Feasibility of an Online Patient-Driven International Parathyroid Registry.

INTRODUCTION: Traditional parathyroid registries are labor-intensive and do not always capture long-term follow-up data. This study aimed to develop a patient-driven international parathyroid registry and leverage community connections to improve patient-centered care for hyperparathyroidism. METHODS: An anonymous voluntary online survey was developed using Qualtrics and posted in an international patient and advocate-run social media group affiliated with over 11,700 members. The survey was developed from a literature review, expert opinion, and discussion with the social media group managers. It consists of seven sections: patient demographics, past medical history, preoperative symptoms, laboratory evaluation, preoperative imaging studies, operative findings, and operative outcomes. RESULTS: From July 30, 2022, to October 1, 2022, 89 complete responses were received. Participants were from 12 countries, mostly (82.0%) from the United States across 31 states. Most participants were female (91.4%), White (96.7%) with a mean (±standard deviation) age of 58 ± 12 y. The most common preoperative symptoms were bone or joint pain (84.3%) and neuropsychiatric symptoms: including fatigue (82.0%), brain fog (79.8%), memory loss (79.8%), and difficulty with concentration (75.3%). The median (interquartile range) length from symptom onset to diagnosis was 40.0 (6.8-100.5) mo. Seventy-one percent of participants had elevated preoperative serum calcium, and 73.2% had elevated preoperative parathyroid hormone. All participants obtained preoperative imaging studies (88.4% ultrasound, 86.0% sestabimi scan, and 45.3% computed tomography). Among them, 48.8% of participants received two, and 34.9% had three imaging studies. The median (interquartile range) time from diagnosis to surgical intervention was 3 (2-9) mo. Twenty-two percent of participants traveled to different cities for surgical intervention. Forty-seven percent of participants underwent outpatient parathyroidectomy. Eighty-four percent of participants reported improved symptoms after parathyroidectomy, 12.4% required oral calcium supplementation for more than 6 mo, 32.6% experienced transient hoarseness after parathyroidectomy, and 14.6% required reoperation after initial parathyroidectomy. CONCLUSIONS: This international online parathyroid registry provides a valuable collection of patient-entered clinical outcomes. The high number of responses over 10 wk demonstrates that participants were willing to be involved in research on their disease. The creation of this registry allows global participation and is feasible for future studies in hyperparathyroidism.

Pre-operative Cinacalcet Administration Reduces Immediate Post-operative Hypocalcemia Following Total Parathyroidectomy in Severe Renal Hyperparathyroidism.

BACKGROUND: In severe renal hyperparathyroidism (RHPT), whether administrating Cinacalcet before total parathyroidectomy can reduce post-operative hypocalcemia remains unclear. We compared post-operative calcium kinetics between those who took Cinacalcet before surgery (Group I) and those who did not (Group II). METHODS: Patients with severe RHPT (defined by PTH ≥ 100 pmol/L) who underwent total parathyroidectomy between 2012 and 2022 were analyzed. Standardized peri-operative protocol of calcium and vitamin D supplementation was followed. Blood tests were performed twice daily in the immediate post-operative period. Severe hypocalcemia was defined as serum albumin-adjusted calcium < 2.00 mmol/L. RESULTS: Among 159 patients who underwent parathyroidectomy, 82 patients were eligible for analysis (Group I, n = 27; Group II, n = 55). Demographics and PTH levels before Cinacalcet administration were comparable (Group I: 169 ± 49 pmol/L vs Group II: 154 ± 45, p = 0.209). Group I had significantly lower pre-operative PTH (77 ± 60 pmol/L vs 154 ± 45, p < 0.001), higher post-operative calcium (p < 0.05), and lower rate of severe hypocalcemia (33.3% vs 60.0%, p = 0.023). Longer duration of Cinacalcet use correlated with higher post-operative calcium levels (p < 0.05). Cinacalcet use for > 1 year resulted in fewer severe post-operative hypocalcemia than non-users (p = 0.022, OR 0.242, 95% CI 0.068-0.859). Higher pre-operative ALP independently correlated with severe post-operative hypocalcemia (OR 3.01, 95% CI 1.17-7.77, p = 0.022). CONCLUSION: In severe RHPT, Cinacalcet led to significant drop in pre-operative PTH, higher post-operative calcium levels, and less frequent severe hypocalcemia. Longer duration of Cinacalcet use correlated with higher post-operative calcium levels, and the use of Cinacalcet for > 1 year reduced severe post-operative hypocalcemia.

