Aggressive nonfunctioning pituitary neuroendocrine tumors.

Nonfunctioning pituitary neuroendocrine tumors (NF-PitNETs) are tumors that are not associated with clinical evidence of hormonal hypersecretion. According to the World Health Organization (WHO), there are some subtypes of PitNETs that exhibit more aggressive behavior than others. Among the types of potentially aggressive PitNETs, three are nonfunctional: silent sparsely granulated somatotropinomas, silent corticotropinomas, and poorly differentiated PIT-1 lineage tumors. Several biological markers have been investigated in NF-PitNETs. However, there is no single biomarker able to independently predict aggressive behavior in NF-PitNETs. Thus, a more complex and multidisciplinary proposal of a comprehensive definition of aggressive NF-PitNETs is necessary. Here, we suggest a combined and more complete criterion for the NF-PitNETs classification. We propose that aggressiveness is due to a multifactorial combination, and we emphasize the need to include new emerging markers that are involved in the aggressiveness of NF-PitNETs and the need to identify.

Impact of Weight Loss With Intragastric Balloon on Bone Density and Microstructure in Obese Adults.

The historical concept that obesity protects against bone fractures has been questioned. Weight loss appears to reduce bone mineral density (BMD); however, the results in young adults are inconsistent, and data on the effects of weight loss on bone microstructure are limited. This study aimed to evaluate the impact of weight loss using an intragastric balloon (IGB) on bone density and microstructure. Forty obese patients with metabolic syndrome (mean age 35.1 ± 7.3 yr) used an IGB continuously for 6 mo. Laboratory tests, areal BMD, and body composition measurements via dual-energy X-ray absorptiometry, and volumetric BMD and bone microstructure measurements via high-resolution peripheral quantitative computed tomography were conducted before IGB placement and after IGB removal. The mean weight loss was 11.5%. After 6 mo, there were significant increases in vitamin D and carboxyterminal telopeptide of type 1 collagen levels. After IGB use, areal BMD increased in the spine but decreased in the total femur and the 33% radius. Cortical BMD increased in the distal radius but tended to decrease in the distal tibia. The observed trabecular bone loss in the distal tibia contributed to the decline in the total volumetric BMD at this site. There was a negative correlation between the changes in leptin levels and the measures of trabecular quality in the tibia on high-resolutionperipheral quantitative computed tomography. Weight loss may negatively impact bone microstructure in young patients, especially for weight-bearing bones, in which obesity has a more prominent effect.

LIMITATIONS OF BASAL CORTISOL IN THE DIAGNOSIS OF CUSHING SYNDROME.

OBJECTIVE: Cushing syndrome (CS) is one of the most challenging diseases to diagnose due to the difficulties that may arise during laboratory test interpretations. A random serum cortisol level is often obtained by a general practitioner as a first step in the work-up of suspected CS patients. In this respect, it is rarely useful and has limitations. METHODS: We report an extremely unusual case of a female patient who presented with adrenocorticotropic hormone-independent CS and corticosteroid-binding globulin (CBG) deficiency. RESULTS: The patient was initially misdiagnosed with and treated for adrenal insufficiency because of persistently low basal cortisol levels, in detriment of her exacerbated Cushing features and symptoms. CONCLUSION: We describe the limitations of using basal cortisol in the diagnosis of CS and review the differential diagnosis of patients with CS who have low basal cortisol. CBG variants may explain the findings of high urinary and salivary cortisol, in the absence of increased serum cortisol.

Twist1 Correlates With Epithelial-Mesenchymal Transition Markers Fibronectin and Vimentin in Adrenocortical Tumors.

