The Role of Surgeon-Performed Office and Preincision Ultrasounds in Localization of Parathyroid Adenomas in Primary Hyperparathyroidism

ObjectiveWe studied the use of surgeon-performed office ultrasound (OU) and preincision ultrasound (PIU) in preoperatively localizing parathyroid adenomas in primary hyperparathyroidism (PHPT).MethodsA retrospective chart review was performed for patients with PHPT who underwent parathyroidectomy between 2013 and 2015. The results of OU and PIU were recorded and compared with the final surgical pathology.ResultsOf 348 patients with PHPT, 285 (81.9%) had single-lesion disease, 49 (14.1%) had double-lesion disease, and 14 (4.0%) had multigland disease with 3 or more lesions. For single-lesion disease, the overall sensitivity and specificity of OU to correctly lateralize the lesion were 64.2% and 91.2%, while those of PIU were 89.4% and 93.6%, respectively. The sensitivity and specificity of PIU were comparable to those of 4-dimensional computed tomography (87.1% and 90.7%, respectively) and ^99mTc-sestamibi scintigraphy (70.4% and 95.9%, respectively). While the majority of PIU cases were preceded by other imaging studies, the accuracy in localizing lesions was not largely affected by the presence of prior computed tomography and/or ^99mTc-sestamibi scintigraphy, as opposed to ultrasounds only. For detecting the presence of multigland disease, the sensitivity and specificity of OU were 26% and 92.2%, while those of PIU were 64.3% and 94.7%, respectively.ConclusionSurgeon-performed OU and PIU are valuable tools in preoperatively localizing the parathyroid adenoma in single-lesion disease, while their utility may be limited for double-lesion or multigland disease. PIU in particular yields high accuracy in detecting parathyroid lesions in combination with other imaging modalities.     

Association Between Aldosterone and Parathyroid Hormone Levels in Patients With Adrenocortical Tumors

ObjectivePatients with primary aldosteronism (PA) can present with high PTH levels and negative calcium balance, with some studies speculating that aldosterone could directly stimulate PTH secretion. Either adrenalectomy or mineralocorticoid receptor blockers could reduce PTH levels in patients with PA. The aim of this study was to assess the relationship between aldosterone levels and parathyroid hormone (PTH)-vitamin D-calcium axis in a cohort of patients with PA, compared with patients with nonsecreting adrenocortical tumors in conditions of vitamin D sufficiency.MethodsWe enrolled a series of 243 patients retrospectively, of whom 66 had PA and 177 had nonsecreting adrenal tumors, and selected those with full mineral metabolism evaluation and 25(OH) vitamin D levels >20 ng/mL at the time of initial endocrine screening. The final cohort was composed of 26 patients with PA and 39 patients, used as controls, with nonsecreting adrenal tumors. The relationships between aldosterone, PTH levels, and biochemistries of mineral metabolism were assessed.ResultsAldosterone was positively associated with PTH levels (r = 0.260, P < .05) in the whole cohort and in the PA cohort alone (r = 0.450; P = .02). In the multivariate analysis, both aldosterone concentrations and urinary calcium excretion were significantly related to PTH levels, with no effect of 25(OH) vitamin D or other parameters of bone metabolism.ConclusionPTH level is associated with aldosterone, probably independent of 25(OH) vitamin D levels and urinary calcium. Whether aldosterone interacts directly with the parathyroid glands remains to be established.     

The Detection of Preoperative Parathyroid Lesions: The Success of Ultrasonography,Technetium-99m Methoxyisobutylisonitrile Parathyroid Scintigraphy,and Single-Photon Emission Computed Tomography–Computed Tomography

