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PubMed2006

[Multiple endocrine neoplasia type 2].

The term multiple endocrine neoplasia (MEN) was introduced by Steiner et al. in 1968 to describe disorders that include a combination of endocrine tumors. The Wermer syndrome was designed as MEN 1 and the Sipple syndrome as MEN 2. Sizemore et al. (1974) completed that the MEN 2 category included 2 subgroups: patients with medullary thyroid carcinoma (MTC), pheochromocytoma, and parathyroid disease and a normal appearance (MEN 2A) and other without parathyroid disease but with mucosal neuromas and mesodermal abnormalities (MEN 2B). MTC is usually the first tumor diagnosed. The diagnosis of MTC has several implications: disease extent should be evaluated, pheochromocytoma and hyperparathyroidism should be screened and whether the MTC is sporadic or hereditary should be determined by a direct analysis of the RET proto-oncogene. Here, the pathological characteristics, genetic abnormalities, and clinical features of MEN 2 are discussed. The diagnostic and therapeutic approaches used to patients with clinical disease and carriers identified through familiar screening are also described. Progresses related especially to genetic screening and earlier intervention have permitted an improvement in the long-term outcome. However, treatment for disseminated disease is still ineffective.

Carcinoma, Medullary↗
PubMed2006

Galectin-3 and Ki-67 expression in multiglandular parathyroid lesions.

Hyperplastic and neoplastic parathyroid lesions may present overlapping morphologic features, and several markers have been proposed to distinguish benign from malignant growths. Recently, it was reported that galectin-3 is a useful marker of malignancy in uniglandular parathyroid diseases. To investigate galectin-3 and Ki-67 immunoexpression in parathyroid hyperplastic disease, 63 multiglandular lesions (13 primary, 40 secondary, and 10 tertiary hyperplasia cases) were analyzed and compared with 45 control cases of parathyroid adenomas and 24 carcinomas. Our data showed that hyperplastic lesions responsible for primary nonfamilial or tertiary hyperparathyroidism, as well as parathyroid adenomas, were negative for galectin-3, as opposed to carcinomas. In addition, secondary and familial primary hyperplasia cases were surprisingly positive for galectin-3 in approximately two thirds of cases. All hyperplastic lesions (positive or negative for galectin-3) had a low Ki-67 index. Based on these findings, secondary hyperplasia has a low proliferative potential but an unexplained galectin-3 reactivity, which reduces its diagnostic role in differentiating benign from malignant nodules in the context of multiglandular parathyroid diseases.

Adenocarcinoma↗
PubMed1984

Nephrogenous cyclic AMP and plasma parathyroid hormone in hypercalcaemia: the influence of renal function.

Immunoreactive parathyroid hormone (PTH) levels and nephrogenous cyclic adenosine monophosphate (cAMP) have been reported to be useful parameters in the diagnosis of hyperparathyroidism. Measurements in hyperparathyroid patients usually give values above the normal range when PTH is measured with a carboxyterminal radioimmunoassay and when nephrogenous cAMP is related to glomerular filtration rate. We tested these two parameters in two groups of hypercalcaemic patients (twelve cases of primary hyperparathyroidism and fourteen cases of hypercalcaemia of non-parathyroid origin) and in two groups of normocalcaemic subjects (twenty-one young healthy volunteers and fourteen elderly subjects without parathyroid disease). Slight impairment of renal function caused elevated values of immunoreactive parathyroid hormone in a carboxyterminal radioimmunoassay and also of nephrogenous cAMP when related to glomerular filtration rate. We found that elevated nephrogenous cAMP without parathyroid disease could be attributed to renal insufficiency and to the mode of expression generally used for the nephrogenous cAMP.

Adolescent↗
PubMed2005

Familial multiple endocrine neoplasia: the first 100 years.

