Excessive Secretion Of Parathyroid Hormone Research Articles

Genetics and Epigenetics of Parathyroid Carcinoma.

Parathyroid carcinoma (PC) is an extremely rare malignancy, accounting less than 1% of all parathyroid neoplasms, and an uncommon cause of primary hyperparathyroidism (PHPT), characterized by an excessive secretion of parathyroid hormone (PTH) and severe hypercalcemia. As opposed to parathyroid hyperplasia and adenomas, PC is associated with a poor prognosis, due to a commonly unmanageable hypercalcemia, which accounts for death in the majority of cases, and an overall survival rate of 78-85% and 49-70% at 5 and 10 years after diagnosis, respectively. No definitively effective therapies for PC are currently available. The mainly employed treatment for PC is the surgical removal of tumoral gland(s). Post-surgical persistent or recurrent disease manifest in about 50% of patients. The comprehension of genetic and epigenetic bases and molecular pathways that characterize parathyroid carcinogenesis is important to distinguish malignant PCs from benign adenomas, and to identify specific targets for novel therapies. Germline heterozygote inactivating mutations of the CDC73 tumor suppressor gene, with somatic loss of heterozygosity at 1q31.2 locus, account for about 50-75% of familial cases; over 75% of sporadic PCs harbor biallelic somatic inactivation/loss of CDC73. Recurrent mutations of the PRUNE2 gene, a recurrent mutation in the ADCK1 gene, genetic amplification of the CCND1 gene, alterations of the PI3K/AKT/mTOR signaling pathway, and modifications of microRNA expression profile and gene promoter methylation pattern have all been detected in PC. Here, we review the current knowledge on gene mutations and epigenetic changes that have been associated with the development of PC, in both familial and sporadic forms of this malignancy.

The clinical practice guidelines for primary hyperparathyroidism, short version

Primary hyperparathyroidism (PHPT) is an endocrine disorder of parathyroid glands characterized by excessive secretion of parathyroid hormone (PTH) with an upper normal or elevated blood calcium level. Classical PHPT refers to a symptomatic, multi-system disorder, wich can lead to a significant decrease in the quality of life, disability of patients, and even an increased risk of premature death. Hypercalcemia and the catabolic effect of PTH on various cells are considered as the main pathogenetic mechanisms of the PHPT associated complications. In the last two decades, there has been an increase in the incidence of PHPT, mainly due to the mild forms of the disease, primarily due to the routine calcium screening in North America, Western Europe and, Asia. High prevalence of the disease, as well as the variety of clinical manifestations, cause the attention of different specialists - physicians, rheumatologists, urologists, nephrologists, cardiologists and other doctors. This review cover the main issues of Russian guidelines for the management of PHPT, approved in 2020, including laboratory and instrumental methods, differential diagnosis, surgical and conservative approach, short-term and long-term follow-up. This guidelines also include the recommendations for special groups of patients with hereditary forms of PHPT, parathyroid carcinoma, PHPT during pregnancy.

КЛИНИЧЕСКИЕ РЕКОМЕНДАЦИИ ПО ПЕРВИЧНОМУ ГИПЕРПАРАТИРЕОЗУ, КРАТКАЯ ВЕРСИЯ

Primary hyperparathyroidism (PHPT) is an endocrine disorder of parathyroid glands characterized by excessive secretion of parathyroid hormone (PTH) with an upper normal or elevated blood calcium level. Classical PHPT refers to a symptomatic, multi-system disorder, wich can lead to a significant decrease in the quality of life, disability of patients, and even an increased risk of premature death. Hypercalcemia and the catabolic effect of PTH on various cells are considered as the main pathogenetic mechanisms of the PHPT associated complications. In the last two decades, there has been an increase in the incidence of PHPT, mainly due to the mild forms of the disease, primarily due to the routine calcium screening in North America, Western Europe and, Asia. High prevalence of the disease, as well as the variety of clinical manifestations, cause the attention of different specialists - physicians, rheumatologists, urologists, nephrologists, cardiologists and other doctors. This review cover the main issues of Russian guidelines for the management of PHPT, approved in 2020, including laboratory and instrumental methods, differential diagnosis, surgical and conservative approach, short-term and long-term follow-up. This guidelines also include the recommendations for special groups of patients with hereditary forms of PHPT, parathyroid carcinoma, PHPT during pregnancy.

