Design From the period 2007-2016, a total of 55 parathyroidtumors (51 adenomas and 4 hyperplasias) with prominent inflammatory infiltrates were identified from more than 2000 parathyroidtumors in the pathology archives, and investigated by immunohistochemistry for CD4 ... No evidence of virus-like sequences in the parathyroidtumors could be found by transcriptome sequencing, suggesting that other factors may contribute to attract the immune system to the parathyroidtumor tissue ...
Immune System Diseases (1) Neoplasms (8), Parathyroid Adenoma (1), Autoimmune Diseases (1), more mentions
... after prior unsuccessful parathyroid exploration, were found to have ectopic parathyroidadenomas in the pyriform sinus... treated by either transoral laser or robotic resection of the parathyroidadenoma.After surgery, the patients had resolution of their hyperparathyroidism.Ectopic parathyroidadenomas in the pyriform sinus are rare, but should be considered ...
... were successfully operated while surgery was unsuccessful in one patient, despite BNE AbstractText: Our study results suggest that endocrinologist-performed US and parathyroid FNA with PTH wash-out increases the number and success of FP. In particular, patients with redo surgery may benefit from this procedure Keyword: 99mTc sestamibi scan. Keyword: Parathyroidadenoma focused surgery. Keyword: Parathyroid hormone wash-out.
... AUC=0.992) for differentiation of parathyroid lesions from thyroid tissue and lymph nodes. A cut-off value of 128.9% showed 95.8% sensitivity and 100% specificity for the identification of parathyroid lesions AbstractText: We propose that percentage arterial enhancement can be used as an objective radiological index for accurate identification of parathyroidadenoma/hyperplasia Keyword: arterial enhancement. Keyword: dual-phase CT.
Hyperparathyroidism (3), Hyperplasia (3), Parathyroid Adenoma (2), more mentions
... fluorocholine PET/CT detected 52 of 54 patients and 52 of 56 lesions with histopathologically proven parathyroidadenomas on patient-based and lesion-based analysis, respectively... the 3 imaging techniques tested simultaneously, FCH PET/CT was superior for accurate preoperative localization of parathyroidadenomas, especially for ectopic or small parathyroid lesions.
The parathyroid oxyphil cell content increases in patients with chronic kidney disease (CKD), and even more in patients treated with the calcimimetic cinacalcet and/or calcitriol for hyperparathyroidism. Oxyphil cells have significantly more calcium-sensing receptors than chief cells, suggesting that the calcium-sensing receptor and calcimimetics are involved in the transdifferentiation of a chief cell to an oxyphil cell type. Here, we compared the effect of the vitamin D analog paricalcitol (a less calcemic analog of calcitriol) and/or cinacalcet on the oxyphil cell content in patients with CKD to further investigate the genesis of these cells. Parathyroid tissue from four normal individuals and 27 patients with CKD who underwent parathyroidectomy for secondary hyperparathyroidism were analyzed. Prior to parathyroidectomy, patients had received the following treatment: seven with no treatment, seven with cinacalcet only, eight with paricalcitol only, or cinacalcet plus paricalcitol in five. Oxyphilic areas of parathyroid tissue, reported as the mean percent of total tissue area per patient, were normal, 1.03; no treatment, 5.3; cinacalcet, 26.7 (significant vs. no treatment); paricalcitol, 6.9 (significant vs. cinacalcet; not significant vs. no treatment); and cinacalcet plus paricalcitol, 12.7. Cinacalcet treatment leads to a significant increase in parathyroid oxyphil cell content but paricalcitol does not, reinforcing a role for the calcium-sensing receptor activation in the transdifferentiation of chief-to-oxyphil cell type. Thus, two conventional treatments for hyperparathyroidism have disparate effects on parathyroid composition, and perhaps function. This finding is provocative and may be useful when evaluating future drugs for hyperparathyroidism.
BACKGROUND: Primary hyperparathyroidism (PHPT) is one of the causes of osteoporosis and is known to increase the fracture risk of bone. However, multiple vertebral compression fracture due to PHPT is extremely rare.