In 1903, Erdheim described the case of an acromegalic patient with a pituitary adenoma and three enlarged parathyroid glands. Fifty years later, Underdahl et al reported 8 patients with a syndrome of pituitary, parathyroid, and pancreatic islet adenomas. In 1954, Wermer found that the syndrome was transmitted as a dominant trait. In 1959, Hazard et al described medullary (solid) thyroid carcinoma (MTC), a tumor that later was found to be a component of two endocrine syndromes. The first of these described by Sipple in 1961 comprised pheochromocytoma, MTC, and parathyroid adenoma. The second, described by Williams et al in 1966, was the combination of mucosal neuromas, pheochromocytoma, and MTC. In 1968, Steiner et al introduced the term "multiple endocrine neoplasia" (MEN) to describe disorders featuring combinations of endocrine tumors; they designated the Wermer syndrome as MEN 1 and the Sipple syndrome as MEN 2. In 1974, Sizemore et al concluded that the MEN 2 category included two groups of patients with MTC and pheochromocytoma: one with parathyroid disease and a normal appearance (MEN 2A) and the other without parathyroid disease but with mucosal neuromas and mesodermal abnormalities (MEN 2B). Later, additional nonendocrine conditions (von Recklinghausen neurofibromatosis and von Hippel-Lindau disease) were found accompanying other more recently described familial MEN syndromes, indicating that these diseases are very complicated disorders.

Endocrinology↗
PubMed2006

Increased plasma concentrations of N-terminal pro-B-type natriuretic peptide in patients with mild primary hyperparathyroidism.

OBJECTIVE: Primary hyperparathyroidism (PHPT) is associated with heart disease. The aims of the present study were to evaluate how cardiac function and secretion of N-terminal pro-B-type natriuretic peptide (NT-proBNP) correlate in patients with mild PHPT, and how the plasma level of NT-proBNP is influenced by cure of the parathyroid disease. DESIGN AND PATIENTS: Forty-two patients with PHPT without symptoms of heart disease were examined before and 1 year after curative parathyroidectomy. MEASUREMENTS: Plasma or serum concentrations of NT-proBNP, calcium, PTH, creatinine, oestradiol, testosterone and SHBG were measured. Cardiac function was evaluated by equilibrium radionuclide angiography (ERNA). RESULTS: At baseline, NT-proBNP levels correlated negatively with systolic function [left ventricular ejection fraction (LVEF), P < 0.001]. Twelve per cent of the patients had NT-proBNP levels above normal reference values preoperatively. One year postoperatively, the corresponding proportion was 21%. The mean plasma concentration of NT-proBNP increased after parathyroidectomy (P < 0.01) in parallel with a dip in diastolic function (peak filling rate, P < 0.05) and a falling trend in systolic function (LVEF, P = 0.08). The postoperative percentage changes in circulating NT-proBNP and total oestradiol correlated positively (P < 0.05). CONCLUSIONS: Patients with mild PHPT and normal renal function may have high levels of circulating NT-proBNP despite the absence of symptomatic heart disease. Cure of the parathyroid disease is followed by a further increase in NT-proBNP secretion in parallel with ERNA measures, indicating subclinical changes in heart function. These results are in line with data indicating an association between PHPT and increased risk of premature death.

Aged↗
PubMed2000

Contributing factors in resistant hypertension. Truly refractory disease is rarely found in a properly conducted workup.

Systematic evaluation of each patient with refractory hypertension is necessary to identify conditions or altered mechanisms of hypertension that are amenable to targeted therapy. Issues that should be carefully investigated are appropriateness of the regimen, possible drug interactions, patient compliance, associated conditions (alcohol or recreational drug use, hyperinsulinemia), pseudohypertension, office hypertension, and volume overload. When these problems are eliminated, causes of secondary hypertension should be sought, the most common being coarctation of the aorta, Cushing's syndrome, primary aldosteronism, pheochromocytoma, renovascular disease, thyroid and parathyroid disease, and renal parenchymal disease. In a few cases, a careful hemodynamic and neurohumoral assessment is needed to direct treatment. When the recommended stepwise workup is followed, hypertension that is truly refractory to treatment is a rare finding.

Algorithms↗
PubMed2005

A critical role for enhanced TGF-alpha and EGFR expression in the initiation of parathyroid hyperplasia in experimental kidney disease.