Normocalcemic Primary Hyperparathyroidism: Need for a Standardized Clinical Approach.

Since normocalcemic primary hyperparathyroidism (NHPT) was first defined at the Third International Workshop on the Management of Asymptomatic Primary Hyperparathyroidism in 2008, many papers have been published describing its prevalence and possible complications. Guidelines for the management of this condition are still lacking, and making the diagnosis requires fulfillment of strict criteria. Recent studies have shown that intermittent oscillations of serum calcium just below and slightly above the normal limits are very frequent, therefore challenging the assumption that serum calcium must be consistently normal to make the diagnosis. There is debate if these variations in serum calcium outside the normal range should be included under the rubric of NHPT or, rather, a milder form of classical primary hyperparathyroidism. Innovative approaches to define NHPT have been proposed that still need to be validated in prospective studies. Non-classical complications, especially cardiovascular complications, have been associated with NHPT, indicating that hyperparathyroidism may be a cardiovascular risk factor. New associations between parathyroid hormone (PTH) and several other comorbidities have also been reported from observational studies, suggesting that excessive PTH secretion might cause tissue dysfunction independent of serum calcium. Heterogeneous studies using different definitions of NHPT, however, make it difficult to draw definitive conclusions regarding the role of PTH excess when complications other than osteoporosis or kidney stones are described. This review will focus on clinical aspects and suggest an approach to NHPT.

Rare Case of Severe Hypercalcemia Secondary to Atypical Sestamibi Negative Parathyroid Cystic Adenoma

Primary hyperparathyroidism (PHPT) is defined as excessive secretion of parathyroid hormone (PTH) originating from the parathyroid gland. The most common cause is a single parathyroid adenoma which is typically solid. Cystic parathyroid adenomas (CPA) are the cause of about 1–2% of cases of primary hyperparathyroidism. It is known that cystic parathyroid adenomas are a result of degeneration of an existing parathyroid adenoma. SestaMIBI is an imaging study based on uptake of radioactive technetium99 and used to localize parathyroid adenomas. We describe an unusual case of severe hypercalcemia secondary to 99mTc sestaMIBI negative atypical parathyroid cystic adenoma. A 56-year-old male presented to our facility with nausea and vomiting. His past medical history included hypertension and hepatitis C with no history of fractures or kidney disease. Physical examination was normal. Upon admission the patient was afebrile with blood pressure of 170/120 mmHg and heart rate of 62 bpm. Chemistry showed Calcium of 14.5 mg/dL (8.6–10.2mg/dL), phosphorus 2.2 (2.7–4.5) mh/dL, magnesium 1.8 (1.7–2.6)mg/dL, intact PTH of 375 (15–65) pg/mL, PTH-related peptide <2.0 pmol/L(<2 pmol/L), 25-OH vitamin D of 19 ng/ml (30–80), Creatinine 1.22 (0.7–1.2)mg/dL, alkaline phosphatase 95 (40–129) units/L. He was started on aggressive hydration, calcitonin 4 units/kg, 4 mg of IV Zolendroninc acid. Neck sonogram revealed a large, complex, predominantly anechoic lesion with solid vascular components and thick internal septations in the inferior and medial aspect of the right thyroid lobe measuring 3 x 2 x 5.5 cm. Findings were confirmed with CT of the neck. Since Sestamibi scan (planar and SPECT/CT) did not show uptake in parathyroid glands, the cyst was thought to be of thyroid origin. Fine needle aspiration was not able to detect cellular material, but PTH was >100 pg/ml on the FNA sample. Otolaryngology service was consulted for parathyroidectomy. During the surgical treatment, the right upper parathyroid gland was removed with no changes in serum PTH. Next, the cystic lesion was removed with normalization of serum PTH (from 218 pg/ml to 35.2 pg/ml respectively). Intraoperative frozen section analysis was read as a cystic parathyroid adenoma. The final pathology report revealed cystic parathyroid tissue favoring parathyroid adenoma with focal atypia. Hypercalcemia resolved. Conclusions: Atypical cystic parathyroid adenomas are a rare cause of PHPT. 90% of parathyroid cysts are nonfunctional. Above mention is a case of a patient presenting with hypercalcemic crisis secondary to cystic parathyroid adenoma, which posed a diagnostic challenge as both neck ultrasound and 99mTc sestaMIBI scan were inconclusive. These findings should trigger suspicion for functional parathyroid lesions. Cystic components should be evaluated for PTH levels and if significantly elevated should be treated as a parathyroid adenoma.

