Subtotal Parathyroidectomy Research Articles

ГИПОКАЛЬЦИЕМИЯ ПОСЛЕ ПАРАТИРЕОИДЭКТОМИИ

The aim of the study was to estimate the frequency and timing of hypocalcemia after surgical treatment for primary, secondary and tertiary hyperparathyroidism. Materials and methods. 21 patients were operated for hyperparathyroidism, 15 - for primary (group 1), 6 - for secondary and tertiary (group 2). In I group the median baseline level of total serum calcium was 3.06 mmol/l, phosphorus0.9 mmol/l, and parathyroid hormone360 pmol/l. In II group all patients were on program dialysis for end-stage chronic kidney failure for at least five years. The median baseline serum total calcium level was 2.29 mmol/l, phosphorus2.64 mmol/l, and parathyroid hormone-1822 pmol/l. Results. A day after removal of the parathyroid adenoma (1 group) the level of calcium and phosphorus was normalized, the content of parathyroid hormone (median 21.4 pmol/l) significantly decreased. In one case (6.7%) on the fifth day there were clinical signs of hypocalcemia and the level of calcium decreased to 1.86 mmol/l. All patients of the second group underwent subtotal parathyroidectomy. After a day the level of parathyroid hormone significantly decreased (median227 pmol/l). The phosphorus content has returned to normal. The calcium level in all cases exceeded 2 mmol/l. On day 4-5 the total calcium content decreased and ranged from 1.14 mmol/l to 2.04 mmol/l. Four patients (66,7%) showed clinical signs of hypocalcemia. It was found that the development of hypocalcemia has a positive correlation of average value with the level of parathyroid hormone, phosphorus and negative with the content of calcium before surgery. Conclusion. The decrease in the level of total calcium with the development of clinical symptoms occurs on 4-5 days after surgery for primary hyperparathyroidism in 6.7% and for secondary or tertiary - in 66.7%. Risk factors for hypocalcemia are the baseline low level of calcium and high of parathyroid hormone, phosphorus.

Network meta-analysis of surgical treatment for secondary hyperparathyroidism.

Main surgical treatments for secondary hyperparathyroidism (SHPT) include subtotal parathyroidectomy (sPTX), total parathyroidectomy with autotransplantation (tPTX+AT), and total parathyroidectomy (tPTX); however, determining the best treatment is debatable. We conducted a network meta-analysis (NMA) comparing three treatments in terms of postoperative hypocalcemia (or hypoparathyroidism), postoperative recurrence, and reoperation. We searched PubMed, Medline, the Cochrane Library, and Embase for relevant research from inception to July 30, 2019. We performed our Bayesian NMA using R 3.51 software to assess odds ratios (OR) and 95% confidence intervals (CI). Network and forest plots displayed study outputs. Potential publication bias was assessed with funnel plots using software Stata/MP 13.0. Twenty-six articles comprising 5063 patients were included in our NMA, which showed that postoperative hypocalcemia (or hypoparathyroidism) occurred more frequently in tPTX than in sPTX (OR=3.50, 95% CI 1.10-11.0) or tPTX+AT patients (OR=1.80, 95% CI 0.66-5.20). Regarding postoperative hypocalcemia (or hypoparathyroidism), there was no significant difference between sPTX and tPTX+AT (OR=0.53, 95% CI 0.24-1.10). As for recurrence rates, statistically significant differences were observed between sPTX and tPTX (OR=25.0, 95% CI 5.1-260), tPTX+AT and tPTX (OR=20.0, 95% CI 4.2-200), and sPTX and tPTX+AT (OR=1.30, 95% CI 0.65-2.50). Regarding reoperation rates, sPTX experienced higher incidence compared with tPTX+AT (OR=1.20, 95% CI 0.53-2.70) or tPTX patients (OR=2.70, 95% CI 1.20-14.00). TPTX+AT is recommended as the most efficient and safe surgical SHPT treatment with minimal adverse effects. Large-scale randomized controlled trials are recommended to confirm the NMA results.

Clinical Features, Treatment, and Surveillance of Hyperparathyroidism-Jaw Tumor Syndrome: An Up-to-Date and Review of the Literature.

Hyperparathyroidism-jaw tumor (HPT-JT) syndrome is an autosomal dominant disorder characterized by parathyroid tumors in association with fibro-osseous jaw tumors and uterine and renal lesions. HPT-JT syndrome is caused by germline mutations of the cell division cycle 73 (CDC73) gene that encodes the parafibromin, a 531-amino acid protein with antiproliferative activity. Primary hyperparathyroidism is the main finding of HPT-JT syndrome, usually caused by a single-gland parathyroid involvement (80% of cases), at variance with other variants of hereditary hyperparathyroidism, in which a multiglandular involvement is more frequent. Moreover, parathyroid carcinoma may occur in approximately 20% of cases. Surgery is the treatment of choice for primary hyperparathyroidism, but the extent of surgery remains controversial, varying between bilateral neck and focused exploration, with subtotal or limited parathyroidectomy. Recently, more limited approaches and parathyroid excisions have been suggested in order to decrease the risk of permanent hypoparathyroidism, the main surgical morbidity following more extensive surgical approaches. Ossifying fibromas of the mandible or maxilla may present only in a minority of cases and, even if benign, they should be surgically treated to avoid tumor growth and subsequent functional limitations. Benign and malignant uterine involvement (including leiomyomas, endometrial hyperplasia, adenomyosis, multiple adenomyomatous polyps, and adenosarcomas) is the second most common clinical feature of the syndrome, affecting more than 50% of CDC73-carrier women. Genetic testing should be performed in all family members of affected individuals, in young patients undergoing surgery for primary hyperparathyroidism, or in presence of other associated tumors, allowing early diagnosis and prompt treatment with more tailored surgery. Moreover, CDC73 mutation carriers should be also periodically screened for primary hyperparathyroidism and the other associated tumors. The present review was aimed to summarize the main clinical features of HPT-JT syndrome, focusing on genetic screening and surgical treatment, and to revise the available literature.

