Francisco Bandeira

Current Issues in the Presentation of Asymptomatic Primary Hyperparathyroidism: Proceedings of the Fourth International Workshop

OBJECTIVE This report summarizes data on traditional and nontraditional manifestations of primary hyperparathyroidism (PHPT) that have been published since the last International Workshop on PHPT. PARTICIPANTS This subgroup was constituted by the Steering Committee to address key questions related to the presentation of PHPT. Consensus was established at a closed meeting of the Expert Panel that followed. EVIDENCE Data from the 5-year period between 2008 and 2013 were presented and discussed to determine whether they support changes in recommendations for surgery or nonsurgical follow-up. CONSENSUS PROCESS Questions were developed by the International Task Force on PHPT. A comprehensive literature search for relevant studies was undertaken. After extensive review and discussion, the subgroup came to agreement on what changes in the recommendations for surgery or nonsurgical follow-up of asymptomatic PHPT should be made to the Expert Panel. CONCLUSIONS 1) There are limited new data available on the natural history of asymptomatic PHPT. Although recognition of normocalcemic PHPT (normal serum calcium with elevated PTH concentrations; no secondary cause for hyperparathyroidism) is increasing, data on the clinical presentation and natural history of this phenotype are limited. 2) Although there are geographic differences in the predominant phenotypes of PHPT (symptomatic, asymptomatic, normocalcemic), they do not justify geography-specific management guidelines. 3) Recent data using newer, higher resolution imaging and analytic methods have revealed that in asymptomatic PHPT, both trabecular bone and cortical bone are affected. 4) Clinically silent nephrolithiasis and nephrocalcinosis can be detected by renal imaging and should be listed as a new criterion for surgery. 5) Current data do not support a cardiovascular evaluation or surgery for the purpose of improving cardiovascular markers, anatomical or functional abnormalities. 6) Some patients with mild PHPT have neuropsychological complaints and cognitive abnormalities, and some of these patients may benefit from surgical intervention. However, it is not possible at this time to predict which patients with neuropsychological complaints or cognitive issues will improve after successful parathyroid surgery.

Vitamin D deficiency: a global perspective

Vitamin D is essential for the maintenance of good health. Its sources can be skin production and diet intake. Most humans depend on sunlight exposure (UVB 290-315 nm) to satisfy their requirements for vitamin D. Solar ultraviolet B photons are absorbed by the skin, leading to transformation of 7-dehydrocholesterol into vitamin D3 (cholecalciferol). Season, latitude, time of day, skin pigmentation, aging, sunscreen use, all influence the cutaneous production of vitamin D3. Vitamin D deficiency not only causes rickets among children but also precipitates and exacerbates osteoporosis among adults and causes the painful bone disease osteomalacia. Vitamin D deficiency has been associated with increased risk for other morbidities such as cardiovascular disease, type 1 and type 2 diabetes mellitus and cancer, especially of the colon and prostate. The prevalence of hypovitaminosis D is considerable even in low latitudes and should be taken into account in the evaluation of postmenopausal and male osteoporosis. Although severe vitamin D deficiency leading to rickets or osteomalacia is rare in Brazil, there is accumulating evidence of the frequent occurrence of subclinical vitamin D deficiency, especially in elderly people.

Hashimoto's Encephalopathy: Systematic Review of the Literature and an Additional Case

Hashimotos encephalopathy, first described in 1966, is still problematic in terms of its pathophysiology, diagnosis, and treatment. The syndrome is more common in women, and is associated with autoimmune antithyroid antibodies. Presentation varies considerably; there may be episodes of cerebral ischemia, seizure, or psychosis, or there may be depression, cognitive decline, and periods of fluctuating consciousness. Because the symptoms respond so well to immunosuppressive treatment, prompt diagnosis and management are important. Here, the authors present a representative case report, along with a comprehensive review of current literature.