CASE DESCRIPTION: A case of acute multiple vertebral compression fracture in a patient with PHPT is described. The fracture occurred suddenly without trauma. The patient had a low T-score (-4.4), and serum hyper-calcemia and phosphatemia were evident. On examination, serum parathyroid hormone (PTH) was found to be elevated, and PHPT was diagnosed by neck sonography and a 99m Tc-MIBI scan. Once the patient was diagnosed with PHPT, we performed subtotal parathyroidectomy and corrective spinal surgery for multiple compression fractures.
CONCLUSION: When a patient has multiple compression fractures without any trauma history and a very low T-score, the presence of other underlying diseases should be investigated.
Muscular and Skeletal Diseases (5) Hyperparathyroidism (3), Osteoporosis (2), more mentions
OBJECTIVES/HYPOTHESIS: To determine the effect of preoperative parathyroid hormone (PTH) level on the extent of surgery and the accuracy of parathyroid imaging in primary hyperparathyroidism.
STUDY DESIGN: Retrospective cohort.
METHODS: Final diagnosis of single-gland adenoma and its location versus multigland disease was established in this retrospective cohort study. Positive predictive value, negative predictive value, and accuracy of imaging were analyzed in relation to preoperative PTH levels.
RESULTS: Eighty-seven percent of the 218 patients enrolled in the study underwent unilateral targeted operation and had a 97.9% (95% confidence interval: 95.8%-100%) success rate. However, in patients with PTH <65 pg/mL, 28.6% had bilateral exploration compared to 10.3% in those with PTH ≥65 pg/mL (P = .042). In patients with PTH <65 pg/mL, 7/21 (33.3%) had inaccurate sestamibi findings compared to 24/174 (13.8%) in patients with PTH ≥65 pg/mL (P = .047).
CONCLUSIONS: Accuracy of sestamibi drops significantly, by threefold, in patients with mild primary hyperparathyroidism and PTH <65 pg/mL. Patients with PTH < 65 pg/mL have a 2.5-fold higher rate of bilateral operation to identify the hypersecreting gland(s) compared to patients with PTH ≥65 pg/mL.
LEVEL OF EVIDENCE: 4. Laryngoscope, 2017.
BACKGROUND: Secondary hyperparathyroidism (SHPT) is a serious major complication in hemodialysis patients with chronic kidney disease. Long-term maintenance of serum phosphate, calcium, and parathyroid hormone (PTH) levels in appropriate ranges in these patients is a major challenge. We investigated the efficacy and safety of long-term treatment with etelcalcetide, a novel intravenous calcimimetic, in Japanese SHPT patients on long-term hemodialysis.
METHODS: This study was a multicenter open-label study. A total of 191 hemodialysis patients with serum intact PTH (iPTH) > 240 pg/mL were enrolled. Etelcalcetide was administered thrice weekly for 52 weeks, with an initial dose of 5 mg and flexibility to adjust the dose between 2.5 and 15 mg and to adjust the dosing of concomitant medications for SHPT. The efficacy endpoint was the proportion of patients with serum iPTH decreased to the target range (60-240 pg/mL).
RESULTS: Serum iPTH levels decreased immediately after etelcalcetide was started. At the end of the study, 87.5% (95% confidence interval 81.4-92.2; 140/160 patients) of patients achieved target serum iPTH levels, with control of serum calcium and phosphate levels. Adverse events, mostly mild to moderate, were reported by 96.8% of patients and led to study discontinuation in 7.4% of patients. Nausea, vomiting, and symptomatic hypocalcemia were found in 4.7, 9.5, and 1.1%, with 0.5, 1.1, and 1.1% considered treatment-related.
CONCLUSIONS: Etelcalcetide effectively maintained serum iPTH, calcium, and phosphate levels in appropriate ranges with concomitant medications for SHPT for 52 weeks in Japanese hemodialysis patients, and was safe and well tolerated.
REGISTRATION NUMBER: JapicCTI-142665.
