Endocrine manifestations in adults with 22q11.2 deletion syndrome: a retrospective single-center cohort study.

INTRODUCTION AND OBJECTIVE: Patients with the 22q11.2 deletion syndrome (22q11DS) frequently display cardiological and psychiatric diseases, but are also at increased risk for endocrine manifestations. The aim of this study was to evaluate the screening, prevalence, and management of hypoparathyroidism and thyroid disease in patients with 22q11DS, to evaluate the metabolic profile, and to compare these results with current literature and guidelines. DESIGN: We performed a retrospective study of patients with genetically confirmed 22q11DS, followed at the center for human genetics of the University Hospitals Leuven, resulting in a cohort of 75 patients. Medical history, medication, and laboratory results concerning hypoparathyroidism, thyroid dysfunction, and the metabolic profile were collected. RESULTS: Of the total cohort, 26 patients (35%) had at least one hypocalcaemic episode. During hypocalcaemia, parathyroid hormone (PTH) was measured in only 12 patients with 11 having normal or low PTH, confirming a diagnosis of hypoparathyroidism. Recurrent episodes of hypocalcaemia occurred in seventeen patients (23%). Adherence to the guidelines was low, with 13% of patients having a yearly serum calcium evaluation, 12% receiving daily calcium supplements, and 20% receiving non-active vitamin D. Hypothyroidism was present in 31 patients (44%) and hyperthyroidism in 6 patients (8%). Information on body mass index (BMI) was available in 52 patients (69%), of which 38% were obese (BMI ≥ 30 kg/m2). CONCLUSION: Hypoparathyroidism, hypothyroidism, and obesity are common endocrine manifestations in patients with 22q11DS but are probably underdiagnosed and undertreated, indicating the need for multidisciplinary follow-up including an endocrinologist.

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.

Incidence and risk factors of hypoparathyroidism and hypocalcemia after hemithyroidectomy.

PURPOSE: The incidence and risk factors for hypoparathyroidism after total thyroidectomy is well-known. However, the characteristics of hypoparathyroidism and hypocalcemia after hemithyroidectomy have not been investigated well. In this study, we aimed to evaluate the incidence, characteristics, and risk factors of hypoparathyroidism and hypocalcemia after hemithyroidectomy. METHOD: We retrospectively analyzed the medical data of 321 patients who underwent hemithyroidectomy, with or without central neck dissection, from January 2012 to April 2019. We analyzed the serum intact parathyroid hormone (iPTH), calcium, and ionized calcium (iCa) levels serially (preoperatively and postoperatively on the operation day; days 1 and 3; and months 1, 3, 6, and 12) and evaluated risk factors for postoperative hypoparathyroidism and hypocalcemia. RESULTS: The mean iPTH and calcium levels decreased significantly after hemithyroidectomy on the operation day and postoperative days 1 and 3, and returned to the preoperative level at the postoperative 1-month follow-up. The mean iCa level decreased significantly on the operation day and postoperative day 1. Transient hypoparathyroidism and transient hypocalcemia occurred in 16 (5%) and 250 (78%) participants, and they recovered to normal levels postoperatively by 1 month. Eight (2.5%) patients had mild symptoms of hypocalcemia necessitating oral calcium supplementation. No permanent hypoparathyroidism or hypocalcemia was observed. Preoperatively low serum iPTH and calcium levels were associated with transient hypoparathyroidism and hypocalcemia after hemithyroidectomy. CONCLUSION: Approximately 5% and 2.5% of participants showed transient hypoparathyroidism and mild symptomatic hypocalcemia after hemithyroidectomy. The risk factors for transient hypoparathyroidism and hypocalcemia include preoperative low serum iPTH and calcium levels.

Hypoparathyroidism-related health care utilization and expenditure during the first postoperative year after total thyroidectomy for cancer: a comprehensive national cohort study.

