Postsurgical Hypoparathyroidism Research Articles

12520 Preliminary Findings From An Ongoing Open-label Phase 2 Study Demonstrate That The Calcilytic Encaleret Can Improve The Relationship Between Blood And Urinary Calcium In Individuals With Post-surgical Hypoparathyroidism

Abstract Disclosure: I.R. Hartley: Research Investigator; Self; Calcilytix Therapeutics, Inc. R.I. Gafni: Research Investigator; Self; Calcilytix Therapeutics, Inc. K.L. Roszko: Research Investigator; Self; Calcilytix Therapeutics, Inc. X. Li: None. E.A. Ferguson: Research Investigator; Self; Calcilytix Therapeutics, Inc. C.A. Moore: Research Investigator; Self; Calcilytix Therapeutics, Inc. K.A. Pozo: Research Investigator; Self; Calcilytix Therapeutics, Inc. K.T. Ampuero: Research Investigator; Self; Calcilytix Therapeutics, Inc. A.V. Sridhar: Employee; Self; Calcilytix Therapeutics, Inc. A.S. Mathew: Employee; Self; Calcilytix Therapeutics, Inc. M. Roberts: Employee; Self; Calcilytix Therapeutics, Inc. S.H. Adler: Employee; Self; Calcilytix Therapeutics, Inc. E.F. Nemeth: Consulting Fee; Self; Calcilytix Therapeutics, Inc. M.T. Collins: Research Investigator; Self; Calcilytix Therapeutics, Inc. Parathyroid hormone (PTH) and the calcium-sensing receptor (CaSR) are the primary regulators of blood and urinary calcium. The independent contributions of PTH and the CaSR on renal calcium handling are not well understood, largely due to their intertwined physiology. In individuals with functioning parathyroid tissue, calcilytics (negative modulators of the CaSR) increase PTH secretion and decrease urinary calcium excretion, leading to increased blood calcium levels. We hypothesized that calcilytic administration to individuals with post-surgical hypoparathyroidism (PSH) may reveal the PTH-independent effects of CaSR modulation on renal calcium handling and clarify the potential therapeutic role of calcilytics in PSH. Four women (26-69y) with PSH enrolled in an ongoing, open-label, phase 2, proof-of-principle study of encaleret, an oral investigational calcilytic (NCT05735015). Encaleret 162 mg was administered every 12 hours for up to 10 doses. Calcitriol was discontinued one day prior to the first dose of encaleret. All participants received calcium supplementation initially. To maintain eucalcemia, 1 participant discontinued calcium supplementation and 3 required re-initiation of low-dose calcitriol (0.25 mcg daily). Results are presented as mean (range) of fasting baseline pre-dose levels compared to fasting levels 12 hours after the last dose of encaleret. Fractional excretion of calcium (FECa), a measure of renal calcium handling that quantifies the relationship between blood and urinary calcium, decreased by 52% (34-78). Albumin-corrected blood calcium increased from 8.4 mg/dL (range 8.1-8.6; nl 8.4-10.2) to 9.3 (8.6-10.7). Urinary calcium excretion decreased from 348 mg/day (range 204-501; nl <250) to 169 (76-350), with normalization in 3 participants and a 30% decrease in the fourth. Baseline PTH of 7.4 pg/mL (range 4.6-10.1; nl 15-65) transiently increased 30 minutes after the first dose to 13.0 (4.5-18.1), then returned to near baseline levels. Bone turnover markers were normal and did not change on encaleret. There were no serious adverse events reported. The only treatment-related adverse events (AEs) were mild hypercalcemia causing headache in 1 participant. Her blood calcium levels continued to be mildly elevated for 60 hours after the last dose of encaleret even after calcium and calcitriol supplementation was discontinued. Despite elevated blood calcium, her 24-hour urine calcium remained <200 mg/day. Encaleret reduced FECa in the first four participants with PSH, improving the relationship between blood and urinary calcium. These preliminary results from this Phase 2 study support continued evaluation of encaleret as an orally administered therapy for the treatment of patients with PSH. Presentation: 6/1/2024

7192 Description Of Patients With Post-surgical Hypoparathyroidism In Clinical Follow-up In Brazil

Abstract Disclosure: L.D. Santos: None. G. Oliveira Martins: None. L. Costa Figueiredo: None. M. Nascimento de Lemos: None. J.V. Lima: None. L.A. Alvares: None. E.N. Sakane: None. N. Scalissi: None. Post-surgical hypoparathyroidism is an event that may occur, especially after extensive procedures in the cervical region. There are few long-term follow-up studies on individuals who develop permanent post-surgical hypoparathyroidism and its long-term complications. Objective: This study aims to assess the clinical and laboratory characteristics of patients diagnosed with permanent hypoparathyroidism at a tertiary care center in Brazil. Methods: We conducted a retrospective analysis of medical records. Results: We evaluated 27 patients with permanent hypoparathyroidism, with an average age of 53 years (SD=10), where 15% were alcohol and tobacco consumers, and 88% were female. The average time of permanent hypoparathyroidism diagnosis was 9 years and 3 months. Regarding the surgical indication, 35% were due to Graves' disease, 25% for thyroid goiter, 25% for thyroid cancer, and 15% for glottic cancer. Only 15% had a description of the parathyroid glands in the pathology report. As for medications, all patients were using calcium carbonate, with an average dose of 1700 mg daily per individual. 90% of the patients were using calcitriol, with an average dose of 0.64 mcg daily, and 55% were using cholecalciferol, with an average weekly dose of 9700 IU. Hydrochlorothiazide was used by 35% of the patients, with an average daily dose of 34 mg. Regarding postoperative exams 24 hours after surgery, only half had the parathyroid hormone (PTH) test requested or available, with only one patient having PTH >10 pg/mL. Regarding chronic complications, 15% presented with nephrolithiasis, 5% with subcapsular cataract, 5% with prophylaxis for seizures, 15% with a diagnosis of depression, and 10% with arrhythmias. Conclusion: Individuals with permanent hypoparathyroidism require attention due to chronic complications, and proper treatment aims to reduce the chance of developing other diseases associated with permanent post-surgical hypoparathyroidism. Presentation: 6/2/2024

