Impact of Dexmedetomidine On Secondary Hyperparathyroidism Recurrence In Uremic Patients Who Received Parathyroidectomy With Auto-Transplantation: A Retrospective Propensity-Matched Study

Background: Recurrence of secondary hyperparathyroidism (SHPT) remains a big challenge in uremic patients who underwent total parathyroidectomy with auto-transplantation (tPTX-AT). However, the relationship between perioperative intervention and recurrence of SHPT remains unclear. Dexmedetomidine has been used safely and effectively in uremic patients’ anesthesia. The aim of the study was to explore the effect of dexmedetomidine on the recurrence of SHPT and speculate the possible mechanism of action.Methods: Records of patients who underwent tPTX-AT between 2017 and 2018 were retrospectively analyzed. The study consisted of patients who received dexmedetomidine intra-operatively and the controls were patients who did not receive dexmedetomidine. The primary endpoint was the difference in the recurrence of SHPT one year after surgery between the two groups. The secondary endpoint was health-related quality of life scores. Analysis included propensity score matching and multivariable logistic regression. Results: Of 354 patients, 133 patients received dexmedetomidine intraoperatively, and the total recurrence rate of SHPT was 10.2%. After propensity score matching, patients who received dexmedetomidine had a 3.80-fold decreased risk of SHPT recurrence (odds ratio, 0.263; 95% confidence interval, 0.081 to 0.854; P=0.026) and exhibited a better quality of life in terms of physical functioning and general health, and less emotional role limitations compared with those in control group.Conclusion: In uremic patients who received tPTX-AT, there was an association between dexmedetomidine use and decreased risk of SHPT recurrence. Further studies are needed to accurately assess the effects and mechanism of action of dexmedetomidine on the prognosis of this population.

A case of a hemodialysis patient with secondary hyperparathyroidism who was resistant to etelcalcetide treatment but not to cinacalcet hydrochloride

Although both cinacalcet and etelcalcetide are calcimimetics that directly inhibit parathyroid hormone (PTH) secretion by activating the calcium (Ca)-sensing receptor (CaSR), their binding sites are different. We report a first case of a hemodialysis (HD) patient with secondary hyperparathyroidism (SHPT), in whom cinacalcet, but not etelcalcetide, could reduce serum intact PTH (i-PTH) levels. A HD patient received total parathyroidectomy (PTx) with auto-transplantation 16 years earlier. Due to SHPT relapse, cinacalcet was started at 7 years after PTx. His i-PTH levels had been controlled with both 75–100 mg of cinacalcet and 4.5 μg/week of calcitriol for a year before switching from cinacalcet to etelcalcetide. At 1 month following the switch, his serum i-PTH level increased to 716 pg/mL. The dose of etelcalcetide was gradually increased and finally reached the maximal dose of 45 mg/week. Because even the maximal dose of etelcalcetide for > 4 months did not reduce his serum i-PTH levels to < 700 pg/mL, etelcalcetide was switched to 50 mg/day of cinacalcet, which reduced the levels to 208 pg/mL at 2 months after the switch. Genomic sequencing test using whole blood revealed no mutation in the portion including Cys 482 of CaSR gene. The patient was resistant to etelcalcetide treatment but not to cinacalcet, suggesting the possibility that the enlarged parathyroid gland has some change in the portion including Cys 482 in the CaSR gene. Therefore, considering the possibility of etelcalcetide resistance during SHPT treatment should be kept in mind.

EP.WE.103223-hour stay following total parathyroidectomy in renal patients

Aim Total parathyroidectomy in end-stage renal failure (ESRF), is an effective way to improve or stabilise calcium and parathormone levels and thus improve renal osteodystrophy. Previous BAEST guidelines were not in favour of true day-case neck surgery due to the risk of airway compromise from bleeding. Additionally, ESRF patients are at risk of profound hypocalcaemia after total parathyroidectomy. Patients undergoing total parathyroidectomy are prescribed Alfacalcidol 4mcg daily for 5 days prior to surgery. Following surgery under GA on a morning list, the potassium and calcium levels are checked in the afternoon. Calcium levels are then monitored daily for 3 days and subsequently when required. Oral Alfacalcidol is continued at the same dose until the nephrologists advise otherwise. Methods All ESRF patients undergoing total parathyroidectomy for secondary hyperparathyroidism were identified between 01/01/2005 and 31/12/2019 from a prospectively maintained electronic database. Demographics, biochemistry, length of stay (LoS) and outcomes were analysed. Results There were 43 (30 male) total parathyroidectomies. The median age was 53 (range 14 – 78), and median LoS 1 day (range 0 -13). 26 patients (60%) were discharged within 23 hours (26% were day-case). Prolonged stay was due to calcium replacement (n = 8) or dialysis (n = 4) requirements. Pre- and post-operative calcium values over 2.49mmol/L were significantly related to 23-hour stay (p = 0.010482 and p = 0.000263 respectively). No 30-day re-admissions were observed Conclusions Careful patient selection and adherence to a perioperative management protocol in total parathyroidectomy may enable early discharge within 23 hours. Preoperative calcium levels help predict this outcome.