Prevalence of osteoporosis and vertebral fractures in postmenopausal women with type 2 diabetes mellitus and their relationship with duration of the disease and chronic complications

UNLABELLED Controversial data suggest that patients with type 2 diabetes mellitus have an increased risk of fractures despite having, in some studies, higher bone mineral density. METHODS The aim of this study was to determine the prevalence of osteoporosis and morphometric vertebral fractures in 148 postmenopausal diabetic women, aged 61.87±7.85 years, and their relationship with clinical and metabolic factors and chronic complications of the disease. RESULTS The prevalence of osteoporosis was 30.4% at lumbar spine (LS) and 9.5% at femoral neck (FN). The prevalence of vertebral fractures was 23%, mostly mild and located at the thoracic spine. Patients with fractures were older (P<.001), had been in the menopause for a long period (P=.005), had lower creatinine clearance (P=.026) had and lower bone mineral density at LS (P=.01) and FN (P=.042). The frequency of fractures increased with age (P<.001), with the duration of the disease (P=.037) and with the presence of retinopathy (P=.030). In patients with fractures, the prevalence of osteoporosis increased to 40% at LS (P=.004) and to 35.7% at FN (P=.049). After logistic regression adjustment, it was observed that the likelihood of presenting vertebral fractures was significantly increased at the age of 60 years or older (P<.001) and with the presence of osteoporosis at LS (P=.006), irrespective of blood glucose control. CONCLUSION We found a high prevalence of osteoporosis and vertebral fractures in postmenopausal women with type 2 diabetes mellitus, irrespective of blood glucose control, and these conditions were more frequent in long-standing disease and in patients with retinopathy and impaired renal function.

Vitamin D deficiency and its relationship with bone mineral density among postmenopausal women living in the tropics

OBJECTIVE To determine vitamin D (25OHD) status and its relationship with bone mineral density (BMD) in 93 postmenopausal women. SUBJECTS AND METHODS Patients were distributed in two groups: Group 1 - 51 to 65 years (n = 45) and Group 2 - 66 to 84 years (n = 48); 25OHD and PTH serum were analyzed and a DXA scan of the lumbar spine (LS) and femoral neck (FN) were taken. RESULTS Mean +/- SD of serum 25OHD levels were 80.6 +/- 43.3 nmol/L (Group 1) and 63.7 +/- 27.6 nmol/L (Group 2); 24% had 25OHD levels < 25 nmol/L and 43.7% < 50 nmol/L. The prevalence of vitamin D deficiency at the 62.5 nmol/L cutoff increased significantly with age. Patients with hypovitaminosis D had a lower BMD at the FN (0.738 +/- 0.102 vs. 0.793 +/- 0.115 g/cm, p = 0.03) and had been postmenopausal for longer (21.0 +/- 8.4 vs. 16.2 +/- 8.4 years, p = 0.01). CONCLUSION We found a high prevalence of hypovitaminosis D in postmenopausal women. Age, years elapsed since menopause and low BMD in the FN were associated with deficiency.

From mild to severe primary hyperparathyroidism: the Brazilian experience

Primary hyperparathyroidism often presents as an asymptomatic disorder. In our institution, routine serum calcium measurements have now been used as part of medical examination for 23 years. Out of 124 patients consecutively seen at our institution, 47% presented with no symptoms related to the disease, while 25% presented with severe skeletal involvement and osteitis fibrosa cystica, 25% with renal stone disease without overt bone involvement, and 2% with the typical neuropsychiatric syndrome. This same pattern is seen in the city of São Paulo. In severe disease pathological fractures are frequently seen, especially in long bones of the lower extremities, and also loss of lamina dura of the teeth and salt-and-pepper appearance of the skull. Bone mineral density is extremely low in these patients but usually show remarkable recovery following surgical cure. Serum PTH and bone markers are considerable higher in severely affected patients, who also have a high rate of vitamin D deficiency, and the parathyroid lesion is easier located compared with asymptomatic patients. From pathological specimens 87% had histological confirmation of a single adenoma, 6.4% multiple gland hyperplasia and 3.8% carcinoma.

Paget's disease of bone

Pagets disease of bone is a focal disorder of bone remodeling accompanied initially by an increase in bone resorption, followed by a disorganized and excessive formation of bone, leading to pain, fractures and deformities. It exhibits a marked geographical variation in its prevalence. In Brazil it predominantly affects persons of European descent. The majority of the reported cases of the disease in Brazil are from Recife, owing to its peculiar mixed European colonization over approximately four centuries. The etiology is complex and involves both genetic and environmental factors. The disease is often asymptomatic and diagnosis is usually based on biochemical markers of bone turnover, radionuclide bone scan and radiological examination. Bisphosphonates, in particular zoledronic acid, are regarded as the treatment of choice for Pagets disease of bone.

