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International Journal of Molecular... Jun 2024Anaplastic thyroid cancer (ATC) is one of the deadliest human cancers and represents <2% of thyroid carcinomas. A therapeutic target for ATC is represented by anaplastic...
Anaplastic thyroid cancer (ATC) is one of the deadliest human cancers and represents <2% of thyroid carcinomas. A therapeutic target for ATC is represented by anaplastic lymphoma kinase (ALK) rearrangements, involved in tumor growth. Crizotinib is an oral small-molecule tyrosine kinase inhibitor of the ALK, MET, and ROS1 kinases, approved in ALK-positive non-small cell lung cancer. Until now, the effect of crizotinib in "primary human ATC cells" (pATCs) with transforming striatin (STRN)-ALK fusion has not been reported in the literature. In this study, we aimed to obtain pATCs with STRN-ALK in vitro and evaluate the in vitro antineoplastic action of crizotinib. Thyroid surgical samples were obtained from 12 ATC patients and 6 controls (who had undergone parathyroidectomy). A total of 10/12 pATC cultures were obtained, 2 of which with transforming STRN-ALK fusion (17%). Crizotinib inhibited proliferation, migration, and invasion and increased apoptosis in 3/10 pATC cultures (2 of which with/1 without STRN-ALK), particularly in those with STRN-ALK. Moreover, crizotinib significantly inhibited the proliferation of AF cells (a continuous cell line obtained from primary ATC cells). In conclusion, the antineoplastic activity of crizotinib has been shown in human pATCs (with STRN-ALK) in preclinical studies in vitro, opening the way to future clinical evaluation in these patients.
Topics: Humans; Crizotinib; Thyroid Carcinoma, Anaplastic; Anaplastic Lymphoma Kinase; Cell Proliferation; Protein Kinase Inhibitors; Apoptosis; Thyroid Neoplasms; Male; Female; Antineoplastic Agents; Middle Aged; Cell Movement; Aged; Oncogene Proteins, Fusion; Tumor Cells, Cultured; Cell Line, Tumor; Calmodulin-Binding Proteins; Membrane Proteins; Nerve Tissue Proteins
PubMed: 38928438
DOI: 10.3390/ijms25126734 -
International Journal of Molecular... Jun 2024We aimed to provide an in-depth analysis with respect to three turning points in pancreas involvement in primary hyperparathyroidism (PHP): hypercalcemia-induced... (Review)
Review
Turning Points in Cross-Disciplinary Perspective of Primary Hyperparathyroidism and Pancreas Involvements: Hypercalcemia-Induced Pancreatitis, Gene-Related Tumors, and Insulin Resistance.
We aimed to provide an in-depth analysis with respect to three turning points in pancreas involvement in primary hyperparathyroidism (PHP): hypercalcemia-induced pancreatitis (HCa-P), MEN1 (multiple endocrine neoplasia)-related neuroendocrine tumors (NETs), and insulin resistance (IR). This was a comprehensive review conducted via a PubMed search between January 2020 and January 2024. HCa-P ( = 9 studies, N = 1375) involved as a starting point parathyroid NETs ( = 7) or pancreatitis ( = 2, N = 167). Case report-focused analysis (N = 27) showed five cases of pregnancy PHP-HCa-P and three reports of parathyroid carcinoma (female/male ratio of 2/1, ages of 34 in women, men of 56). MEN1-NET studies ( = 7) included MEN1-related insulinomas ( = 2) or MEN1-associated PHP ( = 2) or analyses of genetic profile ( = 3), for a total of 877 MEN1 subjects. In MEN1 insulinomas (N = 77), the rate of associated PHP was 78%. Recurrence after parathyroidectomy (N = 585 with PHP) was higher after less-than-subtotal versus subtotal parathyroidectomy (68% versus 45%, < 0.001); re-do surgery was 26% depending on surgery for pancreatic NETs (found in 82% of PHP patients). pathogenic variants in exon 10 represented an independent risk factor for PHP recurrence. A single pediatric study in MEN1 (N = 80) revealed the following: a PHP rate of 80% and pancreatic NET rate of 35% and 35 underlying germline pathogenic variants (and 3/35 of them were newly detected). The co-occurrence of genetic anomalies included the following: gene variant, glucokinase regulatory protein gene pathogenic variant (c.151C>T, p.Arg51*), and CAH-X syndrome. IR/metabolic feature-focused analysis identified ( = 10, N = 1010) a heterogeneous spectrum: approximately one-third of adults might have had prediabetes, almost half displayed some level of IR as reflected by HOMA-IR > 2.6, and serum calcium was positively correlated with HOMA-IR. Vitamin D deficiency was associated with a higher rate of metabolic syndrome ( = 1). Normocalcemic and mildly symptomatic hyperparathyroidism ( = 6, N = 193) was associated with a higher fasting glucose and some improvement after parathyroidectomy. This multilayer pancreas/parathyroid analysis highlighted a complex panel of connections from pathogenic factors, including biochemical, molecular, genetic, and metabolic factors, to a clinical multidisciplinary panel.
