease in 5-HT2 and mu receptors did not differ significantly between the two sexes.

Animals↗
PubMed2005

Arterial stiffening influence of sympathetic nerve activity: evidence from hand transplantation in humans.

Studies in animals and humans suggest that sympathetic activity exerts a stiffening influence on large and middle-sized artery walls. We sought to obtain further evidence on this issue by measuring radial artery distensibility in an allotransplanted and thus denervated hand using the contralateral artery as control. In 2 men, blood pressure was measured by a semiautomatic device (Dinamap). Diastolic diameter, systo-diastolic diameter excursion (ultrasound Wall Track system), and distensibility (Reneman formula) of both radial arteries were measured at a level corresponding to 4 cm below the suture of the transplanted hand 40 days after surgery and every 4 weeks for the next 6 months. After surgery, systo-diastolic diameter excursion and distensibility were much greater in the transplanted radial artery than in the contralateral vessel, reaching values similar to the contralateral ones after 4 months, when signs of reinnervation of the transplanted hands had appeared. Radial deinnervation was accompanied by an increased arterial distensibility, which provides further evidence of the sympathetic stiffening effect on arterial wall in humans.

Adult↗
PubMed2005

New pharmacokinetic and pharmacodynamic tools for interferon-alpha (IFN-alpha) treatment of human cancer.

Interferon alpha (IFN-alpha) has been widely used in the treatment of human solid and haematologic malignancies. Although the antitumour activity of IFN-alpha is well recognised at present, no major advances have been achieved in the last few years. Recent findings have provided new information on the molecular mechanisms of the antitumour activity of the cytokine. In fact, IFN-alpha appears to block cell proliferation, at least in part, through the induction of apoptotic effects. This cytokine can also regulate the progression of tumour cells through the different phases of the cell cycle inducing an increase of the expression of the cyclin-dependent kinase inhibitors p21 and p27. However, it must be considered that IFN-alpha is a physiologic molecule with ubiquitously expressed receptors that is likely to activate survival mechanisms in the cell. We have recently identified an epidermal growth factor (EGF) Ras-dependent protective response to the apoptosis induced by IFN-alpha in epidermoid cancer cells. The identification of tissue- and/or tumour-specific survival pathways and their selective targeting might provide a new approach to improve the efficacy of IFN-alpha-based treatment of human cancer. Moreover, new pegylated species of IFN-alpha are now available with a more favourable pharmacokinetic profile. We will review these achievements, and we will specifically address the topic of IFN-alpha-based molecularly targeted combinatory antitumour approaches.

Antineoplastic Agents↗
PubMed2005

Hypertension in acromegaly and in the normal population: prevalence and determinants.

BACKGROUND: The GH/IGF-I axis has a relevant role to play in the cardiovascular system but its implication in the pathogenesis of hypertension in the normal population and in acromegaly is not yet clear. PATIENTS AND MEASUREMENTS: The aim of this retrospective and controlled study was to evaluate the prevalence and determinants of hypertension in 200 patients with acromegaly and 200 nonacromegalic subjects, matched for sex, age, body mass index (BMI) and smoking habits. RESULTS: Hypertension was found in 46% of patients and in 25% of controls (P < 0.0001), without any difference between men and women. Family history of hypertension occurred in 30% of hypertensive acromegalic patients and in 62% of hypertensive controls (P < 0.0001). In both groups, hypertensive subjects were older than normotensive subjects. Systolic (SBP) and diastolic blood pressures (DBP) in hypertensive acromegalic patients were lower and higher, respectively, than in hypertensive controls. The risk of hypertension increased with age and was higher in the patients than in the controls [hazard ratio (HR) 1.9; P = 0.0002]. Independent predictors of SBP were age and glucose in the acromegalic population, and BMI, age and glucose levels in the controls. Independent predictors of DBP were age and glucose in the patients, and BMI, age and IGF-I in the controls. CONCLUSIONS: In acromegaly, hypertension is more frequent than in the general population, involves predominantly DBP, and occurs earlier, is not related to gender, and is less frequently related to family history of hypertension and IGF-I levels. IGF-I may have a protective role for DBP in the general population.

Acromegaly↗
PubMed2004

Nociceptin/orphanin FQ prevents the antinociceptive action of paracetamol on the rat hot plate test.

