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[Molecular aspects of the etiopathogenesis of the parathyroid gland diseases].

Current views on the molecular aspects of familial parathyroid gland diseases have been presented (familial primary hyperparathyroidism, hypoparathyroidism and psuedohypoparathyroidism). Their inherited mode and genetic abnormalities have been described. Particularly, the following genes: HRPT2, MEN1, RET, CASR, GNAS have been shown. Localization, structure, expression and structural changes (mutations) found in patients with familial parathyroid gland diseases have been presented. Attention has been paid to clinical and histopathologic symptoms, which should indicate the need to undertake genetic studies.

Chromogranins↗

[Imaging in parathyroid gland diseases with relation to surgery].

BACKGROUND: Despite the progress in the imaging techniques, the satisfactory preoperative detection of the hyperactive parathyroid glands has not been guaranteed yet. Many complementary techniques have been introduced including ultrasound imaging, CT-scanning, MRI and scintigraphy, also supported by intraoperative methods (methylene blue injections, gamma-probing, intraoperative PTH level assessment) simplifying the detection of the glands and assuring the surgeon on the adequacy of his/her treatment. DESIGN: The authors describe the methods instituted nowadays, and compare their quality parameters, applicability, indications and limitations. The critical review is accompanied by a brief presentation of own experience including 172 cases of hyperparathyroidism treated in the Department of General, Gastroenterological and Endocrinological Surgery, Medical University of Gdansk, Poland between 1996 and 2003. CONCLUSIONS: The authors conclude that radionuclid-based methods (Tc (99m)-MIBI preoperative scintigraphy and Tc (99m)-MIBI intraoperative gamma-probing) seem to be the most effective in both preoperative and intraoperative detection of hyperfunctioning parathyroids. It is also suggested that the effectiveness of the imaging is higher in primary than in secondary hyperparathyroidism. It is underlined that the effectiveness of the operative treatment is strongly determined by the experience of the operating endocrine surgeon.

Diagnosis, Differential↗

Mortality in sporadic primary hyperparathyroidism: nationwide cohort study of multiple parathyroid gland disease.

BACKGROUND: The risk of dying from primary hyperparathyroidism (pHPT) is controversial and has been explored mainly in single parathyroid gland disease. The present study investigates mortality in pHPT due to multiple parathyroid gland disease. METHODS: We used the nationwide Swedish In-patient Register and Cause-of-Death Registry to compare the mortality in 3485 Swedish patients subjected to parathyroidectomy during 1964 to 1999 with that of the Swedish population (standardized for age, gender, and calendar year). The patient cohort includes 36,596 person years. RESULTS: Increased risk of death beyond the first postoperative year (standardized mortality ratio, 1.4; 95% CI, 1.37-1.52) was found in both sexes and for all age intervals below 80 years. The increased risk persisted more than 15 years postoperatively and related to cardiovascular diseases, diabetes mellitus, urogenital diseases, and malignant disorders. The increased risk of dying in cardiovascular diseases normalized during 1990 to 1999. CONCLUSIONS: pHPT caused by multiple parathyroid gland enlargement is associated with an excessive mortality similar to pHPT of single parathyroid adenoma. The findings substantiate that modern modes of surgical treatment for pHPT normalize the risk of dying from cardiovascular complications and that the hyperpararthyroid state per se is the possible cause of the premature death.

Adult↗

Preoperative diagnosis of occult parathyroid hyperplasia by calcium infusion in patients with multiple endocrine neoplasia, type 2a.