Topics: Humans; Hyperparathyroidism, Primary; Insulin Resistance; Hypercalcemia; Pancreatitis; Female; Male; Proto-Oncogene Proteins; Pancreatic Neoplasms; Multiple Endocrine Neoplasia Type 1; Parathyroid Neoplasms; Adult; Parathyroidectomy; Neuroendocrine Tumors; Pancreas
PubMed: 38928056
DOI: 10.3390/ijms25126349 -
Cureus May 2024Introduction Primary hyperparathyroidism (PHPT) has undergone a considerable change from being symptomatic to asymptomatic. This is the first large study from North...
Introduction Primary hyperparathyroidism (PHPT) has undergone a considerable change from being symptomatic to asymptomatic. This is the first large study from North India to study the clinical and biochemical features and surgical outcomes in the present era. Study design This is a cross-sectional study that was conducted in the Department of Endocrinology (SKIMS) from February 2021 to December 2022, in which 103 patients diagnosed with PHPT were included. Evaluation included measurement of total calcium, phosphorus, alkaline phosphate, intact parathyroid hormone, 25-hydroxy vitamin, 24-hour urinary calcium, radiological survey of hands and skull, Dual Energy X-ray absorptiometry, and ultrasonography (USG) of the abdomen. USG neck and technetium-99m sestamibi scans were used for preoperative localization; however, in cases of discordance between these investigations or suspicions of multi-glandular disease, four-dimensional computerized tomography of the neck was used. Patients were subjected to surgery according to the guidelines and monitored post-surgery for complications like hypocalcemia and hungry bone syndrome and to document the cure. Results The mean age of patients was 42.8±14.73 years, with a female-to-male ratio of 4.4:1. The mean eGFR of patients was 99.1±30.87 ml/min, with 55 (53.4%) of them having renal disease. Osteoporosis and fractures were present in 41 (39.8%) and 5 (4.8%) patients, respectively. Cholelithiasis and pancreatitis were present in 25 (24.3%) and 5 (4.9%) patients, respectively. Hypertension (HTN) and diabetes mellitus (DM) were the commonest comorbidities, which were present in 34 (33.1%) and 15 (14.5%) patients, respectively. Mean preoperative levels of calcium, phosphorus (PO4), alkaline phosphate (ALP), intact parathyroid hormone (iPTH), 25(OH)vitamin D, and 24-hour urinary calcium were 12.1 mg/dl, 2.35 mg/dl, 210.2 U/L, 332.9 pg/ml, 25.7 ng/ml, and 452.1 mg/day, respectively. The most common type was right inferior parathyroid adenoma, present in 45 cases (43.7%), followed by left inferior parathyroid adenoma in 31 cases (30.1%). A total of 75 patients (72.8%) underwent minimally invasive parathyroidectomy, with 68 patients (90.7%) achieving a biochemical cure. The mean adenoma weight was 3.19±2.25 g. There was no statistically significant correlation (r) between preoperative biochemical parameters and adenoma weight. Conclusion Despite improvements in imaging and the easy availability of immunoassays for early diagnosis, renal disease continued to be the most common presentation, followed by skeletal involvement in our population. In developing countries like India, any patient presenting with nephrolithiasis or nephrocalcinosis, low bone mass, or fragility fractures should be evaluated for PHPT.