Nociceptin/orphanin FQ (N/OFQ) is involved in many behavioural patterns; in particular, it exerts a modulating effect on nociception. Like other proposed antiopiates, nociceptin/orphanin FQ has been shown to have analgesic, hyperalgesic as well as antianalgesic properties. Among the various effects proposed on nociceptive sensitivity at supraspinal level, the antagonistic activity toward morphine analgesia seems to be of interest. Therefore, we decided to investigate whether nociceptin/orphanin FQ and [Arg14, Lys15] nociceptin/orphanin FQ (R-K, a nociceptin analogue) can have the same effect on the analgesia produced by nonopioid analgesics. In this study, we examined the antianalgesic effect of nociceptin/orphanin FQ and its analogue R-K on paracetamol-induced analgesia and evaluated by means of the hot plate test in rats. Nociceptin/orphanin FQ was intracerebroventricularly administered, and, after 5 min, a dose of 400 mg/kg paracetamol was injected intraperitoneally, 30 min before the hot plate test. Nociceptin/orphanin FQ and R-K showed a dose-dependent antagonism on the antinociceptive effect of paracetamol, and the activity of both drugs was significantly reduced by the antagonist [Nphe1] Arg14, Lys15-N/OFQ-NH2 (UFP-101). These data indicate that nociceptin/orphanin FQ and R-K have an antianalgesic effect on the analgesia produced by a nonopioid analgesic drug, like paracetamol, that seems to develop within the brain.

Acetaminophen↗
PubMed2004

Colonoscopic screening and follow-up in patients with acromegaly: a multicenter study in Italy.

Acromegaly is an infrequent disease attributable to endogenous excess of GH and IGF-I. Human studies have associated the GH-IGF-I axis with the development of colorectal cancer; however, the question of whether colorectal cancer is a problem in acromegaly is currently unresolved. We performed a cross-sectional study to assess the risk of colonic neoplasia in patients with acromegaly. Colonoscopic screening was performed in 235 patients with acromegaly at five tertiary care hospitals in Italy between January 1, 1996, and December 31, 2001. A repeat colonoscopy was performed in 121 patients after a mean interval of 32.1 months. Colonoscopic findings in patients with acromegaly were compared with those of 233 patients with nonspecific abdominal complaints who were referred for endoscopy during the study period. A total of 65 patients (27.7%) and 36 controls (15.5%) had colonic neoplasia. In 55 patients (23.4%) and 34 control subjects (14.6%), the most important findings were adenomas (odds ratio, 1.7; range, 1.1-2.5), whereas 10 patients (4.3%) and two control subjects (0.9%) had carcinoma (odds ratio, 4.9; range, 1.1-22.4). The risk of colonic neoplasia was higher for younger patients with acromegaly compared with age-matched controls. Patients with acromegaly with or without colonic neoplasia did not differ significantly for IGF-I levels or duration of disease. A neoplastic recurrence was found in 16.5% of patients who underwent follow-up; 90% of them had had a neoplasm removed at the first colonoscopy. Acromegaly carries with it a moderate, but definitive, increase in the risk of colonic neoplasia that occurs at a younger age than in the general population. Patients who are found to harbor a colonic neoplasia are at risk for recurrence.

Acromegaly↗
PubMed2004

The farnesyl transferase inhibitor R115777 (Zarnestra) synergistically enhances growth inhibition and apoptosis induced on epidermoid cancer cells by Zoledronic acid (Zometa) and Pamidronate.

Pamidronate (PAM) and zoledronic acid (ZOL) are aminobisphosphonates (BPs) able to affect the isoprenylation of intracellular small G proteins. We have investigated the antitumor activity of BPs and R115777 farnesyl transferase inhibitor (FTI) against epidermoid cancer cells. In human epidermoid head and neck KB and lung H1355 cancer cells, 48 h exposure to PAM and ZOL induced growth inhibition (IC(50) 25 and 10 microM, respectively) and apoptosis and abolished the proliferative and antiapoptotic stimuli induced by epidermal growth factor (EGF). In these experimental conditions, ZOL induced apoptosis through the activation of caspase 3 and a clear fragmentation of PARP was also demonstrated. A strong decrease of basal ras activity and an antagonism on its stimulation by EGF was recorded in the tumor cells exposed to BPs. These effects were paralleled by impaired activation of the survival enzymes extracellular signal regulated kinase 1 and 2 (Erk-1/2) and Akt that were not restored by EGF. Conversely, farnesol induced a recovery of ras activity and antagonized the proapoptotic effects induced by BPs. The combined treatment with BPs and R115777 resulted in a strong synergism both in growth inhibition and apoptosis in KB and H1355 cells. The synergistic activity between the drugs allowed BPs to produce tumor cell growth inhibition and apoptosis at in vivo achievable concentrations (0.1 micromolar for both drugs). Moreover, the combination was highly effective in the inhibition of ras, Erk and Akt activity, while farnesol again antagonized these effects. In conclusion, the combination of BPs and FTI leads to enhanced antitumor activity at clinically achievable drug concentrations that resides in the inhibition of farnesylation-dependent survival pathways and warrants further studies for clinical translation.