Idiopathic hypoparathyroidism is a rare and probable late disease associated with celiac disease that could be the result of endomysial antibody molecular cross-reactivity with parathyroid gland cells. It is possible that the length of exposure to these antibodies increases the risk for hypoparathyroidism. We present a case of symptomatic idiopathic hypoparathyroidism not controlled with outpatient calcium replacement therapy later discovered to have concomitant celiac disease.
Hypoparathyroidism (5), Celiac Disease (4), Hypocalcemia (1), more mentions
In recent years, there has been increasing interest in understanding the implications of diagnosing normocalcaemic primary hyperparathyroidism (nPHPT). Many patients hope that nPHPT might explain some of their symptoms, but surgeons hesitate to offer treatment to patients whose calcium levels are normal but whose parathyroid hormone (PTH) levels are elevated in the absence of secondary causes of hyperparathyroidism. This potential new diagnosis is not well understood and may lead to inappropriate investigation and possible unnecessary operations. However, because a significant number of patients with nPHPT progress to hypercalcaemic primary hyperparathyroidism (PHPT), some consider nPHPT to be an early or mild form of hypercalcaemia. Rather than being an indolent disease, nPHPT was reported to be associated with systemic complications similar to 'classical' PHPT, and hence there is growing interest to understand who should be offered surgical treatment and who should be monitored. Further standardisation of diagnostic definition, associated complications, patient selection, surgical management and long-term outcomes are necessary. The recommendations outlined in this review are based on limited evidence from non-randomised cohort studies and expert opinion.
PURPOSE: Hypoparathyroidism is a rare endocrine disorder for which replacement therapy of the missing parathyroid hormone is not the standard therapeutic option. Current standard treatment consists of calcium and vitamin D supplementation. The intake of calcium and vitamin D supplementation can lead to complications and therefore might negatively influence patients' quality of life.
METHODS: A systematic literature review was performed to assess the current knowledge on the influence of hypoparathyroidism on patients' quality of life. The literature search was conducted in PubMed and Web of Science; all relevant literature published by August 24, 2016, was included.
RESULTS: In total 372 records were found. After title and abstract screening, 14 studies remained for a full-text screening. The full-text screening resulted in five studies which were included into the systematic review. Comparing the results with a norm-based reference population, three studies reported lower SF-36 scores for hypoparathyroidism patients. Two studies showed a reduced quality of life in hypoparathyroidism patients when their results were compared to control populations.
CONCLUSION: Most hypoparathyroidism patients receiving standard treatment show stable calcium and vitamin D levels. However, hypoparathyroidism patients still report reduced quality of life and experience physical, mental, and emotional symptoms. Therefore, it is assumed that the lack of parathyroid hormone directly influences the patients' quality of life. This review indicates that patients with hypoparathyroidism have a reduced quality of life in comparison to norm-based populations or matched controls. Further studies are required to quantify the effect of hypoparathyroidism on patients' quality of life using disease-specific questionnaires and controlling for the co-morbidities and etiologies of the patients.
BACKGROUND: Urolithiasis may be the only presenting manifestation of primary hyperparathyroidism (PHPT), and early detection of PHPT in such patients may prevent future urolithiasis and other PHPT complications.
OBJECTIVES: To study the prevalence and predictors of PHPT in patients presenting with urolithiasis.
SUBJECTS & METHODS: Consecutive patients presenting with urolithiasis were evaluated for clinical and biochemical manifestations of PHPT with serum and urine calcium, serum intact parathyroid hormone and 25 (OH) vitamin D. We then compared the clinical and biochemical characteristics of patients presenting with urolithiasis with (group A) and without (group B) PHPT.
RESULTS: During the 3-year study period, 381 patients with urolithiasis were seen with a mean age of 38.5±13.9yrs. Nineteen of the 381 patients (5%) had histologically proven PHPT (Group A). Four patients in group A (21%) and 8 in group B (2%) had nephrocalcinosis (p<0.0001), multiple stones (n=>3), calcific pancreatitis and neuropsychiatric manifestations were more common in group A (p<0.0001). Presence of multiple or bilateral stones, and recurrent stone episodes predicted PHPT [OR 3.06 (CI: 0.87, 0.7)].