PubMed: 38910736
DOI: 10.7759/cureus.60965 -
JAMA Otolaryngology-- Head & Neck... Jun 2024Whether F18-choline (FCH) positron emission tomographic (PET)/computed tomographic (CT) scan can replace Tc99m-sestaMIBI (MIBI) single-photon emission (SPE)CT/CT as a...
IMPORTANCE
Whether F18-choline (FCH) positron emission tomographic (PET)/computed tomographic (CT) scan can replace Tc99m-sestaMIBI (MIBI) single-photon emission (SPE)CT/CT as a first-line imaging technique for preoperative localization of parathyroid adenomas (PTA) in patients with primary hyperparathyroidism (PHPT) is unclear.
OBJECTIVE
To compare first-line FCH PET/CT vs MIBI SPECT/CT for optimal care in patients with PHPT needing parathyroidectomy and to compare the proportions of patients in whom the first-line imaging method resulted in successful minimally invasive parathyroidectomy (MIP) and normalization of calcemia 1 month after surgery.
DESIGN, SETTING, AND PARTICIPANTS
A French multicenter randomized open diagnostic intervention phase 3 trial was conducted. Patients were enrolled from November 2019 to May 2022 and participated up to 6 months after surgery. The study included adults with PHPT and an indication for surgical treatment. Patients with previous parathyroid surgery or multiple endocrine neoplasia type 1 (MEN1) were ineligible.
INTERVENTIONS
Patients were assigned in a 1:1 ratio to receive first-line FCH PET/CT (FCH1) or MIBI SPECT/CT (MIBI1). In the event of negative or inconclusive first-line imaging, they received second-line FCH PET/CT (FCH2) after MIBI1 or MIBI SPECT/CT (MIBI2) after FCH1. All patients underwent surgery under general anesthesia within 12 weeks following the last imaging. Clinical and biologic (serum calcemia and parathyroid hormone levels) assessments were performed 1 and 6 months after surgery.
MAIN OUTCOMES AND MEASURES
The primary outcome was a true-positive first-line imaging-guided MIP combined with uncorrected serum calcium levels of 2.55 mmol/l or less 1 month after surgery, corresponding to the local upper limit of normality.
RESULTS
Overall, 57 patients received FCH1 (n = 29) or MIBI1 (n = 28). The mean (SD) age of patients was 62.8 (12.5) years with 15 male (26%) and 42 female (74%) patients. Baseline patient characteristics were similar between groups. Normocalcemia at 1 month after positive first-line imaging-guided MIP was observed in 23 of 27 patients (85%) in the FCH1 group and 14 of 25 patients (56%) in the MIBI1 group. Sensitivity was 82% (95% CI, 62%-93%) and 63% (95% CI, 42%-80%) for FCH1 and MIBI1, respectively. Follow-up at 6 months with biochemical measures was available in 43 patients, confirming that all patients with normocalcemia at 1 month after surgery still had it at 6 months. No adverse events related to imaging and 4 adverse events related to surgery were reported.
CONCLUSIONS
This randomized clinical trial found that first-line FCH PET/CT is a suitable and safe replacement for MIBI SPECT/CT. FCH PET/CT leads more patients with PHPT to correct imaging-guided MIP and normocalcemia than MIBI SPECT/CT thanks to its superior sensitivity.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT04040946.
PubMed: 38900416
DOI: 10.1001/jamaoto.2024.1421 -
Lakartidningen Jun 2024This retrospective observational study aimed to identify complications and re-admissions after unilateral exploration of the parathyroid, hemithyroidectomy or resection... (Observational Study)
Observational Study
This retrospective observational study aimed to identify complications and re-admissions after unilateral exploration of the parathyroid, hemithyroidectomy or resection of the thyroid isthmus in patients that underwent ambulatory surgery at Karolinska University Hospital 2018-2019. The medical records of 280 patients were scrutinized by searching for re-admissions within 10 days or frequent contact with the healthcare provider within 30 days. 256 out of 280 patients underwent ambulatory surgery. 22 patients were converted to inpatient care, one because of postoperative bleeding. Five patients had a complication, one recurrent laryngeal nerve palsy and four postoperative infections. One patient was readmitted within 10 days from surgery, not related to the surgery. Our study supports that with adequate selection of patients and postoperative monitoring, ambulatory endocrine neck surgery can be performed without jeopardizing patient safety.