Multiple endocrine neoplasia type 1 with a frameshift mutation in its gene accompanied by a giant cervical lipoma and multiple fatty deposits in the pancreas: case report

Background Multiple endocrine neoplasia type 1 (MEN1) is a syndrome characterized by pituitary neoplasia, primary hyperparathyroidism and pancreatic endocrine tumor. Here we show a case of MEN1 with a germline frameshift mutation in its gene accompanied by a giant cervical lipoma and multiple fatty deposits in the pancreas. Case presentation A 28-year-old man noticed the decreased visual acuity of both eyes and visited our institution. Since he was diagnosed as visual disturbance and brain computer tomography (CT) showed a mass in the pituitary fossa, he was hospitalized in our institution. Endoscopic trans-sphenoidal hypophysectomy and total parathyroidectomy with auto-transplantation were performed, and a giant cervical lipoma was resected. Furthermore, in genetic search, we found a germline frameshift mutation in MEN1 gene leading to the appearance of a new stop codon. Conclusions We should bear in m ind that giant skin lipoma and multiple abnormal fatty deposits in the pancreas could be complicated with MEN1.

Parathyroid Carcinoma in a Patient With Secondary Hyperparathyroidism and Thyroid Hemiagenesis: A Case Report and Review of the Literature

Parathyroid carcinoma is a rare endocrine tumor. Parathyroid carcinoma in patients with secondary hyperparathyroidism due to chronic kidney disease is also rare. In addition, thyroid hemiagenesis is a rare congenital anomaly. We report an extremely rare case of parathyroid carcinoma in a patient with secondary hyperparathyroidism and thyroid hemiagenesis. We also present a review of the literature of this rare entity. We also discuss the surgical procedure performed for this patient. Our review of the literature found 34 case reports of parathyroid carcinoma in patients undergoing dialysis due to chronic renal failure; 14 reports of thyroid hemiagenesis with parathyroid disease; and no previous reports of thyroid hemiagenesis with secondary hyperparathyroidism and parathyroid carcinoma. Although surgical treatment of parathyroid carcinoma requires combined resection with the thyroid, peritracheal dissection with total parathyroidectomy, and monitoring intact parathyroid hormone as a tumor marker, our procedure preserved the patient’s thyroid function. There has been no evidence of recurrence for over 8 years.

Predictors of early postoperative hypocalcemia in patients with secondary hyperparathyroidism undergoing total parathyroidectomy

Objective To summarize the clinical features of secondary hyperparathyroidism (SHPT) in patients with chronic renal failure and to explore the predictive factors of postoperative hypocalcemia after total parathyroidectomy in these patients. Methods The clinical data of 87 patients admitted to Guangdong Electric Power Hospital from May 2013 to February 2020 were reviewed. All patients underwent total parathyroid resection and sternocleidomastoid microtransplantation. Age, sex, and the serum calcium, phosphorus, alkaline phosphatase (ALP), and intact parathyroid hormone (iPTH) concentrations were analyzed as predictive factors of postoperative hypocalcemia. Results Bone pain was the most common clinical manifestation in this study population, and all 87 patients experienced relief from their clinical symptoms after the surgical procedure. Age and the preoperative serum calcium, ALP, and iPTH concentrations were determined to be early predictive factors of postoperative hypocalcemia. Conclusions Age and the preoperative calcium, ALP, and iPTH concentrations are independent risk factors for postoperative hypocalcemia in patients with SHPT and renal disease who undergo total parathyroidectomy with sternocleidomastoid microtransplantation. These factors can help identify high-risk patients who can be managed by a multidisciplinary team to improve graft survival and quality of life.

