Parathyroid Hormone Production Research Articles

Patients with primary hyperparathyroidism undergoing surgical intervention in two tertiary care hospitals in Sri Lanka

Introduction Autonomous production of parathyroid hormone results in primary hyperparathyroidism. Sri Lankan studies analyzing cases of hyperparathyroidism are scarce. Objective To describe clinical, biochemical, radiological and pathological characteristics of patients with primary hyperparathyroidism undergoing surgical intervention in two tertiary care hospitals in Sri Lanka. Design Data was collected from the available records of all patients who has undergone surgery for primary hyperparathyroidism at Teaching Hospital, Kandy and General Hospital, Badulla from 2016.10.27 to date. A total of ten patients with primary hyperparathyroidism were enrolled for analysis. Out of the ten patients, six were females. Ages ranged from 23 to 65 years (Mean- 44.2). Mode of presentation was fragility fractures in four patients, renal calculi in five patients and acute pancreatitis in one patient. Bone complications (fractures, osteoporosis) were seen in four patients and renal complications (renal calculi, nephrocalcinosis) were seen in six patients. Pre-operative total serum calcium levels ranged from 10.52 to 14.16 mg/dl (mean-12.6). Pre-operative serum phosphate levels ranged from 0.74 to 1.07 mmol/L (mean -0.868). X-ray evidence of skeletal changes of hands were seen in 6 patients (60%), of which 4 showed bony deformities and 2 showed pathological fractures. Renal calculi or nephrocalcinosis was detected by X-ray in five out of six patients and ultrasonically in all 6 patients. Ultrasound scans revealed a parathyroid adenoma in 8 patients (80%), while 2 were negative. Technetium-99-methoxyisonitrile (99m Tc-Sestamibi) scans were performed in 4 patients and three had positive images. Histological analysis revealed 8 patients with single parathyroid adenoma, 1 with parathyroid carcinoma, and one patient with four gland hyperplasia. Discussion and Conclusions All patients had symptoms at the time of diagnosis. Ultrasound scan was a useful tool for the localization.

Water Clear Cell Parathyroid Adenoma: A Report of Two Cases

Primary hyperparathyroidism is a disease characterized by hypercalcemia and excessive production of parathyroid hormone. It is the most common cause of hypercalcemia in outpatient practice and the third common endocrine disorder. The incidence of primary hyperparathyroidism is increasing with age, and it is more common in women than in men. 80-85% of cases of primary hyperparathyroidism are due to single parathyroid adenoma. The majority of parathyroid adenomas contain a mixed cell population with predominance of chief cells. Primary hyperparathyroidism with clear cell adenoma is very rare. Here we are sharing two cases of water clear cell parathyroid adenoma associated with primary hyperparathyroidism presented with deferent clinical manifestations.

Mechanistic study of the cause of decreased blood 1,25-Dihydroxyvitamin D in sepsis

BackgroundVitamin D deficiency, determined by blood levels of 25-hydroxyvitamin D [25(OH) D, i.e. the major vitamin D form in blood], has been shown to associate with all-cause mortalities. We recently demonstrated that blood levels of 1,25-dihydroxyvitamin D [1,25(OH)2D, i.e. the active vitamin D] were significantly lower in non-survivors compared to survivors among sepsis patients. Unexpectedly, despite the well documented roles of 1,25(OH)2D in multiple biological functions such as regulation of immune responses, stimulation of antimicrobials, and maintenance of barrier function, 1,25(OH)2D supplementation failed to improve disease outcomes. These previous findings suggest that, in addition to 1,25(OH)2D deficiency, disorders leading to the 1,25(OH)2D deficiency also contribute to mortality among sepsis patients. Therefore, this study investigated the mechanisms leading to sepsis-associated 1,25(OH)2D deficiency.MethodsWe studied mechanisms known to regulate kidney 25-hydroxylvitamin D 1α-hydroxylase which physiologically catalyzes the conversion of 25(OH) D into 1,25(OH)2D. Such mechanisms included parathyroid hormone (PTH), insulin-like growth factor 1 (IGF-1), fibroblast growth factor 23 (FGF-23), and kidney function.ResultsWe demonstrated in both human subjects and mice that sepsis-associated 1,25(OH)2D deficiency could not be overcome by increased production of PTH which stimulates 1α-hydroxylase. Further studies showed that this failure of PTH to maintain blood 1,25(OH)2D levels was associated with decreased blood levels of IGF-1, increased blood levels of FGF-23, and kidney failure. Since the increase in blood levels of FGF-23 is known to associate with kidney failure, we further investigated the mechanisms leading to sepsis-induced decrease in blood levels of IGF-1. Our data showed that blood levels of growth hormone, which stimulates IGF-1 production in liver, were increased but could not overcome the IGF-1 deficiency. Additionally, we found that the inability of growth hormone to restore the IGF-1 deficiency was associated with suppressed expression and signaling of growth hormone receptor in liver.ConclusionsBecause FGF-23 and IGF-1 have multiple biological functions besides their role in regulating kidney 1α-hydroxylase, our data suggest that FGF-23 and IGF-1 are warranted for further investigation as potential agents for the correction of 1,25(OH)2D deficiency and for the improvement of survival among sepsis patients.

