Long-term pasireotide-LAR treatment in the personalized therapy of patients with complex acromegaly: a collection of clinical experiences.

Pasireotide-LAR is recommended as a second-line treatment for patients with acromegaly. Although the effects of pasireotide-LAR have been well characterized in clinical studies, real-practice evidence is scant, especially in the long term and within the individualization of therapy in patients with comorbidities. To provide additional insight on the individualized approach to acromegaly management, six clinical cases of complex acromegaly treated with pasireotide-LAR for more than 5 years were reported. Pasireotide-LAR allowed the normalization of insulin-like growth factor 1 (IGF1) values in all patients and reduced tumour residue volume where present. A good safety profile and long-term tolerability were also reported.

Frequency of brain ventricular enlargement among patients with diabetes mellitus.

AIMS: To determine the prevalence of dilated ventricles and concomitant high blood glucose measures. METHODS: We retrieved blood glucose measures from the emergency department database and selected a subgroup of individuals having both the radiological marker Evans' index (EI) values and blood glucose measures. RESULTS: Out of 1221 consecutive patients submitted to axial Computed Tomography scans, a blood glucose measure was detected in 841 individuals. 176 scans (21 %) showed an EI > 0.30. According to the blood glucose categorization, diabetic patients were 104 (12 %), 25 of them (24 %) were dilated (mean EI 0.33). The age difference between dilated and not-dilated ventricles is about ten years in not-diabetic participants, whereas it is five years in diabetic participants. The age difference between dilated and not-dilated ventricles is about 10 years in diabetic men, whereas it zero in diabetic women. CONCLUSIONS: Pathological ventricular enlargement is more frequent in men and in the elderly. In diabetic patients (especially women), the cerebral ventricles enlarge faster than in non-diabetic individuals. Age, sex, and diabetes may interact in determining how cerebral ventricle size changes over time, especially in diabetic women, making routine brain imaging advisable in these patients after the age of 70 years.

In acromegalic patients the serum levels of interleukin-33 and Resolvin D1 influence skin perfusion of hands: A pilot study.

AIM: Acromegaly is a rare chronic disease, caused by the over-secretion of growth hormone (GH), that creates a pro-inflammatory state, but the exact mechanisms by which GH or insulin-like growth factor 1 (IGF-I) act on inflammatory cells are not fully understood. Aim of the study was to evaluate Interleukin-33 (IL33) and D-series resolvins 1 (RvD1) and the skin perfusion of hands in patients with acromegaly (AP) and healthy controls (HC). METHODS: IL33 and RvD1 have been assessed in 20 AP and 20 HC. Nailfold videocapillaroscopy (NVC) was performed and skin perfusion of hands was assessed by laser speckle contrast analysis (LASCA) in both populations. RESULTS: IL33 was significantly higher in AP compared to HC [73.08 pg/ml (IQR 47.11-100.80 pg/ml) vs 41.5 4 pg/ml (IQR 20.16-55.49 pg/ml), p < 0.05] and RvD1 was significantly lower in AP than HC [36.1 pg/ml (IQR 27.88-66.21 pg/ml) vs 60.01 pg/ml (IQR 46.88-74.69 pg/ml), p < 0.05]. At LASCA, peripheral blood perfusion (PBP) was significantly lower in AP compared to HC [56.66 pU (IQR 46.29-65.44 pU) vs 87 pU (IQR 80-98 pU), p < 0.001]. The median values of ROI1 and ROI3 were significantly lower in AP compared to HC [112.81 pU (IQR 83.36-121.69 pU) vs 131 pU (IQR 108-135 pU), p < 0.05] and [59.78 pU (IQR 46.84-79.75 pU) vs 85 pU (IQR 78-98 pU), p < 0.05], respectively. The proximal-distal gradient (PDG) was observed in 8 of 20 (40 %) AP. CONCLUSION: Serum IL33 is higher in AP compared to HC; conversely, RvD1 is lower in AP compared to HC. Reduction of PBP of hands was present in AP compared to HC, probably due to endothelial dysfunction.

Partial response to first generation SSA guides the choice and predict the outcome of second line therapy in acromegaly.