Morbidity and long-term outcome of surgery for renal hyperparathyroidism: results from a prospective cohort.

PURPOSES: Surgery remains an important treatment option for renal hyperparathyroidism (rHPT). The number of long-term outcome studies of parathyroidectomy is limited. METHODS: All consecutive patients with a parathyroidectomy for rHPT between 09/2009 and 04/2021 in a Belgian tertiary referral hospital were prospectively enrolled. The main outcomes were (long-term) cured proportion and postoperative morbidity (hypocalcemia, recurrent laryngeal nerve (RLN) palsy, re-intervention for bleeding, and wound morbidity). RESULTS: Sixty patients with a median age of 57 years were analyzed, including 23 patients before kidney transplantation, 23 patients without kidney transplantation, and 14 patients after kidney transplantation. Median time to transplant was 15 (6-24) months after parathyroidectomy. Morbidity was low with only two non-urgent returns to theatre (wound infection and non-compressive hematoma), two temporary RLN paralyses, and no 30-day mortality. Length of hospital stay was longer in patients with parathyroidectomy before kidney transplant, due to a more severe and prolonged need for calcium supplementation. After a median follow-up of 63 months, 37 patients (62%) were still alive, and 11 patients (18%) developed a recurrence. CONCLUSIONS: This single-surgeon, single-center cohort with long-term follow-up confirms the safety and excellent 'cure' proportions of surgery for rHPT but stretches the importance of long-term follow-up.

Effective long-term management of parathyromatosis-related refractory hypercalcemia with a combination of denosumab and cinacalcet treatment.

Parathyromatosis is a rare cause of persistent or recurrent primary hyperparathyroidism and hypercalcemia due to the presence of hyperfunctioning foci of parathyroid tissue in the neck and/or mediastinum. We describe the case of a male patient who presented with severe hypercalcemia and a left-sided palpable parathyroid mass. Over the course of the next 18 years, the patient underwent neck exploration surgery on multiple occasions due to recurrent primary hyperparathyroidism and refractory hypercalcemia, complicated by nephrolithiasis and impairment of renal function, while bone mineral density was preserved. Histological findings and the natural course of the disease were consistent with parathyromatosis. Medical interventions with oral bisphosphonates or high-dose cinacalcet failed to control the patient's hypercalcemia. The combination of monthly denosumab and cinacalcet was, however, successful in maintaining the patient's serum calcium in the normal/upper-normal range over a 36-month period with no significant side effects. This is the first report of off-label denosumab use in combination with cinacalcet in the long-term management of parathyromatosis-related refractory hypercalcemia.

Usefulness of PET/CT with Carbon-11-Labeled Methionine in the Diagnosis of Tertiary Hyperparathyroidism.

Introduction: Tertiary hyperparathyroidism (tHP) may develop in patients treated with hemodialysis or peritoneal dialysis. Parathyroidectomy may result in a significant reduction in the severity of symptoms. For the effective surgical treatment of hyperparathyroidism, proper localization of the parathyroid glands prior to surgery is essential. The sensitivity of scintigraphy in the diagnosis of tHP is lower than in the diagnosis of primary hyperparathyroidism. In recent years, positron emission tomography (PET/CT) has been gaining importance, usually as a complementary technique. Aim: The aim of this study was to determine the usefulness of PET/CT with [11C]MET in the preoperative localization diagnosis of patients with tertiary hyperparathyroidism caused by chronic kidney disease, in whom first-line diagnostic methods did not allow the localization of pathologically parathyroid glands. Material and methods: The study was conducted in a group of 19 adult patients with severe tHP who were resistant or intolerant to non-invasive treatment, with negative results of scintigraphy and ultrasonography of the neck. The study protocol included measurement of the concentration of calcium, phosphorus, and PTH in the blood serum and performing PET/CT with [11C]MET. Results: A positive result of PET/CT was obtained in 89.5% of the patients (17/19). Parathyroidectomy was performed in 52.9% of the patients (9/17) with positive results of PET/CT with [11C]MET, which were fully consistent with the results of the histopathological examinations of the removed parathyroid glands. On this basis, the sensitivity of PET/CT with [11C]MET in the preoperative localization diagnosis of patients with tHP was found to be 100%. Multiple lesions were visualized in 57.9% of the patients (11/19). Ectopic lesions were visualized in 21.1% of the patients (4/19). Conclusions: PET/CT with [11C]MET is a sensitive technique for the second-line preoperative imaging of parathyroid glands in patients with tertiary hyperparathyroidism in whom first-line examinations, such as ultrasound and scintigraphy, has failed.

