Mild Primary Hyperparathyroidism Research Articles

6722 Increase in Femoral Neck BMD After Parathyroidectomy in Patients with Mild Primary Hyperparathyroidism

Abstract Disclosure: F. Abdul Kather: None. G.A. Clines: None. C. Janney: None. D.T. Hughes: None. N.H. Esfandiari: None. S. Saberi: None. Objective: This study aimed to assess changes in bone mineral density (BMD) following parathyroidectomy in patients with mild primary hyperparathyroidism, defined as serum calcium 10.4 mg/dl to 11.2 mg/dl, by comparing distinct patient variables. Hypothesis: Pre-op demographic factors, laboratory values, and BMD significantly influence post-parathyroidectomy BMD. Methods: This retrospective chart review included 93 subjects with primary hyperparathyroidism who underwent parathyroidectomy between 2000-2022 with BMD measurements performed at the same site pre- and post-parathyroidectomy. Exclusion criteria were age <50 years, GFR <30, recurrent primary hyperparathyroidism, chronic oral glucocorticoid use (>1 month), rheumatoid arthritis, suppressed serum TSH, hormone-deprivation therapy, cinacalcet use, and prescription osteoporosis medication therapy. Statistical analyses were performed using ANOVA and a p-value of <0.05 was considered statistically significant. Results: The mean age of the subjects was 63.65 ± 6.58 years, who were mostly female (84.9%) and white (88.2%). Pre-op laboratory values revealed mean uncorrected calcium 10.52 ±0.26 mg/dL, corrected calcium 10.25 ± 0.32 mg/dL, 25-OH vitamin D 35.82 ±15.31 ng/mL, and parathyroid hormone (PTH) 99.12 ±37.06 pg/mL. Pre-op mean bone densities for the lumbar spine, femoral neck, and total hip were 1.04 ± 0.16, 0.81 ± 0.11, and 0.87 ± 0.11 g/cm2, respectively, with corresponding T-scores of -1.13 ± 1.23, -1.60 ± 0.74, and -1.13 ± 0.89. Changes in BMD post-parathyroidectomy were determined by comparing pre-op and post-op DXA scans. No statistically significant differences in DXA were found between ages of 50-55 vs. >55, post-op timing of DXA 1-2 years post parathyroidectomy vs. >2 years post parathyroidectomy, number of parathyroid glands removed, the total weight of resected parathyroid glands, pre-op vitamin D level <30 ng/mL vs. ≥30 ng/mL, or pre-op urinary calcium levels <200 mg/day vs. ≥200 mg/day. Grouping subjects by pre-operative DXA T-scores revealed a statistically significant improvement in femoral neck bone density between osteoporotic and osteopenic subjects (p=0.018) and between osteoporotic and normal bone density subjects (p=0.019). No significant differences were identified in the spine and total hip bone density changes among these groups. Conclusion: In subjects with osteoporosis undergoing parathyroidectomy, a significant improvement in femoral neck bone density was observed, unaffected by pre-op variables of age, timing of DXA post parathyroidectomy, parathyroid gland characteristics, and pre-op vitamin D and urinary calcium levels. These findings underscore the potential for tailored interventions in managing bone health post-parathyroid surgery, emphasizing the need for personalized approaches to optimize outcomes in individuals with mild hyperparathyroidism. Presentation: 6/2/2024

No effect of surgery on kidney and cardiovascular risk factors in mild primary hyperparathyroidism: secondary analyses from a 10-year randomized controlled trial.

Renal function and the skeleton are classic target organs in primary hyperparathyroidism (PHPT), affected by the chronic course of the disease. Most patients diagnosed today exhibit mild PHPT, characterized by slight hypercalcemia and no or unspecific symptoms. Concerns have been raised that PHPT could promote deteriorating kidney function and increase cardiovascular risk directly. To examine the effect of parathyroidectomy (PTX) on mild PHPT on renal function and markers for bone turnover, cardiovascular disease (CVD), and vascular inflammation. Prospective randomized controlled trial. ClinicalTrials.gov: NCT00522028. Eight Scandinavian referral centers. From 1998 to 2005, 191 patients with mild PHPT were included in Sweden, Norway, and Denmark. Of these 150 were included in the present analyses. Seventy patients were randomized to PTX and 80 to observation without intervention (OBS). e-GFR was calculated based on creatinine and cystatin C. Markers of CVD and systemic inflammation: osteoprotegerin, vascular cell adhesion molecule 1, soluble CD40 ligand, interleukin-1 receptor antagonist, von Willebrand factor. Bone turnover markers: C-terminal telopeptide of type 1 collagen (CTX-1) and serum Procollagen type 1 N-terminal propeptide. No differences in the development of renal function or vascular and systemic inflammation were detected. CTX-1 was lower in PTX after 10 years. Secondary analyses of a randomized controlled trial. PTX does not appear to affect renal function or markers of CVD and vascular inflammation in mild PHPT in a ten-year perspective.

