CLINICAL-METABOLIC AND HORMONAL RELATIONSHIPS BETWEEN PARATHYROID DISEASE AND OTHER NON-CANCEROUS ENDOCRINE DISORDERS IN THE CHORNOBYL NPP ACCIDENT SURVIVORS. / KLINIKO-METABOLIChNI TA GORMONAL'NI VZAIeMOZV'IaZKY MIZh PATOLOGIIeIu PRYShchYTOPODIBNYKh ZALOZ TA INShYMY NEZLOIaKISNYMY ENDOKRYNNYMY ZAKhVORIuVANNIaMY U POSTRAZhDALYKh VNASLIDOK AVARIÏ NA ChAES.

OBJECTIVE: to investigate the clinical, hormonal-metabolic and structural features of parathyroid injuries in sur-vivors exposed to ionizing radiation after the Chornobyl NPP accident in adulthood and childhood, both with theirconnections to other non-cancerous endocrine disorders, and to establish the respective interhormonal and dys-metabolic relationships. MATERIALS AND METHODS: Clinical effects of ionizing radiation on the endocrine system in persons affected by theChornobyl NPP accident (n = 224) and their descendants (n = 146), compared with the general population sample(n = 70) were the study object. All patients underwent the ultrasound thyroid and parathyroid examination. Thegenerally recognized clinical, anthropometric (body weight, height, thigh volume, body mass index), instrumental(ultrasound examination of thyroid and parathyroid glands), laboratory (biochemical, hormonal), and statisticalmethods were applied. Parametric and nonparametric statistical methods were used in data processing. The value ofp < 0.05 was considered a statistically significant. RESULTS: No significant difference was found in the incidence of carbohydrate metabolic disorders in the ChornobylNPP (ChNPP) accident consequences clean-up workers (ACCUW), evacuees from the NPP 30-km exclusion zone, res-idents of radiologically contaminated areas and in the control group in whom the parathyroid hyperplasia wasdetected. There was a significant increase in the incidence of arterial hypertension among ACCUW who had parathy-roid hyperplasia (76.9%) vs. the control group (51.2%). In cases of parathyoid hyperplasia the vitamin D levels weresignificantly lower than without it. Vitamin D insufficiency/deficiency was found in 94% of the surveyed subjects.The average level of parathyroid hormone in blood serum was significantly higher in the ACCUW of «iodine¼ period withdiagnosed parathyroid hyperplasia than in the control group: (57.2 ± 2.87) pg / ml against (32.74 ± 3.58) pg / ml,p < 0.05. Results of multivariative analysis indicated a strong association of vitamin 25(OH)D insufficiency/defi-ciency with development of thyroid disease, carbohydrate metabolic disorders, cardiovascular disease, osteo-penia/osteoporosis. parathyroid ultrasound scan was at that an effective diagnostic method for primary screeningfor parathyroid hyperplasia and regular monitoring of the treatment efficiency. When examining children bornto parents irradiated after the ChNPPA the parathyroid hyperplasia (58%) and low serum content of vitamin D(11.6 ± 3.5) nmol / l were most often found in children living on radiologically contaminated territories (RCT).A strong correlation was established between the HOMA insulin resistance index and serum content of vitamin D(r = 0.65), parathyroid hormone (r = 0.60), and free thyroxine (r = 0.68) in the group of children born to parents irra-diated after the ChNPPA, having got chronic autoimmune thyroiditis, which indicated a relationship between thy-roid function, impaired carbohydrate and fat metabolism and the state of parathyroids. CONCLUSIONS: No difference in the incidence of carbohydrate metabolic disorders was found in the ChNPP ACCUW,evacuees from the 30-km exclusion zone, and residents of radiologically contaminated territories in whom parathy-roid hyperplasia was detected vs. the control group. Patients with parathyroid hyperplasia were found to be defi-cient in vitamin D in 94% of cases, and level of latter was significantly lower than under the normal parathyroid size.There was a significant increase in the incidence of diagnosed arterial hypertension among ACCUW who had parathy-roid hyperplasia vs. the control group: (76.9 ± 3.5)% vs. (51.2 ± 3.7)%. According to multivariate analysis a strongassociation between the vitamin 25(OH)D insufficiency/deficiency and development of thyroid disease, carbohydratemetabolic disorders, cardiovascular disease, and osteopenia/osteoporosis was established. The average level of pa-rathyroid hormone in the blood serum of the ChNPP ACCUW of the «iodine¼ period with diagnosed parathyroid hyper-plasia was significantly higher (57.2 ± 2.87) pg / ml against (32.74 ± 3.58) pg / ml; p <0,05) in the control group.