Treatment-Resistant Hypercalcemia Secondary to Ectopic PTH Hypersecretion From Disseminated Ovarian Cancer

Background: Hypercalcemia of malignancy (HCM) can present secondary to hypersecretion of parathyroid hormone (PTH)-related protein (PTHrP) from malignant tumors, but rare cases of HCM have also been documented due to inappropriate PTH secretion from ectopic neoplasms. Here, we report an unusual case of HCM due to hypersecretion of PTH from a disseminated mucinous ovarian adenocarcinoma. Case Presentation: A 45-year-old female presented with confusion, constipation, fatigue, and abdominal pain two weeks after total abdominal hysterectomy with bilateral salpingo-oophorectomy and suboptimal debulking of a newly discovered left ovarian mucinous adenocarcinoma with metastasis to the bladder, parametrium, vagina, right ovary, and rectosigmoid. Subsequent CT revealed numerous bilateral pulmonary nodules, hilar adenopathy, liver lesions, and abdominal adenopathy. On exam, she was tachycardic and hypertensive with diaphoresis, dry mucous membranes, respiratory distress, guarded abdominal tenderness, and altered mental status. Her labs were significant for a serum calcium of 21.7 mg/dL, creatinine of 1.93 mg/dL, ferritin of 2,379 ng/mL, leukocytosis of 21.9 bil/L, PTH of 1,061 pg/mL, and PTHrP of 29 pmol/L. Ectopic PTH secretion was highly suspected after negative parathyroid ultrasound. Pamidronate (60 mg IV), calcitonin (200 U IM), and fluid resuscitation were unable to normalize her serum calcium, resulting in the need for dialysis and subsequent continuous renal replacement therapy. Further intervention with denosumab (120 mg SQ), etelcalcetide (5 mg IV), and cinacalcet (60 mg PO) was also attempted. Serum calcium began to decline, but repeat PTH resulted greater than 2,500 pg/mL. Unfortunately, the patient died just one week into her hospital course from septic shock and multi-organ system failure. Discussion: Hypercalcemia of malignancy typically arises from tumor secretion of PTHrP, cytokine release from osteolytic metastases, or tumor production of calcitriol. In cases of hypercalcemia due to excess PTH secretion, primary parathyroid etiologies are typically considered while ectopic PTH-secreting tumors are rare. PTH staining of biopsy specimens and total body sestamibi scan may prove useful in the early detection and treatment of these tumors, but HCM offers a poor prognosis with mean survival of 2 to 3 months and in-hospital mortality of 6.8%. Currently, there are only three cases in the reported literature of ectopic PTH-induced hypercalcemia related to ovarian cancer. To our knowledge, this is the fourth reported case. Conclusion: Ectopic PTH-secreting tumors carry a poor prognosis and should be considered in cancer patients presenting with PTH-associated hypercalcemia. Biopsy staining for PTH and total body sestamibi scan may assist in the early detection of these tumors, but current treatment strategies offer suboptimal outcomes.