Single gland excision for MEN1-associated primary hyperparathyroidism.

Guidelines advocate subtotal parathyroidectomy (SPTX) or total parathyroidectomy with autotransplantation (TPTX) with bilateral cervical thymectomy for primary hyperparathyroidism (pHPT) associated with multiple endocrine neoplasia type 1 (MEN1). However, both procedures are associated with a significant risk of permanent hypoparathyroidism. The aim of the current study was to compare long-term results of either single gland excision (SGE, 1-2 glands), SPTX and TPTX for the treatment of MEN1-associated pHPT. Data of genetically confirmed MEN1 patients who underwent surgery for pHPT between 1987 and 2017 were retrieved from a prospective database and were retrospectively analysed. Eighty-nine MEN1 patients underwent either TPTX (n=38, 42.7%), SPTX (n=23, 25.8%) or SGE (n=28, 31.5%). The rate of disease persistence after initial surgery was 2.6%, 0% and 14.2% in the TPTX, SPTX and SGE groups, respectively. After median follow-up of 112 (range 7-411) months, the rate of recurrent pHPT was significantly higher in the SGE group (n=19, 21.3%) compared with the TPTX (n=4, 4.4%, P=.001) and the SPTX (n=9, 10.1%, P=.03) groups. Analysis of the recurrence-free time among the surgical groups revealed a significant difference (P=.036). The median time to recurrence was significantly shorter after SGE (101, range 3-301months) than after SPTX (139, range 28-278months, P=.018) and TPTX (204, range 75-396months, P=.049). Twelve (32%) patients who underwent TPTX developed permanent hypoparathyroidism compared with only 4 (17%, P=.06) in the SPTX and 0 in the SGE group (P=.001). Given the high rate of postoperative permanent hypoparathyroidism after TPTX and SPTX, SGE is a valid option for the treatment of MEN1-associated pHPT.

Osteocalcin is an Independent Predictor for Hungry Bone Syndrome After Parathyroidectomy.

Hungry bone syndrome is characterized by prolonged and severe hypocalcemia following parathyroidectomy. Previously, we reported that preoperative alkaline phosphatase is a major factor predicting prolonged hospital stay. Nonetheless, some patients with low alkaline phosphatase levels presented with hungry bone syndrome, suggesting that additional factors may play a role. From September 2010 to December 2017, consecutive dialysis patients who underwent parathyroidectomy for secondary hyperparathyroidism were analyzed. Length of hospital stay was used as a surrogate marker for postoperative bone hunger. A total of 260 patients were included in the study. The median postoperative hospital stay was 3days, and 69 (27%) patients had a stay longer than 3days. Multivariate logistic regression analysis revealed that alkaline phosphatase (odds ratio [OR] = 1.005), osteocalcin (OR = 1.001), and subtotal parathyroidectomy (OR = 0.061) were associated with prolonged hospital stay. Multivariate linear regression analysis indicated that age (β = - 0.170), alkaline phosphatase (β = 0.430), and osteocalcin (β = 0.166) were correlated with the length of stay. After surgery, the median osteocalcin level increased from 264 to 478ng/mL (P < 0.001). Alkaline phosphatase is the main predictor of hungry bone syndrome after parathyroidectomy, and preoperative osteocalcin is an additional independent predictor. Patients with a high osteocalcin level may prone to have a higher demand for calcium supplementation.

MEN1-associated primary hyperparathyroidism in the Spanish Registry: clinical characterictics and surgical outcomes.

Primary hyperparathyroidism is the most frequent manifestation of multiple endocrine neoplasia type 1 (MEN1) syndrome. Bone and renal complications are common. Surgery is the treatment of choice, but the best timing for surgery is controversial and predictors of persistence and recurrence are not well known. Our study describes the clinical characteristics and the surgical outcomes, after surgery and in the long term, of the patients with MEN1 and primary hyperparathyroidism included in the Spanish Registry of Multiple Endocrine Neoplasia, Pheochromocytomas and Paragangliomas (REGMEN). Eighty-nine patients (49 men and 40 women, 34.2 ± 13 years old) were included. Sixty-four out of the 89 underwent surgery: a total parathyroidectomy was done in 13 patients, a subtotal parathyroidectomy in 34 and a less than subtotal parathyroidectomy in 15. Remission rates were higher after a total or a subtotal parathyroidectomy than after a less than subtotal (3/4 and 20/22 vs 7/12, P < 0.05), without significant differences in permanent hypoparathyroidism (1/5, 9/23 and 0/11, N.S.). After a median follow-up of 111 months, 20 of the 41 operated patients with long-term follow-up had persistent or recurrent hyperparathyroidism. We did not find differences in disease-free survival rates between different techniques, patients with or without permanent hypoparathyroidism and patients with different mutated exons, but a second surgery was more frequent after a less than subtotal parathyroidectomy.

Long-Term Outcomes of Parathyroidectomy in Hyperparathyroidism-Jaw Tumor Syndrome: Analysis of Five Families with CDC73 Mutations.

