Recurrent Primary Hyperparathyroidism Research Articles

Preoperative diagnosis of parathyroid gland pathology in patients with persistent or recurrent primary hyperparathyroidism: a retrospective study

INTRODUCTION: Localization of abnormal parathyroid glands in persistent or relapsed patients with primary hyperparathyroidism presents problems for surgeons before repeated surgery. There is no clear standard for the choice of diagnostic modality for localization of PG in this group of patients.OBJECTIVE: To search for the optimal diagnostic protocol of the parathyroid pathology preoperative diagnosis in patients with primary hyperparathyroidism with persistent or recurrent disease.MATERIALS AND METHODS: 55 patients diagnosed with persistence or recurrence of PHPT who underwent repeated surgical treatment were included in the study. Before surgical intervention all patients underwent laboratory and instrumental investigations in the volume of: blood tests for PTH, TTH, ionized calcium, 25(OH)D, creatinine, phosphorus, neck ultrasound, parathyroid scintigraphy by washout method, dual-isotope subtractive scintigraphy of parathyroid glands (early and delayed phases), SPECT of parathyroid glands (with uptake correction), computed tomography of the neck with intravenous bolus contrast.RESULTS: CT and planar subtraction dual-isotope scintigraphy showed the highest DA in the overall group (persistence and recurrence) (78% and 78%), with the DA of these methods differing slightly (88% and 92%) and overall accuracy being higher for CT (90% and 87%). Neck ultrasound showed the lowest rates among all methods (DA — 46%, DS — 80%, OA — 67%). Planar scintigraphy (washout) and SPECT were comparable in their informativeness: DA — 67% and 65%, DS — 96% and 98%, OA — 85% and 86%.DISCUSSION: The most commonly used current diagnostic search algorithm before reoperation is visualization of the thyroid gland by two modalities: Neck ultrasound and parathyroid scintigraphy (washout/subtraction) or SPECT-CT. In doubtful cases, the second step is computed tomography of the neck with contrast or PET/CT. It is extremely difficult to choose one optimal diagnostic method, as none of them has 100% diagnostic accuracy. In addition, each study has limitations, and the availability of some modalities is limited. In our study, the location of pathologically altered thyroid was correctly recognized in 90% of cases by CT with contrast and in 87% of cases by planar subtraction dual-isotope scintigraphy. The informativeness of neck ultrasound showed the lowest values of all modalities. SPECT and planar washout scintigraphy took an intermediate position in terms of diagnostic accuracy.CONCLUSION: Isolated ultrasonography of the neck has low diagnostic accuracy in patients with primary hyperparathyroidism with persistent or recurrent disease. We recommend the combination of US with contrast-enhanced computed tomography of the neck or US with dual isotope subtraction scintigraphy of the parathyroid glands, which have the same diagnostic accuracy. SPECT and planar washout scintigraphy can be used for the diagnosis of abnormal parathyroid glands in persistent or recurrent patients with primary hyperparathyroidism when more informative techniques are unavailable. When the techniques were combined, the combination of ultrasound/CT with contrast and ultrasound/planar subtraction dual isotope scintigraphy showed the best results with DA of 85% and 86%.

Recurrent Primary Hyperparathyroidism in Multiple Endocrine Neoplasia Type 1 Syndrome.

Primary hyperparathyroidism is a common endocrinopathy. Multiple Endocrine Neoplasia Type 1 (MEN1) is a rare autosomal dominantly inherited endocrine tumor predisposition syndrome, with one of main manifestations being primary hyperparathyroidism. We retrospectively evaluated a set of 1011 patients who underwent surgery for primary hyperparathyroidism between the years 2018-2022, and found 78 (8 %) patients who underwent reoperations and 27 patients with MEN1 syndrome. In the group of patients with MEN1 syndrome, 7 (35 %) needed reoperations. Patients with multiple endocrine neoplasia syndrome have a higher risk of needing reoperation. Genetic testing can help identify MEN1 syndrome preoperatively and to better evaluate the approach to surgery.