Intensive calcium monitoring improves outcomes on hungry bone syndrome in hyperparathyroidism.

Objectives. Hungry bone syndrome (HBS) is a severe and underdiagnosed complication of parathyroidectomy in the treatment of primary hyperparathyroidism (PHP) and secondary hyper-parathyroidism to chronic kidney disease (SHP-CKD).Methods. A longitudinal study was conducted to compare the postoperative outcomes of patients who developed HBS in two different time frames: before and after implementing a protocol with an intensive electrolytic monitoring and an algorithm regarding electrolytic supplementation.Results. Overall, 77 parathyroidectomies were included. In PHP, a protocol implementation led to an increased admission of patients in the Intermediate Care Unit for intensive electrolytic monitoring (p<0.001) and an increased rate of oral calcium replacement during hospital stay (p=0.013) compared to pre-protocol era. In SHP-CKD, duration of intravenous calcium replacement was reduced (p=0.010). The prevalence of HBS (9.8% in PHP and 58.3% in SHP-CKD) was similar between the two periods, although its diagnosis had an increased trend in PHP since the protocol implementation. None of the diagnosis of HBS was established due to hypocalcemic symptoms in the post-protocol era (contrary to pre-protocol period, p=0.021). Both hypocalcemia length and duration of surgical ward hospitalization were reduced (p=0.047 and p=0.042, respectively).Conclusions. An improved assessment of hyperparathyroidism and a decrease in HBS severity were noted in the post-protocol era. We strongly recommend the implementation of a standardized protocol with an intensive phosphocalcium monitoring in the high-risk patients who undergo parathyroidectomy due to hyperparathyroidism as it improves the health care and management of HBS.

Anesthetic considerations in hyperparathyroid crisis: A case report.

INTRODUCTION: Hyperparathyroid crisis is a rare and potentially life-threatening complication of severe calcium intoxication. Parathyroidectomy is the only curative method for hyperparathyroid crisis. Several case reports and case series have been published on the medical and surgical treatments for hyperparathyroid crisis, however, few reports have focused on the associated perioperative anesthetic management. PATIENT CONCERNS: A 48-year-old Chinese woman presented with a 2-week history of nausea and vomiting and complained of mental status alteration including confusion and agitation in the 24 hours prior to her admission. She denied any history of past illness. Laboratory tests showed severe hypercalcemia crisis with a serum calcium level of 5.21 mmol/L and a serum intact parathyroid hormone level of > 5000 pg/mL. DIAGNOSIS: The diagnosis was hyperparathyroid crisis, acute kidney injury, acute liver injury, rhabdomyolysis, infection, and shock. INTERVENTIONS: She underwent initial management with aggressive intravenous fluid resuscitation, loop diuretic treatment, vitamin D supplement, intravenous bisphosphonates, and calcitonin therapy. However, her condition worsened, and she was transferred to the operating theater for a parathyroidectomy under general anesthesia. She was under general anesthesia and monitored with electrocardiogram, pulse oxygen saturation, continuous arterial blood pressure, central venous pressure and nasopharyngeal temperature. Cardiac output and stroke volume variation were monitored from the FloTrac system. After liberal fluid rehydration, circulatory support, cooling treatment and calcium supplement after tumor removal, her unstable vital signs gradually improved. OUTCOMES: After meticulous anesthetic management by the anesthesiologist and complete tumor resection by the surgeon, she survived this fatal disease. The patients was discharged on postoperative day 37 without any sequelae. LESSONS: Patients with hyperparathyroid crisis should undergo a thorough preoperative evaluation. Difficult airway, fluid depletion, multiple organ dysfunction, hypercoagulability, and concomitant diseases are the primary challenges in anesthetic management. After tumor removal, the serum calcium level should be monitored closely and calcium should be supplemented in a timely manner to prevent serious complications.