INTRODUCTION: Treatment of acromegaly resistant to first generation somatostatin analogues (first gen-SSA) is often difficult. We aimed to investigate the role of partial response and resistance to first gen-SSA in the choice of second line treatments and their outcomes. PATIENTS AND METHODS: A retrospective and multicenter study was conducted on 100 SSA-resistant acromegaly patients and treated with Pasireotide Lar (Pasi-Lar), Peg-V in monotherapy (m-Peg-V) or in combination with first gen-SSA (c-Peg-V). RESULTS: Thirty-three patients (33%) were treated with m-Peg-V, 36 (36%) with c-Peg-V and 31 with Pasi-Lar (31%). According to logistic regression, m-Peg-V was chosen in older patients (p = 0.01) and with not-invasive adenomas (p = 0.009), c-Peg-V therapy in younger patients (p = 0.001), with invasive adenomas (p = 0.02), Pasi-Lar was in invasive adenomas (p = 0.01) and in patients partially responsive to first-gen SSA (p = 0.01). At the last follow-up, 68 patients (68%) reached the acromegaly control: 22 with m-Peg-V (32.4%), 23 with c-Peg-V (33.8%) and 23 with Pasi-Lar (33.8%). Patients non-responsive to c-Peg-V had higher IGF-I levels (median 3.2 x ULN, IQR: 1.6, p < 0.001) and required higher Peg-V dosage (median 30 mg/daily IQR: 10, p = 0.002) as compared to responsive patients (median IGF-I x ULN: 2.1 IQR: 1.4; median Peg-V dosage 20 mg/daily IQR: 10). All patients responsive to Pasi-Lar were partially responsive to first gen-SSAs (p = 0.02). CONCLUSION: Our data showed that c-Peg-V and Pasi-Lar are chosen for the treatment of invasive tumors. The partial response to first gen-SSA seems to be the main determinant for the choice of Pasi-Lar and positively predicts the treatment outcome.

A New Device for Remote Monitoring of Vital Parameters in Acromegalic Patients: Pilot Study.

INTRODUCTION: Acromegaly is a rare disease that results from growth hormone (GH) excess. Diabetes mellitus, hypertension,cardiomyopathy, and obstructive sleep apnoea syndrome( OSAS) are frequent complications. AIM OF THE STUDY: Identify a useful system to obtain a reliable remote monitoring of glucose and the most important vital parameters in the acromegalic subjects. PATIENTS AND METHODS: Sixteen acromegalic patients (from 30 to 73 years old) were enrolled. We provided health monitor devices to the patients for continuous acquisition of physiological signals including twelve-lead electrocardiography (EKG) and nocturnal SpO2. At the same time, we applied on the same patients the blinded continuous glucose monitoring system(CGMS). RESULTS: The lowest saturation peaks at night (<80%) were achieved in patients with a known diagnosis of OSAS. A positive correlation was demonstrated between the lowest oxygen saturation values and the CGM peaks (pV <0,0001) and between the average values of oxygen saturation and CGM (pV<0,0003). Patients with a previous diagnosis of OSAS, obtained by polysomnography, showed on the multiparametric monitor recordings superimposable to their known condition. Instead we noticed a discordance in the two EKG recording: the wireless mode showed an irregular rhythm in 5/16 patients, which was not confirmed by the recording mode with cables. CONCLUSION: The health monitor device associated with CGM may be a new useful and versatile tool for fragile patients who can self-manage remote monitoring, and for physicians who can obtain real-time information for the clinical and therapeutic management of patients. It is also a useful tool for the follow-up of patients with OSAS. Moreover, once the interference of the OSAS is excluded, the CGM allows us to obtain a more reliable and accurate diagnosis of DM.

The prevalence of secondary neoplasms in acromegalic patients: possible preventive and/or protective role of metformin.