Alkyl and Aryl Transferases↗
PubMed2004

Prevalence and determinants of left ventricular hypertrophy in acromegaly: impact of different methods of indexing left ventricular mass.

BACKGROUND: Left ventricular hypertrophy (LVH) is the most common cardiac abnormality in acromegaly. Left ventricular mass (LVM) is an important parameter measured to detect LVH, but the relationship with body size should be considered by correcting LVM to body surface area (BSA), height or height2.7. All trials concerning acromegaly have detected LVH on the basis of LVM indexed for BSA, but have been criticized for disregarding the effects of obesity. PATIENTS AND MEASUREMENTS: 97 patients with active acromegaly and a control group of 97 nonacromegalic subjects, were compared for the prevalence of LVH, calculated with different corrections of LVM for BSA, height and height2.7. In addition, we evaluated determinants of LVH in acromegalic group. RESULTS: In controls, the prevalence of LVH, determined by correcting LVM for BSA (10.3%) was significantly lower than correcting by LVM/height (21.6%, P = 0.05) and LVM/height2.7 (33%, P < 0.0001). Similarly, in the acromegalic population the prevalence of LVH was significantly higher when measured by LVM/height (86.6%) or LVM/height2.7 (89.7%), than by LVM/BSA (67%) (P = 0.002 and P < 0.0001, respectively). A lower prevalence of LVH detected by LVM/BSA than LVM/height and LVM/height2.7 has been observed in an acromegalic overweight group, while in patients with normal weight there was no significant differences using different corrections. In acromegalic patients with disease duration of 10 years. By separate multiple regression analyses systolic blood pressure was the only independent determinant of LVM/BSA or LVM/height, while systolic blood pressure and GH levels were both predictors of LVM/height2.7. CONCLUSIONS: LVM indexed for height2.7 appears to be the most appropriate method to identify LVH in acromegaly, particularly in overweight patients and those with shorter disease duration.

Acromegaly↗
PubMed2004

Insulin-like growth factor-1 deficiency determines increased intima-media thickness at common carotid arteries in adult patients with growth hormone deficiency.

OBJECTIVE: To investigate the role of IGF-1 on intima-media thickness (IMT) at common carotid arteries by Doppler ultrasonography. SUBJECTS: Thirty-nine patients (17 women, 22 men, aged 25-70 years) with severe GH deficiency (GHD), 19 with normal and 20 with low IGF-1 levels, and 39 sex-, age- and body mass index (BMI)-matched healthy controls. RESULTS: Patients with GHD showed abnormalities in lipid profile, and increased fibrinogen levels, mean IMT (0.88 +/- 0.26 vs. 0.69 +/- 0.14 mm, P < 0.001), and systolic and diastolic peak velocity (P < 0.001) compared to controls. Eight patients (18%) and one control (2.1%, P = 0.04) had well-defined plaques. In controls, but not in patients with GHD, mean carotid IMT was correlated with age (r = 0.78, P < 0.001). In both controls (r = -0.82; P < 0.0001) and patients with GHD (r = -0.84, P < 0.0001), serum IGF-1 levels were inversely correlated with mean IMT at common carotid arteries. At the stepwise multiple regression, the variables most significantly related to IMT in GH-deficient patients were total cholesterol levels (t = 5.2, P < 0.001), followed by disease duration (t = 2.4, P = 0.02), while in controls the variables most significantly related to IMT were IGF-1 levels (t = -9.9, P < 0.001), followed by low density lipoprotein (LDL)-cholesterol levels (t = -2.3, P = 0.02). Compared to patients with normal IGF-1 levels, those with low IGF-1 levels had lower high density lipoprotein (HDL)-cholesterol levels (1.0 +/- 0.2 vs. 1.3 +/- 0.2 mmol/l, P = 0.0002), and higher glucose (54.3 +/- 6.1 vs. 48.9 +/- 5.9 mmol/l, P = 0.008), insulin (25.2 +/- 6.8 vs. 18.8 +/- 6.0 mUl/l, P = 0.004), total cholesterol (7.1 +/- 1.1 vs. 4.9 +/- 0.6 mmol/l, P < 0.0001), total/HDL-cholesterol ratio (7.2 +/- 1.8 vs. 3.9 +/- 0.7, P < 0.0001), fibrinogen levels (319.8 +/- 56.9 vs. 241.8 +/- 53.0 mg/dl, P < 0.0001) and mean IMT at common carotid arteries (1.05 +/- 0.25 vs. 0.69 +/- 0.07 mm, P < 0.0001). Atherosclerotic plaques were found only in GH-deficient patients with low IGF-1 levels. CONCLUSIONS: GH-deficient patients have alterations in lipid profile with an increase in the total/HDL-cholesterol ratio, which is an index of increased cardiovascular risk, but only patients with IGF-1 deficiency have increased IMT.

