Comparison of prognosis after partial and total surgical resection for parathyroid carcinoma: an inverse probability of treatment weighting analysis of the SEER database.

Background: Complete resection of the tumor and the ipsilateral thyroid lobe at the primary surgery is the "gold standard" for the treatment of parathyroid carcinoma (PC). However, differences in the overall survival (OS) of patients with PC who underwent partial and total surgical resection remain to be determined. Methods: Data on patients with PC who underwent partial and total surgical resection were extracted from the Surveillance, Epidemiology and End Results (SEER) database (2000-2018). The X-tile software (https://medicine.yale.edu/lab/rimm/research/software/) was used to define the optimal cut-off values for continuous variables. The inverse probability of treatment weighting (IPTW) method was used to reduce the selection bias. IPTW-adjusted Kaplan-Meier curves and Cox proportional hazards models were used to compare the OS of patients with PC in the partial and total surgical resection groups. Results: A total of 334 patients with PC were included in this study (183 and 151 in the partial and total surgical resection groups, respectively). The optimal cut-off values for age at diagnosis were 53 and 73 years, respectively, while that for tumor size was 34 mm. In both the Kaplan-Meier analysis and univariable Cox proportional hazards regression analysis before IPTW, the difference in OS between the partial and total surgical resection groups was not statistically significant (p>0.05). These findings were confirmed in the IPTW-adjusted Kaplan-Meier analysis and multivariate Cox proportional hazards regression analysis (p>0.05). Subgroup analysis revealed that total surgical resection was beneficial for OS only in the subgroup with unknown tumor size. Conclusion: There was no significant difference in the prognosis of patients who underwent partial and total surgical resection. This finding may provide a useful reference for the treatment of PC.

Investigating the risk of metabolic and cardiovascular comorbidities among patients with parathyroid cancer: a nationwide representative cohort study in Taiwan.

BACKGROUND: This study aimed to determine whether primary parathyroid cancer patients were associated with increased metabolic and cardiovascular comorbidities in comparison to the general population. METHODS: We used the National Taiwan Cancer Registry Database to construct a cohort of patients with parathyroid cancer from January 1, 2004, to December 31, 2019. We compared the incidence of hypertension, diabetes mellitus, hyperlipidemia, atrial fibrillation, coronary heart disease, and heart failure with the general population matched based on a propensity score in a one-to-five fashion. RESULTS: A total of 72 parathyroid cancer patients and 360 matched general population (mean age: 55 years; 59% women) were included, with different exclusive numbers for each metabolic and cardiovascular comorbidity cohort. The number of cases based on a total of 2347.7 person-years of observation included 53 deaths, 29 hypertension, 9 diabetes, 13 hyperlipidemia, 10 atrial fibrillation, 18 coronary artery disease, and 13 heart failure. According to multivariate analysis, parathyroid cancer remained significantly associated with diabetes [hazard ratio (HR): 9.28; 95% confidence interval (CI): 1.72-50.07], hyperlipidemia (HR: 5.86; 95% CI: 1.61-21.31), and heart failure (HR: 4.46; 95% CI: 1.18-16.84). Sub-distribution of competing mortality events and subgroup analysis showed robust evidence of metabolic and cardiovascular comorbidities. This national cohort study demonstrated that adult parathyroid cancer patients had a significantly higher incidence of diabetes mellitus, hyperlipidemia, and heart failure than the general population. CONCLUSIONS: An increased risk of metabolic and cardiac comorbidities among parathyroid cancer patients required great caution.

Non-Linear Correlation Between Tumor Size and Survival Outcomes for Parathyroid Carcinoma: A SEER Population-Based Cohort Study.