Changes in bone turnover markers and bone mineral density after radiofrequency ablation for mild primary hyperparathyroidism: a prospective cohort study

Changes in bone turnover markers and bone mineral density after radiofrequency ablation for mild primary hyperparathyroidism: a prospective cohort study

Thiazide diuretics and primary hyperparathyroidism.

Thiazide diuretics exert a natriuretic and diuretic effect by inhibiting sodium reabsorption in the distal convoluted tubule. Furthermore, thiazide diuretics affect renal calcium handling by increasing calcium reabsorption, leading to hypocalciuria. The effect that thiazide diuretics exert on parathyroid hormone secretion is controversial. Some studies found parathyroid hormone levels were suppressed with the use of thiazide diuretics, while others found that thiazides were associated with initial parathyroid hormone suppression followed by raised parathyroid hormone levels. This makes the relationship between thiazide diuretics and primary hyperparathyroidism interesting. If a patient is taking thiazide diuretics, this may make it harder to establish the aetiology of hypercalcaemia and may unmask normocalcaemic or mild primary hyperparathyroidism. Thiazide diuretics may have a beneficial role in the diagnosis of patients with concomitant hyperparathyroidism and hypercalciuria by distinguishing secondary hyperparathyroidism caused by hypercalciuria from normocalcaemic primary hyperparathyroidism. In addition, thiazide diuretics may have a role in managing patients with primary hyperparathyroidism who have an indication for parathyroidectomy in view of significant hypercalciuria, but are unfit for surgery.

Increased Prevalence of Autoimmune Rheumatologic Diseases in Patients With Primary Hyperparathyroidism.

Background Parathyroid hormone (PTH) and Dickkopf-related protein 1 (DKK-1) have been mentioned together at the intersection of autoimmune rheumatologic diseases (ARDs) and osteoimmunology. However, few studies have evaluated the association between primary hyperparathyroidism (PHPT) and ARDs. Methodology This retrospective study included 225 PHPT patients and 386 patients with thyroid nodules as a control group. The electronic hospital records of all patients were screened going back nine years for the presence of ARDs. Patients who were diagnosed at least three months ago, had complete serologic tests, and were continuing with rheumatologic follow-up were included. Results The prevalence of ARDs in the PHPT group was 9.77% (22/225), while the prevalence of ARDs in the CG was 1.04% (4/386, p < 0.001). The prevalence of rheumatoid arthritis in the PHPT group was 4.4% (10/225), ankylosing spondylitis 3.1% (7/225), systemic lupus erythematosus 0.88% (2/225), Behçet's disease 0.88% (2/225), and mixed connective tissue disease 0.44% (1/225). Of the 22 patients with ARDs, 21 (95.45%) were diagnosed before they were diagnosed with PHPT, and the median time from diagnosis with ARD to the onset of PHPT was 36 months (interquartile range = 61.5). Logistic regression analysis showed a positive correlation between the duration of PHPT and ARDs (odds ratio (OR) = 1.06; 95% confidence interval (CI) = 1.02-1.09, p < 0.001) and a negative correlation between ARDs and calcium levels (OR = 0.26; 95% CI = 0.09-0.79, p = 0.018). Conclusions The prevalence of ARDs increased in PHPT patients and PHPT accompanying ARDs developed after rheumatologic disease. ARDs with PHPT are cases with a prolonged duration of PHPT and mildly elevated calcium, probably preceded by parathyroid hyperplasia. Therefore, the factors that cause ARDs may trigger a process that leads to mild PHPT.

THU522 Symptomatic Hypoglycemia As The First Manifestation Of Multiple Endocrine Neoplasia Type 1 (MEN-1): Case Report