Hereditary multiple endocrine neoplasia, type 2 (MEN 2) comprises medullary thyroid carcinoma (MTC) and bilateral pheochromocytoma; the syndrome includes two major variants, MEN 2a (normal appearance, parathyroid disease common) and MEN 2b (mucosal neuromas, Marfanoid habitus, parathyroid disease rate). Patients with MEN 2a may be normocalcemic, with normal basal serum immunoreactive parathyroid hormone (iPTH) levels, yet have parathyroid hyperplasia discovered during thyroid surgery. In an attempt to predict the presence of this occult parathyroid hyperplasia, we performed calcium infusion (15 mg Ca++/kg/4 hours) in six patients with MEN 2a, seven patients with MEN 2b, and eight normal subjects. iPTH was measured in samples taken at one hour intervals during the infusion with a sensitive radioimmunoassay (antiserum GP 1M [Arnaud]). The iPTH values (expressed as per cent of the basal value) in the normal, MEN 2a, and MEN 2b groups at the fourth hour were 38.0 +/- 3.8% (mean +/- SE), 79.2 +/- 7.2%, and 47.8 +/- 5.2%. These iPTH values for patients with MEN 2a were significantly different from normal (P less than 0.001) and from those of the patients with MEN 2b (P less than 0.001). All MEN 2a patients had parathyroid hyperplasia at cervical exploration; parathyroid histology in the MEN 2b patients was normal. Failure of iPTH suppressibility in the MEN 2a patients was not due either to the plasma calcitonin or to achieved serum calcium concentrations. The normal iPTH suppressibility in MEN 2b is consistent with the concept that the parathyroid disease in MEN 2a is genetically determined, and not secondary to MTC and high plasma calcitonin concentration. Calcium infusion combined with the measurement of serum iPTH levels may detect occult parathyroid hyperplasia in patients with MEN 2a, normocalcemia, and normal basal iPTH values. The identification and follow-up of similar patients should establish the natural history of this unusual parathyroid disease.

Adolescent↗

Effect of growth factors on growth of bovine parathyroid cells in serum-free medium.

Published work has suggested a possible role of the epidermal growth factor receptor (EGFr) in parathyroid disease. Bovine parathyroid cells (BPCs) are frequently used as a tissue model for studying parathyroid disorders. We have studied the effect of the EGFr ligands EGF and transforming growth factor alpha (TGFalpha), alone and with insulin-like growth factors IGF-I and IGF-II on BPC growth. Experiments were run in triplicate and repeated three times. Cell numbers were assessed on day 5 by colorimetric MTT assay as well as by tritiated thymidine uptake. Results show that TGFalpha alone (p < 0.05) and IGF-I and IGF-II alone (p < 0.05) significantly stimulated growth over controls (t-test). Furthermore, the combination of TGFalpha with IGF-I and IGF-II exhibited significant enhancement above that seen with IGF-I and IGF-II alone (p < 0.01). EGF did not stimulate growth over controls. EGFr may be expressed in BPCs, but TGFalpha exhibits a more potent growth stimulus than EGF. Addition of IGF-I or IGF-II to the growth medium further enhances this effect.

Animals↗

[Aging of brain and the maintenance of the function].

Some diseases develop dementia, but they may be dementia-like-situation, such as depression and drugs induced one. There are many causes as an etiology of dementia. Among them a lots of diseases are treatable dementia, like chronic subdural hematoma, normal pressure hydrocephalus, brain abscess, syphilis, herpetic encephalitis, Wilson's disease, hypothyroidism, parathyroid disease, vitamin B12 deficiency, pellagra etc. In examination of patients with dementia, exact history taking, physical examination and laboratory examination should be done carefully. In the patients with Alzheimer's dementia and cerebrovascular disease's dementia, as many risk factors are known, we must try to treat and exclude each risk factor and protect the dementia. Inactivity of physical and mental function is reported to induce the dementia, so activation of them could prevent the development and the progression of dementia. In future the methods of the prevention of apoptosis and cell death would be found in order to prevent the dementia. Free radical scavenger, nerve trophic factor, cytokine, antagonist of glutamate etc. will have the possibility to become the medicine for the dementia. The nerve transplantation, nerve transmitter, nerve peptide etc. might serve as the allopathic treatment for the dementia.

Aging↗

The diagnostic utility of computed tomography for preoperative localization in surgery for hyperparathyroidism.

