Severe Primary Hyperparathyroidism Research Articles

9-year remission of severe primary hyperparathyroidism after high-dose cinacalcet treatment: case report

9-year remission of severe primary hyperparathyroidism after high-dose cinacalcet treatment: case report

Characteristics, management and outcomes of primary hyperparathyroidism from 2009 to 2021: a single centre report from South Africa

BackgroundThere has been a notable shift towards the diagnosis of less severe and asymptomatic primary hyperparathyroidism (PHPT) in developed countries. However, there is a paucity of recent data from sub-Saharan Africa (SSA), and also, no reported data from SSA on the utility of intra-operative parathyroid hormone (IO-PTH) monitoring. In an earlier study from Inkosi Albert Luthuli Central Hospital (IALCH), Durban, South Africa (2003–2009), majority of patients (92.9%) had symptomatic disease. The aim of this study was to evaluate the clinical profile and management outcomes of patients presenting with PHPT at IALCH.MethodsA retrospective chart review of patients with PHPT attending the Endocrinology clinic at IALCH between July 2009 and December 2021. Clinical presentation, laboratory results, radiologic findings, surgical notes and histology were recorded.ResultsAnalysis included 110 patients (87% female) with PHPT. Median age at presentation was 57 (44; 67.5) years. Symptomatic disease was present in 62.7% (n:69); 20.9% (n:23) had a history of nephrolithiasis and 7.3% (n:8) presented with previous fragility fractures. Mean serum calcium was 2.87 ± 0.34 mmol/l; median serum-PTH was 23.3 (15.59; 45.38) pmol/l, alkaline phosphatase 117.5 (89; 145.5) U/l and 25-hydroxyvitamin-D 42.9 (33.26; 62.92) nmol/l. Sestamibi scan (n:106 patients) identified an adenoma in 83.02%. Parathyroidectomy was performed on 84 patients with a cure rate of 95.2%. Reasons for conservative management (n:26) included: no current surgical indication (n:7), refusal (n:5) or deferral of surgery (n:5), loss to follow-up (n:5) and assessed as high anaesthetic risk (n:4). IO-PTH measurements performed on 28 patients indicated surgical success in 100%, based on Miami criteria. Histology confirmed adenoma in 88.1%, hyperplasia in 7.1% and carcinoma in 4.8%. Post-operative hypocalcaemia developed in 30 patients (35.7%), of whom, 14 developed hungry bone syndrome (HBS). In multivariate analysis, significant risk factors associated with HBS included male sex (OR 7.01; 95% CI 1.28, 38.39; p 0.025) and elevated pre-operative PTH (OR 1.01; 95% CI 1.00, 1.02; p 0.008).ConclusionsThe proportion of asymptomatic PHPT has increased at this centre over the past decade but symptomatic disease remains the dominant presentation. Parathyroidectomy is curative in the majority of patients. IO-PTH monitoring is valuable in ensuring successful surgery.

Familial states of primary hyperparathyroidism: an update.

Familial primary hyperparathyroidism (PHPT) includes syndromic and non-syndromic disorders. The former are characterized by the occurrence of PHPT in association with extra-parathyroid manifestations and includes multiple endocrine neoplasia (MEN) types 1, 2, and 4 syndromes, and hyperparathyroidism-jaw tumor (HPT-JT). The latter consists of familial hypocalciuric hypercalcemia (FHH) types 1, 2 and 3, neonatal severe primary hyperparathyroidism (NSHPT), and familial isolated primary hyperparathyroidism (FIHP). The familial forms of PHPT show different levels of PHPT penetrance, developing earlier and with multiglandular involvement compared to sporadic counterpart. All these diseases exhibit Mendelian inheritance patterns, and for most of them, the genes responsible have been identified. DNA testing for predisposing mutations is helpful in index cases or in individuals with a high suspicion of the disease. Early recognition of hereditary disorders of PHPT is of great importance for the best clinical and surgical approach. Genetic testing is useful in routine clinical practice because it will also involve appropriate screening for extra-parathyroidal manifestations related to the syndrome as well as the identification of asymptomatic carriers of the mutation. The aim of the review is to discuss the current knowledge on the clinical and genetic profile of these disorders along with the importance of genetic testing in clinical practice.