Hyperparathyroidism-jaw tumor syndrome (HPT-JT) is a rare disease caused by CDC73 germline mutations, with familial primary hyperparathyroidism (pHPT), ossifying jaw tumors, genito-urinary neoplasms. The present study was aimed at determining the long-term postoperative outcome of parathyroidectomy in HPT-JT. A retrospective analysis of a single-center series of 20 patients from five unrelated HPT-JT families undergoing parathyroid surgery was performed. Pathology confirmed a single-gland involvement in 95% of cases at onset. Parathyroid carcinoma occurred in three patients undergoing en-bloc parathyroidectomy and thyroid lobectomy: parathyroid benign lesions in 17 patients undergoing subtotal parathyroidectomy for evident multiglandular involvement (n = 1) or selective parathyroidectomy for single-gland involvement (n = 16), during bilateral (n = 13) or targeted unilateral neck exploration (n = 7). At a median overall follow-up of 16years (range 2.5-42), patients with parathyroid carcinoma had a persistent/recurrent disease in 66.6%; patients with benign lesions had recurrent pHPT in 23.5% after a prolonged disease-free period; recurrent benign pHPT occurred slightly more often in cases of discordant preoperative localization (60% vs 9%; p = 0.06). pHPT in HPT-JT is generally characterized by a benign and single-gland involvement, with a relatively increased risk of malignancy (15%). Parathyroid carcinoma needs extensive surgery because of high risk of permanent/recurrent disease (66.6%). In benign involvement, targeted unilateral exploration with selective parathyroidectomy may be effective in cases of concordant single-gland localization at preoperative localization imaging techniques. Bilateral neck exploration with subtotal parathyroidectomy might be preferred in cases of negative or discordant preoperative localization, because of the increased risk of multiglandular involvement and long-term recurrences (23.5%).

Subtotal parathyroidectomy versus total parathyroidectomy with autotransplantation for secondary hyperparathyroidism: an updated systematic review and meta-analysis.

The optimal surgical approach of parathyroidectomy for patients with secondary hyperparathyroidism (SHPT) has been controversial. The updated meta-analysis aimed to compare the effectiveness of subtotal parathyroidectomy (SPTX) versus total parathyroidectomy with autotransplantation (TPTX + AT). A thorough systematic search was performed on the databases of PubMed, EMBASE, and Cochrane library to identify eligible studies. Data were extracted and pooled into a meta-analysis. The primary outcomes were the symptomatic improvement, radiological changes, hypocalcemia rate, the requirement for vitamin D analogues, time to recurrence, recurrence, persistence, and reoperation rates of SPTX versus TPTX + AT. A total of 18 studies with 3656 patients (1864 patients in SPTX and 1792 patients in TPTX + AT group) were included, and 15 studies were included in quantitative synthesis. No significant difference was observed in symptomatic improvement (93.3%, 89.0%; P = 0.99), radiological changes (85.4%, 85.3%; P = 0.91), hypocalcemia rate (16.6%, 18.1%; P = 0.29), persistence rate (6.1%, 2.0%; P = 0.16), time to recurrence (mean difference 1.46; P = 0.87), recurrence rate (9.2%, 7.1%; P = 0.76), and reoperation rate (5.3%, 5.8%; P = 0.66) between SPTX and TPTX + AT groups. Longer operative time (150 vs. 120min), prolonged in-hospital stay (5.0 vs. 4.1days), lower 1-month serum calcium level, and higher requirement for vitamin D analogues at 12months were significantly observed in patients who underwent TPTX + AT compared to SPTX. The two surgical approaches were both effective at controlling SHPT in clinical and laboratory terms. However, most of the data shown were not statistically significant. It was acceptable that surgeons chose either SPTX or TPTX + AT for SHPT.

Coexistent papillary thyroid carcinoma diagnosed in surgically treated patients for primary versus secondary hyperparathyroidism: same incidence, different characteristics

BackgroundThe coexistence of hyperparathyroidism and thyroid cancer presents important diagnostic and management challenges. With minimally invasive parathyroid surgery trending, preoperative thyroid imaging becomes more important as concomitant thyroid and parathyroid lesions are reported. The aim of the study was to evaluate the rate of thyroid cancer in patients operated for either primary (PHPT) or secondary hyperparathyroidism (SHPT).MethodsOur retrospective study included PHPT and SHPT patients submitted to parathyroidectomy and, when indicated, concomitant thyroid surgery between 2010 and 2017.ResultsParathyroidectomy was performed in 217 patients: 140 (64.5%) for PHPT and 77 (35.5%) for SHPT. Concomitant thyroid surgery was performed in 75 patients with PHPT (53.6%), and 19 papillary thyroid carcinomas (PTC) were found, accounting for 13.6% from all cases with PHPT and 25.3% from PHPT cases with concomitant thyroid surgery. Thirty-one of operated SHPT patients (40.3%) also underwent thyroid surgery and 9 PTC cases were diagnosed (11.7% of all SHPT patients and 29% of patients with concomitant thyroid surgery).We found differences between PHPT and SHPT patients (p < 0.001) with respect to age (54.6 ± 13y versus 48.8 ± 12y), female-to-male ratio (8:1 versus ~ 1:1), surgical technique (single gland parathyroidectomy in 82.8% PHPT cases; versus subtotal parathyroidectomy in 85.7% SHPT cases) and presurgical PTH (357.51 ± 38.11 pg/ml versus 1020 ± 161.38 pg/ml).Morphopathological particularities, TNM classification and multifocality incidence of PTC were similar in the two groups. All PTC from patients with SHPT were thyroid microcarcinomas (TMC, i.e. tumors with a diameter smaller than 1 cm), whereas seven out of the 19 cases with PTC and PHPT were larger than 1 cm.ConclusionsPTC was frequently and similarly associated with both PHPT and SHPT irrespective of presurgical PTH levels. Thyroid tumors above 1 cm were found only in patients with PHPT. Investigators should focus also on associated thyroid nodular pathology in patients with PHPT.