ObjectiveWe aimed to find and compare the efficacy of ultrasonography (US), technetium-99m methoxyisobutylisonitrile parathyroid scintigraphy (MIBI-S), and single-photon emission computed tomography–computed tomography (SPECT-CT) in detecting the localization of parathyroid adenomas in patients with primary hyperparathyroidism.MethodsIn total, 348 patients were included in this study. Preoperative parathyroid imaging with US, MIBI-S, and SPECT-CT was evaluated and compared with operative findings. The results of the imaging methods were compared with pathology and operation reports.ResultsIn 318 patients (91.3%), one of the imaging methods was able to localize the lesion correctly. US detected the localization of the parathyroid lesions correctly in 268 patients (77%), whereas SPECT-CT and MIBI-S were correct in 254 (73%) and 209 (60%) patients, respectively. There was a statistically significant relationship between the parathyroid hormone (PTH) level and 3 imaging methods’ success rates (P < .05). The PTH cut-off value, which best determined the correct localization, was 152.5 pg/mL for US, 143 pg/mL for MIBI-S, and 143 pg/mL for SPECT-CT. It was observed that the correct localization rate for parathyroid lesions increased with higher PTH levels.ConclusionIn our study population, US was more successful, in most cases, than other imaging methods in localizing parathyroid lesions but SPECT-CT was more accurate in localizing mediastinal lesions. In addition, it was found that preoperative PTH levels affect the accuracy of imaging methods.     

A Retrospective Study of Ultrasonography in the Investigation of Primary Hyperparathyroidism: A New Perspective for Ultrasound Echogenicity Features of Parathyroid Nodules

ObjectiveTo identify and understand parathyroid lesions of patients with primary hyperparathyroidism (PHPT) more accurately under ultrasound.MethodsThis retrospective study involved 423 adult patients with PHPT with a single parathyroid nodule and positive parathyroid ultrasonography between 2018 and 2019. The clinical characteristics of the study patients and histopathologic sections were reviewed.ResultsAccording to the main grayscale echogenicity features of parathyroid nodules, 423 cases were divided into groups: iso-hyperechogenicity solid (61/423), hypoechogenicity solid (304/423), and mixed-echogenicity cyst-solid (58/423) groups. Comparison among the 3 groups showed that the iso-hyperechogenicity group included more asymptomatic patients with PHPT and fewer patients with severe symptoms like bone fractures (P < .05). The mixed-echogenicity group showed higher median serum parathyroid hormone (PTH) and serum calcium levels and larger lesion sizes (P < .05), and the iso-hyperechogenicity group showed the lowest median serum PTH level. No difference in lesion size was noted between the 2 solid groups, but the median serum PTH level in the hypoechogenicity group was higher than that in the iso-hyperechogenicity group (P < .05). According to histopathology, the hypoechogenic area of the samples may contain more functional components (chief cells), whereas the iso-hyperechogenic area has more nonfunctional components (eg, lipocytes and connective tissues).ConclusionThe PHPT nodules distinguished by ultrasound echogenicity features showed different histopathologic components, reflected by different clinical characteristics of the patients with PHPT.     

Parathyroid Hormone Level Changes Following Radioiodine Therapy for Thyroid Cancer: A Prospective Observational Study

ObjectiveOur objective was to analyze the effect of radioiodine (RAI) therapy on parathyroid hormone (PTH) secretion.MethodsA total of 137 patients were included and divided into 2 groups based on pretherapy PTH levels. The residual thyroid tissue volume was classified into 4 grades (0-3), and a value of 0 indicated that there was no apparent residual tissue. We analyzed the PTH level changes among different time points in each group and the factors that could predict the PTH level changes.ResultsIn 113 patients with normal parathyroid gland function, the PTH level at baseline, 1 day, 7 days, 1 month, 3 months, and 6 months after RAI therapy did not show any significant difference; in 24 patients with decreased parathyroid gland function, the level of PTH immediately decreased after the implementation of RAI therapy but gradually returned to a pre-RAI therapy level within 6 months. On the seventh day after therapy, the mean value of PTH in patients with a residual thyroid tissue volume of extent of 0/1 was 8.0 ± 2.3 pg/mL, which was significantly higher than that in patients with a residual thyroid tissue volume of extent of 2/3 (P = .011). Similar phenomena were observed 1 month, 3 months, and 6 months after therapy.ConclusionRAI therapy had a significant transient adverse effect on parathyroid gland function in patients with decreased PTH secretion pretherapy, and the extent was associated with the amount of residual thyroid tissue.     