Objectives: Hypoparathyroidism is the most common complication of total thyroidectomy for cancer, and requires calcium and/or vitamin D supplementation for an unpredictable period of time. The additional cost associated with this complication has not hitherto been assessed. The aim of this study was to assess the economic burden of postoperative hypoparathyroidism after total thyroidectomy for cancer in France. Methods: Based on the French national cancer cohort, which extracts data from the French National Health Data System (SNDS), all adult patients who underwent a total thyroidectomy for cancer in France between 2011 and 2015 were identified, and their healthcare resource use during the first postoperative year was compared according to whether they were treated postoperatively with calcium and/or vitamin D or not. Univariate and multivariate cost analyses were performed with the non-parametric Wilcoxon test and generalized linear model (gamma distribution and log link), respectively. Results: Among the 31,175 patients analyzed (75% female, median age: 52y), 13,247 (42%) started calcium and/or vitamin D supplementation within the first postoperative month, and 2,855 patients (9.1%) were still treated at 1 year. Over the first postoperative year, mean overall and specific health expenditures were significantly higher for treated patients than for untreated patients: €7,233 vs €6,934 per patient (p<0.0001) and €478.6 vs €332.7 per patient (p<0.0001), respectively. After adjusting for age, gender, Charlson Comorbidity index, ecological deprivation index, types of thyroid resection, lymph node dissection and complications, year and region, the incremental cost of overall health care utilization was €142 (p<0.004). Conclusion: Our study found a significant additional cost in respect of health expenditures for patients who had hypoparathyroidism after thyroidectomy for cancer, over the first postoperative year. Five-year follow-up is planned to assess the impact of more severe long-term complications on costs.

Risk of Fractures in Thyroid Cancer Patients With Postoperative Hypoparathyroidism: A Nationwide Cohort Study in Korea.

Postoperative hypoparathyroidism (PO-hypoPT) is an uncommon complication of total thyroidectomy in thyroid cancer patients. Although long-term hypoPT causes characteristic changes in bone metabolism, the risk of fractures in hypoPT remains inconclusive. We investigated the risk of fractures in Korean thyroid cancer patients with PO-hypoPT. This was a retrospective cohort study using data from the Korea Central Cancer Registry and Korean National Health Insurance Service. We analyzed 115,821 thyroid cancer patients aged ≥18 years, who underwent total thyroidectomy between 2008 and 2016. The risk of any fractures, including vertebral, hip, humerus, and wrist fractures, according to parathyroid function after total thyroidectomy, was analyzed using the multivariable Cox proportional hazard model. The PO-hypoPT and preserved parathyroid function groups included 8789 (7.6%) and 107,032 (92.4%) patients, respectively. Over a mean follow-up duration of 4.8 years, 159 (1.8%) and 2390 (2.2%) fractures occurred in the PO-hypoPT and preserved parathyroid function groups, respectively. The risk of any fractures was significantly lower in the PO-hypoPT group than in the preserved parathyroid function group (hazard ratio [HR] = 0.83; 95% confidence interval [CI] 0.70-0.98; p = 0.037) after adjusting for confounders. Regarding the fracture site, only the risk of vertebral fractures was significantly lower in the PO-hypoPT group compared with the preserved parathyroid function group (HR = 0.67; 95% CI 0.47-0.96; p = 0.028) after adjusting for confounders. Subgroup analyses showed that bone mineral density measurements and calcium supplementation interacted with the relationship between PO-hypoPT and the risk of any fractures (p for interactions = 0.010 and 0.017, respectively). PO-hypoPT was associated with a lower risk of fractures in thyroid cancer patients, especially at the vertebra. The relatively low bone turnover caused by PO-hypoPT and appropriate management for PO-hypoPT with active vitamin D and calcium may prevent the deterioration of skeletal health in thyroid cancer patients who can easily be exposed to long-term overtreatment with levothyroxine. © 2023 American Society for Bone and Mineral Research (ASBMR).