Primary Hyperparathyroidism Due to Parathyroid Adenoma: Clinical Case

Primary hyperparathyroidism (PGPT) is an endocrine disease characterized by excessive secretion of parathyroid hormone (PTH) in upper — normal or elevated blood calcium levels due to primary parathyroid gland pathology (osch). Primary hyperparathyrosis, depending on the clinical manifestations, can occur in the normocalcemic, mild and manifest form. This article presents a clinical case of the development of the manifest form by the type of visceral disorders. Which appeared in the form of pathology of the gastrointestinal tract. This form of the disease is an indication for surgical treatment and further correction of calcium-phosphorus metabolism.

Renal excretion function in primary hyperparathyroidism: cardio-renal syndrome

Background. Primary hyperparathyroidism (PHPT) is an endocrine disease, due to the formation of excess parathyroid hormone secretion and a disturbance of phosphorus-calcium metabolism. PHPT is associated with reduced renal function and related increased mortality, therefore renal function impairment defined as a glomerular filtration rate (GFR) less than 60 mL/ min/1.73 m 2 is considered as an indication for surgical treatment. Some patients with PHPT have secondary cardio-renal syndrome (type 5), which is characterized by the presence of combined renal and cardiac pathology. THE AIM: Evaluate the GFR in patients with mild and symptomatic PHPT and its changes after parathyroidectomy and on medical treatment. Patients and methods : A cross-sectional comparative and prospective study was conducted on 100 patients with confirmed PHPT. A clinical and laboratory examination was performed at 6, 12, and/or 24 months and included an assessment of the PHPT complications as well as expression of cardio-renal syndrome according to the selected management tactics. Changes in GFR were evaluated in 29 patients after surgical treatment and in 27 patients on conservative management. Glomerular filtration rate was calculated by the Modification of Diet in Renal Disease Study (MDRD) formula. The chronic kidney disease (CKD) stage was estimated accordingly to current recommendations. Results: We included 100 patients (10 men and 90 women) with PHPT: 33 with mild and 67 with symptomatic PHPT. The median age was 57 years [51;61]. Mean GFR was 84,1 [73,3; 97,9] ml/ min/1,73 m 2 . Prevalence of CKD 3-4 in patients with PHPT was recorded at 11 %. Patient management tactics were determined in accordance with international recommendations. In the long-term period after surgery, we observed the decrease of GFR in patients with mild form within the limits of CKD 1-2 (p=0,013, W-test). No significant changes in GFR were noted during medical management and monitoring. Summary, the cardio-renal syndrome (CKD of any stage and cardiovascular pathology) was revealed in 26 % of patients. Arterial hypertension was registered in 40 %. Conclusions : We found a high frequency of renal function impairment in patients with PHPT, including patients with a mild form of the disease. We did not observe any significant improvement in renal filtration function, after surgical treatment and remission of PHPT. The safety of conservative tactics has been confirmed. The high frequency of cardiovascular pathology in patients with PHPT is beyond doubt and requires prospective studies in the larger cohorts of patients.

Safety and efficacy of common vitamin D supplementation in primary hyperparathyroidism and coexistent vitamin D deficiency and insufficiency: a systematic review and meta-analysis.

Primary hyperparathyroidism (PHPT) is characterized by excessive secretion of parathyroid hormone (PTH). Vitamin D deficiency can stimulate parathyroid secretion. However, whether to correct vitamin D deficiency in patients with PHPT is controversial. We aimed to evaluate the safety and efficacy of vitamin D replacement in patients with PHPT. We searched PubMed, Cochrane Library, and Embase. The relevant data were extracted from the included documents. The methodological items for non-randomized studies score entries were used for evaluation of quality. Review Manager 5.3 and Stata 12.0 were used for statistical analysis. A total of 11 articles were included with a total of 388 patients. The serum calcium mean difference (MD) was -0.06mg/dL [95% confidence interval (95% CI) -0.16, 0.04]. Subgroup analysis showed that serum calcium levels did not change if the intervention time exceeded 1month. The 24-h urinary calcium MD was 36.78mg/day (95% CI -37.15, 110.71), which indicated that there was no significant effect of vitamin D supplementation on 24-h urinary calcium levels. The MD of PTH was -16.01pg/mL (95% CI -28.79, -3.24). Subgroup analysis according to the intervention time showed that vitamin D intervention for more than 1month significantly reduced PTH levels. The ALP MD was -10.81 U/L (95% CI -13.98, -7.63), which indicated Vitamin D supplementation reduced its level. The MD of 25-hydroxyvitamin D was 22.09μg/L (95% CI 15.01, 29.17), and no source of heterogeneity was found. Vitamin D supplementation in patients with PHPT and vitamin D deficiency significantly reduces PTH and ALP levels without causing hypercalcemia and hypercalciuria.

