-
Cureus Apr 2024Primary hyperparathyroidism (PHPT) is an extremely uncommon cause of cerebral calcification. A male patient, aged 45, was admitted to the neurosurgery clinic with a...
Primary hyperparathyroidism (PHPT) is an extremely uncommon cause of cerebral calcification. A male patient, aged 45, was admitted to the neurosurgery clinic with a closed traumatic brain injury, namely a concussion, resulting in symptoms of headache and loss of balance. A CT scan was conducted, which detected bilateral calcifications on the basal ganglia and the tentorium. The blood tests revealed increased levels of serum calcium, phosphate, and parathyroid hormone (PTH), while vitamin D levels were within the normal range. The patient received symptomatic therapy for the cerebral concussion and was referred for further diagnostic procedures. Based on these exams, it was determined that the patient had a parathyroid adenoma, which was responsible for PHPT characterised by increased levels of calcium, phosphate, and PTH. The patient subsequently underwent a successful parathyroidectomy. Half a year following the surgical procedure, the patient remained free of any indications of neurological conditions, and the levels of PTH and calcium in their body were within the expected range. Whenever trying to identify the cause of cerebral calcification, it is important to explore several possible diagnoses. A possible cause that should be taken into account is PHTP.
PubMed: 38721190
DOI: 10.7759/cureus.57826 -
Endocrinology Apr 2024Breast cancer bone metastases (BMET) are incurable, primarily osteolytic, and occur most commonly in estrogen receptor-α positive (ER+) breast cancer. ER+ human breast...
Breast cancer bone metastases (BMET) are incurable, primarily osteolytic, and occur most commonly in estrogen receptor-α positive (ER+) breast cancer. ER+ human breast cancer BMET modeling in mice has demonstrated an estrogen (E2)-dependent increase in tumor-associated osteolysis and bone-resorbing osteoclasts, independent of estrogenic effects on tumor proliferation or bone turnover, suggesting a possible mechanistic link between tumoral ERα-driven osteolysis and ER+ bone progression. To explore this question, inducible secretion of the osteolytic factor, parathyroid hormone-related protein (PTHrP), was utilized as an in vitro screening bioassay to query the osteolytic potential of estrogen receptor- and signaling pathway-specific ligands in BMET-forming ER+ human breast cancer cells expressing ERα, ERß, and G protein-coupled ER. After identifying genomic ERα signaling, also responsibility for estrogen's proliferative effects, as necessary and sufficient for osteolytic PTHrP secretion, in vivo effects of a genomic-only ER agonist, estetrol (E4), on osteolytic ER+ BMET progression were examined. Surprisingly, while pharmacologic effects of E4 on estrogen-dependent tissues, including bone, were evident, E4 did not support osteolytic BMET progression (vs robust E2 effects), suggesting an important role for nongenomic ER signaling in ER+ metastatic progression at this site. Because bone effects of E4 did not completely recapitulate those of E2, the relative importance of nongenomic ER signaling in tumor vs bone cannot be ascertained here. Nonetheless, these intriguing findings suggest that targeted manipulation of estrogen signaling to mitigate ER+ metastatic progression in bone may require a nuanced approach, considering genomic and nongenomic effects of ER signaling on both sides of the tumor/bone interface.
Topics: Bone Neoplasms; Animals; Signal Transduction; Female; Breast Neoplasms; Humans; Mice; Estrogens; Estrogen Receptor alpha; Cell Line, Tumor; Parathyroid Hormone-Related Protein; Osteolysis; Receptors, Estrogen
PubMed: 38715255
DOI: 10.1210/endocr/bqae038 -
The British Journal of Surgery May 2024
Topics: Humans; Parathyroid Neoplasms; Consensus; Parathyroidectomy; Europe
PubMed: 38713608
DOI: 10.1093/bjs/znae108 -
Diagnostic Cytopathology Jul 2024F-fluorodeoxyglucose (FDG) uptake on positron emission tomography/computed tomography (PET/CT) has become the mainstay for staging and post-therapy surveillance of...
Fine needle aspiration diagnosis of benign oncocytic lesions of the head and neck associated with false positive F-fluorodeoxyglucose uptake on positron emission tomography scan.
