Elevated Parathyroid Hormone Levels Research Articles

Pre-Transplant Calcimimetic Use and Dose Information Improves the Accuracy of Prediction of Tertiary Hyperparathyroidism after Kidney Transplantation: A Retrospective Cohort Study

Tertiary hyperparathyroidism (THPT) is characterized by elevated parathyroid hormone and serum calcium levels after kidney transplantation (KTx). To ascertain whether pre-transplant calcimimetic use and dose information would improve THPT prediction accuracy, this retrospective cohort study evaluated patients who underwent KTx between 2010 and 2022. The primary outcome was the development of clinically relevant THPT. Logistic regression analysis was used to evaluate pre-transplant calcimimetic use as a determinant of THPT development. Participants were categorized into four groups according to calcimimetic dose, developing two THPT prediction models (with or without calcimimetic information). Continuous net reclassification improvement (CNRI) and integrated discrimination improvement (IDI) were calculated to assess ability to reclassify the degree of THPT risk by adding pre-transplant calcimimetic information. Of the 554 patients, 87 (15.7%) developed THPT, whereas 139 (25.1%) received pre-transplant calcimimetic treatment. Multivariate logistic regression analysis revealed that pre-transplant calcimimetic use was significantly associated with THPT development. Pre-transplant calcimimetic information significantly improved the predicted probability accuracy of THPT (CNRI and IDI were 0.91 [p < 0.001], and 0.09 [p < 0.001], respectively). The THPT prediction model including pre-transplant calcimimetic information as a predictive factor can contribute to the prevention and early treatment of THPT in the era of calcimimetics.

Skeletal parathyroid hormone hyporesponsiveness: a neglected, but clinically relevant reality in chronic kidney disease.

Defining the optimal parathyroid hormone (PTH) target in chronic kidney disease (CKD) is challenging, especially for bone outcomes, due to the substantial variability in the skeleton's response to PTH. Although PTH hyporesponsiveness is as integral a component of CKD-mineral bone disorder as elevated PTH levels, clinical awareness of this condition is limited. In this review, we will discuss factors and mechanisms contributing to PTH hyporesponsiveness in CKD. This knowledge may provide clues towards a personalized approach to treating secondary hyperparathyroidism in CKD. Indicates a link between disturbed phosphate metabolism and impaired skeletal calcium sensing receptor signaling as an important mediator of PTH hyporesponsiveness in CKD. Further, cohort studies with diverse populations point towards differences in mineral metabolism control, rather than genetic or environmental factors, as drivers of the variability of PTH responsiveness. Skeletal PTH hyporesponsiveness in CKD has a multifactorial origin, shows important interindividual variability, and is challenging to estimate in clinical practice. The variability in skeletal responsiveness compromises PTH as a biomarker of bone turnover, especially when considering populations that are heterogeneous in ethnicity, demography, kidney function, primary kidney disease and mineral metabolism control, and in patients treated with bone targeting drugs.

Association of Hyperparathyroidism with Depression and Anxiety Among Chronic Hemodialysis Patients in the Al Baha Region, Kingdom of Saudi Arabia.

Introduction Anxiety and depression are prevalent psychological issues among hemodialysis patients, adversely affecting their well-being and treatment response. The study aims to identify the relationship between these mental health concerns and hyperparathyroidism in chronic hemodialysis patients from the Al Baha Region, Kingdom of Saudi Arabia. Methods This retrospective study included 143 chronic hemodialysis patients aged 18-85 years. Monthly laboratory records for parathyroid hormone (PTH) levels and the Hospital Anxiety and Depression Scale (HADS) for mental health assessment were utilized. Demographic information and the primary causes of end-stage renal disease were obtained through patient interviews. Statistical analyses, including chi-square tests, odds ratio, and significance tests, were performed to assess associations. Results Elevated PTH levels were associated with increased anxiety and depression in hemodialysis patients. Patients with PTH levels >400 pg/ml exhibited higher rates of abnormal HADS scores for anxiety and depression than those with PTH levels <400 pg/ml. Gender differences were evident, with women showing a higher predisposition to anxiety disorders and men having depression. Additionally, patients with PTH levels <150 pg/ml had a significantly higher proportion of the "normal" depression score than those with PTH levels >800 pg/ml. Conclusion The study underscores the association between hyperparathyroidism and adverse mental health outcomes in chronic hemodialysis patients. Maintaining optimal PTH levels plays a crucial role in mitigating anxiety and depression. Gender differences in mental health outcomes highlight the need for tailored interventions. Routine mental health assessments, utilizing tools such as the HADS, are important in the comprehensive care of hemodialysis patients.

A Rare Ectopic Parathyroid Adenoma in the Prevertebral Space.