Abstract Disclosure: V.D. Oliveira: None. S.C. Tormin: None. B.V. Dias: None. N. Scalissi: None. R.D. Scalco: None. C. Olivati: None. A. de Moricz: None. L.A. Szutan: None. J.V. Lima: None. Introduction: MEN-1 is a rare, autosomal dominant syndrome that occurs due to a pathogenic variant of MEN1. The incidence of insulinoma in MEN-1 is relatively rare. 4-6% of patients with insulinoma will develop MEN-1. Unlike sporadic insulinomas that usually develop after the age of 40, MEN-associated insulinoma usually occur before 40 years of age and even sometimes before 20. CASE REPORT: A 26-year-old male patient had a 3-year history of Whipple's triad associated with significant weight gain with a body mass index (BMI) of 33 kg/m² to 58 kg/m² during this period. His father has a metastatic carcinoid tumor, being treated with palliative chemotherapy. Laboratory tests at the time of hypoglycemia were: blood glucose 42mg/dL (RV 75-99), insulin 39 mU/L (RV &amp;lt; 3) and C-peptide 11.6 ng/dL (RV &amp;lt; 0.2). Magnetic resonance imaging (MRI) of pancreas showed 3 hypervascular nodules, the largest in the tail, measuring 3.3 cm, with neuroendocrine characteristics. Distal pancreatectomy, splenectomy and lymphadenectomy were indicated. After surgery, the episodes of hypoglycemia disappeared, with a weight loss of 25 kg. He required postoperative metformin, with satisfactory glycemic control. During the investigation, a prolactinoma was diagnosed (pituitary MRI, which showed a 4 mm adenoma, prolactin 56ng/mL (LR &amp;lt; 25) and hypogonadotrophic hypogonadism), and cabergoline 0.25 mg/week was started. In addition, diagnosis of mild primary hyperparathyroidism (PTH 188 pg/mL and calcium 10.4mg/dL). Parathyroid scintigraphy with 99mTc-MIBI showed increased uptake in the right lower parathyroid. Genetic testing was performed by Next Generation Sequence (NGS) of the MEN1 gene, which was positive for the pathogenic variant c.825-2A&amp;gt;G in heterozygosis in intron 5. A molecular study was performed on the patient's father and sister, which identified the same pathogenic allelic variant in both. Conclusion: We described a rare case of MEN-1 whose first manifestation was insulinoma. Presentation: Thursday, June 15, 2023

Parathyroid adenoma apoplexy mimicking a thyroid bleeding cyst: a seemingly innocent condition that can be life-threatening.

Primary hyperparathyroidism most commonly presents with hypercalcaemia. Rarely, parathyroid apoplexy or haemorrhage mimicking a thyroid bleeding cyst is the first presentation of a parathyroid adenoma. A woman presented with a sudden-onset painful 'goitre'. Ultrasound showed a cystic nodule located posterior to rather than in the right thyroid lobe, suggesting parathyroid adenoma bleeding. Biochemistry showed mild primary hyperparathyroidism. 99mTc-pertechnetate/sestamibi showed no uptake in the nodule, which was interpreted as a cold thyroid nodule. 18F-fluorocholine PET/CT showed uptake in the nodule, suggestive of a parathyroid adenoma. Persistent mild primary hyperparathyroidism complicated by nephrolithiasis and osteopenia favoured parathyroidectomy over a wait-and-see approach. The patient was referred for parathyroidectomy along with right thyroid lobectomy. Pathology showed an adenoma, with an eccentrically located cystic structure filled with red blood cells surrounded by a thickened fibrous capsule. In conclusion, cervical pain/haemorrhage with hypercalcaemia points to the diagnosis of parathyroid apoplexy, mimicking a thyroid bleeding cyst. Workup with ultrasound and, if available, 18F-choline PET/CT allows for timely surgery, minimizing the risk of recurrent and severe bleeding. A bleeding cyst may be located posterior to rather than in the thyroid, suggesting a parathyroid haemorrhage. Neck pain and/or haemorrhage along with primary hyperparathyroidism point to parathyroid apoplexy. A two-step presentation has been described, with a first phase of local symptoms to be followed by visible and possibly life-threatening compressing bleeding. Therefore, an expedited workup is needed, allowing for timely surgery.

Comparison of Medical Management versus Parathyroidectomy in Patients with Mild Primary Hyperparathyroidism: A Meta-Analysis