BACKGROUND: Acromegaly is a rare disease due to chronic growth hormone (GH) excess and the consequent increase in insulin-like growth factor-1 (IGF-1) levels. Both GH and IGF-1 play a role in intermediate metabolism affecting glucose homeostasis. The association between hyperinsulinemia/impaired glucose tolerance and an increased risk of cancer has been clarified. Insulin has a mitogenic effect through its interaction with the IGF-1 receptor (IGF-1R) that also binds IGF-1. On the other hand, metformin, an anti-hyperglycemic drug that decreases serum levels of insulin and IGF-1, could have a protective role in the treatment of endocrine tumors. METHODS: A retrospective, observational, multicenter study in 197 acromegalic patients, receiving/not receiving metformin, was performed to assess whether the prevalence of neoplasms might be correlated with insulin resistance and could eventually be modified by metformin treatment. RESULTS: In general, the occurrence of secondary neoplasia among our patients was significantly (pV = 0.035) associated with a positive family history of malignancy and with disease duration; a trend towards significance was observed in patients aged > 50 years. Acromegalic subjects who had undergone surgery showed a lower probability of developing a malignant tumor, whereas a higher prevalence of malignancies was observed in obese patients. No significant statistical difference was found when comparing metformin-treated or -untreated subjects for the presence of a second tumor. More interestingly, a trend towards statistical significance (pV = 0.065) was demonstrated in the metformin-treated group for the onset of a benign neoplasm. CONCLUSION: Metformin could act directly on tumor cell metabolism and may have an adjuvant role in benign lesion progression.

Continuous Glucose Monitoring System in Acromegalic Patients: Possible Role in the Assessment of Glycemia Control.

BACKGROUND: Acromegaly is characterized by an insulin resistance condition. There is a significant difference between the different types of therapy in relation to the glycometabolic framework. The blinded continuous glucose monitoring system (CGMS), throughout a period of maximum 6 days for a total of 288 glycemic registrations per day, identifies glycemic excursions and could constitute a valid device to understand the 24-hour glycemic profiles. AIM OF THE STUDY: To compare the oral glucose tolerance test (OGTT) and CGMS methods in acromegalic patients to evaluate their glycemic profiles, in relation to different treatments for acromegaly. METHODS: Thirty-five acromegalic patients were divided into 18 somatostatin analogs (SSA), 9 pegvisomant, and 8 successfully surgically treated. A 72-hour CGM was performed and, immediately after, an OGTT. RESULTS: Results obtained from OGTT: 11/35 impaired fasting glucose, 6/35 impaired glucose tolerance, and 4/35 diabetes mellitus. A positive significant correlation was demonstrated between the OGTT peak and CGM peak in all of the patients, CGM peak of patients treated with SSA and those surgically treated, OGTT average and CGM area under concentration-time curve (AUC) for hyperglycemia of patients treated with SSA and those surgically treated, and CGM AUC for hyperglycemia of patients treated with SSA and those surgically treated. CONCLUSIONS: Our results show a significantly higher response in terms of mean and peak OGTT in patients treated with SSA, both compared to the CGM study, and compared to the group of patients receiving pegvisomant. The CGM system could represent an instrument for the evaluation of the glycemic trend of acromegalic patients.

Infundibuloneurohypophysitis associated with autoimmune thrombocytopenia and chiasmal syndrome: a case report.

Lymphocytic hypophysitis is an uncommon autoimmune disease. It may involve the adenohypophysis, neurohypophysis and pituitary stalk. It is most often encountered in pregnant women. Its diagnosis and management pose a significant challenge, as its clinical manifestation and appearance in imaging studies are difficult to distinguish from more common lesion of the sellar region (e.g., pituitary adenomas). We present the case of a 42-year-old man who presented with a chiasmatic syndrome, diabetes insipidus and hypopituitarism. Brain MRI documented a sellar lesion with suprasellar extension and optic chiasm dislocation. He underwent an endoscopic endonasal transsphenoidal resection of the mass. Histopathological examination revealed a lymphocytic hypophysitis. Visual symptoms improved dramatically postoperatively with permanent diabetes insipidus and panhypopituitarism. We discuss the indication for surgical resection in patients with inflammatory lesions extending to the suprasellar region associated with visual impairment.

Breg Cells in Celiac Disease Isolated or Associated to Hashimoto's Thyroiditis.

