The acromegalic spine: fractures, deformities and spinopelvic balance.

INTRODUCTION: Axial skeleton arthropathy and osteoporotic vertebral fractures are common findings in acromegalic patients and can result in severe spinal deformity. OBJECTIVE: To investigate the presence of spinal fractures and deformities, sagittal imbalances, and spinopelvic compensatory mechanisms in acromegalics. PATIENTS AND METHODS: 58 patients with acromegaly from a referral neuroendocrinology center were prospectively evaluated by panoramic spine radiographs to detect the presence of fractures and scoliosis, to measure thoracic kyphosis, lumbar lordosis (LL), pelvic incidence (PI), pelvic tilt (PT) and sagittal vertical axis (SVA). Sagittal imbalance criteria were considered: thoracic kyphosis > 50°, PI-LL > 10°, PT > 20° and SVA > 5 cm. Their medical records were analyzed for clinical and laboratorial data. RESULTS: The prevalence of fractures was 13.8%, predominantly in the thoracic spine, with mild and anterior wedge compressions. Scoliosis was present in 34.5% of the cases, all with degenerative lumbar curve apex. Thoracic kyphosis > 50º occurred in 36.8% of patients, PI-LL > 10° in 48.3%, PT > 20° in 41.4% and SVA > 5 cm in 12.1%. CONCLUSION: Increased number of vertebral fractures and high prevalence of spinal deformities related to sagittal imbalance were detected, indicating the importance of monitoring bone comorbidities in acromegaly, with radiological evaluation of the spine as part of the follow up.

Gene and protein expression of E-cadherin and NCAM markers in non-functioning pituitary adenomas.

Non-functioning pituitary adenomas (NFPA) are classified as benign tumors of slow growth, but 40% of them present local invasion, a characteristic of behavior still unpredictable with the use of current tumor markers. This work aims to evaluate the tissue markers E-cadherin and NCAM, which act on cell adhesion, in tumor tissue samples of NFPA and its relationship with the degree of local invasiveness. Gene expression of E-cadherin (CDH1) and NCAM (NCAM1) was assessed by real-time PCR and tissue expression by immunohistochemistry. Fifty-three patients with macroadenomas were submitted to transsphenoidal surgery, presented grade II invasive adenomas in 16 cases (30.2%), grade III in 7 (13.2%) and grade IV in 30 (56.6%). In the immunohistochemistry, one case was negative for E-cadherin, 7 showed weak immunostaining, 17 moderate and 28 strong, whereas for NCAM, 5 showed negative, 28 weakly, 14 moderate and 6 strong. Regarding gene expression, 43.3% showed expression for CDH1 (mean of 2.12) and 50% for NCAM1 (mean of 1.86). There was no significant correlation between the immunohistochemical expression of the markers, as well as the gene expression, the degree of invasiveness and clinical data. The results suggest that E-cadherin and NCAM markers are not directly related to the invasiveness in NFPA.

PTTG overexpression in non-functioning pituitary adenomas: Correlation with invasiveness, female gender and younger age.

BACKGROUND: Non-functioning pituitary adenomas (NFPA) are prevalent pituitary neoplasms. Because they do not present with hormonal hypersecretion, there is no marker that indicates regrowth or recurrence, as in other adenomas. OBJECTIVES: Evaluate the immunohistochemical expression of PTTG, CD105 and Ki-67 and their relationships with age, gender, invasiveness, hormonal expression and regrowth or recurrence in the follow-up of NFPA operated and not submitted to radiotherapy. METHODS: Included 56 patients submitted to transsphenoidal surgery. Clinical data were obtained from medical records. The invasion degree was obtained by Hardy's classification. RESULTS: Mean age 55 ±â€¯13.6 years, 62.5% men and 68% invasive. Lesion persistence was present in 62.2% and regrowth in 35.7%. The recurrence-free survival rate was 94.5%, 75.4% and 69.1% (1, 2 and 3 years). No patient presented recurrence. The PTTG was positive in 55.3%, with statistically significant relationship with invasiveness, age and female gender, without relation to regrowth. The microvascular density showed statistically significant relationship with male gender, negative correlation with PTTG (r = -0.434, p = 0.001), and no relation with invasiveness and regrowth. The Ki-67 showed statistically significant relationship with age, tendency towards regrowth (p = 0.054) and, with no relation to invasiveness. CONCLUSIONS: It is suggested that PTTG can be used as a prognostic marker in NFPA.