Background: Parathyroid carcinoma (PC) is a rare malignancy without a commonly acknowledged prognostic assessment and treatment system. This study captures how independent prognostic factors and tumor size correlate with outcomes in patients with PC. Methods: The Surveillance, Epidemiology, and End Results database was used to perform a retrospective analysis on PC patients from 2000 to 2018. Univariate and multivariable survival analyses were performed to evaluate cancer-specific survival (CSS) and overall survival (OS), to identify independent prognostic factors in the PC patient population. A generalized additive model was applied to conduct smooth curve fitting and to examine the association between tumor size and relative risk of death. Results: A total of 590 patients were included. The 5- and 10-year OS were 80.8% and 67.1%, respectively. 5- and 10-year CSS was estimated to be 93.6% and 92.1%, respectively. The association between tumor size and relative risk of death can be generalized as a U-shaped curve. The mortality risk reaches its lowest point when tumor diameter approaches 2cm. At a tumor diameter cutoff of 3cm for CSS and 4cm for OS, there is an abrupt drop in survival rates. Multivariate Cox analysis revealed age, no surgery, and debulking surgery as consistent predictors of lower OS and CSS. Conclusions: A non-linear correlation between tumor size and death risk has been identified in patients with PC, along with an accurate size threshold at which survival rates sharply decrease. Further investigation is needed to determine if these trends are seen in other malignancies with promising prognoses.

Association of biochemical and clinical parameters with parathyroid adenoma weight. Turkish-Bulgarian endocrine and breast surgery study group, hyperparathyroidism registry study.

BACKGROUND: Primary hyperparathyroidism (pHPT) caused by a single benign parathyroid adenoma is a common endocrine disorder that is affected by regional differences. Living in different geographical regions reveals differences in the laboratory results and pathological findings, but studies on this subject are not sufficient. The article focuses on biochemical and pathological effects of geographical differences in parathyroid adenoma. In addition, the present study seeks to elaborate on treatment methods and effectiveness of screening in geographical area of Bulgaria and Turkey. METHOD: In this prospective study, 159 patients were included from 16 centres. Demographic characteristics, symptoms, biochemical markers and pathologic characteristics were analysed and compared between 8 different regions. RESULTS: Patients from Turkish Black Sea had the highest median serum calcium (Ca) level, whereas patients from Eastern Turkey had the lowest median serum phosphorus (P) level. On the other hand, there was no significant difference between Ca, parathormone (PTH) and P levels according to regions. Patients from Eastern Turkey had the highest adenoma weight, while patients from Bulgaria had the lowest adenoma weight. The weight of adenoma showed statistically significant differences between regions (p < 0.001). There was a correlation between adenoma weight and serum PTH level (p = 0.05) and Ca level (p = 0.035). CONCLUSION: This study has provided a deeper insight into the effect of the regional differences upon clinicopathological changing and biochemical values of pHTP patients with adenoma. Awareness of regional differences will assist in biochemical screening and treatment of this patient group.

Multiple endocrine neoplasia type 1 in children and adolescents: Clinical features and treatment outcomes.

BACKGROUND: Clinical manifestations and treatment outcomes in children and adolescents with multiple endocrine neoplasia type 1 are not well characterized. METHODS: We conducted a retrospective cohort study of 80 patients with multiple endocrine neoplasia type 1 who commenced tumor surveillance at ≤18 years of age. RESULTS: Fifty-six patients (70%) developed an endocrine tumor by age ≤18 years (median age = 14 years, range = 6-18 years). Primary hyperparathyroidism occurred in >80% of patients, with >70% undergoing parathyroidectomy, in which less-than-subtotal (<3-gland) resection resulted in decreased disease-free outcomes versus subtotal (3-3.5-gland) or total (4-gland) parathyroidectomy (median 27 months versus not reached; P = .005). Pancreaticoduodenal neuroendocrine tumors developed in ∼35% of patients, of whom >70% had nonfunctioning tumors, >35% had insulinomas, and <5% had gastrinomas, with ∼15% having metastases and >55% undergoing surgery. Pituitary tumors developed in >30% of patients, and ∼35% were macroprolactinomas. Tumor occurrence in male patients and female patients was not significantly different. Genetic analyses revealed 38 germline MEN1 mutations, of which 3 were novel. CONCLUSION: Seventy percent of children aged ≤18 years with multiple endocrine neoplasia type 1 develop endocrine tumors, which include parathyroid tumors for which less-than-subtotal parathyroidectomy should be avoided; pancreaticoduodenal neuroendocrine tumors that may metastasize; and pituitary macroprolactinomas.

Epidemiology and prognosis of parathyroid carcinoma: real-world data using nationwide cohort.