Aldosterone Secretion in Patients With Primary Hyperparathyroidism Without Arterial Hypertension

ObjectiveThere is a direct bidirectional link between parathyroid hormone (PTH) and the renin-angiotensin-aldosterone system (RAAS), but few studies evaluated the RAAS in patients with primary hyperparathyroidism (PHPT), mainly biased from concomitant antihypertensive treatment.MethodsWe retrospectively evaluated a consecutive series of 130 normotensive patients with PHPT comparing aldosterone (ALD) levels and plasma renin activity (PRA) with the demographic, biochemical, or clinical features of PHPT.ResultsNo correlation was found between ALD and PRA, and the demographic, biochemical, and bone densitometry parameters in patients with PHPT without hypertension, with the exception of a negative correlation between age and serum PRA. Moreover, there was no significant correlation between PTH and ALD levels even in patients whose PTH level was >100 ng/L (P = .088).ConclusionIn our normotensive patients with PHPT, the ALD, PRA, and aldosterone/renin ratio were not correlated to PTH and calcium levels. In addition, they were neither related to PHPT clinical presentation nor renal function, vitamin D status, bone mass loss, or the presence of comorbidities such as diabetes and obesity. Further studies are needed to clarify the complex interplay between PTH and the RAAS in the modern PHPT presentation.     

Calcium Challenge to Confirm Secondary Hyperparathyroidism Caused by Decreased Calcium Intake

ObjectiveSecondary hyperparathyroidism commonly occurs in the setting of mid-to low-normal serum calcium levels, often in the setting of chronic kidney disease, phosphate loading, vitamin D deficiency, or insufficient calcium intake or absorption. In this article, we report 9 patients who had adequate kidney function (estimated glomerular filtration rate >60 mL/min/1.73 m²) and normal 25-hydroxy vitamin D level (≥30 ng/dL) and whose secondary hyperparathyroidism resolved after starting adequate oral calcium intake.MethodsOur retrospective case series included 8 women and 1 man; the mean age was 69.0 ± 12.2 years (mean ± standard deviation). The initial intact parathyroid hormone (iPTH) level was 80.6 ± 13.4 pg/mL (reference range [ref], 10-65 pg/mL), corrected serum calcium level was 9.2 ± 0.2 mg/dL (ref, 8.5-10.5 mg/dL), serum phosphate level was 3.6 ± 0.4 mg/dL (ref, 2.5-4.9 mg/dL), 25-hydroxy vitamin D level was 42.2 ± 10.5 mg/dL (ref, 20-50 ng/mL), and estimated glomerular filtration rate was 72.6 ± 14.4 mL/min/1.73 m². Patients were treated clinically with oral calcium 600 mg twice a day.ResultsiPTH was retested after a mean duration of 17.6 ± 12.7 days of calcium supplementation; the iPTH level decreased to 51.0 ± 10.6 pg/mL, with all patients achieving iPTH in the normal range with normocalcemia, consistent with hyperparathyroidism being because of insufficient calcium intake or absorption. All patients were normocalcemic after supplementation.ConclusionSecondary hyperparathyroidism can result from insufficient oral calcium intake. Calcium challenge is an efficacious and cost-effective tool for confirming and treating secondary hyperparathyroidism in the setting of normal vitamin D levels and kidney function.     

Ultrasound-Guided Radiofrequency Ablation for the Treatment of Primary Hyperparathyroidism: An Efficacy and Safety Study

