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Effect of desmopressin on ACTH and cortisol secretion in states of ACTH excess.

To assess the ability of desmopressin administration to stimulate ACTH/cortisol secretion in patients with Cushings disease, either before or after surgery, and in patients with other states characterized by ACTH hypersecretion, and to compare the results with those obtained after CRH testing.

Comparison of different regimens of glucocorticoid replacement therapy in patients with hypoadrenalism

Since the optimal glucocorticoid replacement needs to avoid over and under treatment, the adequacy of different daily cortisone acetate (CA) doses was assessed in 34 patients with primary and central hypoadrenalism. The conventional twice CA 37.5 mg/day dose was administered to all patients (A regimen: 25 mg at 07:00 h, 12.5 mg at 15:00 h), while in 2 subgroups of 12 patients the dose was shifted on 2 thrice daily regimens (B: 25 mg at 07:00, 6.25 mg at 12: 00, 6.25 mg at 17:00; C: 12.5 mg, 12.5 mg, 12.5 mg). In other 12 patients the conventional dose was reduced to a thrice 25 mg/day administration (D regimen: 12.5 mg, 6.25 mg, 6.25 mg). In all patients, urinary free cortisol (UFC) excretion and cortisol day curves were evaluated. During the CA 37.5 mg administration, nadir cortisol levels were significantly higher with the thrice daily regimens (143±31 on B and 151±34 nmol/l on C) than with the conventional twice (85±16 nmol/l). Moreover, UFC, morning cortisol levels and mean cortisol day curves were similar in each group. Finally, during D regimen nadir cortisol levels were higher than in A and similar to B and C regimens. No difference in UFC and in cortisol day curves by reducing the CA dose was found. In conclusion, the thrice daily cortisone regimens, in which more physiological cortisol levels are achieved, perform better as replacement therapy. The administration of 25 mg/day CA confirms that replacement therapy is more adequate with a lower dose, particularly in patients with central hypoadrenalism.

Value of buserelin testing in the evaluation of hirsute women.

It has been recently reported that many hirsute women are affected with functional ovarian hyperandrogenism (FOH) - a term that encompasses the heterogeneous polycystic ovary syndrome - and show an abnormal ovarian steroidogenic response to gonadotropin-releasing hormone (Gn-RH) agonists. The aims of the present study were to determine the prevalence of FOH by the assessment of 17-hydroxyprogesterone (17-OHP) response to the Gn-RH agonist buserelin, to correlate these abnormal responses to other parameters suggestive of PCOS, and to assess the possible adrenal origin of hyperandrogenism. Therefore, in 33 consecutive women with hirsutism serum LH, FSH, 17-OHP, dehydroepiandrosterone sulfate (DHEA-S), androstenedione (A), Cortisol levels were evaluated in basal conditions and after the administration of buserelin (0.5 mg sc) and ACTH (tetracosactide 0.25 mg iv). Two patients were affected with a non classic congenital adrenal hyperplasia (CAH) -21OH deficiency. In 5 other women ACTH test caused a rate increase 17-OHP (30-0)/30 min >19 nmol/L/min (0.25±0.03; mean ± SE), suggesting the possible existence of heterozygote non classic CAH-21OH. One patient showed a DHEA-S response to ACTH (from 10.3 to 17.2 μmol/L), which was compatible with late-onset 3ß-Hydroxy-Δ5steroid dehydrogenase deficiency. Out of the 25 patients with normal responsiveness to ACTH, 11 women (group A) showed higher 17-OHP and A levels, in comparison to normal women, both in basal conditions (17-OHP= 4.18±0.72 vs 1.74±0.34 nmol/L, p<0.005; A=11.8±1.2 vs 6.0±0.7 nmol/L, p<0.05) and after buserelin (17-OHP= 15.61±1.31 vs 6.96±0.9 nmol/L; A=19.0±1.9 vs 7.5±0.8 nmol/L; p<0.001). In 6 of these 11 patients basal and buserelin-stimulated LH levels were higher than in normals. The remaining 14 patients (group B) showed normal baseline and buserelin-stimulated 17-OHP and A concentrations. In this group only 2 patients had high basal and stimulated LH levels. An augmented LH/FSH ratio was present in 5 and 1 cases of groups A and B, and polycystic ovaries at ultrasonography were observed in 7 and 8 cases of groups A and B, respectively. It is to note that an abnormal 17-OHP response to buserelin was present also in 3 of the 5 patients with abnormal 17-OHP rise after ACTH test, suggesting an adrenal and ovarian cause of hyperandrogenism. In conclusion, an abnormal response to one or both stimulation test was present in 57% of cases: an adrenal origin of hirsutism was detected in 15%, a combined adrenal and ovarian origin was found in 9% and an ovarian cause was present in 33%. Buserelin testing is an useful means to reveal the presence of FOH.

