Multicenter retro-prospective observational study on chronic hypoparathyroidism and rhPTH (1-84) treatment.

PURPOSE: The main purpose of this study was to investigate the effects of 12 months of rhPTH (1-84) (Natpar®) treatment in a cohort of patients selected according to the indications of hypoparathyroidism guidelines. The use of recombinant human PTH (1-84) [rhPTH (1-84)] is approved as hormonal replacement therapy in patients with hypoparathyroidism not adequately controlled with conventional therapy. METHODS: It is a multicenter, observational, retro-prospective, open label study. Eleven Italian Endocrinological centers, members of Hypoparathyroidism Working Group of the Italian Society of Endocrinology (HypoparaNET) were involved. Main outcome measures were serum and urinary calcium and phosphate concentration, calcium-phosphate product, renal function, oral calcium and vitamin D doses, and clinical manifestations. RESULTS: Fourteen adult subjects, affected by chronic hypoparathyroidism, were treated with rhPTH (1-84) for 12 months. At 12 months of rhPTH (1-84) treatment, 61.5% of patients discontinued calcium supplement and 69.2% calcitriol. Mean albumin-adjusted total serum calcium levels quickly normalized after initiation of rhPTH (1-84) treatment compared to baseline (p = 0.009), remaining in the normal range until 12 months. Rare hypo-hypercalcemia episodes were reported. Renal function was maintained normal and no renal complications were reported. Serum and urinary phosphate and urinary calcium were maintained in the normal range. Mean phosphatemia levels linearly decreased from 3 months up to 12 months compared to baseline (p = 0.014). No severe adverse events were described. CONCLUSIONS: Biochemical and clinical results confirm the efficacy and safety of rhPTH (1-84) therapy, which represents an important option for hypoparathyroid patients unresponsive to conventional therapy.

[Polycystic ovary syndrome and obesity: non pharmacological approaches]. / Sindrome dell'ovaio policistico e obesità approcci non farmacologici.

In patients affected of polycystic ovary syndrome (PCOS), obesity has an high percent of incidence and represents an important factor increasing its clinic evolution, both in metabolic than in reproductive terms. For these patients non pharmacologic treatments aimed at the reduction of body weight, such as diets and physical exercise, represent the first line therapeutic approach. The aim of this review is to analyze the changes in life style and to highlight their efficacy in reducing the negative effects of PCOS on metabolism and reproductivity. Specifically different types of diet have been compared, in health or PCOS women, such as low glycemic index diets, moderate carbohydrate, high protein and low fat diets, very low carbohydrate and high fat diets and, finally, moderate carbohydrate and high monounsaturated fat diets. In the global view of the approach to the disease, different regimens of physical activity and the usefulness of a behavior therapy were also evaluated. Results obtained in health women suggest that diets higher in proteins and lower in carbohydrates are to be preferred to the conventional diet lower in fats and higher in carbohydrates. Anyway other studies are necessary to justify a similar assertion in women with PCOS. At the same way, the optimum regimen of physical exercise for PCOS women is still to be demonstrated.

[Biomechanical overload of the arm: experience with risk prevention in the Fabrian metal-mechanical industry]. / Sovraccarico biomeccanico dell'arto superiore: esperienza di prevenzione del rischio nell'industria metalmeccanica fabrianese.

In the year 2000, the S.P.S.A.L. of Fabriano territorial zone, after a high number of reported cases of CTS in the Orthopedic Unit of the local hospital, started an informative and preventive study program on the risk of biomechanical overloading of the upper extremities. The study was divided in four main steps: 1. Epidemiological study I. A questionnaire assessing professional and pathological anamnesis, musculoskeletal disorders of the upper extremities as well as the professional and non professional risk factors was administered to 448 assembly line workers in seven metal mechanic factories (2000-2001). 2. Lecture for the proposed institution to communicate the results of study I (2001). 3. Evaluation of the trend on professional diseases reported by medical doctors and verified by INAL during the years 1999-2005. 4. Epidemiological study II. The same questionnaire from the first study has been administered to 448 assembly line workers in the same industries selected for the previous investigation (2005). The first study results, presented in the December 2001 lecture from the supervising institution, indicated the departments at risk and showed the necessity of collaboration between specific departments and specialized medical doctors to achieve a rapid diagnosis of work-related diseases. Following our data, the companies have adopted preventative measures, scientific methods of specific risk evaluation as well specific protocols of health survey. Both the reported and the verified diseases showed an increment starting from 2002. The comparison between the two studies demonstrated that the second group had a reduction in the CTS prevalence and in the other work-related upper extremities disorders; a reduction in the repetitive movements, in the use of vibrating instruments and work force; an increment in the number of working pauses and rotation exercises; an increment in the position switch following the appearance of the disorders. However, the results obtained show a fundamental discrepancy: a better trend has been observed in the big companies, but it is still not sufficient in the smaller companies.

Involvement of phosphodiesterase-cGMP-PKG pathway in intracellular Ca2+ oscillations in pituitary GH3 cells.