Hyperparathyroidism and Peripheral Arterial Disease.

Primary hyperparathyroidism (PHPT) is presented in various forms, including classic PHPT, characterised by increased parathyroid hormone (PTH) secretion, normohormonal PHPT, and normocalcaemic PHPT. Secondary hyperparathyroidism is characterised by increased PTH secretion triggered by factors such as vitamin D deficiency and kidney failure. This review aims to discuss the involvement of hyperparathyroidism (HPT) in atherosclerosis, including peripheral arterial disease (PAD). The increased level of PTH is involved in developing subclinical and overt vascular diseases, encompassing endothelial dysfunction, vascular stiffness, hypertension, and coronary and peripheral arterial diseases. It has been consistently associated with an augmented risk of cardiovascular morbidity and mortality, independent of classical risk factors for atherosclerosis. Chronic hypercalcemia associated with increased levels of PTH contributes to the development of calcification of vessel walls and atherosclerotic plaques. Vascular calcification can occur in the intima or media of the arterial wall and is associated with stiffness of peripheral arteries, which the formation of atherosclerotic plaques and narrowing of the vessel lumen can follow. For treating hyperparathyroidism, particularly SHPT, calcimimetics, novel phosphorus binders and novel vitamin D receptor activators are used. However, they are ineffective in severe PHPT. Therefore, parathyroidectomy remains the primary therapeutic option of PHPT.

Association between preoperative cholecalciferol therapy and hypocalcemia after parathyroidectomy in patients with primary hyperparathyroidism

Primary hyperparathyroidism (PHPT) is a endocrine disorder characterized by excessive secretion of parathyroid hormone (PTH) from parathyroid gland tumors. Parathyroidectomy (PTE) is the main treatment for PHPT, but it can lead to hypocalcemia in up to 46% of cases. Hypocalcemia is associated with seizures and life-threatening cardiac arrhythmias, and vitamin D deficiency can exacerbate PHPT severity and contribute to «hungry bones syndrome,» resulting in severe and persistent postoperative hypocalcemia. To evaluate the association and determine the strength of the relationship between preoperative cholecalciferol therapy and the occurrence of hypocalcemia within 1-3 days after PTE in patients with PHPT. The study was conducted at the Endocrinology Research Centre, during the periods of 1993-2010 and 2017-2020. The inclusion criteria consisted of patients diagnosed with PHPT who required PTE, had a serum 25-hydroxyvitamin D (25(OH)D) level below 20 ng/mL, and a serum total calcium level below 3 mmol/L. The exclusion criterion was the use of medications that affect calcium-phosphorus metabolism, including cinacalcet, denosumab, or bisphosphonates, either as monotherapy or as part of combination therapy. There were 117 patients, including 110 (94%) females and 7 (6%) males. The median age and interquartile range were 58 [49; 65] years. Among the participants, 21 (18%) received cholecalciferol supplementation for a duration of 2 weeks to 2 months prior to PTE, aiming to address vitamin D deficiency. The remaining 96 (82%) participants did not receive -cholecalciferol supplementation. Both groups, i.e., participants receiving cholecalciferol and those who did not, were similar in terms of anthropometric factors (sex and age at the time of surgery), preoperative clinical characteristics (BMD decrease), and laboratory parameters (PTH, total calcium, phosphorus, ALP, OC, CTX-1, and 25(OH)D levels). The occurrence of postoperative hypocalcemia was significantly lower in participants who received cholecalciferol supplementation (10% vs. 63%, p<0,001, FET2). Cholecalciferol intake showed a negative association with hypocalcemia development (RR=0,15, 95% CI (0,03; 0,51)). Preoperative cholecalciferol supplementation for 2 weeks to 2 months before PTE reduces the risk of postoperative hypocalcemia in patients with PHPT by 2-33 times.

