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Journal of Medical Case Reports Sep 2023There is some evidence supporting the idea that double parathyroid adenomas represent a different entity from multiglandular hyperplasia; however, the distinction among...
BACKGROUND
There is some evidence supporting the idea that double parathyroid adenomas represent a different entity from multiglandular hyperplasia; however, the distinction among them is not straightforward.
CASE PRESENTATION
We described a case of primary hyperparathyroidism (PHPT) with pronounced clinical manifestations, caused by a bilateral giant parathyroid adenoma. A 34-year-old Hispanic/Latino male was diagnosed with PHPT caused by two giant parathyroid adenomas. The preoperative tests were neck ultrasound and computed tomography scan (CT-scan), showing two masses in the territory of parathyroid glands, bilaterally distributed (right was 31 × 18 × 19 mm and the left was 38 × 15 × 14 mm); sestamibi scan was not available. Parathyroid hormone (PTH) was highly elevated. Multiple complications of PHPT were present, such as bone lytic lesions, renal and pancreatic calcifications, and cardiovascular disease, the latter of which is an overlooked complication of PHPT. Multiple endocrine neoplasia 1 and 2 (MEN 1/2) were ruled out by the absence of clinical, biochemical, and radiological findings in other endocrine glands. The patient underwent subtotal parathyroidectomy with an intraoperative histopathological study; both intraoperative and definitive histopathology results were consistent with parathyroid adenomas; afterward, adequate suppression of PTH was assured, and later on, the patient presented hungry bone syndrome (HBS).
CONCLUSIONS
The diagnosis of double parathyroid adenomas is difficult. Regarding the similarities between multiglandular hyperplasia and parathyroid adenomas, this case report contributes to the further distinction between these two clinical entities. This case report also represents, in particular, the challenge of difficult diagnosis in places with limited resources, such as developing countries.
Topics: Humans; Adult; Parathyroid Neoplasms; Hyperplasia; Hypocalcemia; Bone Diseases; Parathyroid Hormone
PubMed: 37653552
DOI: 10.1186/s13256-023-04102-w -
Frontiers in Endocrinology 2023Parathyroid carcinoma (PC) affects 0.1-0.3% of the general population and represents the rarest malignant neoplasms among endocrinological diseases, comprising less than... (Observational Study)
Observational Study
BACKGROUND
Parathyroid carcinoma (PC) affects 0.1-0.3% of the general population and represents the rarest malignant neoplasms among endocrinological diseases, comprising less than 1%. The best therapeutic treatment and management methods are still debated in the literature. The aim of this study is to evaluate the management and surgical treatment of parathyroid carcinoma after 6 years of enrolment with the Endocrine Surgery Unit of the University Hospital of Bari.
MATERIALS AND METHODS
A retrospective observational study was carried out using a prospectively maintained database of patients affected by primary hyperparathyroidism between January 2017 and September 2022. Consecutive patients over 18 years old with a final histopathological finding of PC were included in the study. Patients with secondary or tertiary hyperparathyroidism, parathyroid hyperplasia, and parathyroid adenoma were excluded. All patients underwent follow-up every 6 months for the first 2 years, and annually thereafter.
RESULTS
In this study, 9 out of 40 patients affected by hyperparathyroidism were included; 6 (66.6%) were female and 3 (33.3%) were male patients, with a median age of 59 years (IQR 46-62). None had a family history of PC. No mortality was recorded while the incidence of recurrence was 22.2%, with a disease-free survival of 8 and 10 months. Parathyroidectomy was performed in five patients, while four patients underwent parathyroidectomy with concurrent thyroidectomy for thyroid goitre. No intraoperative complications were recorded. Open parathyroidectomy was performed with a mini-cervicotomy in seven patients, while two patients underwent robotic surgery. All patients were discharged on the second postoperative day.
CONCLUSION
PC represents a great challenge in terms of preoperative diagnosis, management and treatment. A surgical approach represents the first best option for PC in referral endocrine surgery units. The early identification of risky patients should be the dominant goal to plan an appropriate therapy and to perform adequate en bloc surgery.
Topics: Humans; Male; Female; Middle Aged; Adolescent; Parathyroid Neoplasms; Follow-Up Studies; Hyperparathyroidism, Primary; Parathyroidectomy; Thyroidectomy
PubMed: 38027123
DOI: 10.3389/fendo.2023.1278178 -
Medicine Jul 2023Hyperparathyroidism is caused by parathyroid tumors combined with gastroenteropancreatic tumors and pituitary tumors, which is common in patients with multiple endocrine... (Review)
Review
RATIONALE
Hyperparathyroidism is caused by parathyroid tumors combined with gastroenteropancreatic tumors and pituitary tumors, which is common in patients with multiple endocrine neoplasia 1 syndrome (MEN-1). As its main pathogenic factor involves genetic mutations, it can cause a variety of different clinical symptoms. However, cases with negative genetic testing results and multiple nonfunctional malignant neuroendocrine tumors (NETs) with metastasis are relatively rare.