Postoperative Hypocalcemia in Hyperthyroid Patients: The Parathyroids Aren't Always to Blame.

INTRODUCTION: Hypocalcemia is commonly reported after thyroidectomy and has multiple possible etiologies including: parathyroid devascularization, reactive hypoparathyroidism from relative hypercalcemia in thyrotoxicosis, and abrupt reversal of thyrotoxic osteodystrophy. In patients that are actively hyperthyroid and undergoing thyroidectomy, it is not known how many experience hypocalcemia from nonhypoparathyroidism etiologies. Therefore, our aim was to examine the relationship among thyrotoxicosis, hypocalcemia, and hypoparathyroidism. METHODS: A retrospective review was performed of prospectively-collected data from all patients undergoing thyroidectomy for hyperthyroidism by 4 surgeons from 2016 to 2020. All patients carried a diagnosis of Graves' disease or toxic multinodular goiter. Patient demographics, preoperative medications, laboratory reports, and postoperative medications were reviewed. Hypocalcemia within the first month of surgery despite a normal parathyroid hormone (PTH) level was the primary outcome of interest and was compared between patients with and without thyrotoxicosis. Secondary outcomes were duration of postoperative calcium use and the relationship between preoperative calcium supplementation and postoperative calcium supplementation. Descriptive statistics, Wilcoxon rank-sum, and chi-square tests were used for bivariate analysis, as appropriate. RESULTS: A total of 191 patients were identified, with mean age of 40.5 y (range 6-86). Most patients were female (80%) and had Graves' disease (80%). At the time of surgery, 116 (61%) had uncontrolled hyperthyroidism (thyrotoxic group, Free Thyroxine >1.64 ng/dL or Free Triiodothyronine > 4.4 ng/dL), with the remaining 75 (39%) considered euthyroid. Postoperative hypocalcemia (calcium < 8.4 mg/dL) developed in 27 (14%), while hypoparathyroidism (PTH < 12 pg/mL) was observed in 39 (26%). Thyrotoxic patients comprised a majority of those with hypocalcemia (n = 22, 81%, P = 0.01) and hypoparathyroidism immediately following surgery (n = 14, 77%, P = 0.04). However, a majority of initially hypocalcemic, thyrotoxic patients had normal PTH values within the first month after surgery (n = 17, 85%), pointing to a potential nonparathyroid etiology. On bivariate analysis, no significant relationship was found for thyrotoxic patients with initial postoperative hypocalcemia (18%) and hypoparathyroidism <1-month after surgery (29%, P = 0.29) or between 1 and 6 mo after surgery (2%, P = 0.24). Of the 19 patients in the nonhypoparathyroidism group, 17 (89%) were off all calcium supplements by 6 mo postop. CONCLUSIONS: In patients with hyperthyroidism, those in active thyrotoxicosis at time of surgery have a higher rate of postoperative hypocalcemia compared to euthyroid patients. When hypocalcemia lasts >1 mo postoperatively, data from this study suggest that hypoparathyroidism may not be the primary etiology in many of these patients, who typically require calcium supplementation no more than 6 mo postoperatively.

Kidney Complications and Hospitalization in Patients With Chronic Hypoparathyroidism: A Cohort Study in Sweden.