Pediatric Neuroendocrine Neoplasia of the Parathyroid Glands: Delving into Primary Hyperparathyroidism.

Our objective was to overview the most recent data on primary hyperparathyroidism (PHP) in children and teenagers from a multidisciplinary perspective. Methods: narrative review based on full-length, English-language papers (from PubMed, between January 2020 and July 2023). Results: 48 papers (14 studies of ≥10 subjects/study, and 34 case reports/series of <10 patients/study). Study-sample-based analysis: except for one case-control study, all of the studies were retrospective, representing both multicenter (n = 5) and single-center (n = 7) studies, and cohort sizes varied from small (N = 10 to 19), to medium-sized (N = 23 to 36) and large (N = 63 to 83); in total, the reviewed studies covered 493 individuals with PHP. Case reports/series (n = 34, N = 41): the mean ages studied varied from 10.2 to 14 years in case reports, and the mean age was 17 years in case series. No clear female predominance was identified, unlike that observed in the adult population. Concerning the assessments, there were four major types of endpoints: imaging data collection, such as ultrasound, 99mTc Sestamibi, or dual-phase computed tomography (CT); gene testing/familial syndrome identification; preoperative findings; and exposure to surgical outcome/preoperative drugs, like cinacalcet, over a 2.2-year median (plus two case reports of denosumab used as an off-label calcium-lowering agent). Single-gland cases (representing 85% of sporadic cases and 19% of genetic PHP cases) showed 100% sensitivity for neck ultrasounds, with 98% concordance with 99mTc Sestamibi, as well as a 91% sensitivity for dual-phase CT, with 25% of the lesions being ectopic parathyroids (mostly mediastinal intra-thymic). Case reports included another 9/41 patients with ectopic parathyroid adenomas, 3/41 with parathyroid carcinomas, and 8/41 subjects with brown tumors. Genetic PHP (which has a prevalence of 5-26.9%) mostly involved MEN1, followed by CDC73, CASR, RET, and CDKN1B, as well as one case of VHL. Symptomatic PHP: 70-100% of all cases. Asymptomatic PHP: 60% of genetic PHP cases. Renal involvement: 10.5% of a cohort with genetic PHP, 71% of sporadic PHP cases; 50% (in a cohort with a mean age of 16.7), 29% (in a cohort with a mean age of 15.2); 0% (in infancy) to 50-62% (in teenagers). Bone anomalies: 83% of the children in one study and 62% of those in two other studies. Gastrointestinal issues: 40% of one cohort, but the data are heterogeneous. Cure rate through parathyroidectomy: 97-98%. Recurrent PHP: 2% of sporadic PHP cases and 38% of familial PHP cases. Hungry bone syndrome: maximum rate of 34-40%. Case reports identified another 7/41 subjects with the same post-parathyroidectomy condition; a potential connection with ectopic presentation or brown tumors is suggested, but there are limited data. Minimally invasive thoracoscopic approaches for ectopic tumors seemed safe. The current level of statistical evidence on pediatric PHP qualifies our study- and case-sample-based analysis (n = 48, N = 534) as one of the largest of its kind. Awareness of PHP is the key factor to benefit our young patients.

Ultrasound-guided microwave ablation in the treatment of recurrent primary hyperparathyroidism in a patient with MEN1: a case report.

Multiple endocrine neoplasia type 1 (MEN1) is an inherited endocrine syndrome caused by the mutation in the tumor suppressor gene MEN1. The recurrence rate of primary hyperparathyroidism (PHPT) in patients with MEN1 after parathyroidectomy remains high, and the management of recurrent hyperparathyroidism is still challenging. We reported a 44-year-old woman with MEN1 combined with PHPT who was diagnosed through genetic screening of the patient and her family members. After parathyroidectomy to remove one parathyroid gland, the patient suffered from persistent high levels of serum calcium and parathyroid hormone, which returned to normal at up to 8 months after ultrasound-guided microwave ablation (MWA) for bilateral parathyroid glands, suggesting an acceptable short-term prognosis. Ultrasound-guided MWA for parathyroid nodules may be an effective therapeutic strategy for recurrent PHPT in MEN1 patients.

