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Endocrine Apr 2019Primary hyperparathyroidism (PHPT) is a common endocrine disorder and is usually diagnosed in adults. PHPT due to ectopic parathyroid adenoma in adolescents is rare. (Review)
Review
PURPOSE
Primary hyperparathyroidism (PHPT) is a common endocrine disorder and is usually diagnosed in adults. PHPT due to ectopic parathyroid adenoma in adolescents is rare.
METHODS
We describe the case of a 15-year-old boy with PHPT due to ectopic parathyroid adenoma. A review of the literature of PHPT in adolescents was performed, focusing on etiology, clinical presentation, preoperative localization methods, pathology, and treatment.
RESULTS
The patient was successfully treated with surgery and was followed up for 5 years with no signs or symptoms of hyperparathyroidism. By reviewing the literature, only seven cases of PHPT associated with ectopic parathyroid lesions in adolescents have been reported. Parathyroidectomy is the only known curative treatment. Accurate preoperative localization of the target lesion is critical.
CONCLUSIONS
This study should raise awareness of the diagnosis and treatment of PHPT due to ectopic parathyroid adenoma/carcinoma in adolescents.
Topics: Adenoma; Adolescent; Humans; Hyperparathyroidism, Primary; Male; Parathyroid Neoplasms
PubMed: 30805889
DOI: 10.1007/s12020-019-01875-3 -
Frontiers in Endocrinology 2022Primary hyperparathyroidism is a common disorder of the parathyroid glands. Parathyroid adenoma (PA) in pregnancy is a relatively rare disease, whose diagnosis and...
OBJECTIVE
Primary hyperparathyroidism is a common disorder of the parathyroid glands. Parathyroid adenoma (PA) in pregnancy is a relatively rare disease, whose diagnosis and treatment is a challenging task. The aim of the present study is to present a new case of parathyroid adenoma during pregnancy and to give a detailed account of all reported cases of parathyroid adenoma during pregnancy in the literature.
STUDY DESIGN
A bibliographic research was performed, and characteristics of parathyroid adenomas in pregnancy such as age, gestational week at diagnosis, ionized calcium levels, genetic testing result, symptomatology, radiological method of localization, treatment method, gestational week at operation, and maternal/fetal complications were recorded.
RESULTS
A 34-year-old woman at her 25 weeks' gestation was diagnosed with parathyroid adenoma and was referred to our Surgical Department due to contraindication for conservative treatment. A parathyroidectomy was performed, and the maternal and fetal postoperative period was uneventful. Two hundred eleven cases of parathyroid adenoma in pregnancy were recorded in the literature, and statistical analysis was performed. The median gestational week at diagnosis was 21 ± 9.61 weeks. The mean level of ionized calcium was 2.69 mmol/l [SD = 0.75 (2.55-2.84 95% CI)]. Most cases were familiar (72.4%), while surgery was the preferred treatment option (67.3%). The majority of cases were asymptomatic (21.7%), and the main radiological method applied for localization was ultrasound (63.4%).
CONCLUSION
Parathyroid adenoma in pregnancy is a rare condition. The early diagnosis is of great importance as surgical treatment at the second trimester of pregnancy outweighs the maternal and fetal risks.
Topics: Humans; Female; Pregnancy; Adult; Parathyroid Neoplasms; Calcium; Adenoma; Pregnancy Complications, Neoplastic; Parathyroidectomy
PubMed: 36325457
DOI: 10.3389/fendo.2022.975954 -
Revista Medica de Chile Mar 2021Parathyroid carcinoma is a rare malignant disease that presents as a sporadic or familial primary hyperparathyroidism (PHP). The latter is associated with some genetic...
