Julia Fernanda Semmelmann Pereira-Lima

Immunohistochemical expression of aromatase and estrogen, androgen and progesterone receptors in normal and neoplastic human meningeal cells

Evidence suggests that sex hormones may play a role in the tumorigenesis of meningiomas, and studies have demonstrated the expression of hormone receptors in these tumors. Aromatase expression has been detected in several normal tissues, including neurons in the CNS, and tumor tissues. We aim to assess the expression of aromatase (ARO) and of progesterone receptor (PR), estrogen receptor (ER) and androgen receptor (AR) in both normal and neoplastic meningeal cells. A cross‐sectional study was conducted with 126 patients diagnosed with meningioma (97 women and 29 men; mean age, 53.6 years) submitted to neurosurgery at Hospital São José, Complexo Hospitalar Santa Casa de Porto Alegre, southern Brazil. Control sections of normal meningeal cells, 19 patients, were obtained by evaluating the arachnoid tissue present in the arachnoid cyst resected material. Immunohistochemistry was applied to assess ARO, PR, ER and AR. Aromatase expression was detected in 100% of the control patients and in 0% of the patients with meningioma. ER was present in 24.6% of the meningiomas and in 0% of the controls, AR in 18.3% of the meningiomas and in 0% of the controls, and PR in 60.3% of the meningiomas and in 47.4% of the controls. A positive association was observed between the presence of AR and ER (OR 3.7; P = 0.01) in meningiomas. There were no significant differences in the presence of hormone receptors between meningioma histological subtypes. PR expression in women with meningioma was significantly higher than that found in men (OR 2.3; P = 0.08). Behavior pattern differences observed between aromatase expression, present in normal tissues and absent in meningiomas, and estrogen and androgen hormone receptors, absent in normal tissues and present in meningiomas, suggest that there is heterogeneity in modulation by sex steroids in the development of these tumors.

Evaluation of angiogenesis in 77 pituitary adenomas using endoglin as a marker

Angiogenesis, a fundamental process for the development and growth of a tumor, is less expressive in adenomas than in the normal pituitary tissue. There is controversy about the behavior of angiogenesis as a function of hormonal secretion or other characteristics of pituitary tumors. Endoglin (CD105) is a proliferation‐associated antigen on endothelial cells, as well as an endothelial progenitor cell marker. We used the anti‐endoglin antibody, a glycoprotein expressed in endothelial cells and conjunctive tissue, as a new marker particularly associated with neovascularization, in order to determine microvascular density (MVD) in pituitary adenomas. There were 77 samples, 31 males and 46 females, carriers of micro‐ (n = 24) or macroadenomas (n = 53). No significant difference was found in MVD concerning the variables of age, clinical presentation, and immunohistochemical phenotype or tumor size. MVD in males (median 5.4) was significantly higher (P = 0.001) than in females (median 3.0). Cell proliferation, as evaluated by the MIB‐1 antibody (a cellular proliferation index [Ki‐67 antigen], which is present in all stages of the cellular cycle except for the resting cells), ranged from 0% to 19.58%. No correlation was found between MIB‐1 and MVD. It is possible to infer that the lower MVD found in pituitary adenomas in females reflects an inhibitory estrogen action on TGF‐β1, a protein involved in vascular remodeling. Because of its role as a TGF receptor ligand, endoglin proved to be sensitive in detecting this gender difference in pituitary tumor angiogenesis.

Immunohistochemical Detection of Estrogen Receptor Alpha in Pituitary Adenomas and Its Correlation with Cellular Replication

