Integrative clinical, hormonal, and molecular data associate with invasiveness in acromegaly: REMAH study.

INTRODUCTION: Growth hormone (GH)-secreting pituitary tumors (GHomas) are the most common acromegaly cause. At diagnosis, most of them are macroadenomas, and up to 56% display cavernous sinus invasion. Biomarker assessment associated with tumor growth and invasion is important to optimize their management. OBJECTIVES: The study aims to identify clinical/hormonal/molecular biomarkers associated with tumor size and invasiveness in GHomas and to analyze the influence of pre-treatment with somatostatin analogs (SSAs) or dopamine agonists (DAs) in key molecular biomarker expression. METHODS: Clinical/analytical/radiological variables were evaluated in 192 patients from the REMAH study (ambispective multicenter post-surgery study of the Spanish Society of Endocrinology and Nutrition). The expression of somatostatin/ghrelin/dopamine system components and key pituitary/proliferation markers was evaluated in GHomas after the first surgery. Univariate/multivariate regression studies were performed to identify association between variables. RESULTS: Eighty percent of patients harbor macroadenomas (63.8% with extrasellar growth). Associations between larger and more invasive GHomas with younger age, visual abnormalities, higher IGF1 levels, extrasellar/suprasellar growth, and/or cavernous sinus invasion were found. Higher GH1 and lower PRL/POMC/CGA/AVPR1B/DRD2T/DRD2L expression levels (P < .05) were associated with tumor invasiveness. Least Absolute Shrinkage and Selection Operator's penalized regression identified combinations of clinical and molecular features with areas under the curve between 0.67 and 0.82. Pre-operative therapy with DA or SSAs did not alter the expression of any of the markers analyzed except for DRD1/AVPR1B (up-regulated with DA) and FSHB/CRHR1 (down-regulated with SSAs). CONCLUSIONS: A specific combination of clinical/analytical/molecular variables was found to be associated with tumor invasiveness and growth capacity in GHomas. Pre-treatment with first-line drugs for acromegaly did not significantly modify the expression of the most relevant biomarkers in our association model. These findings provide valuable insights for risk stratification and personalized management of GHomas.

Can the metabolic control targets established for patients with type 1 diabetes be achieved in clinical practice?

OBJECTIVE: To evaluate the quality of healthcare in patients with type 1 diabetes attended in the Endocrinology and Clinical Nutrition Unit of the Hospital Puerta del Mar in Cadiz (Spain). METHODOLOGY: : The database included in the computer application HP-Doctor used for all patients attended in our unit (admissions, consultations and peripheral centers) was analyzed. All patients with a principal or secondary diagnosis of type 1 diabetes were included. The quality indicators analyzed were selected from the main clinical practice guidelines for these patients. RESULTS: A large cohort of patients with type 1 diabetes (n=489) followed-up from 2005 to 2007 was analyzed. During the study period, the mean glycated hemoglobin level (HbA(1c)) decreased from 7.78% to 7.36%, the percentage of patients with HbA(1c) lower than 7% increased from 24.6% to 27.1% and the percentage patients with a mean HbA(1c) of more than 8% decreased from 42.6% to 38.7%. In 2007, only 35.5% of patients maintained low-density lipoprotein concentrations of less than 100 mg/dl. CONCLUSIONS: Despite the improvement obtained in metabolic control parameters, most of the patients with type 1 diabetes studied showed inadequate glycemic and lipid control.

Differences in thyroid-infiltrating B lymphocytes in patients with Graves' disease: relationship to autoantibody detection.

OBJECTIVE: Thyroid-infiltrating B (Thyr-B) lymphocytes are thought to play an important role in the pathogenic mechanisms underlying Graves' disease. DESIGN AND METHODS: In this study, a broad phenotypic analysis of these cells has been performed in 15 consecutive patients who underwent thyroidectomy. RESULTS: Data reveal the occurrence of two distinct types of Thyr-B cell infiltrates. Type 1 was present in most of the cases (10/15) and consisted of a combination of IgM+ IgD(low to-) B lymphocytes showing features of marginal zone B cells, and IgG+ classic memory B cells. In contrast, in 5 of the 15 cases, a second type of Thyr-B cell infiltrate occurred, exhibiting the profile IgM- IgD- CD44(low to-) CD38++ CD71+ CD95+. This phenotype is highly suggestive of germinal center (GC) B cells, a finding not always anticipated from routine histologic examination. The presence of these ectopic GC was closely associated with the elevated serum level of anti-thyroid peroxidase (TPO), but not with anti-thyrotropin receptor (TSHR), autoantibodies. Moreover, local active anti-thyroglobulin (Tg) antibody secretion was only detected in cultures of type 2 Thyr-B cells. CONCLUSION: These findings indicate that high titers of anti-TPO, but not anti-TSHR antibody, might be associated with intrathyroidal GC development.

Hospital discharge records under-report the prevalence of diabetes in inpatients.

The objective of our study was to estimate the hospital inpatient prevalence of diabetes mellitus in a Spanish tertiary care teaching hospital. We analyzed a cohort of 1036 patients consecutively admitted over a 7-day period to our hospital. We classified this total of hospitalized patients based on information obtained from individual analysis of medical history and values of plasma glucose after fasting, into groups with the following conditions: recognized diabetes, unrecognized diabetes, other hyperglycaemic situations, impaired fasting glucose (IFG) or non diabetes. One hundred and seventy-eight patients were estimated to have diabetes (total prevalence: 17.2%), including 158 patients with recognized diabetes and 20 patients with diabetes unrecognized before admission. Additionally, 25 patients were considered to have other hyperglycaemic situations and 20 patients were estimated to have IFG. The mean age of the diabetic patients was 65+/-13.7 years (50.5% men), and 94.4% had type 2 diabetes. Diabetes disproportionately affects the elderly inpatient, with a prevalence of 30.9% in people older than 64 years. Of the total number of patients with diabetes, only 144 (diabetes prevalence: 13.8%) were registered in hospital discharge records as having diabetes. We conclude that the extent of hospital diabetes prevalence considerably exceeds levels reported in the literature, suggesting that true diabetes prevalence in hospitals could be significantly under-reported, resulting in a serious underestimate of required expenditures.