No abstract

Since 1997 there is an online National Registry of acromegalic patients in Spain (REA). We aimed to study changes in acromegaly treatment and outcomes over the last four decades in Spain. In REA clinical and biochemical data are collected at diagnosis and updated every one to 2 years. We analyzed the first treatment received and the different treatments administered according to decade of diagnosis of acromegaly: prior to 1980, 1980-1989, 1990-1999 and 2000-2009. Surgical cure rates according to pretreatment with long-acting somatostatin receptor ligands (SRLs) were also analyzed. 1,658 patients were included of which 698 had accurate follow-up data. Treatment of acromegaly changed over time. Surgery was the main treatment option (83.8 %) and medical treatment was widely used (74.7 %) both maintained over decades, while radiation therapy declined (62.8, 61.6, 42.2 and 11.9 % over decades, p < 0.001). First treatment type also changed: surgery was the first line option up until the last decade in which medical treatment was preferred (p < 0.001). Radiotherapy was barely used as first treatment. Treatment combinations changed over time (p < 0.001). The most common treatment combination (surgery plus medical therapy), was received by 24.4, 16.4, 25.3 and 56.5 % of patients over decades. Medical treatment alone was performed in 7.3, 6, 7.2 and 14.7 % over decades. Type of medical treatment also changed, SRLs becoming the first medical treatment modality in the last decades, whereas dopamine agonist use declined (p < 0.001). Surgical cure rates improved over decades (21, 21, 36 and 38 %, p = 0.002) and were not influenced by SRL pre-surgical use. Acromegaly treatment has changed in Spain in the last four decades. Surgery has been the main treatment option for decades; however, medical therapy has replaced surgery as first line in the last decade and radiotherapy rates have clearly declined. SRLs are the most used medical treatment.

We analyzed serum 25(OH) cholecalciferol [25(OH)D] levels and factors related to deficiency (<20 ng/ml) or insufficiency (<30 ng/ml) in a cohort of Spanish HIV-infected patients and compared them with an age- and latitude-matched population from another study. We prospectively assessed 25(OH)D deficiency/insufficiency in a cohort of 352 HIV patients during 2009-2010. Predisposing factors were recorded and their relationship to low levels was assessed by logistic regression; a nutritional survey examined intake, nutritional status, and sunlight exposure in a subgroup of 92 patients. We studied the correlation of 25(OH)D with parathyroid hormone (PTH) and alkaline phosphatase. Age-, sex-, and race/ethnicity-adjusted vitamin D deficiency (<20 ng/ml) was 44.0% (95% CI, 38.8-49.4%) and insufficiency (<30 ng/ml) was 71.6% (95% CI, 66.9-76.3). Deficiency was 16.4% more prevalent in our sample than in non-HIV-infected Spaniards. Lower sunlight exposure was the only factor related to lower levels in the lifestyle and nutritional survey (p=0.045). In multiple logistic regression, higher body mass index (BMI), black race/ethnicity, lower seasonal sunlight exposure, men who have sex with men (MSM), and heterosexual transmission categories, efavirenz exposure and lack of HIV viral suppression were independently associated with deficiency/insufficiency. These variables predicted 79% of cases [AUC=0.872 (95% CI, 0.83-0.91)]. Patients receiving protease inhibitors (PIs) [OR 4.0 (95% CI, 1.3-12.3); p=0.014] or NNRTI [OR 3.6 (95% CI, 1.7-11.2); p=0.025] had higher odds of increased PTH levels; this was significant only in 25(OH)D-deficient patients (p=0.004). As in less insolated areas, the prevalence of vitamin D deficiency/insufficiency was high in HIV-infected patients in Spain; among treated patients, levels were higher with PIs than with efavirenz.

Objective: Specific germline mutations in the RET proto-oncogene are correlated with clinical features in multiple endocrine neoplasia type 2A (MEN2A); however, data are scarce regarding differences in clinical profiles dependent on the type of nucleotide and amino acid substitution at the same codon. We aimed to analyse differences in clinical risk profiles and outcomes among different amino acids encoded by codon 634. Design: The study was retrospective and multicentric. Methods: We collected data included in the Spanish Online National Database from patients with MEN2A carrying a RET proto-oncogene mutation on codon 634. The mean follow-up time was 7.6G6.9 years (1-32). Results: Patients (nZ173) from 49 unrelated families were C634Y carriers, and 26 patients from eight different families had C634R mutation. We found higher penetrance of medullary thyroid carcinoma, phaeochromocytoma and hyperparathyroidism (P!0.001, PZ0.007 and P!0.001 respectively) in C634R carriers than in C634Y carriers. The Kaplan-Meier estimate of cumulative lymph node and distant metastases rates showed that these events occurred earlier in patients harbouring the C634R mutation (P!0.001). A multivariate adjusted Cox regression analysis indicated that the C634R mutation was an independent factor for persistent/recurrent disease (hazard ratio, 3.17; 95% CI: 1.66-6.03; P!0.001). Conclusions: Our results suggest that there could be clinical differences caused by different amino acid substitutions at codon 634; specifically, the C634R mutation was associated with a more aggressive MEN2A phenotype than the C634Y mutation.