ObjectiveTo evaluate the efficacy and safety of radiofrequency ablation (RFA) for the treatment of primary hyperparathyroidism (pHPT).MethodsOur study enrolled 25 patients who were treated with RFA for pHPT from September 2015 to January 2020. The serum intact parathyroid hormone (iPTH), calcium, and phosphate levels were tested within 1 week before RFA and at 1 day, 1 month, 3 months, 6 months, and 12 months after ablation. The ablation areas were evaluated using ultrasound at 1, 3, 6, and 12 months after RFA. Postoperative complications, including voice hoarseness, hematoma, postoperative pain, incision infections, hypoparathyroidism, and hypocalcemia, were recorded.ResultsA total of 25 patients with pHPT (mean age, 53.9 ± 10.9 years; 22 women and 3 men) with 29 enlarged parathyroid glands were treated with RFA. Of the 25 patients, 22 were treated in 1 session and 3 were treated in 2 sessions. Serum iPTH and calcium levels decreased significantly on day 1 after RFA (all P < .05). A total of 21 patients had normal levels of serum iPTH and calcium after RFA, with a cure rate of 84%. At the 12-month follow-up, 26 treated parathyroid glands exhibited a volume reduction rate of >70%. There were only a few minor complications, including 4 cases of postoperative pain (in 4 of the 25 patients [16%]) and 1 case of mild postoperative transient hypocalcemia (in 1 of the 25 patients [4%]).ConclusionUltrasound-guided RFA is an effective and safe technique for the treatment of carefully selected patients with pHPT. However, larger sample size and longer follow-up are still needed to further confirm its clinical value.     

Echocardiographic Findings in Patients With Normocalcemic Primary Hyperparathyroidism Compared With Findings in Hypercalcemic Primary Hyperparathyroid Patients and Control Subjects

ObjectiveThere are no data regarding echocardiographic parameters in patients with normocalcemic primary hyperparathyroidism (NCPHPT). We compared the echocardiographic findings in postmenopausal women with NCPHPT with those in patients with hypercalcemic primary hyperparathyroidism (PHPT) and controls.MethodsSeventeen consecutive Caucasian postmenopausal women with NCPHPT were compared with 20 women with hypercalcemic PHPT and 20 controls. Obesity, diabetes, kidney failure, and previous cardiovascular diseases were considered exclusion criteria. Each patient underwent biochemical evaluation, bone mineral density scan, and echocardiographic measurements. Patients with parathyroid disorders underwent kidney ultrasound evaluation.ResultsPatients with PHPT had significantly higher mean total serum calcium, ionized calcium, 24-hour urinary calcium, and parathyroid hormone and lower mean phosphorus levels compared with those in the controls (all P < .05). The only differences between patients with NCPHPT and PHPT were significantly lower mean total serum calcium, ionized calcium, and 24-hour urinary calcium and higher phosphorus levels in patients with NCPHPT (all P < .05). The only biochemical difference between patients with NCPHPT and the controls was a higher level of mean parathyroid hormone in patients with NCPHPT. There were no differences in cardiovascular risk factors between patients with NCPHPT and PHPT and the controls. Hypertension was the most frequent cardiovascular risk factor, diagnosed in 65% of patients with PHPT. This high prevalence was not statistically significant compared with that observed in patients with NCPHPT (59%) and in the controls (30%). Echocardiography parameters were not different between patients with NCPHPT and PHPT and the controls when subdivided according to the presence of hypertension (ANOVA followed by Bonferroni correction).ConclusionIn a population with a low cardiovascular risk, we found no differences in cardiovascular risk factors and echocardiographic parameters between patients with NCPHPT and PHPT and the controls.     

Correlation of Body Mass Index and Age with Osteoporosis Probability in Patients with Primary Hyperparathyroidism

ObjectiveCurrently, there are limited markers to predict the osteoporosis probability in patients with primary hyperparathyroidism. We studied the relationship between various parameters and results of DXAs at various skeletal sites.MethodsRetrospective review of data for 218 patients with primary hyperparathyroidism was performed. Age, BMI, bone mineral density, serum total calcium, ionized calcium, intact parathyroid hormone, albumin, alkaline phosphatase, phosphate, 25-hydroxy vitamin D, 1,25-dihydroxy vitamin D, 24-hour urinary calcium levels and parathyroid tumor weight were analyzed. Two different statistical models- linear regression and multivariate logistic regression were performed.ResultsAt the lumbar spine, with the linear model, BMI (P < .001), alkaline phosphatase (P < .001), and ionized calcium (P < .001) significantly correlated with T scores; whereas with the logistic model, BMI was the only variable predicting osteoporosis probability.At the femoral neck, BMI (P < .022), 25-hydroxy vitamin D (P < .001), 1,25-dihydroxy vitamin D (P < .034) correlated with T scores; whereas both BMI (P < .029) and age (P < .051) were the significant variables that predicted osteoporosis.At the total hip, BMI (P < .001) and age (P < .001) correlated with T scores; whereas with the logistic model, only BMI (P < .016) predicted osteoporosis. At the forearm, a model could not be generated due to limited number.ConclusionIn patients with primary hyperparathyroidism, BMI strongly correlated with T scores and probability of osteoporosis.     