Background: Parathyroidectomy is the definitive cure for patients with primary hyperparathyroidism (pHPT) and has an annual prevalence of 0.2–1% in the United States. Some patients with mild disease are medically managed effectively using calcium-lowering medications and drugs against complications such as osteoporosis; however, many maintain a persistently high calcium level that negatively impacts their skeletal, renal, and psychogenic systems over the long term. This meta-analysis aims to compare the outcomes of medical management versus parathyroidectomy in patients with mild pHPT. Study Design: This meta-analysis was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines using PubMed, Embase, and Web of Science by two teams of investigators. Analysis was run using R packages. Results: A total of 12 publications including seven randomized control, two prospective, and three retrospective trials with a total of 1346 patients were included for analysis. The average follow-up for all patients was 41 ± 23.8 months. Demographics, pre-treatment calcium, PTH, and bone mineral density (BMD) were similar between the medical (N = 632) and surgical (N = 714) cohorts. Post-treatment calcium and PTH levels were significantly higher in the medical cohort (10.46 vs. 9.39, p &lt; 0.01), (106.14 vs. 43.25, p = 0.001), respectively. Interestingly, the post-treatment PTH in the medical cohort increased when compared to pre-treatment (83.84 to 106.14). Patients in the medical cohort had lower BMD in lumbar (0.48 g/cm2; OR = 0.42, 95% CI = 0.21, 0.83), femoral (0.48; OR = 0.42, 95% CI = 0.29, 0.61), and hip (0.61; OR = 0.33, 95% CI = 0.13, 0.85). Incidences of fracture, nephrolithiasis, cardiovascular death, or overall mortality were not significantly different between the cohorts. Conclusions: The present study is the most comprehensive meta-analysis on mild pHPT to date. Our findings reflect that parathyroidectomy is the superior option in the treatment of mild pHPT patients as opposed to medical management.

Abstract #1398160: A Rare Case of Water Clear Cell Parathyroid Adenoma Escaping Sestamibi Scan and Neck Ultrasound – A Diagnostic Conundrum of a Rare Pathological Intity with a Rare Presentation

Parathyroid water-clear cell hyperplasia (WCCH) and water-clear cell adenoma (WCCA) are extremely rare causes of primary hyperparathyroidism (PHPT). WCCH contributes to < 1% of all PHPT however WCCA is exceptionally rare and has been reported only in less than 30 case reports. We are presenting a very rare indolent pathological entity with a very rare presentation escaping common diagnostic measures of Sestamibi scan and neck ultrasound. A 63-year-old female presented for evaluation of severe osteoporosis with a T-score of -3.6. Laboratory workup revealed elevated parathyroid hormone (PTH) of 122 pg/ml (reference range 12-88 pg/ml), Normal calcium 9.8 mg/dl, Normal vitamin D 50 ng/ml, and normal magnesium 2.2 mg/dl. 24-hour urine calcium was 421 mg/24H. Diagnosis was consistent with normocalcemic PHPT and meeting surgical criteria with osteoporosis and high urine calcium. Sestamibi scan did not identify any focal activity. CT H&N revealed an 8 mm mass inferior and posterior to right thyroid lobe with partial washout and slightly different enhancement compared to thyroid gland. Neck ultrasound (US) reported that previously noted tissue activity on the CT H&N is not visualized and most likely represents normal thyroid tissue. Patient was referred to otolaryngology surgery and underwent four gland explorations, including right inferior and left superior parathyroidectomy. Pathology of superior parathyroid gland revealed parathyroid water clear cell adenoma. 3-month Postoperative PTH 29.4 pg/ml and calcium level of 9.3 mg/dl. Solitary parathyroid adenoma (SPA) attributes to 80-85% of PHPT. Majority of cases is due to Chief cell adenomas, less frequent pathologies include oxyphil cell adenoma, lipoadenoma, WCCA or mixed type. Scientific literature regarding WCCA presentation and diagnosis is blurred due to its rarity. Clinical presentation of WCCA resembles other etiologies of PHPT, though some data suggest that is frequently indolent and manifests with mild PHPT. Literature suggests that WCCA has low biochemical activity and most cases had normal to mildly elevated calcium-our patient support this hypothesis-. Hypercalcemia does not manifest until significant growth of the adenoma, though few reported cases manifested with hypercalcemia. Unlike other SPA where Sestamibi scan sensitivity is 91%, literature suggests possibility of false-negative results with WCCA which is hypothesized to be attributed to its different histology of glycogen-rich vacuolized cytoplasm that leads to fast Sestamibi wash-out, for the same reason data suggest that US is more decisive given high water content of cells -Our patient didn’t follow this rule and escaped Sistamibi and US though seen on CT- which still makes the diagnosis of WCCA a conundrum. Some cases underwent surgical excision based on clinical diagnosis which led to revision of PHPT and/or hypercalcemia. There is no available data suggesting different long-term follow-up regimens for WCCA compared to other SPA. Further literature with longer follow-up is needed for this extremely rare entity for a comprehensive understanding of its natural course.

FCH-PET/CT in Primary Hyperparathyroidism With Discordant/Negative MIBI Scintigraphy and Ultrasonography.