Hashimoto's thyroiditis (HT) may occur associated with celiac disease (CD). Regulatory B cells (Breg) subsets have been shown to play a significant role in autoimmune processes. Therefore, we have characterized their distribution in the peripheral blood obtained from 10 patients with isolated HT, 10 patients with HT + CD, 9 patients with isolated CD, and 9 healthy donors (HD). Th17 cells were significantly increased in patients with HT and in patients bearing both HT and CD, while patients with isolated CD exhibited a lower percentage of Th17, as compared with healthy donors. CD24hiCD38hi Breg cells were significantly higher in patients with HT + CD and in patients with isolated CD as compared to both HD patients and patients with isolated HT (p = 0.0010). On the contrary, Breg memory phenotypes (CD24hiCD38- and CD24hiCD27+) significantly decreased in patients with HT + CD as compared with the isolated disorders. Following CpG oligodeoxynucleotide stimulation, IL-10+ CD24hiCD38hi Breg cells were similar in all groups of patients, despite these cells would have been higher in CD patients. In conclusion, celiac disease, isolated and even more when associated with HT, determines a peculiar behavior of Breg cells which are increased in number but possibly functionally defective. Furthermore, the association CD + HT was characterized by a reduction of Breg memory subsets as compared with the isolated disorders. The behavior of Th17 subset in patients with celiac disease associated with HT might have been sensitive to the effect of long-lasting GFD, and it is essentially determined by the presence of thyroid autoimmunity.

Long-term treatment of somatostatin analog-refractory growth hormone-secreting pituitary tumors with pegvisomant alone or combined with long-acting somatostatin analogs: a retrospective analysis of clinical practice and outcomes.

BACKGROUND: Pegvisomant (PEGV) is widely used, alone or with somatostatin analogs (SSA), for GH-secreting pituitary tumors poorly controlled by SSAs alone. No information is available on specific indications for or relative efficacies of PEGV+SSA versus PEGV monotherapy. Aim of our study was to characterize real-life clinical use of PEGV vs. PEGV+SSA for SSA-resistant acromegaly (patient selection, long-term outcomes, adverse event rates, doses required to achieve control). METHODS: A retrospective analysis of data collected in 2005-2010 in five hospital-based endocrinology centers in Rome was performed. Sixty-two adult acromegaly patients treated ≥6 months with PEGV (Group 1, n=35) or PEGV+SSA (Group 2, n=27) after unsuccessful maximal-dose SSA monotherapy (≥12 months) were enroled. Groups were compared in terms of clinical/biochemical characteristics at diagnosis and before PEGV or PEGV+SSA was started (baseline) and end-of-follow-up outcomes (IGF-I levels, adverse event rates, final PEGV doses). RESULTS: Group 2 showed higher IGF-I and GH levels and sleep apnea rates, higher rates residual tumor tissue at baseline, more substantial responses to SSA monotherapy and worse outcomes (IGF-I normalization rates, final IGF-I levels). Tumor growth and hepatotoxicity events were rare in both groups. Final daily PEGV doses were similar and significantly increased with treatment duration in both groups. CONCLUSIONS: PEGV and PEGV+SSA are safe, effective solutions for managing SSA-refractory acromegaly. PEGV+SSA tends to be used for more aggressive disease associated with detectable tumor tissue. With both regimens, ongoing monitoring of responses is important since PEGV doses needed to maintain IGF-I control are likely to increase over time.

Enhancing treatment of obesity by using a distracting mini-meal: a new approach to an old problem.

OBJECTIVE: The management of obesity, apart from exercise, mainly involves a calorie restriction regimen. A pharmaceutical treatment is often used to improve patient compliance and diet effectiveness, although several side-effects have previously been described. To improve patient compliance and diet effectiveness without incurring unpleasant side-effects, we evaluated whether a distracting mini-meal can physiologically decrease the absorption of fats and carbohydrates. DESIGN: Two minutes before each of the three meals consumed daily, 32 obese patients were treated with a distracting mini-meal, 32 with metformin, and 32 with placebo. At baseline and after 1, 3, and 6 months of treatment, body weight, body mass index, waist circumference, fasting/post-prandial insulinaemia and glycaemia, homeostasis model assessment-index, triacylglycerols, and total cholesterol were evaluated. RESULTS: All patients showed good compliance. With the exception of post-prandial glycaemia, a significant reduction in all parameters was documented in every group, albeit the greater variation was observed in patients treated with a distracting mini-meal or metformin. No one showed noteworthy side-effects. CONCLUSIONS: Our study focuses on a distracting mini-meal that could become a useful tool in enhancing weight loss. The beneficial effect of a distracting meal on insulin resistance, glucose, and lipid metabolism suggest its possible use to prevent or mitigate obesity-related disorders.