PURPOSE: Parathyroid carcinoma (PC) is an exceedingly rare endocrine malignancy with a poor prognosis. Due to the rarity, the natural course and prognostic factors of the disease are yet unclear. Therefore, we aimed to identify the incidence, prognosis, and prognostic factors of PC in the nationwide cohort study. METHODS: The study is a nationwide study using the National Health Insurance Services database in Korea from 2002 to 2017. PC was defined as patients with ICD-10 code of PC and a procedural code for parathyroidectomy. RESULTS: From 2002 to 2017, 255 patients were diagnosed with PC whose mean age was 53.2 years, and 155 (60.2%) were women. The crude and age-standardized incidence were 10.2 and 6.6/10,000,000 person-year in 2016, rising from 4.1 and 3.8/10,000,000 person-year in 2003 (p < 0.001), respectively. The 5- and 10-year survival rates were 86.5 and 72.9%, respectively. In survival analysis, age over 50 years, thyroidectomy at the initial surgery, and reoperation had increased risk of mortality with HRs of 4.83 (95% CI 1.47-15.90), and 4.21 (95% CI 1.60-11.08), and 1.05 (95% CI 1.02-1.08) in multivariate analysis, respectively. CONCLUSION: Incidence of PC has been rising over time, similar to the trends in Western countries. The prognostic factors for mortality were old age, parathyroidectomy alone, and recurrence, emphasizing the importance of preoperative suspicion of the disease. The study is clinically meaningful in the first Asian nationwide study to reveal the natural course of PC.

Parathyroid Carcinoma: An Experience from the Indian Primary Hyperparathyroidism Registry.

OBJECTIVE: To describe the details of widely invasive parathyroid carcinoma (WIPC) patients admitted in the Endocrinology department of our institute during the last 22 years and to compare their clinical, biochemical, and hormonal profile with minimally invasive parathyroid carcinoma (MIPC) and sporadic parathyroid adenoma patients. METHODS: This is a retrospective analysis of data from the Indian primary hyperparathyroidism registry. RESULTS: Of the 547 primary hyperparathyroidism patients in the registry, 5 (2 men and 3 women) had WIPC (0.9%) and 7 (1 man and 6 women) had MIPC (1.3%), with median ages of 45 (interquartile range, 41-51) years and 47 (interquartile range, 28-48) years, respectively. Among the patients with WIPC, renal manifestations were present in 5 patients, skeletal manifestations in 4 patients, and palpable neck masses in 4 patients. Three patients had distant metastases and 2 had cervical lymph node involvement. All 5 patients had surgical resection of their cancers, with persistent disease in 4 patients, but all patients died within 2 years after surgery. One patient with MIPC had a palpable parathyroid nodule; none had lymph nodal or distant metastases. None of the patients with MIPC died during the median follow-up of 18 (interquartile range, 12-18) months. Patients with WIPC had significantly higher serum calcium level compared with sporadic parathyroid adenoma patients with skeletal and renal manifestations. CONCLUSION: Accurate histopathologic classification of parathyroid carcinoma is important as WIPC is associated with a more aggressive clinical course and a higher risk of mortality than MIPC.

Environmental chemicals and metabolic disruption in primary and secondary human parathyroid tumors.

BACKGROUND: The incidence of primary hyperparathyroidism has increased 300% in the United States in the past 30 years, and secondary hyperparathyroidism is almost universal in patients with end-stage renal disease. We assessed the presence of environmental chemicals in human hyperplastic parathyroid tumors as possible contributing factors to this increase. METHODS: Cryopreserved hyperplastic parathyroid tumors and normal human parathyroids were analyzed by gas chromatography and liquid chromatography coupled to ultra-high-resolution mass spectrometry, bioinformatics, and biostatistics. RESULTS: Detected environmental chemicals included polychlorinated biphenyls, polybrominated diphenyl ethers, dichloro-diphenyl-trichloroethane derivatives, and other insecticides. A total of 99% had p,p'-dichlorodiphenyldichloroethylene. More than 50% contained other environmental chemicals, and many classified as endocrine disruptors. Polychlorinated biphenyl-28 and polychlorinated biphenyl-49 levels correlated positively with parathyroid tumor mass. Polybrominated diphenyl ether-47 concentrations in tumors were inversely correlated with patients' serum calcium levels. Cellular metabolites in pathways of purine and pyrimidine synthesis and mitochondrial energy production were associated with tumor growth and with p,p'-dichlorodiphenyldichloroethylene in primary hyperparathyroidism tumors. In normal parathyroids, p,p'-dichlorodiphenyldichloroethylene , polychlorinated biphenyl-28, polychlorinated biphenyl-74, and polychlorinated biphenyl-153, but not p,p'-dichlorodiphenyldichloroethylene or polychlorinated biphenyl-49, were detected. CONCLUSION: Environmental chemicals are present in human parathyroid tumors and warrant detailed epidemiologic and mechanistic studies to test for causal links to the growth of human parathyroid tumors.