Retrosternal parathyromatosis in a patient with prior total parathyroidectomy

Abstract Parathyromatosis is a rare cause of recurrent primary hyperparathyroidism that often follows surgical removal of the parathyroid gland. Foci of parathyromatosis are most commonly found in the neck, mediastinum, and sites of autotransplantation. A 36-year-old male with renal failure and prior parathyroidectomy presented with generalized bone pain, for which laboratory investigations revealed hyperparathyroidism. Preoperative coil localization was utilized followed by thoracoscopy using fluoroscopy for resection of ectopic parathyroid tissue. The specimen was sent to histopathology, which revealed multiple nodules of hypercellular parathyroid tissue, consistent with the diagnosis of parathyromatosis. Parathyromatosis is a rare cause of recurrent hyperparathyroidism, with surgical removal being the only curative option. Follow-up is essential as it can commonly recur.

Recurrent primary hyperparathyroidism

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Two cases of parathyromatosis in patients with recurrent primary hyperparathyroidism

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Update on the current management of persistent and recurrent primary hyperparathyroidism after parathyroidectomy

Primary hyperparathyroidism (pHPT) is the third most common endocrine disease. The surgical procedure aims for permanent cure, but recurrence has been reported in 4%-10% of pHPT patients. Preoperative localization imaging is highly valuable. It includes ultrasound, computed tomography (CT), single-photon-emission CT, sestamibi scintigraphy and magnetic resonance imaging. The operation has been defined as successful when postoperative continuous eucalcemia exists for more than the first six months. Ongoing hypercalcemia during this period is defined as persistence, and recurrence is defined as hypercalcemia after six months of normocalcemia. Vitamin D is a crucial factor for a good outcome. Intraoperative parathyroid hormone (PTH) monitoring can safely predict the outcomes and should be suggested. PTH ≤ 40 pg/mL or the traditional decrease ≥ 50% from baseline minimizes the likelihood of persistence. Risk factors for persistence are hyperplasia and normal parathyroid tissue on histopathology. Risk factors for recurrence are cardiac history, obesity, endoscopic approach and low-volume center (at least 31 cases/year). Cases with double adenomas or four-gland hyperplasia have a greater likelihood of persistence/ recurrence. A 6-mo calcium > 9.7 mg/dL and eucalcemic parathyroid hormone elevation at 6 mo may be associated with recurrence necessitating long-term follow-up. 18F-fluorocholine positron emission tomography and 4-dimensional CT in persistent and recurrent cases can be valuable before reoperation. With these novel advances in preoperative imaging and localization as well as intraoperative PTH measurement, the recurrence rate has dropped to 2.5%-5%. Six-month serum calcium ≥ 9.8 mg/dL and parathyroid hormone ≥ 80 pg/mL indicate a risk of recurrence. Negative sestamibi scintigraphy, diabetes and elevated osteocalcin levels are predictors of multiglandular disease, which brings an increased risk of persistence and recurrence. Bilateral neck exploration was considered the gold-standard diagnostic method. Minimally invasive parathyroidectomy and neck exploration are both effective surgical techniques. Multidisciplinary diagnostic and surgical management is required to prevent persistence and recurrence. Long-term follow-up, even up to 10 years, is necessary.

Molecular and Clinical Spectrum of Primary Hyperparathyroidism.

Recent data suggest an increase in the overall incidence of parathyroid disorders with primary hyperparathyroidism (PHPT) being the most prevalent parathyroid disorder. PHPT is associated with morbidities (fractures, kidney stones, chronic kidney disease) and increased risk of death. The symptoms of PHPT can be non-specific, potentially delaying the diagnosis. Approximately 15% of patients with PHPT have an underlying heritable form of PHPT which may be associated with extra-parathyroidal manifestations, requiring active surveillance for these manifestations as seen in multiple endocrine neoplasia type 1 and 2A. Genetic testing for heritable forms should be offered to patients with multi-glandular disease, recurrent PHPT, young onset PHPT (age ≤ 40 years) and those with a family history of parathyroid tumors. However, the underlying genetic cause of majority of patients with heritable forms of PHPT remains unknown. Distinction between sporadic and heritable forms of PHPT is useful in surgical planning for parathyroidectomy and has implications for family. The genes currently known to be associated with heritable forms of PHPT account for approximately half of the sporadic parathyroid tumors. But the genetic cause in approximately half of the sporadic parathyroid tumors remains unknown. Furthermore, there is no systemic therapy for parathyroid carcinoma, a rare but potentially fatal cause of PHPT. Improved understanding of the molecular characteristics of parathyroid tumors will allow us to identify biomarkers for diagnosis and novel targets for therapy.