The contribution of [18F]F-fluorocholine (FCH)-positron emission tomography (PET)/computed tomography (CT) in normocalcemic primary hyperparathyroidism (nPHPT) remains unknown. To evaluate the sensitivity and specificity of FCH-PET/CT in a cohort of osteoporotic patients with nPHPT and discordant or negative [99mTc]Tc-sestamibi scintigraphy and ultrasonography who all underwent parathyroidectomy (PTX). Longitudinal retrospective cohort study in patients referred for osteoporosis with mild biological primary hyperparathyroidism. Tertiary referral center with expertise in bone metabolism and surgical management of hyperparathyroidism. Among 109 patients with PHPT analyzed, 3 groups were individualized according to total serum calcium (tCa) and ionized calcium (iCa): 32 patients with hypercalcemia (HtCa group), 39 patients with normal tCa and elevated iCa (NtCa group), and 38 patients with both normal tCa and iCa (NiCa). All patients had biochemical follow-up confirming or not the success of PTX. To evaluate the performance of FCH-PET/CT in terms of sensitivity and specificity, and to compare with first-line imaging procedures in the setting of nPHPT. The sensitivity of FCH-PET/CT was 67% in the hypercalcemic group, 48% in the NtCa group (P = .05 vs HtCa), and 33% in the NiCa group (P = .004 vs HtCa). Specificity ranged from 97% to 99%. FCH-PET/CT was positive in 64.3% of patients with negative conventional imaging, with biochemical resolution after PTX in 77.8% of patients. Triple negative imaging was observed in 20 patients, with PHPT resolution in 85% of these patients. This study highlights the contribution of FCH-PET/CT in a well-phenotyped cohort of normocalcemic patients with discordant or negative findings in [99mTc]Tc-sestamibi scintigraphy and ultrasonography. However, negative imaging in nPHPT does not rule out the possibility of surgical cure by an experienced surgeon.

Evolving Role of [18F]Flurocholine PET/CT in Assessing Primary Hyperparathyroidism: Can It Be Considered the First-Line Functional Imaging Approach?

The accurate detection of hyperfunctioning parathyroid tissue (HFPT) is pivotal in the preoperative assessment of primary hyperparathyroidism (PHPT). PET/CT using [18F]fluorocholine ([18F]FCH) showed superior diagnostic performance compared to conventional functional imaging modalities. We aimed to evaluate the diagnostic performance of [18F]FCH PET/CT as a first-line functional imaging approach in patients with clinically diagnosed PHPT. The imaging and clinical data of 321 PHPT patients, including 271 overt PHPT and 50 mild PHPT, who underwent [18F]FCH PET/CT as first-line imaging were analysed in this retrospective study. Histopathology was the reference standard. In case of no available histopathology evaluation (conservative management), imaging and clinical follow-ups were considered reference standards. In the overt group (n = 271), [18F]FCH PET/CT showed sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of 0.99, 0.91, 1.00, 0.80, and 0.99, respectively. Regarding the correlation of the index lesions and initial laboratory data, all [18F]FCH PET/CT parameters (SUVs, SULs, and mSAD) were significantly correlated with the serum iPTH level. Additionally, SUVmax, SULpeak, and mSAD were significantly associated with the serum calcium level. In the mild group (n = 50), [18F]FCH PET/CT showed a sensitivity, specificity, PPV, NPV, and accuracy of 0.93, 0.75, 0.95, 0.67, and 0.90. In conclusion, [18F]FCH PET/CT revealed high diagnostic performance in the detection of HFPTs and the potential to be considered as a first-line imaging modality in the assessment of PHPT, including both overt and mild types. However, its cost-benefit concerning the clinical impact of early PHPT detection should be investigated in future studies.

Primary hyperparathyroidism and fracture probability.

Primary hyperparathyroidism (PHPT) is associated with an increase in the risk of fracture. In FRAX, the increase in risk is assumed to be mediated by low bone mineral density (BMD). However, the risk of death is also increased and its effect on fracture probability is not known. The aim of this study was to determine whether PHPT affects hip fracture and major osteoporotic fracture risk independently of bone mineral density (BMD) and whether this and any increase in mortality affects the assessment of fracture probability. A register-based survey of patients with PHPT and matched controls in Denmark were identified from hospital registers. The incidence of death, hip fracture, and major osteoporotic fracture were determined for computing fracture probabilities excluding time after parathyroidectomy. The gradient of risk for fracture for differences in BMD was determined in a subset of patients and in BMD controls. The severity of disease was based on serum calcium and parathyroid hormone levels. We identified 6884 patients with biochemically confirmed PHPT and 68,665 matched population controls. On follow-up, excluding time after parathyroidectomy in those undergoing surgery, patients with PHPT had a higher risk of death (+52%), hip fracture (+48%), and major osteoporotic fracture (+36%) than population controls. At any given age, average 10-year probabilities of fracture were higher in patients with PHPT than population controls. The gradient of fracture risk with differences in BMD was similar in cases and controls. Results were similar when confined to patients not undergoing parathyroidectomy. Fracture probability decreased with the severity of disease due to an increase in mortality rather than fracture risk. The risk of hip and other major osteoporotic fracture is increased in PHPT irrespective of the disease severity. Fracture probability was attenuated due to the competing effect of mortality. The increased fracture risk in patients treated conservatively argues for widening the indications for parathyroidectomy in mild PHPT.