Intra-operative parathyroid hormone evaluation is superior to frozen section analysis in parathyroid surgery.

BACKGROUND: Surgery is currently the only treatment option for patients with primary hyperparathyroidism (PHPT). Recently, minimally invasive parathyroidectomy (MIP) has begun to replace traditional bilateral neck exploration (BNE). OBJECTIVE: The aim of this study is to compare the results of parathyroidectomies performed in our hospital over the past decade that were guided by intra-operative parathyroid hormone (IOPTH) sampling or frozen section (FS) analysis. MATERIAL AND METHODS: Data on 697 patients who underwent parathyroidectomies in the Department of Endocrine Surgery, Dokuz Eylul University between January 2005 and 2018 were included in this study. Patients with malignancies other than thyroid papillary microcarcinoma and parathyroid cancer were excluded from the study. RESULTS: The concomitant use of neck ultrasound (US) and technetium 99m Sestamibi (99mTc MIBI) scintigraphy successfully localized the hyperfunctioning parathyroid glands in nearly 96% of cases. As compared with the IOPTH group, the operation time was longer in the FS group (p < 0.001), and the need for postoperative calcium (Ca) supplementation was higher (p < 0.001). The duration of hospitalization (days) was significantly higher in the FS group (4.2 ± 3.4 vs. 2.6 ± 1.9) as compared with that in the IOPTH group (p < 0.001). In addition, the recurrence rate in the FS group was significantly higher than that in the IPOTH group (p = 0.002). CONCLUSION: IOPTH sampling is a safe and effective method when performed by experienced surgeons and with appropriate preoperative screening. This study emphasizes that IOPTH sampling. We believe that the success in parathyroid surgery is due to three factors: correct indication, accurate localization and experienced surgeon.

Correlation Between the Parathyroid Glands Size and Parathormones Value in Patients with Hyperparathyroidism.

INTRODUCTION: Hyperparathyroidism is a common endocrine disorder with potential complications of bone, renal, neurocognitive and cardiovascular system. AIM: To determine the correlation between the size of parathyroid glands and parathormone values in the patients with hyperparathyroidism. METHODS: We analyzed a retrospective-prospective database of 79 consecutive patients who underwent parathyroidectomy for hyperparathyroidism at our institution between January 2011 and February 2018. The values of parathormone, calcium and phosphorus were determined in all patients before and after surgery. Ultrasonography were performed before surgery. Imaging results were confirmed by pathology. We analyzed the correlation between the sizes parathyroid glands obtained trough ultrasonography and pathology with parathormone values. RESULTS: The median age of the patients were 51 age (range 20-73) and 67,1% of the patients were female. Our study demonstrated that between actual glands sizes (volumes), expresses in millimeters, measured on pathohistological analysis and ultrasound examination and size value of parathormone its increased value does not affect the size of the gland. We investigate the correlation between the size of glands measured according to the pathohistological finding and the value of parathormone we obtained the correlation results close to the statistical features. The correlation value of parathormone and glands sizes according to the pathohistological finding measured trough the determined assessment scale we determined the statistically important of medium value. CONCLUSION: One of the important factors for parathyroidectomy is the value of parathormone. Serum parathormone level might be predictable by a total size of parathyroid glands and could be an effective the predictor of gland localisation.

Recurrent tertiary hyperparathyroidism due to supernumerary parathyroid glands in a patient receiving long-term hemodialysis: a case report.