Use of Preoperative Imaging in Primary Hyperparathyroidism.

CONTEXT: Preoperative imaging is performed routinely to guide surgical management in primary hyperparathyroidism, but the optimal imaging modalities are debated. OBJECTIVE: Our objectives were to evaluate which imaging modalities are associated with improved cure rate and higher concordance rates with intraoperative findings. A secondary aim was to determine whether additive imaging is associated with higher cure rate. DESIGN, SETTING, AND PATIENTS: This is a retrospective cohort review of 1485 adult patients during a 14-year period (2004-2017) at an academic tertiary referral center that presented for initial parathyroidectomy for de novo primary hyperparathyroidism. MAIN OUTCOME MEASURES: Surgical cure rate, concordance of imaging with operative findings, and imaging performance. RESULTS: The overall cure rate was 94.1% (95% confidence interval, 0.93-0.95). Cure rate was significantly improved if sestamibi/single-photon emission computed tomography (SPECT) was concordant with operative findings (95.9% vs. 92.5%, P = 0.010). Adding a third imaging modality did not improve cure rate (1 imaging type 91.8% vs. 2 imaging types 94.4% vs. 3 imaging types 87.2%, P = 0.59). Despite having a low number of cases (n = 28), 4-dimensional (4D) CT scan outperformed (higher sensitivity, specificity, positive predictive value, negative predictive value) all imaging modalities in multiglandular disease and double adenomas, and sestamibi/SPECT in single adenomas. CONCLUSIONS: Preoperative ultrasound combined with sestamibi/SPECT were associated with the highest cure and concordance rates. If pathology was not found on ultrasound and sestamibi/SPECT, additional imaging did not improve the cure rate or concordance. 4D CT scan outperformed all imaging modalities in multiglandular disease and double adenomas, and sestamibi/SPECT in single adenomas, but these findings were underpowered.

Prevalence of Parathyroid Carcinoma and Atypical Parathyroid Neoplasms in 153 Patients With Multiple Endocrine Neoplasia Type 1: Case Series and Literature Review.

Purpose: The occurrence of parathyroid carcinoma (PC) and atypical parathyroid neoplasm (APN) in multiple endocrine neoplasia type 1 (MEN1) is rare. The present paper reports the cases of 3 MEN1-PC/APN patients at our center and discusses the prevalence in a Chinese MEN1 cohort. Methods: This report is a retrospective analysis of 153 MEN1-associated primary hyperparathyroidism (MEN1-HPT) patients at our center, which included 3 MEN1-associated PC/APN (MEN1-PC/APN) patients. The clinical manifestations, biochemical indices, pathological findings, and therapy have been summarized along with the report of the genetic testing of the 3 patients. Results: Of the 153 MEN1-HPT patients, 1 (0.7%) was histopathologically diagnosed with PC and 2 (1.3%) with APN. Three heterozygous mutations were identified in the 3 MEN1-PC/APN patients (c.917 T > G, c.431T > C, and c.549 G > C). The cumulative findings of 3 cases with 18 previously reported MEN1-PC/APN cases revealed that the mean serum calcium (Ca) level was 3.15 ± 0.44 mmol/L and the median parathyroid hormone (PTH) level was 327 pg/mL (214.1, 673.1), both of which were significantly higher as compared to the respective levels in non-PC/APN MEN1 patients at our center [Ca: 2.78 mmol/L [2.61, 2.88], PTH: 185.5 pg/mL [108.3, 297.0]; P = 0.0003, 0.0034, respectively]. Conclusion: MEN 1-PC/APN is a rare disease, with a prevalence of only 2.0% among the MEN1-HPT cohort at our center. The affected patients recorded higher serum Ca level and PTH levels than those with MEN1-associated benign tumors. However, the diagnosis of MEN1-PC/APN is based upon pathology most of the times.

ARMC5 Alterations in Patients With Sporadic Neuroendocrine Tumors and Multiple Endocrine Neoplasia Type 1 (MEN1).