8317 Biochemical Adequacy And Renal Complications In Long-Term Management Of Patients With Postsurgical Hypoparathyroidism

Abstract Disclosure: A. Hong: None. J. Park: None. W. Choi: None. J. Yoon: None. H. Kim: None. H. Kang: None. Background: Hypoparathyroidism (HypoPT) most commonly develops after neck surgery, particularly thyroid surgery. Permanent postsurgical HypoPT necessitates calcium and active vitamin D supplementation for 12 months or more due to irreversible parathyroid damage following surgery. This study investigated the biochemical adequacy of conventional therapy (i.e., active vitamin D and/or calcium) in patients with permanent postsurgical HypoPT based on recent guidelines and assessed the incidence of renal complications. Materials and Methods: The study included 62 adult patients with permanent postsurgical HypoPT who underwent total thyroidectomy for papillary thyroid cancer at Chonnam National University Hwasun Hospital. Biochemical parameters, including albumin-adjusted serum total calcium, ionized calcium, phosphate, creatinine, parathyroid hormone, magnesium, 25-hydroxyvitamin D (25[OH]D), and 24-h urine calcium, were measured. Renal ultrasound and KUB X-ray were performed for all patients. Results: The mean age of the patients was 55.5 ± 12.4 years, with 48 (77.4%) being female. The median follow-up duration after surgery was 10.6 years (interquartile range 9.0-15.5 years). At the time of evaluation, all patients were treated with calcitriol. Additional treatment, including calcium carbonate or cholecalciferol, was received by 43 (69.4%), and 28 (45.2%) were given thiazide diuretics. Thirty-seven (59.7%) patients had values below the recommended serum calcium (albumin-adjusted or ionized) concentration, while three (4.8%) had values above the upper normal limit of serum phosphate level. Serum 25(OH)D levels were maintained within the normal range (30-50 ng/mL) in 27 (43.5%) patients, and 47 (75.8%) patients met normal serum magnesium levels. Hypercalciuria, defined as >7.5 mmol/day in men and >6.25 mmol/day in women, was observed in 12 (19.4%) patients. Nephrolithiasis and nephrocalcinosis were present in 2 (3.2%) patients each. No patient had chronic kidney disease (CKD), defined as an estimated glomerular filtration rate <60 mL/min/1.73 m2. Conclusion: Conventional management for permanent postsurgical HypoPT appears suboptimal for certain patients. However, the incidence of renal complications, such as hypercalciuria, nephrolithiasis/nephrocalcinosis, and CKD, was not commonly observed in a real-world setting during the 10 years of follow-up. This observation may be associated with a higher prescription rate of thiazide diuretics. Presentation: 6/2/2024

12609 Navigating The Therapeutic Challenge Of Post-surgical Hypoparathyroidism And Refractory Hypocalcemia

Abstract Disclosure: D. Fawcett: None. A. Domingo: None. Introduction: Post-surgical hypoparathyroidism poses a challenge due to calcium metabolism disturbances, ranging from mild to life-threatening complications. Despite advancements, vigilant monitoring and tailored interventions are vital for optimizing outcomes. Refractory hypocalcemia, resistant to standard therapies, underscores the need for specialized care to prevent prolonged hospitalization and morbidity. Case description: A 68-year-old woman with a history of Graves' disease and parathyroid carcinoma underwent total thyroidectomy and parathyroidectomy in January 2024. She presented to the emergency department for the second time with a recurrence of bilateral hand and perioral paresthesias, along with numbness, tingling, and weakness throughout her body. Notably, she had a prior hospital admission with similar symptoms and was discharged on calcium carbonate, magnesium, calcitriol, and vitamin D3. Vital signs were not provided. Initial laboratory workup revealed a calcium level of 4.3, with corrected calcium at 5.8, and magnesium levels at 1.8, supplemented with magnesium oxide. A 24-hour urine calcium test, vitamin D, and malabsorptive workup for celiac disease were unremarkable. Immunoglobulin A was low; however, tissue transglutaminase IgA and anti-gliadin antibodies were negative. An electrocardiogram showed a normal sinus rhythm with QT prolongation to 570 ms. Despite resuming her home regimen, her calcium level remained low, prompting initiation of calcium infusion. Consultations with endocrinology and nephrology were made, necessitating close monitoring and uptitration of calcium and vitamin D supplements for achievement and maintenance of low normal calcium levels. High doses of 3g TID of calcium and calcitriol 2mcg PO TID allowed for symptom control and discharge with outpatient follow-up with endocrinology and nephrology. Conclusion: Supplemental therapy with calcium and vitamin D analogues is standard for managing post-surgical hypoparathyroidism. Early identification and adequate management prevent hypocalcemia-related complications, including tetany, seizures, and cardiovascular anomalies such as QTc prolongation, as seen in our patient, which can result in torsade de pointes. Multidisciplinary care alongside nephrology was paramount. Serum calcium should be maintained in the low normal range, and 24-hour urine calcium excretion should also be closely monitored. Daily hydrochlorothiazide can be used to prevent hypercalciuria. In recurrent cases, as in our patient, titration of calcium and vitamin D analogues is imperative. Long-term consequences, including renal dysfunction, osteoporosis, and increased cardiovascular risk, underscore the necessity for timely diagnosis and management. Presentation: 6/2/2024

