Prolactinomas are the most common pituitary adenomas (approximately 40% of cases), and they represent an important cause of hypogonadism and infertility in both sexes. The magnitude of prolactin (PRL) elevation can be useful in determining the etiology of hyperprolactinemia. Indeed, PRL levels > 250 ng/mL are highly suggestive of the presence of a prolactinoma. In contrast, most patients with stalk dysfunction, drug-induced hyperprolactinemia or systemic diseases present with PRL levels < 100 ng/mL. However, exceptions to these rules are not rare. On the other hand, among patients with macroprolactinomas (MACs), artificially low PRL levels may result from the so-called "hook effect". Patients harboring cystic MACs may also present with a mild PRL elevation. The screening for macroprolactin is mostly indicated for asymptomatic patients and those with apparent idiopathic hyperprolactinemia. Dopamine agonists (DAs) are the treatment of choice for prolactinomas, particularly cabergoline, which is more effective and better tolerated than bromocriptine. After 2 years of successful treatment, DA withdrawal should be considered in all cases of microprolactinomas and in selected cases of MACs. In this publication, the goal of the Neuroendocrinology Department of the Brazilian Society of Endocrinology and Metabolism (SBEM) is to provide a review of the diagnosis and treatment of hyperprolactinemia and prolactinomas, emphasizing controversial issues regarding these topics. This review is based on data published in the literature and the authors' experience.

The occurrence and antimicrobial resistance pattern of Shigella isolates obtained from persons in community and hospital-based studies of diarrhea and matched controls in northeastern Brazil were studied. The isolation rate of Shigella spp. from patients with diarrhea during 1988 to 1993 varied from 4.5% (26 of 575) for the urban community of Gonçalves Dias to 6.7% (12 of 179) and 5.9% (7 of 119) for Hospital Infantil and Hospital Universitário, respectively. Of the 55 Shigella isolates (45 from patients with diarrhea, 8 from controls, and 2 undetermined) 73% (40 of 55) were Shigella flexneri, 16% (9 of 55) were S. sonnei, 7% (4 of 55) were S. boydii, and 4% (2 of 55) were S. dysenteriae. Of 39 S. flexneri strains, over half were resistant to ampicillin, trimethoprim-sulfamethoxazole, or both. Over 64% were resistant to streptomycin, chloramphenicol, and tetracycline. Overall, 82% of all S. flexneri isolates were resistant to four or more antimicrobial agents tested. As elsewhere, in the northeast of Brazil, ampicillin and trimethoprim-sulfamethoxazole are no longer reliable for treatment of S. flexneri infection. Most Shigella strains were resistant to four or more antimicrobial agents. Nalidixic acid was still useful for treatment of infections due to S. flexneri.

Context:The biological significance of GH-induced changes in serum TH concentrations is unknown. It has been suggested that serum free T 4 (FT 4 ) should be targeted at the high-normal range during GH replacement.Objective: Our objective was to evaluate the effects of GH replacement on T 4 biological effects. Hypothesis:If GH modulates thyroxine biological effects, serum FT 4 should be targeted accordingly. Design and Setting:We conducted observational (study 1) and interventional (studies 2 and 3)/outpatient studies.Patients: Thirty-two GH-deficient patients (13 off GH; 22 on L-T 4 ) participated in the study. Interventions:In study 2, levothyroxine was administered to increase FT 4 (Ͼ1.0 ng/dl). In study 3, GH was administered or withdrawn. Main Outcome Measures:We measured FT 4 , total T 3 (TT 3 ), myocardial isovolumic contraction time (ICT), and resting energy expenditure (REE). Results:In study 1, off-GH and on-GH groups had similar FT 4 , but off GH showed lower TT 3 (P Ͻ 0.01) and REE (P ϭ 0.02), higher ICT (P Ͻ 0.05) than on-GH and controls. On GH, ICT and REE correlated only with TT 3 (r ϭ Ϫ0.48; r ϭ 0.58; P Ͻ 0.05). Off GH, ICT correlated only with FT 4 (P Ͻ 0.01). In study 2, off GH, levothyroxine intervention increased FT 4 (P ϭ 0.005) and TT 3 (P ϭ 0.012), decreased ICT (P ϭ 0.006), and increased REE (P ϭ 0.013); ICT and FT 4 changes correlated (r ϭ Ϫ0.72; P ϭ 0.06). On GH, levothyroxine increased FT 4 (P ϭ 0.0002), TT 3 (P ϭ 0.014), and REE (P ϭ 0.10) and decreased ICT (P ϭ 0.049); REE and TT 3 changes correlated (r ϭ 0.60; P ϭ 0.05). In study 3, GH decreased FT 4 , increased TT 3 , decreased ICT, and increased REE (P Ͻ 0.05). REE correlated (P Ͻ 0.05) with IGF-I (r ϭ 0.57) and TT 3 (r ϭ 0.64). ICT correlated only with TT 3 (r ϭ Ϫ0.46). C ENTRAL HYPOTHYROIDISM (CH) is a common disorder in patients with hypothalamic-pituitary disease. It results from decreased stimulation of an otherwise normal thyroid gland by a decreased and/or biologically less active TSH (1, 2). At diagnosis, serum TSH levels in CH may be decreased, normal, or slightly elevated and consistently decline to low/undetectable levels during physiological levothyroxine replacement (3). Thus, both diagnosis and adequacy of levothyroxine replacement in CH have to rely on serum T 4 levels, which show intraindividual variations much narrower than the normal reference range (4). In addition, GH deficiency (GHD) is usually present in patients with CH, and GH replacement is known to change serum concentrations of thyroid hormones (TH), decreasing T 4 and increasing T 3 through peripheral mechanisms (5-9). ConclusionsIn practice, a low serum T 4 in patients with hypothalamicpituitary disease is highly specific, but insensitive, to diagnose CH given the high prevalence of CH in that population. Biochemical markers of peripheral TH action like cholesterol, SHBG, angiotensin-converting enzyme, carboxyl-terminal telopeptide of type I collagen, osteocalcin, and bone ␥-carboxyglutamic acid protein have all been proved insufficiently sensitive and/...