PATIENT CONCERNS
A 33-year-old man was admitted to the hospital for hyperparathyroidism. Imaging examination revealed multiple nodules in the parathyroid gland, pancreas, thymus, and adrenal gland, and multiple metastases to the lung, liver, thoracolumbar, as well as mediastinal lymph nodes.
DIAGNOSES
After multidisciplinary consultation, this patient was diagnosed with MEN-1 syndrome with various original tumors and multiple systemic metastases.
INTERVENTIONS
The patient underwent parathyroid tumor resection and metastasis biopsy.
OUTCOMES
The patient received denosumab and sorafenib treatment.
LESSONS
As an autosomal dominant hereditary disease, MEN-1 patients present with parathyroid hyperplasia, pancreatic and intestinal tumors, pituitary tumors, and so on, which are caused by genetic mutations. These patients would have hyperparathyroidism, hypoglycemia, gastric ulcer, and gastrointestinal diseases. However, some patients with MEN-1 syndrome cannot be diagnosed by genetic testing and simultaneously present with multiple nonfunctional NETs with systemic metastasis. This increases the difficulty of diagnosis and the subsequent treatment.
Topics: Male; Humans; Adult; Multiple Endocrine Neoplasia Type 1; Neuroendocrine Tumors; Pituitary Neoplasms; Multiple Endocrine Neoplasia; Hyperparathyroidism; Parathyroid Neoplasms; Pancreatic Neoplasms
PubMed: 37478229
DOI: 10.1097/MD.0000000000034350 -
JCEM Case Reports Jan 2024Parathyroid adenoma (PA) and parathyroid hyperplasia (PH) are common causes of primary hyperparathyroidism (PHPT), for which the only definitive treatment is surgery....
Parathyroid adenoma (PA) and parathyroid hyperplasia (PH) are common causes of primary hyperparathyroidism (PHPT), for which the only definitive treatment is surgery. Abnormalities in the parathyroid glands can be identified with various imaging modalities including ultrasound (US), sestamibi scan (MIBI), 4-dimensional computed tomography (4D-CT), and positron emission tomography/computed tomography (PET/CT). While it is not uncommon for parathyroid pathology to be undetected on imaging, this is more typical of low-volume hyperplasia and smaller-sized adenomas. We present the case of a 65-year-old man with PHPT who initially had a solitary parathyroid mass detected by US, but who was ultimately discovered to have massive PH with hyperplastic glands not visualized on US or MIBI. This atypical presentation may help guide providers in decisions on ordering and interpreting various imaging modalities for patients with PHPT. In this case, 4D-CT was the only modality in which large hyperplastic glands were identified, suggesting superior sensitivity. This case also highlights the importance of intraoperative parathyroid hormone testing to aid in diagnostic prediction.
PubMed: 38188905
DOI: 10.1210/jcemcr/luad173 -
The Lancet Regional Health. Europe Dec 2023Neck ultrasound (US) is a widely used and accessible operator-dependent technique that helps characterize thyroid nodules and pathologic parathyroid glands (PPGs)....
BACKGROUND
Neck ultrasound (US) is a widely used and accessible operator-dependent technique that helps characterize thyroid nodules and pathologic parathyroid glands (PPGs). However, thyroid nodules may sometimes be confused with PPGs. PARATH-US study aims at identifying US characteristics to differentiate PPGs from thyroid nodules, as there is no study, at present, which directly compares the US features of these two common neoplasms.
METHODS
PARATH-US is a single-center study that was conducted at a tertiary referral center, including consecutive lesions from patients undergoing neck US examination from 2016 to 2022.
FINDINGS
176 PPGs (158 patients: serum calcium levels 2.91 [IQR 2.74-3.05] mmol/L, PTH levels 173 [112-296] ng/L) were compared to 232 size- and volume-matched thyroid nodules (204 age- and sex-matched patients). The morphologic patterns, echoic content and vascular status were all different between PPGs and thyroid neoplasms (p < 0.01 for all comparisons). The combined parameters maximally discriminated PPGs from thyroid nodules (OR, 7.6; 95% CI: 3.4, 17.1, p < 0.0001). When applying risk stratification systems developed for thyroid malignancies, 58-63% of PPGs were classified as high-risk lesions. Parathyroid adenomas had larger sizes and volumes than hyperplasias (p = 0.013 and p = 0.029). Serum calcium and PTH levels were significantly correlated with PPG size and volume (p < 0.0001 for all comparisons).