BACKGROUND: Renal hyperparathyroidism is a common complication of chronic kidney disease (CKD) or end-stage renal disease (ESRD) characterized by elevated parathyroid hormone levels secondary to derangements in the homeostasis of calcium, phosphate, and vitamin D. Rapid correction of severe and prolonged hyperparathyroidism by surgical parathyroidectomy in long-term hemodialysis patients occasionally causes hungry bone syndrome. These patients then exhibit severe and long-lasting secondary or tertiary hyperparathyroidism with high bone turnover. CASE PRESENTATION: We report a case of recurrent tertiary hyperparathyroidism after total parathyroidectomy due to supernumerary parathyroid gland in a patient with long-term hemodialysis. Supplementation with intravenous calcium, oral calcium, and vitamin D immediately after patient surgery helps to prevent and treat hungry bone syndrome. CONCLUSIONS: We should prompt a search for the supernumerary parathyroid glands in ESRD patients, who have recurrent or persistent hyperparathyroidism after total parathyroidectomy. ESRD patients are more likely to develop hungry bone syndrome after parathyroidectomy. Prevention and treatment of hungry bone syndrome may be required after ectopic parathyroidectomy in clinical practice.

Perioperative hyperkalemia in hemodialysis patients undergoing parathyroidectomy for renal hyperparathyroidism.

The present study investigates the incidence of perioperative hyperkalemia and the influence factors of serum potassium levels during and after parathyroidectomy (PTX) in hemodialysis patients with renal hyperparathyroidism (rHPT). A total of 204 hemodialysis patients with refractory rHPT undergoing successful total parathyroidectomy with autotransplantation (tPTX + AT) were analyzed retrospectively. Hyperkalemia was defined as serum potassium levels ≥ 5.5 mmol/L. The preoperative baseline level of serum potassium (K base+ ) was defined as a mean of the three preoperative prehemodialysis serum potassium levels. The higher levels of serum potassium during and immediately after surgery were recorded as K d0+ and the peak prehemodialysis serum potassium levels 3 days after surgery as K d3+ . 136/204 (66.7%) patients suffered from hyperkalemia during or immediately after surgery and 65/204 (31.9%) patients were affected with prehemodialysis hyperkalemia 3 days after surgery. K base+ was the only influencing factor for K d0+ . Serum K base+ , preoperative serum alkaline phosphatase, and total calcium supplement dosage during intravenous calcium supplement were the influencing factors for K d3+ . In the case of PTX, the serum potassium levels of patients with higher serum K base+ and severe postoperative hypocalcemia need to be monitored with extended attention perioperatively.

Electrolytes: Calcium Disorders.

A normal serum calcium level is 8 to 10 mg/dL. The diagnosis of hypercalcemia (ie, levels 10.5 mg/dL or greater) should be confirmed with an albumin-adjusted or ionized calcium level. The two most common causes of hypercalcemia are hyperparathyroidism and malignancy. Drugs, notably lithium and thiazide diuretics, also can cause hypercalcemia. Patients with severe or symptomatic hypercalcemia should be treated initially with hydration to decrease calcium levels. The evaluation should include a parathyroid hormone (PTH) level. If the PTH level is low, cancer is a likely cause, particularly multiple myeloma, breast cancer, or lymphoma. If the PTH level is normal or elevated, hyperparathyroidism is the likely cause. Symptomatic patients with hyperparathyroidism and patients with certain clinical markers should be considered for surgery. For patients with mild disease, monitoring is an option. Hypocalcemia often is caused by vitamin D deficiency. Symptomatic patients and patients with calcium levels less than 7.6 mg/dL should be treated with intravenous calcium gluconate; concomitant magnesium deficiency should be addressed. There is no evidence that routine calcium and vitamin D supplementation reduces the risk of fractures, but studies have shown that vitamin D supplementation does decrease the number of falls in older adults at risk.

Parathyroidectomy in Persistent Post-transplantation Hyperparathyroidism - Single-center Experience.