Adult↗
PubMed2004

Six months of treatment with cabergoline restores sexual potency in hyperprolactinemic males: an open longitudinal study monitoring nocturnal penile tumescence.

This open longitudinal study investigated the prevalence of depressed sexual potency by monitoring erectile dysfunction using nocturnal penile tumescence (NPT) in 51 consecutive men with hyperprolactinemia (41 macroprolactinomas and 10 microprolactinomas) and evaluated potential reversibility of sexual failure after 6 months of treatment with cabergoline. Fifty-one healthy men served as controls. Compared with controls, the patients with either micro- or macroprolactinoma had low testosterone levels with severe alterations of erectile function. Testosterone deficiency was present in 73.2% of macro- and 50% of microprolactinomas; reduced libido and sexual potency were referred by 53.6% of macroprolactinomas, 50% of microprolactinomas, and none of controls. Fewer than three erectile events per night by NPT were found in 96.7% of patients and 13.7% of controls (P < 0.0001). After 6 months of cabergoline treatment, prolactin levels normalized in 74.5% of patients: 73.2% of macroprolactinomas and 80% of microprolactinomas. Testosterone levels normalized in 68.6% of patients, whereas NPT normalized in 60.6% of patients who had normalized prolactin levels and in 7.7% of patients who did not. In conclusion, at study entry, 50% of the patients complained of sexual disturbances, 96.7% of whom had an impairment of erectile events per night compared with 13.7% of controls. Six months of treatment with cabergoline normalized testosterone levels in most cases, thus restoring and maintaining during treatment the capability of normal sexual activity in hyperprolactinemic males.

Adult↗
PubMed2004

Outcome of cabergoline treatment in men with prolactinoma: effects of a 24-month treatment on prolactin levels, tumor mass, recovery of pituitary function, and semen analysis.

The outcome of 24 months of cabergoline treatment on prolactin (PRL) normalization, tumor shrinkage, restoration of pituitary function, and semen alterations was prospectively investigated in 41 men with macro- (age 17-70 yr) and 10 with microprolactinoma (age 18-53 yr). Fifty-one age-matched men served as controls for semen analysis. At study entry, of the 41 patients with macroprolactinoma, 17 (41.4%) had visual field defects, 14 (34.1%) had headache, eight (19.5%) had galactorrhea, 22 (53.6%) had hypopituitarism apart from hypogonadism, and 30 (73.2%) had low testosterone levels; of the 10 patients with microprolactinoma, none had visual field defects, galactorrhea, or hypopituitarism apart from hypogonadism, two had headache (20%), and five had low testosterone levels (50%; P = 0.3). After 24 months of therapy, 1) PRL levels normalized in 31 patients with macro- (75.6%) and in eight with microprolactinoma (80%; P = 0.9), and galactorrhea disappeared in all patients; 2) maximal tumor diameter reduced by 73.7 +/- 22.6% in macro- and 72.8 +/- 28.3% in microprolactinomas (P = 0.91), and 15 macro- (30%) and seven microprolactinomas (46.7%; P = 0.37) disappeared; 3) visual field defects disappeared in 15 (75%) patients with macroprolactinoma, and headache disappeared in 15 (83%) patients with macro- and in one with microprolactinoma (50%); 4) GH secretion recovered in 62.5% and ACTH secretion in 60% of patients; 5) testosterone levels normalized in 25 patients with macro- (60.9%) and six with microprolactinoma (60%) after 6 months, and 20 patients required testosterone or gonadotropin replacement (in 14 or six patients, respectively); and 6) sperm volume and count normalized in all patients who normalized testosterone levels, whereas motility normalized in more than 80%. Cabergoline therapy was well tolerated; only 4.5% of patients had side effects at high doses. These data demonstrate that cabergoline treatment is as effective and safe in men as in women with prolactinoma and can be successfully used as primary therapy even in men bearing large macroprolactinomas.

Adolescent↗