INTRODUCTION
F-fluorodeoxyglucose (FDG) uptake on positron emission tomography/computed tomography (PET/CT) has become the mainstay for staging and post-therapy surveillance of cancer as malignant neoplasms generally demonstrate higher FDG uptake that benign entities. However, there are certain benign lesions, most notably oncocytic tumors, that can display very high uptake and fine needle aspiration (FNA) is usually done to confirm malignancy. Therefore, it is important to recognize that benign oncocytic lesions of the head and neck may also present as FDG-avid lesions to avoid a diagnostic pitfall.
METHODS
Electronic search of institutional surgical and cytopathology archives was conducted to identify cases of benign oncocytic lesions involving the head and neck region diagnosed by FNA from January 2012 to April 2022. Chart review was used to assess whether lesions were initially discovered via PET scanning.
RESULTS
One hundred and twenty-five cases of oncocytic lesions were identified; 12 (9%) PET positive lesions were identified in the head and neck region from patients being evaluated for metastasis or for suspicion of malignancy. Cytopathology of all 12 cases demonstrated benign oncocytic lesions; eight (67%) of these cases were consistent with Warthin tumor, one (8.3%) was a benign oncocytic lesion, and one (8.3%) was consistent wit a parathyroid adenoma. Most (58%) of the PET-positive lesions were in parotid region, two from thyroid gland (17%), one from submandibular gland (8%), one from paratracheal area (8%). The PET scan SUVs ranged from 3.3 to 19.5 g mL.
CONCLUSIONS
Oncocytic lesions including Warthin tumors can result in false-positive FDG uptake on PET scans. Clinicians and cytopathologists should be aware of PET-positive benign oncocytic head and neck lesions.
Topics: Humans; Fluorodeoxyglucose F18; Biopsy, Fine-Needle; Middle Aged; Female; Male; Head and Neck Neoplasms; Aged; Adult; False Positive Reactions; Positron Emission Tomography Computed Tomography; Positron-Emission Tomography; Aged, 80 and over; Radiopharmaceuticals; Adenolymphoma
PubMed: 38712593
DOI: 10.1002/dc.25331 -
Phytomedicine : International Journal... Jul 2024Anaplastic thyroid carcinoma (ATC) is recognized as the most aggressive and malignant form of thyroid cancer, underscoring the critical need for effective therapeutic...
BACKGROUND
Anaplastic thyroid carcinoma (ATC) is recognized as the most aggressive and malignant form of thyroid cancer, underscoring the critical need for effective therapeutic strategies to curb its progression and improve patient prognosis. Halofuginone (HF), a derivative of febrifugine, has displayed antitumor properties across various cancer types. However, there is a paucity of published research focused on the potential of HF to enhance the clinical efficacy of treating ATC.
OBJECTIVE
In this study, we thoroughly investigated the antitumor effects and mechanisms of HF in ATC, aiming to discover lead compounds for treating ATC and reveal novel therapeutic targets for ATC tumors.
METHODS
A series of assays, including CCK8, colony formation, tumor xenograft models, and ATC tumor organoid experiments, were conducted to evaluate the anticancer properties of HF both in vitro and in vivo. Techniques such as drug affinity responsive target stability (DARTS), western blot, immunofluorescence, and immunohistochemistry were employed to pinpoint HF target proteins within ATC. Furthermore, we harnessed the GEPIA and GEO databases and performed immunohistochemistry to validate the therapeutic potential of the glutamyl-prolyl-tRNA-synthetase (EPRS)- activating transcription factor 4 (ATF4)- type I collagen (COLI) pathway axis in the context of ATC. The study also incorporated RNA sequencing analysis, confocal imaging, and flow cytometry to delve into the molecular mechanisms of HF in ATC.
RESULTS
HF exhibited a substantial inhibitory impact on cell proliferation in vitro and on tumor growth in vivo. The DARTS results highlighted HF's influence on EPRS within ATC cells, triggering an amino acid starvation response (AASR) by suppressing EPRS expression, consequently leading to a reduction in COLI expression in ATC cells. The introduction of proline mitigated the effect of HF on ATF4 and COLI expression, indicating that the EPRS-ATF4-COLI pathway axis was a focal target of HF in ATC. Analysis of the expression levels of the EPRS, ATF4, and COLI proteins in thyroid tumors, along with an examination of the relationship between COLI expression and thyroid tumor stage, revealed that HF significantly inhibited the growth of ATC tumor organoids, demonstrating the therapeutic potential of targeting the EPRS-ATF4-COLI pathway axis in ATC. RNA sequencing analysis revealed significant differences in the pathways associated with metastasis and apoptosis between control and HF-treated cells. Transwell assays and flow cytometry experiments provided evidence of the capacity of HF to impede cell migration and induce apoptosis in ATC cells. Furthermore, HF hindered cell metastasis by suppressing the epithelial-mesenchymal transition (EMT) pathway, acting through the inhibition of FAK-AKT-NF-κB/Wnt-β-catenin signaling and restraining angiogenesis via the VEGF pathway. HF also promoted apoptosis through the mitochondrial apoptotic pathway.