Changes the cytokine profile and calcium-regulating hormones in rheumatoid arthritis.

The aim was to study the level of some cytokines (İL-2, İL-6, İL-8 TNFα) and calcium regulating hormones (calcitonin, parathyroid hormone, 25 (OH) D) in the blood of patients with rheumatoid arthritis (RA) depending on rheumatoid factor (RF) and the assessment of the role of the revealed violations in the pathogenesis of bone loss in this pathology. For this purpose, 74 patients with RA (59 women, 15 men) aged from 27 to 71 were examined. On the basis of RF in the blood serum, the patients were divided into 2 groups: seronegative and seropositive RA. The control group included 16 healthy individuals (13 women, 3 men). The results obtained that the serological variant of RA affects the serum levels of proinflammatory cytokines and calcium-regulating hormones: more pronounced changes were found in seropositive RA. The high production of IL-2, IL-6, IL-8, TNF-α and parathyroid hormone detected in both groups of patients undoubtedly contributes to the mechanisms of bone loss in RA. In both groups we detected hypovitaminosis D. This results recommended to use this vitamin in the complex treatment of RA.

CHANGES THE CYTOKINE PROFILE AND CALCIUM-REGULATING HORMONES IN RHEUMATOID ARTHRITIS

The aim was to study the level of some cytokines (İL-2, İL-6, İL-8 TNFα) and calcium regulating hormones (calcitonin, parathyroid hormone, 25 (OH) D) in the blood of patients with rheumatoid arthritis (RA) depending on rheumatoid factor (RF) and the assessment of the role of the revealed violations in the pathogenesis of bone loss in this pathology. For this purpose, 74 patients with RA (59 women, 15 men) aged from 27 to 71 were examined. On the basis of RF in the blood serum, the patients were divided into 2 groups: seronegative and seropositive RA. The control group included 16 healthy individuals (13 women, 3 men). The results obtained that the serological variant of RA affects the serum levels of proinflammatory cytokines and calcium-regulating hormones: more pronounced changes were found in seropositive RA. The high production of IL-2, IL-6, IL-8, TNF-α and parathyroid hormone detected in both groups of patients undoubtedly contributes to the mechanisms of bone loss in RA. In both groups we detected hypovitaminosis D. This results recommended to use this vitamin in the complex treatment of RA.

Risk of vertebral fractures in hypoparathyroidism.

Parathyroid hormone (PTH) exerts both anabolic and catabolic actions on bone,depending on the duration and periodicity of exposure. Hypoparathyroidism is defined by inadequate production of PTH in the presence oflow serum calcium. In hypoparathyroidism it has been reported an increase in corticaland trabecular bone mass, but it is still unknown if these quantitative variations maybe accompanied by qualitative ones and increased bone strength. Despite the extensive data available on the effects of hypoparathyroidism on bone, itseffect on the hard end point in this area which is the risk of fractures still remainsunresolved and highly debated. As a matter of fact no previous review has focused onthis relevant clinical topic. This review will deal with the various aspects of bone metabolism (turn-over,density, quality) in hypoparathyroidism, focusing on the few data available on therisk of fracture and in particular of morphometric vertebral fractures, the emerging way to assess actual skeletal fragility particularly in secondary forms of osteoporosis.