Cardiovascular consequences of parathyroid disorders in adults.

PTH is a metabolic active hormone primarily regulating calcium and phosphate homeostasis in a very tight and short term-manner. Parathyroid disorders in adult patients reflect a variety of different conditions related either to the parathyroid glands itself or to the effects of the secreted hormone. The clinical spectrum varies from the common disease primary hyperparathyroidism (PHPT) to the orphan conditions pseudohypoparathyroidism (Ps-HypoPT) and chronic hypoparathyroidism (HypoPT). The purpose of this review is to describe the consequences of disturbances in levels or action of PTH for cardiac function and cardiovascular risk in adult patients with these disorders. Most patients with PHPT achieve the diagnose by chance and have minor or no specific symptoms. Still, these patients with mild PHPT do possess cardiovascular (CV) morbidity, however so far not proven ameliorated by surgery in controlled trials. In severe cases, the CV risk is increased and with a potential reversibility by treatment. Patients with Ps-HypoPT have resistance to PTH action, but not necessarily total resistance in all tissues. So far, no clear CV morbidity or risk has been demonstrated, but there are several aspects of interest for further studies. Most patients with HypoPT do get their hormonal deficiency syndrome following neck surgery. These patients do experience multiple symptoms and do have an increased CV-risk before the primary surgery. Based on existing data, their CV mortality do not deviate from the expected when adjusting for the preexisting increased risk. Patients with nonsurgical (NS-) HypoPT do demonstrate increased CV-risk also associated with exposure time. Endocrine disorders with alterations in PTH function have major impact on the cardiovascular system of importance for morbidity and mortality, wherefore management of these specific diseases should be optimized currently, as new data become available, however also avoiding over-treating asymptomatic patients.

Pediatric parathyroid disease.

Parathyroid glands are critical for calcium and phosphate homeostasis. Parathyroid disease is relatively rare in the pediatric population, but there are some important pediatric-specific considerations and conditions. This article reviews parathyroid physiology, disorders of hyper- and hypo- function, operative management, and uniquely pediatric diagnoses such as neonatal severe hyperparathyroidism. Advances in preoperative imaging, intra-operative gland identification, and management of post-thyroidectomy hypocalcemia are also presented in detail. This article combines a review of fundamentals with recent advances in care, emphasizing pediatric-specific publications.

Fine-needle aspiration with rapid parathyroid hormone assay to identify parathyroid gland in thyroidectomy.

To determine the levels of parathyroid hormone (PTH) in the fluids of various tissues for identification of parathyroid glands during thyroidectomy.Our study comprised 31 patients with thyroid cancer who underwent lobectomy with central compartment dissection at our hospital from October 2014 to February 2015. A total of 186 tissue samples, including 28 from parathyroid glands and 158 from non-parathyroid tissues, were obtained during the operations. Tissue fluids were collected via fine-needle aspiration to measure PTH levels; the tissue was punctured 3 times with a 26-gauge syringe needle and washed with 0.5 mL normal saline. Tissues were also prepared for pathological examination.PTH concentrations were significantly higher in parathyroid tissues than non-parathyroid tissues. None of the patients had irremediable parathyroid dysfunction after surgical resection.Use of fine-needle aspiration for quantification of PTH levels in tissue fluids rapidly, safely, and effectively identifies the parathyroid glands during thyroidectomy.

Genetic Disorders of Parathyroid Development and Function.