OBJECTIVES/HYPOTHESIS: Successful unilateral or minimal-access parathyroid exploration and reoperative surgery of the parathyroid glands requires accurate preoperative localization of parathyroid disease. Although ultrasound and nuclear imaging techniques have an established role in this regard, the use of computed tomography (CT) for parathyroid exploration is not well understood. The purpose of the present study was to better define the diagnostic utility of CT in preoperative localization of the abnormal gland in surgery for hyperparathyroidism. STUDY DESIGN: Retrospective cohort study. METHODS: All parathyroid explorations performed at Oregon Health and Science University (Portland, OR) between 2000 and 2002 were reviewed. The study group was limited to patients with hyperparathyroidism in whom localization failed preoperatively using ultrasound and/or sestamibi scanning and subsequent investigation using CT imaging was performed. Operative, pathological, and imaging reports were then analyzed to assess the accuracy of CT imaging for localizing parathyroid disease. RESULTS: Twenty-two patients with hyperparathyroidism were investigated preoperatively using CT imaging. Parathyroid exploration was successful in all but one patient, leaving 21 patients in all in the cohort. The majority of cases (67%) were reoperative, and all patients had previously undergone inconclusive ultrasound and/or sestamibi scanning. Computed tomography correctly localized parathyroid disease in 18 (86%) of the 21 patients who underwent successful extirpation of parathyroid disease and was able to identify abnormal glands with equal utility in the neck and the chest. CONCLUSION: When ultrasound or sestamibi are unsuccessful, CT imaging can provide valuable preoperative localizing information before surgery for hyperparathyroidism, particularly in patients with recurrent or persistent disease.

Adolescent↗

Parathyroid hormone and parathyroid hormone-related protein in the investigation of hypercalcaemia in two hospital populations.

BACKGROUND AND OBJECTIVE: Parathyroid hormone-related protein (PTHrP) produced by cancers has a central role as a humoral mediator of hypercalcaemia in patients with malignancy. Since the prevalences of hypercalcaemia of malignancy and parathyroid disease reflect the population studied, hypercalcaemic patients from a district general hospital (DGH) and an oncology centre (OC) were studied in order to assess the diagnostic role of assays for serum PTH and plasma PTHrP in different clinical settings. DESIGN: A prospective study of consecutive patients presenting with their first episode of hypercalcaemia during an 18-month period. PATIENTS: A total of 123 patients (DGH, n = 69; OC, n = 54) had corrected serum calcium concentrations > 2.65 mmol/l. MEASUREMENTS: PTH, PTHrP, calcium and albumin were measured together with urine calcium and creatinine, enabling fractional calcium excretion to be assessed. Urine cyclic adenosine monophosphate was also measured. RESULTS: Hypercalcaemia was attributed to malignancy alone in 72 patients (DGH, n = 20; OC, n = 52), benign causes in 42 (DGH, n = 42) and parathyroid disease coexisting with malignancy in 9 (DGH, n = 7; OC, n = 2). Plasma PTHrP levels were increased in 59/72 (82%) patients with hypercalcaemia due to malignancy. Measurements of both analytes contributed to a change in the final diagnosis in 12 patients (10%). Thus serum PTH was increased in seven patients with parathyroid disease coexisting with malignancy, and plasma PTHrP was increased in five patients with previous undiagnosed malignancy. Median survival for patients with parathyroid disease and coexisting malignancy was 13 months compared with 3 months for those with hypercalcaemia due to malignancy alone (P < 0.02). CONCLUSIONS: Since hypercalcaemia was attributable to parathyroid disease in 10% of all patients with malignancy we advise measurement of serum PTH at the initial presentation of hypercalcaemia in all patients, while plasma PTHrP may be useful to identify those patients in whom malignancy may not be clinically apparent, or coexist with primary hyperparathyroidism.

Calcium↗

Management of primary hyperparathyroidism caused by multiple gland disease.