Neonatal Severe Primary Hyperparathyroidism—Presentation, Management, and Follow-up of Seven Cases

Neonatal Severe Primary Hyperparathyroidism—Presentation, Management, and Follow-up of Seven Cases

Vitamin D Deficiency and the Presentation of Primary Hyperparathyroidism: A Mini Review.

The clinical presentation of primary hyperparathyroidism (PHPT) has evolved over the years from a symptomatic disorder to a predominantly asymptomatic condition. Altered vitamin D metabolism seems to play a role in the presentation of PHPT and may exacerbate the severity of disease. The epidemiology of PHPT differs in the developing versus the developed world, where more severe phenotypes occur in regions where vitamin D deficiency is common. Although it has been validated that patients with PHPT should be vitamin D sufficient, the threshold to supplement in relation to the severity of PHPT and the degree of vitamin D deficiency remains controversial. This review will highlight some of the controversy regarding vitamin D deficiency and the different phenotypes of PHPT.

Parathyroid carcinoma case-report in a patient with multinodular goiter and chronic kidney disease: difficulties in diagnosis and treatment (observation from practice)

We would like to present a clinical case of severe primary hyperparathyroidism due to a parathyroid carcinoma of atypical location in a patient with chronic kidney disease of complex etiology and multinodular goiter. Patient S., 59 years old, was followed-up for a long time in tertiary referral hospitals for “chronic tubulointerstitial nephritis with nephrosclerosis”, secondary hyperparathyroidism due to chronic kidney disease (CKD) G3–4, osteoporosis, and a multinodular euthyroid colloid goiter. In July 2021 she was referred to the Endocrinology Research Centre in order to clarify the diagnosis because of the persistence of an extremely high level of parathyroid hormone (PTH) despite cinacalcet treatment. During examination, primary hyperparathyroidism, a left parathyroid gland lesion, multinodular goiter with subclinical thyrotoxicosis, and vitamin D deficiency were diagnosed. After the removal of the left parathyroid gland lesion (histologically confirmed parathyroid carcinoma) and a left-sided hemithyroidectomy, hypocalcemia («hungry bone syndrome») developed, but the level of parathyroid hormone remained elevated. After 3–18 months after surgery, no data for relapse of primary hyperparathyroidism was obtained. The persistent moderate increase in PTH was regarded as secondary hyperparathyroidism in CKD and hypocalcemia. Complex therapy of osteoporosis with the antiresorptive drug denosumab, vitamin D and its active metabolite, calcium preparations, and parathyroidectomy led to a significant increase in bone mineral density (BMD) and no repeated fractures 18 months after surgery.Conclusion. In patients with pre-dialysis CKD and high PTH levels, it is necessary to make a differential diagnosis between primary (PHPT) and secondary hyperparathyroidism (SHPT). Severe manifestations of primary hyperparathyroidism can be suspicious for parathyroid carcinoma.

Parenteral bisphosphonate therapy is effective and safe when given prior to parathyroid surgery in severe primary hyperparathyroidism

Parenteral bisphosphonate therapy is effective and safe when given prior to parathyroid surgery in severe primary hyperparathyroidism

SAT178 EZH2 Upregulation And Lysine 27 Trimethylation at Histone 3 Is Associated With Severe Sporadic Primary Hyperparathyroidism