Parathyroid carcinoma is a rare malignant disease that presents as a sporadic or familial primary hyperparathyroidism (PHP). The latter is associated with some genetic syndromes. It occurs with equal frequency in both sexes, unlike PHP caused by parathyroid adenoma that is more common in women. It should be suspected in cases of severe hypercalcemia, with high parathyroid hormone levels and a palpable cervical mass. Given the difficulty in distinguishing between parathyroid carcinoma and adenoma prior to the surgery, the diagnosis is often made after parathyroidectomy. The only curative treatment is complete surgical resection with oncologic block resection of the primary tumor to ensure free margins. Adjuvant therapies with chemotherapy or radiation therapy do not modify overall or disease-free survival. Recurrences are common and re-operation of resectable recurrent disease is recommended. The palliative treatment of symptomatic hypercalcemia is crucial in persistent or recurrent disease after surgery since morbidity and mortality are more associated with hypercalcemia than with tumor burden.
Topics: Female; Humans; Hypercalcemia; Hyperparathyroidism, Primary; Male; Neoplasm Recurrence, Local; Parathyroid Hormone; Parathyroid Neoplasms; Parathyroidectomy
PubMed: 34479319
DOI: 10.4067/s0034-98872021000300399 -
Der Chirurg; Zeitschrift Fur Alle... Jan 2015Despite new technologies and progress in parathyroid gland imaging, missed parathyroid adenomas are still a problem. In reoperations most adenomas were found in eutopic... (Review)
Review
Despite new technologies and progress in parathyroid gland imaging, missed parathyroid adenomas are still a problem. In reoperations most adenomas were found in eutopic positions. Adenoma in atypical positions were mostly situated in the thymus or in the esophageal-tracheal groove. Positive parathyroid imaging can be helpful but does not necessarily result in a better success rate than conventional bilateral exploration by an experienced surgeon, which is > 95 %. The knowledge of anatomy and embryological development of parathyroid glands is most important. Intraoperative determination of parathyroid hormone levels can help localize the site of the adenoma. Thyroid resection should only be performed if preoperative or intraoperative ultrasound indicates a tumor in the thyroid gland. The most important factor for a successful parathyroid operation is an experienced surgeon.
Topics: Adenoma; Choristoma; Delayed Diagnosis; Humans; Hyperparathyroidism, Primary; Intraoperative Complications; Parathyroid Glands; Parathyroid Hormone; Parathyroid Neoplasms; Radionuclide Imaging; Technetium Tc 99m Sestamibi; Ultrasonography
PubMed: 25591414
DOI: 10.1007/s00104-014-2820-0 -
The Journal of Clinical Endocrinology... Oct 2021Atypical parathyroid adenomas (APAs) are neoplasms with uncertain malignant potential but lack unequivocal histological signs of malignancy.
CONTEXT
Atypical parathyroid adenomas (APAs) are neoplasms with uncertain malignant potential but lack unequivocal histological signs of malignancy.
OBJECTIVE
This work aims to retrospectively evaluate the clinical and biochemical profiles of patients with APA, the outcome after parathyroidectomy (PTX), and the presence of CDC73 germline and somatic mutations.
METHODS
This monocentric study was conducted on consecutive patients undergoing PTX for primary hyperparathyroidism (PHPT) between June 2000 and December 2020. Fifty-eight patients with a confirmed histopathological diagnosis of APA, and age- and sex-matched controls with parathyroid adenoma (PA) were also included.
RESULTS
Fifty-four patients had sporadic PHPT and 4 had familial isolated hyperparathyroidism (FIHP). Thirty-four patients (59%) had symptomatic disease. Serum calcium and parathyroid hormone (PTH) levels were significantly higher in symptomatic compared to asymptomatic patients (P = .048 and .008, respectively). FIHP patients were younger than their sporadic counterparts (30 ± 17 years vs 55 ± 13 years). APA patients had significantly higher serum calcium and PTH levels and lower 25-hydroxyvitamin D concentration, bone mineral density, and T score at one-third distal radius compared to those with PA. Four of 56 APA patients displayed a CDC73 germline mutation. No somatic CDC73 mutation was identified in 24 tumor specimens. The mean follow-up after surgery was 60 ± 56.4 months. All but 6 patients (90%), 5 with apparently sporadic PHPT and 1 with FIHP, were cured after surgery.