With the aim of evaluating the relationship between pituitary tumorigenesis and the presence of estrogen receptor-α (ERα) by immunohistochemistry (IH) and their relevance to patients’ clinical presentation, hormonal phenotypes of adenomas, preoperative neuroimaging findings, and the index of cellular replication MIB-1, a study was conducted with material from 91 women and 67 men with pituitary adenomas. The patients had acromegaly (29.7%), Cushing’s disease (14.6%), hyperprolactinemic syndrome (20.9%), and clinically nonfunctioning tumors (34.8%). Of the patients, 14.6% had microadenomas, 52.5% had macroadenomas with or without suprasellar growth, 28.5% had invasive macroadenomas and in 4.4% the adenoma was not visualized. IH showed that 43 were positive for growth hormone (GH), 16 for corticotropin (ACTH), 18 for prolactin (PRL), 18 for PRL+GH, 6 for luteinizing hormone (LH) and follicle-stimulating hormone (FSH), 15 had a plurihormonal reaction, and 42 had nonfunctioning adenomas. The presence of ERα was positive in 9/158 adenomas with a median value for the percentage of labeled cells of 42.89%, and in 6/16 controls (autopsy samples) with a median value for the percentage of labeled cells of 0.024%. ERα was significantly more prevalent in controls than in patients with adenomas (37.5 versus5.7%; p = 0.001); however, the mean ERα concentration in adenomas was significantly greater than in controls (42.89 versus 0.024%; p < 0.001). No significant difference in the concentration of ERα was found across the clinical presentations, hormonal phenotypes or findings of preoperative CT. Among the ERα-positive adenomas, ERα values were significantly greater in invasive macroadenomas (80%) than in microadenomas (3.33%). MIB-1 values did not differ significantly between ERα-positive and -negative adenomas, nor did the correlation between ERα values and the MIB-1 index attain significance in the total sample, even when only ERα-positive adenomas and positive MIB-1 indexes were considered. It was concluded that, when present in pituitary tumors, ERα exhibits a high concentration, and is more common in nonfunctioning and invasive adenomas, but absent in ACTH-secreting ones.

Oronasal complications in patients after transsphenoidal hypophyseal surgery

UNLABELLED Transsphenoidal surgery is the most commonly used surgical procedure to handle the hypophyseal region, sometimes associated with oronasal complications. MATERIAL AND METHODS/AIM To evaluate prospectively (specific questionnaire, clinical evaluation) undiagnosed chronic oronasal complications in patients submitted to conventional transsphenoidal adenomectomy surgery, operated at different neurosurgery services more than 6 months ago. RESULTS 49 patients were evaluated, 37/45 presented macroadenoma. 28,5% were submitted to more than one intervention, 2/5 transsphenoidally. Transsphenoidal approach 92.8% through sublabial route. No patient had spontaneous complaint. With the specific questionnaire 63.2% presented complaints. One patient presented an oronasal fistula, 1 stenosis of the nasal valve area with external nasal deformity. Rhinoscopy detected alterations in 77.5%, nasal endoscopy in 87.7%. Septal perforation was present in 10/12 patients with scabs and 2 with purulent secretion. All 4 patients submitted to 2 transsphenoidal approaches presented septal perforation and nasal synechiae. In the endonasal, synechiae (2), alteration in medium meatus (1) and stenosis of the nasal valve area (1) were observed. Only two patients presented normal evaluation. CONCLUSION A high incidence of nasal complications after conventional transsphenoidal surgery observed through examination and not reported spontaneously point to the need of otorhinolaryngological investigation complemented by nasal endoscopy in patients submitted to procedures through this route.

Complicações oronasais em pacientes pós-abordagem hipofisária via transesfenoidal

Transsphenoidal surgery is the most commonly used surgical procedure to handle the hypophyseal region, sometimes associated with oronasal complications. Mate...

Acquired Factor VIII and von Willebrand Factor (aFVIII/VWF) Deficiency and Hypothyroidism in a Case With Hypopituitarism

This article reports a female who presented with bleeding, acquired factor VIII and von Willebrand factor (aFVIII-VWF) deficiency, and central deficiency in the thyroid and adrenal axis (Sheehan’s syndrome). After starting hormone replacement therapy, relief of bleeding manifestations was associated with correction of both FVIII and VWF to normal. This report draws attention to a rare association between the acquired form of von Willebrand disease and hypothyroidism of central origin.

Diastolic function study with conventional and pulsed tissue Doppler echocardiography imaging in acromegalic patients.

Acromegaly is associated with myocardial hypertrophy and it can progress to diastolic and systolic dysfunction. Purpose: To evaluate diastolic function in acromegalic patients through conventional echocardiography (CD) and tissue Doppler imaging (TDI). Methods: Seventeen acromegalic patients were submitted to CD and TDI, and early (E) and atriogenic (A) transmitral flow were evaluated in mitral, septal, and tricuspid regions. Results: In comparison with controls the means of conventional (1.06), septal (1.01), and tricuspid (0.98) E/A ratio were significantly lower in acromegalic patients. E/A ratio <1.0 was demonstrated in 41% and 49% of acromegalics by DC and TDI, respectively, with no statistical difference among the two methods. An inverse linear correlation was shown between mitral E/A ratio and acromegalic age (r =−0.7). Conclusion: In this study, DC and TDI were equally effective in demonstrating diastolic dysfunction, a common finding in acromegalic patients. (ECHOCARDIOGRAPHY, Volume 26, July 2009)

Bone mineral density in early-onset hypogonadism and the effect of hormonal replacement.

