High Ki-67 expression is associated with prolactin secreting pituitary adenomas.

Pituitary adenomas represent the third most common primary intracranial tumor in neurosurgical practice. To understand the biological behaviour of the pituitary adenomas previous studies have determined the tumor proliferation rate using monoclonal antibodies targeted against the Ki-67 antigen. The aim of this study was to correlate the Ki-67 index with hormonal profiles of pituitary adenomas. The study included 50 pituitary adenomas. For histopathologic evaluation, the sections were stained with routine hematoxylin and eosin method. Additional paraffin sections from each tumor were immunostained using primary antibodies against the following pituitary hormones: somatotropin (STH), prolactin (PRL), adrenocorticotrophic hormone (ACTH), thyroid-stimulating hormone (TSH), follicle-stimulating hormone (FSH), and luteinizing hormone (LH). To detect the expression of Ki-67 we used a mouse anti-human monoclonal antibody (clone K2). The percentage of Ki-67 positive nuclei (Ki-67 labeling index) was assessed by counting approximately 1000 nuclei of the tumor cells at ×400 magnification. Out of the 50 tumor samples, 31 (62%) pituitary adenomas showed proliferative activity, and the proliferation rate was variable in this group. The overall mean Ki-67 labeling index was 1.59 ± 1.47, ranging from 0.3% to 6.6%. In 5 cases, the Ki-67 index was >3%, all of them being prolactinomas. The Ki-67 index was higher in PRL-secreting adenomas (mean ± SD was 3.37 ± 1.80, range 0.9 - 6.6%). Our study provides the evidence that a higher Ki-67 value is associated with pituitary adenomas that secrete PRL (prolactinomas and mixed STH/PRL-secreting adenomas).

Impact of neuropathy on the adherence to diabetes-related self-care activities: a cross-sectional study.

PURPOSE: The purpose of this study was to evaluate the impact of the presence and severity of neuropathy and depression on the patient's adherence to diabetes-related self-care activities (DRSCA) in a cohort of patients with type 2 diabetes mellitus (T2DM). PATIENTS AND METHODS: In this cross-sectional, noninterventional study, 198 patients with T2DM were enrolled according to a population-based, consecutive-case enrollment principle. In all patients, the adherence to DRSCA was evaluated using the Summary of Diabetes Self-Care Activities (SDSCA) questionnaire; a higher SDSCA score is associated with a better adherence. The presence and severity of neuropathy was assessed using the Michigan Neuropathy Screening Instrument (MNSI) and the severity of depression using the Patient Health Questionnaire-9 (PHQ-9). RESULTS: The presence of neuropathy was associated with a decreased SDSCA score (26 points vs 37 points; P<0.001), an increased severe depression prevalence (24.7% vs 4.3%; P<0.001), and an increased PHQ-9 score (12 points vs 7 points; P<0.001). The MNSI score was reverse correlated with SDSCA score (r=-0.527; P<0.001) and positively correlated with PHQ-9 score (r=0.495; P<0.001). The reverse correlation between MNSI score and SDSCA score was present for all the subcomponents of SDSCA questionnaire (diet, exercise, glycemic monitoring, and foot care). CONCLUSION: The presence of neuropathy is associated with decreases in the quality of adherence to DRSCA in patients with T2DM and with increases in the symptomatology of depression. The significant, negative association between the severity of T2DM and the quality of disease self-management points to a possible loop-type relationship between these two components, being possible a reciprocal augmentation with negative consequences on the global management of the disease.

The usefulness of quantifying intraepidermal nerve fibers density in the diagnostic of diabetic peripheral neuropathy: a cross-sectional study.