The Interplay Between the Renin-Angiotensin-Aldosterone System and Parathyroid Hormone.

The renin-angiotensin-aldosterone system (RAAS) is the regulatory system by which renin induces aldosterone production. Angiotensin II (Ang II) is the main effector substance of the RAAS. The RAAS regulates blood pressure and electrolyte balance by controlling blood volume and peripheral resistance. Excessive activation of the RAAS is an important factor in the onset of cardiovascular disease and the deterioration of this disease. The most common RAAS abnormality is primary aldosteronism (PA). Parathyroid hormone (PTH) is a peptide secreted by the main cells of the parathyroid gland, which promotes elevated blood calcium (Ca2+) levels and decreased blood phosphorus (Pi) levels. Excessive secretion of PTH can cause primary hyperparathyroidism (PHPT). Parathyroidism is highly prevalent in postmenopausal women and is often associated with secondary osteoporosis. PA and PHPT are common endocrine system diseases. However, studies have shown a link between the RAAS and PTH, indicating a positive relationship between them. In this review, we explore the complex bidirectional relationship between the RAAS and PTH. We also point out possible future treatment options for related diseases based on this relationship.

Ultrasound combined with biochemical parameters can be used to differentiate parathyroid carcinoma from benign tumors in patients with primary hyperparathyroidism.

Primary hyperparathyroidism (PHPT) results from excessive secretion of parathyroid hormone from parathyroid tumors. Differentiating parathyroid tumors can be challenging before operation. To differentiate parathyroid carcinoma from benign tumors in patients with PHPT by the application of ultrasound and biochemical parameters. This study is a retrospective study. The study enrolled 17 patients with parathyroid carcinoma (PC) and 57 patients with parathyroid adenoma (PA), confirmed by postoperative pathology, between September 2010 and July 2017. This study retrospectively compared the ultrasonic features of the tumors included echotexture, maximum lesion diameter, shape, margin, blood flow inside the mass, intralesional calcifications, cysts in the mass, and biochemical parameters included serum calcium, phosphorus, parathyroid hormone (PTH), alkaline phosphatase (ALP) levels, gender distribution and age of patients between patients with PC and those with PA. In the US images, the two groups showed significant differences in heterogeneity, the appearance of a taller-than-wide shape, irregular or lobulated margins, and intralesional calcifications (p < #x003C;< #x200A;0.05). However, no significant difference was found in echogenicity, maximum lesion diameter, blood flow, and cystic components of the mass (p > #x003E;> #x200A;0.05). The mean PTH levels were significantly different between the two groups (p < #x003C;< #x200A;0.05). The PC and PA patients did not differ significantly in terms of mean serum calcium, mean serum phosphorus, and mean ALP levels (p > #x003E;> #x200A;0.05). There were significant differences to distinguish PC from PA in calcifications in mass or/and taller-than-wide shape combine with PTH > #x003E;> #x200A;1000 pg/mL (p < #x003C;< #x200A;0.05). Significant difference existed in the age between the two groups (p < #x003C;< #x200A;0.001). No significant difference existed in the gender distribution between the two groups (p > #x003E;> #x200A;0.05). Ultrasound features especially intralesional calcifications and taller-than-wide shape combine with an extremely high serum PTH (>1000 pg/mL) are helpful in differentiating between benign and parathyroid tumors in patients with PHPT.