Clinical and Economic Evaluation of Ultrasound-Guided Radiofrequency Ablation vs. Parathyroidectomy for Patients with Primary Hyperparathyroidism: A Cohort Study

To compare the clinical and economic effects of ultrasound (US)-guided radiofrequency ablation (RFA) with parathyroidectomy (PTX) for primary hyperparathyroidism (PHPT). From April 2014 to April 2021, 123 PHPT patients who received US-guided RFA or PTX were studied. Propensity score (PS) matching was used to balance the baseline data of the two groups. The rates of cure, recurrent and persistent PHPT, and complications were compared. A Chinese healthcare system perspective cost minimization analysis was conducted. After PS matching, 37 patient pairs (1:1) were created for the two groups. Follow-up was 27.2 ± 10.6 months and 28.8 ± 16.1 months for the RFA and PTX groups, respectively. At the last follow-up, there was no evidence of differences regarding clinical cure rate between the two groups (RFA vs. PTX, 91.9% vs. 94.6%, p=1.000). Recurrent PHPT did not develop in any patient. One patient in each group had persistent PHPT. The incidence of complications and side effects, except postoperative pain (RFA vs. PTX, 16.2% vs. 40.5%, p=0.020), were no significant difference between the two groups (all, p > 0.05). The incremental cost was -$284.00; thus, RFA was more cost-effective. For patients with employee medical insurance or resident medical insurance, the incremental costs (RFA vs. PTX) were -$391.94 and -$49.43, respectively. There were no significant differences in efficacy and safety between RFA and PTX. As the incremental cost for RFA compared with PTX was negative, RFA may be used as a more cost-effective nonsurgical treatment alternative for PHPT.

Dual-tracer 99mTc-sestamibi/ 123I imaging in primary hyperparathyroidism.

Surgery is the only curative treatment for primary hyperparathyroidism (PHPT). Preoperative imaging is always recommended. 99mTc-sestamibi scintigraphy is often used in combination with neck ultrasonography as first-line imaging. 99mTc-sestamibi scintigraphy plays a major role in depicting ectopic parathyroid lesions, as well as in guiding a targeted, minimally invasive parathyroidectomy (MIP). Detecting multiple gland disease (MGD) is important to reduce the risks of surgical failure or unplanned conversion to bilateral surgery. However, the ability to recognize MGD varies greatly depending on the 99mTc-sestamibi imaging protocol that is used. Dual-tracer 99mTc-sestamibi/123I highly improves MGD detection compared to single-tracer "dual-phase" 99mTc-sestamibi imaging. It can thus improve patient selection for MIP. The main requirements for successful dual-tracer imaging are: 1) to acquire 99mTc-sestamibi and 123-iodine images simultaneously, thus avoiding motion artifacts on subtraction images; to use neck pinhole imaging, in addition to planar imaging, to improve resolution and MGD detection; to follow with dual-tracer SPECT/CT imaging to better define anatomic position of detected parathyroid lesions. If dual-tracer 99mTc-sestamibi/123I and neck ultrasonography are negative or inconclusive, the second-line imaging in our practice is 18F-fluorocholine PET/CT. The CT component of 18F-fluorocholine PET/CT is performed as non-enhanced acquisition plus a contrast-enhanced arterial phase acquisition, to minimize the risk from false-positives due to choline uptake in inflammatory lymph nodes. We use the same strategy of first-line dual-tracer 99mTc-sestamibi/123I plus neck ultrasonography, followed if necessary by second-line contrast-enhanced 18F-fluorocholine PET/CT, in patients requiring reoperation for persistent or recurrent PHPT. Additional localization techniques are now rarely necessary.

