Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It has been previously suggested that inherited thyroxine-binding globulin (TBG) abnormalities in man may be due to mutations at a single X-chromosome-linked locus controlling TBG synthesis. However, abnormalities in TBG degradation have not been excluded. The availability of purified human TBG and its successful labeling with radioiodide allowed us to examine such possibility. Human TBG was purified by affinity chromatography, labeled under sterile conditions with 131I or 125I,, and mixed with [125I]thyroxine (T4) or [131I]T4, respectively, before their intravenous injection. Blood and urine samples were collected over a 10-day period, and the turnover parameters were calculated. In eight normal volunteers mean values +/-SD for TBG and T4 respectively, were as follows: Half time (t1/2) 5.3 +/- 0.4 and 7.0 +/- 0.6 days; distribution space (DS) 7.2 +/- 1.0 and 10.8 +/- 1.2 liters; and total daily degradation (D) 0.211 +/- 0.053 and 0.088 +/- 0.011 mumol/day. In all subjects, t1/2 of TBG was shorter than that of T4; and the DS was smaller. 2.4 mol of TBG was degraded for each mole of T4. In five of six subjects from four families, comprising hemizygous and heterozygous carriers of TBG absence, decrease, and excess, the t1/2 and DS for TBG were within the normal range. The D of TBG was proportional to the serum concentration of the protein. Changes in the T4 kinetics in these patients were compatible with euthyroidism and with the known alterations in the extrathyroidal T4 pool associated with the changes in serum TBG concentration. A striking decrease in the t1/2 of TBG was found only in a patient with acquired diminution in TBG concentration and in patients with thyrotoxicosis or other conditions apparently unrelated to thyroid dysfunction. TBG t1/2 was 2.5 days in a patient with multiple myeloma and 3.6 days in two patients with thyrotoxicosis. Decreased TBG t1/2 was also observed in three of six patients with nonthyroidal pathology and was associated with an increase in TBG D disproportionate to their level of serum TBG. These studies indicate that changes in TBG concentration in patients with X-chromosome-linked TBG abnormalities are due to alterations in its rate of synthesis. In other conditions, abnormalities of TBG degradation and/or rate of synthesis may be found.
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PMID:Metabolism of thyroxine-binding globulin in man. Abnormal rate of synthesis in inherited thyroxine-binding globulin deficiency and excess. 5 42

In two patients with extensive pulmonary tuberculosis who developed hypercalcaemia and hypokalaemia the hypercalcaemia appeared related to the use of small doses of vitamin D, which suggested patients with tuberculosis were hypersensitive to vitamin D. They were thus similar to patients with sarcoidosis, and it is interesting that the Kveim test result was positive in both cases. The hypercalcaemia was quickly suppressed with steroids. Hyperparathyroidism, thyrotoxicosis, Addison's disease, and multiple myeloma were excluded on clinical grounds and by the appropriate tests. The hypokalaemia was associated with increased renal excretion of potassium, and was probably due to distal tubular damage from hypercalcaemia.
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PMID:Hypercalcaemia and hypokalaemia in tuberculosis. 69 98

Obviously, the relentless decrease in bone mass that accompanies aging will continue the long sought "elixir of youth" is discovered. Individuals, because of race, sex, environmental, dietary, genetic or activity differences, will be more or less predisposed to symptomatic osteoporosis with increasing age. The careful and knowledgeable physician should, however, make every attempt to rule out potentially remediable, subtle forms of demineralizing disorders, such as apathetic or T3-thyrotoxicosis, hyperparathyroidism, malabsorption and osteomalacia or multiple myeloma. Not only do these diseases result in an accelerated loss of bone mass and an increased incidence of skeletal fractures but they mimic postmenopausal or senile osteoporosis radiologically. Once the metabolic or malignant disorders of bone metabolism have been effectively considered and ruled out, the senescent or postmenopausal osteoporotic patient should be treated judiciously with short-term estrogen therapy, a diet sufficient in vitamin D and calcium content and continued attempts to insure adequate skeletal mobilization. The addition of sodium fluoride and/or calcitonin to this regimen should not be attempted without extreme caution until the potentially harmful systemic effects of prolonged therapeutic trials have been appropriately assessed.
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PMID:Senile and postmenopausal osteoporosis. 76 91