Bone disease in primary hyperparathyroidism

Bone disease in severe primary hyperparathyroidism (PHPT) is described classically as osteitis fibrosa cystica (OFC). Bone pain, skeletal deformities and pathological fractures are features of OFC. Bone mineral density is usually extremely low in OFC, but it is reversible after surgical cure. The signs and symptoms of severe bone disease include bone pain, pathologic fractures, proximal muscle weakness with hyperreflexia. Bone involvement is typically characterized as salt-and-pepper appearance in the skull, bone erosions and bone resorption of the phalanges, brown tumors and cysts. In the radiography, diffuse demineralization is observed, along with pathological fractures, particularly in the long bones of the extremities. In severe, symptomatic PHPT, marked elevation of the serum calcium and PTH concentrations are seen and renal involvement is manifested by nephrolithiasis and nephrocalcinosis. A new technology, recently approved for clinical use in the United States and Europe, is likely to become more widely available because it is an adaptation of the lumbar spine DXA image. Trabecular bone score (TBS) is a gray-level textural analysis that provides an indirect index of trabecular microarchitecture. Newer technologies, such as high-resolution peripheral quantitative computed tomography (HR-pQCT), have provided further understanding of the microstructural skeletal features in PHPT.

Vascular Effects of Bisphosphonates—A Systematic Review

Background Osteoporosis and cardiovascular disease are interconnected entities with pathophysiological similarities. Bisphosphonates are therapeutic options available for resorptive bone diseases; however, experimental evidence has demonstrated a role for bisphosphonates in the inhibition of atherogenesis. Methods A systematic review of the vascular effects of bisphosphonates on atherosclerosis was performed. Vascular effects were evaluated by the thickening of the intima-media of carotid arteries and calcification of the coronary and aorta arteries. Electronic databases PubMed, The Cochrane Library, and Embase from January 1980 to May 2011 were searched. Results Of 169 potentially relevant articles, 9 clinical trials were selected. Two articles showed the benefit of the use of etidronate (–0.038 mm, P <0.005) and alendronate (–0.025 mm, P <0.05) on carotid artery intima-media thickening (CIMT) after one year. One article found no changes associated with the use of alendronate. The use of risedronate was associated with a reduction of plaque score on the carotid arteries (decrease of 1% at 1 year, P = 0.015). Of those studies that evaluated the effect on coronary artery calcification (CAC), the results are conflicting: one study showed no changes with use of etidronate and in another, etidronate resulted in inhibition of the process of CAC after 1 year of follow-up (–372 mm3 in CAC score, P <0.01). Three studies showed positive effects of etidronate on the aortic calcificaton (AC) score, showing no effect with use of ibandronate, and another showed a inhibition in the progression of the abdominal AC score with use of risendronate (P = 0.043). Conclusion Bisphosphonates seem to have an inhibitory effect on the atherosclerotic process; however, larger placebo-controlled studies are needed to better clarify this issue.

Prevalência de osteoporose e fraturas vertebrais em mulheres na pós-menopausa atendidas em serviços de referência

Este estudo tem por objetivo verificar a prevalencia de osteoporose e a presenca de fraturas vertebrais em mulheres na pos-menopausa. Foram estudadas, em servicos de referencias, 627 mulheres com idade acima de 50 anos, com media de idade de 63,9 ± 8,3 anos, tempo de menopausa de 16,2 ± 8,6 anos, e indice de massa corporea de 26,6 ± 4.3 Kg/m2. A prevalencia de osteoporose foi de 28,8% na coluna lombar e de 18,8% no colo do femur. Esta foi maior nas pacientes que apresentaram historia de fraturas quando jovens. Na faixa entre 60 a 69 anos, 33,2% tinham osteoporose na coluna lombar e entre 70 e 79 anos, 38,2%. Das pacientes com mais de 80 anos 54,5% apresentam osteoporose na coluna lombar e 72,7% no colo do femur. Trinta e sete por cento tinham fraturas, sendo que 9% apresentam fraturas grau I, e 10,9% fraturas severas. Considerando-se os diversos grupos etarios, a prevalencia de fraturas vertebrais foi de 20% entre 50 e 59 anos, 25,6% entre 60 e 69 anos, 58,3% entre 70 e 79 anos, e 81,8% entre 80 e 89 anos. Em mulheres na pos-menopausa, a maioria sem sintomas clinicos, verificamos uma alta taxa de prevalencia de osteoporose, e fraturas vertebrais.