Ectopic parathyroid adenomas are an uncommon etiology of primary hyperparathyroidism. We present a case of a patient admitted to the hospital with severe hypercalcemia and elevated parathyroid hormone levels, in whom imaging revealed two distinct parathyroid masses in the prevertebral space, representing a rare and atypical location for parathyroid tissue. This case highlights the importance of considering ectopic parathyroid adenomas as a potential cause of hyperparathyroidism and discusses the diagnostic challenges and management strategies associated with such cases.

Explainable Classification of Patients with Primary Hyperparathyroidism Using Highly Imbalanced Clinical Data Derived from Imaging and Biochemical Procedures

Primary hyperthyroidism (PHPT) is a common endocrine disorder characterized by hypercalcemia and elevated parathyroid hormone (PTH) levels. The most common cause is a single parathyroid adenoma, though the rest of the cases are due to multiglandular disease [double adenoma/hyperplasia]. The main focus driving this work is to develop a computer-aided classification model relying on clinical data to classify PHPT instances and, at the same time, offer explainability for the classification process. A highly imbalanced dataset was created using biometric and clinical data from 134 patients (six total features, 20.2% multiglandular instances). The features used by the current study are age, sex, max diameter index, number of deficiencies, Wisconsin index, and the reference variable indicating the type of PHPT. State-of-the-art machine learning (ML) classification algorithms were used in order to create trained prediction models and give predicted classifications based on all features/indexes. Of the ML models considered (Support Vector Machines, CatBoost, LightGBM, and AdaBoost), LightGBM was able to procure the best performing prediction model. Given the highly imbalanced nature of the particular dataset, oversampling was opted for, so as to increase prediction robustness for both classes. The ML model’s performance was then evaluated using common metrics and stratified ten-fold validation. The significance of this work is rooted in two axes: firstly, in the incorporation of oversampling to smooth out the highly imbalanced dataset and offer good prediction accuracy for both classes, and secondly, in offering an explainability aspect to an otherwise black-box ML prediction model. The maximum achievable accuracy for adenoma is 86.9% and for multigland disease 81.5%. Summarizing the above, this study demonstrates the potential for an ML approach to improve the diagnosis of PHPT and also highlights the importance of explainable artificial intelligence (AI).

Risk Factors and Clinical Characterization of Cardiovascularand Cerebrovascular Events in Elderly Hemodialysis Patients.

The purpose of this study was to assess the risk factors and clinical characteristics of cardiovascular and cerebrovascular events in elderly hemodialysis patients. Elderly patients undergoing hemodialysis (HD) at Deqing County People's Hospital in Zhejiang, China, from May 2020 to May 2023 were enrolled in this study. They were divided into two groups depending on the occurrence of cardiovascular or cerebrovascular events: the case group and the control group. A total of 106 patients were enrolled in this study. Among them, 49 patients experienced cardiovascular or cerebrovascular events, resulting in an incidence rate of 46.23%. According to whether cardiovascular or cerebrovascular events occurred, 57 patients were assigned to the control group, and 49 patients were assigned to the case group. Comparing the basic information and clinical indicators of the two groups, significant differences were observed in patients with hypertensive nephropathy and diabetic nephropathy (P < .05). There were also significant differences in dialysis duration, smoking history, systolic and diastolic blood pressures, uric acid, blood glucose, total cholesterol (TC), lowdensity lipoprotein cholesterol (TG), C-reactive protein (CRP), and PTH (parathyroid hormone) levels and platelet-to-lymphocyte ratio (PLR), between the two groups (P < .05). Multivariate logistic regression analysis revealed that longer dialysis duration, higher systolic and diastolic blood pressures, elevated uric acid, TC, TG, LDL-C, PTH, and blood glucose levels, smoking history, elevated PLR, and CRP were independent risk factors for cardiovascular and cerebrovascular events. The ROC curve showed that these risk factors predicted cardiovascular and cerebrovascular events in patients. Patients with underlying diseases such as hypertensive or diabetic nephropathy are more likely to experience cardiovascular and cerebrovascular events. Longer dialysis duration, higher systolic and diastolic blood pressures, elevated uric acid, TC, TG, LDL-C, PTH and blood glucose levels, and boosted inflammatory reaction are risk factors for these events among elderly HD patients. The purpose of this study is to provide practical guidelines for clinical treatment. Comprehensive measures such as active intervention of risk factors, rational drug use and regular examination should be taken to improve the overall health level to the greatest extent for elderly patients with high-risk HD. DOI: 10.52547/ijkd.7877.