CONTEXT: Kidney complications may be considerably higher in patients with chronic hypoparathyroidism (hypoPT) treated with activated vitamin D and calcium supplementation. OBJECTIVE: We aimed to investigate the risk of chronic kidney disease (CKD), urolithiasis, and hospitalization in patients with chronic hypoPT. METHODS: In this population-based cohort study in Sweden, national registries (Swedish National Patient Register, Swedish Prescribed Drug Register, and Total Population Register, 1997-2018) were used to identify patients with chronic hypoPT and controls matched by sex, age, and county of residence. We determined time to CKD and urolithiasis diagnosis, and incidence rates of hospitalization. RESULTS: A total of 1562 patients with chronic hypoPT without preexisting CKD and 15 620 controls were included. The risk of developing CKD was higher in patients with chronic hypoPT compared with controls (hazard ratio [HR] 4.45; 95% CI, 3.66-5.41). In people without prior urolithiasis (n = 1810 chronic hypoPT and n = 18 100 controls), the risk of developing urolithiasis was higher in patients with chronic hypoPT (HR 3.55; 95% CI, 2.84-4.44) compared with controls. Patients with chronic hypoPT had higher incidence rates for all-cause hospitalization (49.59; 95% CI, 48.50-50.70, per 100 person-years vs 28.43; 95% CI, 28.15-28.71, respectively) and for CKD (3.46; 95% CI, 3.18-3.76, per 100 person-years vs 0.72; 95% CI, 0.68-0.77, respectively), compared with controls. Men with hypoPT appear to have a higher risk of CKD than women. CONCLUSION: Patients with chronic hypoPT had an increased risk of CKD, urolithiasis, and hospitalization compared with controls.

Does Time Matter in Deficit of Calcium after Total Thyroidectomy in Subjects with Previous Bariatric Surgery?

Background: Hypoparathyroidism-related hypocalcemia is a common complication after total thyroidectomy (TT), particularly if there is a history of prior bariatric surgery. However, it is still unknown if it is the surgery timing or the type of bariatric intervention that increases the risk of developing this complication. Methods: We compared the risk of hypocalcemia (serum calcium levels < 8 mg/dL) and hypoparathyroidism (both transient and permanent) between patients with restrictive procedures (LSG and GB) and patients without a history of obesity surgery in the immediate post-operative period and after 12 months. Hypoparathyroidism was considered permanent if the plasma parathyroid hormone (PTH) levels at 6 months were less than 15 pg/mL and the patient still required oral calcium (calcium carbonate) and vitamin D supplementation, in addition to the supplements that were taken routinely before thyroidectomy. Results: From the 96 patients who underwent TT, 50% had a history of bariatric surgery: 36 LSG and 12 GB. The risk of hypocalcemia was similar in patients with a history of restrictive procedures (31.35%) and in controls (25%) (p = 0.49). Furthermore, hypocalcemia risk was similar between patients with a history of LSG (30.5%) and GB (33%) (p = 0.85). The prevalences of transient and permanent hypoparathyroidism were similar between patients with a history of restrictive procedures and in controls; similarly, no differences were detected between subjects undergoing LSG and GB. Conclusions: Restrictive bariatric surgery (LSG and GB) is not a risk factor for post-thyroidectomy hypocalcemia and hypoparathyroidism and thus did not require a different perioperative supplementation protocol compared to subjects without history of bariatric surgery undergoing TT.

Hyperphosphatemia is associated with cardiac valve calcification in chronic hypoparathyroidism.

PURPOSE: To evaluate the association between metabolic abnormalities and cardiovascular risk factors in patients with chronic hypoparathyroidism (HPP). PATIENTS AND METHODS: Patients 18 years and older, glomerular filtration > 30 mL/min/1.73 m2 and no documented coronary artery disease were selected. Serum calcium, phosphorus, glucose, lipids, PTH, 25(OH)D and FGF23 were measured. Cardiovascular risk was estimated by the European Society of Cardiology (ESC) calculator. Transthoracic echocardiogram and carotid ultrasound were performed to detect carotid plaques (CP), carotid intima-media thickness (IMT), cardiac valve calcification (CVC), and left ventricular hypertrophy (LVH). RESULTS: Thirty-seven patients (94.6% female), aged 56.0 ± 13.5 years and HPP duration 7.0 (4.0; 11.3) years, were included. Fifteen were classified as low cardiovascular risk, 9 as intermediate risk, 9 as high risk and none as very high risk. The prevalence of CP, CVC and LVH was 24.3%, 24.3% and 13.5%, respectively. IMT values were within normal ranges in all cohort. FGF23 were not associated with CP, IMT, CVC or LVH. After logistic regression, phosphorus was the only significant metabolic variable impacting CVC in univariate analysis (OR 2.795; 95% CI 1.132-6.905; p = 0.026), as well as in the multivariate analysis (OR 3.572; 95% CI 1.094-11.665; p = 0.035). Analysis by ROC curve showed serum phosphorus > 5.05 mg/dL (AUC 0.748; CI 0.584-0.877; p = 0.05) as the best cutoff point associated with valve heart calcification (sensitivity 78%; negative predictive value 91.3%). CONCLUSION: Hyperphosphatemia was associated with CVC in HPP patients. Further studies are needed to investigate whether the control of hyperphosphatemia may reduce cardiovascular risk in this population.