Cystic Parathyroid Adenomas: An Enigmatic Entity and Role of Tc-99 m Sestamibi Scintigraphy

ObjectiveFunctional cystic lesion of the parathyroid gland is a rare cause of primary hyperparathyroidism (PHPT). They have been postulated to arise from the hemorrhage and cystic degeneration in the parathyroid adenoma (PA). We intended to analyze their scintigraphic and histopathological findings since available literature is sparse.MethodsDual-phase ^{99 m}Tc-sestamibi planar and SPECT/CT scans performed from January 2014 to January 2020 in patients presenting with PHPT were retrospectively analyzed. The clinical, biochemical, and ultrasound features were collected. Planar and SPECT/CT imaging parameters were analyzed. Detailed histopathological analysis, along with post-surgical clinical and biochemical features of the patients who underwent surgery, was reviewed with a mean follow-up of 21.8 ± 20.1 months.ResultsOf the 979 scans analyzed, 10 showed cystic parathyroid lesions (M:F- 3:7, mean age 45.6 ± 15 years, range: 23-66). The predominant presenting features in patients were abdominal pain and renal stone disease, present in 60% of the patients. On planar scintigraphy, 90% of the patients had tracer avid distinct lesions, whereas tracer activity was seen in the solid part of the cystic lesions in all 10 patients on SPECT/CT, with cystic areas showing an attenuation of 23.1 ± 7.6 HU. Eight of these patients underwent surgery, with all showing PA with cystic changes on histopathology. Two of these patients also showed hemorrhage within the cystic spaces.ConclusionHemorrhage within a PA may give rise to cystic parathyroid lesions with PHPT. ^{99 m}Tc-sestamibi scintigraphy with dual-phase imaging and SPECT/CT may help in detecting this rare entity.     

The Added Value of Second-Look Ultrasound in Patients With Primary Hyperparathyroidism With Discordant or Negative Previous Imaging Findings

ObjectiveThe preoperative localization for patients with primary hyperparathyroidism with negative or discordant previous imaging results has always been a difficult problem to be solved in clinical practice. Second-look ultrasound (US) is a viable but underestimated method. This study aimed to assess the added value of second-look US and explore the attributing factors.MethodsAmong 711 surgically confirmed patients with primary hyperparathyroidism, 63 patients with negative or discordant first-time US and ^99mTc-MIBI imaging results were retrospectively studied. All 63 patients underwent second-look US, and the results were compared with intraoperative findings and histopathologic diagnosis. The diagnostic value of second-look US was calculated, and the reasons for changed second-look US results were analyzed.ResultsSixty-three parathyroid lesions were found in 63 patients. The sensitivity, positive predictive value, and accuracy of second-look US were 92.1%, 95.1%, and 88.1%, respectively. Comparing the results of first-time and second-look US, we found that 54.0% of the patients got benefits from second-look US because 34 patients with negative results in the first-time US revealed localization with second-look US. Second-look US was more likely to produce changes in results for lesions with a lower location (OR, 3.23; 95% CI, 1.11-9.43, P < .05) and larger length-to-thickness ratio (3.0 vs 2.4, P < .05).ConclusionSecond-look US is a promising method to determine preoperative localization in patients with negative or discordant results of previous imaging findings. Lesions with elongated shape and lower location are more expected to be detected in second-look US when missed at the first time.     

Parathyroid Carcinoma: An Experience from the Indian Primary Hyperparathyroidism Registry

ObjectiveTo 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.MethodsThis is a retrospective analysis of data from the Indian primary hyperparathyroidism registry.ResultsOf 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.ConclusionAccurate 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.     