Michelangelo buonarroti's code in the frescoes of the sistine chapel - an allusion to gematria of the hebrew/greek alphabet and the Golden Ratio.

According to Giorgio Vasari (1511-1574), the great genius of anatomy, Michelangelo Buonarroti (1475-1564), in painting the frescoes on the ceiling of the Sistine Chapel (1508-1512), demonstrated to the world a new dimension/perspective of painting, especially in the sublime manner with which the artist represented the anatomical details of the characters that made up his frescoes. Since then, the Sistine Chapel has received millions of tourists annually, who marvel at the anatomical beauty of the characters depicted on its ceiling. It has also received many scholars of art and even anatomists, who have often tried to infer theses and explanations regarding Michelangelo's real intentions in elaborating this great work. However, even after five centuries, the Vatican's own official explanations of the true intentions of the artist remain quite uncertain. In an attempt to elucidate Michelangelo's possible intentions in the design of this memorable work, this article presents unpublished evidence that all the frescoes on the ceiling of the Sistine Chapel were organized by the artist according to a code based on the number of characters in each fresco, the gematria of the Hebrew/Greek alphabet, and the Golden Ratio. This decoding process could reveal a key factor influencing the artist's intentions in ordering the elements in this work. Clin. Anat. 31:948-955, 2018. © 2018 Wiley Periodicals, Inc.

Pagan symbols associated with the female anatomy in the Medici Chapel by Michelangelo Buonarroti.

Numerous studies have shown that many works of art from the Renaissance period contain hidden symbols and codes that could have religious, mathematical and/or pagan significance and even anatomical allusions. In this context, the present manuscript offers new evidence that the great genius of anatomy, Michelangelo Buonarroti (1475-1564), included pagan symbols associated with female anatomy in the funerary monuments found in the Sagrestia Nuova/Medici Chapel (1519-1533) in Florence, Italy. The interpretation of the symbols provided in this study will interest those with a passion for the history of anatomy. Clin. Anat. 30:572-577, 2017. © 2017 Wiley Periodicals, Inc.

A case of sibutramine-induced hyperprolactinemia.

INTRODUCTION: Several drugs may cause hyperprolactinemia, especially antipsychotic drugs and prokynetic drugs. Serum prolactin concentrations increase within hours after acute administration of these drugs and return to normal within two to four days after cessation of chronic therapy. So far, sibutramine, a sympathomimetic drug used in the management of obesity, was not described to be associated with altered prolactin levels. OBJECTIVE: The purpose of this study is to present a case of sibutramine-induced hiperprolactinemia. CASE REPORT: A 38-year-old white female patient seeks medical attention complaining of weight gain (Body mass index: 35) associated with anxiety. She started sibutramine treatment and presented with amenogalactorrhea. Hyperprolactinemia was diagnosed (prolactin of 46 and 89.6 ng/mL) with normal thyroid, renal and hepatic function, and a negative pregnancy test. A sella MRI was performed and sibutramine was suspended. Prolactin levels returned to normal within 15 days of sibutramine cessation and remained normal within 90 days of follow-up, with resolution of the amenogalactorrhea syndrome. CONCLUSION: sibutramine may be considered in differential diagnosis of drug-induced hyperprolactinemia.

Lipid profile and response to statin therapy in patients with hypopituitarism.