The Russian Registry of Chronic Hypoparathyroidism.

INTRODUCTION: Chronic hypoparathyroidism is a relatively rare disease associated with multicomponent medical therapy and various complications. The analysis of large databases of patients with chronic hypoparathyroidism is a necessary tool to enhance quality of medical care, as well as to determine the optimal clinical and therapeutic approaches, and prognostic markers of the disease. THE AIM: of this study is to estimate the clinical and biochemical profile, long-term complications, medical therapy and disease control of the patients with chronic postsurgical and non-surgical hypoparathyroidism. MATERIALS AND METHODS: the cross-sectional, observational, continuous study was based on the Russian Registry of patients with hypoparathyroidism. 544 patients from 63 regions of the Russian Federation were included in this study. RESULTS: The majority of cases had postsurgical etiology (88.4%). Postsurgical hypoparathyroidism prevailed in females (р<0.001). About a half of patients had blood calcium and phosphorus targets, 56 and 52% respectively. Nephrolithiasis was confirmed in 32.5%, nephrocalcinosis - in 12.3% of cases. The risk of nephrocalcinosis/nephrolithiasis increased by 1.85 times with disease duration more than 4.5 years. The cataract was found in 9.4%. The cut-off point for the development of cataracts was 9.5 years, with a 6.96-fold increased risk. The longer duration of hypoparathyroidism of any etiology was associated with more frequent cataract (p=0.0018).We found brain calcification in 4%, arrhythmias in 7.2% and neuropsychiatric symptoms in 5.15% of cases. Generally, the BMD in the studied group corresponded to age values, and there was no evidence for the phenomenon of high bone density. TBS was consistent with normal bone microarchitectonics. In our study, the majority of patients (83.5%) was treated with standard therapy of calcium and vitamin D supplements. 5 patients with severe disease course were treated with rhPTH (1-34). CONCLUSIONS: Analysis of the presented database indicates insufficient diagnosis of the complications associated with chronic hypoparathyroidism. Overall, hypoparathyroidism is associated with higher risks of renal stone formation, decreased GFR, cataract especially in patients with longer duration of disease.

Hypoparathyroidism after thyroidectomy: A 20-year experience at a children's hospital.

INTRODUCTION: Hypoparathyroidism (HP) is the most common complication of total thyroidectomy and can be an emergency. OBJECTIVES: To describe the prevalence of HP after total thyroidectomy in children under 14 years of age, the variables related to its appearance and its clinical expression. PATIENTS AND METHODS: Retrospective study at a children's hospital in the last 20 years. HP was defined by the need to supplement calcium after the intervention and was considered permanent if it could not be suspended within 12 months. Fisher's statistical method of comparison of proportions. RESULTS: Thirty-nine children and adolescents (26 females) with an age range of 3.67-14.00 years. In 25 patients, the intervention was prophylactic and in 14 it was therapeutic; 14 suffered accidental excision of some parathyroid gland, but none more than two of them; 12 presented HP, of which 3 were permanent; 5 presented clinical symptoms; 1 of them was an emergency. The frequency of HP was 4/4 when 2 parathyroids were dissected, 2/10 when one was dissected, and 6/25 when none were dissected (p = 0.02). In the prophylactic interventions, it was 6/25 compared to 6/14 in the therapeutic ones (p = 0.29). The three cases of permanent HP were in children under 6 years of age, and it did not occur in any older children (p = 0.09). CONCLUSIONS: HP is a common and sometimes serious complication in children after total thyroidectomy. It can occur, and even be permanent, even if the intervention is prophylactic and parathyroid glands remain in situ. Younger age could be a risk factor.