The parathyroid hyperplasia secondary to kidney disease is associated with enhanced expression of the growth promoter transforming growth factor-alpha (TGF-alpha). TGF-alpha stimulates growth through activation of its receptor, the epidermal growth factor receptor (EGFR), normally expressed in the parathyroid glands. Because enhanced coexpression of TGF-alpha and EGFR causes aggressive cellular growth, these studies utilized highly specific inhibitors of EGFR tyrosine kinase, a step mandatory for TGF-alpha-induced EGFR activation, to assess the contribution of growth signals from enhanced expression of TGF-alpha exclusively or both TGF-alpha and EGFR to the rapid parathyroid growth induced by kidney disease and exacerbated by high-phosphorus (P) and low-calcium (Ca) diets in rats. The enhancement in parathyroid gland weight and proliferating activity (proliferating cell nuclear antigen/Ki67) induced by kidney disease and aggravated by either high P or low Ca intake, within the first week after 5/6 nephrectomy, in rats, coincided with simultaneous increases (2- to 3-fold) in TGF-alpha and EGFR content. Conversely, prevention of the increases in both TGF-alpha and EGFR paralleled the efficacy of either P restriction or high-Ca intake in ameliorating uremia-induced parathyroid hyperplasia. More importantly, suppression of TGF-alpha/EGFR signaling, through prophylactic administration of potent and highly selective inhibitors of ligand-induced EGFR activation, completely prevented both high-P- and low-Ca-induced parathyroid hyperplasia as well as TGF-alpha self-upregulation. Thus enhanced parathyroid TGF-alpha/EGFR expression, self-upregulation, and growth signals occur early in kidney disease, are aggravated by low-Ca and high-P intake, and constitute the main pathogenic mechanism of the severity of parathyroid hyperplasia.

Animals↗
PubMed2000

[A clinical study of the nonrecurrent inferior laryngeal nerve in seven patients].

Nonrecurrent inferior laryngeal nerves (NRILNs) are generally discovered during thyroid or parathyroid gland surgery. If the presence of the NRILN is unknown, nerve injury can easily occur during surgery. Here we report seven cases of NRILN, describe how to identify a NRILN, and discuss whether preoperative or postoperative examination is necessary. Between October 1998 and March 2000, we performed cervicotomy in 1889 patients for thyroid and parathyroid disease and identified a NRILN in 7 of them (0.37%). A NRILN was found in 7 of 903 patients (0.78%) on the right side but in none of 855 patients on the left. The NRILN branched off the vagus nerve at the level of the upper or middle third of the thyroid in 5 patients, and in the other 2 patients branched off the vagus nerve at the level of the lower third of the thyroid. We had not predicted the presence of NRILN before surgery in any of these 7 NRILN patients. Clinically, three patients with NRILN had mild dysphagia and the sensation of a foreign body in the throat. Three patients had abnormal chest X-ray findings showing a linear aortic arch shadow, a sign regarded as evidence of arteria lusoria. Three patients underwent MR angiography, and an aberrant right subclavicular artery was identified. Surgery was performed safely, and no postoperative vocal cord palsy occurred in any of the seven NRILN patients. It is to some extent possible to predict the presence or absence of NRILN by routine diagnostic examinations before surgery for thyroid and parathyroid disease. We emphasize that digital subtraction angiography, MR angiography, or barium esophagography is not necessary for all patients before surgery, since NRILN is a relatively rare anomaly, and such examinations are either invasive or not cost-effective. When a NRILN has been identified during surgery, there is no need to examine for the presence of a vascular anomaly: Its presence is a matter of course. Surgery must be performed however, with knowledge of the possibility of a NRILN.

Abnormalities, Multiple↗
PubMed2006

Basic and clinical aspects of parathyroid hyperplasia in chronic kidney disease.