The association of milk and multiple food avoidance with growth parameters in infants and children

BackgroundRecent studies reported that strict avoidance of milk products in cow's milk allergy (CMA) affects growth and bone turnover, causing negative calcium balance and changes in bone metabolism. ObjectiveTo investigate biochemical parameters to predict bone turnover and its relations with height and weight measurements and nutritional intake. MethodsHeight, weight, and body mass index z scores were plotted for age according to the World Health Organization. A 3-consecutive day food record was analyzed for nutritional values of foods. The blood levels of calcium, phosphorus, alkaline phosphatase, vitamin D, and parathyroid hormone (PTH) were determined. ResultsThe study included 69 controls, 66 children with isolated CMA, and 59 children with multiple food allergy (FA). The z scores for weight, height, and body mass index were lower in isolated CMA and multiple FA groups than controls (P < .001, P = .004, and P = .002, respectively). The nutritional intakes of protein, fat, carbohydrates, vitamins B2 and B12, niacin, calcium, and phosphorus were significantly lower in isolated CMA and multiple FA than controls. In infants (≤2 years of age), although blood calcium level was in normal range, it was significantly lower in isolated CMA and multiple FA than in controls (P < .001). In children older than 2 years, PTH level was significantly higher in isolated CMA and multiple FA groups than in controls (P = .003). ConclusionOur study revealed that children with isolated CMA and multiple FA had a high nutrition gap, growth deceleration, and unbalanced bone metabolism, as illustrated by low blood calcium and elevated PTH levels.

Factores de progresión en pacientes con ERC-3 KDOQI (estudio PROGRESER)

IntroductionThe PROGRESER study is a multicentre, prospective, observational, 3-year follow-up study of a cohort of patients with stage3 chronic kidney disease (CKD) from different nephrology departments of hospitals in the Spanish healthcare system. The primary study objective was to analyse risk factors for CKD progression, identifying possible differences between patients with and without diabetes mellitus (DM). The secondary objective was to analyse the factors associated with hospitalizations and mortality. Patients and methodsA total of 462 patients (342 men and 120 women; mean age 66.5±11.5 years) were recruited from 25 participating sites in Spain. Clinical, epidemiological and analytical data were recorder in an electronic register each six months. Biological samples were obtained and frozen for a biobank record at baseline and at 18 and 36 months. ResultsThe initial mean glomerular filtration rate estimated by MDRD and after that reestimated by CKD-EPI was 43.9±7.9mL/min/1.73m2; and 29±6,8mL/min/1,73m2 at 3years. 27.3% of patients had microalbuminuria and 22.5% had macroalbuminuria. Two-thirds of the patients (66.2%) presented renal damage progression according to the study criteria (decrease of more than 15% in eGFR over the baseline value). 38.7% presented a reduction in eGFR ≥30%; 20.3% had a reduction in eGFR ≥40%; 10.4% had a reduction ≥50% and 6.9% had a reduction ≥57%. Of the 199 diabetics, 134 (67.3%) suffered renal damage progression. Of the 263 non-diabetics, 172 (65.3%) presented progression (P=.456). 27.3% of patients had microalbuminuria and 22.5% proteinuria. The study found that CKD progression to a higher stage was not greater in diabetic compared to non-diabetic patients. Multivariate analysis revealed that the presence of arterial hypertension bordered on significance as a progression factor in non-diabetic patients (P=.07), and that, in diabetic patients, lower calcium levels and elevated intact parathyroid hormone levels at baseline were associated with progression. ConclusionIn our study we have not found new factors for progression of renal damage, different from the yet well known traditional factors. DM per se was not a differential factor for progression in relation with non DM patients. Progression of renal damage in patients with CKD-3 KDOQI may be interpreted in a multifactorial context. The search for new biomarkers, different from traditional ones, is necessary to establish new therapeutic strategies to prevent the progression of CKD.

Simultaneous Papillary Thyroid Carcinoma and Primary Hyperparathyroidism: Unusual Presentation

The coexistence of Primary Hyperparathyroidism (PHPT) with Papillary Thyroid Carcinoma (PTC) is a rare clinical occurrence. Thyroid pathology is reported in 20% to 84% of Primary Hyperparathyroidism (PHPT) cases, with malignancies identified in 2% to 20% of instances. We report a case of a 49-year-old woman referred for evaluation of left iliac wing and hip pain with elevated parathyroid hormone levels. Imaging revealed a toxic multinodular goiter with a parathyroid adenoma. The patient underwent total thyroidectomy with parathyroid adenoma excision. Subsequent histological examination unexpectedly identified a papillary thyroid microcarcinoma associated with the parathyroid adenoma. The association between PHPT and PTC is complex, influenced by shared embryological origins and genetic factors. Elevated PTH levels in PHPT may contribute to thyroid cell proliferation, and hypercalcemia is suggested to promote thyroid carcinogenesis. Molecular analyses suggest the involvement of pathways like MAPK and Wnt/β-catenin. The coexistence of PHPT and PTC highlights the necessity for thorough preoperative assessment and the ongoing need for research. While minimally invasive parathyroid surgery is favored, the risks associated with coexisting thyroid pathology should be carefully considered. Routine thyroid ultrasonography in PHPT patients is crucial to exclude nodular thyroid disease, emphasizing the role of research in guiding clinical practices. A balanced approach integrating technical advancements and thoughtful risk assessment is essential in navigating this complex clinical scenario.

An Ectopic Parathyroid Adenoma of the Retropharynx in a Patient with Primary Hyperparathyroidism and Papillary Thyroid Cancer-A Rare Case.