Hypoparathyroidism is characterized by hypocalcemia and hyperphosphatemia and is due to insufficient levels of circulating parathyroid hormone. Hypoparathyroidism may be an isolated condition or a component of a complex syndrome. Although genetic disorders are not the most common cause of hypoparathyroidism, molecular analyses have identified a growing number of genes that when defective result in impaired formation of the parathyroid glands, disordered synthesis or secretion of parathyroid hormone, or postnatal destruction of the parathyroid glands.

The Parathyroid Gland and Heart Disease.

The parathyroid glands are critical to maintaining calcium homeostasis through actions of parathyroid hormone (PTH). Recent clinical and molecular research has shown that direct and indirect actions of PTH also affect the heart and vasculature through downstream actions of G protein-coupled receptors in the myocardium and endothelial cells. Patients with disorders of the parathyroid gland have higher incidences of hypertension, arrhythmias, left ventricular hypertrophy, heart failure, and calcific disease which translate into increased cardiac morbidity and mortality. Importantly, clinical research also suggests that early treatment of parathyroid disorders through medical or surgical management may reverse cardiovascular remodeling and mitigate cardiac risk factors.

Assessment of Vocal Fold Function Using Transcutaneous Laryngeal Ultrasonography and Flexible Laryngoscopy.

IMPORTANCE: Evaluation of preoperative and postoperative vocal fold function is important in patients undergoing thyroid or parathyroid surgical procedures. Transcutaneous laryngeal ultrasonography (TLUSG) has been proposed as a promising noninvasive technique and alternative to flexible fiberoptic laryngoscopy. OBJECTIVE: To determine whether TLUSG can be an alternative to flexible laryngoscopy in evaluating vocal fold function. DESIGN, SETTING, AND PARTICIPANTS: A prospective study was performed from March 1, 2013, to July 31, 2014. Patients who were scheduled to undergo thyroid or parathyroid surgery by a single surgeon at a North American, university-based tertiary care center and who agreed to undergo preoperative and postoperative TLUSG and flexible fiberoptic laryngoscopy were enrolled. Patients were divided into 2 groups: nonoverweight (body mass index [calculated as weight in kilograms divided by height in meters squared] <25) and overweight or obese (body mass index ≥ 25). Follow-up was completed on February 28, 2015, and data were analyzed from March 1, 2013, to February 28, 2015. INTERVENTIONS: Preoperative and postoperative TLUSG and flexible fiber optic laryngoscopic assessments of vocal fold function. MAIN OUTCOMES AND MEASURES: The findings of TLUSG and flexible fiber optic laryngoscopy were compared for all patients and each body mass index group to assess the accuracy of TLUSG in assessing vocal fold function. RESULTS: A total of 250 patients (500 vocal folds) underwent evaluation, of whom 208 (83.2%) were women and with a mean (SD) age of 52.7 (14.3) years. On flexible fiberoptic laryngoscopy findings, 13 patients had preoperative vocal fold paralysis (VFP), and 14 postoperative new incidents of VFP were identified. Only 7 (53.9%) of the preoperative cases of VFP and 15 (55.6%) of the postoperative cases of VFP were identified by TLUSG. The sensitivity, specificity, and accuracy of preoperative TLUSG were 53.8%, 50.5%, and 50.6%, respectively; for postoperative TLUSG, 55.6%, 38.7%, and 39.6%, respectively. In the nonoverweight group, the preoperative TLUSG sensitivity, specificity, and accuracy were 100%, 70.0%, and 70.5%, respectively; in the overweight-obese group, 45.4%, 43.4%, and 43.5%, respectively (odds ratio, 3.16; 95% CI, 2.06-4.84; P < .001). Postoperative visualization of the vocal folds was more challenging, with a sensitivity, specificity, and accuracy of 83.3%, 55.6%, and 56.8%, respectively, in the nonoverweight group, and 47.6%, 32.6%, and 33.4%, respectively, in the overweight-obese group (odds ratio, 2.62; 95% CI, 1.75-3.94; P < .001). CONCLUSIONS AND RELEVANCE: When evaluation of vocal fold function is indicated in patients undergoing thyroid and parathyroid surgery, TLUSG should not be considered as an alternative to the current practice of flexible fiberoptic laryngoscopy. Adequate ultrasonographic visualization of the vocal folds and arytenoids is challenging, especially in overweight and obese patients and in the postoperative setting.