OBJECTIVE: Dyslipidemia is prevalent among patients with hypopituitarism, especially in those with growth hormone (GH) deficiency. This study aimed to evaluate the response to statin therapy among adult patients with dyslipidemia and hypopituitarism. METHODS: A total of 113 patients with hypopituitarism following up at a neuroendocrinology unit were evaluated for serum lipid levels. Dyslipidemia was diagnosed in 72 (63.7%) of these patients. A control group included 57 patients with dyslipidemia and normal pituitary function. The distribution of gender, age, weight, and dyslipidemia type was well balanced across both groups, and all participants were treated with simvastatin at doses adjusted to obtain normal lipid levels. RESULTS: Patients with hypopituitarism and dyslipidemia presented deficiency of TSH (69%), gonadotropins (69%), ACTH (64%), and GH (55%) and had a similar number of deficient pituitary axes compared with patients with hypopituitarism but without dyslipidemia. All patients with dyslipidemia (with and without hypopituitarism) had lipid levels well controlled with doses of simvastatin ranging from 20-40 mg/day. The mean daily dose of simvastatin was not significantly different between patients with and without hypopituitarism (26.7 versus 23.5 mg, p = 0.10). Similarly, no significant variation in simvastatin dose was observed between patients with different causes of hypopituitarism, presence or absence of GH deficiency, number of deficient pituitary axes, prior pituitary radiation therapy or not, and presence or absence of obesity. CONCLUSION: Patients with GH deficiency without GH replacement showed good response to simvastatin at a mean dose equivalent to that used in individuals with dyslipidemia and normal pituitary function.

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.

DNA repair and cell synthesis proteins: immunohistochemical expression and correlation with recurrence-regrowth in meningiomas.

Meningiomas are considered the second most common neoplasm of the central nervous system in adults. Most of them are benign with slow growth, frequent in women and with a high recurrence rate. In tumors, DNA error repair processes lose efficacy, providing mutagenesis and genomic instability. This work evaluated the expression of proteins involved in cell synthesis (cyclin D1) and DNA errors repair (MUTYH, XPF, XPG) in meningiomas, relating them to clinical, tumor and survival variables. The study included 85 patients, with a mean age of 52 ± 13.3 years and most of them women (2:1 ratio). Sixty-seven cases were grade I (79%). Grade II tumors were independent predictors of recurrence-regrowth (HR: 2.8; p = 0.038). The high expression of cyclin D1 was associated with grade II (p = 0.001) and low MUTYH expression with grade I (p = 0.04). Strong expression of XPF and XPG was associated with grade II (p = 0.002; p < 0.001) and with recurrence-regrowth (p = 0.04; p = 0.003). Strong XPF expression was significantly related to large tumors (p = 0.03). An association of cyclin D1, MUTYH and XPF were found. Survival was not associated with the expression of any of the proteins studied. To know the role of DNA repair proteins and cell synthesis is important for understanding the processes of origin and tumor development. Grade II meningiomas and strong expression of XPF and XPG were predictors of recurrence or regrowth and may assist in clinical management, considering the high recurrence of meningiomas and the absence of consensus regarding treatment.

Evaluation of the potential of the Ki67 index to predict tumor evolution in patients with pituitary adenoma.

The aggressive course of a number of pituitary adenomas requires the investigation of potential predictors. This study aimed to investigate the proliferation marker Ki67 as a predictor of postoperative outcome in patients with pituitary adenoma regarding recurrence and regrowth of the tumor, using a Ki67 cut-off value of 3%. This retrospective study included 52 patients with pituitary adenoma who had undergone adenomectomy and had a pituitary image taken at least 1 year after surgery. Patients were divided according to Ki67 expression into high (≥3%) vs. low (<3%) levels of Ki67. The two groups were similar regarding the preoperative tumor invasion grade. The Ki67 index ranged from 0 to 30%; in 23 cases, Ki67 was ≥3%. The two groups were similar regarding tumor recurrence and regrowth: 4 cases (28%) of recurrence in the Ki67<3% group vs. none in the Ki67≥3% group (P=0.26); and 2 cases (13%) of regrowth in the Ki67<3% group vs. 7 cases (43%) in the Ki67≥3% group (P=0.11). A subgroup analysis was performed for nonfunctioning adenomas. Recurrence rates remained similar between groups (Ki67<3% group: 1 case [20%]; Ki67≥3% group: none; P>0.99), whereas regrowth rates were higher in the Ki67≥3% group (6 cases [67%] vs. 2 cases [17%] in the Ki67<3% group; P=0.03). The patient with the highest Ki67 index (30%) developed pituitary carcinoma. The results allow us to suggest the adoption of a stricter control of image monitoring in nonfunctioning adenomas with incomplete resection associated with a Ki67 index ≥3%.