MON-180 EVEROLIMUS ASSOCIATED OSTEONECROSIS OF THE JAW IN KIDNEY TRANSPLANT RECIPIENT

Mammalian target of rapamycin (mTOR) inhibitors, used in kidney transplant recipients, inhibit T-cell activation and vascular endothelial growth factor (VEGF) pathways, thereby exerting antiproliferative and antiangiogenic effects. Osteonecrosis of the jaw (ONJ) is a serious side-effect of antiresorptive and anti-angiogenic therapies. We report a unique case of osteonecrosis of the jaw associated with use of everolimus in a kidney transplant recipient. A 65-year-old man with polycystic kidney disease and subtotal parathyroidectomy for tertiary hyperparathyroidism, received a deceased donor kidney transplant in 2015 with basiliximab, tacrolimus, mycophenolate and prednisolone immunosuppression. He suffered non-immune delayed graft function and recovered with a 12-month serum creatinine of 230umol/L (eGFR 25ml/min/1.73sq.m). Tacrolimus was changed to everolimus to optimise renal function and retard interstitial fibrosis secondary to CNI use. In November 2017, he presented with swollen gums and left maxillary tenderness with gingival inflammation, exposed maxilla and purulent discharge, indicating infective periodontal disease. He was managed conservatively with antibiotics and dental extractions. His renal function was stable on everolimus 1mg BD with a trough level (C0) at 3.0-4.0 ng/ml. Six months later, he had progressive severe pain limiting oral intake, with 10kg weight loss. A CT head showed progressive bony destruction of maxilla, erosion of the maxillary sinus floor and an oro-antral fistula, consistent with ONJ. Bone biopsy ruled out malignancy, showing necrotic bony trabeculae filled with bacteria. He had never received bisphosphonate, denosumab or radiotherapy. He was on everolimus 0.75mg BD (C0= 3.0ng/ml). Tests revealed relatively low bone turnover markers in the context of active osteonecrosis: parathyroid hormone (PTH) <1.1pmol/L (1.6-6.0pmol/L), procollagen type 1 N propeptide (P1NP) 17ug/L(15-80ug/L), alkaline phosphatase (ALP) 69 U/L (30-110U/L), and C-telopeptide (CTX) 432ng/L (100-600ng/L). In view of its anti-proliferative and possible inhibitory effects on bone turnover, everolimus was ceased. He underwent surgical exploration of the sinuses, debridement of the palate with full upper dental clearance. He was treated with teriparatide 20ug monthly to stimulate bone turnover. Four-months later, the osteonecrotic process had abated, the exposed bone was stable and there were signs of healing. His nutrition status improved and he gained back his lost weight. This is the first case of everolimus associated ONJ in a kidney transplant recipient, despite being on relatively low dose therapy. The suppression of bone resorption via parathyroidectomy and additional inhibitory effect of everolimus resulted in the uncoupling of bone resorption and formation processes. This case not only underlies the importance of considering the potential of ONJ with everolimus in transplant recipients, particularly in those with poor dentition, malignancy, hypoparathyroidism or previous parathyroidectomy, and renal bone disease but also indicates possible therapeutic role of teriparatide in this situation.

Management of primary hyperparathyroidism in pregnancy: a case series.

SummaryPrimary hyperparathyroidism (PHPT) is characterised by the overproduction of parathyroid hormone (PTH) due to parathyroid hyperplasia, adenoma or carcinoma and results in hypercalcaemia and a raised or inappropriately normal PTH. Symptoms of hypercalcaemia occur in 20% of patients and include fatigue, nausea, constipation, depression, renal impairment and cardiac arrythmias. In the most severe cases, uraemia, coma or cardiac arrest can result. Primary hyperparathyroidism in pregnancy is rare, with a reported incidence of 1%. Maternal and fetal/neonatal complications are estimated to occur in 67 and 80% of untreated cases respectively. Maternal complications include nephrolithiasis, pancreatitis, hyperemesis gravidarum, pre-eclampsia and hypercalcemic crises. Fetal complications include intrauterine growth restriction; preterm delivery and a three to five-fold increased risk of miscarriage. There is a direct relationship between the degree of severity of hypercalcaemia and miscarriage risk, with miscarriage being more common in those patients with a serum calcium greater than 2.85 mmol/L. Neonatal complications include hypocalcemia. Herein, we present a case series of three women who were diagnosed with primary hyperparathyroidism in pregnancy. Case 1 was diagnosed with multiple endocrine neoplasia type 1 (MEN1) in pregnancy and required a bilateral neck exploration and subtotal parathyroidectomy in the second trimester of her pregnancy due to symptomatic severe hypercalcaemia. Both case 2 and case 3 were diagnosed with primary hyperparathyroidism due to a parathyroid adenoma and required a unilateral parathyroidectomy in the second trimester. This case series highlights the work-up and the tailored management approach to patients with primary hyperparathyroidism in pregnancy.Learning points:Primary hyperparathyroidism in pregnancy is associated with a high incidence of associated maternal fetal and neonatal complications directly proportionate to degree of maternal serum calcium levels.Parathyroidectomy is the definitive treatment for primary hyperparathyroidism in pregnancy and was used in the management of all three cases in this series. It is recommended when serum calcium is persistently greater than 2.75 mmol/L and or for the management of maternal or fetal complications of hypercalcaemia. Surgical management, when necessary is ideally performed in the second trimester.Primary hyperparathyroidism is genetically determined in ~10% of cases, where the likelihood is increased in those under 40 years, where there is relevant family history and those with other related endocrinopathies. Genetic testing is a useful diagnostic adjunct and can guide treatment and management options for patients diagnosed with primary hyperparathyroidism in pregnancy, as described in case 1 in this series, who was diagnosed with MEN1 syndrome.Women of reproductive age with primary hyperparathyroidism need to be informed of the risks and complications associated with primary hyperparathyroidism in pregnancy and pregnancy should be deferred and or avoided until curative surgery has been performed and calcium levels have normalised.