The frequency of concurrent thyroid cancer in patients with primary hyperparathyroidism (pHPT) varies. While the pathological association between thyroid and parathyroid disorders is frequently noted, the co-occurrence of parathyroid adenoma and papillary thyroid cancer is exceptionally rare. Furthermore, an ectopic parathyroid adenoma in the retropharyngeal space is exceedingly rare. Therefore, anatomical variations through the utilization of relevant diagnostic tools play a crucial role in guiding decisions pertaining to clinical manifestations, diagnostic methods, surgical interventions, and operative strategies for parathyroid tumors. We present a case of a 51-year-old female patient with papillary thyroid carcinoma in the right thyroid lobe and an ectopic parathyroid adenoma in the retropharyngeal space confirmed through surgical intervention. The elevated preoperative levels of serum calcium and parathyroid hormone, along with low serum phosphate, returned to normal ranges after surgery. This case sheds light on the unusual occurrence of an ectopic parathyroid adenoma in the retropharyngeal region within a thyroid cancer patient, providing valuable insights into the realm of thyroid malignancies.

Transplantation and Noninvasive Longitudinal In Vivo Imaging of Parathyroid Cells: A Proof-of-Concept Study.

The parathyroid cell is a vital regulator of extracellular calcium levels, operating through the secretion of parathyroid hormone (PTH). Despite its importance, the regulation of PTH secretion remains complex and not fully understood, representing a unique interplay between extracellular and intracellular calcium, and hormone secretion. One significant challenge in parathyroid research has been the difficulty in maintaining cells ex vivo for in-depth cellular investigations. To address this issue, we introduce a novel platform for parathyroid cell transplantation and noninvasive in vivo imaging using the anterior chamber of the eye as a transplantation site. We found that parathyroid adenoma tissue transplanted into the mouse eye engrafted onto the iris, became vascularized, and retained cellular composition. Transplanted animals exhibited elevated PTH levels, indicating a functional graft. With in vivo confocal microscopy, we were able to repetitively monitor parathyroid graft morphology and vascularization. In summary, there is a pressing need for new methods to study complex cellular processes in parathyroid cells. Our study provides a novel approach for noninvasive in vivo investigations that can be applied to understand parathyroid physiology and pathology under physiological and pathological conditions. This innovative strategy can deepen our knowledge on parathyroid function and disease.

Neonatal Severe Hyperparathyroidism: A Case Report

Background: Neonatal severe hyperparathyroidism is an extremely rare condition that presents in the first few months of life. Recognition at the early stage followed by prompt surgical intervention are of vital importance for survival. Hypotonia, respiratory distress, lethargy and delay in growth and development occur in association with the elevated serum parathormone levels and hypercalcemia. Definitive therapy involves total parathyroidectomy. Case Description: We are presenting a case with Neonatal severe hyperparathyroidism, who underwent total parathyroidectomy. The patient had been followed up with medical therapy until. Parathormone levels rapidly declined following total parathyroidectomy and the patient was discharged with full recovery. Literature Review: Sestamibi scintigraphy might fail to show an ectopic parathyroid gland. In such conditions, on table confirmation of parathyroid glands by frozen section and Intraoperative parathormone monitoring is vital at this point. Persistently elevated parathormone levels might suggest a remnant parathyroid tissue at the surgical site or an ectopic parathyroid gland that should be excised. Clinical Relavance: Neonatal severe hyperparathyroidism is a life-threatening disease. In the present case surgery performed at the early is life-saving due to the failure of medical therapy to control the disease.

흉선에서 발생한 이소성 부갑상선 선종 1예

Primary hyperparathyroidism (PHPT) is a common endocrine disorder with elevated serum parathyroid hormone levels. In most cases, the disease involves a single parathyroid adenoma, followed by parathyroid hyperplasia. Parathyroid glands are rare, but can be present in a variety of locations because it migrates long distance during fetal period. Therefore, the incidence of ectopic parathyroid adenoma is rare and it is not easy to diagnose ectopic parathyroid adenomas and to specify the location before surgery. Recently, we diagnosed ectopic parathyroid adenoma at the thymus and treated successfully. So, we report this case with literature review.

Normocalcemic hyperparathyroidism: Intervention to differentiate primary from secondary hyperparathyroidism