8115 Evaluation Of The Incidence Of Hypoparathyroidism In Patients Undergoing Anterior Cervical Surgery

Abstract Disclosure: L.D. Santos: None. G. Oliveira Martins: None. J.V. Lima: None. L.A. Alvares: None. M.N. Lemos: None. L. Costa Figueiredo: None. E.N. Sakane: None. N. Scalissi: None. Introduction: The consensus published in 2022 suggests that a parathyroid hormone (PTH) level below 10 pg/mL may predict permanent hypoparathyroidism. However, these data have not yet been tested in the Brazilian population.Objective: To assess the clinical and laboratory characteristics of patients undergoing anterior cervical surgery, aiming to identify whether a postoperative PTH level below 10 pg/mL is associated with permanent hypoparathyroidism in a tertiary center in Brazil. Methods: We conducted a retrospective study with a chart review analysis. Results: We analyzed 59 patients who underwent anterior cervical surgery, with a mean age of 53 years (SD= +/- 17). 81% of the patients were alcohol consumers, and 76% were smokers. Regarding the surgical indication, 60.34% were for thyroid cancer, 17.24% for thyroid goiter, 13.79% for Graves' disease, 5.17% for glottic cancer, and 3.45% for primary hyperparathyroidism. Of the total operated patients, 49.15% were diagnosed with permanent hypoparathyroidism. The distribution of patients with permanent hypoparathyroidism was as follows: thyroid cancer 34.5%, Graves' disease 24.1%, goiter 24.1%, glottic cancer 10.3%, and primary hyperparathyroidism 7%. There was no significant difference in the occurrence of post-surgical hypoparathyroidism concerning the type of surgical indication (p>0.05). Regarding PTH 24 hours after surgery, a significant difference was observed between the group with permanent hypoparathyroidism and the group without the disease, with a mean PTH of 5.0 pg/mL and 10 pg/mL, respectively (p<0.05). As for serum calcium collected 24 hours post-surgery, there was no significant difference between the groups with and without permanent hypoparathyroidism (7.5 x 8.0 mg/dL; p>0.05). Conclusion: The PTH measurement in the first 24 hours postoperatively has proven to be more discriminative than the serum calcium measurement during the same period in identifying patients with permanent hypoparathyroidism. Presentation: 6/2/2024

Predictors of lumbar spine trabecular bone score in women with postsurgical hypoparathyroidism

Hypoparathyroidism is a rare disease that markedly reduces bone remodeling, leading to increased bone mineral density and changes in bone microarchitecture. However, it is currently unclear how these changes affect fracture risk. In this study, we investigated bone mass by dual-energy x-ray absorptiometry, the occurrence of morphometric vertebral fractures, and bone microarchitecture by assessing trabecular bone score in women with postsurgical hypoparathyroidism. We included 67 women with hypoparathyroidism aged 52.9 ± 12.3 years and 63 age (52.9 ± 12.3 years) and body mass index-matched controls, which were assessed for femoral and lumbar spine bone mineral density, trabecular bone score, and vertebral fractures by dual-energy x-ray absorptiometry. Women with hypoparathyroidism had significantly higher bone mineral density at the lumbar spine, femoral neck, and total hip compared with controls despite similar trabecular bone score values. Vertebral fracture assessment indicated that two women with hypothyroidism presented vertebral fractures, both aged over 65 years. Conversely, no vertebral fractures were detected in control women. In a multivariate linear regression model, we found that older age, diabetes, and lower lumbar spine mineral density were significant predictors of lower trabecular bone score values. Our findings indicate that vertebral fractures are not common among women with postsurgical hypoparathyroidism aged under 65 years. Moreover, trabecular bone score values were similar in women with hypoparathyroidism and age-matched controls and were associated with traditional risk factors for fractures, such as older age, type 2 diabetes, and lower spine bone mineral density. Lay summaryChronic parathyroid hormone deficiency decreases bone turnover and modifies skeletal properties, although the impact of these changes on fracture risk remains unclear. We studied 67 women with postsurgical hypoparathyroidism and 63 age and body mass index-matched healthy controls and found that bone mineral density is increased in women with hypoparathyroidism despite similar trabecular bone score values and a low occurrence of morphometric vertebral fractures. This suggests that the low bone turnover in hypoparathyroidism increases bone mass, but this is not accompanied by improved bone microarchitecture, indicating that trabecular bone score may be a valuable tool to complement the assessment of skeletal health and the risk of fractures in this condition.