Primary hyperparathyroidism: clinical forms and their features. Retrospective study

Background: Primary hyperparathyroidism (PHPT) is a disease characterized by autonomous production of parathyroid hormone (PTH) from one or more parathyroid glands. Over the past 50 years asymptomatic form of the disease have become more prevalent in developed countries. Aims: To evaluate the clinical forms of PHPT presented in recent years and to specify the clinical and laboratory features in patients with symptomatic and asymptomatic forms of the disease. Materials and methods: We reviewed medical records of 449 patients admitted to three Medical Centers (Saint-Petersburg, Russia) between 2011–2018. Anamnesis, anthropometric data, laboratory (PTH, serum total calcium and ionized calcium, phosphorus, alkaline phosphatase, 24-h calciuria level, 25(OH)D) and instrumental (ultrasonography, scintigraphy, CT/MRI scan, DXA) tests were analyzed. Results: Patients’ average age was 59 years, with 93.1% women, and an F:M ratio of 13.5:1. Symptomatic form of PHPT was identified in 310 patients (69%), while 139 were asymptomatic. 4.2% of patients had PHPT as part of MEN syndrome. Almost half of the male population had urolithiasis and 45% of women had osteoporosis. Cardiovascular diseases were present in 64.4% of cases. 25(OH)D level was determined only in 20% of cases and was higher in asymptomatic patients (32.2 & 18.6 ng/ml, p = 0.003). Normocalcemic form of PHPT was diagnosed in 37 patients (8.2%) and was characterized not only by normocalcemia and lower PHT level, but also by smaller adenoma size ( p = 0.01) and hypocalcemic syndrome after surgery. Conclusions: Study results showed that symptomatic PHPT is more prevalent in the Russian population, that there are gender distinctions affecting the clinical presentation, and that the frequency of cardiovascular disease is high in this patient population. PHPT as part of MEN syndrome was detected in 4.2% of cases and required molecular genetic testing. Normocalcemic form of PHPT with postoperative hypocalcemia was present in every fourth patient. Rare determination of 25(OH)D level imposes the need of mandatory assessment of vitamin D supplementation and the reduction of its deficiency as part of the preoperative preparation of PHPT patients.

Surgical treatment of uremic secondary hyperparathyroidism complicated with thyroid nodules

Objective:To investigate the surgical treatment of secondary hyperparathyroidism(SHPT) with thyroid nodule(TN) in uremic patients.Method:The clinical data of 26 patients diagnosed as SHPT combined with TN were retrospectively analyzed.Result:The patients underwent total parathyroidectomy and parathyroid granuless were transplanted subcutaneously into the forearm. The levels of parathyroid hormone,alkaline phosphatase,serum calcium,serum phosphorus and calcium-phosphorus product in 6 months and 12 months after operation were significantly lower than those before operation(P<0.01).The quality of life assessed by KDQOL-SF scale was significantly higher than that before operation(P<0.01). Concomtiant TN was operated simultaneously, and gravel calcification was significantly associated with papillary thyroid carcinoma(P<0.01).Conclusion:Total parathyroidectomy plus subcutaneous minimal forearm autograft and concurrent surgery with TN are feasible, and can not only properly treat TN, but also significantly improve SHPT-related prognosis and quality of life. We should be alert to the possibility of malignant TN in SHPT background, especially those with grit calcification.