Electrocardiographic changes in the most frequent endocrine disorders associated with cardiovascular diseases. Review of the literature.

Car- diovascular abnormalities associated with endocrine diseases are often frequent and due to complex relationships between endocrine glands (with internal secretion) and cardiovascular system (heart and vessels). Certain hormones secreted by the endocrine glands (particularly the thyroid and pituitary gland) excesses or deficiencies, are involved in morphogenesis, growth processes and activity regulation of cardiovascular system, most often in connection with the autonomic nervous system. There are also a lot of electrocardiographic changes caused by hormonal disorders that requires differential diagnosis and represents the source of erroneous diagnosis. Endocrine pathology occurred later than a heart disease, may worse heart function. Ignoring the cardiovascular events that may occur in the evolution of endo- crine diseases, may induce increased mortality due to cardiovascular complications.

Multiple hormonal resistances: Diagnosis, evaluation and therapy.

Molecular alterations of cAMP-mediated signaling affect primarily the signaling of the PTH/PTHrp receptor, and, with different severities the signaling of other hormones, including TSH. The identification of PTH and other hormonal resistances implies to look for the genetic disorder supporting the metabolic disorder.

Quiste paratiroideo funcionante gigante de localización mediastínica: una causa insólita de disnea de esfuerzo y disfagia de carácter leve / Giant Functioning Mediastinal Parathyroid Cyst: An Unusual Cause of Exertional Dyspnea and Mild Dysphagia

No disponible

Parathyroid hormone-related protein: an update.

PTHrP was identified as a cause of hypercalcemia in cancer patients 25 yr ago. In the intervening years, we have learned that PTHrP and PTH are encoded by related genes that are part of a larger "PTH gene family." This evolutionary relationship permits them to bind to the same type 1 PTH/PTHrP receptor, which explains why humoral hypercalcemia of malignancy resembles hyperparathyroidism. This review will outline basic facts about PTHrP biology and its normal physiological functions, with an emphasis on new findings of the past 5-10 yr. The medical and research communities first became aware of PTHrP because of its involvement in a common paraneoplastic syndrome. Now, research into the basic biology of PTHrP has suggested previously unrecognized connections to a variety of disease states such as osteoporosis, osteoarthritis, and breast cancer and has highlighted how PTHrP itself might be used in therapy for osteoporosis and diabetes. Therefore, the story of this remarkable protein is a paradigm for translational research, having gone from bedside to bench and now back to bedside.

Inflammatory diseases of the parathyroid gland.

AIMS: Inflammatory disorders of the parathyroid gland are very rare as compared with those of other endocrine organs. The aim of this study was to provide the first systematic review of this condition. METHODS AND RESULTS: A 42-year-old patient underwent surgery for recurrent secondary hyperparathyroidism. Histology showed hyperplastic parathyroiditis defined by a mixed inflammatory infiltrate with active germinal centres. Molecular markers revealed significant upregulation of CD68 in an ischaemic background (hypoxia-inducible factor 1 upregulation) with mitochondrial reaction (malate dehydrogenase 2 upregulation) and hyperparathyroidism (carbonic anhydrase 4 upregulation). Our case demonstrates true intraparathyroid inflammation with terminal B-cell differentiation. We searched PubMed, ISI Thompson and Google Scholar up to January 2011, using the terms 'parathyroiditis', 'inflammation of parathyroid gland', 'lymphocytic infiltrate', 'tuberculosis of the parathyroid', 'sarcoidosis', and 'graulomatous inflammation'. Three autopsy series, 27 articles and 96 case reports with inflammatory parathyroid disorders were identified. Autopsy series showed lymphocytic infiltrates in up to 16% of all cases. The entire material reported lymphocytic infiltrates (n=69), parathyroiditis with germinal centres (n=15), sarcoidosis (n=6), tuberculosis (n=4), and other granulomatous diseases (n=2). CONCLUSIONS: Distinct inflammatory and granulomatous processes in the parathyroid gland are rare. Scanty lymphocytic infiltrates are common, and occur in generalized inflammatory conditions or venous congestion. We note the surprising absence of an association between histological proof of parathyroiditis and hypoparathyroidism.