ODP107 Oral Ulcerations, A Rare Side Effect of Intravenous Zoledronic Acid

Abstract Introduction Zoledronic acid is an intravenous bisphosphonate known for its anti-resorptive effects and osteoporotic fracture risk reduction. A common adverse reaction with this medication is mild to moderate flu-like symptoms, which are transient and attributed to an acute phase reaction post treatment. A less common side effect, of oral ulcers is associated with oral bisphosphonates, attributed to incorrect oral intake but the real mechanism is still not well understood. We present a patient that developed oral ulcers after use of both oral and intravenous bisphosphonates, leading to suspicion of other underlying mechanisms other than incorrect oral intake of bisphosphonates. Case Report We present a 73 year old male with history of mild primary hyperparathyroidism and osteoporosis. Patient opted for medical management of his mild primary hyperparathyroidism in addition to having non-localizing studies. Treatment for osteoporosis was recommended due to femoral neck T score -2.4, FRAX score of 3.3% risk for hip fractures and history of low impact right foot fracture. The primary care team started treatment with alendronate 70 mg once a week, but patient developed oral blisters within a week of starting the treatment. Stopping alendronate led to resolution of the oral symptoms without any additional supportive treatment. Patient was later started on intravenous zoledronic acid, attributing the previous history of oral ulcers to a local effect of the oral bisphosphonates. Two days after the zoledronic acid infusion patient developed fatigue, fever, and oral ulcers. The oral ulcers were described as painful, located at the base and lateral aspects of the tongue. The ulcers later progressed to the buccal mucosa. No gingival ulcers were reported. Development of the oral blisters led to significant discomfort in eating and talking. Patient was treated with liquid nystatin 10,000 units/mL and lidocaine 2% viscous liquid. Patient had resolution of the painful ulcers approximately 2 weeks after the initial appearance. No recurrence of the oral ulcers has been reported, 4 months post treatment with zoledronic acid. Discussion Intuitively oral bisphosphonate induced mucosal injury is thought to be related to direct contact of the tablet with the oral mucosa or inappropriate ingestion of the medication and is not thought to be a systemic reaction. Our patient developed oral ulcers from both oral and intravenous bisphosphonates suggesting a possible systemic mechanism involved. Understanding potential side effects such as mucosal injury from intravenous bisphosphonates will be helpful for patient education and timely care. Presentation: No date and time listed

Mortality and Morbidity in Mild Primary Hyperparathyroidism: Results From a 10-Year Prospective Randomized Controlled Trial of Parathyroidectomy Versus Observation.

Primary hyperparathyroidism (PHPT) is a common endocrine disorder associated with increased risk for fractures, cardiovascular disease, kidney disease, and cancer and increased mortality. In mild PHPT with modest hypercalcemia and without known morbidities, parathyroidectomy (PTX) is debated because no long-term randomized trials have been performed. To examine the effect of PTX on mild PHPT with regard to mortality (primary end point) and key morbidities (secondary end point). Prospective randomized controlled trial. (ClinicalTrials.gov: NCT00522028). Eight Scandinavian referral centers. From 1998 to 2005, 191 patients with mild PHPT were included. Ninety-five patients were randomly assigned to PTX, and 96 were assigned to observation without intervention (OBS). Date and causes of death were obtained from the Swedish and Norwegian Cause of Death Registries 10 years after randomization and after an extended observation period lasting until 2018. Morbidity events were prospectively registered annually. After 10 years, 15 patients had died (8 in the PTX group and 7 in the OBS group). Within the extended observation period, 44 deaths occurred, which were evenly distributed between groups (24 in the PTX group and 20 in the OBS group). A total of 101 morbidity events (cardiovascular events, cerebrovascular events, cancer, peripheral fractures, and renal stones) were also similarly distributed between groups (52 in the PTX group and 49 in the OBS group). During the study, a total of 16 vertebral fractures occurred in 14 patients (7 in each group). During the study period, 23 patients in the PTX group and 27 in the OBS group withdrew. Parathyroidectomy does not appear to reduce morbidity or mortality in mild PHPT. Thus, no evidence of adverse effects of observation was seen for at least a decade with respect to mortality, fractures, cancer, cardiovascular and cerebrovascular events, or renal morbidities. Swedish government, Norwegian Research Council, and South-Eastern Norway Regional Health Authority.