Persistent and Recurrent Primary Hyperparathyroidism: Etiological Factors and Pre-Operative Evaluation.

Primary hyperparathyroidism (pHPT) is the most common cause of hypercalcemia and currently the only definitive treatment is surgery. Although the success rate of parathyroidectomy is over 95% in experienced centers, surgical failure is the most common complication today. Persistent HPT (perHPT) is defined as persistence of hypercalcemia after parathyroidectomy or recurrence of hypercalcemia within the first 6 months, and recurrence of hypercalcemia after a normocalcemic period of more than 6 months is defined as recurrent HPT (recHPT). In the literature, perHPT is reported to be 2-22%, and the rate of recHPT is 1-15%. perHPT is often associated with misdiagnosed pathology or inadequate resection of hyperfunctioning parathyroid tissue, recHPT is associated with newly developing pathology from potentially pathologically natural tissue left in situ at the initial surgery. In the pre-operative evaluation, the initial diagnosis of pHPT and the diagnosis of perHPT or rec HPT should be confirmed in patients who are evaluated with a pre-diagnosis (suspect) of perHPT and recHPT. Surgery is recommended if it meets any of the recommendations in surgical guidelines, as in patients with pHPT, and there are no surgical contraindications. The first preoperative localization studies, surgical notes, operation drawings, if any, intraoperative PTH results, pathological results, and post-operative biochemical results of these patients should be examined. Localization studies with preoperative imaging methods should be performed in all patients with perHPT and recHPT with a confirmed diagnosis and surgical indication. The first-stage imaging methods are ultrasonography and Tc99m sestamibi single photon tomography Tc99mMIBI SPECT or hybrid imaging method, which is combined with both single-photon emission computed tomography and computed tomography (SPECT/CT). The combination of USG and sestamibi scintigraphy increases the localization of the pathological gland. In the secondary stage, Four-Dimensional computer tomography (4D-CT) or dynamic 4-dimensional Magnetic Resonance Imaging (4D-MRI) can be applied. It is focused on as a secondary stage imaging method, especially when the lesion cannot be detected by conventional methods. Positron Emission Tomography (PET) and PET/CT examinations with 11C-choline or 18F-fluorocholine are promising imaging modalities. Invasive examinations can rarely be performed in patients in whom suspicious, incompatible or pathological lesion cannot be detected in noninvasive imaging methods. Bilateral jugular vein sampling, selective venous sampling, parathyroid arteriography, imaging-guided fine-needle aspiration biopsy, and parathormone washout are invasive methods.

Parathyroid Carcinoma Presenting as Recurrent Primary Hyperparathyroidism and Neck Mass: A Case Report.

Parathyroid carcinoma is a rare endocrine neoplasm that accounts for <1% of cases of primary hyperparathyroidism. The management of parathyroid carcinoma is a challenge due to the high rate of local recurrence of the tumour. We report the case of a middle-aged north Indian woman who presented with recurrent primary hyperparathyroidism due to parathyroid carcinoma. She presented with a recurrent palpable hard neck mass and underwent radical dissection of the neck six times. At the time of writing this report, she was referred for external beam radiotherapy to the neck. Parathyroid carcinoma is a rare malignancy with an indolent but tenacious course. Complete resection at the time of initial surgery determines the prognosis of the neoplasm. Chemotherapy and radiotherapy are usually ineffective. Hypercalcaemia needs to be aggressively managed. A multidisciplinary team is required to effectively manage parathyroid carcinoma.

Persistent and Recurrent Primary Hyperparathyroidism: Intraoperative Supplemental Methods, Basic Principles of Surgery, and Other Treatment Options.