BACKGROUND/AIM: Although the knowledge regarding adrenocortical carcinomas (ACC) tumorigenesis has significantly improved during the last decade, it still remains to be completely determined. Epithelial-mesenchymal transition (EMT) is a well described transcription factor induced process, postulated as an essential step toward cancer progression and metastasis development. In this context, Twist1 has been described as the EMT master-regulator. The aim of this study was to assess the association among Twist1, fibronectin, vimentin and E-cadherin gene expression in adrenocortical tumor samples. MATERIALS AND METHODS: Twist1, fibronectin, vimentin and E-cadherin gene expression in 18 adrenal adenomas, 18 ACC, and 24 childhood onset adrenocortical tumors were assessed in formalin-fixed paraffin-embedded tissues. The fold expression was calculated according to the 2ΔCt method. RESULTS: A significant correlation between mRNA levels of Twist1, fibronectin and vimentin was evident. Although their expression was inversely proportional, no association was observed between Twist1 and E-cadherin expression. CONCLUSION: The expression of Twist1, the major regulator of EMT, is directly correlated to the expression of mesenchymal markers fibronectin and vimentin in ACC samples.

Vitamin D Deficiency and Its Influence on Bone Metabolism and Density in a Brazilian Population of Healthy Men.

Vitamin D supplementation is universal for postmenopausal women, but not for elderly men, in whom osteoporosis is also commonly neglected. This study aimed to evaluate vitamin D deficiency and its association with secondary hyperparathyroidism, bone resorption, and bone density in Brazilian men. A total of 120 men, 20-93 years, were evaluated for serum calcium, phosphorus, creatinine, 25-hydroxyvitamin D (25(OH)D), parathyroid hormone, biochemical markers of bone resorption (carboxy-terminal telopeptide, carboxy-terminal peptide of type I collagen), and bone mineral density (dual-energy X-ray absorptiometry). Glomerular filtration rate (GFR) below 30 mL/min/1.73 m2, chronic diseases, and medications affecting bone were the exclusion criteria. No participant reported previous low-impact fractures. In the overall population, 25(OH)D levels were below 30 ng/mL in 46.7%, and below 20 ng/mL in 27.6%. Among the 93 patients 50 years and older, 28 had osteoporosis. In those 70 years and older, the prevalence of vitamin D deficiency (42.1%), secondary hyperparathyroidism (46.4%), high bone resorption (39.6%), decreased GFR (39.2%), and osteoporosis (41.4%) was significantly higher than in the younger subjects (p < 0.005 for all comparisons). Serum parathyroid hormone increased with aging and declining GFR, but was not significantly associated with 25(OH)D or bone mineral density. There was a clear contribution of vitamin D deficiency to increased bone resorption and osteoporosis. Binary logistic regression model considering age, 25(OH)D, and bone resorption identified age ≥70 years as the main determinant of osteoporosis. Our data demonstrate a high prevalence of vitamin D deficiency in a male population living in Rio de Janeiro, and emphasize its participation on the pathogenesis of age-related bone loss. (Vitamin D deficiency and osteoporosis are common in elderly Brazilian men.).

Inhaled glucocorticoids are associated with vertebral fractures in COPD patients.

Chronic obstructive pulmonary disease (COPD) is an independent risk factor for osteoporosis. Oral glucocorticoids are deleterious to bone; however, the impact of inhaled glucocorticoids (ICS) remains unclear. Our objective was to determine whether ICS contribute to osteoporosis and fragility fractures. Sixty-one COPD patients, 35 current users of ICS and 26 who had never received glucocorticoids, were evaluated for bone mineral density (BMD) and body composition and underwent vertebral fracture assessment (VFA). The risk factors for bone disease considered for analysis were age, gender, ICS use, body mass index (BMI), muscle mass index (MMI), and the Global Initiative for Chronic Obstructive Lung Disease (GOLD) category. The Fracture Risk Assessment Tool (FRAX) calculation tool for the Brazilian population was also employed. The groups did not differ regarding gender, BMI, MMI, GOLD class, lowest values of the BMD T-score and Z-score, prevalence of osteoporosis, or low BMD for age. Vertebral fractures were identified via VFA in seven patients using ICS and in none of those not receiving glucocorticoids (p = 0.02). There was a trend for an association between MMI and osteoporosis (p = 0.05) and for a progressive decrease in the BMD Z-score according to the COPD severity assessed via the GOLD score (p = 0.08). Vertebral fractures were not associated with osteoporosis (p = 0.69) or low MMI (p = 0.12). The fracture risk was not estimated by FRAX. ICS may lead to bone fragility before a significant decrease in BMD. Low muscle mass and COPD severity may contribute to bone disease.