Surgical Treatment of Hyperparathyroidism After Kidney Transplant

Chronic renal impairment is often associated with complex bone disorders. Improvement of secondary hyperparathyroidism (HPT) is expected after kidney transplant (KT) if the glomerular filtration rate is normalized. Patients and MethodsThere were 888 KTs performed between 1996 and 2017 at our department. A total of 558 general patients have been operated on for HPT during the same period. The 2 populations had a common part: out of the 558, a total of 69 (12.4%) were in end-stage renal failure when operated on because of secondary HPT. That also means that 7.8% of all KTs were associated with HPT. Retrospective, single-center analysis was performed using the patients' medical records. The aim of our study was to analyze the results of parathyroidectomies after KT. ResultsParathyroid surgery was performed on 19 patients (2.14%) because of HPT after KT. The applied surgical technique was total parathyroidectomy with autotransplant in 6 cases, subtotal parathyroidectomy in 3 cases, and selective parathyroidectomy in 10 cases. In all cases, histology revealed benign disease. Complications were observed in 10 cases (52%); there were 6 cases of postoperative hypocalcaemia (31.58%), 1 case of transient laryngeal recurrent nerve paresis (5.26%), and 6 cases of recurrent HPT (31.58%). SummaryThe first step of HPT management is calcimimetic drug treatment. It is essential to prevent possible complications with regular laboratory monitoring. If the proper conservative therapy is refractory or severe in complications, surgery should be chosen. If the patient is already waiting for a KT, it is worth performing the parathyroid surgery before KT. Close collaboration with endocrinologists and nephrologists is needed to achieve successful therapy.

SUN-LB085 Complicated Hungry Bone Syndrome Due to Tertiary Hyperparathyroidism in a Patient with Kidney Transplant: A Case to Remember

Introduction: Hyperparathyroidism with parathyroid hyperplasia can result from prolonged stimulation of parathyroid glands in chronic kidney disease which may persist after kidney transplant. Timing of parathyroidectomy is still matter of study. Here we present a case of hungry bone syndrome in a patient with tertiary hyperparathyroidism due to ESRD after subtotal parathyroidectomy 13 years after kidney transplant. Case presentation: A 54-year-old female, with past medical history of type 1 diabetes mellitus, celiac disease and tertiary hyperparathyroidism (status post living donor right kidney transplantation in 13 years ago) was admitted to the hospital for elective subtotal parathyroidectomy. The patient was previously being managed with vitamin D analogs, however, due to progression of her osteoporosis and systemic symptoms despite normal renal function after the transplant, decision was made to proceed for surgical intervention. The patient underwent subtotal parathyroidectomy (3 gland removal) and her postoperative period was complicated by the development of hungry bone syndrome. She developed persistent severe hypocalcemia with ionized calcium of 3.7mg/dl (normal range 4.5-5mg/dl) and total serum calcium of 6.1mg/dl (normal range 8.4-10mg/dl) associated with generalized weakness and perioral numbness and tingling which was treated with high doses of calcitriol and intravenous calcium gluconate. Frequent electrolyte and EKG monitoring with appropriate supplementation was provided to maintain electrolyte balance and prevent cardiac arrhythmias. The patient was treated successfully and was discharged to home on oral medication after total 15 days of hospitalization once appropriate and steady calcium levels were reached. Discussion: Transient hypocalcemia is common after parathyroidectomy; however, hunger bone syndrome is a life-threatening complication after total or subtotal parathyroidectomy for the long-term tertiary hyperparathyroidism. Close postoperative monitoring and prompt treatment are necessary to treat the severe electrolytes deficiency, especially refractory hypocalcaemia. There are no clear recommendations about whether parathyroidectomy for tertiary hyperparathyroidism due to ESRD after kidney transplant is superior to that before kidney transplant in terms of decreasing the risk of development of Hunger Bone syndrome.