Reoperative parathyroid surgery is challenging even for experienced surgeons. Cure rates are lower than primary surgery. Good anatomical and embryological knowledge is important. Preoperatively, a comprehensive surgical strategy should be planned. Pre-operative imaging modalities should be used extensively to find the overlooked gland to have a possibility to perform focused parathyroid surgery to avoid possible complications. One of the important developments is the new ancillary methods to find overlooked parathyroid glands. Orthotopic and possible ectopic locations should be known well by the surgeon to increase the surgical success rate. Reoperative parathyroid surgery needs a distinctive approach compared to primary parathyroid surgery. Basic principles include the selection of the incision and route for entering the thyroid region, use of ancillary methods, and intraoperative nerve monitoring and also require a meticulous dissection. Obtaining a surgical cure is difficult and high surgical caution is needed. Post-operative complication rates are higher compared to primary parathyroid surgery. Other treatment methods and medical treatment options may be evaluated in a patient who cannot undergo surgery.

Supernumerary Mediastinal Parathyroid Carcinoma Resulting in Recurrent Primary Hyperparathyroidism and Hypercalcemic Crisis: A Case Report

Supernumerary Mediastinal Parathyroid Carcinoma Resulting in Recurrent Primary Hyperparathyroidism and Hypercalcemic Crisis: A Case Report

Mediastinal parathyroidectomy by VATS for persistent, sporadic primary hyperparathyroidism in an adolescent

Primary hyperparathyroidism (PHPT) is an endocrine disorder that is commonly diagnosed in adults. PHPT is less commonly seen in the pediatric age range, and when identified, non-syndromic disease is unusual. PHPT caused by an ectopic parathyroid gland is rare, especially in the adolescent population, and may contribute to disease persistence. Because parathyroidectomy is the only known curative treatment for PHPT, localization of the abnormal gland(s) preoperatively is often attempted, and is critical prior to re-operation. Recurrent or persistent PHPT continues to be a surgical challenge because parathyroidectomy via traditional cervical incision may not be feasible for parathyroid adenomas located in an ectopic location. When identified in the thymus, minimally invasive approaches are preferred over sternotomy or thoracotomy because of decreased morbidity rates and improved patient outcomes. Recently, parathyroidectomy via video-assisted thoracoscopic surgery (VATS) for mediastinal parathyroid adenomas has been described in the literature. We report a case of a non-syndromic adolescent with persistent PHPT who was cured after undergoing mediastinal parathyroidectomy via VATS approach while utilizing intraoperative parathyroid hormone guidance and frozen-section pathologic analysis.

Changes in the pathophysiology of primary hyperparathyroidism and analysis of postoperative recurrence cases at a regional core hospital in Japan: experience of 35 years in Shinshu University Hospital.

Since reoperation for recurrent primary hyperparathyroidism (PHPT) increases the risk of complications, such as recurrent laryngeal nerve palsy, it is vital to prevent recurrence as much as possible when performing the initial surgery. Therefore, we retrospectively analyzed the PHPT cases at Shinshu University Hospital from 1986 to 2020 for changes in the characteristics of PHPT over time and features of the recurrent cases to establish treatment strategies to prevent a postoperative recurrence. Hereditary PHPT was diagnosed through endocrinological tests, systemic imaging, and/or genetic testing. Localization of swollen parathyroid glands was identified through neck ultrasonography (US), contrast-enhanced computed tomography, magnetic resonance imaging (MRI), and 99mTc-sestamibi scintigraphy. Among the 536 patients with PHPT (374 women and 162 men) with a mean age of 56.9±13.6 years, 90 (16.8%) had hereditary PHPT, while the other 446 (83.2%) had sporadic PHPT. Overall, 314 (58.6%) patients were asymptomatic, whereas 132 (24.6%) had symptoms related to PHPT. Asymptomatic PHPT was significantly more prevalent after 2001 (81.8%) than before 2001 (51.2%) (P<0.01), although the number of PHPT cases increased during the last decade. Resection of an enlarged parathyroid gland alone was performed for sporadic PHPT, while focused parathyroidectomy was performed after 2001. Total parathyroidectomy (TPTx) with autotransplantation was performed in patients with hereditary PHPT. In addition, the intraoperative rapid pathological diagnosis of the resected gland throughout the period and intraoperative serum intact parathyroid hormone (PTH) measurement from 2014 were used. Overall, 11 patients with hereditary PHPT (2.1%) developed recurrence. A recurrent parathyroid gland was identified in 10 of 11 cases through 99mTc-sestamibi scintigraphy. Although the incidence of asymptomatic PHPT has been increasing recently, focused parathyroidectomy is considered an appropriate procedure for sporadic PHPT that has been carefully examined preoperatively. Therefore, in the future, it will be necessary to conduct genetic testing for sporadic PHPT cases as much as possible to accurately diagnose the disease type and decide on a treatment strategy.