The present study investigates the potential role of the Ca2+-calmodulin-dependent type I phosphodiesterase (PDE)-cGMP-protein kinase G (PKG) pathway in spontaneous [Ca2+]i oscillations in GH3 cells using fura-2 single cell videoimaging. Vinpocetine (2.5-50 microM), a selective inhibitor of type I PDE, induced a concentration-dependent inhibition of spontaneous [Ca2+]i oscillations in these pituitary cells, and at the same time produced an increase of the intracellular cGMP content. The cell permeable cGMP analog N2,2'-O-dibutyryl-cGMP (dB-cGMP) (1 mM) caused a progressive reduction of the frequency and the amplitude of spontaneous [Ca2+]i oscillations when added to the medium. KT5823 (400 nM), a selective inhibitor of cGMP-dependent protein kinase (PKG), produced an increase of baseline [Ca2+]i and the disappearance of spontaneous [Ca2+]i oscillations. When KT5823 was added before vinpocetine, the PKG inhibitor counteracted the [Ca2+]i lowering effect of the cGMP catabolism inhibitor. Finally, the removal of extracellular Ca2+ or the blockade of L-type voltage-sensitive calcium channels (VSCC) by nimodipine produced a decrease of cytosolic cGMP levels. Collectively, the results of the present study suggest that spontaneous [Ca2+]i oscillations in GH3 cells may be regulated by the activity of type I PDE-cGMP-PKG pathway.

Evidence for altered adipocyte function in polycystic ovary syndrome.

BACKGROUND: Adipocytokines are produced by adipose tissue and have been thought to be related to insulin resistance and other health consequences. We measured leptin, adiponectin, and resistin simultaneously in women with polycystic ovary syndrome (PCOS) and age- and weight-matched controls. Our hypothesis was that these simultaneous measurements would help determine whether adipocytokine secretion is abnormal in PCOS independent of body mass and whether these levels are related to insulin resistance as well as other hormonal changes. METHODS: Fifty-two women with PCOS and 45 normal ovulatory women who were age- and weight-matched were studied. Blood was obtained for adipocytokines (leptin, adiponectin, and resistin) as well as hormonal parameters and markers of insulin resistance as assessed by the quantitative insulin-sensitivity check index. Body mass index (BMI) was stratified into obese, overweight, and normal subgroups for comparisons between PCOS and controls. RESULTS: Adiponectin was lower (P < 0.05) and resistin was higher (P < 0.05) while leptin was similar to matched controls. Breakdown of the groups into subgroups showed a strong body mass relationship for leptin with no changes in resistin although adiponectin was lower in PCOS, even controlling for BMI. In controls, leptin and adiponectin and leptin and resistin correlated (P < 0.05) but not in PCOS. In controls, all adipocytokines correlated with markers of insulin resistance but not in PCOS. CONCLUSIONS: When matched for BMI status, decreased adiponectin in PCOS represent the most marked change. This alteration may be the result of altered adipose tissue distribution and function in PCOS but no correlation with insulin resistance was found.

Role of the Na(+)-Ca2+ and Na(+)-H+ antiporters in prolactin release from anterior pituitary cells in primary culture.

2',4'-dimethylbenzamilamiloride (DMB), a somewhat selective inhibitor of the Na(+)-Ca2+ exchanger, in concentrations of 10, 30 and 100 microM did not produce any significant effect on baseline prolactin release from anterior pituitary cells in primary culture. When prolactin secretion was stimulated by the inhibitor of the Na(+)-K(+)-ATPase, ouabain, that activates the Na(+)-Ca2+ exchanger as a Ca(2+)-influx pathway, DMB was able to produce inhibition of prolactin secretion. 5-(N,N-hexamethylene) amiloride (HMA), another amiloride analog which specifically inhibits the Na(+)-H+ antiporter and has no inhibitory activity on the Na(+)-Ca2+ exchanger, at the concentrations of 0.1, 1 and 10 microM, did not affect basal prolactin release whereas it significantly reduced prolactin release stimulated by thyrotropin releasing hormone (TRH) (1 microM). These results suggest that the Na(+)-Ca2+ antiporter is involved in the process of prolactin release elicited by the inhibition of the Na(+)-K(+)-ATPase whereas the Na(+)-H+ antiporter is involved in the prolactin secretion elicited by TRH.

[Progress of studies promoted by the MODS collaborative group]. / Fase di avanzamento degli studi promossi dal gruppo collaborativo MODS.

In industrialised countries, carpal tunnel syndrome (CTS) is considered an epidemic work-related disease. We have set up the MODS (Malattie Occupazionali Da Sovraccarico biomeccanico, biomechanical overload-related occupational diseases) collaborative group, formed by epidemiologists, ergonomists and occupational physicians to investigate CTS in Italy, applying the methods that epidemiologists commonly use to understand epidemics. Several studies are already ongoing. Two different descriptive studies based on current hospitalisation data are in the reporting phase. A pilot case-control multicentre study (260 cases and 520 controls in 13 centres) is in the final phase of data collection. A longitudinal study on a cohort of 3000 subjects exposed to different risk factors has reached the third year of follow-up. Moreover, a surveillance system has been set up to cover selected districts of the Emilia Romagna region. These studies will generate new information about the prevalence and incidence of CTS in Italy, along with identification of regional, high-risk job titles and work sectors, and the relative influence of non-occupational factors.