Outcomes of Patients with Scirrhous Hepatocellular Carcinoma: Insights from the National Cancer Database

IntroductionScirrhous hepatocellular carcinoma (HCC) is a rare primary liver tumor characterized by extensive fibrosis and production of parathyroid hormone–related peptide. There have been conflicting reports on patient survival in scirrhous versus non-scirrhous HCC. The objective of the present study was to define the clinical features, practice patterns, and long-term outcomes of patients with scirrhous HCC versus non-scirrhous HCC in a propensity score–matched cohort. MethodsA propensity score–matched cohort was created using data from the National Cancer Database for 2004 to 2015. A multivariable Cox proportional hazards regression analysis was performed to assess the effect of the scirrhous HCC variant on overall survival. ResultsAmong the 70,426 patients with a diagnosis of HCC who met the inclusion criteria, 99.8% had non-scirrhous HCC (n = 70,290) whereas a small subset had scirrhous HCC (n = 136, 0.19%). While 20,330 (28.9%) patients underwent liver-directed therapy (resection, ablation, and transplantation), the majority did not (n = 50,096, 71.1%). After propensity matching, there were no difference in 1-, 3-, or 5-year overall survival among patients with scirrhous versus non-scirrhous HCC (1-year overall survival (OS), 53.7% versus 51.0%; 3-year OS, 34.6% versus 28.7%; and 5-year OS, 18.0% versus 21.0%, respectively; p = 0.52). While the scirrhous HCC variant was not associated with survival (hazard ratio [HR] 0.93, 95% CI 0.74–1.16), non-receipt of liver-directed therapy (HR 0.24, 95% CI 0.18–0.32), advanced AJCC stage (III/IV) (HR 2.14, 95% CI 1.55–2.95), and non-academic facilities (HR 0.60, 95% CI 0.49–0.73) remained associated with worse survival. ConclusionPatients with the scirrhous variant had a comparable overall survival compared with individuals who had non-scirrhous HCC. Failure to receive liver-directed therapy, advanced AJCC stage (III/IV), and treatment at a non-academic facility was strongly associated with a worse long-term prognosis.

Parathyroid glands: the normal development, anatomy and histological structure

Parathyroid glands (PG) are endocrine glands, which are the most important humoral regulators of calcium and phosphorus metabolism in the body. They were first described by an Englishman Richard Owen in 1849. Most of patients have four PG – upper and lower. In 13% of cases there are more than four PG. The glands arise as diverticula from the endoderm of the third and fourth branchial pouches between the fifth and twelfth week of gestation. The IV branchial pouch forms the upper gland, and III pouch forms the inferior gland.&#x0D; The parathyroid hormone production has been demonstrated as early as 83/7 weeks gestational age. The formation, migration, differentiation and functioning of the PGs are determined by a number of genes and changes in them could lead to disfunction in these processes. The ectopic of PG is possible when migration violation (up to 22% of cases). The most common location of the ectopic PG is parenchyma of the thymus and thyroid gland. Each PG is richly vascularized and it is surrounded by a thin connective tissue. In adults, there are two types of parenchymal cells: the chief cells (active and inactive forms) and the oxyphil cells. During the life, the ratio of types of parenchymal cells and their activity have been changing, as well as the characteristics of the stroma.

Diagnosis and Evaluation of Primary Hyperparathyroidism.

Primary hyperparathyroidism (PHPT) is a common endocrine disorder, resulting from the autonomous production of parathyroid hormone from 1 or more abnormal parathyroid glands. Disease presentation ranges from asymptomatic to multiorgan involvement (skeletal, renal, neurocognitive, and gastrointestinal). This article outlines the epidemiology, clinical presentation, and diagnostic algorithm for PHPT. Key laboratory assessments are discussed, as are imaging studies for preoperative localization. Indications for surgical intervention are detailed, as are potential indications for surveillance. Sporadic and genetic syndromes associated with PHPT are also described.

Advances in Using Hansenula polymorpha as Chassis for Recombinant Protein Production.