MON-531 Pattern of Health-Related Quality of Life Six Months after Parathyroidectomy in Patients with Multiple Endocrine Neoplasia Type 1 and Main Modifying Factors

Background: Surgery is the elective therapy for primary hyperparathyroidism (HPT) in patients with multiple endocrine neoplasia type 1 (MEN1). As MEN1 mutation carriers invariably will develop HPT up to 50 years, the annual periodic screening have allowed an early diagnosis of HPT in MEN1 syndrome, frequently before manifestation of clinical symptoms. Health-related quality of life (HR-QoL) both before after parathyroidectomy (PTx) has been poorly described. As the ideal timing to indicate PTx is yet controversial and undefined and, most recently, the value of less extensive surgeries has been considered for some groups, data on HR-QoL may be useful to clarify better these conflicting issues. Objectives: To investigate post-operative HR-QoL aspects of patients submitted to PTx for MEN1-related HPT (HPT/MEN1). Methods: Prospective analysis of HPT/MEN1 patients submitted to total PTx with immediate forearm autograft (TPTx+A) or subtotal parathyroidectomy (SPTx) in single institution. A psychologist applied Short Form 36 Health Survey Questionnaire immediately before and 6 months after surgery. Changes of both Physical Component Summary Score (PCS) and Mental Component Summary Score (MCS) were analyzed considering persistence of HPT, hypoparathyroidism and pancreatectomy after the PTx. Results: Of 19 patients (mean age 38.4±14.4, 7 men), 8 underwent TPTx+A and 11 had SPTx. Overall, median (interquartiles ranges) of pre-operative PCS and MCS were 73.8 (50.0-88.0) and 65.0 (44.5-83.2), respectively. At 6 months, median PCS was 71.2 (55.8-91.0) and median MCS was 80.2 (46.8-88.0). There were five (4, PTxT+A; 1, SPTx) patients with postoperative hypoparathyroidism, one with persistent HPT (SPTx) and 13 with normal parathyroid function (4, TPTx+A; 9, SPTx) six months after PTx. PCS worsened in four cases with hypoparathyroidism (80%) and in five euparathyroid (36%), but without statistical significance (p, 0.14). MCS worsened in four cases with hypoparathyroidism (80%), but in only one euparathyroid (7%) (p, 0.0061). The worst decrease of both PCS and MCS occurred in two patients submitted to pancreatectomy during the follow-up after parathyroidectomy (PCS decreased 79% in one case and 53% in the other; MCS decreased 75% and 37%, respectively). Conclusion: Hypoparathyroidism worsens the HR-QoL after PTx in HPT/MEN1, particularly in patients undergoing subsequent pancreatectomy.

SUN-499 An Unusual Case of a Misleading Elevated Parathyroid Hormone Level

Background: Subtotal parathyroidectomy with reimplantation of parathyroid tissue into the forearm might be necessary in less common cases of primary hyperparathyroidism, due to multiple adenomas, hyperplasia or ectopic adenoma. An elevated PTH level after surgery is concerning for persistent or recurrent disease but could also be due to blood sampling. We present a case of erroneously elevated PTH due to lab draws near implanted parathyroid tissue. Clinical Case: A 63 y.o. female presented for follow up in 2017. She had a history of hypercalcemia due to primary hyperparathyroidism and had resection of 2 parathyroid glands together with a thyroidectomy in 2007. She had persistent hypercalcemia afterwards, and was suspected to have an ectopic parathyroid adenoma in the mediastinum based on Sestamibi and contrast-enhanced CT scans. She had a transcervical thymectomy with resection of an anterior mediastinal parathyroid adenoma and reimplantation of parathyroid tissue into the left forearm in 2012. PTH and calcium levels normalized afterwards. Her medical history included hypertension, GERD, vitamin D deficiency, osteopenia and postsurgical hypothyroidism. She had no history of renal disease and no family history of parathyroid disorders. She took levothyroxine 100 mcg daily, and intermittently took ergocalciferol 50,000 IU weekly. On exam, she had a well healed thyroidectomy scar and no cervical lymphadenopathy. Her thyroid gland was not palpable. Labs showed an elevated PTH level of 1389 pg/mL (17-66), a normal calcium level of 9.2 mg/dL (8.4-10.5), and a low/normal 25-OH vitamin D level of 30 ng/mL (25-80). She had normal creatinine and TSH levels. There was concern for validity of the results, but repeat labs again revealed a significantly elevated PTH level of 4643 pg/mL. Calcium level was normal at 9.0 mg/dL, and 25-OH vitamin D was 22 ng/mL. Given concern for skewed lab results from implanted parathyroid tissue in the left arm, the PTH level was redrawn from both arms. The PTH level in the right arm was 25 pg/mL, and in the left arm was 2865 pg/mL, indicating variability based on location. PTH level was normal at subsequent visits when drawn from the right arm. Conclusion: Aberrant PTH levels can be seen if labs are drawn upstream from the graft site. Limited case report data showed a difference in PTH levels between the grafted forearm and the remote site ranged from 328 to 3643 ng/l. The frequency of this phenomenon has been estimated to be around 4% (1). If a clinician acts on spurious levels, the patient could be subjected to unnecessary testing or surgery. PTH levels should be drawn distant from the graft site, preferably in the other arm, to make sure that true systemic levels are obtained. Reference: 1) Khalil D, Kerr P. PTH monitoring after total parathyroidectomy with forearm autotransplantation: potential for spuriously high levels from grafted forearm. J Otolaryngol-Head N. 2017; 46:49.

SAT-232 Is There a Role for Genetic Testing in Guiding the Management of Primary Hyperparathyroidism in Pregnancy?