Headache and memory impairment. Study on 100 headache patients.

The aim of the present study was to explore the association between memory impairment and primary headache. 100 headache patients (71 females, 29 males, mean age 35.6 +/- 13.8) and 20 healthy subjects (14 females, 6 males, mean age 37.3 +/- 12.1) as control group, were examined: a significant difference between the two groups was found (p < 0.001). The patients were divided into different groups according to the kind of headache, the use of analgesics, the pain side and the illness length: significant differences were found between patients who made a low use of analgesics and the others (p < 0.001); the illness duration also seems to be relevant in the progressive memory impairment, because it strengthens some immunologic and biochemical mechanisms able to favour a progressive mnemonic damage.

Evidence for biventricular involvement in acromegaly: a Doppler echocardiographic study.

To investigate left and right ventricular involvement in acromegaly, 20 patients were studied by Doppler echocardiography. Nine of them had systemic hypertension. Right ventricular free wall thickness was significantly increased in acromegalic patients (8 +/- 2 vs 4 +/- 1 mm; P < 0.001). Left ventricular mass index was augmented both in the whole group and in the subgroup of normotensive acromegalics, as compared with normals (134 +/- 33 and 115 +/- 20 vs 80 +/- 18 g.m-2; P < 0.01). Ejection phase indices were normal in the patient group, while impaired left and right ventricular diastolic filling was found. In fact isovolumic relaxation time was prolonged (118 +/- 21 vs 78 +/- 12 ms; P < 0.001), ratio of early to late mitral (0.9 +/- 0.3 vs 1.8 +/- 0.5; P < 0.001) and tricuspid (1.0 +/- 0.2 vs 1.4 +/- 0.3; P < 0.001) flow velocities were significantly decreased as compared with controls. Superior vena cava flowmetry was also abnormal showing a marked decrease of diastolic filling wave and, consequently, of the ratio between peak diastolic and peak systolic flow velocity. No significant differences were observed between normotensive and hypertensive acromegalics, except for left ventricular mass index (115 +/- 20 vs 156 +/- 31 g.m-2; P < 0.01). These findings indicate that abnormal diastolic filling patterns of transmitral, transtricuspid, and superior vena cava flowmetry suggesting 'impaired relaxation' associated with increased left and right ventricular mass, frequently occur in acromegaly.

Reproductive endocrine disorders in women with primary generalized epilepsy.

It is known that women suffering from temporal lobe epilepsy may frequently present reproductive endocrine disorders (REDs). We hypothesized that a high occurrence of REDs could be found also in primary generalized epilepsy (PGE), and therefore investigated the hormonal and ovarian echographic profiles in 20 PGE female patients of reproductive age. Fourteen reported normal menstrual cycles, while 6 complained of longstanding menstrual irregularities. All but three patients were receiving antiepileptic drug (AED) therapy. In all subjects, the basal levels of gonadotropins, prolactin, and gonadal steroids were assayed. The response of luteinizing hormone (LH) to gonadotropin-releasing hormone was also investigated and ovarian ultrasonographic findings were evaluated. In five of six patients with menstrual problems (25% of the group), a well-defined RED was diagnosed (polycystic ovarian disease in three cases and hypothalamic ovarian failure in two). The 14 patients with normal menstrual cycles showed an elevation of mean basal follicle-stimulating hormone and prolactin, and a blunting of mean LH response. Our results suggest that a high occurrence of REDs may be found also in PGE. We hypothesize that a neurotransmitter dysfunction might be the common pathogenetic mechanism resulting in both REDs and PGE. The hormonal alterations observed in the patients with normal menstrual cycles seem to support our hypothesis. Previous data seem to rule out a possible AED effect accounting for the hormonal findings observed in our series. However, further studies are needed to confirm our preliminary results.

Stimulation of growth hormone release in multiple system atrophy, Parkinson's disease and idiopathic cerebellar ataxia.

Clonidine has been proposed to differentiate multiple system atrophy (MSA) from idiopathic Parkinson's disease (IPD), as it does not increase growth hormone (GH) release in MSA. We studied GH release in response to clonidine in 7 IPD patients, 6 MSA patients, 4 patients affected by idiopathic late-onset cerebellar ataxia (ILOCA) and 8 healthy controls. In addition, we investigated the effects of GH releasing hormone plus arginine (GHRH-Arg) on GH release in the same patients. Both clonidine and GHRH-Arg raised serum GH levels in all groups examined. Clonidine failed to differentiate MSA from IPD and ILOCA. GHRH-Arg showed a lower increase of serum GH in MSA patients than in other groups, even if such difference was not statistically significant. We suggest that stimulation of GH release with GHRH-Arg rather than clonidine could differentiate MSA from IPD and ILOCA, but this hypothesis would need to be confirmed by further investigations.

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.