Hypogonadism is associated with reduction of bone mineral density (BMD), especially if sex steroid deficiency occurs early in life. In this situation, the effect of hormonal replacement therapy on bone mass is controversial. We evaluated the BMD through dual-energy X-ray absorptiometry (DXA) in patients with genetically determined hypogonadism or hypogonadism acquired in adulthood. The results of the BMD of patients never treated (pretreatment) or under treatment were compared with population standards and were submitted to pair analysis. Thirty-three patients were evaluated: group 1: BMD evaluated pretreatment (24); group 2: BMD evaluated under treatment (21); group 3: BMD evaluated pretreatment and under treatment (12). In group 1, there was a significant reduction of bone mass in all regions, with no gender differences. In patients with concomitant growth hormone (GH) deficiency, the total body (-3.60) and lumbar spine (-4.10) BMDs were significantly reduced compared to patients without associated GH deficiency (-2.37 and -2.35, respectively). In group 2, a significant reduction of bone mass was detected in all regions. In group 3, the patients showed statistically significant improvement in BMD with hormonal replacement therapy in all regions in both sexes. We conclude that the early onset of hypogonadism reduces the BMD significantly. This effect is increased when there is associated GH deficiency. Gonadal steroid replacement therapy increases the BMD in all bone regions, and the increase is similar in both sexes. However, although hormone replacement improves bone mass, it still remains significantly lower in comparision with population standards.

Pituitary metastasis from adenocarcinoma

. CASE A 50-year-old male patient sought medical care com -plaining of cephalalgia for 4 months, diplopia and ptosis of the left eyelid for 30 days. He reported loss of libido and erectile dysfunction in the previous six months. He was before a salutary individual. Physical examination: body mass index (BMI) 24, with ptosis and ophthalmo-plegia of the left eye, arterial pressure of 140/80 mmHg. No other alterations. Magnetic resonance imaging (Figure) showed hetero -geneous mass into the sella turcica with suprasellar ex-tension, causing displacement of optic chiasm and third ventricle floor, with intense opacification after contrast.The laboratory exams showed normal thyroid func-tion, low levels of gonadotropins and total testosterone, normal levels of basal cortisol and IGF-1 and very small increase in serum prolactin. Renal function, serum so-dium and urine density were within normal limits. Cen -tral hypogonadism and slight hyperprolactinemia were de -tected, without evidence of posterior pituitary alteration. An endoscopic transsphenoidal pituitary surgery were performed and anatomopathological exam showed metastasis of moderately differentiated adenocarcinoma of unknown primary site. Postoperative exams showed anemia, increased GGt, FA and CA 19-9. Immunohisto -chemical analysis indicated origin in the gastrointestinal tract, imaging of thorax and abdomen showed lymphade -nopathies and small irregularities on the antral mucosa wall of the stomach. Upper gastrointestinal endoscopy with biopsy showed stomach antral adenocarcinoma.DISCUSSIONMetastatic tumors of the pituitary gland are rare complications

Determination of Cell Proliferation Using Mcm2 Antigen and Evaluation of Apoptosis and TGF-β1 Expression in GH-secreting or Clinically Nonfunctioning Pituitary Adenomas

Pituitary adenomas (PA) occasionally show aggressive behavior, with invasion of the surrounding tissues. The identification of markers able to recognize aggressive PA in early stages remains a challenge. We aimed to determine the expression of a new cell proliferation marker, Mcm2, and the presence of apoptosis in PA, and to evaluate the association of clinicopathological features with the apoptotic and proliferative indices. Additionally, the TGF-β1 expression, an inducer of apoptosis, was determined. The proliferative index was determined in GH-secreting or clinically nonfunctioning PA using immunohistochemical (IH) methods for Mcm2 and Ki-67 antigens. The apoptosis was assessed by the TUNEL method and the TGF-β1 expression by IH. A significant positive correlation was found between log Mcm2 index and log Ki-67 index (p < 0.001). Mcm2 and Ki-67 detected a similar number of proliferating cells. Mcm2 index showed a significant association with tumor extension (p = 0.02), but not with tumor invasion. Apoptosis was detected in 17% of the adenomas, with a maximum apoptotic index of 0.77%. Immunoreactivity to TGF-β1 was observed in 77% of the adenomas, showing an association with tumor extension. We concluded that, in this sample, Mcm2 was similar to Ki-67 in the identification of the proliferating cells and that apoptosis was rare.