Pituitary Hyperplasia in a Female Patient with a Severe Childhood Abuse History.

A 24-year-old Caucasian female patient was referred to our endocrinology service to investigate a structural magnetic resonance imaging (sMRI) finding of "pituitary mass". The first two sMRI were identified as pituitary adenoma but the following two examinations suggested the possibility of pituitary hyperplasia (PH). The patient was referred to our service for diagnostic clarification and therapy due to the divergence in sMRI reports and the surgical procedure indicated by the neurosurgical team of the other institution. The patient had no complaints, laboratory tests were all normal, and the sMRI clearly showed a PH. However, what caught our attention was her behavior. During the interview she was intermittently talking and acting like a child even though her age was 24. She reported being a foster child and was severely mistreated during childhood. Parallel psychiatric evaluation was requested and an association between the PH and the childhood abuse was identified. Early life stress may be associated with accelerated pituitary gland volume development, but there is still a paucity of data in literature about this issue. We should be aware of other cases like this one, and a correct differential diagnosis may contribute to contraindicate transsphenoidal surgery. When a childhood abuse history is present, we recommend admission to a psychiatric facility for adequate treatment.

Periodontal profile and radiographic characterization of the jaws in a patient with autosomal dominant osteopetrosis.

Osteopetrosis (OP) comprehends a rare group of conditions, presenting on radiographs increased bone density, deriving from irregularities in osteoclast differentiation or function. In the autosomal dominant osteopetrosis (ADO), some patients stay asymptomatic for some time, or only develop mild symptoms. The dental surgeon is often the first to presuppose the disease during routine imaging examinations, referring the patient to a specialized medical group. Furthermore, osteomyelitis is one of the major OP complications, and should be refrained through frequent dental monitoring. Signals of cortical interruption, sclerotic sequestra or periosteal new bone formation, should be looked for in these patients. Their dental management is complex and procedures encompassing bone tissue, such as implant procedures, tissue regenerations, tooth extractions, maxillofacial surgeries and orthodontic treatments, when elected, should be avoided. This case report describes a case of ADO with a diagnosis of moderate generalized chronic periodontitis, not statistically related to plaque index. This is the first case to describe such a condition, in which the systemic component and the altered bone metabolism seem to be related to the loss of periodontal apparatus, independent of the biofilm. Concerning prevention, we can reinforce the need for frequent dental monitoring to avoid further interventions in those cases. LEARNING POINTS: This paper reports a case in which the systemic component and the altered bone metabolism seem to have been related to the loss of periodontal attachment apparatus, independent of the biofilm.The periodontal damage observed in the OP patient was not related to the dental plaque, which leads us to suggest that the cases of periodontitis in OP patients should be diagnosed as periodontitis as a manifestation of systemic diseases.The periodontitis prevention should be longed for in OP patients thus, we propose that doctors responsible for patients with OP refer them to a dental service as soon as possible and that dentists should be aware of the preventive dentistry value as well as the most appropriate dental management for those cases.

Recurrence and mortality prognostic factors in childhood adrenocortical tumors: Analysis from the Brazilian National Institute of Cancer experience.

Prognostic markers that can help identifying precocious risk of unfavorable outcomes in patients with childhood adrenocortical tumors (ACTs) are still unclear. This observational and retrospective study aimed to identify clinical and pathology prognostic factors of recurrence and death in a tertiary cancer center population. Clinical, pathology, demographic, staging, and therapy data from patients with childhood ACT (median age: 3.6 years) treated at the Brazilian National Institute of Cancer between 1997 and 2015 were assessed. Univariate and bivariate analyses were used to study the association of clinical and pathology characteristics with recurrence and mortality. Recurrence and disease-related mortality were the main outcomes. Twenty-seven patients were included. Complete tumor resection was performed in 21 cases. The median tumor size was 8.2 cm. Mitotane was the most common adjuvant/palliative therapy (n = 13). Recurrence occurred in 6 patients, after a median time of 7.2 months, and was more common among those with larger tumors (P =.008), higher Weiss score (P =.001), and microscopic tumoral necrosis (P =.002). Ten patients died from the disease. Older age (P =.04), larger tumor size (P =.002), metastatic disease (P =.003), previous recurrence (P =.003), incomplete resection (P =.002), intraoperative tumor spillage (P =.005), higher Weiss score (P =.03), microscopic necrosis (P =.005), and capsular invasion (P =.02) were all associated with increased death risk. Even though complete tumor resection was performed in most cases, a considerable number of cases of childhood ACT resulted in recurrence and death. Early identification of unfavorable outcomes is essential to determine ideal therapy and appropriate surveillance.

