isolated aldosterone deficiency in two infants mistakes and dilemmas in the diagnosis and treatment of a rare disease

In this article, we describe the clinical picture and follow-up of two children diagnosed as suffering from pseudohypoaldosteronism when they were infants, and it was later recognized as isolated aldosterone deficiency in both. We illustrate the clinical differences between the two patients in terms of hydroelectrolytic balance, laboratory data and growth. In fact, while the growth and hematological parameters of the electrolytes and acid-base balance were normal in the first patient, and also without treatment with fludrocortisone thanks to very high renin activity, in the second patient, this treatment was vitally necessary to maintain normal growth and biochemical data. Despite the absence of a molecular analysis which could have confirmed this diagnosis, we believe that the description of the clinical evolution of these two cases from the moment of the incorrect diagnosis until the correct diagnosis and action taken, could be useful to highlight the extreme clinical variability of this rare disease

Morphology of the toe flexor muscles in older people with toe deformities

Objective: Despite suggestions that atrophied, or weak toe flexor muscles are associated with the formation of toe deformities, there has been little evidence to support this theory. This study aimed to determine whether the size of the toe flexor muscles differed in older people with and without toe deformities. Methods: Forty-four older adults (>60 years) were recruited for the study. Each participant had their feet assessed for the presence of hallux valgus or lesser toe deformities. Intrinsic and extrinsic toe flexor muscles were imaged with an ultrasound system using a standardised protocol. Assessor blinded muscle thickness and cross-sectional area was measured using Image J software. Results: Participants with lesser toe deformities (n=20) were found to have significantly smaller quadratus plantae (p=0.003), flexor digitorum brevis (p=0.013), abductor halluces (p=0.004) and flexor halluces brevis (p=0.005) muscles than the participants without any toe deformities (n=19). Female participants with hallux valgus (n=10) were found to have significantly smaller abductor hallucis (p=0.048) and flexor halluces brevis (p=0.013) muscles than the female participants without any toe deformities (n=10; p<0.05). Conclusion: This is the first study to use ultrasound to investigate the size of the toe flexor muscles in older people with hallux valgus and lesser toe deformities compared to otherwise healthy older adults. The size of the abductor hallucis and flexor hallucis brevis muscles were decreased in participants with hallux valgus whereas the quadratus plantae, flexor digitorum brevis, abductor hallucis and flexor halluces brevis muscles were smaller in those participants with lesser toe deformities

Il coinvolgimento polmonare nelle connettiviti

Con il termine connettiviti si indica un gruppo eterogeneo di malattie reumatiche ad eziologia multifattoriale e patogenesi autoimmune,caratterizzate dall'infiammazione cronica del tessuto connettivo. Considerando la diffusione ubiquitaria di esso, tali malattie sono definite sistemiche e possono interessare qualunque distretto del corpo umano. Le connettiviti che con maggiore frequenza si associano a manifestazioni polmonari sono la Sclerosi sistemica progressiva , l Artrite Reumatoide e il Lupus Eritematoso sistemico. E estremamente importante dinanzi ad una qualunque diagnosi di connettivite, valutare la possibilità di un eventuale coinvolgimento polmonare, attraverso esami radiologici mirati e prove di funzionalità respiratoria. Un approccio di questo genere ovviamente richiede la sensibilizzazione di più competenze mediche e una stretta collaborazione plurispecialistica. Al fine di verificare se quanto riportato dalla letteratura internazionale trova riscontro nella nostra realtà locale e con quali connotazioni specifiche l associazione tra IP e connettiviti si presenta, ho analizzato alcune cartelle cliniche della S.S.D Reumatologia dell'Ospedale S. Croce e Carle di Cuneo presso cui lavoro come Dirigente Medico della Struttura Semplice Dipartimentale di Reumatologia. Lo studio è stato finalizzato ad individuare e descrivere i casi di pazienti affetti da connettivite con coinvolgimento polmonare mettendo in evidenza in modo particolare le caratteristiche funzionali di questi pazienti, il tipo di pattern radiologico attraverso cui la loro patologia si presentava, ed infine la presenza o meno di ipertensione polmonare