Hyperparathyroidism (primary) NICE guideline: diagnosis, assessment, and initial management.

Parathyroid hormone (PTH) is secreted from four parathyroid glands situated behind the thyroid gland. PTH regulates calcium and phosphate levels by its promotion of phosphate excretion and calcium reabsorption in the kidneys; stimulation of osteoclastic activity in the bone resulting in raised serum calcium; and increased intestinal absorption of calcium. Hyperparathyroidism is excessive secretion of PTH and can be primary, secondary, or tertiary: This article summarises the new National Institute for Health and Care Excellence (NICE) guideline for the diagnosis, assessment, and initial management of primary hyperparathyroidism (PHPT).2 This article highlights areas of particular importance for primary care. The causes and management of hypercalcaemia outside of the diagnosis and management of PHPT are beyond the scope of this article. The signs and symptoms of PHPT are predominantly brought about by hypercalcaemia and include thirst, increased …

Clinical and Molecular Genetics of Primary Hyperparathyroidism

Calcium homeostasis is maintained by the actions of the parathyroid glands, which release parathyroid hormone into the systemic circulation as necessary to maintain the serum calcium concentration within a tight physiologic range. Excessive secretion of parathyroid hormone from one or more neoplastic parathyroid glands, however, causes the metabolic disease primary hyperparathyroidism (HPT) typically associated with hypercalcemia. Although the majority of cases of HPT are sporadic, it can present in the context of a familial syndrome. Mutations in the tumor suppressor genes discovered by the study of such families are now recognized to be pathogenic for many sporadic parathyroid tumors. Inherited and somatic mutations of proto-oncogenes causing parathyroid neoplasia are also known. Future investigation of somatic changes in parathyroid tumor DNA and the study of kindreds with HPT yet lacking germline mutation in the set of genes known to predispose to HPT represent two avenues likely to unmask additional novel genes relevant to parathyroid neoplasia.

The Total Testing Process of Intra-Operative Parathyroid Hormone. A Narrative Review.

Primary hyperparathyroidism (pHPT) is a common endocrine disorder, due to an excessive secretion of parathyroid hormone (PTH) from one or more parathyroid gland(s), where the only cure remains surgery. The surgical approach has become less invasive over the years, thanks to the advances in the preoperative localization of the enlarged parathyroid gland, as well as to the possibility to measure intra-operative parathyroid hormone (IOPTH). After the targeted removal of a parathyroid gland, IOPTH can confirm biochemically the cure of pHPT, such that it helps the surgeon to judge if the parathyroidectomy has been successful and there is no need of additional dissection. As with all laboratory tests, the quality of IOPTH total testing process is essential to the best utilization of patients' results. However, this can be affected by errors occurring in different phases. This review aims to describe the total testing process of IOPTH. We performed a search in Pubmed and a review of the literature on the current management of pHPT and the total testing process of IOPTH measurement. Compared to previous studies focusing on single aspects of the IOPTH testing process, here we have analyzed all the steps crucial for the quality of IOPTH from the "pre-pre" to the "post-post" analytical phase. Clinicians and laboratory scientists should be aware of all the potential sources of errors in IOPTH measurement in order to improve their daily management of pHPT.

Primary hyperparathyroidism with PTH values within the reference range: clinical case of a patient with recurrent nephrolithiasis

Hyperparathyroidism is an endocrine disease characterized by excessive secretion of parathyroid hormone (PTH) by the parathyroid glands. Primary hyperparathyroidism (PHPT) can be diagnosed biochemically with the combination of hypercalcemia and upper-normal or elevated levels of PTH. There are few descriptions of PHPT with normal intact PTH secretion in the literature. The incidence of PHPT among patients with recurrent urolithiasis is 28%. We present a clinical case of diagnosing PHPT in a 64-year-old female patient with rare variant of the disease. Before establishing the diagnosis, the main patient complaints were long-term recurrent nephrolithiasis and nephrocalcinosis. Surgical treatment made it possible to achieve rapid normalization of biochemical parameters of calcium-phosphorus metabolism, increase bone mineral density in the lumbar spine, improve the general condition of the patient. This clinical case demonstrates errors and late diagnosis of PHPT associated with poor knowledge of the manifestations of hyperparathyroidism and its masks. The authors recommend to determine the concentrations of total calcium, albumin, serum levels of PTH in patients with clinical picture of PHPT, in order to exclude the disease.