ROLE OF IMAGING TESTS FOR PREOPERATIVE LOCATION OF PATHOLOGIC PARATHYROID TISSUE IN PATIENTS WITH PRIMARY HYPERPARATHYROIDISM.

OBJECTIVE: Primary hyperparathyroidism (PHPT) can be cured by parathyroidectomy, and the preoperative location of enlarged pathologic parathyroid glands is determined by imaging studies, especially cervical ultrasonography and scintigraphy scanning. The aim of this retrospective study was to evaluate the use of preoperative cervical ultrasonography and/or parathyroid scintigraphy in locating pathologic parathyroid tissue in a group of patients with PHPT followed in the same endocrine center. METHODS: We examined the records of 61 patients who had undergone parathyroidectomy for PHPT following (99m)Tc-sestamibi scintigraphy scan and/or cervical ultrasonography. Scintigraphic and ultrasonographic findings were compared to histopathologic results of the surgical specimens. RESULTS: Ultrasonography detected enlarged parathyroid glands in 87% (48/55) of patients with PHPT and (99m)Tc-sestamibi scintigraphy in 79% (37/47) of the cases. Ultrasonography was able to correctly predict the surgical findings in 75% (41/55) of patients and scintigraphy in 72% (34/47). Of 7 patients who had negative ultrasonography, scintigraphy correctly predicted the surgical results in 2 (29%). Of 10 patients who had negative scintigraphy, ultrasonography correctly predicted the surgical results in 4 (40%). When we analyzed only patients with solitary eutopic parathyroid adenomas, the predictive positive values of ultrasonography and scintigraphy were 90% and 86%, respectively. CONCLUSION: Cervical ultrasonography had a higher likelihood of a correct positive test and a greater predictive positive value for solitary adenoma compared to (99m)Tc-sestamibi and should be used as the first diagnostic tool for preoperative localization of affected parathyroid glands in PHPT. ABBREVIATIONS: Ca = calcium IEDE = Instituto Estadual de Diabetes e Endocrinologia Luiz Capriglione PHPT = primary hyperparathyroidism PTH = parathyroid hormone.

Assessment of Predictive Response Factors to Intragastric Balloon Therapy for the Treatment of Obesity.

BACKGROUND: Obesity is a worldwide epidemic that is difficult to control with non-invasive treatments, which usually present poor results. In this context, the intragastric balloon (IGB) is an important tool that presents a mean body weight loss (BWL) estimated at approximately 12%, although individual responses are highly variable. OBJECTIVES: This study assesses whether there are factors that can predict responses to IGB therapy either before or early after placement of the device. MATERIALS AND METHODS: A total of 50 obese patients underwent insertion of IGB placed endoscopically, and patients were monitored for 6 months. The evaluated predictive factors involved general characteristics and psychological, social, and dyspeptic aspects, and the preliminary results obtained in the first month after balloon placement. RESULTS: The mean weight loss was 11.5%, and 48% of the participants presented BWL >10%. Among the factors analyzed before IGB placement, only advanced age (P = .04) and higher scores obtained in the social relationships domain of a shorter version of the World Health Organization's Quality of Life questionnaire (P = .02) were significant. Analysis of the factors evaluated after IGB placement revealed that the BWL amounts observed in week 2 (P = .001) and week 4 (P < .001) and the intensity of dyspeptic symptoms in week 2 (P < .001) were positive predictive factors. CONCLUSIONS: The assessment of predictive factors may help to manage patients with IGB.

Low Frequency of Cardiomyopathy Using Cardiac Magnetic Resonance Imaging in an Acromegaly Contemporary Cohort.