Type 1 diabetes mellitus and celiac disease: endothelial dysfunction.

Many reports indicate a hypercoagulative state in diabetes mellitus as result of endothelial damage. Experimental evidence suggests that a metabolic derangement triggers a cascade of biochemical events that lead to vascular dysfunction. The net effect is to convert the endothelium from thromboresistant to thrombogenic surface. In literature, a strong association between type 1 diabetes mellitus (DM1) and celiac disease (CD) has been reported. We do not have information about the hemostatic system in these associated conditions. Our study aims at evaluating whether the presence of CD in a group of DM1 patients is associated with a different expression of some hemostatic factors and with a different manifestation and/or progression of microvascular complications of DM1 in comparison with patients with only diabetes. Ninety-four adult DM1 patients were enrolled in the study and subsequently screened for CD. Anti-endomysial antibodies (EMA) were positive in 13 of 94 DM1 patients (13.8%). CD diagnosis was confirmed by histology and organ culture. The mean age and duration of DM1 of patients also affected by CD were similar to those of only diabetic patients, but the metabolic control and the hemocoagulative parameters were significantly different between the two groups: DM1 patients also affected by CD presented significantly lower concentrations of glycosylated hemoglobin (HbA1c) (P < 0.05), cholesterol (P < 0.001), triglycerides (P < 0.001), factor VII antigen (FVII:ag) (P < 0.005), factor VII coagulant activity (FVII:c) (P < 0.05), and prothrombin degradation fragments (F1+2) (P < 0.001), as well as higher values of activated C protein (APC) (<0.001). No retinal abnormalities and no signs of renal damage were observed in DM1 patients also affected by CD. Our results suggest a potential protective role of CD in the prothrombotic state of DM1.

Characterization of pigments and ligands in a wall painting fragment from Liternum archaeological park (Italy).

Spectroscopic and MS techniques were used to characterize the pigments and the composition of polar and nonpolar binders of a stray wall painting fragment from Liternum (Italy) archaeological excavation. X-ray fluorescence and diffraction analysis of the decorations indicated mainly the presence of calcite, quartz, hematite, cinnabar, and cuprorivaite. Infrared spectroscopy, GC coupled to flame-ionization detector, and MS analysis of the polar and nonpolar components extracted from paint layers from three different color regions revealed the presence of free amino acids, sugars, and fatty acids. Interestingly, LC-MS shotgun analysis of the red painting region showed the presence of αS1-casein of buffalo origin. Compared to our previous results from Pompeii's wall paintings, even though the Liternum painting mixture contained also binders of animal origin, the data strongly suggest that in both cases a tempera painting technique was utilized.

Atypical celiac disease as cause of increased need for thyroxine: a systematic study.

OBJECTIVE: Replacement T4 dose in hypothyroid patients bearing both chronic autoimmune thyroiditis and atypical celiac disease (CD) has been analyzed. DESIGN: Replacement T4 dose has been analyzed in 35 hypothyroid patients with Hashimoto's thyroiditis (HT) and atypical CD, as defined by the American Gastroenterological Association. We have evaluated the ability of the same dose of T4 to reach target TSH in 21 patients before and during gluten-free diet (GFD). In the remaining 14 patients, noncompliant with GFD, we analyzed replacement T4 dose and compared it with that in a similar group consisting of 68 patients with hypothyroid HT but no evidence of celiac sprue or other conditions interfering with T4 absorption. RESULTS: In patients with isolated HT, the desired serum TSH (median=1.02 mU/liter) was reached in all patients after 5±2 months of treatment at a median T4 dose of 1.31 µg/kg·d. After a similar period and dose of T4, higher levels of TSH (median=4.20 mU/liter) were observed in patients with HT and CD. In 21 CD patients, target TSH (median TSH=1.25 mU/liter) has been attained after 11±3 months of GFD without increasing T4 dose (1.32 µg/kg·d). In the remaining 14 patients, who were noncompliant with GFD, target TSH has also been achieved but at a higher T4 dose (median=1.96 µg/kg·d; +49%; P=0.0002) than in hypothyroid patients without CD. CONCLUSIONS: Atypical CD increases the need for T4. The effect was reversed by GFD or by increasing T4 dose. Malabsorption of T4 may provide the opportunity to detect CD that was overlooked until the patients were put under T4 therapy.