CONCLUSION: One out of every 20 patients with urolithiasis had PHPT, which is higher than the prevalence of PHPT in general population. Presence of nephrocalcinosis, multiple, bilateral and recurrent stone disease increased the risk of PHPT among stoneformers.
Urolithiasis (9), Hyperparathyroidism (3), Nephrocalcinosis (2), more mentions
PURPOSE: Parathyroid venous sampling (PAVS) is usually reserved for patients with persistent or recurrent hyperparathyroidism after parathyroidectomy with inconclusive noninvasive imaging studies. A retrospective study was performed to evaluate the diagnostic efficacy of super-selective PAVS (SSVS) in patients needing revision neck surgery with inconclusive imaging.
MATERIALS AND METHODS: Patients undergoing PAVS between 2005 and 2016 due to persistent or recurrent hyperparathyroidism following surgery were reviewed. PAVS was performed in all patients using super-selective technique. Single-value measurements within central neck veins performed as part of super-selective PAVS were used to simulate selective venous sampling (SVS) and allow for comparison to data, which might be obtained in a non-super-selective approach.
RESULTS: 32 patients (mean age 51 ± 15 years; 8 men and 24 women) met inclusion and exclusion criteria. The sensitivity and positive predictive value (PPV) of SSVS for localizing the source of elevated PTH to a limited area in the neck or chest was 96 and 84%, respectively. Simulated SVS, on the other hand, had a sensitivity of 28% and a PPV of 89% based on the predefined gold standard. SSVS had a significantly higher sensitivity compared to simulated SVS (p < 0.001).
CONCLUSION: SSVS is highly effective in localizing the source of hyperparathyroidism in patients undergoing revision surgery for hyperparathyroidism in whom noninvasive imaging studies are inconclusive. SSVS data had also markedly higher sensitivity for localizing disease in these patients compared to simulated SVS.
BACKGROUND: The optimal surgery for patients with renal hyperparathyroidism has been controversial, as either subtotal parathyroidectomy (subtotal PTX) or total parathyroidectomy with auto-transplantation (total PTX-AT) may be employed.
METHODS: Adult patients having subtotal PTX or total PTX-AT for secondary hyperparathyroidism were identified from the American College of Surgeons National Surgical Quality Improvement Program, 2005-2013.
RESULTS: Of 1130 patients, the majority (n = 765, 68%) underwent subtotal PTX. Total PTX-AT was associated with longer operative time (median 150 vs. 120 min, p < 0.001). Rates of complications, reoperation, readmission, and 30-day mortality were not significantly different. After adjustment, the odds of having a complication [OR 0.97, p = 0.88] and being readmitted within 30 days [OR 0.86 p = 0.62] were similar between the two procedures. Total PTX-AT was associated with prolonged hospital stay [Adjusted mean 5.0 vs. 4.1 days; (RR) 1.22, p < 0.001] compared to subtotal PTX.
CONCLUSIONS: Subtotal PTX and total PTX-AT have similar rates of complications, readmission, and 30-day mortality, but subtotal PTX is less likely to have extended hospital stay. These findings have important cost implications for patients, payers, and hospitals.
PURPOSE: Leptin has been implicated in bone metabolism, but the association with parathyroid gland function has not been fully clarified. This review aimed to summarize evidence of the association between leptin and hyperparathyroidism, both primary and secondary, elucidating the potential pathophysiologic and therapeutic consequences between leptin and parathyroid hormone, hopefully prompting the design of new studies.
RESULTS: Experimental studies indicate a positive loop between leptin and parathyroid hormone in primary hyperparathyroidism. Dissimilar, parathyroid hormone seems to inhibit leptin expression in severe secondary hyperparathyroidism. Data from clinical studies indicate higher leptin levels in patients with primary hyperparathyroidism than controls, but no association between parathyroid hormone and leptin levels, as well as a minimal or neutral effect of parathyroidectomy on leptin levels in patients with primary hyperparathyroidism. Clinical data on secondary hyperparathyroidism, mainly derived from patients with chronic kidney disease, indicate a potential inverse association between leptin and parathyroid hormone in some, but not all studies. This relationship may be affected by the diversity of morbidity among these patients.