BACKGROUND: Hyperparathyroidism is a common complication in chronic kidney disease and might persist in up to 25% of patients after transplantation. In this setting, vitamin D analogues further aggravate persistent hypercalcemia and cinacalcet has not been approved for these patients, some of whom will require parathyroidectomy to correct post-transplantation hyperparathyroidism. OBJECTIVES: In this single-center, retrospective study we aimed to analyze the long-term effect of parathyroidectomy on calcium, phosphorus, and parathyroid hormone (PTH) levels and its effect on allograft function in kidney transplantation patients submitted to parathyroidectomy. PATIENTS AND METHODS: Fifteen patients underwent parathyroidectomy between January 2005 and January 2015; median age 54 years old; 8 (53.3%) were receiving cinacalcet at the time of surgery. Pre-parathyroidectomy median values of intact PTH, calcium, and phosphorus were, respectively, 262 pg/mL, 10.8 mg/dL, and 2.4 mg/dL. Surgery consisted of uniglandular parathyroidectomy in 5 (33.3%) patients, biglandular in 4 (26.7%), and subtotal in 6 (40%). There was no surgery-related mortality. RESULTS: Compared with baseline, there was a decrease of PTH (262 pg/mL vs. 106 pg/mL, P = .001), calcium, and phosphorus levels (10.8 mg/dL vs. 10.4 mg/dL, P = .3; 2.4 vs. 2.9 mg/dL, P = .05) 1 year after surgery; with normalization of serum calcium at the end of follow-up (10.8 mg/dL vs. 9.4 mg/dL, P = .04). A decrease in estimated glomerular filtration rate occurred 1 month post-surgery (62.7 mL/m vs. 49.7 mL/m, P = .006) but returned to baseline 1 year after surgery (62.7 mL/m vs. 60.8 mL/m, P = .73). CONCLUSION: Parathyroidectomy appears to be a safe procedure and should be considered in kidney transplantation patients with persistent post-transplantation hyperparathyroidism. Although there was an acute estimated glomerular filtration rate decrease, we observed no long-term deterioration in allograft function.

Hungry bone syndrome.

PURPOSE OF REVIEW: In the United States, the number of parathyroidectomies among patients with chronic dialysis has remained stable in the last decade. A fall in serum calcium concentration is common postparathyroidectomy in patients with hyperparathyroidism, which usually resolves in 2-4 days. A severe drop in serum total calcium concentration less than 2.1 mmol/L and/or prolonged hypocalcemia for more than 4 days postparathyroidectomy is called hungry bone syndrome (HBS). Concomitant hypophosphatemia, hypomagnesemia, and hyperkalemia can be seen. Hypocalcemia and hypophosphatemia can persist for months to years. In contemporary clinical practice, HBS may be more commonly seen in patients with secondary compared to primary hyperparathyroidism. Preoperative radiological changes in bone, elevated serum alkaline phosphatase and parathyroid hormone (PTH) levels, and high numbers of osteoclasts on bone biopsy may identify patients at risk. Treatment consists of high-dose oral calcium and calcitriol supplementation. A low-dose pamidronate infusion 1-2 days prior to surgery may prevent HBS. RECENT FINDINGS: Recent in-vitro studies reported net calcium movement into bone because of a sudden fall in serum PTH level after a prolonged period of elevation. This supports a previous hypothesis that a sudden drop in serum PTH level after surgery results in the unopposed action of osteoblasts and influx of calcium into bone. SUMMARY: Incidence of HBS and its association with morbidity and mortality remains unclear in contemporary clinical practice. It is more common to encounter HBS in chronic dialysis patients with secondary hyperparathyroidism than those with primary hyperparathyroidism that undergo parathyroidectomies. Use of bisphosphonates to prevent HBS should be explored in future studies.

Survival, Risk Factors, and Effect of Treatment in 101 Patients With Calciphylaxis.

OBJECTIVE: To report on the survival and the associations of treatments upon survival of patients with calciphylaxis seen at a single center. PATIENTS AND METHODS: Using the International Classification of Diseases, Ninth Revision diagnosis code of 275.49 and the keyword "calciphylaxis" in the dismissal narrative, we retrospectively identified 101 patients with calciphylaxis seen at our institution between January 1, 1999, through September 20, 2014, using a predefined, consensus-developed classification scheme. RESULTS: The average age of patients was 60 years: 81 (80.2%) were women; 68 (68.0%) were obese; 19 (18.8%) had stage 0 to 2 chronic kidney disease (CKD), 19 (18.9%) had stage 3 or 4 CKD; 63 (62.4%) had stage 5 or 5D (dialysis) CKD. Seventy-five patients died during follow-up. Six-month survival was 57%. Lack of surgical debridement was associated with insignificantly lower 6-month survival (hazard ratio [HR]=1.99; 95% CI, 0.96-4.15; P=.07) and significantly poorer survival for the entire duration of follow-up (HR=1.98; 95% CI, 1.15-3.41; P=.01), which was most pronounced in stage 5 or 5D CKD (HR=1.91; 95% CI, 1.03-3.56; P=.04). Among patients with stage 5/5D CKD, subtotal parathyroidectomy (performed only in patients with hyperparathyroidism) was associated with better 6-month (HR=0.12; 95% CI, 0.02-0.90; P=.04) and overall survival (HR= 0.37; 95% CI, 0.15-0.87; P=.02). CONCLUSION: Calciphylaxis is associated with a high mortality rate. Significantly effective treatments included surgical debridement and subtotal parathyroidectomy in patients with stage 5/5D CKD with hyperparathyroidism. Treatments with tissue-plasminogen activator, sodium thiosulfate, and hyperbaric oxygen therapy were not associated with higher mortality.

