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Journal of Internal Medicine Dec 2016Primary hyperparathyroidism (pHPT) is a common endocrine disease characterized by excessive secretion of parathyroid hormone and an increased level of serum calcium.... (Review)
Review
Primary hyperparathyroidism (pHPT) is a common endocrine disease characterized by excessive secretion of parathyroid hormone and an increased level of serum calcium. Overall, 80-85% of pHPT cases are due to a benign, single parathyroid adenoma (PA), and 15% to multiglandular disease (multiple adenomas/hyperplasia). Parathyroid carcinoma (PC) is rare, accounting for <0.5-1% of pHPT cases. Secondary hyperparathyroidism (sHPT) is a complication of renal failure, with the development of parathyroid tumours and hypercalcaemia. Recurrent mutations in the MEN1 gene have been confirmed by the whole-exome sequencing in 35% of PAs, suggesting that non-protein-coding genes, regulatory elements or epigenetic derangements may also have roles in the majority of PAs. DNA translocations with cyclin D1 overexpression occur in PAs (8%). In PCs, mutations in CDC73/HRPT2 are common. Activation of the WNT/β-catenin signalling pathway (accumulation of nonphosphorylated β-catenin) by an aberrantly truncated LRP5 receptor has been seen for the majority of investigated PAs and sHPT tumours, and possibly by APC inactivation through promoter methylation in PCs. Promoter methylation of several other genes and repressive histone H3 lysine 27 trimethylation by EZH2 of the HIC1 gene may also contribute to parathyroid tumorigenesis. It is possible that a common pathway exists for parathyroid tumour development. CCND1 (cyclin D1) and EZH2 overexpression, accumulation of nonphosphorylated β-catenin and repression of HIC1 have all been observed to occur in PAs, PCs and sHPT tumours. In addition, hypermethylation has been observed for the same genes in PAs and PCs (e.g. SFRP1, CDKN2A and WT1). Whether β-catenin represents a 'hub' in parathyroid tumour development will be discussed.
Topics: Epigenesis, Genetic; Humans; Hyperparathyroidism, Primary; Jumonji Domain-Containing Histone Demethylases; MicroRNAs; Mutation; Parathyroid Neoplasms; Wnt Signaling Pathway
PubMed: 27071708
DOI: 10.1111/joim.12458 -
Endocrinology Dec 2023
Topics: Humans; Calcium; Vitamin D; Cyclin D1; Parathyroid Glands; Parathyroid Hormone; Vitamin D Deficiency; Carcinogenesis
PubMed: 38104244
DOI: 10.1210/endocr/bqad189 -
International Journal of Molecular... May 2022Parathyroid tumors are very prevalent conditions among endocrine tumors, being the second most common behind thyroid tumors. Secondary hyperplasia can occur beyond... (Review)
Review
Parathyroid tumors are very prevalent conditions among endocrine tumors, being the second most common behind thyroid tumors. Secondary hyperplasia can occur beyond benign and malignant neoplasia in parathyroid glands. Adenomas are the leading cause of hyperparathyroidism, while carcinomas represent less than 1% of the cases. Tumor suppressor gene mutations such as and were demonstrated to be involved in tumor development in both familiar and sporadic types; however, the epigenetic features of the parathyroid tumors are still a little-explored subject. We present a review of epigenetic mechanisms related to parathyroid tumors, emphasizing advances in histone modification and its perspective of becoming a promising area in parathyroid tumor research.
Topics: Epigenesis, Genetic; Epigenomics; Histone Code; Humans; Hyperparathyroidism; Parathyroid Neoplasms
PubMed: 35628190
DOI: 10.3390/ijms23105378 -
Surgical Pathology Clinics Mar 2023Parathyroid disease typically presents with parathyroid hyperfunction as result of neoplasia or a consequence of non-neoplastic systemic disease. Given the parathyroid... (Review)
Review
Parathyroid disease typically presents with parathyroid hyperfunction as result of neoplasia or a consequence of non-neoplastic systemic disease. Given the parathyroid gland is a hormonally active organ with broad physiologic implications and serologically accessible markers for monitoring, the diagnosis of parathyroid disease is predominantly a clinical pathologic correlation. We provide the current pathological correlates of parathyroid disease and discuss preoperative, intraoperative, and postoperative pathology consultative practice for optimal patient care.
Topics: Humans; Parathyroid Glands; Parathyroid Neoplasms; Parathyroid Hormone; Parathyroidectomy; Monitoring, Intraoperative
PubMed: 36739169
DOI: 10.1016/j.path.2022.10.001 -
American Journal of Surgery Mar 2018The purpose of this study was to determine if there are clinical features that raise suspicion for parathyroid hyperplasia.
INTRODUCTION
The purpose of this study was to determine if there are clinical features that raise suspicion for parathyroid hyperplasia.
MATERIALS & METHODS
We retrospectively reviewed patients with primary hyperparathyroidism who underwent parathyroidectomy from 1991 to 2017, analyzing demographics, calcium and PTH, and localizing studies for patients with hyperplasia and single adenoma.