CONCLUSIONS: Data from experimental studies suggest a different association between leptin and parathyroid hormone in primary and secondary hyperparathyroidism. Data from clinical studies are conflicting and potentially affected by confounders. More focused, well-designed studies are warranted to elucidate a potential association between leptin and parathyroid hormone, which may have specific clinical implications, i.e., targeting obesity and hyperleptinemia in patients with hyperparathyroidism.
Anti-Obesity and Weight Loss (2), Kidney Disease (1) Hyperparathyroidism (11), Obesity (2), Chronic Kidney Diseases (1), more mentions
BACKGROUND: Hypercalcemic crisis (HC) is a potentially life-threatening manifestation of primary hyperparathyroidism (PHPT). This study aimed to identify patients with PHPT at greatest risk for developing HC.
METHODS: This retrospective cohort study included patients with a preoperative calcium of at least 12 mg/dL undergoing initial parathyroidectomy for PHPT from 11/2000 to 03/2016. We compared those with HC, defined as needing hospitalization for hypercalcemia, to those without HC.
RESULTS: The study cohort included 29 patients (15.8%) with HC and 154 patients (84.2%) without HC. Demographics and comorbidities were similar between the groups. Patients with HC were more likely to have a history of kidney stones (31.0% versus 14.3%, P = 0.039), higher preoperative calcium (median 13.8 versus 12.4 mg/dL, P < 0.001), higher parathyroid hormone (PTH) (median 318 versus 160 pg/mL, P = 0.001), and lower vitamin D (median 16 versus 26 ng/mL, P < 0.001) than patients without HC. Cure rates with parathyroidectomy were similar, but nearly double the proportion of patients with HC had multigland disease (24.1 versus 12.3%, P = 0.12). In multivariable analysis, higher preoperative calcium (odds ratio [OR] 1.7, 95% confidence interval [CI] 1.1-2.5), higher PTH (OR 1.0, 95% CI 1.0-1.0), and kidney stones (OR 3.0, 95% CI 1.1-8.2) were independently associated with HC. A Classification and Regression Tree revealed that HC developed in 91% of patients with a calcium ≥13.25 mg/dL and a Charlson Comorbidity Index ≥4.
CONCLUSIONS: These data indicate that calcium, PTH, and kidney stones are important in predicting who are at greatest risk of HC. The Classification and Regression Tree can further help stratify risk for developing HC and allow surgeons to expedite parathyroidectomy accordingly.
Hyperparathyroidism (4), Kidney Calculi (3), Hypercalcemia (2), more mentions
INTRODUCTION: Primary hyperparathyroidism is associated with a cluster of cardiovascular manifestations, including hypertension, leading to increased cardiovascular risk.
PURPOSE: The aim of our study was to investigate the ambulatory blood pressure monitoring-derived short-term blood pressure variability in patients with primary hyperparathyroidism, in comparison with patients with essential hypertension and normotensive controls.
METHODS: Twenty-five patients with primary hyperparathyroidism (7 normotensive,18 hypertensive) underwent ambulatory blood pressure monitoring at diagnosis, and fifteen out of them were re-evaluated after parathyroidectomy. Short-term-blood pressure variability was derived from ambulatory blood pressure monitoring and calculated as the following: 1) Standard Deviation of 24-h, day-time and night-time-BP; 2) the average of day-time and night-time-Standard Deviation, weighted for the duration of the day and night periods (24-h "weighted" Standard Deviation of BP); 3) average real variability, i.e., the average of the absolute differences between all consecutive BP measurements.
RESULTS: Baseline data of normotensive and essential hypertension patients were matched for age, sex, BMI and 24-h ambulatory blood pressure monitoring values with normotensive and hypertensive-primary hyperparathyroidism patients, respectively. Normotensive-primary hyperparathyroidism patients showed a 24-h weighted Standard Deviation (P < 0.01) and average real variability (P < 0.05) of systolic blood pressure higher than that of 12 normotensive controls. 24-h average real variability of systolic BP, as well as serum calcium and parathyroid hormone levels, were reduced in operated patients (P < 0.001). A positive correlation of serum calcium and parathyroid hormone with 24-h-average real variability of systolic BP was observed in the entire primary hyperparathyroidism patients group (P = 0.04, P = 0.02; respectively).