Digestive manifestations of parathyroid disorders.

The parathyroid glands are the main regulator of plasma calcium and have a direct influence on the digestive tract. Parathyroid disturbances often result in unknown long-standing symptoms. The main manifestation of hypoparathyroidism is steatorrhea due to a deficit in exocrine pancreas secretion. The association with celiac sprue may contribute to malabsorption. Hyperparathyroidism causes smooth-muscle atony, with upper and lower gastrointestinal symptoms such as nausea, heartburn and constipation. Hyperparathyroidism and peptic ulcer were strongly linked before the advent of proton pump inhibitors. Nowadays, this association remains likely only in the particular context of multiple endocrine neoplasia type 1/Zollinger-Ellison syndrome. In contrast to chronic pancreatitis, acute pancreatitis due to primary hyperparathyroidism is one of the most studied topics. The causative effect of high calcium level is confirmed and the distinction from secondary hyperparathyroidism is mandatory. The digestive manifestations of parathyroid malfunction are often overlooked and serum calcium level must be included in the routine workup for abdominal symptoms.

Circulating sclerostin in disorders of parathyroid gland function.

CONTEXT: Sclerostin, a protein encoded by the SOST gene in osteocytes and an antagonist of the Wnt signaling pathway, is down-regulated by PTH administration. Disorders of parathyroid function are useful clinical settings to study this relationship. OBJECTIVE: The objective of the study was to evaluate sclerostin in two different disorders of parathyroid function, primary hyperparathyroidism and hypoparathyroidism, and to analyze the relationship between sclerostin and PTH, bone markers, and bone mineral density. DESIGN: This is a cross-sectional study. SETTING: The study was conducted at a clinical research center. PATIENTS: Twenty hypoparathyroid and 20 hyperparathyroid patients were studied and compared to a reference control group. RESULTS: Serum sclerostin was significantly higher in hypoparathyroid subjects than in hyperparathyroid subjects (P < 0.0001) and controls (P < 0.0001). PTH was negatively associated with sclerostin, achieving statistical significance in hypoparathyroidism (r = -0.545; P = 0.02). The bone turnover markers, cross-linked C-telopeptide of type I collagen (CTX) and amino-terminal propeptide of type I collagen (P1NP), were differently associated with sclerostin according to the parathyroid disorder. In primary hyperparathyroidism, bone turnover markers were associated negatively with sclerostin (for P1NP, r = -0.490; P = 0.03). In hypoparathyroidism, bone turnover markers were associated positively with sclerostin (for CTX, r = +0.571; P = 0.01). Although there was no significant correlation between bone mineral density and sclerostin in either parathyroid disorder, there was a significant positive relationship between sclerostin and bone mineral content in hypoparathyroidism. CONCLUSIONS: The results are consistent with the hypothesis that PTH is a regulator of sclerostin in human disorders of parathyroid function. In addition, the results suggest that bone mineral content may be another factor that influences sclerostin.

Molecular genetics of parathyroid disease.