Abstract Disclosure: P. Kumari: None. A.K. Arya: None. D. Dahiya: None. N. Sachdeva: None. J. Kaur: None. U.N. Saikia: None. S. Bhadada: None. S.D. Rao: None. Introduction: The enhancer of zeste homolog 2 (EZH2) is a histone methyltransferase that regulates gene activity through histone modifications of lysine (K) at H3 histone and has a crucial role in tumor development. However, the level of methylation at H3 histone and its association with EZH2 expression in sporadic primary hyperparathyroidism (PHPT) are not known. This study was designed to investigate how global levels of histone methylation were associated with altered expression of EZH2 in promoting parathyroid tumorigenesis. Methodology: A total of 30 parathyroid tumors (15 non-severe, 15 severe, and 5 normal parathyroid tissues) were collected during 2020-2021. The global histone methylation of major methylation sites at lysine (K) K4, K9, K27, K36, and K79 was evaluated from blood and tissue samples using a calorimetric ELISA (H3 global modification kit, Epegentek, USA). Gene and protein expression of EZH2 were performed by quantitative real-time PCR and immunohistochemistry respectively. Histone methylation and expression data were correlated with indices of disease severity. Results: We found that the global levels of H3K27me1 and me3 were significantly upregulated, whereas, H3K4me3 and H3K36me2 were significantly downregulated in tumors from patients with severe PHPT compared to tumors from non-severe PHPT and controls. Moreover, H3K27me3 showed the highest upregulation (8-fold) in severe PHPT. Additionally, EZH2 gene expression was significantly upregulated in severe PHPT [Mean ± S.E; (9.1 ± 1.6 vs. 1.2 ± 0.3, p = 0.005), but not in non-severe (4.2 ± 2.7 vs. 1.2 ± 0.3, p = 0.4) PHPT, compared to normal parathyroid tissues. Furthermore, the protein expression was also consistent with the gene expression, with 86% (n= 13/15) nuclear positivity for EZH2 in tumors from severe PHPT and 40% (6 of 15) in tumors from non-severe PHPT compared to normal parathyroid tissue (negative staining). Correlation analysis revealed that EZH2 gene expression is positively related with S.Ca (r = 0.44, p = 0.003), PTH (r = 0.59, p = 0.000), tumor weight (r = 0.455, p = 0.002), EZH2 protein expression (r = 0.7, p = 0.000), and Ki67 proliferative marker (r = 0.66, p = 0.002). Conclusions: Increased global trimethylation of K27 at histone 3 (H3K27me3) was associated with increased EZH2 expression in sporadic PHPT and was predictive of a more severe clinical phenotype. Sources of research support: (ICMR), New Delhi Extramural Research Grant 2020. Presentation: Saturday, June 17, 2023

SAT187 A Case Of CDC73 Mutation Related Primary Hyperparathyroidism With Ectopic Parathyroid Hyperplasia

Abstract Disclosure: T. Wu: None. N. Dhir: None. M. Bollineni: None. Introduction: Primary hyperparathyroidism is the most common cause of hypercalcemia, and most cases are sporadic. However, in 5-10% cases, it may occur as a syndromic and hereditary disease, like Multiple endocrine neoplasia type 1, type 2A, type 4, or CDC73 mutation related hereditary benign or malignant hyperparathyroidism. In patients with severe or early onset primary hyperparathyroidism, screening for genetic etiology should be considered. Case Presentation: A 35-year-old woman with a medical history of hypertension, kidney stones, and post-operative hypothyroidism presented to the endocrinology clinic due to recurrent hyperparathyroidism. She initially had a parathyroidectomy in 2008 and her calcium corrected at that time. She was again diagnosed with hypercalcemia due to primary hyperparathyroidism in 2021. She underwent re-exploration and had a right thyroid lobectomy with removal of three parathyroid glands. Her PTH was still 309 pg/mL (9-77 pg/mL) and calcium was 11.2 mg/dL (8.6-10.5 mg/dL), and she was started on Cinacalcet. The patient continued to have elevated calcium, bone pain, fatigue, and constipation. A 4D CT scan was ordered, which localized activity to a 1.5 cm arterial enhancing nodule in the anterior mediastinum, with intrathymic location. She underwent right video-assisted thoracoscopic total thymectomy with en bloc and the nodule was found to be ectopic parathyroid tissue. Post-operatively, her calcium normalized to 8.6 mg/dL and PTH was undetectable. She underwent genetic testing due to her recurrent hyperparathyroidism, which showed a CDC73 mutation. She is currently on calcitriol and calcium supplements, and serum calcium has been maintained in the low-normal range. Discussion: The CDC73 gene encodes a protein called parafibromin, which acts as a tumor suppressor, prohibiting cells from proliferating. Mutations in this gene are linked to jaw-tumor syndrome, familial isolated primary hyperparathyroidism (FIHP), and parathyroid carcinoma. These three CDC73-related disorders are clinically overlapping and inherited in an autosomal dominant manner. Biallelic mutations of the CDC73 gene are associated with a high risk of parathyroid cancer since the parafibromin protein is usually absent in parathyroid carcinoma and occasionally in atypical adenomas. FIHP tends to have a more severe clinical presentation with earlier onset (younger than 45 years). Additionally, patients with CDC73 related disorders are more prone to developing ossifying fibroma(s) of the jaw, uterine tumors, and various renal lesions. In summary, this case highlights the diagnostic and therapeutic challenges in a patient with persistent primary hyperparathyroidism after a failed second surgery. Genetic testing is vital for early detection, surveillance, and familial genetic counseling in patients with CDC73 related disorders. Presentation: Saturday, June 17, 2023