CONCLUSION: Systolic blood pressure variability is increased in normotensive patients with primary hyperparathyroidism and is reduced by parathyroidectomy, and may potentially represent an additional cardiovascular risk factor in this disease.
Cardiovascular Diseases (4) Hyperparathyroidism (9), Hypertension (4), more mentions
OBJECTIVE: Symptomatic primary hyperparathyroidism (PHPT) is thought to be related to increased cardiovascular morbidity and mortality. In our study, we aimed to investigate endothelial dysfunction and markers of subclinical atherosclerosis in patients with PHPT. Also we aimed to demonstrate the effect of vitamin D supplementation on these parameters.
MATERIALS AND METHODS: Twenty-nine patients followed by medical treatment (A), 25 preoperative (B) and 23 postoperative patients with PHPT (C), and 26 normocalcaemic subjects (D) were included. Groups were assessed by measurements of flow-mediated dilation (FMD), carotid intima-media thickness (CIMT), serum levels of sCD40L, high-sensitivity CRP (hs-CRP) and interleukin-8 (IL-8). Thirteen patients with low levels of 25-hydroxy-vitamin D (25OHD) in the medical treatment group were assessed before and 3 months after vitamin D replacement.
RESULTS: The median FMD was 5% in group A, 5.1% in group B, 7.6% in group C and 7.7% in group D. The FMD measurement in group A was significantly lower than groups C and D (P=.02) and was similar to the FMD measurement in group B. FMD measurements of group B were not significantly lower than groups C and D. In 13 patients with low 25OHD in group A, the median FMD increased to 7.07% from 4.71% after vitamin D replacement (P=.02).
CONCLUSION: Flow-mediated dilation was impaired in patients with PHPT, particularly in the medically observed group. Vitamin D supplementation seems to provide improvements in FMD in medically observed PHPT patients with low 25OHD levels, and this was the novel observation of our study.
Cardiovascular Diseases (1) Hyperparathyroidism (3), Atherosclerosis (1), more mentions
PURPOSE: Prostate cancer is the most common tumor in men. To the best of our knowledge a systematic assessment of bone and mineral abnormalities has not been performed in prostatic cancer patients consecutively enrolled.
METHODS: This study was therefore carried out to investigate changes of skeletal and mineral metabolism in patients with prostate cancer (n = 69). A population of patients with cancer of various origin was also investigated as a control group (n = 53), since a comparison with non-prostate cancer patients has not been previously reported.
RESULTS: In the prostatic cancer group, one patient had extremely high values of C-terminal Fibroblast Growth Factor 23, low values of tubular reabsorption of phosphate and very high values of bone alkaline phosphatase, suggesting the diagnosis of oncogenic osteomalacia. We found nine patients with primary hyperparathyroidism in the group of prostate cancer vs. only one in cancer patients group (p < 0.026). We stratified the population on the basis of Gleason score, prostate specific antigen and hormonal therapy. Using a generalized linear model with a logit link to predict the probability of developing primary hyperparathyroidism, only Gleason score, C-terminal fibroblast growth factor 23 and hormonal therapy had a significant effect (p < 0.05). Controlling for other covariates, a rise in fibroblast growth factor 23 increases the odds of developing primary hyperparathyroidism by 2% (p = 0.017), while patients with higher values of Gleason score have a much greater probability of developing primary hyperparathyroidism (log-odds = 3.6, p < 0.01). The probability decreases with higher values of Gleason score while on hormonal therapy; a further decrease was observed in patients on hormonal treatment and lower values of GS. Finally, lower grade of Gleason score without hormonal therapy have a significant protective factor (p < 0.01) decreasing the odds of developing primary hyperparathyroidism by 8%.
CONCLUSION: We showed a remarkable prevalence of primary hyperparathyroidism in men with prostate cancer; the multivariate analysis demonstrates that higher aggressiveness of prostate cancer, as determined by Gleason score, is a significant predictor of increased risk of developing primary hyperparathyroidism.