Deficiency in the secreted protein Semaphorin3d causes abnormal parathyroid development in mice

Primary hyperparathyroidism (PHPT) is a common endocrinopathy characterized by hypercalcemia and elevated levels of parathyroid hormone. The primary cause of PHPT is a benign overgrowth of parathyroid tissue causing excessive secretion of parathyroid hormone. However, the molecular etiology of PHPT is incompletely defined. Here, we demonstrate that semaphorin3d (Sema3d), a secreted glycoprotein, is expressed in the developing parathyroid gland in mice. We also observed that genetic deletion of Sema3d leads to parathyroid hyperplasia, causing PHPT. In vivo and in vitro experiments using histology, immunohistochemistry, biochemical, RT-qPCR, and immunoblotting assays revealed that Sema3d inhibits parathyroid cell proliferation by decreasing the epidermal growth factor receptor (EGFR)/Erb-B2 receptor tyrosine kinase (ERBB) signaling pathway. We further demonstrate that EGFR signaling is elevated in Sema3d-/- parathyroid glands and that pharmacological inhibition of EGFR signaling can partially rescue the parathyroid hyperplasia phenotype. We propose that because Sema3d is a secreted protein, it may be possible to use recombinant Sema3d or derived peptides to inhibit parathyroid cell proliferation causing hyperplasia and hyperparathyroidism. Collectively, these findings identify Sema3d as a negative regulator of parathyroid growth.

Importance of Parathyroid Hormone Needle Aspiration Washout in Adenoma Localization in Primary Hyperparathyroidism.

BackgroundPrimary hyperparathyroidism is an endocrine disease characterized by excessive secretion of parathyroid hormone and hypercalcemia. Although scintigraphy is commonly used for pre-operative localization, it does not always localize the parathyroid lesion. In such patients, ultrasonography can visualize the suspected lesion and needle washout sample for parathyroid hormone titer can be used to confirm parathyroid tissue. The aim of this study was to investigate the accuracy of the parathyroid hormone needle aspiration washout method in detecting the localization of parathyroid adenoma.Material/MethodsPatients with primary hyperparathyroidism who underwent surgery between 2010 and 2017 at the Dicle University Medical Faculty Hospital were retrospectively evaluated using medical records. Patients undergoing parathyroid hormone needle aspiration washout were performed in the suspected lesion were included in the study. Accompanied by ultrasonography, the suspected area was penetrated with needle, and negative aspiration was performed. Pre-operative scintigraphic data of patients were evaluated. Patients with positive scintigraphy, negative scintigraphy or patients who did not undergo scintigraphy were included in our study. Demographic data were presented as continuous data means ± standard deviation. Categorical variables were presented as frequency and percentage.ResultsForty-nine patients (female/male, 40/9) who underwent parathyroid hormone needle aspiration washout were included in the study. Parathyroid hormone washout result was positive in 47 patients (47/49) and negative in 2 patients (2/49), sensitivity/positive predictive value (PPV) 95.91%. Twenty-six patients who had negative/suspicious scintigraphic results were diagnosed using the parathyroid hormone needle aspiration washout method (24/26, 92.3% accuracy). Parathyroid hormone needle aspiration washout without scintigraphy was performed in 13 patients (13/13, 100% accuracy).ConclusionsParathyroid adenoma localization can be easily done using parathyroid hormone needle aspiration washout in centers experienced in adenoma localization in primary hyperparathyroidism cases in which scintigraphic results are negative or scintigraphy cannot be performed. We believe that primary parathyroid hormone needle aspiration washout can be a new localization method for adenoma localization.