Increased expression of urokinase plasminogen activator and its cognate receptor in human seminomas.

BACKGROUND: The urokinase plasminogen activating system (uPAS) is implicated in neoplastic progression and high tissue levels of uPAS components correlate with a poor prognosis in different human cancers. Despite that, relative few studies are available on the expression and function of the uPAS components in human seminomas. In the present study we characterized the expression of the urokinase plasminogen activator (uPA), its cognate receptor (uPAR) and the uPA inhibitors PAI-1 and PAI-2 in normal human testis and seminomas. METHODS: The expression of the above genes was evaluated by means of quantitative RT-PCR, western blot, zymographic analysis and immunohistochemistry. RESULTS: Quantitative RT-PCR analysis of 14 seminomas demonstrated that uPA and uPAR mRNAs were, with respect to control tissues, increased in tumor tissues by 3.80 +/- 0.74 (p < 0.01) and 6.25 +/- 1.18 (p < 0.01) fold, respectively. On the other hand, PAI-1 mRNA level was unchanged (1.02 +/- 0.24 fold), while that of PAI-2 was significantly reduced to 0.34 +/- 0.18 (p < 0.01) fold. Western blot experiments performed with protein extracts of three seminomas and normal tissues from the same patients showed that uPA protein levels were low or undetectable in normal tissues and induced in tumor tissues. On the same samples, zymographic analysis demonstrated increased uPA activity in tumor tissue extracts. Western blot experiments showed that also the uPAR protein was increased in tumor tissues by 1.83 +/- 0.15 fold (p < 0.01). The increased expression of uPA and uPAR was further confirmed by immunohistochemical staining performed in 10 seminomas and autologous uninvolved peritumoral tissues. Finally, variation in the mRNA level of PAI-1 significantly correlated with tumor size. CONCLUSIONS: We demonstrated the increased expression of uPA and uPAR in human seminomas with respect to normal testis tissues, which may be relevant in testicular cancer progression.

The eligibility of MIVA approach in thyroid surgery.

INTRODUCTION: Thyroid size, by preoperative ultrasound evaluation, is a very important criterion of minimally invasive video-assisted thyroidectomy (MIVAT) exclusion because the working space provided by the technique is limited. The aim of this work is to verify the suitability of MIVAT and its applicability in clinical practice in patients with a thyroid volume up to 50 ml. METHODS: From January 2003 to February 2006, 33 patients were selected for MIVAT. A completely gas-less procedure was carried out through a central skin incision performed "high" between the cricoid and jugular notch. RESULTS: The skin incision performed was from 20 to 35 mm (mean 24.88 mm +/- 2.74) for different thyroid sizes. We obtained in all cases excellent results about patients cure rate and comfort, few cases of postoperative pain, and attractive cosmetic results. CONCLUSION: In this study, we demonstrated that the MIVAT, for thyroids up to 50 ml in volume, is feasible and safe. This procedure allows more patients, who would have been excluded before, to take advantage of this minimally invasive approach with good cosmetic results, highly regarded by young female patients, and reduced paresthetic consequences.

The size criteria in minimally invasive video-assisted thyroidectomy.

BACKGROUND: Thyroid size is a very important criteria of MIVAT exclusion because the working space provided by the technique is limited. The aim of this work has been to verify the suitability of MIVAT and its applicability in clinical practice, not only in patients with a thyroid volume up to 25 ml but also in patients with a thyroid volume included from 25 to 50 ml. METHODS: From January 2003 to February 2006, 33 patients have been selected for MIVAT. A completely gasless procedure was carried out through a central 20 to 35 mm skin incision performed "high" between the cricoid and jugular notch. RESULTS: The patients were separated in 2 groups. The first group (less than 25 ml) included 23 patients, the second group (from 25 to 50 ml) included 10 patients. The skin incision performed was from 20 to 25 mm (mean 23.61 mm +/- 1.83) long in the first group and from 25 to 35 mm (mean 27.8 mm +/- 2.20) long in the second one; this difference is significant (t test p < 0.001). CONCLUSION: Our study suggest that the MIVAT using for thyroids bigger than 25 ml and up to 50 ml in volume is feasible and safe. This way allows more patients, excluded before, to take the advantages of minimally invasive approach.