CONCLUSION
This study provided inaugural evidence suggesting that HF could emerge as a promising therapeutic agent for the treatment of ATC. The EPRS-ATF4-COLI pathway axis stood out as a prospective biomarker and therapeutic target for ATC.
Topics: Thyroid Carcinoma, Anaplastic; Activating Transcription Factor 4; Humans; Animals; Cell Line, Tumor; Thyroid Neoplasms; Piperidines; Quinazolinones; Mice; Mice, Nude; Xenograft Model Antitumor Assays; Signal Transduction; Cell Proliferation; Mice, Inbred BALB C
PubMed: 38704915
DOI: 10.1016/j.phymed.2024.155670 -
American Journal of Otolaryngology 2024For minimally invasive surgery of parathyroid adenomas, exact localization diagnostics are essential. Main imaging modalities used for diagnostics are sonography, SPECT...
PURPOSE
For minimally invasive surgery of parathyroid adenomas, exact localization diagnostics are essential. Main imaging modalities used for diagnostics are sonography, SPECT with/without CT (traditional imaging) and F-choline-PET. The aim of our study was to identify predictors for inconclusive SPECT imaging and subsequently determine in which cases F-choline-PET is needed.
METHODS
Retrospective analysis of 138 patients with histologically confirmed primary hyperparathyroidism (pHPT). After sonography, patients underwent SPECT or SPECT/CT imaging, with subsequent F-choline-PET in cases of disconcordant results. Logistic regression analysis was used to identify clinical and laboratory factors predictive for negative SPECT results.
RESULTS
Sensitivity rates for sonography, SPECT, SPECT/CT, and choline-PET were 47 %, 49 %, 71.7 %, and 97 %, respectively. Logistic regression revealed lower PTH levels (p < 0.001), presence of structural thyroid disease (p = 0.018), and negative sonography (p < 0.001) as predictive of negative/equivocal SPECT outcome. An additional traditional imaging CT scan to a SPECT enhanced detection odds, as did greater adenoma weight. Urolithiasis, osteoporosis, and calcium values as measurement of activity and duration of disease showed no significant association with the detection rate. Furthermore, our study demonstrated that F-choline-PET exhibited remarkable sensitivity in detecting adenomas among patients with negative/equivocal SPECT results.
CONCLUSION
Our study reveals potential predictive factors for a negative/equivocal SPECT outcome in pHPT. Identifying these factors might allow minimizing futile SPECT examinations and perhaps encourage timely utilization of F-choline-PET imaging. Our study reinforces the clinical significance of F-choline-PET, especially in complex cases with disconcordant results by conventional parathyroid imaging methods.
Topics: Humans; Hyperparathyroidism, Primary; Male; Female; Middle Aged; Retrospective Studies; Choline; Aged; Parathyroid Neoplasms; Tomography, Emission-Computed, Single-Photon; Adenoma; Positron-Emission Tomography; Adult; Predictive Value of Tests; Ultrasonography; Sensitivity and Specificity; Fluorine Radioisotopes; Radiopharmaceuticals
PubMed: 38701728
DOI: 10.1016/j.amjoto.2024.104315 -
Medicine May 2024Primary hyperparathyroidism, though relatively prevalent among endocrine disorders, affecting 1% of the general population, often presents diagnostic challenges. Given...
RATIONALE
Primary hyperparathyroidism, though relatively prevalent among endocrine disorders, affecting 1% of the general population, often presents diagnostic challenges. Given its potential to precipitate severe complications including nephrolithiasis and fractures, timely diagnosis, and effective management are crucial.
PATIENT CONCERNS
A 38-year-old woman with hypercalcemia was referred to the Department of Nuclear Medicine for a Tc-99m MIBI scan.
DIAGNOSES
Tc-99m MIBI scan showed focal increased uptake in the left thyroid gland area, initially suggesting a parathyroid adenoma. Further examination using SPECT/CT revealed a nodular lesion within the left thyroid gland showing high Tc-99m MIBI uptake.