BackgroundNormocalcemic hyperparathyroidism can occur, but surgery should not be considered until common etiologies for secondary hyperparathyroidism are comprehensively excluded. Calcium deficiency is an underrecognized cause of normocalcemic parathyroid hormone elevation, and we aim to determine if the implementation of a preoperative calcium challenge can be used to reduce unnecessary parathyroidectomy. MethodsConsecutive patients referred for parathyroidectomy (1/21–6/22) with normocalcemia (serum calcium <10 mg/dL) and concurrently elevated parathyroid hormone levels were routinely treated with supplemental calcium and vitamin D3, and follow-up laboratory studies were assessed. ResultsA total of 29/314 (9%) patients had normocalcemic parathyroid hormone elevation with mean calcium, parathyroid hormone, and vitamin D 25OH levels of 9.5 ± 0.3 mg/dL, 109.9 ± 34.9 pg/mL, and 42.7 ± 23.8 ng/mL respectively. Confounding factors included estimated glomerular filtration rate <60 in 2, loop diuretic use in 4, and prior gastric bypass or gastric sleeve surgery in 4. Follow-up biochemical evaluation was available in 27 (92%); results were unchanged in 7 patients (26%); normalization of parathyroid hormone levels with persistently normal calcium levels occurred in 15 (55%), thus confirming secondary hyperparathyroidism and hypercalcemia with elevated parathyroid hormone levels (classic primary hyperparathyroidism) was diagnosed in 5 (19%). Parathyroid exploration has been completed for 3 of 5 patients with classic primary hyperparathyroidism to date. ConclusionA preoperative calcium challenge was prospectively initiated in normocalcemic patients with parathyroid hormone elevation, and there was high compliance (92%). Short-interval calcium supplementation revealed ∼50% to have resolved secondary hyperparathyroidism due to insufficient calcium intake, which avoided unnecessary surgery. In contrast, classic patients were unveiled in 20%, allowing for prompt and correct surgical intervention.

Brown tumor due to primary hyperparathyroidism in a familial case: a case report

BackgroundPrimary hyperparathyroidism (PHPT) is an uncommon disorder characterised by hypercalcemia with an increased parathyroid hormone level. We reported a PHPT familial case with two subjects, a father and a daughter, and both of them had suffered from the brown tumor.Case presentationThe proband, a 43-year-old patient, developed parathyroid adenomas at the age of 15; a histologically confirmed right parathyroid adenoma was removed by parathyroidectomy; and after six months follow-up, the serum calcium level was normalised. At the age of thirty-three, a CT scan of his head and neck revealed a mass in the right maxilla, as well as PHPT (i.e., left inferior parathyroid adenoma). Then, he underwent a biopsy of an exophytic lesion in the right maxilla and was diagnosed by pathology as a brown tumor, with the serum calcium and PTH levels at 2.78 mmol/L and 221 pg/mL, respectively. Subsequently, the patient took a left inferior parathyroid microwave ablation with ultrasound guidance. After three months of follow-up, the serum calcium and PTH levels returned to normal, and the brown tumor was resolved. After three years, it mineralised as revealed in a CT scan. By the time he was 43 years old, during the 28-year follow-up period, the serum calcium and PTH levels were still within the normal range, and there was no discomfort reported. He has consistently taken calcium supplements throughout the 28 years. Since the initial diagnosis, his blood indicators of kidney function have been normal, and ultrasound showed renal calculus in the right kidney and a normal left kidney. The proband’s daughter, a 15-year-old girl, experienced left upper extremity pain for ten months. CT scan revealed a mass in the distal left radius, and a giant cell tumor was suspected. A surgical internal fixation was performed, and the pathology showed a brown tumor. Laboratory tests revealed a serum parathyroid hormone (PTH) level of 1554pg/mL, calcium level of 3.14 mmol/L, phosphorus level of 0.72 mmol/L, and alkaline phosphatase level of 1892 U/L. Given the osteitic changes and elevated levels of calcium and PTH, ultrasonography was performed, after which a mass was detected measuring 19 × 9 × 7 mm mixed with solid components and cystic fluid in the right thyroid gland. The results of 99mTc-MIBI scintigraphy confirmed the abnormal accumulation of 99mTc-MIBI in the right thyroid gland but not seen in the bilateral parathyroid glands. The patient underwent thyroidectomy, and the postoperative pathology report indicated an intra-thyroid ectopic parathyroid adenoma. The serum calcium and PTH levels became normal at 4 h after surgery. One to three months after operation, the serum calcium level was low, while the serum PTH level was high. Then, the patient was advised to take calcium supplements. Until the sixth month after the operation, the serum calcium level and serum PTH level returned to normal, and the bone pain was relieved. The patient’s blood tests for kidney function remained normal. There was no evidence of bilateral kidney disease (such as nephrolithiasis or nephrocalcinosis) detected by ultrasound scan. There were several similarities in the state of illness between these two subjects. Both the father and the daughter developed parathyroid adenomas at the age of 15, and there was no lesion in other endocrine glands. And genetic testing revealed mutations in the CDC73 genes in both father and daughter. On the other hand, there were also a few differences. The father’s first signs of brown tumor were in the right maxilla, while the daughter’s appeared in the distal left radius. The father presented pathological changes in the left and right parathyroid glands, whereas the daughter presented with an ectopic parathyroid adenoma in the right thyroid gland.ConclusionWe report a familial case in which father and daughter were diagnosed to have brown tumors due to parathyroid adenoma and ectopic parathyroid adenoma, and genetic testing revealed CDC73 gene mutations in both. Therefore, in the diagnostic and differential process of young patients having bone disease, clinicians should not only focus on the clinical manifestations of the skeleton, but also implement a comprehensive analysis of systemic symptoms, considering the possibility that the patient has familial PHPT.