Surgery for primary hyperparathyroidism.

Primary hyperparathyroidism (PHPT) is a hypercalcemic disorder that occurs when one or more parathyroid glands produces excessive parathyroid hormone (PTH). PHPT is typically treated with surgery, and it remains the only definitive therapy, whose techniques have evolved over previous decades. Advances in preoperative localization exams and the intraoperative PTH monitoring have become the cornerstones of recent parathyroidectomy techniques, as minimally invasive techniques are appropriate for most patients. Nevertheless, these techniques, are not suitable for PHPT patients who are at risk for multiglandular disease, especially in those who present with familial forms of PHPT that require bilateral neck exploration. This manuscript also explores other conditions that warrant special consideration during surgical treatment for PHPT: normocalcemic primary hyperparathyroidism, pregnancy, reoperation for persistent or recurrent PHPT, parathyroid carcinoma, and familial and genetic forms of hyperparathyroidism.

LBSAT144 Single-center Experience With Hyperparathyroidism-jaw Tumor Syndrome - Where Do We Stand?

Abstract Background Hyperparathyroidism-jaw tumor (HPT-JT) syndrome is a heritable form of primary hyperparathyroidism (PHPT) associated with tumors in parathyroid, jaw, kidney, and uterus. This work aims to provide a natural history of HPT-JT from a long-term follow-up of a large single-institution cohort. Methods We identified patients with HPT-JT seen under the natural history study of parathyroid disorders from 1991-2020 and analyzed their disease manifestations and treatment outcomes. Results Sixty-six patients (50% males) from 32 kindreds with HPT-JT (genotype-positive: 46, presumed genotype-positive: 20). Median age at presentation of index patients was 24 [19-33] years. PHPT was prevalent in 51/61(84%) patients, of which seven had ectopic parathyroid tumors and 20/50 (40%) had multi-gland disease. Eighty-two parathyroid tumors were removed from 52 patients through 66 surgeries -17/66 (26%) unilateral; 23/66 (35%) bilateral neck explorations. Parathyroid cancer (PC) was seen in 16/78 tumors (21%), atypical parathyroid in 2/78(3%), parathyroid adenoma (PA) in 12/78 (15%), hyperplasia in 27/78 (35%) and microscopically normal but enlarged parathyroid in 21/78 (27%). PAs had median tumor size 10 [7-17] mm, PC: 19 [11-25] mm. We found a significant correlation between tumor size and serum PTH (r=0.55, p=0. 007). Uterine tumor was second most common disease manifestation (10/36 females, 28%) - initial manifestation in 5/10. Median age of presentation was 18 [15-21] years with presentations of menorrhagia, abdominal pain, or miscarriage. The histology of uterine tumors included adenomyoma, fibroids or leiomyomata. JT was noted in 5/70 (7%) patients (three mandibular, two maxillary tumors) - initial manifestation in 3/5. Median age of presentation with JTs was 23 [20-31] years. Microscopically, JTs were diagnosed as cysts (n=2), cemento-ossifying fibroma (n=2) and fibro-osteoid lesions (n=1). Kidney tumors were observed in three patients - one presented with abdominal pain, two were diagnosed on surveillance scans. Median age at presentation was 25 [6-44] years. Two related patients had bilateral mixed epithelial and stromal tumors while a 6-year-old male had Wilm's tumor. Median age at last follow-up was 37 [28-49] years. Recurrent PHPT was seen in 5/35(14%) patients with PA or hyperplasia (Median recurrence time: 10[7 - 16] years) and 12/15(80%) with PC (Median recurrence time: 2[1 - 5] yeas. Co-existing psychiatric disorder, mainly depression and anxiety were seen in 16/68 (24%) patients, consistent with published literature for other chronic conditions. Conclusion Most (60%) patients with HPT-JT have single-gland disease with recurrence seen in only a minority of patients (14%) with PAs. JTs are not as common as the name suggests while uterine tumors appear to be relatively frequent. Acknowledgement: This research is supported by the Intramural Research Program of NIDDK and NCI. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