Klebsiella pneumoniae is an important nosocomial pathogen with an extraordinary resistant phenotype due to a combination of acquired resistant-elements and efflux mechanisms. In this study a detailed molecular characterization of 11 K. pneumoniae isolates of clinical origin was carried out. Eleven clinical isolates were tested for their susceptibilities, by disk diffusion and broth microdilution and interpreted according to CLSI guidelines. Efflux activity was determined by measuring the extrusion of ethidium bromide and biofilm formation was assessed following static growth in Müeller-Hinton and minimal media M9 broths at two temperatures and time points. Template DNA from all 11 isolates was extracted and sequenced. The study collection was found to be resistant to several (extended-spectrum beta-lactam) ESBL-type compounds along with several (fluoro)quinolones (FQ). Resistance to tetracycline accounted for 55% of the study collection (n = 6) and three of the 11 isolates were resistance to carbapenems. Genotyping identified blaCTX-M-15 (82%), blaSHV-12 (55%), and blaTEM-1B (45%) ESBL encoding genes and FQ resistance was associated the presence of the oqxAB operon, identified in 10 of the 11 isolates and qnrB gene in one isolate. The polymorphisms detected in the quinolone resistance-determining regions (QRDRs) were associated with isolates of the clonal group CG15. Sequence types (ST) identified were representative of previously described clonal groups including CG258 (n = 7), CG15 (n = 3), and CG147 (n = 1). Plasmid replicon type databases were queried indicating the presence of IncFII and IncFIB replicon types in the majority of the isolates (91%), followed by IncFIA (45%), and IncR (45%). Two of the 11 isolates were found positive for yersiniabactin siderophore-encoding genes. No differences in the ability to efflux ethidium bromide were identified. Biofilm formation was stronger when the isolates were grown under stressed conditions at 37°C for a period up to 96 h. These data confirm the fact that well-recognized clonal groups of K. pneumoniae of importance to human health carries a diverse repertoire of antimicrobial resistance determinants, particularly related to critically important drugs in the ESBL and FQ classes. The capacity of most isolates to form strong biofilms, when stressed under laboratory-simulated conditions, supports the risk to human health associated with nosocomial infections deriving from indwelling medical devices.

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Objective: The diagnosis of subclinical central hypothyroidism in hypothalamic-pituitary patients cannot be established by serum markers of thyroid hormone action. Myocardial function by echocardiography has been shown to reflect thyroid hormone action in primary thyroid dysfunction. We evaluated the performance of echocardiography in diagnosing subclinical central hypothyroidism. Design: Cross-sectional and before and after. Methods: Echocardiography and serum thyroid hormones were assessed in overt primary (nZ20) and central (nZ10) hypothyroidism, subclinical primary hypothyroidism (nZ10), hypothalamic-pituitary disease with normal free thyroxine (FT 4 ; nZ25), and controls (nZ28). Receiver operating characteristic (ROC) curves were generated using overt hypothyroidism patients and selected cut-off values were applied to detect both primary and central subclinical hypothyroidism. After levothyroxine (L-T 4 ) intervention, patients were echocardiographically reevaluated at predefined targets: normal thyrotropin (TSH) in primary hypothyroidism, normal FT 4 in overt central hypothyroidism, and higher than pretreatment FT 4 in echo-defined subclinical central hypothyroidism.

Class II radical hysterectomy has provided appropriated disease control of cervix cancer with low morbidity in our experience. Furthermore, tumor size and compromised vaginal margin were significantly associated to recurrence. These factors and lymph node metastasis were also associated to lower 5-year survival according to our analysis.

The sialic acid-binding immunoglobulin-type lectin Siglec-15 is a promising target to cancer immunotherapy in several tumor types. The present study aimed to investigate Siglec-15 expression in gastric cancer (GC) patient tissue and to evaluate its clinical value. Siglec-15 expression was evaluated by immunohistochemistry with 71 patients. Siglec-15 staining was observed in tumor cells of 53 (74.64%) patients, with significant association with histologic classification and angiolymphatic invasion (p<0.05). Immunohistochemistry analysis also detected Siglec-15 in tumor-associated stroma cells (macrophages/myeloid cells). There was no significant association with outcomes parameters. Siglec-15 expression in well differentiated histological GC tissues and in the tumor microenvironment are potential targets to be further investigated as a novel prognostic factor for GC.