SAT209 Metastatic Parathyroid Carcinoma And The Challenge Of Maintaining Calcium Balance

Abstract Disclosure: K.M. Tuna: None. S. Badour: None. E.P. Monsour: None. G. Acosta Garcia: None. D. Barb: None. Background: Parathyroid carcinoma is a rare malignancy representing less than 1% of all parathyroid disorders. Presentation is significant for highly elevated calcium (Ca) and parathyroid hormone (PTH) levels, and usually a palpable neck mass (&amp;gt;3cm). Diagnosis is often made after surgery based on histopathology findings. The primary treatment modality remains surgical, but there is no effective approach for metastatic disease. Case presentation: A 51-year-old woman initially presented with multinodular goiter and compressive symptoms in 2008. Workup showed an elevated Ca of 14.4 mg/dl (normal 8.4-10.2 mg/dl) and PTH of 502 pg/ml (normal 12-88 pg/ml) while albumin 4.3 g/dl (normal 3.5-5.2 g/dl) and normal thyroid function tests. Radioactive Iodine uptake scan showed a 4.4 cm cold nodule on the right inferior pole. Sestamibi scan showed increased left upper pole activity. The patient underwent total thyroidectomy with surgical exploration for parathyroid adenoma. Pathology showed right intrathyroidal parathyroid carcinoma with lymphovascular invasion. The patient was lost to follow-up until 2022 when she was admitted with severe hypercalcemic crisis (Ca 15.8 mg/dl, Albumin 3.9 g/dl, and PTH 805 pg/ml). The patient was treated with IV fluids, calcitonin, and multiple rounds of bisphosphonates, and was then maintained on high-dose cinacalcet due to refractory and recurrent hypercalcemia. Repeat Sestamibi and neck US were unremarkable, although CT chest showed a 1.3 cm nodule in the right lower lung lobe. This was not FDG- nor DOTATATE-avid on PET-CT. The patient underwent laparoscopic wedge resection of the right lung nodule, and the pathology was consistent with metastatic parathyroid carcinoma. Her Ca and PTH levels normalized immediately after surgery (PTH decreased from 883 to 27 pg/ml) suggesting possible remission. Prior to discharge, she was started on oral calcium and vitamin D due to dropping Ca levels and clinical signs of hungry bone syndrome. She was readmitted one month later for preexistent heart failure exacerbation and declining renal function. Her PTH was noted to be elevated again, although Ca remained normal, raising concern for recurrent or persistent disease. However, the patient’s renal impairment and lung effusion limited further imaging. Ca and PTH were monitored frequently during hospitalization and weekly after discharge. PTH levels peaked at 634 pg/ml and then dropped to 127 pg/ml without intervention. Ca remained in the normal range while on calcium citrate and calcitriol. Conclusion: Treatment of metastatic parathyroid carcinoma remains a challenge. Mortality is secondary to complications of hypercalcemia; therefore, controlling calcium levels should be the main therapeutic goal. Hungry bone syndrome should be considered after surgery. Metastatic disease may occur even after 20 years; thus, lifelong close monitoring is indicated. Presentation: Saturday, June 17, 2023

FRI691 Intrathyroidal Parathyroid Adenoma With Congenitally Absent Contralateral Thyroid Lobe Treated With Thermal Ablation

Abstract Disclosure: L. Bilandzic: None. L. Bilandzic: None. H. Korkusuz: None. We present a rare case of primary hyperthyroidism with ectopic adenoma located in the right thyroid lobe with congenitally absent left thyroid lobe which was treated with thermal ablation. A 60-year-old woman was referred to endocrinology clinic for further evaluation of her elevated total serum calcium of 11.4 mg/dL (reference range 8.5-10.5), elevated parathyroid hormone (PTH) level of 106 (10-60 pg/mL). Bone mineral densitometry showed a total T score of -2.9 in L1-L4. Other results were vitamin D 25-OH 30 ng/mL (ref. range 30 - 100), TSH 3.36 µIU/mL (ref range 0.4-5.0), eGFR 83 (normal &amp;gt; 59 mL/min/ 1.73 m²). She was asymptomatic and had no history of kidney stones. Other causes of hypercalcemia were refuted. Given the osteoporosis in her lumbar spine, parathyroid localization and surgery were suggested. Thyroid and parathyroid sonography demonstrated a solid hypoechoic nodule in the right thyroid lobe, 12x10x11mm, with smooth margins, no calcifications, classified as ACR TI-RADS T4. Left thyroid lobe was not appreciated and was considered to be congenitally absent since the patient did not have a history of a previous thyroid resection. Further localization studies (99mTc Sestamibi parathyroid scintigraphy and 4D-CT of the neck) did not reveal any other possible candidates for parathyroid adenomas. Eventually, a fine needle aspiration of the nodule in the right thyroid lobe was performed. PTH needle wash showed a PTH value of 633 pg/mL whereas the PTH value ≥ 100 pg/mL is suggestive of the presence of PTH secreting tissue. Given the thyroid anatomy found with this patient, a right lobe hemithyroidectomy would result with a permanent substitution dependent hypothyroidism. As an alternative, thermal ablation was presented as a treatment option for which the patient opted. She underwent the procedure in local anesthesia. Sonographic imaging of the adenoma was followed by the percutaneous insertion of the coagulation electrode. The utilized high frequency ablator was used with an output of 9 to 40 W and a frequency of 470 ± 10 kHz. There were no complications developed during or after the procedure. Two weeks after the thermal ablation, PTH level was measured at 55 pg/mL, total serum calcium at 9.5 mg/dL, TSH 1.01 µIU/mL. Sonography showed a hyperechoic nodule at the former location of the parathyroid adenoma, which was evaluated as a scar tissue. Three months after the procedure total calcium was at 9.3 mg/dL, PTH at 58 pg/mL, hence no biochemical evidence of pHPT. This is a rare case of ectopic parathyroid adenoma located in the thyroid gland with hemi agenesis of the contralateral lobe. A minimally invasive thermal ablation was performed with the goal of inactivation of the adenoma and preserving the euthyroid function. Presentation: Friday, June 16, 2023