Summary for Patients: Mortality and Morbidity in Mild Primary Hyperparathyroidism.

Summary for Patients: Mortality and Morbidity in Mild Primary Hyperparathyroidism.

Insulin resistance is more severe in patients with primary hyperparathyroidism

BackgroundPrimary hyperparathyroidism is associated with an increased cardiovascular mortality, and its underlying mechanisms remain unclear. Insulin resistance has been suggested with low level of evidence. The goal of this study was to evaluate glucose metabolism and insulin resistance in primary hyperparathyroidism patients, to compare with control subjects, and to identify risk factors for insulin resistance in patients with primary hyperparathyroidism. MethodsCross-sectional study of consecutive primary hyperparathyroidism patients without history of diabetes or severe chronic kidney disease (glomerular filtration rate ≤30 mL/min/1.73 m2). Fasting glucose and insulin were evaluated before parathyroidectomy. Glucose metabolism was compared with population-based control subjects (n = 171). ResultsOne hundred and seventy-four patients with primary hyperparathyroidism (140 females) were included. Mean fasting glucose was 0.983 ± 0.129 g/L, and 63 patients (36%) had prediabetes (>1.0 g/L). Mean Homeostatic model assessment of insulin resistance (HOMA-IR) was 3.386 ± 3.111 mUI/L, and 78 patients (45%) had insulin resistance (HOMA-IR >2.6). Blood calcium levels (0.171; P = .023) and body mass index (0.450; P < .001) were correlated positively with HOMA-IR. Insulin secretion (HOMA-B%) was correlated positively with preoperative systolic blood pressure in mm Hg (0.187; P = .013). In multivariate analysis, classic hypercalcemic primary hyperparathyroidism (18.47, 6.84–49.87; <.001), mild hypercalcemic primary hyperparathyroidism (5.35, 2.40–11.95; <.001), and body mass index (1.27, 1.17–1.38; <.001) remained independent predictors for insulin resistance (HOMA-IR >2.6). When compared with control subjects, mean HOMA-IR was significantly higher in primary hyperparathyroidism patients (3.386 ± 3.111 vs 1.919 ± 1.158; P < .001). ConclusionInsulin resistance was significantly higher in primary hyperparathyroidism patients than in control subjects. The impact of parathyroidectomy on insulin resistance should be evaluated in patients with higher calcium levels.

Effect of Parathyroidectomy on Metabolic Homeostasis in Primary Hyperparathyroidism.

Background: The benefits of parathyroidectomy on cardiovascular risk in primary hyperparathyroidism (PHPT) are controversial. This monocentric, observational, prospective study aimed to assess the effects of parathyroidectomy on glucose and lipid metabolism in classic or mild PHPT. Methods: Patients who underwent parathyroidectomy for classic (calcemia >2.85 mmol/L) or mild PHPT (calcemia ≤2.85 mmol/L) between 2016 and 2019 were included. A metabolic assessment was performed before and 1 year after parathyroidectomy. Patients with a history of diabetes were excluded. Results: Nineteen patients had classic and 120 had mild PHPT. Ninety-five percent were normocalcemic 6 months after surgery. Fasting plasma glucose and insulin levels decreased after parathyroidectomy in patients with mild PHPT (p < 0.001). HOMA-IR decreased after surgery in the overall population (p < 0.001), while plasma adiponectin concentrations increased in patients with both classic (p = 0.005) and mild PHPT (p < 0.001). Plasma triglyceride levels decreased significantly only in patients with classic PHPT (p = 0.021). Plasma PCSK9 levels decreased in patients with mild PHPT (p < 0.001). Conclusions: Parathyroidectomy for PHPT improves insulin resistance and decreases plasma triglyceride levels in classic PHPT and plasma PCSK9 levels in mild PHPT. Further studies are needed to better characterize the consequences of such metabolic risk factors’ improvements on cardiovascular events.

Surgical management of MILD hyperparathyroidism.