The methylotrophic yeast Hansenula polymorpha, known as a non-conventional yeast, is used for the last 30 years for the production of recombinant proteins, including enzymes, vaccines, and biopharmaceuticals. Although a large number of reviews have been published elucidating the applications of this yeast as a cell factory, the latest was released about 10 years ago. Therefore, this review aimed at summarizing available information on the use of H. polymorpha as a host for recombinant protein production in the last decade. Examples of chemicals and virus-like particles produced using this yeast also are discussed. Firstly, the aspects that feature this yeast as a host for recombinant protein production are highlighted including the techniques available for its genetic manipulation as well as strategies for cultivation in bioreactors. Special attention is given to the novel genomic editing tools, mainly CRISPR/Cas9 that was recently established in this yeast. Finally, recent examples of using H. polymorpha as an expression platform are presented and discussed. The production of human Parathyroid Hormone (PTH) and Staphylokinase (SAK) in H. polymorpha are described as case studies for process establishment in this yeast. Altogether, this review is a guideline for this yeast utilization as an expression platform bringing a thorough analysis of the genetic aspects and fermentation protocols used up to date, thus encouraging the production of novel biomolecules in H. polymorpha.

A mathematical model of parathyroid gland biology.

Altered parathyroid gland biology in patients with chronic kidney disease (CKD) is a major contributor to chronic kidney disease‐mineral bone disorder (CKD‐MBD). This disorder is associated with an increased risk of bone disorders, vascular calcification, and cardiovascular events. Parathyroid hormone (PTH) secretion is primarily regulated by the ionized calcium concentration as well as the phosphate concentration in the extracellular fluid and vitamin D. The metabolic disturbances in patients with CKD lead to alterations in the parathyroid gland biology. A hallmark of CKD is secondary hyperparathyroidism, characterized by an increased production and release of PTH, reduced expression of calcium‐sensing and vitamin D receptors on the surface of parathyroid cells, and hyperplasia and hypertrophy of these cells. These alterations happen on different timescales and influence each other, thereby triggering a cascade of negative and positive feedback loops in a highly complex manner. Due to this complexity, mathematical models are a useful tool to break down the patterns of the multidimensional cascade of processes enabling the detailed study of subsystems. Here, we introduce a comprehensive mathematical model that includes the major adaptive mechanisms governing the production, secretion, and degradation of PTH in patients with CKD on hemodialysis. Combined with models for medications targeting the parathyroid gland, it provides a ready‐to‐use tool to explore treatment strategies. While the model is of particular interest for use in hemodialysis patients with secondary hyperparathyroidism, it has the potential to be applicable to other clinical scenarios such as primary hyperparathyroidism or hypo‐ and hypercalcemia.

Clinical Characteristics of Mineral Bone Disease Among Patients with Chronic Kidney Disease in Southern, Nigeria

Mineral bone disease (MBD) is a common complication in patients with chronic kidney disease (CKD). The objective of this study is to determine the characteristics of CKD-MBD among adult patients with CKD in South-South, Nigeria. One hundred and fifty consecutive consenting chronic kidney disease patients who fulfilled the inclusion criteria for this study were recruited. Patients had a detailed clinical assessment, biochemical and radiological evaluations for CKD-MBD. Biochemical investigations included serum calcium, phosphate, parathyroid hormone (PTH) and alkaline phosphatase while the radiological investigations included X-ray of the skull, spine, wrist and phalanges. The age range of the patients was 22-80 years, with a mean of 45.1 (±11.9) years. There were 90 males and 60 females with male to female ratio of 1.5:1. Symptoms suggestive of CKD-MBD in the study population were bone pain and pruritus occuring in 34.9% and 12.0% of the CKD-MBD patients. Other symptoms presented by the patients included leg swelling in 126 (84%), frothiness of urine in 123 (82%), vomiting in 109 (72.7%), facial puffiness in 102 (68%), haematuria in 18 (12%) and chest pain in 73 (48.7%) of the patients. The mean values for serum PTH, serum calcium, serum phosphate, alkaline phosphatase and caxpo4 product among the CKD-MBD patients were 205.06±112.6 pg/ml, 2.56±0.73mmol/l, 1.63±0.63mmol/l, 109.26±65.57IU/L and 4.07±1.28mmol2/l2 respectively. There was hypercalcaemia in 44.6%, hypocalcaemia in 26.0%, hypophosphataemia in 12.0% and hyperphosphataemia in 29.3% of the patients. High alkaline phosphatase was observed in 36.0% while 8.7% had low alkaline phosphatase. There was high calcium x phosphate product in 34.0% of the patients. Radiological features in keeping with CKD-MBD was present in only 6% of those with CKD-MBD. Hypercalcemia is the major biochemical abnormalilty in patients with CKD-MBD in our environment.