Hyperprolactinemia and immunohistochemical expression of intracellular prolactin and prolactin receptor in primary central nervous system tumors and their relationship with cellular replication.

The role of prolactin (PRL) in the CNS remains uncertain. We evaluated the presence of hyperprolactinemia, intracellular prolactin (ICP), and prolactin receptor (PRL-R) in primary CNS tumors, and their relationship with cellular replication with a prospective cross-sectional study of 82 consecutive patients with primary CNS tumors admitted for neurosurgical resection between October 2003 and September 2005. Patients submitted to a questionnaire, and venous blood samples were obtained for measurement of serum PRL and TSH. Immunohistochemical analyses were performed to evaluate the presence of ICP, PRL-R, and Ki-67. Serum PRL levels ranged from 2 to 70 ng/ml, and hyperprolactinemia was detected in 25 cases (30.5%). ICP was detected in 18 patients (21.9%), in whom PRL ranged from 2 to 32 ng/ml. A positive correlation was found between PRL levels and the presence of ICP (Student's t test, P = 0.022). The PRL-R was observed immunohistochemically in 32 cases (39%). The frequencies of hyperprolactinemia, ICP, and PRL-R were similar across the several histological types of CNS tumors. Ki-67 index was similar in all groups. Hyperprolactinemia and intracellular presence of PRL and PRL-R were common findings in this population, suggesting a role for PRL in CNS tumor genesis.

Association between systemic lupus erythematosus, rheumatoid arthritis, hyperprolactinemia and thyroid autoantibodies.

BACKGROUND: Hyperprolactinemia (hyperPRL) has been associated with autoimmune rheumatic disorders and the presence of thyroid autoantibodies (tAb). The interrelation between these variables was the focus of this prospective study. METHODS: The study assessed six groups of individuals: 26 with systemic lupus erythematosus (SLE), 20 with rheumatoid arthritis (RA), 28 with tAb (tAb+), 14 with untreated hyperprolactinemia (hyperPRL), 10 with treated hyperPRL, and a control group (n = 28). Prolactin (PRL), free thyroxin, TSH, antibodies against thyroglobulin (TgAb), thyroid microsomal antigen (MsAb) and/or thyroid peroxidase (TPOAb) were determined in all patients. Those with hyperPRL had macroprolactin investigated by the polyethylene glycol (PEG) precipitation method. RESULTS: PRL (ng/mL) levels in the SLE, RA, and tAb+ groups were, respectively, 21.3 +/- 12.6, 11.5 +/- 7.4, and 12.5 +/- 8.6, and were significantly greater in the SLE group (p = 0.006) than in the controls (12.5 +/- 6.5) and in the other groups. Five patients had hyperPRL: three with SLE, one with RA, and one with tAb+. Macroprolactinemia was detected in three of the untreated hyperprolactinemic patients and in the hyperprolactinemic patient of the tAb+ group. Positivity for any of the tAb was 15% in the SLE, 15% in the RA, 57.1% in the untreated hyperPRL, 10% in the hyperPRL on treatment, and 3.6% in the control group. The presence of antibodies was significantly more frequent in the untreated hyperPRL group than in the control group (p = 0.001). CONCLUSIONS: The results indicate that the PRL level is higher in SLE patients and that in the presence of hyperPRL there is increased prevalence of antithyroid antibodies, evidencing the association of PRL and autoimmunity and pointing to the appropriateness of assessing and monitoring the progress of these markers in patients affected by these disorders.

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.

A proposito de um caso de granulomatose de células de Langerhans / Apropos of a case of granulomatosis of Langerhans cells

Granulomatosis de células de Langerhans es diagnosticada en una niña de dos años, que consulta al neurólogo infantil por presentar lesiones óseas craneanas y diabetes insípida. Los autores discuten los aspectos clínicos de esta patología, las alteraciones endócrinas, la investigación realizada, destacándose los métodos de radioimagen y el tratamiento actual