CONTEXT: Left ventricular hypertrophy (LVH) and myocardial fibrosis are considered common findings of the acromegaly cardiomyopathy in echocardiography studies. OBJECTIVE: To evaluate the frequency of LVH, systolic dysfunction and myocardial fibrosis was undertaken in patients with acromegaly using cardiac magnetic resonance imaging (CMRi) before and after 12 months of octreotide long-acting repeatable treatment. PATIENTS AND METHODS: Consecutive patients with active acromegaly submitted to biochemical analysis and CMRi before and after 12 months of treatment. Additionally, echocardiography was performed before treatment. RESULTS: Forty consecutive patients were evaluated using CMRi at baseline and 30 patients were reevaluated after 12 months of treatment. Additionally, 29 of these patients were submitted to echocardiography. Using CMRi, the frequency of LVH was 5%. The mean left ventricular mass index (LVMi) was 61.73 ± 18.8 g/m(2). The mean left ventricular ejection fraction (LVEF) was 61.85 ± 9.2%, and all patients had normal systolic function. Late gadolinium enhancement was present in five patients (13.5%), and one patient (3.5%) had an increased extracellular volume. After treatment, 12 patients (40%) had criteria for disease control. No clinically relevant differences in cardiac variables before and after treatment were observed. Additionally, there was no difference in LVMi and LVEF among patients with and without disease control. Using echocardiography, 31% of the patients had LVH, mean LVMi was 117.8 ± 46.3 g/m(2) and mean LVEF was 67.3 ± 4.4%. All patients had normal systolic function. CONCLUSIONS: We demonstrated by CMRi, the gold-standard method, that patients with active acromegaly might have a lower prevalence of cardiac abnormalities than previously reported.

Insulin-like growth factor (IGF)-I, IGF binding protein-3, and prostate cancer: correlation with Gleason score.

INTRODUCTION: Non-androgenic growth factors are involved in the growth regulation of prostate cancer (PCa). OBJECTIVE: This is the first Brazilian study to correlate, in a population of patients operated for PCa, PSA, total testosterone, insulin-like growth factor-I (IGF-I) and insulin-like growth factor-binding protein-3 (IGFBP-3) with Gleason score and to compare with a control group with benign prostate hyperplasia (BPH). MATERIALS AND METHODS: This retrospective single-center study included 49 men with previously diagnosed PCa and 45 with previously diagnosed BPH. PSA, testosterone, IGF-I, IGFBP-3 were determined in both groups. RESULTS: PSA and IGFBP-3 levels were significantly higher in the PCa group as compared to the BPH group (p < 0.001 and p=0.004, respectively). There was a significant difference when we compared the PSA before surgery (p < 0.001) and at the inclusion in the study (p < 0.001) and IGFBP3 (0.016) among patients with Gleason < 7, ≥7 and BPH. In the PCa group, PSA, testosterone, IGF-I and IGFBP-3 levels were comparable between Gleason < 7 and ≥7. CONCLUSIONS: Our data suggest that in localized PCa, the quantification of PSA and, not of IGF-1, may provide independent significant information in the aggressiveness. IGFBP-3 could be a biochemical marker of disease control in PCa patients.

Truncated somatostatin receptor variant sst5TMD4 confers aggressive features (proliferation, invasion and reduced octreotide response) to somatotropinomas.

The GH/IGF1 response of somatotropinomas to somatostatin analogues (SSA) is associated with their pattern of somatostatin receptor (sst1-sst5) expression. Recently, we demonstrated that expression of a truncated sst5-variant (sst5TMD4) can influence the secretory response of somatotropinomas to SSA-therapy; however, its potential relationship with aggressive features (e.g. invasion/proliferation) is still unknown. Here, we show that sst5TMD4 is present in 50% of non-functioning pituitary-adenomas (NFPA) (n = 30) and 89% of somatotropinomas (n = 36), its expression levels being highest in somatotropinomas > > NFPAs > > > normal pituitaries (negligible expression; n = 8). In somatotropinomas, sst5TMD4 mRNA and protein levels correlated positively, and its expression was directly associated with tumor invasiveness (cavernous/sphenoid sinus), and inversely correlated with age and GH/IGF1 reduction after 3-6 months with octreotide-LAR therapy. GNAS+ somatotropinomas expressed lower sst5TMD4 levels. ROC analysis revealed sst5TMD4 expression as the only marker, within all sst-subtypes, capable to predict tumor invasiveness in somatotropinomas. sst5TMD4 overexpression increased cell viability in cultured somatotropinoma (n = 5). Hence, presence of sst5TMD4 associates with increased aggressive features and worse prognosis in somatotropinomas, thereby providing a potentially useful tool to refine somatotropinoma diagnosis, predict outcome of clinical response to SSA-therapy and develop new therapeutic targets.

