Cristina Bandeira

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.

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.

RELATIONSHIP BETWEEN SERUM VITAMIN D STATUS AND CLINICAL MANIFESTATIONS OF PRIMARY HYPERPARATHYROIDISM

OBJECTIVE To compare vitamin D status represented by serum 25-hydroxyvitamin D (25-OHD) levels in a group of patients with primary hyperparathyroidism, stratified by clinical manifestations. METHODS We studied 22 patients (18 women and 4 men) with primary hyperparathyroidism--5 patients with severe osteitis fibrosa cystica, 10 symptomatic patients with active renal stone disease without overt bone disease, and 7 asymptomatic patients. Bone mineral density (BMD) measurements (T-scores) were done at the lumbar spine, femoral neck, and distal radius, and laboratory data for the three subgroups were analyzed. RESULTS Although considerably younger than the asymptomatic group, patients with osteitis fibrosa had significantly lower mean serum 25-OHD levels (16.7 +/- 1.1 ng/mL versus 29.9 +/- 2.9 ng/mL; P = 0.003). Moreover, patients with osteitis fibrosa had significantly lower BMD in comparison with patients who had renal stone disease as well as asymptomatic patients for all sites measured. Serum parathyroid hormone levels were significantly higher in patients with osteitis fibrosa than in asymptomatic patients (1,352.8 +/- 297.2 pg/mL versus 145.0 +/- 43.7 pg/mL; P<0.02) as well as in comparison with patients who had renal stone disease (P<0.02). Patients with osteitis fibrosa had urinary N-telopeptide levels that were significantly higher than those in asymptomatic patients (501.5 +/- 201.7 versus 51.3 +/- 6.4 nmol/mmol creatinine; P = 0.02) and those in patients with renal stone disease (P = 0.01). CONCLUSION The findings in this study demonstrate that vitamin D deficiency or insufficiency may contribute to disease severity in primary hyperparathyroidism.

Differences in Accuracy of 99mTc-Sestamibi Scanning Between Severe and Mild Forms of Primary Hyperparathyroidism

Preoperative localization of the parathyroids using 99mTc-sestamibi scanning has not yet been established as a routine diagnostic procedure for primary hyperparathyroidism. Several studies have demonstrated a variable degree of accuracy (70%–98%) in asymptomatic patients. Methods: We evaluated the accuracy of this technique in 64 patients who underwent scanning between January 2000 and January 2005 according to the clinical manifestations of the disease. Results: The study included 25 asymptomatic patients (group I), 18 nephrolithiasis patients without overt bone disease (group II), and 21 patients with severe bone involvement and osteitis fibrosa cystica (group III). Mean serum calcium in groups I, II, and III was 10.98 ± 0.02, 11.32 ± 0.17, and 13.35 ± 0.35 mg/dL, respectively. Mean serum parathyroid hormone in groups I, II, and III was 135.45 ± 13.50, 165.85 ± 15.06, and 579.6 ± 628.4 pg/mL, respectively. The 99mTc-sestamibi scan results were positive in 64% of the patients in group I, in 83% of those in group II, and in 100% of those in group III. Of the patients with severe bone disease, 70% showed increased uptake on the initial images, whereas in the other groups, increased uptake was seen only on the delayed images, as expected. Conclusion: Our data show a high degree of accuracy for the use of 99mTc-sestamibi scanning as a localizing procedure in severe primary hyperparathyroidism.

Prevalence of cortical osteoporosis in mild and severe primary hyperparathyroidism and its relationship with bone markers and vitamin D status.

Studies on the prevalence of site-specific osteoporosis in patients with different clinical presentations of primary hyperparathyroidism (PHPT) are scarce in the literature. The present study aims to determine the prevalence of cortical osteoporosis in such patients by using 3-site dual-energy X-ray absorptiometry (lumbar spine, femoral neck, 1/3 radius). We studied 49 patients, 12 males and 37 females, with PHPT, who were separated into 3 groups: asymptomatic (AS), renal stone disease (RS), and osteitis fibrosa cystica (OF). Osteoporosis occurred as follows: lumbar spine-48% for AS, 17.6% for RS, and 100% for OF (p=0.0004); femoral neck-20% for AS, 12% for RS, and 85.7% for OF (p=0.0014); 1/3 radius-71% for AS, 53% for RS, and 86% for OF (p=0.2845). Serum calcium, parathyroid hormone, alkaline phosphatase, and beta-carboxy-terminal telopeptide were significantly higher in the OF group. The mean values for 25-hydroxyvitamin D were lower in OF group than AS and RS groups (15.2+/-6.3 ng/mL vs. 22.7+/-11.9 ng/mL and 20.3+/-7.0 ng/mL; p=0.2139). Based on these results, we conclude that the prevalence of osteoporosis is high in all sites studied and is almost universal in the OF patients. The great prevalence of cortical osteoporosis is seen even in young patients with less severe forms of the disease.

CHAPTER 22 – Clinical Presentation of Primary Hyperparathyroidism: India, Brazil, and China

The pattern of presentation of hyperparathyroidism has changed in the West such that nearly 70–80% patients are asymptomatic and do not usually suffer from its skeletal or renal complications. In contrast, primary hyperparathyroidism presents its traditional manifestations in the East and in some regions of the Southern Hemisphere. In these regions, it is associated with more symptoms, large parathyroid tumors, and a higher incidence of parathyroid cancers. Many of the similarities between traditional primary hyperparathyroidism of the West and contemporary primary hyperparathyroidism of the East are explained by the differences in prevailing surveillance patterns and vitamin D and calcium nutrition of the populations. The higher prevalence of parathyroid cancers may be a reflection of an exaggerated growth behavior of abnormal parathyroid tissue partly influenced by vitamin D and calcium nutritional status of the individual. It is reasonable to infer that more severe bone disease—such as osteitis fibrosa cystica, brown tumors, and pathologic fractures are likely only when excess parathyroid hormone secretion is accompanied by profound and prolonged vitamin D and calcium malnutrition. Continued observations and comparisons of patients with primary hyperparathyroidism from different parts of the world are likely to provide even greater insights into this ever-changing disease.

Mínimas alterações hormonais em paciente com grande feocromocitoma

We present a case report that the patient had symptoms suggesting pheochromocytoma, a large tumor (> 50 g) and a single minimally altered laboratorial test, exemplifying a diagnostic pitfall. A 31 y.o. male patient had two acute abdominal events, the last one accompanied by headache, arterial hypertension, facial flushing, perspiration and cutaneous pallor. In another admission, the patient had sustained arterial hypertension and cardiac arrhythmia. From laboratory analysis, the vanililmandelic acid was slightly modified. Scintigraphy disclosed a large adrenal mass suggesting pheochromocytoma. Histopathology confirmed this hypothesis. This report points out that patients with symptoms suggesting pheochromocytoma, even when plasma catecholamines and urinary metanephrines levels are normal, may harbor large tumors with a high catecholamines turnover or that had undergone hemorrhagic necrosis.