The Impact of Moderate Hypophosphatemia on the Clinical Management of Primary Hyperparathyroidism.

Background and objective The impact of moderate hypophosphatemia (hypoP) on primary hyperparathyroidism (PHPT) and its use as an independent surgical criterion has not been adequately evaluated in the literature. In light of this, we conducted this study to address the scarcity of data on this topic. Methods We conducted a retrospective evaluation of data related to 164 (133 females and 31 males) patients with PHPT who met the criteria for inclusion in the study. HypoP, which is indicated by phosphorus (P) levels lower than 2.5 mg/dL, was found in 78 (47.5%) patients, and moderate hypoP (1-1.99 mg/dL) was found in 25 patients (15.2%). Results PHPT severity was worse in hypoP patients than non-hypoP patients, as evidenced by higher levels ofmean serum calcium (12.9 ±1.0 mg/dL vs. 11.1 ±0.3 mg/dL respectively,p<0.001), parathormone (PTH) [median (interquartile range, IQR): 455.3 (455.3)ng/L vs.124.0 (84.0)ng/L respectively, p<0.001] and mean 24-hour urinary calcium (414.6 ±168.5 mg/day vs. 291.5 ±161.4 mg/day respectively, p=0.026) as well as lower levels of mean BMI (25.6 ±3.9 kg/m2vs. 29.0 ±4.0 kg/m2 respectively, p=0.18) and mean 25-hydroxy vitamin D3 (13.8 ±7.3 µg/L vs. 18.2 ±7.8 µg/L respectively, p=0.001). Among the whole study populationas well as among patients with Ca levels <1.0 mg/dLaccording to the upper limit of normal, P level was determined to be an independent factor affecting the indication for surgical treatment [β: -1.96,p=0.038, odds ratio (OR): 0.14, 95% confidence interval (CI): 0.02-0.89 and β: -2.3, p=0.034, OR: 0.10, 95% CI: 0.12-0.84 respectively]. Conclusion We found a strong correlation between moderate hypoP and the severity of the biochemical manifestations of PHPT. In asymptomatic PHPT patients, moderate hypoP was predictive of surgical indication, independent of age and level of hypercalcemia.

Approach to the Patient With Parathyroid Carcinoma.

Parathyroid carcinoma (PC) is usually associated with severe symptomatic primary hyperparathyroidism (PHPT) and accounts for less than 1% of all cases of PHPT and approximately 0.005% of all cancers. PC most commonly occurs as a sporadic disease and somatic CDC73 mutations can be detected in up to 80% of cases. Approximately 30% of patients harbor a germline mutation of the CDC73 gene. Preoperative diagnosis of PC is difficult because no disease-specific markers are available, and PC should be suspected in patients with severe hypercalcemia and end-organ complications. The diagnosis is based on the evidence of invasive tumor growth at histology and/or metastases. En bloc resection of the tumor, together with the ipsilateral thyroid lobe and adjacent structures, should be performed by an experienced surgeon when PC is suspected. This surgical approach reduces the risk of recurrence and metastasis and offers the highest chance of cure. Nonetheless, PC has a recurrence rate of 40% to 60% and, if feasible, multiple surgical procedures should be performed. When surgery is no longer an option, medical treatment is aimed to reduce hypercalcemia and target organ complications. Targeted agents have been effectively used in a few cases. We describe herein a patient with severe PHPT due to PC and provide a systematic diagnostic and treatment approach. A thorough review of the medical history, a typical clinical and biochemical phenotype and, in some cases, the revision of the histological examination provide the clues for the diagnosis of PC.

