Alberto Rebora

Significant tumour shrinkage after 12 months of lanreotide Autogel-120 mg treatment given first-line in acromegaly

Objective  To evaluate GH and IGF‐I control and tumour shrinkage in newly diagnosed patients with acromegaly treated first‐line with lanreotide‐Autogel (ATG) 120 mg.

Computed Tomography Colonography in Acromegaly

INTRODUCTION AND AIM Acromegalic patients have an increased risk for the development of colorectal cancer. For this reason, since 1996, screening colonoscopy has been recommended in all patients with acromegaly. The aim of our study was to assess the feasibility and to evaluate the results of computed tomography (CT)-colonography in acromegaly. PATIENTS AND METHODS We examined 23 acromegalic patients with no history of colorectal cancer (11 females and 12 males; age range 18-79 yr; disease duration range 1-15 yr) with CT-colonography. Twenty of them underwent traditional colonoscopy after the CT-colonography. RESULTS CT-colonography examination results were adequate in 17 of 23 cases (73%). CT-colonography found 12 polyps in eight patients, 95% confirmed by traditional colonoscopy. One polyp was a sigmoid cancer, and the diagnosis was confirmed at surgery. There were no polyps found by traditional colonoscopy that CT-colonography was not able to identify. The lesions were located in right colon (two), transversum (three), left colon (five), and sigmoid colon (two). Patient acceptance of the technique was good in 65%, medium in 20%, and poor in 15%. CONCLUSION For the first time we have demonstrated that CT-colonography has the potential ability to replace traditional colonoscopy in acromegalic patients. CT-colonography could be used as a screening modality for colon cancer in acromegaly.

Role of Dopamine Receptors in Normal and Tumoral Pituitary Corticotropic Cells and Adrenal Cells

The recent depiction of dopamine receptors (DRs) in tumors that cause Cushing’s syndrome (CS) has renewed the debate about the dopamine control on pituitary-adrenal axis, and opened interesting new perspectives for medical treatment of CS. The new insights arise from the recent accurate characterization of DR subtypes expression within tumors causing CS, the discovery of new mechanisms, such as the dimerization between DRs and other G-protein coupled receptors (CPCRs), including somatostatin receptors (SSTRs), and the recent availability of new agents targeting these receptor subtypes. Corticotropic adenomas express DR subtype 2 (D2R), together with different SSTR subtypes (ssts), in particular sst5. In vitro, activation of D2R inhibits ACTH release in the majority of cultures of corticotropic cells, whereas, in vivo, dopaminergic agents display an inhibitory effect on cortisol levels in a subset of patients with CS. In animal models the receptor profile can be deeply modulated in specific environmental conditions, that may resemble the different clinical phases of CS. The new insights about DRs and receptor-targeting drugs may offer different approaches for medical treatment of CS: combination therapies with different types of compounds, treatment with novel molecules (hybrid compounds) with a wider spectrum of activity, or even pretreatment manipulation of receptor profile. Finally, recent studies showed that D2R is also significantly expressed in ectopic ACTH-secreting tumors and in both normal and tumoral adrenal tissues. Dopamine-agonists may decrease cortisol levels in a number of these patients, strengthening the current (re)emerging interest in DRs as possible targets for medical treatment of CS.

Leptin, ghrelin, and adiponectin evaluation in transsexual subjects during hormonal treatments.

Gender differences in leptin, ghrelin, and adiponectin levels have been described in a normal population. This is important for understanding differences between males and females in the regulation of food intake, weight gain, body fat distribution, and cardiovascular risk. It is unclear how endogenous and exogenous sex hormones may regulate circulating levels of these factors. Transsexuals during hormonal treatment may represent an ideal model to ascertain the role of exogenous sex hormones on these parameters. In this study, our objective was to evaluate adiponectin, ghrelin, and leptin levels in transsexual subjects during hormone therapy and to compare the results of males and females. Subjects were 26 nondiabetic transsexuals, which included 15 male-to-female (M-to-F, group 3) and 11 female-to-male (F-to-M, group 4) individuals, and 29 age- and BMI-matched controls, which included 15 males (group 1) and 14 females (group 2). Results showed that leptin levels were significantly lower in group 1 compared with group 2 (P = .04) and group 3 (P = .01); no differences were recorded between the other groups. Adiponectin levels were significantly higher in group 3 compared with group 4 (P = .03). No differences were found between the 4 groups for ghrelin levels. In conclusion, our data confirm the sexual dimorphism in serum leptin levels in normal subjects and demonstrate an increase in M-to-F transsexuals. While ghrelin does not show any sexual differences and seems not to be influenced by exogenous sex hormone administration, the lower adiponectin levels in F-to-M transsexuals during treatment confirm that androgens may decrease plasma adiponectin levels. This latter observation suggests that F-to-M transsexual patients could have a higher cardiovascular risk.

Increased mammographic breast density in acromegaly: quantitative and qualitative assessment.