Tumor Volume Can Be Used as a Parameter Indicating the Severity of Disease in Parathyroid Cancer

ObjectiveTo determine whether tumor volume and tumor size are related to disease severity in parathyroid cancer (PC).MethodsPatients treated for PC at our institution were retrospectively identified. Data were collected about clinical and pathologic characteristics, laboratory parameters, tumor volume, recurrence, metastasis, and mortality. Correlation analysis was applied to laboratory parameters, tumor volume, and tumor size in PC patients.ResultsThe study included 20 patients diagnosed with PC at our center. The median follow-up was 33 months. Serum calcium (median, 12.5 mg/dL), serum parathormone (PTH) (median, 743 pg/mL), and serum alkaline phosphatase (ALP) (median, 298 U/L) levels were found to be increased, and 25-hydroxyvitamin D (25[0H)D) (median, 12.3 ng/mL) and serum phosphorus (median, 2.1 mg/dL) levels were decreased. Magnesium level was within normal limits (median, 1.9 mg/dL). The median tumor volume was 5.7 mL and median tumor size was 2.5 cm. Significant positive correlations were found between tumor volume and calcium, ALP, and PTH levels. A significant negative correlation was found between tumor volume and 25(OH)D level. There were no significant correlations between tumor size and calcium, ALP, PTH, and 25(OH)D.ConclusionThese results found that the tumor volume affected PTH, calcium, ALP, and 25(OH)D levels. The morbidity and mortality associated with PC were usually associated with PTH secretion and hypercalcemia. Therefore, tumor volume may be a more effective parameter than tumor size when evaluating the severity of disease.     

Diagnostic Values of Intraoperative (1-84) Parathyroid Hormone Levels are Superior to Intact Parathyroid Hormone for Successful Parathyroidectomy in Patients With Chronic Kidney Disease

ObjectivePersistent secondary hyperparathyroidism (SHPT) may occur because of residual cervicothoracic parathyroids in parathyroidectomy (PTX) patients with chronic kidney disease. We prospectively compared the predictive values of intraoperative plasma (1-84) parathyroid hormone (PTH) and intact PTH (iPTH) levels to improve the safety and efficacy of PTX.MethodsWe included 100 healthy controls, 162 stage 5 chronic kidney disease patients without SHPT, and 214 patients who underwent PTX because of SHPT. Plasma iPTH and (1-84) PTH levels were measured before incision (io-iPTH0 and io-[1-84]PTH0, respectively) and 10 minutes (io-iPTH10 and io-[1-84]PTH10, respectively) and 20 minutes (io-iPTH20 and io-[1-84]PTH20, respectively) after removing all parathyroids. The percentage reduction of iPTH and (1-84) PTH at 10 minutes (io-iPTH10% and io-[1-84]PTH10%, respectively) and 20 minutes (io-iPTH20%, and io-[1-84]PTH20%, respectively) was calculated. iPTH and (1-84) PTH were measured using second- and third-generation PTH assays, respectively.ResultsCompared with the controls and non-PTX patients, the PTX group had more obvious mineral metabolism disorders. There were 187 successful PTXs, 19 patients with persistent SHPT, and 8 patients lost to follow-up. The receiver operating characteristic curves revealed that io-(1-84)PTH10% >86.6% and io-(1-84)PTH20% >87.5% suggested successful PTX. The sensitivity of io-iPTH20% and io-(1-84)PTH20% were higher than those at the timepoint of 10 minutes. Moreover, the specificity and sensitivity of the (1-84) PTH reduction percentage were superior to that of iPTH.ConclusionIntraoperative reduction percentages of plasma (1-84) PTH levels are superior to iPTH for accurately predicting successful PTX, especially at 20 minutes after all cervicothoracic parathyroids had been resected.     