Comparative Gene Expression Profiles in Parathyroid Adenoma and Normal Parathyroid Tissue.

Parathyroid adenoma is the main cause of primary hyperparathyroidism, which is characterized by enlarged parathyroid glands and excessive parathyroid hormone secretion. Here, we performed transcriptome analysis, comparing parathyroid adenomas with normal parathyroid gland tissue. RNA extracted from ten parathyroid adenoma and five normal parathyroid samples was sequenced, and differentially expressed genes (DEGs) were identified using strict cut-off criteria. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using DEGs as the input, and protein-protein interaction (PPI) networks were constructed using Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) and visualized in Cytoscape. Among DEGs identified in parathyroid adenomas (n = 247; 45 up-regulated, 202 down-regulated), the top five GO terms for up-regulated genes were nucleoplasm, nucleus, transcription DNA-template, regulation of mRNA processing, and nucleic acid binding, while those for down-regulated genes were extracellular exosome, membrane endoplasmic reticulum (ER), membrane, ER, and melanosome. KEGG enrichment analysis revealed significant enrichment of five pathways: protein processing in ER, protein export, RNA transport, glycosylphosphatidylinositol-anchor biosynthesis, and pyrimidine metabolism. Further, PPI network analysis identified a densely connected sub-module, comprising eight hub molecules: SPCS2, RPL23, RPL26, RPN1, SEC11C, SEC11A, RPS25, and SEC61G. These findings may be helpful in further analysis of the mechanisms underlying parathyroid adenoma development.

Primary Hyperparathyroidism.

The 4 parathyroid glands derive from the third and fourth pharyngeal pouches and descend caudally to the anterior neck. Through the secretion of parathyroid hormone (PTH), the parathyroid glands are primarily responsible for maintaining extracellular calcium and phosphorus concentrations. Hypercalcemia may be distinguished in parathyroid-hypercalcemia and nonparathyroid hypercalcemia. The most common disorders include primary hyperparathyroidism (PHPT), malignancy, granulomatous diseases, and medications. PHPT is a disease characterized by excessive secretion of PTH. PHPT is most commonly due to a single benign parathyroid adenoma (80%) and with multiglandular disease seen in approximately 15-20% of patients. PHPT is due to multiglandular involvement consisting of either multiple adenomas or hyperplasia of all 4 glands (5-10%), and very rarely parathyroid carcinoma (<1%). In most patients the disease is sporadic, without a personal or family history of PHPT. The genetic syndromes associated with PHPT include multiple endocrine neoplasia type 1 (MEN1), MEN2A, and MEN4, hyperparathyroidism-jaw tumor syndrome, familial isolated PHPT, familial hypocalciuric hypercalcemia, and neonatal severe hyperparathyroidism. The asymptomatic clinical presentation is most common in countries where biochemical screening is routine. Conversely, target organ involvement at presentation dominates the clinical landscape of PHPT in other countries, such as China and India, where biochemical screening is not routine practice.

Secondary and tertiary hyperparathyroidism in chronic kidney disease

In the treatment of secondary hyperparathyroidism of end-stage chronic kidney disease, vitamin D receptor activation and allosteric modulators of the calcium-sensing receptor – inhibit glandular hyperplasia, reduce parathyroid hormone levels, impact on bone turnover and mineral density. But the use of calcimimetic and vitamin D analogs or mimetics did not reduce the need for parathyroidectomy for refractory hyperparathyroidism. The enlarged parathyroid gland and gland nodular transformation became refractory to medical therapy and patient need for parathyroidectomy. Tertiary hyperparathyroidism is a state of excessive secretion of parathyroid hormone after a long period of secondary hyperparathyroidism and renal transplantation.&#x0D; In this article, we present the case of a Caucasian male with chronic kidney disease (end-stage on chronic hemodialysis and after kidney transplantation) and different forms of hyperparathyroidism (secondary and tertiary). Our case study shows that only a multi-interventional strategy is likely to be more effective treatment in cases of severe and refractory to medical therapy hyperparathyroidism.