CONCLUSION
The large majority of patients with APA, despite a moderate/severe phenotype, have a good prognosis. Germline CDC73 mutation-positive patients had a higher rate of persistent/recurrent disease. CDC73 gene alterations do not seem to have a relevant role in the tumorigenesis of sporadic APA.
Topics: Adenoma; Adolescent; Adult; Aged; Aged, 80 and over; Female; Follow-Up Studies; Germ-Line Mutation; Humans; Male; Middle Aged; Parathyroid Neoplasms; Parathyroidectomy; Prognosis; Retrospective Studies; Tumor Suppressor Proteins; Young Adult
PubMed: 34157106
DOI: 10.1210/clinem/dgab452 -
Endocrine-related Cancer Jul 2019Atypical parathyroid adenomas represent a group of intermediate form of parathyroid neoplasms of uncertain malignant potential which show some atypical histological... (Review)
Review
Atypical parathyroid adenomas represent a group of intermediate form of parathyroid neoplasms of uncertain malignant potential which show some atypical histological features that represent a challenge for the differential diagnosis with parathyroid carcinomas. They may occur as sporadic or as a part of hereditary syndromes. The molecular signature of these neoplasms is still unknown and the germline CDC73 mutations appears to be the most common anomaly in this setting suggesting that these cases might represent variants of the hyperparathyroidism-jaw tumor syndrome. The identification of markers predicting the outcome is of great importance to guide an adequate postoperative monitoring and, the same time, relieve of the anxiety of relatively strict monitoring patients not at risk. This review will summarize the current knowledge of the clinical, biochemical, molecular and histological profile of atypical parathyroid adenomas.
Topics: Adenoma; Biomarkers, Tumor; Diagnosis, Differential; Fibroma; Germ-Line Mutation; Humans; Hyperparathyroidism; Jaw Neoplasms; Parathyroid Neoplasms; Prognosis; Tumor Suppressor Proteins
PubMed: 31085770
DOI: 10.1530/ERC-19-0135 -
Clinical and Translational Medicine Jun 2024Sporadic parathyroid adenoma (PA) is the most common cause of hyperparathyroidism, yet the mechanisms involved in its pathogenesis remain incompletely understood.
BACKGROUND
Sporadic parathyroid adenoma (PA) is the most common cause of hyperparathyroidism, yet the mechanisms involved in its pathogenesis remain incompletely understood.
METHODS
Surgically removed PA samples, along with normal parathyroid gland (PG) tissues that were incidentally dissected during total thyroidectomy, were analysed using single-cell RNA-sequencing with the 10× Genomics Chromium Droplet platform and Cell Ranger software. Gene set variation analysis was conducted to characterise hallmark pathway gene signatures, and single-cell regulatory network inference and clustering were utilised to analyse transcription factor regulons. Immunohistochemistry and immunofluorescence were performed to validate cellular components of PA tissues. siRNA knockdown and gene overexpression, alongside quantitative polymerase chain reaction, Western blotting and cell proliferation assays, were conducted for functional investigations.
RESULTS
There was a pervasive increase in gene transcription in PA cells (PACs) compared with PG cells. This is associated with high expression of histone-lysine N-methyltransferase 2A (KMT2A). High KMT2A levels potentially contribute to promoting PAC proliferation through upregulation of the proto-oncogene CCND2, which is mediated by the transcription factors signal transducer and activator of transcription 3 (STAT3) and GATA binding protein 3 (GATA3). PA tissues are heavily infiltrated with myeloid cells, while fibroblasts, endothelial cells and macrophages in PA tissues are commonly enriched with proinflammatory gene signatures relative to their counterparts in PG tissues.
CONCLUSIONS
We revealed the previously underappreciated involvement of the KMT2A‒STAT3/GATA3‒CCND2 axis and chronic inflammation in the pathogenesis of PA. These findings underscore the therapeutic promise of KMT2A inhibition and anti-inflammatory strategies, highlighting the need for future investigations to translate these molecular insights into practical applications.