Topics: Humans; Ambulatory Surgical Procedures; Thyroidectomy; Retrospective Studies; Male; Female; Middle Aged; Postoperative Complications; Adult; Aged; Parathyroidectomy; Patient Readmission; Patient Safety
PubMed: 38895760
DOI: No ID Found -
Diagnostics (Basel, Switzerland) May 2024Parathyroid carcinoma (PC) associated with primary hyperparathyroidism (PHPT) has been well investigated in recent years. Data regarding PC evolution in secondary...
Parathyroid carcinoma (PC) associated with primary hyperparathyroidism (PHPT) has been well investigated in recent years. Data regarding PC evolution in secondary hyperparathyroidism (SHPT) due to chronic kidney disease (CKD) are, however, scarce. Most features that raise the suspicion of PC in PHPT are part of the usual SHPT evolution in CKD, mirroring the natural changes undergone by the parathyroid glands. Therefore, pre-surgically establishing the malignant or benign character of the lesions is cumbersome. We present two cases of PC in end-stage renal disease, one of which was bilateral, diagnosed after total parathyroidectomy in a high-volume parathyroid surgery center. A literature review of the data was also performed. A systematic search of the PubMed/MEDLINE database until January 2024 identified 42 cases of PC associated with SHPT. Understanding the PC features in CKD might improve associated bone and mineral disease management, and reduce the risk of metastasis, parathyromatosis, or recurrence. Irradiation, prolonged immunosuppression, long dialysis vintage, and genotype may predispose to the malignant transformation of chronically stimulated parathyroids. Despite postsurgical diagnosis, favorable outcomes occurred when distant metastases were absent, even without "en bloc" resection. Further research is warranted to delineate specific diagnostic and therapeutic approaches tailored to this particular patient subpopulation.
PubMed: 38893652
DOI: 10.3390/diagnostics14111127 -
Journal of Clinical Medicine Jun 2024Transient hypoparathyroidism (TH) is the main post-thyroidectomy complication, significantly impacting surgical outcomes, hospitalization length, and perceived...
Transient hypoparathyroidism (TH) is the main post-thyroidectomy complication, significantly impacting surgical outcomes, hospitalization length, and perceived perceived quality of life understood as mental and physical well-being. This study aims to identify possible associated risk factors. We analyzed 238 thyroidectomies (2020-2022), excluding instances of partial surgery, primary hyperparathyroidism, neck irradiation history, and renal failure. The variables considered were as follows: demographics, histology, autoimmunity, thyroid function, pre- and postoperative Vitamin D levels (where available), type of surgery, number of incidentally removed parathyroid glands (IRP), and surgeons' experience (>1000 thyroidectomies, <500, in training). Univariate analysis applied: χ, Fisher's exact test for categorical variables, and Student's -test for continuous variables. Subsequently, logistic multivariate analysis with stepwise selection was performed. Univariate analysis did not yield statistically significant results for the considered variables. The 'No Complications' group displayed a mean age of 55 years, whereas the TH group showed a mean age of 51 (-value = 0.055). We considered this result to be marginally significant. Subsequently, we constructed a multivariate logistic model. This model (AIC = 245.02) indicated that the absence of incidental parathyroidectomy was associated with the age class >55 years, presenting an odds ratio (OR) of 9.015 (-value < 0.05). Simultaneously, the age class >55 years exhibited protective effects against TH, demonstrating an OR of 0.085 (-value < 0.01). Similarly, the absence of incidental parathyroidectomy was found to be protective against TH, with an OR of 0.208 (-value < 0.01). Multivariate analysis highlighted that having "No IRP" was protective against TH, while younger age was a risk factor. Surgeon experience does not seem to correlate with IRP or outcomes, assuming there is adequate tutoring and a case volume close to 500 to ensure good results. The effect of reimplantation has not been evident in transient hypoparathyroidism.
PubMed: 38893037
DOI: 10.3390/jcm13113326 -
Endokrynologia Polska Jun 2024Not required for Clinical Vignette.
Not required for Clinical Vignette.