CONTEXT: Adrenal lesions are frequent among patients with sporadic neuroendocrine tumors (spNETs) or multiple endocrine neoplasia type 1 (MEN1). Armadillo repeat-containing 5 (ARMC5)-inactivating variants cause adrenal tumors and possibly other neoplasms. OBJECTIVE: The objective of this work is to investigate a large cohort spNETs or MEN1 patients for changes in the ARMC5 gene. PATIENTS AND METHODS: A total of 111 patients, 94 with spNET and 17 with MEN1, were screened for ARMC5 germline alterations. Thirty-six tumors (18 spNETs and 18 MEN1 related) were collected from 20 patients. Blood and tumor DNA samples were genotyped using Sanger sequencing and microsatellite markers for chromosomes. ARMC5 and MEN1 expression were assessed by immunohistochemistry. RESULTS: In 76 of 111 (68.4%) patients, we identified 16 different ARMC5 germline variants, 2 predicted as damaging. There were no differences in the prevalence of ARMC5 variants depending on the presence of MEN1-related adrenal lesions. Loss of heterozygosity (LOH) at chromosome 16p and ARMC5 germline variants were present together in 23 or 34 (67.6%) tumors; in 7 of 23 (30.4%) their presence led to biallelic inactivation of the ARMC5 gene. The latter was more prevalent in MEN1-related tumors than in spNETs (88.9% vs 38.9%; P = .005). LOH at the chromosome 16p (ARMC5) and 11q (MEN1) loci coexisted in 16/18 MEN1-related tumors, which also expressed lower ARMC5 (P = .02) and MEN1 (P = .01) proteins compared to peritumorous tissues. CONCLUSION: Germline ARMC5 variants are common among spNET and MEN1 patients. ARMC5 haploinsufficiency or biallelic inactivation in spNETs and MEN1-related tumors suggests that ARMC5 may have a role in modifying the phenotype of patients with spNETs and/or MEN1 beyond its known role in macronodular adrenocortical hyperplasia.

Gender Predilection in Sporadic Parathyroid Adenomas.

Primary hyperparathyroidism is a common endocrinopathy that is mainly caused by benign parathyroid adenomas. The frequency, clinical presentation and complications of the disease show significant differences between genders, with the majority of cases being reported in postmenopausal women. Due to this gender predilection, several studies have investigated the role of sex hormones in the pathogenesis of the disease and their potential use as targets for optimal and gender-specific management. Epigenetic mechanisms that regulate gene transcription may also contribute to these differences between genders. In this review, we outline what is currently known regarding the role of sex hormones and the recent data on the role of non-coding RNAs in the differences between genders in primary hyperparathyroidism due to sporadic parathyroid adenomas.

Influence of common clinical variables on intraoperative parathyroid hormone monitoring during surgery for primary hyperparathyroidism.

BACKGROUND: Intraoperative monitoring of parathyroid hormone (IOPTH) is a reliable method of predicting the cure of primary hyperparathyroidism (PHPT). The aim of this study is to assess whether common clinical variables (CCV) frequently encountered in patients with PHPT may affect the magnitude of PTH drop or the likelihood of patients meeting the intraoperative cure criterion. DESIGN: Patients who were surgically cured from PHPT caused by single gland disease (SGD) and had full IOPTH protocol (4 measurements) were stratified according to age, gland weight, renal function, vitamin D status and severity of hypercalcemia. The percentage of IOPTH drop and the frequency of patients who had true positive IOPTH test results were compared among groups. RESULTS: 762 patients had surgery for PHPT, of whom 746 were (98%) cured. Of these 746 patients, 511 who had SGD and a full IOPTH protocol were included in this study. The median IOPTH drop was significantly higher among younger patients, those with severe hypercalcaemia at 5, 10, 15 min after gland excision, giant glands (at 5-min only), patients with vitamin D deficiency (at 10, 15 min), and those with normal renal function (at 15 min only). The likelihood of the patients meeting the intraoperative cure criterion was not significantly affected among the groups except in patients with mild hypercalcaemia, who were significantly less likely to have 50% IOPTH drop than those with severe hypercalcaemia at all time points. The frequency of mildly hypercalcaemic patients who met cure criterion was significantly improved by extending measurement to 15 min. CONCLUSIONS: IOPTH monitoring has the ability to mitigate the variability of IOPTH kinetics associated with most clinical variables. Mildly hypercalcemic patients in particular may benefit from waiting for 15-min measurement before any surgical decision is made.