Multiple gland parathyroid disease is the pathological finding in primary hyperparathyroidism (HPT) in about 10% to 20% of all patients and in approximately a third of all patients with persistent or recurrent disease. The variability of multiple gland disease spans from 2 adenomas to diffuse hyperplasia in patients with multiple endocrine neoplasia type 1. This variability calls into question the proposed common pathophysiologic background in all of these cases. As primary treatment of multiple gland primary HPT, subtotal parathyroidectomy and thymectomy or total parathyroidectomy and heterotopic autotransplantation including thymectomy can be equally advocated. Recurrent hyperparathyroidism frequently occurs in cases of diffuse parathyroid hyperplasia. This must be considered especially in patient follow up and before each surgical procedure. Thus, a defined but adaptable therapeutic regimen might prevent permanent hypoparathyroidism and persistent hyperparathyroidism.

Humans↗

Thyroid carcinoma and hyperparathyroidism after radiation therapy for adolescent acne vulgaris.

Thyroid and parathyroid disease after head and neck irradiation in infancy and childhood is well known. Patients irradiated for facial acne were older and received a comparatively lower dose of radiation. These mitigating factors suggest a decreased incidence of thyroid and parathyroid disease in these patients. Over the past 28 years (1961 through 1989), 347 consecutive patients were operated on for radiation-associated thyroid and/or parathyroid disease. One hundred and ten patients in this group were irradiated for treatment for adolescent facial acne vulgaris. The interval between radiation exposure and thyroidectomy ranged from 7 to 57 years (mean, 30 years). The overall incidence of thyroid carcinoma was 31% (34 of 110 patients). Regional metastases in 10 patients (29%) were treated with modified radical neck dissection. Hyperparathyroidism, detected in 31% (34 of 110 patients) of this population, was treated with sub-total parathyroidectomy in all cases. The association of thyroid carcinoma and hyperparathyroidism after adolescent radiation exposure for acne vulgaris appears to be more than coincidental. The incidence of thyroid and parathyroid disease may be independent of the timing and dosage of radiation treatment. These thyroid and parathyroid tumors may develop decades after the initial radiation exposure.

Acne Vulgaris↗

Alfacalcidol in the therapy of renal bone disease.

Parathyroid hormone increases due to hypocalcemia even in the early phases of renal insufficiency. At the same time, hyperphosphatemia develops due to decreasing renal excretion which, in turn, intensifies secondary hyperparathyroidism. The cornerstones for prevention and therapy of renal osteopathy are, therefore, efficient lowering of phosphate levels and the early substitution of vitamin-D3 metabolites. In a post marketing surveillance (PMS) of almost 2,000 dialysis patients with renal osteopathy, the course of therapy with Alfacalcidol (Bondiol) was observed over a 6-month period. In 55.9% of cases, Alfacalcidol was administered at a daily dose of 0.25 microg. In 26.6% of patients, Alfacalcidol was administered every second day at a dose of 0.25-1 microg/d. In 16.1% of patients, Alfacalcidol was administered as pulse-therapy, mostly at a dose of 1-2 microg once or twice per week. To lower phosphate levels, 54.8% of patients received calcium compounds, 9.2% aluminium compounds, and 21.7% aluminium compounds in combination with calcium compounds. 14.3% of patients did not receive phosphate binding agents. Two thirds of patients had received active vitamin-D3-metabolites prior to commencing therapy with alfacalcidol, most frequently calcitrol. In 58.1%, the dialysis solution used had a calcium concentration of 1.5 mmol/l (44.8%) or lower; whereas in 41.9%, a higher calcium concentration was used--mostly 1.75 mmol/l (3 8%). During the observation period, serum concentrations of calcium and phosphate remained constant, suggesting that the risk of hypercalcemia due to therapy with Alfacalcidol was not increased. It was found that elevated alkaline phosphatase and parathyroid hormone levels could be significantly lowered (statistically). These effects could be observed both in patients who had been previously treated with vitamin-D3-metabolites and in patients without prior therapy. Efficacy and tolerability of therapy with Alfacalcidol was assessed to be very high by the attending nephrologists.

Adolescent↗