There is no consensus for management of Mild primary hyperparathyroidism (MILD-pHP). Specific management has been suggested by some authors. We have compared the surgical management of the patients with MILD-pHP to those with Classic primary hyperparathyroidism (C-pHP) treated by surgery according to The Fourth International Workshop on pHP. Data of 173 patients who underwent a parathyroidectomy were reviewed and retrospectively analysed. Management of 32 patients with MILD-pHPT (18.5%) patients were compared to that of 141 (81.5%) patients with C-pHPT. MILD-pHP group was more often discovered after non-fractured osteoporosis (21.9% vs 7.1%, p = 0.02) and surgery for chondrocalcinosis was more often carried out (6.3% vs 0%, p = 0.03) in the MILD-pHP group. A Mini-Invasive Parathyroidectomy (MIP) was carried out in 81.3% of cases, and 87.5% of patients had a single adenoma. The rate of multiglandular pathology was not different. Same day discharge was significantly higher in MILD-pHP group (37.5% vs 17.7%, p = 0.01). Success was obtained in 87.5% in the MILD-pHP group, there was no significant difference with the C-pHP group (92.9%, p = 0.48). There was no significant difference in the imaging performances. Imaging discordance was observed in 18.8% of cases in MILD-pHP and 33.6% in C-pHP (p = 0.38) without correlation with surgical failure. This study suggests that, by selecting patients on the basis of concordant imaging and international recommendations, there is no difference in outcome between MILD-pHP and C-pHP treated surgically.

Meta-analysis on the Effect of Mild Primary Hyperparathyroidism and Parathyroidectomy Upon Arterial Stiffness.

Current data about the cardiovascular manifestations of mild primary hyperparathyroidism (pHPT) are often conflicting. Pulse wave velocity (PWV) is the gold standard for assessing aortic stiffness, and it predicts cardiovascular morbidity and mortality. Primary outcomes were to investigate if mild pHPT was associated with higher PWV and if parathyroidectomy (PTX) reduced PWV in mild pHPT. Secondary outcome was to investigate blood pressure changes after PTX. Sources were PubMed, Google Scholar, SCOPUS, Web of Science, and the Cochrane Library. Eligible studies included reports of PWV in patients with mild pHPT and controls, or in patients with mild pHPT before and after PTX. Two investigators independently identified eligible studies and extracted data. Pooled mean difference (MD) was the summary effect measure. Data were presented in forest plots with outlier and influential case diagnostics. Nine observational studies and one randomized clinical trial were selected, including 433 patients with mild pHPT, 171 of whom underwent PTX, and 407 controls. PWV was significantly higher in mild pHPT than in controls (MD = 1.18, 0.67 to 1.68, P < .0001). Seven studies evaluated the effect of PTX on PWV. PTX significantly reduced PWV (MD = -0.48, -0.88 to -0.07, P = .022). Aortic stiffness is increased in patients with mild pHPT, supporting the notion that mild pHPT is also associated with adverse cardiovascular manifestations. PTX significantly reduced arterial stiffness in mild pHPT, indicating that the benefit of PTX over cardiovascular manifestations should not be dismissed but it deserves further studies.

Risk of fractures in primary hyperparathyroidism: a systematic review and meta-analysis.

An increased risk of fractures in primary hyperparathyroidism (PHPT) has been reported in a number of relatively small studies. Performing a systematic literature search, we identified available studies and calculated common estimates by pooling results from the individual studies in a meta-analysis. Searching EMBASE and PubMed, we identified published studies reporting the risk of fractures in PHPT compared to a control group. We calculated odds ratio (OR) with 95% confidence interval (CI). A total of 804 studies were identified of which 12 studies were included. Risk of any fracture was increased compared to controls (OR 2.01; 95% CI, 1.61-2.50; I2 46%, 5 studies). Analysis of fracture risk at specific sites showed an increased risk of fracture at the forearm (OR 2.36; 95% CI, 1.64-3.38; I2 0%, 4 studies) and spine (OR 3.00; 95% CI, 1.41, 6.37, I2 88%, 9 studies). Risk estimate for hip fractures was non-significantly increased (OR 1.27; 95% CI, 0.97-1.66; I2 0%, 3 studies). Risk of vertebral fractures (VFx) was also increased if analyses were restricted to only studies with a healthy control group (OR 5.76; 95% CI, 3.86-8.60; I2 29%, 6 studies), studies including patients with mild PHPT (OR 4.22; 95% CI, 2.20-8.12; I2 57%, 4 studies) or studies including postmenopausal women (OR 8.07; 95% CI, 4.79-13.59; I2 0%, 3 studies). PHPT is associated with an increased risk of fractures. Although a number of studies are limited-it seems that the risk is increased across different skeletal sites including patients with mild PHPT and postmenopausal women.