Secondary and Tertiary Hyperparathyroidism in Chronic Kidney Disease: An Endocrine and Renal Perspective.

Secondary Hyperparathyroidism (SHP) seen as a frequent complication in Chronic Kidney Disease (CKD) has many pathogenetic peculiarities that are still incompletely defined and understood. During the long course of chronic renal failure, SHP can also transform sometimes into the hypercalcemic state characterized by quasi-autonomous production of Parathyroid Hormone from the parathyroid glands: a disorder that is termed Tertiary Hyperparathyroidism. The clinical consequences of SHP in CKD are protean, encompassing bone and mineral abnormalities but as recently identified, also several metabolic and cardiovascular problems, the most important of which is vascular calcification. There have been several advances in the therapeutic armamentarium available for the treatment of SHP, though clear demonstration of a benefit regarding major clinical outcomes with any of the new agents is still lacking. This narrative review summarizes the current understanding about this disorder and highlights some of the recent research on the subject.

The Emerging Role of Nutritional Vitamin D in Secondary Hyperparathyroidism in CKD.

In chronic kidney disease (CKD), hyperphosphatemia induces fibroblast growth factor-23 (FGF-23) expression that disturbs renal 1,25-dihydroxy vitamin D (1,25D) synthesis; thereby increasing parathyroid hormone (PTH) production. FGF-23 acts on the parathyroid gland (PTG) to increase 1α-hydroxylase activity and results in increase intra-gland 1,25D production that attenuates PTH secretion efficiently if sufficient 25D are available. Interesting, calcimimetics can further increase PTG 1α-hydroxylase activity that emphasizes the demand for nutritional vitamin D (NVD) under high PTH status. In addition, the changes in hydroxylase enzyme activity highlight the greater parathyroid 25-hydroxyvitmain D (25D) requirement in secondary hyperparathyroidism (SHPT); the higher proportion of oxyphil cells as hyperplastic parathyroid progression; lower cytosolic vitamin D binding protein (DBP) content in the oxyphil cell; and calcitriol promote vitamin D degradation are all possible reasons supports nutritional vitamin D (NVD; e.g., Cholecalciferol) supplement is crucial in SHPT. Clinically, NVD can effectively restore serum 25D concentration and prevent the further increase in PTH level. Therefore, NVD might have the benefit of alleviating the development of SHPT in early CKD and further lowering PTH in moderate to severe SHPT in dialysis patients.

Adaptive Neuro-Fuzzy Inference System-Based Exploration of the Interrelationships of 25-Hydroxyvitamin D, Calcium, Phosphorus with Parathyroid Hormone Production.

The rationale of the current study was to assess the prevalence of 25-hydroxyvitamin D (25-OHD) deficiency and hyperparathyroidism in South Indian population and to explore interrelationships of 25-OHD, Ca, P towards parathyroid hormone (PTH) production using adaptive neuro-fuzzy inference system (ANFIS). A total of 407 subjects (228 men 179 women) with the mean age 56.8 ± 14.1 were tested for these parameters. In view of the skewed distribution of biochemical variables, data segregation was performed in tertiles and this data was trained to generate fuzzy interference system based on subclusters. The optimized model had 358 nodes and followed 44 fuzzy rules for prediction. This ANFIS model demonstrates that the deficiency of 25-OHD and Calcium triggers PTH production. PTH elevation is significant when Phosphorus is in the highest tertile. The associations observed by this model were consistent with the Kendall-Tau correlation matrix, which revealed inverse associations of Ca with P; and Ca with PTH and positive associations of P with PTH, and Ca with 25-OHD. Furthermore, the association statistics of the machine learning algorithm were also consistent, which suggested that depletion of Ca below 8.245mg/dl was shown to elevate PTH levels greater than 167pg/ml when P > 4.66. Subnormal depletion in 25-OHD (9.3-16.2ng/ml) is associated with subnormal elevation in PTH (47-73.6pg/ml). To conclude, ANFIS and machine learning algorithm are in agreement with each other in stating that 25-OHD deficiency triggers lower calcium levels, lower calcium and higher phosphorus trigger PTH production.