The minimally invasive open video-assisted approach in surgical thyroid diseases.

BACKGROUND: The targets of minimally invasive surgery (MIVA) could be summarised by: achievement of the same results as those obtained with traditional surgery, less trauma, better post-operative course, early discharge from hospital and improved cosmetic results. The minimally invasive techniques in thyroid surgery can be described as either endoscopic "pure" approach (completely closed approach with or without CO2 insufflation), or "open approach" with central neck mini-incision or "open video-assisted approach". Traditionally, open thyroidectomy requires a 6 to 8 cm, or bigger, transverse wound on the lower neck. The minimally invasive approach wound is much shorter (1.5 cm for small nodules, up to 2-3 cm for the largest ones, in respect of the exclusion criteria) upon the suprasternal notch. Patients also experience much less pain after MIVA surgery than after conventional thyroidectomy. This is due to less dissection and destruction of tissues. Pathologies treated are mainly nodular goiter; the only kind of thyroid cancer which may be approached with endoscopic surgery is a small differentiated carcinoma without lymph node involvement. The patients were considered eligible for MIVA hemithyroidectomy and thyroidectomy on the basis of some criteria, such as gland volume and the kind of disease. In our experience we have chosen the minimally invasive open video-assisted approach of Miccoli et al. (2002). The aim of this work was to verify the suitability of the technique and the applicability in clinical practice. METHODS: A completely gasless procedure was carried out through a 15-30 mm central incision about 20 mm above the sternal notch. Dissection was mainly performed under endoscopic vision using conventional endoscopic instruments. The video aided group included 11 patients. All patients were women with a average age of 54. RESULTS: We performed thyroidectomy in 8 cases and hemithyroidectomy in 3 cases. The operative average time has been 170 minutes. CONCLUSION: Nowadays this minimally invasive surgery, in selected patients, clearly demonstrates excellent results regarding patient cure rate and comfort, with shorter hospital stay, reduced postoperative pain and most attractive cosmetic results.

The long-term efficacy of conventional radiotherapy in patients with GH-secreting pituitary adenomas.

OBJECTIVE: To assess the long-term efficacy and safety of conventional radiotherapy (RT) in the control of acromegaly according to recent stringent criteria of cure. DESIGN: A retrospective longitudinal study. PATIENTS AND METHODS: Forty-seven patients with active acromegaly were treated with conventional RT between 1982 and 1994. All patients were first operated on and successively irradiated at a dose of 45-50 Gy in 25-28 fractions for persistent (n = 40) or recurrent (n = 7) disease. MEASUREMENTS: Long-term GH/IGF-I secretion and local tumour control were evaluated regularly, and possible side-effects were searched for systematically, especially in terms of secondary endocrine dysfunction. Biochemical cure of acromegaly was defined by glucose-suppressed plasma GH levels below 1 microg/l during an oral glucose tolerance test (OGTT) and normal age-corrected IGF-I values. RESULTS: The 5-, 10- and 15-year overall survival rates were 98%, 95% and 93%, respectively. Suppression of GH during OGTT was seen in 9% of patients at 2 years, 29% at 5 years, 52% at 10 years, and 77% at 15 years. Age-corrected IGF-I levels were normal in 8% of patients 2 years after RT, and this proportion increased to 23%, 42% and 61% after 5, 10 and 15 years, respectively. Normalization of GH/IGF-I mainly depended on pre-RT levels. Local tumour control was 95% at 5, 10 and 15 years after treatment. Late toxicity was mainly represented by progressive hypopituitarism, which was present in 33% of patients at baseline and increased to 57%, 78% and in 85% of patients at 5 10 and 15 years after RT, respectively. CONCLUSION: Conventional RT is effective in the long-term control of GH-secreting pituitary adenomas, although with a high prevalence of progressive hypopituitarism. At present, it remains a suitable option in acromegalic patients uncontrolled by surgery or medical therapy.