SAT215 Sagliker Syndrome In A Filipino Female With End Stage Renal Disease

Abstract Disclosure: M.R. Pajanel: None. E. Clarito: None. K. Uytiepo: None. P. De La Peña: None. This is a case of a 29-year-old Filipina, with chronic kidney disease secondary to chronic glomerulonephritis, undergoing hemodialysis for 10 years. She presented with maxillary mass, associated with other craniofacial deformities such as mandibular enlargement and widening of teeth spaces. Other associated symptoms include difficulty in swallowing solid food, difficulty in ambulation due to bone pains, and with noted shortening of stature. Workup revealed elevated intact parathyroid hormone (iPTH) 1638.8pg/mL(20x ULN), low Vitamin D, elevated ALP, but with normal levels of calcium and phosphorus. Sestamibi scan showed focal uptake and retention along medial aspect of the right thyroid bed and inferior to both thyroid beds suggestive of parathyroid adenoma or hyperplasia. Parathyroid ultrasound was consistent with findings of Sestamibi scan which also showed parathyroid nodules in the middle segment right thyroid lobe, and inferior to right thyroid lobe. Bone mineral density is below the expected range for age. Right parathyroidectomy was done and she was discharged well. She came in for follow-up with persistent elevated PTH 4765pg/ml(60x ULN), still with symptoms. Repeat imaging on ultrasound showed a parathyroid nodule posterior to the superior aspect of left thyroid 0.9 x0.5cm. Sestamibi scan confirmed a functioning parathyroid adenoma left inferior and superior thyroid bed. Left parathyroidectomy was done with a histopathologic result of left superior parathyroid consistent with parathyroid hyperplasia. On follow up, repeat intact PTH still elevated at 3677pg/mL and persistently elevated 2 months after at 3626pg/mL. Parathyroid ultrasound showed Parathyroid nodule, left, measuring 1.5x1.7x0.9 cm, inferior and posterior to the inferior border of the left thyroid gland. 99mTc-Sestamibi scan was consistent with the ultrasound in the left thyroid lobe suggestive of parathyroid adenomas or hyperplasia. Completion Parathyroidectomy was done on November 2018. Pre-operative iPTH was 4205pg/mL, which decreased to 291.3pg/mL postoperatively. She was discharged improved. On followup in 2022, she reports of decrease bone pain and now able to ambulate without difficulty. Repeat bone mineral density has improved and now within expected range for age. CONCLUSION: Sagliker syndrome is an entity described as an “uglyfying face syndrome” seen in patients with chronic kidney disease, presenting with facial deformities. Patients usually present with elevated parathyroid hormone (PTH) levels, and has been refractory to medical therapy. Surgical treatment has been the course of approach to prevent further clinical decline of patients. Identification of the syndrome is important for clinicians to know when to maximize medical management, and to identify patients who will benefit with early surgical management. The patient’s quality of life improved even 4 years post-surgery. Presentation: Saturday, June 17, 2023

OR23-01 The Nonredundant Role Of Beta-Amyloid In Mediating Tonic PTH Secretion In Physiological And Pathological States