Whole-Exome Sequencing Identifies Novel Recurrent Somatic Mutations in Sporadic Parathyroid Adenomas.

Primary hyperparathyroidism is commonly caused by excess production of parathyroid hormone from sporadic parathyroid adenomas. However, the genetic architecture of sporadic primary hyperparathyroidism remains largely uncharacterized, especially in the Chinese population. To identify genetic abnormalities that may be involved in the etiology of sporadic parathyroid adenomas and to determine the mutation frequency of previously identified genes in the Chinese population, we performed whole-exome sequencing of 22 blood-tumor pairs from sporadic parathyroid adenomas. The most important finding is the recurrently mutated gene, ASXL3, which has never been reported in parathyroid tumors before. Moreover, we identified two different somatic mutations in the CDC73 gene and one somatic mutation in the EZH2 gene. The Y54X mutation in the CDC73 gene was previously identified in parathyroid carcinomas, which proved that parathyroid adenomas and carcinomas might possess similar molecular signatures. No mutations in the MEN1 or CCND1 genes were observed in our study. Thus, our data provide insights into the genetic pathogenesis of sporadic parathyroid adenomas and are valuable for the development of diagnostic and therapeutic approaches for sporadic primary hyperparathyroidism.

Physiology of the Calcium-Parathyroid Hormone-Vitamin D Axis.

Classic endocrine feedback loops ensure the regulation of blood calcium. Calcium in the extracellular fluid (ECF) binds and activates the calcium sensing receptor (CaSR) on the parathyroid cells, leading to an increase in intracellular calcium. This in turn leads to a reduced parathyroid hormone (PTH) release. Hypocalcemia leads to the opposite sequence of events, namely, lowered intracellular calcium and increased PTH production and secretion. PTH rapidly increases renal calcium reabsorption and, over hours to days, enhances osteoclastic bone resorption and liberates both calcium and phosphate from the skeleton. PTH also increases fibroblast growth factor 23 (FGF23) release from mature osteoblasts and osteocytes. PTH stimulates the renal conversion of 25-hydroxyvitamin D (25[OH]D) to 1,25(OH)2D, likely over several hours, which in turn will augment intestinal calcium absorption. Prolonged hypocalcemia and exposure to elevated PTH may also result in 1,25(OH)2D-mediated calcium and phosphorus release from bone. These effects restore the ECF calcium to normal and inhibit further production of PTH and 1,25(OH)2D. Additionally, FGF23 can be released from bone by 1,25(OH)2D and can in turn reduce 1,25(OH)2D concentrations. FGF23 has also been reported to decrease PTH production. When ECF calcium is in the hypercalcemic range, PTH secretion is reduced and renal 1,25(OH)2D production is decreased. In addition, the elevated calcium per se stimulates the renal CaSR, thus inducing calciuria. Therefore, suppression of PTH release and 1,25(OH)2D synthesis and stimulation of the renal CaSR lead to reduced renal calcium reabsorption, decreased skeletal calcium release, and decreased intestinal calcium absorption, resulting in the normalization of the elevated ECF calcium.

ACTUALITIES IN ENDOCRINOLOGY- PARATHYROID IMAGING.

Parathyroid imaging modalities have been used to guide clinicians and surgeons in finding the source of hyperparathyroidism for over 40 years. Primary hyperparathyroidism (PHPT) is generally caused by a parathyroid gland(s) autonomous production of parathyroid hormone (PTH), associated by enlargement of one or more glands. Noninvasive imaging procedures that are used in the management of hyperparathyroidism are anatomical (ultrasound, computer tomography, magnetic resonance imaging) and/or functional (nuclear medicine techniques: planar scintigraphy, single photon emission tomography, positron emission imaging) and/or hybrid imaging.