Persistent/Recurrent Primary Hyperparathyroidism: Does the Number of Abnormal Glands Play a Role?

BACKGROUND: Persistent/recurrent hyperparathyroidism occurs in 2%-5% of patients with sporadic primary hyperparathyroidism (PHPT). In this study, the incidence and time to recurrence in patients with single-gland disease (SGD), double adenomas (DAs), or four-gland hyperplasia (FGH) at initial parathyroidectomy were compared. METHODS: This retrospective review included adult patients with sporadic PHPT who underwent initial parathyroidectomy with intraoperative parathyroid hormone monitoring (IOPTH) from 1/2000 to 12/2016 with ≥6 mo follow-up. An abnormal parathyroid was defined by a gland weight of ≥50 mg. A concurrent serum calcium >10.2 mg/dL and parathyroid hormone >40 pg/mL was defined as persistent PHPT if present <6 mo and recurrent PHPT if present ≥6 mo postoperatively after initial normocalcemia. RESULTS: Of 1486 patients, 1203 (81%) had SGD, 159 (11%) DA, and 124 (8%) FGH. Among the 3 groups, there was no difference in the percent decrease from the baseline or time of excision to final postexcision IOPTH levels between groups (79% versus 80% versus 80%, respectively; P = 0.954) or in the proportion of patients with a final IOPTH ≥40 (22% versus 18% versus 14%; P = 0.059). Overall, 22 (1.5%) had persistent PHPT and 26 (1.7%) had recurrent PHPT. Persistent PHPT was more frequent with DAs (6; 3.8%) than other groups (SGD: 16, 1.3%; FGH: 0; P = 0.02). At median follow-up of 33 mo (IQR, 18-60), there was no difference in recurrence rate (1.6% versus 2.5% versus 2.4%; P = 0.57) or median time (mo) to recurrence (SGD: 59 [IQR, 21-86], DAs: 36 [IQR, 29-58], FGH: 23 [IQR, 17-40]; P = 0.46). CONCLUSIONS: Recurrent PHPT occurred in 1.7% of patients who underwent curative initial parathyroidectomy, with no difference in incidence or time to recurrence between groups based on the number of glands removed. Patients with DA more commonly had persistent PHPT, raising the possibility of unrecognized FGH.

[Endocrine tumours in Stockholm - increasing general incidence]. / Incidensökning av endokrina tumörer - Kraftig ökning av diagnostiserade tumörer i sköldkörtel, bisköldkörtel och binjure i stockholm mellan 1992 och 2017.

In recent years, a significantly increased incidence of endocrine tumours has been observed worldwide, not least papillary thyroid cancer - with improved diagnostics and various biological factors being two possible causes of the upsurge. In this material from the Karolinska University Hospital, to date the largest tertiary endocrine surgery unit in the Nordic region, we see a near five-fold increase in the number of diagnosed thyroid cases and a distinct rise in the incidence of tumour cases in the thyroid, parathyroid and adrenal glands. The increase can only partly be explained by an accommodation of patients to tertiary units and should therefore be considered as a true increase in incidence across the Swedish population. Our findings therefore verify the international reports regarding a surge in endocrine tumours and highlight the need for efficient patient care - from diagnosis to treatment.

Atypical parathyroid adenomas: challenging lesions in the differential diagnosis of endocrine tumors.

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.

The surgical management of sporadic primary hyperparathyroidism.

Sporadic primary hyperparathyroidism (pHPT) is the commonest cause of hypercalcaemia in the ambulatory population. It has a female preponderance and its incidence is increasing. In 85% of cases it is caused by a single parathyroid adenoma, with four gland hyperplasia in up to 20%. Parathyroidectomy is the only cure and bilateral neck exploration remains the gold standard to achieve this. Several adjuncts have been developed to improve success rates or limit the extent of surgery. Pre-operative localisation permits planned targeted surgery. Ultrasound scanning and scintigraphy are the most commonly employed, although 4DCT has become a useful modality in complex cases. However, excellent rates of biochemical cure can be achieved in specialist centres when pre-operative imaging is negative. Pre-operative prediction models and intra-operative parathyroid hormone (ioPTH) assist, with high sensitivity, to predict single gland disease. Reoperations present a major challenge to the endocrine surgeon.