Hypercalcemia With Non Suppressed Parathyroid Hormone in a Young Female- A Rare Case of Calcium Sensing Receptor Gene Related Familial Hypocalciuric Hypercalcemia-1

Background: Familial Hypocalciuric Hypercalcemia (FHH) is a rare disorder, associated with hypercalcemia and hypocalciuria and inherited in an autosomal dominant manner. Its true prevalence is unknown, and is estimated to be around 1 in 78,000 as compared to primary hyperparathyroidism (PHPT) which is around 1 in 1000. There are 3 mutations known to cause FHH. FHH-1 is caused by inactivating mutation in the calcium sensing receptor (CaSR) gene. Mutations associated with FHH-2 and FHH-3 are GNA11 and AP2S1 respectively. Case Presentation: 38-year-old female presented to endocrinology, for evaluation of hypercalcemia (10.8 mg/dL, with normal albumin). She was not on any calcium supplements or any other medications which can cause hypercalcemia. She did not have any prior fracture or nephrolithiasis or renal insufficiency. Her father reported to have hypercalcemia; no further evaluations of her father were available. Examination revealed an obese female with no skeletal or dental or other physical abnormalities. Laboratory evaluations: PTH= 37 pg/ml (15–65), 25 OH vitamin=D-30 pg/ml, Mg=2 mg/dL (1.5–2.6), phosphorus=3.1 mg/dl (2.5–4.8), 24 hour urine calcium=0.151 g/24 hours-with 24 hour urine calcium clearance of 0.008. Therefore, evaluations were highly suggestive of FHH. Subsequently, she had genetic evaluation which confirmed heterozygous CaSR mutation, confirming FHH-1. Her mother had genetic testing and was not found to have the mutation. So, it was concluded that the patient likely inherited the gene from her father, who also had hypercalcemia. She is being monitored clinically and with serial laboratory evaluations to monitor her calcium levels. Discussion: CaSR is expressed in parathyroid glands and kidneys which plays a key role in calcium regulation. CaSR inactivating mutation (seen in FHH-1) leads to hypocalciuria and hypercalcemia. 24 hour urine calcium clearance (urine Ca x serum Cr/ serum Ca x urine Cr) of &lt;0.01 is highly suggestive of FHH. Furthermore, higher concentration of calcium is required to suppress PTH release leading to high or nonsuppressed PTH. This finding can mislead towards the diagnosis of PHPT and unnecessary parathyroid surgery, if the diagnosis of FHH is missed. FHH is usually a benign disorder; subtotal parathyroidectomy does not cure the disease. FHH, rarely can cause atypical complications such as pancreatitis and total parathyroidectomy may be indicated to prevent further episodes of pancreatitis. Conclusions: This is a rare case presentation of hypercalcemia due to CaSR inactivating mutation related FHH. FHH and PHPT are competing diagnoses, when a patient presents with hypercalcemia and has nonsuppressed PTH. FHH is rare, however needs to be suspected in a young patient with family history of hypercalcemia, to avoid misdiagnosis of PHPT and unnecessary surgical intervention.

Risk Factors for Severe Hypocalcemia in Patients with Secondary Hyperparathyroidism after Total Parathyroidectomy

Background. Hypocalcemia is the most common complication of total parathyroidectomy in secondary hyperparathyroidism (SHPT) and is associated with adverse consequences such as spasms, epilepsy, and arrhythmia and even death if the serum calcium level decreases rapidly. Previous studies have identified several risk factors for postoperative severe hypocalcemia (SH) in patients with SHPT, but the sample sizes were small and thus the results may not be reliable. Objectives. This study was performed to investigate the risk factors for SH after total parathyroidectomy without autotransplantation (tPTX) in a large sample of patients with uremic hyperparathyroidism. Methods. We retrospectively investigated the records of 1,095 patients with SHPT treated with tPTX between January 2008 and December 2018. Based on the postoperative serum calcium concentration, the patients were grouped into SH and non-SH groups. The clinical characteristics and biochemical results were analyzed, and binary logistic regression analysis was used to identify the risk factors for SH. Results. After surgery, 25.9% of the patients developed SH. Age, diastolic blood pressure (DBP), heart rate, frequency of bone pain, weight of resected glands, preoperative serum calcium, intact parathyroid hormone (iPTH), alkaline phosphatase (ALP), and hemoglobin levels differed between the two groups. Binary logistic regression analyses identified preoperative serum calcium, iPTH, and ALP levels as independent predictors of SH after surgery. Conclusions. The preoperative serum calcium, iPTH, and ALP levels can be used to assess the risk of postoperative SH in patients with SHPT. Such patients should thus be monitored closely in order to initiate prompt interventions to avoid SH.