RF27 | LBSUN361 Understanding The Genetics Of Multiple Endocrine Neoplasia Type 1: The Road Ahead

Abstract Background About 10-30% patients have genotype-negative (GN)-MEN1. Here, we compare our cohort of comprehensively phenotyped GN-MEN1 and genotype-positive (GP)-MEN1 patients. We also investigate somatic mosaicism as a cause of GN-MEN1. Methods GN-MEN1 patients showed no mutations in MEN1 or other primary hyperparathyroidism (PHPT) genes (CASR, RET, CDKN1B, CDC73, AIP, GNA11, AP2S1, GCM2) performed per clinical indication. Index patients (first patient in kindred to be diagnosed with MEN1) or probands (first patient in kindred to be evaluated at our center) from kindreds with GP-MEN1 were identified. All patients underwent testing for tumor biomarkers, imaging and evaluation for Zollinger-Ellison syndrome (ZES). Whole exome sequencing was performed on multiple tumors from 13 GN-MEN1 patients. GP-MEN1 patients were also categorized into high-impact (nonsense, frameshift, splice site, whole or partial gene deletion) or low-impact (missense or in-frame indels) mutation-bearing groups. Results We identified 43 (31 females, 12 males) patients with GN-MEN1 and 160 (102 index, 58 probands) patients with GP-MEN1 (98 females, 62 males). Among GP-MEN1, 97 had high impact and 34 had low-impact mutations. Mean age at last follow-up was 56 (±14) years for GN-MEN1 and 52 (±16) years for GP-MEN1 patients. Among the GN-MEN1 patients, 38/42 developed PHPT - 3/38 (8%) had recurrent disease. In GP-MEN1, 144/149 developed PHPT - 83/144 (58%) with recurrent disease. Median age of index presentation with PHPT significantly differed between the groups (27.5 years in GP-MEN1 vs 53 years in GN-MEN1 (χ2 (1)=5.5: p &amp;lt;0.05)). 33/42 GN-MEN1 patients had a pituitary adenoma (22/33 functioning - 9/22 prolactinomas; 8/22 GH-secreting). In comparison, 94/145 GP-MEN1 patients developed a pituitary adenoma (51 functioning - 37/51 prolactinomas, no GH-secreting tumors). In the GN-MEN1 group, 12/42 (29%) patients developed a gastro-entero-pancreatic (GEP)-NET. In comparison, 86/130 (66%) patients with GP-MEN1 had a GEP-NET. Somatic variants in MEN1, CDC73 or CDKI were observed in six tumors. However, these mutations were not seen in another tumor/s or germline DNA from the patient. All patients with high-impact mutations had PHPT (63% had recurrent disease), 70% had pituitary tumors (35% with macro-adenomas) and 61% developed GEP-NETs (29% with distant metastases). In comparison, 91% patients with low-impact mutations developed PHPT (41% with recurrent disease), 69% developed pituitary tumors (23% with macro-adenomas) and 65% developed GEP-NETs (35% with distant metastases). Conclusion Patients with GP-MEN1 generally experience younger age of onset, greater likelihood of recurrent PHPT and co-occurrence of GEP-NETs in comparison to GN-MEN1. Our findings do not support somatic mosaicism as a cause of GN-MEN1. No apparent correlation in phenotype between high-impact vs. low-impact mutations is noted. Presentation: Monday, June 13, 2022 12:51 p.m. - 12:56 p.m.