Prevalence of chronic postsurgical hypoparathyroidism not adequately controlled: an analysis of a nationwide cohort of 337 patients.

The identification of patients with chronic hypoparathyroidism who are adequately (AC) or not adequately controlled (NAC) has clinical interest, since poor disease control is related to complications and mortality. We aimed to assess the prevalence of NAC patients in a cohort of subjects with postsurgical hypoparathyroidism. We performed a multicenter, retrospective, cohort study including patients from 16 Spanish hospitals with chronic hypoparathyroidism lasting ≥3 years. We analyzed disease control including biochemical profile and clinical wellness. For biochemical assessment we considered three criteria: criterion 1, normal serum calcium, phosphorus and calcium x phosphorus product; criterion 2, the above plus estimated glomerular filtration rate ≥60 ml/min/1.73 m2; and criterion 3, the above plus normal 24-hour urinary calcium excretion. A patient was considered AC if he or she met the biochemical criteria and was clinically well. We included 337 patients with postsurgical hypoparathyroidism (84.3% women, median age 45[36-56] years, median time of follow-up 8.9[6.0-13.0] years). The proportions of NAC patients with criteria 1, 2 and 3 were, respectively, 45.9%, 49.2% and 63.1%. Patients who had dyslipidemia at the time of diagnosis presented a significantly higher risk of NAC disease (criterion 3; OR 7.05[1.44-34.45]; P=0.016). NAC patients (criterion 2) had a higher proportion of subjects with incident chronic kidney disease and eye disorders, and NAC patients (criterion 3) had a higher proportion of incident chronic kidney disease, nephrolithiasis and dyslipidemia than AC patients. The present study shows a strikingly high prevalence of NAC patients in the clinical practice of Spanish endocrinologists. Results suggest that NAC disease might be associated with some prevalent and incident comorbidities.

Postoperative parathyroid hormone (PTH) is equivalent to perioperative PTH drop in predicting postsurgical hypoparathyroidism.

Postoperative surgical hypoparathyroidism (PoSH) following thyroid surgery is an established complication. Several predictive factors have been identified including perioperative parathyroid hormone (PTH) levels. The aim of the study is to compare the drop in perioperative PTH to postoperative day 1 PTH in predicting hypocalcaemia and hypoparathyroidism. Records of consecutive patients who had either total or completion thyroidectomy with or without central neck dissection in a 3-year period in a single thyroid surgery unit were accessed to retrieve data on demographics, pathology, surgery, perioperative biochemistry and management. Of 295 included patients, there were 227 (76.9%) females. Forty-five (15.3%) had completion thyroidectomy, and the rest had total thyroidectomy. Seventy-eight (26.4%) had concomitant central neck dissection. Sixty-four (21.7%) had hypocalcaemia on the day after surgery. Hypoparathyroidism persisted in 10.5% of patients at 6 months. Both day 1 PTH and a drop in PTH predicted day 1 hypocalcaemia (p < 0.001) and 6-month hypoparathyroidism (p < 0.001). The area under the receiver operating characteristic (ROC) curves for day 1 PTH and drop in PTH for the prediction of day 1 hypocalcaemia (0.729 vs 0.726, respectively) and for 6-month hypoparathyroidism (0.964 vs 0.958, respectively) were similar, albeit slightly better for day 1 PTH. Day 1 PTH is equivalent to (if not better than) drop in PTH in predicting short- and long-term PoSH. Preoperative PTH measurements may not be needed in the detection and/or management of PoSH after thyroid surgery.

Long-term kidney outcomes in patients with permanent hypoparathyroidism after total thyroidectomy for benign disease: A population-based study

BackgroundPermanent hypoparathyroidism is a significant complication after total thyroidectomy. This study aimed to evaluate the long-term impact of postoperative permanent hypoparathyroidism on kidney outcomes. MethodsData of patients undergoing total thyroidectomy from 1999 to 2014 were retrieved. The estimated glomerular filtration rate was determined from serum creatinine results. Permanent hypoparathyroidism was defined as requiring oral calcium and vitamin D supplements postoperatively for at least 6 months. The primary outcome was a sustained decline in the estimated glomerular filtration rate from baseline by ≥50%. Secondary outcomes were end-stage kidney disease (a composite of sustained estimated glomerular filtration rate <15 mL/min/1.73 m2, need for dialysis, and kidney transplantation) and rate of estimated glomerular filtration rate decline. Patients with and without permanent hypoparathyroidism were compared. Multivariable Cox regression analysis was performed to identify independent risk factors for sustained estimated glomerular filtration rate decline by ≥50%. ResultsIn total, 3,245 patients were eligible for analysis; 418 patients (12.9%) had permanent hypoparathyroidism. Upon median follow-up of 11.6 years, more patients with permanent hypoparathyroidism had a sustained decline in estimated glomerular filtration rate from baseline by ≥50% compared to those without (15.6% vs 6.9%, P < .001). Similar findings were obtained on Kaplan–Meier analysis (P < .001). Permanent hypoparathyroidism was an independent risk factor for sustained estimated glomerular filtration rate decline by ≥50% (adjusted hazard ratio 2.77, P < .001). Other risk factors included age, preoperative estimated glomerular filtration rate <60 mL/min/1.73m2, and diabetes mellitus. Patients with permanent hypoparathyroidism had a more rapid estimated glomerular filtration rate decline (–1.60 vs –0.70 mL/min/1.73 m2/year, difference –0.91 mL/min/1.73m2/year, P < .001). ConclusionPatients with postsurgical permanent hypoparathyroidism were at greater risk of renal impairment. Further research is warranted to improve the identification and preservation of parathyroid glands during thyroidectomy to minimize patient morbidity.