BACKGROUND: Distal symmetric polyneuropathy (DSPN) is the most common complication of type 2 diabetes mellitus (T2DM) and the most common form of peripheral neuropathy. DSPN increases the risk of foot ulceration up to seven-fold, and is a significant risk factor in more than 60 % of the amputations of the lower limbs in patients with T2DM. The aims of our study were to evaluate the difference in the density of intraepidermal nerve fibers (IENF) in patients with respectively without DSPN, to evaluate the strength of the relationship between the symptomatology of the DSPN and IENF density and to define a cutoff value of the IENF density for the diagnosis of DSPN. METHODS: We enrolled, according to a consecutive, population-based method, 36 patients with T2DM admitted in our Clinic. For all patients, we measured HbA1c, lipid profile, body mass index and we assessed the presence and severity of DSPN using the evaluation of clinical symptoms, nerve conduction velocity and IENF density quantification. RESULTS: The presence of neuropathy was significantly associated with a decreased density of IENF for both the proximal (11.6 vs. 14.9 fibers/mm; p = 0.014) and the distal biopsies (7.2 vs. 8.6 fibers/mm; p = 0.020). The optimal threshold value of IENF density (the point with the maximum sum of specificity and sensitivity), according to our model, was 10.1 fibers/mm. CONCLUSIONS: Skin biopsy followed by IENF density quantification is a valid, reliable tool for the diagnosis of DSPN.

Geographic-Related Differences of Pituitary Adenomas Hormone Profile: Analysis of Two Groups Coming from Southeastern and Eastern Europe.

We compared the immunoprofile of pituitary adenomas from Romania and Moldova. One hundred and eighty cases coming from Romania (94 cases, group 1) and Moldova (86 cases, group 2) were assessed by immunohistochemistry regarding all six basic hormones expressed in pituitary adenomas. Specific differences and similarities were found and stated for both groups. In group 1, 70% of cases were pituitary adenomas positive for one hormone, 13% were plurihormonal, while 17% were negative. In group 2, 50,3% of the cases expressed only one hormone and 12,5% were negative for all hormones. The highest difference was observed for plurihormonal adenomas, found in about 37,2% of cases for group 2 (2.86 times higher for group 2 compared with group 1). A higher incidence of GH-secreting adenomas characterized group "1," while group "2" had the highest percent of LH-secreting adenomas, 55% of cases being positive. Triple association was noticed in 4.25% of cases of group 1 and in 8,13% out of total cases, from group 2. Four-hormone association was found only in group 2, noticed in 15,56% of the cases. The present paper highlights strong evidences of a particular and different immunoprofile of pituitary adenomas coming from Romania and Moldova.

Crosstalk between tumor blood vessels heterogeneity and hormonal profile of pituitary adenomas: evidence and controversies.

AIM: Pituitary adenomas are intracranial tumors with controversial histopathology and heterogeneous clinical behaviour. Angiogenesis and tumor blood vessels' role in pathogenesis, remain one of the great pituitary tumor mysteries. No connection between tumor vessel heterogeneity, hormonal profile and biological behaviour has been reported. We aimed to study pituitary adenomas blood vessels concerning their immature, intermediate or mature phenotype and microvessel density, correlated with immunohistochemical hormonal profile and hormone values in serum and cerebrospinal fluid. MATERIALS AND METHODS: We classified pituitary adenomas according to hormone profile and we applied a double immunostaining highlighting both endothelial and perivascular cells for a more accurate assessment of blood vessel types. RESULTS: Overall microvessel density was found to be highest in growth hormone-secreting adenomas (48.51 ± 12.15) and lowest in prolactinomas (29.15 ± 18.78). When we differentially counted tumor blood vessels we observed a predominance of immature and intermediate blood vessels compared to mature ones. A significant correlation was found between immature tumor blood vessels and tissue prolactin expression, as assessed by immunhistochemistry (p=0.044). A partial correlation was found between serum (p=0.036) and cerebrospinal prolactin values (p=0.006) with immature and intermediate blood vessels. Also, a partial correlation has been reported only between mature blood vessels and cerebrospinal fluid prolactin values (p=0.008). No correlation was obtained for other types of pituitary adenomas. CONCLUSION: Our results suggest a strong involvement of prolactin with a dual role in pituitary adenomas vasculature remodelling by acting both on endothelial and perivascular cells, a finding that could partially explain discrepancies between clinical diagnosis and hormonal profile.