INTERPRETATION
We demonstrate the presence of distinct US characteristics in PPGs, which help differentiate them from thyroid nodules. When mistaken for thyroid nodules, PPGs bear high-risk US features. When dealing with high-risk cervical lesions detected on US, a PPG should be suspected, and an assessment of calcium levels recommended to avoid unnecessary invasive procedures.
FUNDING
CYTO-TRAIN, C2022DOSRH053, funded by the French Regional Health Agency.
PubMed: 37915399
DOI: 10.1016/j.lanepe.2023.100751 -
Ceskoslovenska Patologie 2024The diagnosis of pathological conditions of the parathyroid glands is the answer to clinically more frequently detected hypercalcemic conditions, including MEN... (Review)
Review
The diagnosis of pathological conditions of the parathyroid glands is the answer to clinically more frequently detected hypercalcemic conditions, including MEN syndromes. In routine biopsy practice, enlarged bodies are also a differential diagnosis for the diagnosis of thyroid nodules. In the chapter of parathyroid tumors, the 5th edition of the WHO classification brings changes influenced similarly to other endocrine organs by the increase in genetic information. At the terminological level, the concept of hyperplasia has been narrowed down to secondary hyperplasia, most of the previously primary hyperplasias are referred to as multiglandular parathyroid disease due to evidence of multiglandular clonal proliferations. The term atypical parathyroid tumor replacing atypical adenoma is newly introduced - the uncertain biological behaviour is emphasized. The basic examination includes parafibromin immunohis- tochemistry, the deficiency of parafibromin being an indicator of an inactivating CDC73 mutation and an increased risk of familial forms, or MEN. Methodologically, refinements are introduced in the quantification of mitotic activity per 10 mm2. Oncocytic subtypes have an arbitrarily declared threshold of more than 75% oncocytes. The definition of lipoadenoma (multiplication of both components, more than 50% of adipose tissue in the tumor) is similarly specified. The diagnosis of cancer remains histopathological with unequivocal evidence of invasion, or microscopically verified metastasis.
Topics: Humans; Parathyroid Neoplasms; World Health Organization; Adenoma
PubMed: 38697830
DOI: No ID Found -
Virchows Archiv : An International... May 2024Primary hyperparathyroidism with parathyroid tumors is a typical manifestation of Multiple Endocrine Neoplasia Type 1 (MEN1) and is historically termed "primary...
Primary hyperparathyroidism with parathyroid tumors is a typical manifestation of Multiple Endocrine Neoplasia Type 1 (MEN1) and is historically termed "primary hyperplasia". Whether these tumors represent a multi-glandular clonal disease or hyperplasia has not been robustly proven so far. Loss of Menin protein expression is associated with inactivation of both alleles and a good surrogate for a MEN1 gene mutation. The cyclin-dependent kinase inhibitor 1B (CDKN1B) gene is mutated in MEN4 and encodes for protein p27 whose expression is poorly studied in the syndromic MEN1 setting.Here, we analyzed histomorphology and protein expression of Menin and p27 in parathyroid adenomas of 25 patients of two independent, well-characterized MEN1 cohorts. The pattern of loss of heterozygosity (LOH) was assessed by fluorescence in situ hybridization (FISH) in one MEN1-associated parathyroid adenoma. Further, next-generation sequencing (NGS) was performed on eleven nodules of four MEN1 patients.Morphologically, the majority of MEN1 adenomas consisted of multiple distinct nodules, in which Menin expression was mostly lost and p27 protein expression reduced. FISH analysis revealed that most nodules exhibited MEN1 loss, with or without the loss of centromere 11. NGS demonstrated both subclonal evolution and the existence of clonally unrelated tumors.Syndromic MEN1 parathyroid adenomas therefore consist of multiple clones with subclones, which supports the current concept of the novel WHO classification of parathyroid tumors (2022). p27 expression was lost in a large fraction of MEN1 parathyroids and must therefore be used with caution in suggesting MEN4.
Topics: Humans; Parathyroid Neoplasms; Multiple Endocrine Neoplasia Type 1; Male; Proto-Oncogene Proteins; Cyclin-Dependent Kinase Inhibitor p27; Middle Aged; Female; Adult; Adenoma; Aged; Loss of Heterozygosity; Hyperparathyroidism, Primary; Biomarkers, Tumor; Young Adult; High-Throughput Nucleotide Sequencing; In Situ Hybridization, Fluorescence
PubMed: 38244045
DOI: 10.1007/s00428-023-03730-3 -
Discovery Medicine May 2024The number of chronic kidney disease (CKD) patients requiring renal replacement therapy is increasing, often exhibiting oral manifestations including periodontal... (Review)
Review
The number of chronic kidney disease (CKD) patients requiring renal replacement therapy is increasing, often exhibiting oral manifestations including periodontal disease, gingival hyperplasia, altered saliva composition, and uremic stomatitis. Uremic stomatitis, xerostomia, and candidiasis are very frequent, particularly among patients undergoing dialysis or kidney transplant recipients. CKD patients also experience profound alterations in bone metabolism inherent in the homeostasis of calcium, phosphorus, vitamin D, parathyroid hormone, and fibroblast growth factor (FGF). These alterations lead to demineralization of the jaw bones, reduced bone trabeculae, reduced cortical bone thickness, fibrocystic bone lesions, bone fractures, and delayed wound healing post-tooth extraction. Consequently, oral health management of elderly hemodialysis patients poses serious clinical problems. This review focused on the oral health and rehabilitation of patients with CKD or on dialysis.
