The claimed ability of non-steroidal antiandrogens to preserve libido and sexual potency is sought as a potential improvement in the palliative management of prostate cancer. A critical issue for the clinical use of these compounds is, however, the reported evidence in the rat of an excessive increase in testosterone concentrations as a consequence of the androgen negative feedback interruption. On the other hand, the recovery of testicular function after long-term inhibition by luteinizing hormone-releasing hormone (LHRH) analogs is also an important concern in view of the proposed use of these compounds for the treatment of several non-malignant conditions. We addressed these issues by studying the long-term endocrine effects induced by the administration of either the non-steroidal antiandrogen nilutamide or the depot preparation of d-Trp6-LHRH in men with prostate cancer. Treatment with the antiandrogen induced a marked increase in gonadotropin levels, LH concentrations rising from a mean (sem) of 17.5±1.6 to a maximum of 56.6±6.9 kU/l (p<0.001), while mean testosterone and 17β estradiol-concentrations rose only by about 50% and 70% over pretreatment values, testosterone levels reaching a plateau after 1 month of treatment. In the subjects treated with the LHRH agonist, 6 months after discontinuation of long-term administration the mean (±sem) LH had risen to 36.9±6.8 IU/l while mean testosterone levels were still as low as 1.7±0.7 and rose only to a maximum of 4.2±1 nmol/l after high-dose human chorionic gonadotropin loadings. We conclude that in elderly men with prostate cancer: (i) stimulation of the entire axis by non-steroidal antiandrogens induces only a mild testosterone increase, the testis being the site of the reduced response; (ii) prolonged inhibition of the pituitary-gonadal axis induced by LHRH agonists may not be reversible at the testicular level.
Andrea Decensi, Rosalba Torrisi, Vincenzo Fontana, Paola Marroni, Paola Padovani, Domenico Guarneri, Francesco Minuto, and Francesco Boccardo
Salvatore Crisafulli, Nicoletta Luxi, Janet Sultana, Andrea Fontana, Federica Spagnolo, Giuseppe Giuffrida, Francesco Ferrau, Daniele Gianfrilli, Alessia Cozzolino, Maria Cristina De Martino, Federico Gatto, Francesco Barone-Adesi, Salvatore Cannavò, and Gianluca Trifirò
Objective: To date, no systematic reviews and meta-analysis on the global epidemiology of acromegaly are available in literature. The aims of this study are to provide a systematic review and a meta-analysis of the global epidemiology of acromegaly and to evaluate the quality of study reporting for the identified studies.
Methods: MEDLINE, EMBASE and The Cochrane Library databases were searched for studies assessing the epidemiology of acromegaly from inception until 31st January 2020. We included original observational studies written in English, reporting acromegaly prevalence and/or incidence for a well-defined geographic area. Two reviewers independently extracted data and performed quality assessments. Prevalence and incidence pooled estimates were derived performing a random-effects meta-analysis.
Results: A total of 32 studies were included in the systematic review, and 22 of them were included in the meta-analysis. The pooled prevalence of acromegaly was 5.9 (95%CI: 4.4-7.9) per 100,000 persons, while the incidence rate (IR) was 0.38 (95%CI: 0.32-0.44) cases per 100,000 person-years. For both prevalence and IR, a considerable between-study heterogeneity was found (I2= 99.3% and 86.0%, respectively). The quality of study reporting was rated as medium for 20 studies and low for 12 studies.
Conclusions: Although the largest amount of heterogeneity was due to the high precision of the studies’ estimates, data source and geographic area could represent relevant study-levels factors which could explain about 50% of the total between-study variability. Large-scale high quality studies on the epidemiology of acromegaly are warranted to help the public health system in making decisions.
Riccardo Bonfanti, Dario Iafusco, Ivana Rabbone, Giacomo Diedenhofen, Carla Bizzarri, Patrizia Ippolita Patera, Petra Reinstadler, Francesco Costantino, Valeria Calcaterra, Lorenzo Iughetti, Silvia Savastio, Anna Favia, Francesca Cardella, Donatella Lo Presti, Ylenia Girtler, Sarah Rabbiosi, Giuseppe D’Annunzio, Angela Zanfardino, Alessia Piscopo, Francesca Casaburo, Letizia Pintomalli, Lucia Russo, Valeria Grasso, Nicola Minuto, Mafalda Mucciolo, Antonio Novelli, Antonella Marucci, Barbara Piccini, Sonia Toni, Francesca Silvestri, Paola Carrera, Andrea Rigamonti, Giulio Frontino, Michela Trada, Davide Tinti, Maurizio Delvecchio, Novella Rapini, Riccardo Schiaffini, Corrado Mammì, Fabrizio Barbetti, and the Diabetes Study Group of ISPED
Transient neonatal diabetes mellitus (TNDM) is caused by activating mutations in ABCC8 and KCNJ11 genes (KATP/TNDM) or by chromosome 6q24 abnormalities (6q24/TNDM). We wanted to assess whether these different genetic aetiologies result in distinct clinical features.
Retrospective analysis of the Italian data set of patients with TNDM.
Clinical features and treatment of 22 KATP/TNDM patients and 12 6q24/TNDM patients were compared.
Fourteen KATP/TNDM probands had a carrier parent with abnormal glucose values, four patients with 6q24 showed macroglossia and/or umbilical hernia. Median age at diabetes onset and birth weight were lower in patients with 6q24 (1 week; −2.27 SD) than those with KATP mutations (4.0 weeks; −1.04 SD) (P = 0.009 and P = 0.007, respectively). Median time to remission was longer in KATP/TNDM than 6q24/TNDM (21.5 weeks vs 12 weeks) (P = 0.002). Two KATP/TNDM patients entered diabetes remission without pharmacological therapy. A proband with the ABCC8/L225P variant previously associated with permanent neonatal diabetes entered 7-year long remission after 1 year of sulfonylurea therapy. Seven diabetic individuals with KATP mutations were successfully treated with sulfonylurea monotherapy; four cases with relapsing 6q24/TNDM were treated with insulin, metformin or combination therapy.
If TNDM is suspected, KATP genes should be analyzed first with the exception of patients with macroglossia and/or umbilical hernia. Remission of diabetes without pharmacological therapy should not preclude genetic analysis. Early treatment with sulfonylurea may induce long-lasting remission of diabetes in patients with KATP mutations associated with PNDM. Adult patients carrying KATP/TNDM mutations respond favourably to sulfonylurea monotherapy.