Isolated aldosterone deficiency in two infants: Mistakes and dilemmas in the diagnosis and treatment of a rare disease

In this article, we describe the clinical picture and follow-up of two children diagnosed as suffering from pseudohypoaldosteronism when they were infants, and it was later recognized as isolated aldosterone deficiency in both. We illustrate the clinical differences between the two patients in terms of hydroelectrolytic balance, laboratory data and growth. In fact, while the growth and hematological parameters of the electrolytes and acid-base balance were normal in the first patient, and also without treatment with fludrocortisone thanks to very high renin activity, in the second patient, this treatment was vitally necessary to maintain normal growth and biochemical data. Despite the absence of a molecular analysis which could have confirmed this diagnosis, we believe that the description of the clinical evolution of these two cases from the moment of the incorrect diagnosis until the correct diagnosis and action taken, could be useful to highlight the extreme clinical variability of this rare disease

Paediatric and adult-onset male hypogonadism

The hypothalamic–pituitary–gonadal axis is of relevance in many processes related to the development, maturation and ageing of the male. Through this axis, a cascade of coordinated activities is carried out leading to sustained testicular endocrine function, with gonadal testosterone production, as well as exocrine function, with spermatogenesis. Conditions impairing the hypothalamic–pituitary–gonadal axis during paediatric or pubertal life may result in delayed puberty. Late-onset hypogonadism is a clinical condition in the ageing male combining low concentrations of circulating testosterone and specific symptoms associated with impaired hormone production. Testosterone therapy for congenital forms of hypogonadism must be lifelong, whereas testosterone treatment of late-onset hypogonadism remains a matter of debate because of unclear indications for replacement, uncertain efficacy and potential risks. This Primer focuses on a reappraisal of the physiological role of testosterone, with emphasis on the critical interpretation of the hypogonadal conditions throughout the lifespan of the male individual, with the exception of hypogonadal states resulting from congenital disorders of sex development.Fil: Salonia, Andrea. Università Vita-Salute San Raffael; ItaliaFil: Rastrelli, Giulia. University of Florence; ItaliaFil: Hackett, Geoffrey. University of Bedfordshire; Reino UnidoFil: Seminara, Stephanie B.. Massachusetts General Hospital ; Department Of Medicine ; Harvard Medical School; Estados UnidosFil: Huhtaniemi, Ilpo T.. University College London; Estados UnidosFil: Rey, Rodolfo Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; ArgentinaFil: Hellstrom, Wayne J. G.. University of Tulane; Estados UnidosFil: Palmert, Mark R.. University of Toronto; CanadáFil: Corona, Giovanni. University of Florence; ItaliaFil: Dohle, Gert R.. Erasmus University Medical Centre; Países BajosFil: Khera, Mohit. Baylor College of Medicine;Fil: Chan, Yee-Ming. Harvard Medical School; Estados UnidosFil: Maggi, Mario. University of Florence; Itali