Ki-67 is a predictor of acromegaly control with octreotide LAR independent of SSTR2 status and relates to cytokeratin pattern.

INTRODUCTION: Only one study has evaluated Ki-67 as a predictor of the response to somatostatin analog therapy in acromegaly; however, other predictors like somatostatin receptor type 2 (SSTR2) and cytokeratin pattern expressions were not considered. OBJECTIVE: To evaluate whether Ki-67 is a predictor of octreotide LAR (OCT-LAR) response in somatotropinomas independent of SSTR2 and cytokeratin expression patterns. METHODS: Protein expression was analyzed by immunohistochemistry. The percentage of cell nuclei that were immunolabeled for Ki-67 and the percentage of cells with positive SSTR2 staining were calculated. SSTR2 expression was considered high when ≥25%, and a cutoff of 2.3% was designated for Ki-67. Tumors were classified as densely or sparsely granulated according to the cytokeratin pattern. RESULTS: Thirty-one somatotropinomas were studied. Fourteen patients (45.2%) were controlled with OCT-LAR therapy. The median Ki-67 labeling index (LI) was higher in patients not controlled with OCT-LAR than in those controlled (1.63 and 0.15 respectively, P=0.002). Higher SSTR2 expression and densely granulated tumors were correlated with control as well (P=0.04 and 0.038 respectively). There was no difference in Ki-67 levels between patients with high and low SSTR2 expression (P=0.651). After multivariate analysis, both Ki-67 and SSTR2 remained statistically significant as predictors of OCT-LAR response (P=0.017 and 0.012 respectively). The Ki-67 LI was higher in sparsely than in densely granulated tumors (P=0.047). CONCLUSIONS: Ki-67 is a predictor of response to OCT-LAR in acromegaly, independent of SSTR2 expression and relates to cytokeratin patterns.

Acromegaly has a negative influence on trabecular bone, but not on cortical bone, as assessed by high-resolution peripheral quantitative computed tomography.

INTRODUCTION: Acromegaly is one of the causes of secondary osteoporosis, although studies of bone mineral density (BMD) have yielded conflicting results and none of them have evaluated the bone properties. OBJECTIVES AND PATIENTS: Our objective was to correlate, in a cohort of 82 acromegalic patients, BMD and bone microarchitecture, using dual-energy x-ray absorptiometry and high-resolution peripheral quantitative computed tomography, with the presence of type 2 diabetes mellitus (T2DM), disease activity, and gonadal status and to compare these bone parameters between 45 eugonadal acromegalic patients and 45 healthy controls. RESULTS: Acromegalic patients with T2DM had lower trabecular density and trabecular bone volume to tissue volume ratio in the distal tibia. Patients with active acromegaly exhibited a higher BMD and T-score in the lumbar spine (P = .02 for both) and a higher cortical density in the distal tibia when compared with those with controlled acromegaly (P = .001). After multiple linear regression (including age, presence of T2DM, acromegaly activity, and gonadal status), eugonadism remained the main determinant of bone parameters. The 45 acromegalic patients with eugonadism were compared with 45 age- and sex-matched controls and exhibited lower trabecular densities and impaired microstructures. CONCLUSIONS: Acromegaly appears to have a deleterious effect on trabecular bone microarchitecture, and in this specific population, the gonadal status might be more important than T2DM or acromegaly activity in determining bone health. High-resolution peripheral quantitative computed tomography seems promising for evaluating acromegalic bone properties and for addressing the limitations posed by dual-energy x-ray absorptiometry.

Vertebral fracture assessment in acromegaly.