HIGHLIGHTS
Single-cell RNA-sequencing reveals a transcriptome catalogue comparing sporadic parathyroid adenomas (PAs) with normal parathyroid glands. PA cells show a pervasive increase in gene expression linked to KMT2A upregulation. KMT2A-mediated STAT3 and GATA3 upregulation is key to promoting PA cell proliferation via cyclin D2. PAs exhibit a proinflammatory microenvironment, suggesting a potential role of chronic inflammation in PA pathogenesis.
Topics: Humans; Parathyroid Neoplasms; Adenoma; Inflammation; Histone-Lysine N-Methyltransferase; Myeloid-Lymphoid Leukemia Protein; Proto-Oncogene Mas; Cell Proliferation
PubMed: 38888967
DOI: 10.1002/ctm2.1734 -
European Journal of Radiology Sep 2016This study prospectively determines the shear wave elastography characteristics of parathyroid adenomas using virtual touch imaging quantification, a non-invasive...
OBJECTIVES
This study prospectively determines the shear wave elastography characteristics of parathyroid adenomas using virtual touch imaging quantification, a non-invasive ultrasound based shear wave elastography method.
METHODS
This prospective study examined 57 consecutive patients with biochemically proven primary hyperparathyroidism and solitary parathyroid adenoma identified by ultrasound and confirmed by at least one of the following: surgical resection, positive Technetium-99m Sestamibi Scintigraphy (MIBI) scan, or fine needle aspiration biopsy with positive PTH washout (performed only in MIBI negative patients). Vascularity and shear wave elastography were performed for all patients. Parathyroid adenoma stiffness was measured as shear wave velocity in meters per second.
RESULTS
The median (range) pre-surgical value for PTH and calcium were 58pg/mL (19, 427) and 10.8mg/dL (9.5, 12.1), respectively. 37 patients had positive MIBI scan. 20 patients had negative MIBI scan but diagnosis was confirmed with positive PTH washout. 42 patients underwent parathyroidectomy, and an adenoma was confirmed in all. The median (range) shear wave velocity for all parathyroid adenomas enrolled in this study was 2.02m/s (1.53, 2.50). The median (range) shear wave velocity for thyroid tissue was 2.77m/s (1.89, 3.70). The shear wave velocity of the adenomas was independent of adenoma size, serum parathyroid hormone concentration, or plasma parathyroid hormone concentration.
CONCLUSIONS
Tissue elasticity of parathyroid adenoma is significantly lower than thyroid tissue. B-mode features and distinct vascularity pattern are helpful tools in diagnosing parathyroid adenoma with ultrasound. Shear wave elastography may provide valuable information in diagnosing parathyroid adenoma.
Topics: Adult; Aged; Aged, 80 and over; Elasticity Imaging Techniques; Female; Humans; Male; Middle Aged; Parathyroid Glands; Parathyroid Neoplasms; Prospective Studies; Reproducibility of Results; Young Adult
PubMed: 27501893
DOI: 10.1016/j.ejrad.2016.06.009 -
Endocrinology and Metabolism (Seoul,... Apr 2021We investigated the clinical characteristics of parathyroid adenomas according to radioactivity on 99mTc-methoxyisobutylisonitrile (99mTc-MIBI) single-photon emission...
BACKGROUND
We investigated the clinical characteristics of parathyroid adenomas according to radioactivity on 99mTc-methoxyisobutylisonitrile (99mTc-MIBI) single-photon emission computed tomography/computed tomography (SPECT/CT) in primary hyperparathyroidism (PHPT) patients.
METHODS
The study included 217 patients diagnosed with PHPT from 2000 to 2019 at Seoul National University Hospital who underwent 99mTc-MIBI SPECT/CT scans. On SPECT/CT, the radioactivity of parathyroid adenomas was measured as the ratio of the mean radioactivity count of the parathyroid adenoma to that of the contralateral thyroid.