Evaluation and management of thyroid incidentalomas detected prior to the parathyroid surgery.

BACKGROUND: We investigated the management of thyroid incidentalomas associated with cases of parathyroid lesions in order to suggest a practical approach to their management from a surgical point of view. METHODS: 639 patients underwent radiological and ultrasound investigation of the thyroid area because of parathyroid disorders and parathyroidectomy and had at least three years of follow-up. All follow-up data for these cases were investigated from the moment the lesion was detected and up to the last report. RESULTS: Out of 639 cases, incidental or asymptomatic thyroid nodules were found in 179 patients (28%), of which, 22 patients were operated (parathyroidectomy + thyroidectomy) and 157 remained with the nodules. For these patients, the average period of follow-up was 7 years 5 mo. Following the results of the follow-up, 52 patients (33%) were suggested to have surgery of the thyroid gland and 49 were operated (16 total thyroidectomies and 33 hemithyroidectomies). The complications after the second surgery included recurrent laryngeal nerve palsy (n = 3), superior laryngeal nerve palsy (n = 1), permanent hypocalcaemia (n = 8), and surgical damage to the internal jugular vein (n = 1). All complications occurred at the previously operated side of the neck. CONCLUSION: While surgery remains the management of choice for malignant thyroid incidentalomas, for benign cases, if an asymptomatic thyroid nodule was detected inside the thyroid lobe on the side of planned parathyroidectomy and if the size of the nodule is ˃1.5 cm we suggest combined parathyroidectomy + hemithyroidectomy.

Tumor Size and Presence of Metastatic Disease at Diagnosis are Associated with Disease-Specific Survival in Parathyroid Carcinoma.

BACKGROUND: The incidence of parathyroid carcinoma is reported to be rising. There is minimal data on prognostic variables associated with cancer-specific survival. The objectives of this study were to evaluate the trends in incidence and assess prognostic factors. METHODS: A retrospective review of the SEER database between 1973 and 2014 was performed, identifying 520 patients with parathyroid carcinoma. Population-adjusted incidence rates were calculated in 4-year intervals. A Cochrane-Armitage test was performed to analyze changes in trend in incidence, tumor size, and extent of disease. Age, year of diagnosis, race, gender, extent of disease, surgical resection, treatment with radiation, tumor size, and lymph node status were assessed using Mantel-Cox log rank test. Multivariate analysis was performed by Cox regression analysis. RESULTS: The incidence of parathyroid carcinoma has been increasing since 1974 from 2 to 11 cases per 10 million people but has since stabilized at 11 cases per 10 million people since 2001. The increasing incidence was attributed to locoregional disease and tumor size < 3 cm. The presence of metastatic disease [hazard ratio (HR) 111.4, 95% confidence interval (CI) 20.6-601.8, p < 0.0001) and tumor size > 3 cm (HR 5.6, 95% CI 1.5-21.2, p = 0.011] were associated with worse cancer-specific survival by univariate and multivariate analyses. CONCLUSIONS: The incidence of parathyroid carcinoma has remained stable over the past decade. Tumor size < 3 cm and regional disease have increased in incidence. Patients with metastatic disease and tumors > 3 cm have worse cancer-specific survival. These findings can be incorporated in the development of a staging system for parathyroid carcinoma.

Genetics of parathyroids disorders: Overview.

Several familial forms of primary hyperparathyroidism (PHTP) have been discovered over the past 25 years, and molecular test for their risk assessment has been widely increasing. These syndromic and non-syndromic forms have received benefits from the identification of the responsible genes whose mutations account for the genetic susceptibility to develop parathyroid tumours as also other endocrine and nonendocrine tumours. In recent years, care options have been made available to patients and families with hereditary PHPT, and the process of systematically assessing the genetic risk has been becoming increasingly important. The aim of this review is to help health providers not frequently dealing with genetic testing use, introducing general concepts with regard to genetic diagnosis issues. The role and the practical usefulness of DNA-based diagnosis in patients affected by different forms of "congenital" PHPT is described, closely looking on why, when and how genetic testing should be performed in these subjects and their relatives. Moreover, this review will provide some practical suggestions and recommendations concerning on how to deal with a suspected or known case of familial PHPT.