Most vertebral fractures (VFs) are asymptomatic and incidentally found on X-rays. The effects of acromegaly on bone mineral density (BMD) are still controversial, and the prevalence of VFs in this specific population remains uncertain. The objective of this study was to assess VFs in acromegaly through vertebral fracture assessment (VFA) by dual-energy X-ray absorptiometry (DXA). Seventy-five acromegalic patients from the same center (53 female; age: 48.9±14.5yr) were enrolled in this study. None of them referred previous fragility fracture. They were divided according to the presence or absence of moderate or severe VFs on VFA, a densitometric spine imaging. Age, gender, estimated duration of disease, insulin-like growth factor I levels, disease control and gonadal status, as well as BMD and body composition (analyzed by DXA) were compared between these 2 groups. A prevalence of 10.6% of clinically unapparent VFs was observed. Eight patients had 13 moderate or severe VFs, and only one of them had osteoporosis at densitometry. There was a trend to longer duration of acromegaly before diagnosis, higher prevalence of hypogonadism, and higher BMD Z-score at lumbar spine and femoral neck in fractured patients, without reaching statistical significance. There is a significant prevalence of moderate and severe VFs in acromegalic patients, independently of BMD. More longitudinal and controlled studies are needed to recommend the use of VFA in all acromegalic patients submitted to DXA scan. VFA is simple, practical, uses low radiation, and may provide important information in the management of acromegaly.

Association of dengue hemorrhagic fever with multiple risk factors for pituitary apoplexy.

OBJECTIVE: To describe pituitary apoplexy that developed during the course of dengue hemorrhagic fever. METHODS: We describe the clinical findings, laboratory test results, imaging findings, and clinical course of the study patients. RESULTS: Patient 1 was a 40-year-old man who developed clinical signs and symptoms of dengue, which was confirmed by serologic testing. He presented with thrombocytopenia and developed severe headache and vomiting. During hospitalization, acromegaly was suspected because of the characteristic disease phenotype. Magnetic resonance imaging confirmed the diagnosis of pituitary apoplexy. Subsequently, the biochemical diagnosis of acromegaly was confirmed, and the patient underwent transsphenoidal surgery. Histopathologic examination showed signs of recent bleeding. Patient 2 was a 38-year-old man with a macroprolactinoma, who had been treated with cabergoline for 10 weeks and had shown improvement on laboratory testing and imaging. The patient then presented with clinical symptoms of dengue (confirmed serologically) and thrombocytopenia. He developed bilateral hemianopsia, and magnetic resonance imaging showed enlargement of the pituitary adenoma with signs of intratumoral bleeding. The patient underwent transsphenoidal surgery, and histopathologic examination documented a pituitary adenoma diffusely infiltrated by blood cells. CONCLUSIONS: We describe dengue as a probable novel condition for pituitary apoplexy because it may be associated with multiple risk factors for pituitary infarction or bleeding. Physicians should suspect pituitary apoplexy in patients with dengue hemorrhagic fever who develop a rapid onset of severe headache and vision defects, even in those without known pituitary adenomas.

Growth of an aggressive tumor during pregnancy in an acromegalic patient.

Pregnancy in acromegalic patients is a rare event, but is usually uneventful, with stable GH and IGF-I levels and no tumor enlargement. Medical treatment can usually be withdrawn without problems and although no major adverse event has been reported, the suspension of drug treatments is generally recommended. No case report exists in the literature regarding evolution of a somatotropinoma with invasiveness markers throughout pregnancy. We report a case of an acromegalic patient who was submitted to surgery and treated with octreotide LAR maintaining a stable residual tumor and an IGF-I close to the normal levels. Her tumor presented with a high Ki-67 (11.6%) and a low aryl hydrocarbon receptor-interacting protein (AIP) expression. When she became pregnant, octreotide LAR was withdrawn, and despite remaining asymptomatic during pregnancy, tumor growth occurred with compression of surrounding structures. In conclusion, pregnancy in acromegalic patients has usually a favorable prognosis with no tumor growth. However, in the presence of high Ki-67 labeling index and low AIP expression, tumor enlargement may occur and somatostatin analogue treatment throughout the pregnancy should be considered.