PubMed: 38887118
DOI: 10.5603/ep.99387 -
JBMR Plus Jul 2024Data on epidemiology and secular trend in primary hyperparathyroidism (PHPT) in adults are relatively limited in Asian countries. This study aims to provide an overview...
Data on epidemiology and secular trend in primary hyperparathyroidism (PHPT) in adults are relatively limited in Asian countries. This study aims to provide an overview of the secular trends in incidence, clinical characteristics, and treatment patterns of PHPT in South Korea. We used Korea's National Health Insurance Claim database (2005-2020) to identify newly diagnosed PHPT cases. Individuals with age below 19, fewer than 2 E21.0 diagnoses, fewer than 2 PTH measurements, secondary hyperparathyroidism, undergoing dialysis or kidney transplantation within a year of diagnosis, parathyroidectomy (PTX) within a year prior to the diagnosis code, and diagnosis of multiple endocrine neoplasm or parathyroid carcinoma were excluded from the analysis. A total of 6837 patients with PHPT (PTX, = 2989; non-surgery, = 3848) were compared with 1:10 age- and sex-matched controls ( = 68 370). The mean age of patients with PHPT was 56.0 years, with 77.4% being women. The annual incidence of PHPT increased from 0.23/100 000 persons in 2005 to 1.75 in 2020, with higher rate in women than in men. Compared with 2005-2010 ( = 675), the number of newly diagnosed PHPT cases increased up to 3.1-fold ( = 2119) in 2011-2015 and 6.0-fold ( = 4043) in 2016-2020 periods. Among all patients with PHPT, 43.7% of patients underwent PTX, with decrement of proportion of bilateral surgery among PTX group across time (11.9% in 2005-2010 to 8.9% in 2016-2020, for trend .033). Among all patients with PHPT, non-surgery group increased from 41.6% in 2005-2010 to 58.0% in 2016-2020 ( for trend <.001). Patients with PHPT had higher odds of osteoporosis (odds ratio [OR] 7.03), renal stones (OR 10.55), chronic kidney diseases (OR 7.42), and cardiovascular, metabolic, and neurological conditions after adjustment for comorbidity index. In summary, the incidence of PHPT increased from 2005 to 2020 with predominance of non-surgical treatment, which calls for research focus on improving non-surgical management.
PubMed: 38868595
DOI: 10.1093/jbmrpl/ziae065 -
Heliyon Jun 2024Hyperparathyroidism is common with African American patients historically experiencing disparate outcomes. With a comprehensive outreach program and systematic treatment...
BACKGROUND
Hyperparathyroidism is common with African American patients historically experiencing disparate outcomes. With a comprehensive outreach program and systematic treatment plans, we sought to evaluate our institution's ability to reduce disparities in hyperparathyroidism.
METHODS
We performed a retrospective review of prospectively collected data at a single medical center for all patients undergoing parathyroidectomy by endocrine surgeons from 2015 to 2021 for primary (PHPT) and tertiary (THPT) hyperparathyroidism. Patient demographics, pre-and post-operative clinical and biochemical data were collected and analyzed by race.
RESULTS
Of the 757 patients included, 675 patients had PHPT with 135 (20 %) African-American (AA) and 528(78 %) female. Of 82 patients with THPT, 44 (53 %) were AA and 34 (32 %) were female. AA patients were younger than Caucasian (CA) patients with a mean age (±SD) of 56 ± 15 vs 60 ± 14 years in PHPT (p < 0.01) and 50 ± 10 vs 55 ± 10 years in THPT (p = 0.02).Median (IQR) preoperative PTH was higher in AA with PHPT 134 (97-190) vs 102 (75-144) pg/mL (p < 0.01) and in AA with THPT 285 (189-544) vs 218 (145-293) (p = 0.01) pg/mL. AA PHPT patients had significantly higher preoperative mean (±SD) calcium levels 10.9 ± 0.8 vs 10.6 ± 0.8 mg/dL(p < 0.001). Biochemical cure rates at 6 months and complication rates were not different between races.
CONCLUSIONS
AA patients with PHPT and THPT disease experienced similar cure rates to their CA counterparts despite having a more severe biochemical disease. Health care disparities may be ameliorated with treatment by high volume surgeons embedded in a comprehensive health care system.
PubMed: 38868057
DOI: 10.1016/j.heliyon.2024.e32244