A Parathyroid Hormone–Guided Calcium and Calcitriol Supplementation Protocol Reduces Hypocalcemia-Related Readmissions Following Total Thyroidectomy

ObjectiveTo determine the effect of a 4-hour postoperative serum parathyroid hormone (PTH)–guided calcium (Ca) and calcitriol supplementation protocol on the incidence of hypocalcemia and hospital readmissions in patients undergoing total thyroidectomy.MethodsThis was a single-institution, retrospective chart review of patients who underwent total thyroidectomy; 148 and 389 of the patients underwent surgery prior to and after the protocol implementation, respectively. The risk of hypocalcemia was stratified as low (PTH level of >30 pg/mL), medium (15-30 pg/mL), and high (<15 pg/mL), using serum PTH values obtained 4 hours postoperatively. Hypocalcemia was defined as a total serum Ca level of <8 mg/dL. Baseline demographic and operative characteristics and postoperative outcome were recorded for both groups. The Fisher exact test and Wilcoxon rank sum test were used to compare the characteristics of the 2 groups. A multivariate logistic regression model was applied to account for potentially confounding variables.ResultsPostoperative hypocalcemia occurred significantly less frequently in the protocol group compared with that in the preprotocol group (10.3% vs 20.9%, P = .002). The reduction in hypocalcemia in the protocol group was observed in both patients with (16.3% vs 25.6%) and without (8.4% vs 19.3%) cervical lymph node dissection. The protocol group had a significantly lower incidence of hospital readmission events than the preprotocol group (1.0% vs 4.7%, P = .013).ConclusionCompared with a historical cohort, a PTH-guided protocol for Ca and calcitriol supplementation significantly reduces the postoperative hypocalcemia and hospital readmission rates in patients undergoing total thyroidectomy.     

Parathyroidectomy Is Associated With Reversed Nondipping Heart Rate That Impacts Mortality in Chronic Kidney Disease Patients

ObjectiveNondipping heart rate (HR), defined as a night/day HR ratio >0.90, has been associated with increased mortality in epidemiologic studies. However, its prognostic value in stage 5 chronic kidney disease (CKD5) patients and the effects of parathyroidectomy (PTX) on nondipping HR remain unknown.MethodsThis case-control study of 162 healthy controls and 502 CKD5 patients was performed between 2011 and 2018, in which CKD5 patients were further divided into non-PTX (n = 186) and severe secondary hyperparathyroidism (SHPT) with PTX (n = 316) subgroups. Each participant underwent 24-hour Holter monitoring for HR ratio. Mortality was followed up in CKD5 patients (median time: 46.0 months).ResultsThe HR ratio in CKD5 patients was higher than in controls (0.92 ± 0.08 vs 0.81 ± 0.08, P <.001), associated with a 44% increase in mortality risk per 0.1 increment (hazard ratio, 1.44; 95% CI: 1.02-2.03; P =.04), and was positively related to serum intact parathyroid hormone levels (P <.001). PTX reversed nondipping HR in SHPT patients (n = 50, median time: 6.3 months, P <.001). Survival probabilities for PTX (n = 294) were better than non-PTX (n = 47) (hazard ratio, 0.31; 95% CI: 0.14-0.67; P <.01) in SHPT patients (serum intact parathyroid hormone >500.0 pg/mL).ConclusionCKD5 patients displayed a nondipping HR pattern, which is a prognostic marker of all-cause mortality. PTX for SHPT patients was associated with a reversal in nondipping HR ratio, which may mediate a better outcome.     

Association of Serum Parathyroid Hormone Levels With All-Cause and Cause-Specific Mortality Among U.S. Adults