Rare Presentation of Primary Hyperparathyroidism in a Young Woman.

Even though primary hyperparathyroidism (PHPT) is a common endocrine disorder, due to better and more regular screening, the usual presentation is only seen in less than 15% of cases of PHPT. The authors present the case of a young female patient with a previous medical history of depression and nephrolithiasis, with one year of bone pain, that had become progressively worse and disabling. In the initial work-up, several lytic bone lesions and moderate hypercalcemia were found, leading to admission of the patient in the Internal Medicine ward for investigation and treatment. The ensuing investigation revealed PHPT due to hyperfunctioning parathyroid adenoma. The patient underwent a parathyroidectomy and at the follow-up assessment two months after discharge, she reported no symptoms and a computer tomography scan showed regression of the lytic lesions. This case is a reminder that severe symptomatic PHPT, a rare form in developed countries nowadays, still exists, and even though it is a medical condition, collaboration with surgical specialties is necessary to ensure the best possible treatment and prognosis.

Localization of Brown Tumors With 18 F-Fluorocholine PET/CT Imaging in Severe Primary Hyperparathyroidism.

We present the case of a 68-year-old woman with a painful tibial tumor and fatigue. Histology and laboratory studies were consistent with a brown tumor secondary to initially unrecognized, severe primary hyperparathyroidism. 18 F-fluorocholine PET/CT revealed a large hypermetabolic parathyroid mass and multiple bone foci considered as brown tumors. Unilateral neck exploration confirmed a large parathyroid adenoma. Serum calcium and parathyroid hormone levels normalized quickly, and symptoms subsided gradually after parathyroidectomy. Brown tumors are a rare complication of severe hyperparathyroidism. 18 F-fluorocholine PET/CT allows the localization of parathyroid adenomas and brown tumors, and can be used as a single imaging modality.

Abstract #1406955: Two Parathyroidectomies in the Third Trimester for Severe Primary Hyperparathyroidism (PHPT) Resulting in Distinct Maternal and Fetal Outcomes

Parathyroidectomy (PTX) is well-tolerated in the second trimester of pregnancy in women with severe PHPT. We present two women requiring PTX in the third trimester of pregnancy due to the severity of the disease. Case 1: 30 y.o female presented at 33 weeks’ gestation with leg pain and severe PTH-mediated hypercalcemia; serum corrected calcium 4.2mmol/L (NR: 2.15-2.6), PTH 147.9 pmol/L (NR:1.6-6.9). She was symptomatic for 2 yrs prior and had a history of nephrolithiasis; the renal US showed 10-20 non-obstructing renal calculi. Femur X-ray demonstrated an aggressive lesion, identified as a brown tumor, on histopathology with additional bone lesions on skeletal survey. Severe hypercalcemia was managed with IV fluids, calcitonin and cinacalcet 30 mg BID. Neck-CT showed a 4cm parathyroid adenoma with no overt malignant features. Subtotal PTX was performed at 33w2d, and PTH dropped to 4.7pmol/L postop. Histopathology reported atypical parathyroid adenoma. Post PTX patient went into premature rupture of membranes, c-section done at 34 weeks’ gestation. Day 8 post PTX, the patient developed hungry bone syndrome, she also had a mechanical fall and sustained a pathological fracture of the femur, the site of brown tumor. Baby was admitted to NICU with hypoparathyroidism, resolved at 3 months of age. Case 2: 32 y.o female presented at 27 weeks’ gestation with incidental hypercalcemia and high PTH. Nausea and vomiting worsened from the 18th week of gestation. No end-organ involvement. Corrected calcium 3.04 mmol/L, PTH 17.1 pmol/L. Managed with IV fluids, and remained symptomatic with no improvement in hypercalcemia. PTX for parathyroid adenoma was performed at 30 weeks’ gestation with excellent maternal and fetal outcomes. PTH dropped to 2.0 pmol/L postop. Had spontaneous vaginal delivery at 39 weeks’ gestation, no neonatal hypocalcemia. Baby has normal milestones. Biochemical workup for Multiple Endocrine Neoplasia type1 (MEN1) was unremarkable for both patients, DNA testing is outstanding. The duration of PHPT, the severity of hypercalcemia, and the involvement of end-organ damage are critical factors that may influence both maternal and fetal outcomes in women with PHPT who undergo PTX in the third trimester.