Marked parathyroid hyperplasia develops in patients with chronic kidney disease, especially those with long dialysis vintage. Although progression of hyperplasia is associated with downregulation of vitamin D receptor and calcium-sensing receptor, initial abnormality that triggers and maintains parathyroid cell proliferation, as well the critical abnormality for the progression of diffuse hyperplasia to nodular hyperplasia, still remains to be elucidated. It is quite important for the optimal management of renal osteodystrophy to recognize the development of nodular hyperplasia, because the cells in nodular hyperplasia are usually resistant to medical therapy and further treatment of such patients often leads to vascular calcification. For this purpose, size and blood supply of enlarged parathyroid glands have been used as good clinical markers. Furthermore, we have recently shown that the serum fibroblast growth factor 23 level can be used for predicting refractory hyperparathyroidism. Once nodular hyperplasia develops in any of the enlarged parathyroid glands, such patients need to be treated by parathyroid intervention including percutaneous ethanol injection therapy. In addition, as direct vitamin D injection therapy has been shown to induce regression of hyperplasia, it may become possible to reverse or normalize established nodular hyperplasia if we can develop new agents with such effects in the near future.

Anti-Infective Agents, Local↗
PubMed1976

Hyperparathyroidism with coexisting hyperthyroidism.

Diagnosis of parathyroid disease in patients with hyperthyroidism may be difficult on clinical findings alone. Radiologic examination of the bones suggested the possibility of parathyroid disease in this patient. Confirmation of the diagnosis was made when serum calcium levels remained elevated in spite of adequate antithyroid medication. Measurement of serum parathyroid hormone levels may prove to be of greatest value. Of additional interest is the fact that the patient, before her symptoms became apparent, delivered an infant with congenital hypoparathyroidism.

Adult↗
PubMed1989

Parathyroid subtraction imaging--pitfalls in diagnosis.

Since 1985 when parathyroid subtraction scintigraphy was presented in atlas form in this journal, the T1-201-Tc-99m computer subtraction studies have become more and more popular. Although the study has been quite accurate in localizing abnormal parathyroid pathology, the rate of false positive studies has been somewhat excessive, usually due to thyroid pathology. This atlas is an update of that previous work with the goal of presenting a scheme of interpretation that lessens the incidence of false positive studies as well as presenting many of the pitfalls in diagnosis of parathyroid disease.

False Positive Reactions↗
PubMed1992

Imaging of the thyroid and parathyroid.

The radiologic armamentarium for imaging of thyroid and parathyroid diseases includes scintigraphy, ultrasonography, CT, and MR imaging. Continued refinements of these diagnostic tools have been made during the past year. This paper reviews those recent advancements in the fields of parathyroid and thyroid imaging.

Diagnostic Imaging↗
PubMed1987

Improvement of vocal cord paresis after thyroidectomy.

Iatrogenic vocal cord paralysis is a well-publicized complication of thyroid and parathyroid operations. Less appreciated is the improvement of vocal cord function after resection of a thyroid or parathyroid tumor. Over the last 22 years, 14 patients presented with vocal cord paresis in the presence of thyroid or parathyroid tumors. Of these 14 patients, nine had complete resolution of paresis following resection of the thyroid or parathyroid tumors: three had a thyroid carcinoma impinging upon the nerve, three had large colloid goiters, two had a follicular adenoma and one had a parathyroid adenoma displacing the nerve. In five of the 14 patients the vocal cord paralysis persisted after operation. In three, the pathology accounted for the vocal cord paralysis and was not amenable to operative improvement: one patient had an unresectable anaplastic thyroid carcinoma, one patient had long-standing idiopathic unilateral vocal cord paralysis, and one patient had laryngeal adenoid cystic carcinoma with thyroid invasion. The fourth patient had an extensive thyroid hemangioma. The paralysis persisted after resection. The fifth patient had long-standing idiopathic vocal cord palsy. A preoperative vocal cord paresis in a patient with thyroid or parathyroid disease does not indicate permanent loss of recurrent nerve function, even in the presence of carcinoma. In this series, vocal cord function was restored in 9 of 10 patients with resectable thyroid or parathyroid tumors.

Adult↗
PubMed2003

[Imaging of the parathyroid gland].