A study of clinical renal and endocrinologic status was undertaken to determine whether the lowest maximal bone mass observed in premenopausal women, aged 20-40 years, was a result of undiagnosed disease or represented a continuum of measurement in young adult women. A clinical sample (n = 53) was generated from an epidemiologic cross-sectional study (n = 535) designed to characterized correlates of maximal bone mass. Cases were 28 premenopausal women whose femoral bone mass as in the lowest 5th percentile of the distribution, less than 0.75 g/cm2 at the femoral neck. Controls were 25 randomly selected premenopausal women whose femoral bone mass was within 1 SD of the mean of the femoral bone mass distribution. There was no indication of increased frequency of disease among the cases as compared with the controls. No occult hypogonadism, thyrotoxicosis, hyperparathyroidism, myeloma, or renal insufficiency was observed to explain lower bone mass measurement. However, cases had significantly lower estradiol levels (75 versus 106 pg/ml, P less than 0.05) and higher luteinizing hormone levels (3.8 versus 3.1 mIU/ml, P less than 0.07) than controls. Though preliminary, these findings suggest that lower estradiol levels may contribute to significant differences in bone mass even among healthy women at the time of maximal bone accumulation.
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PMID:Health and hormonal characteristics of premenopausal women with lower bone mass. 222 87

Osteoporosis is increasingly recognised in men. Low bone mass, risk factors for falling and factors causing fractures in women are likely to cause fractures in men. Bone mass is largely genetically determined, but environmental factors also contribute. Greater muscle strength and physical activity are associated with higher bone mass, while radial bone loss is greater in cigarette smokers or those with a moderate alcohol intake. Sex hormones have important effects on bone physiology. In men, there is no abrupt cessation of testicular function or 'andropause' comparable with the menopause in women; however, both total and free testosterone levels decline with age. A common secondary cause of osteoporosis in men is hypogonadism. There is increasing evidence that estrogens are important in skeletal maintenance in men as well as women. Peripheral aromatisation of androgens to estrogens occurs and osteoblast-like cells can aromatise androgens into estrogens. Human models exist for the effects of estrogens on the male skeleton. In men aged > 65 years, there is a positive association between bone mineral density (BMD) and greater serum estradiol levels at all skeletal sites and a negative association between BMD and testosterone at some sites. It is crucial to exclude pathological causes of osteoporosis, because 30 to 60% of men with vertebral fractures have another illness contributing to bone disease. Glucocorticoid excess (predominantly exogenous) is common. Gastrointestinal disease predisposes patients to bone disease as a result of intestinal malabsorption of calcium and colecalciferol (vitamin D). Hypercalciuria and nephrolithiasis, anticonvulsant drug use, thyrotoxicosis, immobilisation, liver and renal disease, multiple myeloma and systemic mastocytosis have all been associated with osteoporosis in men. It is possible that low-dose estrogen therapy or specific estrogen receptor-modulating drugs might increase BMD in men as well as in women. In the future, parathyroid hormone peptides may be an effective treatment for osteoporosis, particularly in patients in whom other treatments, such as bisphosphonates, have failed. Men with idiopathic osteoporosis have low circulating insulin-like growth factor-1 (IGF-1; somatomedin-1) concentrations, and IGF-1 administration to these men increases bone formation markers more than resorption markers. Studies of changes in BMD with IGF-1 treatment in osteoporotic men and women are underway. Osteoporosis in men will become an increasing worldwide public health problem over the next 20 years, so it is vital that safe and effective therapies for this disabling condition become available. Effective public health measures also need to be established and targeted to men at risk of developing the disease.
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PMID:Osteoporosis in men. New insights into aetiology, pathogenesis, prevention and management. 988 98