RESULTS
549 patients underwent parathyroidectomy: 464 (85%) with adenoma, 44 (8%) with double adenoma, 38 (7%) with hyperplasia, and 3 (1%) with cancer. Compared to patients with a single adenoma, patients with hyperplasia were more likely to have negative sestamibi, ultrasound or both exams (92% vs 6%, p < 0.001; 96% vs 4%, p < 0.001; and 91% vs 2%, p < 0.001) and lower gland weights (619 ± 1067 mg vs. 1466 ± 1899 mg, p < 0.001).
CONCLUSION
Parathyroid hyperplasia should be suspected in patients with lower gland weights and negative imaging.
Topics: Adenoma; Adult; Aged; Female; Humans; Hyperparathyroidism, Primary; Hyperplasia; Male; Middle Aged; Parathyroid Glands; Parathyroid Neoplasms; Parathyroidectomy; Retrospective Studies
PubMed: 29174770
DOI: 10.1016/j.amjsurg.2017.10.051 -
Endocrine-related Cancer Jan 2016Five syndromes share predominantly hyperplastic glands with a primary excess of hormones: neonatal severe primary hyperparathyroidism, from homozygous mutated CASR,... (Review)
Review
Five syndromes share predominantly hyperplastic glands with a primary excess of hormones: neonatal severe primary hyperparathyroidism, from homozygous mutated CASR, begins severely in utero; congenital non-autoimmune thyrotoxicosis, from mutated TSHR, varies from severe with fetal onset to mild with adult onset; familial male-limited precocious puberty, from mutated LHR, expresses testosterone oversecretion in young boys; hereditary ovarian hyperstimulation syndrome, from mutated FSHR, expresses symptomatic systemic vascular permeabilities during pregnancy; and familial hyperaldosteronism type IIIA, from mutated KCNJ5, presents in young children with hypertension and hypokalemia. The grouping of these five syndromes highlights predominant hyperplasia as a stable tissue endpoint and as their tissue stage for all of the hormone excess. Comparisons were made among this and two other groups of syndromes, forming a continuum of gland staging: predominant oversecretions express little or no hyperplasia; predominant hyperplasias express little or no neoplasia; and predominant neoplasias express nodules, adenomas, or cancers. Hyperplasias may progress (5 of 5) to neoplastic stages while predominant oversecretions rarely do (1 of 6; frequencies differ P<0.02). Hyperplasias do not show tumor multiplicity (0 of 5) unlike neoplasias that do (13 of 19; P<0.02). Hyperplasias express mutation of a plasma membrane-bound sensor (5 of 5), while neoplasias rarely do (3 of 14; P<0.002). In conclusion, the multiple distinguishing themes within the hyperplasias establish a robust pathophysiology. It has the shared and novel feature of mutant sensors in the plasma membrane, suggesting that these are major contributors to hyperplasia.
Topics: Adenoma; Adult; Child; Endocrine Glands; Female; Hormones, Ectopic; Humans; Hyperplasia; Hyperthyroidism; Male; Parathyroid Glands; Parathyroid Neoplasms; Pregnancy; Puberty, Precocious
PubMed: 26407873
DOI: 10.1530/ERC-15-0171 -
Endokrynologia Polska 2022Parathyroid carcinoma is a rare condition and accounts for < 1% of cases of sporadic primary hyperparathyroidism. It accounts for 0.005% of all cancers. Often the...
INTRODUCTION
Parathyroid carcinoma is a rare condition and accounts for < 1% of cases of sporadic primary hyperparathyroidism. It accounts for 0.005% of all cancers. Often the differentiation between adenoma and carcinoma is challenging and requires multidisciplinary cooperation. Complete surgical resection is the treatment of choice. We present a retrospective analysis of 29 patients who were surgically treated for parathyroid cancer.
MATERIAL AND METHODS
Between the years 1983 and 2018, 71 (7.0%) patients were treated for suspicion of parathyroid cancer among a group of 1019 operated for primary hyperparathyroidism.
RESULTS
We confirmed the diagnosis of parathyroid cancer in 29 (2.8%) patients, 12 men and 17 women, aged 27 to 77 years, mean 55.1 years. That constituted 43.9% of the 71 patients with initial suspicion of cancer diagnosis. All operated patients were under long-term observation.
CONCLUSIONS
A diagnosis of parathyroid carcinoma should always be considered during surgery in patients diagnosed with primary hyperparathyroidism, especially in patients with severe hypercalcaemia, significantly enlarged neck circumference, and concomitant diseases of the renal and skeletal system. Parathyroid carcinoma is rarely definitively diagnosed preoperatively or even intraoperatively, and the final diagnosis can be made exclusively after operation. The optimal treatment is a complete surgical resection at a reference centre - specialized in parathyroid surgery - to improve outcomes and provide the best chance of recovery.