The American Association of Endocrine Surgeons Guidelines for Definitive Management of Primary Hyperparathyroidism.

Importance: Primary hyperparathyroidism (pHPT) is a common clinical problem for which the only definitive management is surgery. Surgical management has evolved considerably during the last several decades. Objective: To develop evidence-based guidelines to enhance the appropriate, safe, and effective practice of parathyroidectomy. Evidence Review: A multidisciplinary panel used PubMed to review the medical literature from January 1, 1985, to July 1, 2015. Levels of evidence were determined using the American College of Physicians grading system, and recommendations were discussed until consensus. Findings: Initial evaluation should include 25-hydroxyvitamin D measurement, 24-hour urine calcium measurement, dual-energy x-ray absorptiometry, and supplementation for vitamin D deficiency. Parathyroidectomy is indicated for all symptomatic patients, should be considered for most asymptomatic patients, and is more cost-effective than observation or pharmacologic therapy. Cervical ultrasonography or other high-resolution imaging is recommended for operative planning. Patients with nonlocalizing imaging remain surgical candidates. Preoperative parathyroid biopsy should be avoided. Surgeons who perform a high volume of operations have better outcomes. The possibility of multigland disease should be routinely considered. Both focused, image-guided surgery (minimally invasive parathyroidectomy) and bilateral exploration are appropriate operations that achieve high cure rates. For minimally invasive parathyroidectomy, intraoperative parathyroid hormone monitoring via a reliable protocol is recommended. Minimally invasive parathyroidectomy is not routinely recommended for known or suspected multigland disease. Ex vivo aspiration of resected parathyroid tissue may be used to confirm parathyroid tissue intraoperatively. Clinically relevant thyroid disease should be assessed preoperatively and managed during parathyroidectomy. Devascularized normal parathyroid tissue should be autotransplanted. Patients should be observed postoperatively for hematoma, evaluated for hypocalcemia and symptoms of hypocalcemia, and followed up to assess for cure defined as eucalcemia at more than 6 months. Calcium supplementation may be indicated postoperatively. Familial pHPT, reoperative parathyroidectomy, and parathyroid carcinoma are challenging entities that require special consideration and expertise. Conclusions and Relevance: Evidence-based recommendations were created to assist clinicians in the optimal treatment of patients with pHPT.

HRPT2- (CDC73) RELATED HEREDITARY HYPERPARATHYROIDISM: A CASE SERIES FROM WESTERN INDIA.

OBJECTIVE: To describe a case series of HRPT2- (CDC73) related hereditary primary hyperparathyroidism (PHPT) from western India. METHODS: We present a case series of 4 families (7 patients) with PHPT caused by CDC73 gene mutations. RESULTS: The mean age of presentation of the 4 index cases was 27.25 ± 9.8 years. Two family members were identified through biochemical screening (Cases 1b and 2b), while 1 mutation-positive family member did not manifest any features of PHPT or hyperparathyroidism jaw tumor syndrome (HPT-JT) syndrome (Case 2c). Biochemistry showed increased serum calcium (mean: 13.21 ± 1.24 mg/dL), low serum phosphorus (mean: 1.78 ± 0.44 mg/dL), and high parathyroid hormone (PTH, mean: 936 ± 586.9 pg/mL). All patients had a uniglandular presentation and underwent single adenoma excision initially except Cases 2a and 2b, who underwent subtotal parathyroidectomy at baseline. Two cases experienced PHPT recurrence (Cases 3 and 4), while 1 remained uncured due to parathyroid carcinoma (Case 1a). Other associated syndromic features like ossifying jaw fibromas were present in 2 patients, renal cysts in 3 patients, and uterine involvement in 2 patients. Two families had novel germline CDC73 mutations (Families 1 and 3), while the other 2 had reported mutations. Family 2 had familial isolated PHPT without any other features of HPT-JT syndrome. CONCLUSION: Our findings reaffirm the need for genetic analysis of patients with PHPT, especially those with younger age of disease onset; recurrent disease; and associated features like polycystic kidneys, endometrial involvement, ossifying jaw tumors, or parathyroid carcinoma.