Abstract Disclosure: C. Tu: None. Z. Cheng: None. K.A. Pena: None. N. Szeto: None. J.A. Sosa: None. J. Vilardaga: None. J. Koh: None. W. Chang: None. Understanding the mechanisms driving parathyroid hormone (PTH) hypersecretion in primary hyperparathyroidism (PHPT) is essential for better management of this common endocrinopathy. Prior studies showed that reduced Ca2+-sensing receptor (CaSR) expression and the subsequent increases in heterodimerization of the CaSR with the type B γ-aminobutyric acid receptor 1 (GABAB1R) are causally linked to PTH hypersecretion in PHPT mouse models (Nat Metab 2:243-255). We further showed that expression of the putative GABAB1R ligands, amyloid precursor protein (APP) and its proteolytic product, β-amyloid (Aβ1-42), is significantly upregulated in adenomas of PHPT patients associated with vitamin D insufficiency/deficiency when compared to normal donor controls. The current study aims to delineate the actions of Aβ1-42 in promoting tonic PTH secretion and its interactions with vitamin D receptor (VDR) signaling in parathyroid glands (PTGs) in basal and PHPT states. We show that Aβ1-42 (200 nM) stimulated tonic PTH secretion in cultures of normal human PTGs without shifting the calcium/PTH secretion setpoint (Ca2+-setpoint). In contrast, conditional knockout (KO) of the App gene in the parathyroid cell (PTC) of PTCAppΔflox/Δflox mice significantly reduced serum PTH levels (KO: 64±13 pg/ml vs Control: 109±12 pg/ml; p&amp;lt;0.05, n=8) despite hypocalcemia, indicating hypoparathyroidism. In PTGs cultured from the PTCAppΔflox/Δflox mice, supplementation of Aβ1-42 dose-dependently (EC50=5.6 nM, p&amp;lt;0.001) increased PTH secretion without altering the Ca2+-setpoint. However, the stimulatory effects of Aβ1-42 on tonic PTH secretion were completely abrogated in the PTGs with concurrent deletions of App, Casr and Gabbr1 genes, supporting a direct action of Aβ1-42 on CaSR and/or GABAB1R. The latter notion is further supported by the ability of Aβ1-42 to stimulate cAMP production in cells co-expressing CaSR and GABAB1R. PTC-specific deletion of the Vdr gene in the PTCVdrΔflox/Δflox mice led to elevated serum PTH levels in vivo and increased tonic PTH secretion with unaffected Ca2+-setpoint in PTGs in vitro. Concurrent ablation of the App gene completely normalized serum PTH levels in the PTCVdrΔflox/Δflox mice and prevented PTH hypersecretion in their PTGs in culture. These findings support a critical role of the APP-derived Aβ1-42 in mediating tonic PTH secretion in the normal physiological state and suggest a new mechanism driving PTH hypersecretion in PHPT due to vitamin D deficiency. Presentation: Saturday, June 17, 2023

THU234 An Adolescent Patient With Asymptomatic Hypocalcemia And Extensive Cerebral Calcification Due To Pseudohypoparathyroidism Type 1B: A Care Report

Abstract Disclosure: R. Alemzadeh: None. J.D. Ross: None. D. Guillen-Mendoza: None. Background: Pseudohypoparathyroidism (PHP) is a heterogeneous group of disorders due to renal resistance to parathyroid hormone (PTH) resulting in biochemical hypoparathyroidism but with skeletal sensitivity to PTH. Case Presentation: A 15-year-old African American male was incidentally found to have biochemical evidence of severe hypocalcemia during routine evaluation of his bilateral slipped capital-femoral epiphyses. The patient was at age-appropriate stage of puberty with normal height and without any features of hereditary osteodystrophy. However, he had history of mild developmental delay requiring school accommodations. On physical exam, there was some mild dyscoordination with finger and toe-tapping and a Myerson’s sign, negative tetany signs. The biochemical screening revealed markedly low serum calcium (4.9 mg/dL) with elevated phosphorus (7.8 mg/dL) and PTH (1314 pg/mL) levels. His hypocalcemia was accentuated by the presence of severe 25 hydroxy-vitamin D deficiency (7.5 ng/mL) with mild hypomagnesemia (1.4 mg/dL). He had normal renal and thyroid function tests with normal growth factors. There were minimal plasma cyclic AMP responses to a single dose of intravenous teriparatide (Ellsworth-Howard test) consistent with diagnosis of pseudohypoparathyroidism. The skeletal survey showed bowing and under-tubulation of the radius, ulna, tibia, and fibula as well as slipped capital femoral epiphysis bilaterally. His brain CT scan showed symmetrical severe dense calcifications in the basal ganglia, bilateral frontal, parietal and temporal subcortical white matter, pons and right dentate nucleus. Genetic testing did not reveal any GNAS mutations. The patient was initially treated with parenteral calcium followed by high-dose oral calcium supplements and calcitriol. His coexisting hypovitaminosis D and hypomagnesemia were corrected with oral high-dose cholecalciferol and magnesium sulfate, respectively. Conclusions: An incidental finding of severe asymptomatic hypocalcemia and elevated PTH without hereditary osteodystrophy phenotype raised the clinical suspicion of pseudohypoparathyroidism type 1B. This was associated with cerebral calcifications with increasing risk of worsening learning disabilities and minimal neurological findings. Presentation: Thursday, June 15, 2023