INTERVENTIONS
Left thyroid lumpectomy confirmed the lesion as follicular thyroid carcinoma. On the second Tc-99m MIBI scan conducted after total thyroidectomy, a parathyroid adenoma was eventually detected in the right lower area, enabling the subsequent appropriate treatment, a right lower parathyroidectomy.
OUTCOMES
Thirteen days after the parathyroidectomy, serum levels of total calcium and parathyroid hormone returned to normal. Furthermore, bone mineral density evaluated using DEXA remained within the expected range for her age even after 14 months.
LESSONS
When interpreting the Tc-99m MIBI scan, it is essential to keep in mind that various tumors rich in mitochondria, such as thyroid carcinoma, could show a high uptake of Tc-99m MIBI.
Topics: Humans; Female; Adult; Parathyroid Neoplasms; Technetium Tc 99m Sestamibi; Incidental Findings; Adenocarcinoma, Follicular; Diagnosis, Differential; Thyroid Neoplasms; Radiopharmaceuticals; Adenoma; Single Photon Emission Computed Tomography Computed Tomography
PubMed: 38701245
DOI: 10.1097/MD.0000000000038107 -
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 -
Rozhledy V Chirurgii : Mesicnik... 2024Thoracic surgery is increasingly influenced by the development of minimally invasive approaches which have also influenced surgery in the area of the anterior...
Thoracic surgery is increasingly influenced by the development of minimally invasive approaches which have also influenced surgery in the area of the anterior mediastinum. The previously standard approach to the thymus via partial sternotomy was gradually replaced by the videothoracoscopic approach in most cases. In recent years, robotically assisted surgery has been gaining ground worldwide in this area, as well. The aim of our paper is to provide a comprehensive overview of procedures in the field of the thymus, including their indications, and to share our first experience with robot-assisted thymus surgery. At the 3rd Department of Surgery, since the start of the robot-assisted thymus surgery program, 23 thymectomies have been performed using this approach, of which 17 were performed for thymoma, 3 for myasthenia gravis, and 3 for parathyroid adenoma localized in thymus tissue. From our experience and the available data, it follows that the length of hospitalization, the rate of complications and the resulting effect of robot-assisted procedures is comparable to VTS procedures; however, the robot-assisted surgery also allows for mini-invasive treatment even in significantly obese patients and in patients with advanced thymic tumors who would otherwise be indicated for open thymectomy.
Topics: Humans; Robotic Surgical Procedures; Thymectomy; Thymus Neoplasms; Thymoma; Myasthenia Gravis; Parathyroid Neoplasms; Thymus Gland; Male
PubMed: 38697812
DOI: 10.33699/PIS.2024.103.2.40-47 -
Medicina 2024Primary hyperparathyroidism (PHPT) is characterized by elevated levels of calcium and parathyroid hormone (PTH). However, the interpretation of diagnostic tests, such as...
Primary hyperparathyroidism (PHPT) is characterized by elevated levels of calcium and parathyroid hormone (PTH). However, the interpretation of diagnostic tests, such as serum calcium and PTH levels, is complex in pregnant women. The aim of this report is to present a case of PHTP in a pregnant adolescent, with a special emphasis on an uncommon complication, as well as diagnostic and treatment strategies. A 17-year-old pregnant female presented with hyperemesis gravidarum and neurological symptoms, leading to the diagnosis of cerebral venous thrombosis. Further investigations revealed hypercalcemia and persistently elevated PTH levels, consistent with PHPT. After localization studies, the patient underwent an emergency parathyroidectomy with a diagnosis of parathyroid adenoma. During follow-up, intrauterine growth restriction and severe preeclampsia developed, necessitating an emergency cesarean section. Both the mother and neonate had favorable outcomes. PHPT is an infrequent condition in the pregnant population, and its diagnosis can be challenging due to the overlap of symptoms with normal physiological changes during pregnancy. The occurrence of uncommon complications, such as thrombotic phenomena, highlights the need for a comprehensive approach to ensure early detection and management. In most cases, parathyroidectomy is the treatment of choice.
Topics: Humans; Female; Pregnancy; Hyperparathyroidism, Primary; Parathyroid Neoplasms; Adolescent; Parathyroidectomy; Adenoma; Parathyroid Hormone; Pregnancy Complications, Neoplastic; Pregnancy Complications; Hyperemesis Gravidarum; Hypercalcemia; Cesarean Section
PubMed: 38683521
DOI: No ID Found