Familial parathyroid tumours-comparison of clinical profiles between syndromes.

Primary hyperparathyroidism (PHPT) caused by parathyroid tumours is mostly sporadic, with a genetic cause identified in 5-10% of cases. Familial parathyroid tumours can be included in complex syndromes, such as multiple endocrine neoplasia (MEN) type 1, 2A and 4 or hyperparathyroidism-jaw tumour syndrome (HPT-JT). Characterisation of the familial parathyroid tumours followed-up at our centre and comparison of the different clinicopathological manifestations between the syndromes. Retrospective analysis of 48 patients with familial parathyroid tumours harbouring RET (n = 11), CDC73 (n = 20) and MEN1 (n = 17) germline mutations was performed. Cases of PHPT in MEN2A syndrome presented with lower serum PTH (sPTH) and serum calcium (sCa) levels at diagnosis (sPTH = 108.0 (IQR 53.3) pg/mL, sCa = 10.6 ± 1.1mg/dL) than MEN1 (sPTH = 196.9 (IQR 210.5) pg/mL, sCa = 11.7 ± 1.2mg/dL) (p = 0.01, p = 0.03, respectively) or HPT-JT cases (sPTH = 383.5 (IQR 775.8) pg/mL, sCa = 12.9 ± 1.8mg/dL) (p = 0.01; p < 0.001, respectively). There was a statistical difference in sCa levels between MEN1 and HPT-JT (p = 0.02), but not between sPTH (p = 0.07). The predominant first manifestation of the syndrome in MEN1 was gastroenteropancreatic neuroendocrine tumour (GEP-NET) in 47.1% of the cases, in MEN2A was medullary thyroid cancer (90.9%) and in HPT-JT was PHPT in 85% patients. In MEN1 syndrome, the number of affected parathyroid glands was significantly higher than in MEN2A (p < 0.001) and HPT-JT (p = 0.01). The first manifestation of the syndrome in MEN1 cases was GEP-NET and not PHPT. Although presenting at similar ages, patients with MEN2A exhibit less severe biochemical and clinical PHPT at diagnosis than the other familial syndromes.

Effects of primary hyperparathyroidism on oral health. Alongitudinal register-based study.

To analyze the effects of primary hyperparathyroidism on oral health and to investigate if the effects are linked to severity of the disease. This prospective cohort study involved 6151 primary hyperparathyroidism patients registered in the Scandinavian Quality Registry of Thyroid, Parathyroid, and Adrenal surgery and the National Cancer Register after parathyroidectomy (exposure) during 2011-2017 (patient cohort) and 60,654 individuals without primary hyperparathyroidism (reference cohort), matched by age, gender, and county of resident at the date of parathyroidectomy. The outcomes were tooth extractions and periodontal interventions. The risk for the outcomes was assessed by Poisson regression models. After adjusting for covariates, the patient cohort had a higher incidence rate of tooth extraction during the two-year period after parathyroidectomy (IRR=1.15; 95% CI=1.01-1.31), but a lower incidence rate of periodontal interventions during the four- to six-year period after parathyroidectomy (IRR=0.88; 95% CI=0.79-0.99). Furthermore, patients with more severe primary hyperparathyroidism were more likely to have tooth extractions and periodontal interventions after parathyroidectomy. The risk of tooth extraction increased slightly during the first two years after parathyroidectomy. Thereafter, the oral health effects subsided. Pre-surgical serum ionized calcium levels and adenoma weight may indicate negative dental outcomes after parathyroidectomy.