ObjectiveTo examine whether parathyroid hormone (PTH) is associated with mortality among U.S. adults.MethodsThis study included 8286 U.S. adults aged ≥20 years with a measurement of serum intact PTH from the National Health and Nutrition Examination Survey 2003-2006 linked to national mortality data through 2015. Multivariable Cox proportional hazard regression models were employed to estimate the adjusted hazard ratio (aHR) of all-cause and cause-specific (cardiovascular and cancer) mortality according to intact PTH levels (low or low-normal, <38; middle-normal, 38-56; high-normal, 57-74; high, >74 pg/mL). We also stratified the analyses by serum albumin-adjusted calcium and 25-hydroxy vitamin D (25OHD) levels.ResultsDuring a median follow-up of 10.1 years, the mean age was 49 years, and 48% were men. After adjusting for potential confounders, both the high-normal and high PTH groups showed higher risks of all-cause mortality than the low or low-normal PTH group (high-normal PTH, aHR, 1.28; 95% confidence interval [CI], 1.10-1.48; high PTH, aHR, 1.42; 95% CI, 1.19-1.69]. When stratified by calcium and 25OHD levels, the association between high PTH and mortality was also found among participants with albumin-adjusted calcium levels of ≥9.6 mg/dL (aHR, 1.53; 95% CI, 1.17-2.01) and those with 25OHD levels of ≥20 ng/mL (aHR, 1.46, 95% CI, 1.17-1.82). We found no evidence of the increased cause-specific mortality risks in the high PTH group.ConclusionHigher PTH levels were associated with an increased risk of all-cause mortality, particularly among participants with albumin-adjusted calcium levels of ≥9.6 mg/dL or 25OHD levels of ≥20 ng/mL.     

Differences in Primary Hyperparathyroidism Between Pre- and Postmenopausal Women in India

ObjectivePrimary hyperparathyroidism (PHPT) is a common endocrine disorder in women which becomes more prevalent after menopause. In this study, we compared the demographic, clinical, and biochemical variables between premenopausal (pre-M) and postmenopausal (post-M) women with PHPT.MethodsA retrospective analysis (from 2005 to 2019) of enrolled women PHPT patients from an online Indian PHPT registry.ResultsOf the women with PHPT, 232 and 122 were pre-M and post-M, respectively. The number of post-M PHPT cases registered had a 3.3-fold increase in 2015-2019 from 2005-2009 compared with only a 2.5-fold increase in pre-M cases in the same duration. The majority were symptomatic (90%), although pre-M had a higher proportion of symptomatic than post-M (92% vs 85%; P = .04). Pre-M women showed more prevalence of osteitis fibrosa cystica than post-M women (28% vs 13%; P = .03), although hypertension and gallstone disease were seen more frequently in post-M PHPT women. Pre-M women had a significantly higher median PTH (403 vs 246 pg/mL; P = .02) and median alkaline phosphatase (202 vs 145 pg/mL; P = .02) than post-M women, and vitamin D deficiency was more common in pre-M women (58% vs 45%; P = .03). Gland localization, tumor weight, and disease cure rates did not differ according to menopausal status.ConclusionPHPT was more prevalent in pre-M women, although the number of post-M cases had significantly increased in the last 10 years. Pre-M women had generally more severe clinical and biochemical variables than post-M PHPT women.     

The Importance of Periodical Screening for Primary Hyperparathyroidism in a Pituitary Tumor Cohort in Searching Patients With MEN1 and Its Genetic Profile

ObjectiveMultiple endocrine neoplasia type 1 (MEN1) is a rare genetic syndrome characterized by parathyroid, anterior pituitary, and/or duodenopancreatic neuroendocrine tumors. Studies have indicated that investigating primary hyperparathyroidism (pHPT) with subsequent genetic screening may be an essential tool for the early diagnosis of MEN1 in patients with pituitary tumors (PTs). This study aimed to investigate the presence of pHPT in patients with PTs and, subsequently, to screen for genetic mutations and related tumors in patients with MEN1 syndrome.MethodsThis study included 255 patients with PTs who were assessed for the presence of MEN1 by serum calcium and parathyroid hormone measurements. Mutation screening of the MEN1, CDKN1B, and AIP genes was performed in the index cases showing the MEN1 phenotype.ResultsFive patients with PTs presented a clinical condition compatible with MEN1. These patients had a younger age of onset and a more severe clinical condition. Genetic analysis identified a frameshift mutation in the MEN1 gene in one of the cases with the MEN1 phenotype, but point mutations in CDKN1B and AIP were not detected in any of these patients.ConclusionOur results show that periodic screening for pHPT in patients with PTs may be useful to detect MEN1 syndrome; thus, it is recommended in those patients with both findings a genetic analysis of MEN1 gene and an additional search of related tumors. By contrast, our data suggest that CDKN1B and AIP mutations do not seem to play a relevant role in the pathogenesis of MEN1.