Impaired Quality of Life in Patients with Post-Surgical Hypoparathyroidism.

Hypoparathyroidism is characterized by chronic hypocalcemia with low or abnormal parathyroid hormone levels. Thyroid surgery remains a predominant cause of hypoparathyroidism, often preventable by partial thyroidectomy. Although hypoparathyroidism can impair quality of life (QOL), data remain limited for Latin America. We aimed to characterize clinical manifestations and QOL in patients with postsurgical hypoparathyroidism. This case-control study included patients (&gt;18 years) who underwent total thyroidectomy (TT) for differentiated thyroid cancer (DTC) with postsurgical hypoparathyroidism (Group 1, Cases) and those with DTC who underwent TT without postsurgical hypoparathyroidism (Group 2, Controls). Clinical records were collected, and the SF-36v2 QOL survey and a structured symptom survey were applied. A logistic multivariate regression analysis was performed. This study included 106 subjects (Group 1, N=41; Group 2, N=65). Group 1 patients were younger, had a higher frequency of lymph node resection, and more frequently received Ι-131 than Group 2 patients (p&lt;0.05). In the SF-36v2 survey, Group 1 had fewer physical-functioning scores (odds ratio, 3.8; 95% confidence interval, 1.2-11.7) and lower scores in mental and physical components than Group 2 and national records. Commonly reported symptoms include paresthesia, daily fatigue, and memory alterations. Treatment adherence rates were 56% and 71% for calcium and calcitriol, respectively. Furthermore, 24% of patients experienced one or more hypoparathyroidism drug-related adverse effects. Patients with postsurgical hypoparathyroidism had an impaired QOL, a high frequency of disease-associated symptoms, and limited treatment adherence. These results should be considered when deciding the best surgical alternative for DTC.

Impact of autofluorescence-guided surgery of parathyroid glands during total thyroidectomy in experienced surgeons: A randomized clinical trial.

Post-surgical hypoparathyroidism often occurs after total thyroidectomy (TT). The aim of this study is to investigate whether the use of near-infrared autofluorescence (NIRAF) of parathyroid glands (PGs) can aid experienced surgeons in identifying more PGs during surgery, potentially reducing unintended resection, and assessing its impact on post-surgical hypoparathyroidism. All patients undergoing at least a TT by two experienced surgeons, between 2020 and 2021, were enrolled and randomized into two cohorts: NIRAF group (NG) and CONTROL group (CG). Transient hypoparathyroidism was defined by serum concentration of PTH<12ng/mL at the 1st post-operative day and permanent by the need of calcium-active vitamin D treatment >6months from the surgery with still undetectable PTH or <12ng/m. Among 236 patients (111 in NG, 125 in CG), the number of PGs identified was higher in NG (93.9%, 417/444) compared to CG (81.4%, 407/500) (p<0.001), with a mean of 3.76±0.44 PGs per patient in NG and 3.25±0.79 in CG. The number of unintendedly resected PGs was 14 in NG and 42 in CG (p<0.0001). Transient hypoparathyroidism was observed in 18 patients (16.2%) in NG and 40 patients (32.0%) in CG (p=0.004). Permanent hypoparathyroidism affected 1 patient in NG and 7 patients in CG (p=0.06). The mean operative time was longer in NG (104.3±32.08min) compared to CG (85.5±40.62min) (p<0.001). NIRAF enhances the identification of PGs, preventing their inadvertent resection and reducing the overall incidence of post-surgical hypoparathyroidism.

Hypoparathyroidism update.

Since the release of the 2022 Second International Workshop Evaluation and Management of Hypoparathyroidism Summary Statement and Guidelines, updates and advances are now available in the cause, complications, and treatment of adult chronic hypoparathyroidism (hypoPTH). This review aims to highlight these new findings and implications to patient care. Postsurgical hypoparathyroidism remains the most common cause, immune-related hypoparathyroidism from checkpoint inhibitors is an emerging autoimmune cause. In a large retrospective cohort study of thyroidectomies, incident fracture was lower, particularly in the vertebra, in the hypoPTH cohort, compared with postthyroidectomy control group. Hypercalciuria increases risk for renal calculi in hypoPTH independent of disease duration and treatment dose. Quality of life is impaired in hypoPTH patients on conventional therapy, improvement was noted post-PTH replacement. TranCon PTH phase 3 RCT reported eucalcemia with reduced renal calcium excretion, normalization of bone turn-over markers, stable BMD and improved quality of life. HypoPTH is a chronic disease associated with significant morbidity and poor Quality of Life. Awareness of treatment targets and follow-up investigations can alleviate patient anxiety regarding over-treatment and under-treatment. Progress in long-acting PTH replacement strategies might provide accessible, feasible alternatives to conventional therapy in brittle hypoPTH patients.