Recovery of parathyroid hormone secretion and function in postoperative hypoparathyroidism: a case series.

CONTEXT: Transient and permanent postoperative hypoparathyroidism are recognized complications of neck surgery. Postoperative hypoparathyroidism is usually considered permanent when it persists for 6 months; in rare cases, recovery of hypoparathyroidism through 1 year has been described. Recovery of hypoparathyroidism years after diagnosis has not previously been reported. OBJECTIVE: We report four patients being treated with PTH(1-84) in a research protocol who recovered from postoperative hypoparathyroidism many years after onset. METHODS: Recovery from hypoparathyroidism was established by: 1) serum calcium and PTH levels within the normal range off PTH(1-84) treatment for at least 1 week; 2) requirement for daily calcium supplementation reduced to ≤1 g; and 3) no supplemental active vitamin D therapy. RESULTS: Hypoparathyroidism developed in three subjects after repeated neck surgery for primary hyperparathyroidism and in one subject after total thyroidectomy for Graves' disease. Parathyroid tissue autotransplant was performed in two of the four subjects. Two had undetectable PTH levels at study entry, whereas the other two subjects had detectable, although low, PTH levels. Hypoparathyroidism had been present for at least 8 years, and in one case for 16 years. The recovery of parathyroid function followed treatment with PTH(1-84) for 36 to 63 months. CONCLUSIONS: Although it remains relatively rare, this report documents recovery of long-term postoperative hypoparathyroidism many years after the initial diagnosis. A potential role for exogenous PTH is intriguing with several plausible mechanisms.

Morbidity after thyroid surgery: patient perspective.

OBJECTIVES/HYPOTHESIS: To evaluate patient perception of morbidity after thyroid surgery. STUDY DESIGN: Survey of consecutive patients (case series). METHODS: A standardized questionnaire was mailed to 312 patients who underwent thyroid surgery during a 3-year period (January 2008 to December 2010). RESULTS: Replies were received from 202 (64%) patients (56 male, 166 female; age, 55 ± 16 years) at 6 to 39 months (median, 23 months) after lobectomy (n = 119) or total thyroidectomy (n = 76) for benign (n = 160) or malignant (n = 42) conditions. Subjective voice assessment using a visual analogue scale was normal in 111 patients, deteriorated in 80 patients, and improved in 21 patients. Voice handicap index scores were normal in 126 (62%) patients and increased in 76 (38%) patients to a median of 17 (range, 11-29). Voice-related quality of life was excellent in 107 (53%) patients, fair to good in 66 patients, and poor to fair in 29 patients. Subjective assessment of swallowing was reported as normal in 84 patients, moderately affected in 56 patients (score, 11-15) and severely affected in 62 patients (score, 16-40; median, 23). Calcium supplements prescribed routinely after bilateral surgery were interrupted within 2 to 4 weeks in 56 patients and within 3 to 6 months in 18 patients. None of the respondents had persistent hypoparathyroidism. Appearance of the scar assessed using the Manchester score ranged from 5 to 16 (median, 7). Asked whether they would consider robotic thyroid surgery to avoid a cervical scar, only 38 patients said they were definitely interested. CONCLUSIONS: A large proportion of patients report persistent moderate voice and swallowing problems after thyroid surgery. These findings are similar to a recent international multicenter survey of more than 2,000 patients with thyroid cancer. Hypocalcemia and cosmetic outcome raised no significant concerns.