BACKGROUND: Primary hyperparathyroidism (HPT) is often caused by a benign parathyroid tumor, adenoma; less commonly by multiglandular parathyroid disease/hyperplasia; and rarely by parathyroid carcinoma. Patients with multiple tumors require wider exploration to avoid recurrence and have increased risk for hereditary disease. Secondary HPT is a common complication of renal failure. Improved knowledge of the molecular background of parathyroid tumor development may help select patients for appropriate surgical treatment and can eventually provide new means of treatment. The present contribution summarizes more recent knowledge of parathyroid molecular genetics. METHODS: A literature search and review was made to evaluate the level of evidence concerning molecular biology and genetics of primary, secondary, and familial HPT according to criteria proposed by Sackett, with recommendation grading by Heinrich et al. RESULTS: Most parathyroid adenomas and hyperplastic glands are monoclonal lesions. Cyclin D1 gene (CCND1) translocation and oncogene action occur in 8% of adenomas; cyclin D1 overexpression is seen in 20% to 40% of parathyroid adenomas and in 31% of secondary hyperplastic glands. Somatic loss of one MEN1 allele is seen in 25% to 40% of sporadic parathyroid adenomas, half of which have inactivating mutation of the remaining allele. Inactivating somatic HRPT2 mutations are common in parathyroid carcinoma, often causing decreased expression of the protein parafibromin involved in cyclin D1 regulation. Aberrant regulation of Wnt/beta-catenin signaling may be important for parathyroid tumor development. CONCLUSIONS: Molecular genetic studies of parathyroid tumors are well designed basic experimental studies providing strong level III evidence, with data frequently confirmed by subsequent studies.

Diferencias en la función de los péptidos paratiroideos. ¿Qué estamos midiendo? / Differences in the function of parathyroid peptides. What are we measuring?

No disponible

No disponible

Regulatory mechanisms of circulating fibroblast growth factor 23 in parathyroid diseases.

Fibroblast growth factor-23 (FGF-23) is a circulating factor regulating phosphate and vitamin D homeostasis. Phosphate intake and an administration of 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) increase circulating FGF-23 levels, and elevated FGF-23 prevents hyperphosphatemia and vitamin D toxicity by hyperphosphaturia and suppression of circulating 1,25(OH)(2)D level, comprising a feedback loop to maintain phosphate and vitamin D homeostasis. Excess secretion of parathyroid hormone (PTH), another phosphaturic factor, elevates the serum calcium level in primary hyperparathyroidism. PTH also elevates circulating FGF-23 level, which cooperatively enhances the phosphaturia, resulting in hypophosphatemia. The circulating FGF-23 level increases as renal function declines in chronic kidney disease (CKD), and it exhibits significant and positive correlations with serum phosphate, calcium, and PTH in CKD patients on maintenance hemodialysis, suggesting that these parameters regulate circulating FGF-23 level. Tight associations between circulating FGF-23 and calcium levels were observed both in patients with primary hyperparathyroidism and in CKD patients on maintenance hemodialysis, suggesting the role of serum calcium on FGF-23 regulatory mechanisms. FGF-23 may have a physiological role in preventing tissue damage such as ectopic calcifications, partly via suppressing the serum calcium x phosphate product by accelerating urinary phosphate excretion and suppressing vitamin D activation.

Dermatologic manifestations of parathyroid-related disorders.

Dermatologic manifestations of parathyroid-related disorders, although rare in sporadic cases, are not uncommon in familial syndromes. Patients with familial hyperparathyroidism have several types of skin lesions. In multiple endocrine neoplasia 1, patients commonly have angiofibromas (85%) and collagenomas (70%), lesions that show loss of one 11q13 allele, the molecular abnormality in multiple endocrine neoplasia 1. They can also present with lipomas or café-au-lait spots. Cutaneous amyloidosis, an entity that can occur sporadically, has been described in multiple endocrine neoplasia 2a and is usually localized to the interscapular area. Metastatic calcification is an entity commonly encountered in patients with hyperparathyroidism and renal failure. It can be complicated by infections and necrosis. It is best treated by controlling hypercalcemia, hyperphosphatemia, hyperparathyroidism, antibiotics, and analgesia. Parathyroidectomy is reserved for refractory cases. Hypoparathyroidism presenting in the context of polyglandular failure type 1 is characterized by mucocutaneous candidiasis. Pseudohypoparathyroidism, an inherited disorder with end-organ unresponsiveness to parathyroid hormone, is characterized by Albright hereditary osteodystrophy. Patients present with short stature, round facies, brachydactyly, and short fourth or fifth metacarpals.