Topics: Humans; Oral Health; Renal Insufficiency, Chronic; Dental Implants; Oral Surgical Procedures; Renal Dialysis
PubMed: 38798248
DOI: 10.24976/Discov.Med.202436184.82 -
JCI Insight Jan 2024The resting zone of the postnatal growth plate is organized by slow-cycling chondrocytes expressing parathyroid hormone-related protein (PTHrP), which include a subgroup...
The resting zone of the postnatal growth plate is organized by slow-cycling chondrocytes expressing parathyroid hormone-related protein (PTHrP), which include a subgroup of skeletal stem cells that contribute to the formation of columnar chondrocytes. The PTHrP-Indian hedgehog feedback regulation is essential for sustaining growth plate activities; however, molecular mechanisms regulating cell fates of PTHrP+ resting chondrocytes and their eventual transformation into osteoblasts remain largely undefined. Here, in a mouse model, we specifically activated Hedgehog signaling in PTHrP+ resting chondrocytes and traced the fate of their descendants using a tamoxifen-inducible Pthrp-creER line with patched-1-floxed and tdTomato reporter alleles. Hedgehog-activated PTHrP+ chondrocytes formed large, concentric, clonally expanded cell populations within the resting zone ("patched roses") and generated significantly wider columns of chondrocytes, resulting in hyperplasia of the growth plate. Interestingly, Hedgehog-activated PTHrP+ cell descendants migrated away from the growth plate and transformed into trabecular osteoblasts in the diaphyseal marrow space in the long term. Therefore, Hedgehog activation drives resting zone chondrocytes into transit-amplifying states as proliferating chondrocytes and eventually converts these cells into osteoblasts, unraveling a potentially novel Hedgehog-mediated mechanism that facilitates osteogenic cell fates of PTHrP+ skeletal stem cells.
Topics: Mice; Animals; Chondrocytes; Parathyroid Hormone-Related Protein; Growth Plate; Receptor, Parathyroid Hormone, Type 1; Hedgehog Proteins; Red Fluorescent Protein
PubMed: 38051593
DOI: 10.1172/jci.insight.165619 -
BMC Nephrology Oct 2023Parathyroid carcinoma and parathyromatosis are very rare diseases in patients on hemodialysis. Its pathogenesis, clinical features, preoperative diagnosis, and surgery...
BACKGROUND
Parathyroid carcinoma and parathyromatosis are very rare diseases in patients on hemodialysis. Its pathogenesis, clinical features, preoperative diagnosis, and surgery are challenging. We describe a rare case of recurrent hyperparathyroidism due to synchronous parathyroid carcinoma and parathyromatosis.
CASE PRESENTATION
A 46-year-old Chinese woman was diagnosed with end-stage renal disease and received regular hemodialysis. Four years later, she experienced discomfort due to itching and was diagnosed with drug-resistant secondary hyperparathyroidism. Parathyroidectomy was performed, and her parathyroid hormone (PTH) levels were reduced. The pathology also revealed that the four nodules were parathyroid nodular hyperplasia without evidence of malignancy. Five years after surgery, the right subcutaneous nodule and left inferior nodule were detected by multiple imaging modalities, and the nodules were accompanied by recurrence itching and elevation of PHT. A complete resection of two nodules was performed, and the patient was diagnosed with parathyroid carcinoma and parathyromatosis. At 8 months postsurgery, her PHT and serum calcium levels were stable, and there were no signs of recurrence.
CONCLUSIONS
This is a rare case of synchronous parathyroid carcinoma and parathyromatosis in a patient with secondary hyperparathyroidism after parathyroidectomy. We suggest meticulous handling of parathyroid hyperplasia to avoid rupture and spillage during surgery, and precise pro-operation location by multiple imaging modalities is crucial for successful parathyroidectomy.
Topics: Humans; Female; Middle Aged; Parathyroid Neoplasms; Hyperplasia; Parathyroid Glands; Hyperparathyroidism, Primary; Hyperparathyroidism, Secondary; Parathyroidectomy; Renal Dialysis; Pruritus; Recurrence; Parathyroid Hormone
PubMed: 37794407
DOI: 10.1186/s12882-023-03328-6