The ageing population is expected to increase the burden of osteoporosis on the health care system. Secondary causes of osteoporosis are found in a proportion of patients. There is much controversy regarding the best work-up for patients who have been diagnosed as having osteoporosis based on bone mineral density. It is difficult to decide where interventions should be targeted both from a patient's perspective and for cost effectiveness. We evaluated the utility of a standard panel (full blood count, plasma viscosity, plasma protein, electrophoresis, urine Bence Jones protein, thyroid function test, bone profile, fasting lipids and liver function test) of biochemical investigations in 327 consecutive patients (287 females, 40 males) referred to the new patient osteoporosis clinic from April 1999 to March 2000. Patients were characterised after measurement of spinal/femoral neck bone mineral density after a dual energy X-ray absorptiometry (DEXA) scan. There were 88 patients with osteoporosis, 91 with osteopenia, 130 had normal bone mineral density and 20 who did not have a bone scan. No case of multiple myeloma was found in this cohort of patients. There was no difference in the mean plasma viscosity of patients with and without osteoporosis (P=0.182). There was no significant difference in the abnormal urine calcium/creatinine (Ca/Cr ratio) in patients with osteoporosis and those without osteoporosis (P=0.316). There was no significant difference in the prevalence of hypothyroidism (P=0.213) or thyrotoxicosis (P=0.138) in patients with and without osteoporosis. There was no strong correlation between cholesterol concentrations and osteoporosis (r=0.069). We found no utility in performing a myeloma screen. A small proportion of patients had abnormalities of calcium homeostasis or thyroid disease. We recommend that a screening biochemical evaluation should be restricted to calcium/bone profile and thyroid function tests in patients with a presumptive diagnosis of osteoporosis.
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PMID:Utility of biochemical screening in the context of evaluating patients with a presumptive diagnosis of osteoporosis. 1668 94

Antithyroid drugs as thionamides are largely used in the treatment of the thyrotoxicosis. Side effects were reported in less than 10% of the cases, especially hematological, hepatic or skin allergies. One of the most severe manifestations is agranulocytosis, probably based on an immune mechanism that is exacerbated by the presence of the thyroid autoimmune disease itself. If the presence of the severe leucopenia is actually an epiphenomenon of a preexisting hematological disturbance as multiple myeloma is debated. The myeloma may also be correlated with an autoimmune predisposition. We present the case of a 56 years old female patient diagnosed with Graves' disease, who developed agranulocytosis after 8 months of therapy with thiamazole. Two months after antithyroid drug's withdrawal, the granulocytes number increased and she received therapy with radioiodine. Two years later she came back for diffuse bone pain that turned out to be caused by a multiple myeloma, confirmed by bone marrow biopsy. It might be a connection between the severe form of leucopenia that the patient developed and the medullar malignancy.
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PMID:Antithyroid drugs induced agranulocytosis and multiple myeloma: case report and general considerations. 2415 85

A 45-year-old man presented with a 3-month history of involuntary weight loss, anorexia, postural dizziness and intermittent fever. On investigation, he was found to have parathyroid hormone (PTH)-independent hypercalcaemia, with negative workup for 25-hydroxyvitamin D or 1,25-dihydroxyvitamin D excess, thyrotoxicosis, multiple myeloma and bony metastases. On further evaluation, he was detected to have primary hypoadrenalism with bilateral adrenal enlargement, secondary to adrenal histoplasmosis. Hypercalcaemia improved with hydration and physiological steroid replacement even before initiation of antifungal therapy, confirming adrenal insufficiency as the cause for hypercalcaemia. Hypercalcaemia resulting from hypoadrenalism secondary to adrenal histoplasmosis is rare and should be suspected whenever evaluating a patient with PTH-independent hypercalcaemia.
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PMID:Hypercalcaemia, adrenal insufficiency and bilateral adrenal histoplasmosis in a middle-aged man: a diagnostic dilemma. 3146 57