Early parathyroid hormone (PTH) level as a predictor of post-surgical hypoparathyroidism

Introduction Post-operative hypocalcemia and postoperative persistent hypoparathyroidism remain the most common complications after thyroidectomy. Many approaches have been developed to prevent them, but actually, a common protocol is not yet individuated. Materials and methods We retrospectively analyzed the results of a prospectively collected database. We dosed PTH preoperatively and 4 h after surgery (PTH_4); calcium was evaluated preoperatively, on the first (I_POD) and on the second postoperative day (II_POD). Hypocalcemia was defined when calcium <8 mg/dl. PTH_4 and I_POD calcium serum levels are identified to predict postoperative hypocalcemia. Results Three hundred and forty-eight patients were enrolled, 37 patients resulted as hypocalcemic on I_POD and 41 on the II_POD. PTH_4 is related to I_POD (p < 0.001, r = 0.45) and II_POD (p < 0.001, r = 0.44) calcemia. PTH_4-cut-off predicting I_POD hypocalcemia was 10.50 pg/ml (sensitivity: 78.7%, specificity: 72.7%). A PTH_4 value of 11.5 pg/ml is able to predict hypocalcemia during II_POD (sensitivity: 76.5%, specificity: 69.2%). We set up a combined test to predict II_POD hypocalcemia, using PTH_4 and I_POD calcium (sensitivity: 77.8%, specificity: 89.9%). Conclusion This research shows the association between PTH_4 and postoperative hypocalcemia. The PTH_4 cut-off to predict I_POD-hypocalcemia was 10.5 pg/ml. We analyzed the calcemia trend during the postoperative period and we realized a combined test using PTH_4 and I_POD-calcemia. This test improves the accuracy of the previous test. Further studies, in particular multicentric, with a larger sample are necessary to validate the combined model.

Green Tea Intake: A Protective Factor Against Postsurgical Hypothyroidism and Hypoparathyroidism

PurposeTea and coffee are the most common consumed types of drinks, identified with multiple health benefit. However, the association between tea and coffee intake and postsurgical hypothyroidism and hypoparathyroidism (PHypoTP) is still unclear. Therefore, the objective of this study is to explore the effect of tea and coffee intake on the risk of PHypoTP. DesignTwo-sample Mendelian randomization (MR). MethodsThe primary approach for MR estimates was the inverse-variance weighted (IVW) method. MR-Egger, MR Pleiotropy RESidual Sum and Outlier (PRESSO), weighted median, simple mode and weighted mode were used to detect pleiotropy and heterogeneity. FindingsWe found that green tea intake was causally associated with the decreased risk of PHypoTP (β = -0.019; 95% confidence interval [CI]: -0.038 to -0.001; P = 0.029). However, there was no significant association between coffee intake and risk of PHypoTP. No heterogeneity or pleiotropy in these results was detected. ConclusionsOur findings provide the genetic evidence supporting that green tea intake was a protective factor against PHypoTP. Accordingly, we may suggest the patients after thyroidectomy to add green tea into their habitual diet during nursing education.

Performance in Behavioral Testing in an Animal Model of Post-Surgical Hypoparathyroidism.

Hypoparathyroidism (HypoPT) is characterized by hypocalcemia and undetectable/inappropriately low PTH. Post-surgical HypoPT (PS-HypoPT) is the most common cause. Patients with PS-HypoPT present neuropsychological symptoms, probably due to the PTH deprivation in the central nervous system (CNS). However, these mechanisms are still not elucidated. The aim of this study was to evaluate the effects of PTH deprivation on CNS in an animal model of PS-HypoPT via a cognitive/behavioral assessment approach. A surgical rat model of PS-HypoPT was obtained and treated with calcium to maintain normocalcemia. Twenty PS-HypoPT rats and twenty sham-operated controls (Crl) underwent behavioral testing in a Morris Water Maze (MWM), Open Field (OF), and Elevated Plus Maze (EPM). In the MWM, PTx rats showed a higher Escape Latency Time compared to Crl rats (p < 0.05); we observed a statistically significant improvement in the performance (day 1 to 8 p < 0.001), which was less pronounced in PTx group. In the OF test, the time and distance spent in the zone of interest were significantly lower in the PTx group compared with the Crl (p < 0.01 and p < 0.01). In the EPM experiment, the time spent in the close arm was significantly higher in the PTx group compared with the Crl (p < 0.01). This animal model of PS-HypoPT shows an impairment in spatial memory, which improved after training, and a marked anxiety-like behavior, resembling the condition of patients with PS-HypoPT. Further studies are needed to elucidate mechanisms.

Restless leg syndrome as a complication of primary hyperparathyroidism: insights from a retrospective study.

Restless leg syndrome (RLS) is an invalidating neurological disorder with a complex, largely unknown pathophysiology. While RLS is observed in Parkinson's disease and in renal failure, idiopathic cases are common. Limited reports associate RLS with parathyroid hormone (PTH). This study analyzes a cohort of patients with primary hyperparathyroidism (PHPT) and chronic post-surgical hypoparathyroidism (hypo PTH), to investigate RLS prevalence, and associated risk factors. Ninety-five patients (54 PHPT, 41 hypo PTH) were consecutively enrolled at the bone metabolism outpatient clinic. The revised IRLSSG diagnostic criteria were used to diagnose RLS, with assessments conducted through face-to-face interviews and neurological examination. When RLS was confirmed, the RLS severity scale was applied. Retrospective records included calcium-phosphate metabolism-related parameters, surgery details, renal lithiasis, fragility fractures, and densitometric features (T-score). RLS was diagnosed in 22.2% PHPT patients, compared to 4.9% of patients with hypo PTH (p = 0.02). Of RLS diagnosed patients, 91.7% had a history of parathyroidectomy, compared to 47.6% of patients without RLS (p = 0.01). Most of the operated patients reported that surgery determined an improvement of symptoms; however, mean score severity of RLS at our evaluation was 15/40, defined as moderate. PTH and calcium levels were not statistically associated to the presence of RLS. Our study suggests that PHPT may be one of the etiologies of RLS. Parathyroidectomy alleviates symptoms in the vast majority of the cases but does not remove them.