Introduction Primary hyperparathyroidism (PHPT) in pregnancy is rare, with a reported incidence of <1%. It is associated with serious maternal and foetal complications, and is genetically determined in ~10% of cases. Confirming a genetic diagnosis can guide management of inherited PHPT, and enables screening for syndrome-related diseases. This case series highlights the role of genetic testing in the tailored management of patients with PHPT in pregnancy. Clinical cases Case 1 is a 20 year old female who was diagnosed with PHPT at 5 weeks gestation after presentation with nausea. She was hypercalcaemic (2.78 mmol/L at diagnosis; 2.98 mmol/L pre-parathyroidectomy), had negative neck ultrasonography and a MEN1 mutation (exon 2, c.236_237del, p.(Pro79fs)) on genetic testing in pregnancy. After initial management with oral and IV rehydration, her severe symptomatic hypercalcaemia required treatment with open neck exploration and a 3 gland parathyroidectomy in the 2nd trimester. The standard surgical approach of a 3.5 gland parathyroidectomy was avoided due to the risk of inducing hypoparathyroidism. Intra-operative PTH dropped 53.8% post 3 gland parathyroidectomy. Parathyroid hyperplasia on histology was consistent with the diagnosis of MEN1 syndrome. The patient’s symptoms resolved post-operatively and foetal investigations are normal at 28 weeks gestation. She is receiving close obstetric follow-up including 3-weekly foetal growth scans due to the increased risk of IUGR. She was counseled on her increased risk of pancreatic and pituitary tumours and her 1st degree relatives are undergoing genetic screening. Case 2 is a 40 year old female with a known diagnosis of PHPT who was awaiting parathyroidectomy prior to pregnancy. She was hypercalcaemic (2.78 mmol/L at 7 weeks; 2.99 mmol/L pre-parathyroidectomy), and had a lower left parathyroid adenoma on ultrasound and pre-pregnancy SPECT-CT. Genetic testing was not performed as she was 40 at diagnosis and had no contributory family history. After failure of conservative management, parathyroidectomy of the left superior parathyroid gland was performed in the 2nd trimester. Histology results confirmed a left inferior parathyroid adenoma, concordant with the radiological findings. Her symptoms improved post-operatively; she is receiving close obstetric follow-up. Clinical lessons Genetic testing enables the management of PHPT to be tailored appropriately. It can better inform the surgical approach; including the need for subtotal parathyroidectomy and bilateral neck exploration in those cases at risk of multiple parathyroid gland disease, as demonstrated in our case with MEN1. Finally this case series demonstrates that surgical management of PHPT should be considered for select cases in pregnancy and thus far no maternal or foetal complications have arisen in these featured cases following surgical intervention.

MON-LB085 Blurred Vision and Hypocalcemia after Denosumab Injection in a Patient with Tertiary Hyperparathyroidism

Background: Denosumab is a human monoclonal antibody that targets the receptor activator of nuclear factor kappa B ligand (RANKL). It inhibits osteoclast-mediated bone resorption by binding to receptor. Denosumab prevents skeletal-related events (SREs) from osteoporosis and bone metastasis. However, there has been arising concern about hypocalcemia that is more vulnerable for patients with renal impairment due to elevated total osteoblast mass, coexisting calcitriol deficiency, inhibition by fibroblast growth factor 23. Clinical Case: A 66-year-old woman with ESRD on HD was transferred our endocrinology clinic for hypercalcemia and elevated intact parathyroid hormone(PTH); corrected calcium, 10.8 mg/dL(normal range: 8.5-10.2) and PTH, 164 pg/mL(8.00-72.00). I thought she had tertiary hyperparathyroidism(HPT). It is observed in patients with chronic secondary HPT who have been on dialysis therapy for years. I planned to examine sestamibi scan and neck ultrasonography to localize hypertrophied parathyroid glands. And then, I prescribed denosumab and a combined oral calcium/vitamin D supplement for her because she had persistent hypercalcemia and no medication for osteoporosis(DEXA T score is -3.8, -3.1 and -3.7 in L1-4, right femoral total, and neck respectively). After two weeks, she presented to our hospital for blurred vision of left eye. Papilledema and inferior visual field defect of left eye were observed in ophthalmology examination. Furthermore she had been receiving multiple dose of calcium and calcitriol injection during dialysis due to severe hypocalcemia at local dialysis center. Laboratory finding of dialysis clinic revealed corrected calcium decreased to 6.6 mg/dL(8.5-10.2) and PTH extremely increased to 3066 pg/mL(8.00-72.00). After rechecking her blood, laboratory work up showed corrected calcium, 7.7 mg/dL(8.5-10.2); 25(OH)vitamin D, 16.26 ng/mL(30-80); PTH, 1739 pg/mL(8.00-72.00). I examined sestamibi scan and neck USG. The results of sestamibi scan indicated hyperfunctioning parathyroid adenoma/hyperplasia in upper pole level of right thyroid gland and lower pole level of left thyroid gland that were matched with hypoechoic nodules of neck USG. We considered surgical interventions, total parathyroidectomy with autotransplantation or subtotal parathyroidectomy paying attention to postoperative complications such as hungry bone syndrome. Conclusion: Denosumab is an effective, tolerable anti-resorptive agent that has no nephrotoxicity, however, the risk of hypocalcemia is increasing, especially patients with chronic kidney disease. Hypocalcemia is a potentially life-threatening biochemical disorder that cause papilledema leading to the loss of vision. Therefore we should be aware of importance of monitoring calcium levels and renal function before and during denosumab therapy. Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. s presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.

Postsurgical Evaluation of Secondary Nephrogenic Hyperparathyroidism.