Diseases of the parathyroid gland are rare and are especially in case of hyperparathyroidism associated with hyperacalcaemia. Enlarged glands are, therefore, generally not detected with imaging modalities. The aim of imaging studies is to locialize abnormal glands. Ultrasound is the modality of choice for the primary investigation followed by nuclear medicine studies. Computed tomography or angiography with vein sampling should only be performed if the results of other investigations are equivocal. Magnetic resonance imaging is performed rarely in Austria with its high prevalence of endemic goiter.

Adenoma↗
PubMed2005

Is parathyroid carcinoma indeed a lethal disease?

BACKGROUND: Parathyroid carcinoma is a rare malignancy with a wide range of aggressiveness. There is no current staging system. Our primary aim was to review the presentation, diagnosis, surgical treatment, and outcomes of patients, with the goal of assessing the incidence of death related to parathyroid carcinoma. METHODS: The authors present a retrospective chart review on patients with parathyroid carcinoma from 1975 to 2004, identified by the tumor registry of a single tertiary-care center. Diagnoses were confirmed histologically, clinical and radiographical data were recorded, and statistical analyses were performed. RESULTS: Twenty-three cases were identified. The mean patient age was 54 years. The female:male ratio was 1.5:1. Follow-up ranged from 1 month to 23 years (median, 134 months). Mean preoperative calcium was 12.9 mg/dL. Median parathyroid hormone was 290 pg/mL. Two patients (9%) had an asymptomatic presentation, and five (22%) presented with a palpable neck mass. Only nine (39%) underwent initial comprehensive en-bloc resection. Median survival was 22 years. Five- and 10-year survival was 85.9% and 69.4%, respectively. Five- and 10-year survival with en-bloc resection was 90% and 67.5%, respectively. Local resection resulted in survival rates of 82.5% and 70.7%. Three of ten deaths were attributed to parathyroid carcinoma. In recurrent disease, computed tomography and scintigraphy had localization rates of 53% and 67%, respectively, with a concordance of 22%. CONCLUSIONS: Long-term survival is possible with parathyroid carcinoma. Death associated with parathyroid carcinoma was uncommon. A staging may be warranted despite the rarity of this disease.

Adult↗
PubMed1995

Thyroid and parathyroid imaging.

This article reviews the current roles of imaging in the diagnosis of thyroid and parathyroid disorders, with an emphasis on ultrasound evaluation. Imaging of the thyroid and parathyroid can be performed with nuclear medicine, ultrasound, CT, and MRI. Indications for thyroid and parathyroid imaging studies have recently changed. The availability of experienced endocrine surgeons, as well as the development of accurate laboratory tests, fine-needle aspiration (FNA) biopsy, and high-resolution ultrasound, have dramatically influenced the evaluation of thyroid and parathyroid disease. In patients with thyroid nodular disease, a clinical examination by an experienced clinician with appropriate lab values and palpation-guided FNA is the current diagnostic protocol of choice. Ultrasound evaluation of high-risk patients and ultrasound-guided FNA both augment this protocol when necessary. In patients with diffuse thyroid glandular disease, radionuclide imaging and color Doppler sonography both can be used for evaluation. When preoperative imaging is clinically necessary, sonography or scintigraphy can be used for parathyroid adenoma localization in patients with primary hyperparathyroidism. The recent development of technetium-99m sestamibi as a parathyroid imaging agent has improved the sensitivity of scintigraphy for parathyroid adenoma localization. Ultrasound and radionuclide imaging have also become valuable imaging techniques for parathyroid localization in patients with recurrent or persistent hyperparathyroidism.

Adenoma↗
PubMed1993

Asymptomatic and normocalcemic parathyroid adenoma: detection by preoperative ultrasound.

Hyperparathyroidism is often detected in the asymptomatic stage at the present time with the advent of mass screening for hypercalcemia. There may be patients with parathyroid disease who are asymptomatic and who do not have detectable elevations of their serum calcium. Many patients who undergo surgery for thyroid conditions may have synchronous parathyroid disease which is asymptomatic and not detectable by routine laboratory screening. Preoperative ultrasound scans may be of utility in identifying coexistent disease in those patients scheduled for thyroid surgery so that both disease entities may be treated at the same operation.

Adenoma↗