Topics: Adenoma; Adult; Aged; Female; Humans; Hyperparathyroidism; Male; Middle Aged; Parathyroid Neoplasms; Parathyroidectomy; Retrospective Studies
PubMed: 35156702
DOI: 10.5603/EP.a2022.0003 -
Materia Socio-medica 2023The most comon patohistological finding in primary hyperparathyroidism is adenoma of the parathyroid gland, followed by hyperplasia and the rarest is carcinoma. However,...
BACKGROUND
The most comon patohistological finding in primary hyperparathyroidism is adenoma of the parathyroid gland, followed by hyperplasia and the rarest is carcinoma. However, hyperplasia of the parathyroid glands (PTG) is most commonly found in secondary and tertiary hyperparathyroidism.
OBJECTIVE
To determine the relationship between the localization of the parathyroid glands and pathological diagnosis, as well as the prevalence of individual pathological diagnosis after surgery in patients with hyperparathyroidism.
METHODS
Analysis of retrospective-prospective database of 79 patiens who underwent parathyreoidectomy for hyperparathyroidism in the 7-year study period. Diagnostic methods were used to identify enlarged parathyroid glands as well as to determine their localization: ultrasound examination, scintigraphy and operative finding. Standard hematoxylin eosin staining was used for pathohistological diagnosis. A correlation analysis between parathyroid gland localization and pathohistological diagnosis was performed.
RESULTS
The median age of the patients were 51 age (range 20-73) and 67,1% of the patients were female. In the total number of surgically removed parathyroid glands (182), the most common pathohistological diagnosis was hyperplasia. Parathyroid adenoma was found in 21 cases. Other diagnoses (thyroid nodule / tissue, lymph node, thymus, cancer) were found in 11 cases, while a normal finding was found in 12 glands. Pathohistological diagnosis of hyperplasia and adenoma were more common in the lower parathyroid glands. Using the chi-square test, no association was found between pathohistological diagnosis and localization of enlarged parathyroid glands.
CONCLUSION
The most common pathohistological diagnosis in hyperparathyroidism was hyperplasia and was most commonly found in the inferior parathyroid glands. Adenoma as pathohistological diagnosis is also most commonly found in the lower parathyroid glands, but without statistical significance.
PubMed: 37701350
DOI: 10.5455/msm.2023.35.130-134 -
Minerva Endocrinology Jun 2022Hyperparathyroidism is caused by parathyroid adenoma, hyperplasia or carcinoma. Parathyroid adenomas are the most common cause of parathyroid disease (85-88%) while...
BACKGROUND
Hyperparathyroidism is caused by parathyroid adenoma, hyperplasia or carcinoma. Parathyroid adenomas are the most common cause of parathyroid disease (85-88%) while atypical parathyroid adenomas and carcinomas are the least frequently seen parathyroid neoplasms which cause diagnostic difficulty. This series aims to identifiy lesions of parathyroidectomy specimens in our center and draw attention to borderline cases in between parathyroid adenoma and carcinoma.
METHODS
The study included 638 parathyroidectomy materials diagnosed in our center between the years 2005 and 2016 and examined retrospectively, and all were included in the study.
RESULTS
In all the 638 parathyroidectomy cases evaluated, 427 were diagnosed with adenoma, 117 with hyperplasia, 54 with normal parathyroid tissue, 32 with parathyroid neoplasm with uncertain malignant potential, 7 with parathyroid carcinoma and 1 with normal thyroid tissue.
CONCLUSIONS
Parathyroid neoplasm with uncertain malignant potential defines cases with suspicious histopathological features of carcinoma but doesn't meet the criteria for parathyroid carcinoma. In our series, these cases are identified as atypical parathyroid adenoma. We present clinical and morphological features of our parathyroidectomy cases in an 11-year period and aim to raise concern about borderline cases in between adenoma and carcinoma. We think that such tumors, similar to the thyroid neoplasm classification, should be defined as parathyroid neoplasms with uncertain malignant potential and should be followed closely.
Topics: Adenoma; Carcinoma; Humans; Hyperplasia; Parathyroid Neoplasms; Parathyroidectomy; Retrospective Studies
PubMed: 33103869
DOI: 10.23736/S2724-6507.20.03171-5 -
European Journal of Case Reports in... 2020Pheochromocytoma, papillary thyroid carcinoma and hyperparathyroidism have rarely been reported together. Whether this association is coincidental or results from an...
UNLABELLED
Pheochromocytoma, papillary thyroid carcinoma and hyperparathyroidism have rarely been reported together. Whether this association is coincidental or results from an unknown genetic predisposition is difficult to ascertain. We present the case of a patient who was diagnosed with pheochromocytoma, bilateral papillary thyroid carcinoma and parathyroid hyperplasia with primary hyperparathyroidism. A genetic mutation was hypothesized as the connection between these lesions. Previously described mutations were explored.
LEARNING POINTS
Parathyroid hyperplasia, primary hyperparathyroidism and papillary thyroid carcinoma individually are common conditions, but association with each other, although possibly incidental, should trigger genetic testing.Further research is needed to reliably explain the relationship between primary hyperparathyroidism and non-medullary thyroid cancer.
PubMed: 33194854
DOI: 10.12890/2020_001818