Parathyroidectomy is useful for the treatment of secondary hyperparathyroidism (SHPT) caused by chronic renal failure. The following three types of parathyroidectomy can be performed: subtotal parathyroidectomy, total parathyroidectomy and total parathyroidectomy plus autologous transplantation (tPTX+AT). Each of the three types of surgery has advantages and disadvantages. The present study retrospectively analyzed the efficacy of tPTX+AT for the treatment of SHPT over 1 year. Thirty-seven patients who were diagnosed with secondary nephrogenic hyperparathyroidism and treated with tPTX+AT were selected between September 2014 and October 2016 and followed up for 1 year. Their average age was 66.5±46.0 years, and the average time of dialysis was 48.1±8.2 months. The patients' conditions, including the levels of intact parathyroid hormone (iPTH) and bone metabolism, were compared preoperatively and 1 and 7 days and 1, 3, 6 and 12 months after surgery. In addition, the postoperative complications, pathological data, SHPT recurrence and prognosis were examined. The results showed that the postoperative level of ostalgia and cutaneous pruritus significantly decreased in the patients. An inspection of the parathyroid tissues during the operation confirmed the presence of parathyroid gland hyperplasia with no carcinoma detected. Three patients with hoarseness recovered within 1 month, and 1 patient with unilateral recurrent laryngeal nerve injury improved after 6 months of voice training. Compared to the preoperative condition, the postoperative serum iPTH, serum calcium and serum phosphate levels were significantly decreased (P<0.001), and these differences remained significant 12 months after surgery. Compared to the preoperative condition, the alkaline phosphatase (ALP) concentration was decreased on postoperative day 1 (P<0.05), but no differences were observed on day 7 or at 1 month (P>0.05). The ALP levels continuously decreased at 3, 6 and 12 months (P<0.01). In conclusion, tPTX+AT significantly improves the quality of life and serum biomarker levels of these patients. The convenient surgical removal of the hyperplastic parathyroid gland for postoperative recurrence supports tPTX+AT as the recommended treatment for relevant patients.

A Case of Asymptomatic Multiple Endocrine Neoplasia Type I with Thymic Carcinoid

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant hereditary disorder caused by germline mutation of the MEN1 gene. It is characterized by tumors of the anterior pituitary gland, parathyroid glands, and endocrine pancreas. Thymic carcinoid tumor is uncommon and associated with a high mortality, but its natural history has not been investigated yet. We report a case of asymptomatic MEN 1 with a thymic carcinoid tumor. A 37-year-old man underwent a routine medical checkup and upper gastrointestinal endoscopy revealed a duodenal neuroendocrine tumor (NET). Further studies showed the coexistence of pancreatic tumor, parathyroid hyperplasia, pituitary adenoma, and thymoma. The patient underwent duodenal endoscopic mucosal resection, distal pancreatectomy, subtotal parathyroidectomy, and thymectomy. The pathological test revealed a duodenal NET, pancreatic NET, parathyroid hyperplasia, and thymic carcinoid tumor. He was treated for MEN 1. We report this asymptomatic case of MEN 1 with a literature review. Key words: Hyperparathyroidism; Multiple endocrine neoplasia type 1; Neuroendocrine tumors; Thymoma

Could the Less-Than Subtotal Parathyroidectomy Be an Option for Treating Young Patients With Multiple Endocrine Neoplasia Type 1-Related Hyperparathyroidism?

Background: The surgical treatment of primary hyperparathyroidism (HPT) in patients with multiple endocrine neoplasia type 1 (MEN1) has evolved due the concern of permanent hypoparathyroidism. As the diagnosis has increased, the extent of operation has decreased. Most MEN1 patients requiring parathyroidectomy are younger than 50 years and they pose a difficult balance to achieve between persistent HPT and life-long hypoparathyroidism. The aim of the present study is to review our experience with a large series of patients with MEN1-related HPT (HPT/MEN1) treated at a single institution in order to find clues to a better treatment decision in these younger cases.Method: Retrospective analysis of consecutive HPT/MEN1 cases treated at a single institution with different operations: total parathyroidectomy and immediate forearm autograft (TPTX-AG), subtotal (STPTX), unintentional less than subtotal (U-LSTPTX) and intentional less than subtotal parathyroidectomy (I-LSTPTX).Results: Considering 84 initial cases operated on since 2011 (TPTX-AG, 39; STPTX, 22, U-LSTPTX, 13, and I-LSTPTX, 10), the rates of hypoparathyroidism were 30.8% (U-LSTPTX), 28.2% (TPTX-AG), 13.6% (STPTX), and 0% (I-LSTPTX). Two-thirds of them (68%; 57/84) were young (<50 years) or asdolescents. MIBI scan was more sensitive to show parathyroid glands and bilateral disease. Considering the concordance of MIBI and ultrasound for the possibility of unilateral clearance, it would be suitable to 22.6% of the cases. Intra-operative parathormone showed a significant decay even after unilateral exploration, but longer follow up is necessary. Overall, there were seven (4%) adolescents in 161 cases treated from 1987 to 2018, three underwent TPTX-AG and four had U-LSTPTX. Five are euparathyroid, one had mild recurrence, and one required a reoperation after 8 years due to the residual gland.Conclusions: Young patients are the most frequent candidates to parathyroidectomy. Less extensive procedures may be planned only if carefully reviewed preoperative imaging studies suggest a localized disease. Patients and their relatives should be fully informed of the risks and benefits during consent process. Future research with larger cohorts and long-term results are necessary to clarify if less than I-LSPTX or unilateral clearance are really adequate in selected groups of patients with HPT/MEN1 presenting lower volume of disease detected by preoperative imaging studies.