Development and First Validation of a Disease Activity Score for Gout

none51OBJECTIVE: To develop a new composite disease activity score for gout and provide its first validation. METHODS: Disease activity has been defined as the ongoing presence of urate deposits that lead to acute arthritis and joint damage. Every measure for each Outcome Measures in Rheumatology core domain was considered. A 3-step approach (factor analysis, linear discriminant analysis, and linear regression) was applied to derive the Gout Activity Score (GAS). Decision to change treatment or 6-month flare count were used as the surrogate criteria of high disease activity. Baseline and 12-month followup data of 446 patients included in the Kick-Off of the Italian Network for Gout cohort were used. Construct- and criterion-related validity were tested. External validation on an independent sample is reported. RESULTS: Factor analysis identified 5 factors: patient-reported outcomes, joint examination, flares, tophi, and serum uric acid (sUA). Discriminant function analysis resulted in a correct classification of 79%. Linear regression analysis identified a first candidate GAS including 12-month flare count, sUA, visual analog scale (VAS) of pain, VAS global activity assessment, swollen and tender joint counts, and a cumulative measure of tophi. Alternative scores were also developed. The developed GAS demonstrated a good correlation with functional disability (criterion validity) and discrimination between patient- and physician-reported measures of active disease (construct validity). The results were reproduced in the external sample. CONCLUSION: This study developed and validated a composite measure of disease activity in gout. Further testing is required to confirm its generalizability, responsiveness, and usefulness in assisting with clinical decisions.noneScirè, Carlo A; Carrara, Greta; Viroli, Cinzia; Cimmino, Marco A.; Taylor, William J.; Manara, Maria; Govoni, Marcello; Salaffi, Fausto; Punzi, Leonardo; Montecucco, Carlomaurizio; Matucci-Cerinic, Marco; Minisola, Giovanni; Ariani, Alarico; Galossi, Alessandra; Lauriti, Ciro; Fracassi, Elena; Idolazzi, Luca; Bardelli, Marco; Selvi, Enrico; Tirri, Enrico; Furini, Federica; Inverardi, Flora; Calabrò, Andrea; Porta, Francesco; Bittelli, Raffaele; Venturino, Francesco; Capsoni, Franco; Prevete, Immacolata; Sebastiani, Giandomenico; Selmi, Carlo; Fabbriciani, Gianluigi; D'Avola, Giovanni; Botticella, Giulia; Serale, Francesca; Seminara, Giulia; D'Alessandro, Giuseppe; Santo, Leonardo; Longato, Lorena; Zaccara, Eleonora; Sinigaglia, Luigi; Atteritano, Marco; Broggini, Marco; Caprioli, Marta; Favero, Marta; Sallì, Salvatore; Scarati, Marco; Parisi, Simone; Malavolta, Nazzarena; Corvaglia, Stefania; Scarpato, Salvatore; Veneto, VittorioScirè, Carlo A; Carrara, Greta; Viroli, Cinzia; Cimmino, Marco A.; Taylor, William J.; Manara, Maria; Govoni, Marcello; Salaffi, Fausto; Punzi, Leonardo; Montecucco, Carlomaurizio; Matucci Cerinic, Marco; Minisola, Giovanni; Ariani, Alarico; Galossi, Alessandra; Lauriti, Ciro; Fracassi, Elena; Idolazzi, Luca; Bardelli, Marco; Selvi, Enrico; Tirri, Enrico; Furini, Federica; Inverardi, Flora; Calabrò, Andrea; Porta, Francesco; Bittelli, Raffaele; Venturino, Francesco; Capsoni, Franco; Prevete, Immacolata; Sebastiani, Giandomenico; Selmi, Carlo; Fabbriciani, Gianluigi; D'Avola, Giovanni; Botticella, Giulia; Serale, Francesca; Seminara, Giulia; D'Alessandro, Giuseppe; Santo, Leonardo; Longato, Lorena; Zaccara, Eleonora; Sinigaglia, Luigi; Atteritano, Marco; Broggini, Marco; Caprioli, Marta; Favero, Marta; Sallì, Salvatore; Scarati, Marco; Parisi, Simone; Malavolta, Nazzarena; Corvaglia, Stefania; Scarpato, Salvatore; Veneto, Vittori

Palbociclib plus endocrine therapy in HER2 negative, hormonal receptor-positive, advanced breast cancer: A real-world experience

Data from 423 human epidermal growth factor receptor 2-negative (HER2 12), hormone receptor-positive (HR+) advanced breast cancer (aBC) patients treated with palbociclib and endocrine therapy (ET) were provided by 35 Italian cancer centers and analyzed for treatment outcomes. Overall, 158 patients were treated in first line and 265 in second/later lines. We observed 19 complete responses and 112 partial responses. The overall response rate (ORR) was 31% (95% confidence interval [CI], 26.6\u201335.4) and clinical benefit was 52.7% (95% CI, 48\u201357.5). ORR was negatively affected by prior exposure to everolimus/exemestane (p = 0.002) and favorably influenced by early line-treatment (p < 0.0001). At 6 months, median progression-free survival was 12 months (95% CI, 8\u201316) and median overall survival was 24 months (95% CI, 17\u201330). More favorable outcomes were associated with palbociclib in early lines, no visceral metastases and no prior everolimus/exemestane. The main toxicity reported was neutropenia. Our results provide further support to the use of palbociclib with ET in HER2 12, HR+ aBC. Differences in outcomes across patients subsets remain largely unexplained