CONTEXT Mammographic density is a strong independent risk factor for breast cancer, whose prevalence in acromegaly is still controversial. OBJECTIVE To compare breast density in premenopausal acromegalic patients and controls and to determine whether density correlated with disease duration, GH, and IGF1 levels. DESIGN, SETTING AND PARTICIPANTS A prospective study involving 30 patients and 60 controls matched for age and body mass index. INTERVENTIONS A quantitative computer-aided mammographic density estimation (MDEST) and a qualitative blind evaluation by two experienced radiologists using the breast imaging reporting and data system (BI-RADS) was performed. Totally, 60 (acromegaly) and 120 (controls) craniocaudal and mediolateral oblique mammograms were evaluated in both patients and controls. MAIN OUTCOME MEASURES Breast density. RESULTS Patients showed a significantly (P<0.01) increased mammographic breast density with both methods (MDEST: 0.33 ± 0.21% and BI-RADS category: 2.81 ± 0.78) in comparison with controls (MDEST: 0.26 ± 0.19% and BI-RADS category: 2.35 ± 0.61). The agreement between the two methods and inter-observer agreement between the two radiologists were excellent (k=0.63 and k=0.85). In patients grouped according to disease activity (17 controlled and 13 uncontrolled) and medical therapy (15 treated and 15 untreated), no differences were found. All these groups had significantly increased mammographic breast density compared with controls (P<0.01). A positive correlation was found between mammographic breast density, IGF1 values and disease duration (r=0.29 and r=0.39), whereas it was not found with GH (r=-0.02). CONCLUSIONS Mammographic breast density in premenopausal acromegalic patients is significantly higher than controls and positively correlated with IGF1 and disease duration.

Biochemical diagnosis and assessment of disease activity in acromegaly: a two-decade experience

The objective of this study is to assess the secretory pattern of GH after Oral Glucose Tolerance Test (OGTT) or day-curve (DC), in relation with IGF-I and to evaluate the influence of therapy on OGTT. A retrospective analysis in 279 OGTTs performed in 93 acromegalic patients in our unit from January 1988 to December 2005, in 77 patients also DC data were retrived. GH concentration was evaluated by 3 different systems (RIA, IRMA and chemiluminescence assays), and IGF-I by two RIAs. About 12% of OGTT samples were discordant with the baseline, while discordance between nadir and 120th minute was much lower (5%), with all discordant values, except one, near the cut-off lines. Correlation between DC and OGTT data was around 0.99 among all values, discordance rate between nadir and minimum DC was much lower than that with mean DC. In almost 80% of cases there was a complete concordance between OGTT and DC results, and in about 30% IGF-I was discordant with GH. Correlation analysis between IGF-I and GH was highest with DC data and lowest with OGTT baseline (T0). Considering different treatments discrepancy rates between GH and IGF-I were comparable. The best GH parameter is the minimum GH DC, although in the clinical practice the evaluation of OGTT GH in association with IGF-I is the most practical approach. In this case, the basal and T120 GH values can replace multiple sampling. Different treatment modalities do not influence the discordance rate between GH and IGF-I.

A minimalist approach to path following among unknown obstacles

The article proposes a feedback control system for path following in presence of obstacles that is an extension of previous work and is made of two components: (i) a sensor-based, real-time model that generates and periodically updates the path on-line in order to avoid both known and unforeseen obstacles, and (ii) a feedback-control model that is capable of driving a unicycle vehicle along the collision free path. The system has some unique characteristics, among which it requires very few computational resources as a consequence of its extreme simplicity.

Le terapie combinate nell’acromegalia: pro e contro

RiassuntoGrazie ai progressi dell’industria, i farmaci oggi a disposizione per la terapia medica dell’acromegalia sono diversificati e hanno permesso, rispetto al passato, e in associazione alla chirurgia, di aumentare la percentuale di pazienti che raggiunge l’obiettivo terapeutico. Tuttavia, nonostante la disponibilità di diverse strategie terapeutiche, ancora una significativa quota di pazienti non raggiunge il controllo di malattia ed è considerata resistente alla monoterapia. Per questo motivo la ricerca sta sviluppando nuove molecole e formulazioni per la cura dell’acromegalia, ma soprattutto si stanno avvicendando in questi ultimi anni anche nuove strategie e schemi innovativi, come le terapia combinate, mirate a migliorare l’outcome della terapia medica stessa. Oltre alla chirurgia, quindi, oggi nella pratica clinica gli analoghi della somatostatina (SSA) rappresentano il farmaco di prima scelta e sono infatti ampiamente utilizzati in prima linea, o come pre-trattamento all’intervento, oltre che nel classico schema adiuvante. I dopamino-agonisti (DA), di largo impiego soprattutto in passato, sono oggi utilizzati in casi selezionati con minima attività di malattia, o in associazione agli SSA. Il pegvisomant, l’unico antagonista del recettore del GH oggi disponibile, indicato in pazienti già sottoposti a intervento chirurgico e che risultino resistenti o intolleranti alla terapia con SSA, permette di normalizzare i livelli di IGF-I in un’alta percentuale di pazienti non controllati, anche questo farmaco, non agendo sul tumore ipofisario, viene frequentemente impiegato in associazione agli SSA. Per pazienti resistenti anche a queste strategie, sono in sviluppo nuovi farmaci (panligandi e molecole chimeriche somatostatina/dopamina) i cui risultati preliminari sembrano essere molto promettenti.