Epidemiology of HIV‐1 subtypes in an urban area of northern Italy

The distribution of the different subtypes of HIV varies from one region of the world to another. Subtype B is predominant in Europe and the USA, but there has been a gradual increase in non-B subtypes as a result of migration from regions where they are endemic, and this may have important implications for the control of HIV-1. The aim of this study was to assess the prevalence of HIV-1 subtypes in an urban area of northern Italy in the period 1997-2008. Forty-nine (12.2%; 95% CI, 9.00-15.40) of 401 patients investigated carried a non-B subtype, the prevalence of which was 7.7% (95% CI, 4.96-10.44) among native Italians and 55.3% (95% CI, 39.49-71.11) among non-Italians, 1.6% (95% CI, 0.00-3.81) among ex-intravenous drug addicts, 7.6% (95% CI, 1.21-13.99) among homosexual/bisexual men and 20.5% (95% CI, 14.83-26.17) among heterosexuals, 6.8% (95% CI, 3.37-10.23) among Italians infected as a result of sexual contacts in Italy, and 55.0% (95% CI, 33.20-76.80) among Italians infected abroad or by foreign partners. Overall prevalence increased from 2.9% (95% CI, 0.00-6.11) before 1993 to 23.0% (95% CI, 16.31-29.69) in the period 2001-2008. The results demonstrate that there has been an increase in non-B subtypes (especially sexually transmitted infections), particularly among patients infected abroad or by foreign partners.

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 Δ4 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), Δ4 (3.2±0.5 nmol/l) and DHEAS levels (2.4±0.3 μmol/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, Δ? 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.

HBV infection in Italian and non-Italian patients in northern Italy.

Aims: The introduction of HBV vaccination in Italy has reduced the incidence and prevalence of HBV infection. However, increasing immigration from countries in which HBV is endemic has led to a wave of new HBsAg-positive subjects and their clinical impact needs evaluation. We compared the serological, clinical and epidemiological data relating to Italian and non-Italian subjects referred to a hospital in Northern Italy. Study Design: We retrospectively analysed the laboratory and clinical records of 488 subjects, including 107 (21.9%) non-Italians, in order to find data concerning clinical diagnoses, possible routes of infection, anti-HCV and anti-HDV antibodies. Results: The differences in gender distribution and mean age between the non-Italian Research Article British Journal of Medicine & Medical Research, 3(1): 1-12, 2013 2 and Italian patients were statistically significant (p<.001). There were no significant differences in the prevalence of anti-HCV (2.9% vs 4.9%, p=.86) or anti-HDV (4.7% vs 5.0%, p=.89) co-infection, or the presence of HBeAg in chronic infection. There were no differences in the rates of acute (3.3% vs 5.1%; p=.68) or chronic infections (96.7% vs 94.9%; p=.68) infections, but there were statistically significant differences (p<.001) in the rates of prevalent (54.5% vs 85.3%) and incident cases (45.5% vs 14.7%). The differences in the rates of asymptomatic (70.6% vs 34.9%) and symptomatic patients (29.4% vs 65.1%) were also statistically significant (p<.001). The only significant differences in terms of risk factors related to transfusions (0% vs 6.8%; p=.04), and vertical/perinatal transmission (44.1% vs 6.8%; p<.001). Conclusion: The non-Italian HBsAg-positive subjects were mainly women and younger than their Italian counterparts, and had a recent diagnosis. They were predominantly asymptomatic and probably considered themselves healthy and fit to emigrate. Perinatal transmission among non-Italians is still an important risk factor that reflects the epidemiological situation of their countries of origin.

HIV clinical pathway: A new approach to combine guidelines and sustainability of anti-retroviral treatment in Italy

The present article describes the case study of a “real world” HIV practice within the debate concerning the strategic role of Clinical Governance (CG) tools in the management of a National Healthcare System’s sustainability. The study aimed at assessing the impact of a Clinical Pathway (CP) implementation, required by the Regional Healthcare Service, in terms of effectiveness (virological and immunological conditions) and efficiency (economic resources absorption), from the budget holder perspective. Data derived from a multi-centre cohort of patients treated in 6 Hospitals that provided care to approximately 42% of the total HIV+ patients, in Lombardy Region, Italy. Two phases were compared: Pre-CP (2009–2010) vs. Post-CP implementation (2011–2012). All HIV infected adults, observed in the participating hospitals during the study periods, were enrolled and stratified into the 3 categories defined by the Regional CP: first-line, switch for toxicity/other, and switch for failure. The study population was composed of 1,284 patients (Pre-CP phase) and 1,135 patients (Post-CP phase). The results showed that the same level of virological and immunological effectiveness was guaranteed to HIV+ patients: 81.2% of Pre-CP phase population and 83.2% of Post-CP phase population had undetectable HIV-RNA (defined as <50 copies/mL) at 12-month follow up. CD4+ cell counts increased by 28 ± 4 cells/mm3 in Pre-CP Phase and 39 ± 5 cells/mm3 in Post-CP Phase. From an economic point of view, the CP implementation led to a substantial advantage: the mean total costs related to the management of the HIV disease (ART, hospital admission and laboratory tests) decreased (-8.60%) in the Post-CP phase (p-value < 0.0001). Results confirmed that the CP provided appropriateness and quality of care, with a cost reduction for the budget holder.