ODP561 Unilateral Vestibular Schwannoma as the Presentation and Aggravation to be Severe Primary Hyperparathyroidism

Abstract Background A rare benign and slow-growing tumor as vestibular schwannoma (acoustic neuroma) usually presents with asymptomatic/unilateral hearing loss or tinnitus and loss of balance between the ages of 49 to 60 years. 90% of vestibular schwannoma are unilateral and not specifically grown in patients with neurofibromatosis type2 (NF2) (1). The association of schwannoma and parathyroid adenoma has been published not much but consistently until now. However, those were not mention to the relationship between pre- and post-treatment of schwannoma with parathyroid hormone level. Clinical case: A 65-year-old woman, previously healthy, presented with progressive fatigue and loss of balance for 1 month. She developed hearing loss, dysarthria and facial palsy within 1 week. At her first visited, she looked drowsiness and had slow verbal and motor response with right facial palsy, lower motor neuron type. She lost only her right facial sensation by pinprick and hyperreflexia without significant other neurological deficits and abnormal skin lesions. She denied family history of NF2. Severe hypercalcemia (17.66 mg/dL) with markedly elevated parathyroid hormone (PTH 1,115.1 pg/mL; 15-68.3) levels and mild elevation of serum creatine (Cr 1.32 mg/dL) was revealed. MRI brain showed an extra-axial enhancing mass at right CPA-IAC region size 3.7×4.2×2.9 cm possible vestibular schwannoma, this mass causing pressure effect to right sided of pons, medulla, cerebellar hemisphere and fourth ventricle. After treatment with saline hydration, her serum creatinine was recovered to normal range with slightly high normal serum calcium (11.85 mg/dL) but not being well. She came back to hospital again with fatigue and polyuria for 3 days. Her serum calcium rose up to 21.3 mg/dL with very high PTH level; 1,643 pg/mL and elevation of serum creatine (Cr 1.71 mg/dL). Again, she was treated with saline hydration for 3 days before receiving zoledronate 4 mg intravenously. After that her serum calcium and creatinine returned to normal level (Ca 10.32 mg/dL, Cr 1. 08 mg/dL) with being better. She was undergone surgery for removal right vestibular tumor and proved to be schwannoma in pathology. During further investigation of hyperparathyroidism, she had normocalcemia and her PTH level dropped to about 400 pg/mL. Conclusion Our patient showed the contribution of vestibular schwannoma to rise up the level of PTH as same level as parathyroid carcinoma. There could be some relationships of mechanism between there two diseases that should be explored further. Reference: 1. Carlson ML, Link MJ. Vestibular Schwannomas. Review article. N Engl J Med 384;14,Apr 8, 2021. Presentation: No date and time listed

Management of severe and symptomatic primary hyperparathyroidism in the first trimester of unplanned pregnancy.

SummaryPrimary hyperparathyroidism (PHP) is the most common aetiology for hypercalcaemia. The incidence of PHP in pregnant women is reported to be 8/100 000 population/year. It presents a threat to the health of both mother (hyperemesis, nephrolithiasis) and fetus (fetal death, congenital malformations, and neonatal severe hypocalcaemia-induced tetany). However, there is a lack of clear guidance on the management of primary hyperparathyroidism in pregnancy. In this study, we describe the case of a 26-year-old female patient who presented with severe hypercalcaemia secondary to PHP and underwent successful parathyroid adenectomy under local anaesthesia.Learning pointsPrimary hyperparathyroidism is a rare complication in pregnancy, but the consequences for mother and fetus can be severe.A perceived risk of general anaesthesia to the fetus in the first trimester has resulted in a general consensus to delay parathyroid surgery to the second trimester when possible – although the increased risk of fetal loss may occur before planned surgery.If the patient presents with severe or symptomatic hypercalcaemia, minimally invasive surgery under local anaesthetic should be considered regardless of the gestational age of the pregnancy.