Incidence of post-surgical hypoparathyroidism (POSH) after total thyroidectomy

Post-surgical hypoparathyroidism (POSH) is a recognised complication of total thyroidectomy, leading to hypocalcaemia and its associated adverse effects. This retrospective study aimed to determine the incidence of POSH and identify perioperative predictors for its development. Data from patients who underwent total or completion thyroidectomy between January 2017 and July 2022 were retrospectively analysed. The incidence of POSH was assessed, and patients were categorised into transient or prolonged POSH at six months postoperatively. Potential predictors for POSH were investigated including gender, histological diagnosis, and preoperative thyroid function. A total of 133 adult patients were included in the study. The incidence of patients recovering from transient POSH within six months was 15%, and 5% had prolonged POSH beyond six months of surgery. Parathyroid hormone (PTH) levels normalised in 83% of prolonged POSH patients within 14–33 months, reducing the incidence of persistent POSH to 0.75%. Despite normal PTH levels, overall, 3% had persistent marginally low calcium levels (mean 2.11 mmol/L) in keeping with relative parathyroid insufficiency. Histological diagnosis of malignancy was the only significant risk factor for both transient and prolonged POSH (RR 2.95, CI 1.54 to 5.67, p = 0.001) in this cohort. Cautious capsular dissection during thyroidectomy and protection of the parathyroid glands and vascular supply produce a low incidence of POSH. Although the vast majority of patients with POSH recover after six months, hypocalcaemia may persist due to relative parathyroid insufficiency, requiring long-term calcium supplementation. Further research is needed to determine the best strategies for preventing and treating this condition.

SAT233 Clinical And Economic Burden Of Postsurgical Chronic Hypoparathyroidism: A US Medicare Retrospective Analysis

Abstract Disclosure: W. Noori: Employee; Self; Ascendis Pharma, Inc. S. Inguva: Employee; Self; OPEN Health. Other; Self; Research Funding (institution): Ascendis. C.T. Sibley: Employee; Self; Ascendis Pharma, Inc. V. Chirikov: Employee; Self; OPEN Health. Stock Owner; Self; OPEN Health. Other; Self; Research Funding (institution): Ascendis. A.R. Smith: Employee; Self; Ascendis Pharma, Inc. Background: Hypoparathyroidism is a rare endocrine disease characterized by insufficient parathyroid hormone (PTH) production and is associated with substantial burden of illness. Individuals with hypoparathyroidism often report physical, emotional, and cognitive symptoms indicating impaired health-related quality of life (HRQoL). Objective: To describe demographics, clinical characteristics, healthcare resource utilization (HCRU), and costs among individuals with postsurgical chronic hypoparathyroidism compared to individuals without hypoparathyroidism in Medicare Fee-For-Service (FFS). Methods: Adults with newly diagnosed postsurgical chronic hypoparathyroidism were identified from the Medicare 100% Limited Data Set between July 1, 2017, to March 31, 2020. All had a confirmed diagnosis within 6-12 months after index diagnosis. Individuals were required to be continuously enrolled for ≥6 months pre- and ≥12 months post-index for baseline and follow-up assessments. Those with a prior hypoparathyroidism diagnosis in the baseline period were excluded. A random sample of enrollees without hypoparathyroidism was synthetically assigned an index date of diagnosis to ensure similar baseline and follow-up periods as individuals with postsurgical chronic hypoparathyroidism. Baseline demographics and comorbidities were compared descriptively. All-cause HCRU and costs during baseline and follow-up were evaluated. All costs were inflated to 2021 US dollars. Results: Individuals with postsurgical chronic hypoparathyroidism (N=1,166) were older than those without hypoparathyroidism (N=11,258) (median age of 69 vs 64 years) and more were female (76% vs 57%); they also had higher Charlson Comorbidity Index scores at baseline (3.24 vs 0.73) and a higher prevalence of moderate or severe renal disease (28.8% vs 5.6%), nephrolithiasis (8.3% vs 1.0%), urinary tract infections (9.9% vs 2.2%), hospitalizations for infections (11.9% vs 2.5%), congestive heart failure (13.1% vs 3.0%), among others. Over a median follow-up of 30 months, mean [SD] all-cause medical costs per patient per year (PPPY) were significantly higher among individuals with postsurgical chronic hypoparathyroidism ($199,297 [$443,294] vs $61,897 [$210,825]). This difference was largely attributable to higher all-cause medical utilization among individuals with postsurgical chronic hypoparathyroidism (22.0 vs 11.6 inpatient days PPPY; 15.3 vs 5.8 outpatient visits PPPY). Individuals with postsurgical chronic hypoparathyroidism also had higher mortality compared to those without hypoparathyroidism (HR=2.75 (95% CI: 2.15-3.51). Conclusions: The clinical and economic burden of individuals with postsurgical chronic hypoparathyroidism in Medicare FFS is substantial, highlighting the need for innovative treatment options to replace the missing PTH hormone. Presentation: Saturday, June 17, 2023