RESULTS
Tumors were localized by MIBI scans in 190 patients (MIBI [+] group) and by ultrasound or parathyroid four-dimensional CT in 27 patients (MIBI [-] group). The mean age was 55 years, and mean body mass index was 23.4 kg/m2. Patients in the MIBI (+) group had higher parathyroid hormone (iPTH) and lower 25-hydroxy vitamin D levels than those in the MIBI (-) group (168.0 pg/mL [interquartile range, IQR, 111.0 to 250.7] vs. 134.7 pg/mL [IQR, 98.2 to 191.2], P=0.049; 15.4 ng/mL [IQR, 11.1 to 20.8] vs. 21.2 ng/mL [IQR, 13.9 to 24.8], P=0.012, respectively). Patients in the MIBI (+) group had larger tumor volumes, but lower iPTH/volume ratios than those in the MIBI (-) group (1,216.66 [IQR, 513.40 to 2,663.02], 499.82 mm3 [IQR, 167.77 to 1,229.80], P=0.002; 0.18 [IQR, 0.08 to 0.46], 0.40 pg/mL/mm3 [IQR, 0.16 to 1.29], P=0.016, respectively). Adenoma radioactivity was positively correlated with calcium, iPTH, and volume (r=0.180, P=0.020; r=0.208, P=0.006; r=0.288, P<0.001, respectively), but not with iPTH/volume.
CONCLUSION
Parathyroid adenomas with positive MIBI scans had larger volumes and higher iPTH than adenomas with negative scans, but lower iPTH per unit volume.
Topics: Humans; Middle Aged; Parathyroid Glands; Parathyroid Hormone; Parathyroid Neoplasms; Radioactivity; Technetium Tc 99m Sestamibi
PubMed: 33820395
DOI: 10.3803/EnM.2020.823 -
The Journal of Clinical Endocrinology... Apr 2022Multiglandular and familial parathyroid disease constitute important fractions of primary hyperparathyroidism (PHPT). Germline missense variants of GCM2, a regulator of...
CONTEXT
Multiglandular and familial parathyroid disease constitute important fractions of primary hyperparathyroidism (PHPT). Germline missense variants of GCM2, a regulator of parathyroid development, were observed in familial isolated hyperparathyroidism and sporadic PHPT. However, as these previously reported GCM2 variants occur at relatively high frequencies in the population, understanding their potential clinical utility will require both additional penetrance data and functional evidence relevant to tumorigenicity.
OBJECTIVE
Determine the frequency of GCM2 variants of interest among patients with sporadic multigland or familial parathyroid disease and assess their penetrance.
DESIGN AND PATIENTS
DNA-encoding PHPT-associated GCM2 germline variants were polymerase chain reaction-amplified and sequenced from 107 patients with either sporadic multigland or suspected/confirmed familial parathyroid tumors.
RESULTS
GCM2 variants were observed in 9 of 107 cases (8.4%): Y282D in 4 patients (6.3%) with sporadic multigland disease; Y394S in 2 patients (11.1%) with familial PHPT and 3 (4.8%) with sporadic multigland disease. Compared with the general population, Y282D was enriched 5.9-fold in multigland disease, but its penetrance was very low (0.02%). Y394S was enriched 79-fold in sporadic multigland disease and 93-fold in familial PHPT, but its penetrance was low (1.33% and 1.04%, respectively).
CONCLUSIONS
Observed in vitro-activating GCM2 variant alleles are significantly overrepresented in PHPT patients with multiglandular or familial disease compared to the general population, yet penetrance values are very low; that is, most individuals with these variants in the population have a very low risk of developing PHPT. The potential clinical utility of detecting these GCM2 variants requires further investigation, including assessing their possible role as pathogenic/low-penetrance alleles.
Topics: Germ-Line Mutation; Humans; Hyperparathyroidism, Primary; Nuclear Proteins; Parathyroid Neoplasms; Transcription Factors
PubMed: 34967908
DOI: 10.1210/clinem/dgab929