SAT218 Refractory Hypocalcemia From Combined Autosomal Dominant Hypocalcemia Type 2 And Postsurgical Hypoparathyroidism

Abstract Disclosure: M. Sonmez Ince: None. F. Hannan: None. N. Esfandiari: None. M. Hussain: None. M.R. Haymart: None. R.V. Thakker: None. G.A. Clines: None. Background: Autosomal dominant hypocalcemia type 2 (ADH2), due to activating mutations in GNA11, is a rare disorder that causes hypocalcemia with low or inappropriately normal PTH. Postsurgical hypoparathyroidism (PSHP) is the most common etiology for hypoparathyroidism. The patient described was afflicted by both conditions and had persistent hypocalcemia despite aggressive management. Clinical Case: A 50-year-old female was found to have an enlarged thyroid on exam and subsequently diagnosed with papillary thyroid cancer (PTC). She underwent a total thyroidectomy without parathyroid autotransplantation since parathyroid glands were not identified during intraoperative pathologic survey. Surgical pathologic examination confirmed PTC with the identification of a single and small intrathyroidal parathyroid gland. Due to the patient’s low risk (T1N0M0), radioactive iodine ablation was not performed. Before thyroidectomy, serum corrected calcium was 6.4-8.5 mg/dL (8.6-10.3 mg/dL) and PTH was 9-21 pg/mL (10-65 pg/mL) during the previous 20 years. Following thyroidectomy, the patient had multiple emergency department visits due to hypocalcemia, hand cramping, and paresthesias. The patient was diagnosed with postsurgical hypoparathyroidism: corrected calcium 5.6-6.7 mg/dL, 24-hour urine calcium 112 mg (100-300 mg/24hour), magnesium 1.4-1.9 mg/dL (1.6-2.6 mg/dL), phosphorus 3-8.2 mg/dL (2.7-4.6 mg/dL). PTH remained &amp;lt;6 pg/mL. The patient was then referred to an academic endocrinology. TSH, AM cortisol, 25-vitamin D, iron, ceruloplasmin, copper, and 21-hydroxylase antibody concentrations were normal. Genetic testing revealed a pathogenic GNA11 variant (c.178C&amp;gt;T, p.(Arg60Cys)); no mutations were identified with CASR or AP2S1. Despite aggressive management with total daily oral calcitriol up to 12 mcg daily, calcium 8 grams, and chlorthalidone, the patient required calcium infusions thrice weekly. Despite the addition of teriparatide 20 mcg BID, the patient remained dependent on calcium infusions, with improvement after the addition of IV calcitriol. Recently, continuous teriparatide delivery was started using an Omnipod insulin pump that has significantly reduced the patient’s dependence on calcium infusions with serum calcium that are now 8-9 mg/dL. Conclusion: ADH2, due to gain-of-function mutations of GNA11, that encodes the Gα11 protein, causes life-long hypocalcemia that is often asymptomatic and undiagnosed. We report here the first documented case of combined ADH2 and PSHP. This case highlights that patients with ADH2 likely have hypoplastic parathyroid glands and that caution is required with procedures that may disrupt parathyroid gland function. Furthermore, the refractory nature of this patient’s hypocalcemia may suggest that GNA11 mutations in the kidney and skeleton reduce the effectiveness of standard hypocalcemia treatments. Presentation: Saturday, June 17, 2023

Chronic hypoparathyroidism is associated with increased cortical bone density evaluated using high-resolution peripheral quantitative computed tomography.

This cross-sectional study aimed to assess bone mineral density (BMD), bone microarchitecture and fracture prevalence in women with chronic postsurgical hypoparathyroidism (hypoPT). Twenty-seven women with postsurgical hypoPT and 44 age-matched healthy women were included. Dual-energy X-ray absorptiometry was used to evaluate areal BMD and vertebral fracture assessment. High-resolution peripheral quantitative computed tomography assessed microarchitecture and volumetric BMD at the distal radius and tibia. Biochemical parameters, including fibroblast growth factor 23, C-terminal cross-linking telopeptide of type I collagen (ICTP), and procollagen type I N-terminal propeptide (P1NP), were also measured. Previous low-impact fractures were assessed and the 10-year fracture risk was estimated using the FRAX tool for the Brazilian population. No participant had prevalent clinical fractures, and both groups showed low risk for major and hip based on FRAX tool, but two hypoPT patients had moderate to severe morphometric vertebral fractures. Women with hypoPT had increased aBMD in the lumbar spine, femoral neck and total hip (p < 0.05) and higher cortical vBMD in the radius (p = 0.020) and tibia (p < 0.001). Trabecular bone was not affected. Both P1NP and ICTP suggested low bone turnover rates, but no significant correlation was observed between bone density or microstructure and any of the biochemical parameters. The prevalence of fragility fractures was low in HypoPT women and compatible with low fracture risk estimated by the FRAX tool. Patients had a higher aBMD and cortical vBMD than those of healthy control women, but the association with decreased bone turnover remains unclear.