Outcome of parathyroid function after total thyroidectomy when calcium supplementation is administered routinely versus exclusively to symptomatic patients: A prospective randomized clinical trial.

PURPOSE: Current guidelines for calcium supplementation for parathyroid function recovery after thyroidectomy are based on low-quality evidence. The present trial compared the effects of oral calcium and vitamin D supplementation on the recovery of parathyroid function when administered routinely or exclusively to symptomatic patients. METHODS: This prospective, randomized, open-label clinical trial analyzed 203 patients who underwent total thyroidectomy and developed hypoparathyroidism on postoperative day 1 (POD1) with median age of 41 years and proportion of women of 77.8%. Participants were randomized to group A (calcium and vitamin D supplementation administered only to symptomatic patients) and group B (routine supplementation). The primary outcome was the incidence of protracted hypoparathyroidism in the two groups. Secondary outcomes included risk factors for postoperative protracted hypoparathyroidism and the incidence of symptomatic hypocalcemia. RESULTS: The incidence of protracted hypoparathyroidism was not significantly different between group A and group B (11 of 99 vs. 17 of 104, P = 0.280). Parathyroid hormone (PTH) in group B exhibited a better recovery tendency. The incidence of postoperative symptomatic hypocalcemia in group B was significantly lower than group A (26.92% vs. 42.42%, P = 0.020). Independent factors predicting protracted hypoparathyroidism included sex, preoperative serum calcium, and POD1 PTH. CONCLUSION: Calcium and vitamin D supplementation administered exclusively to symptomatic patients achieved the same effect on protracted hypoparathyroidism as routine supplementation. However, routine supplementation significantly reduced postoperative hypocalcemia. Extra attention is necessary in female patients with high preoperative serum calcium and patients with low POD1 PTH. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR), ChiCTR1900022194. Registered March 30, 2019.

Persistent Postthyroidectomy Hypoparathyroidism in the Netherlands.

Importance: Hypoparathyroidism is one of the most common complications after total or completion thyroidectomy. The reported incidence rate of hypoparathyroidism in the literature is highly variable. Data that provide a better understanding of the magnitude of this postoperative complication are warranted and can provide a stepping stone for further collaborations that aim to reduce complication rates and establish uniform treatment protocols. Objective: To evaluate the incidence of postoperative, persistent hypoparathyroidism after total or completion thyroidectomy in patients who were referred to university hospital centers and assess the association of different definitions with the incidence of hypoparathyroidism. Design, Setting, and Participants: This retrospective multicenter cohort study conducted throughout 2016 in 7 Dutch university hospital centers included 200 patients who were undergoing a total or completion thyroidectomy. Data analysis was conducted in January 2021. Main Outcomes and Measures: We report on the incidence of persistent hypoparathyroidism, defined as the need for active vitamin D with or without calcium supplementation longer than 1 year after surgery. Results: A total of 200 patients (143 women [71.5%]; mean [IQR] age, 49.0 [37.0-62.0] years) were included and 30 patients (15.0%) developed persistent hypoparathyroidism. The incidence of persistent hypoparathyroidism varied between 14.5% (calcium and active vitamin D 1 year postsurgery) to 28.5% (calcium and/or active vitamin D 6 months postsurgery) depending on the definition used. Conclusions and Relevance: In this cohort study, the risk of persistent hypoparathyroidism after total or completion thyroidectomy was 15% in patients who were referred to university hospital centers. The high rate of persistent hypoparathyroidism warrants efforts to reduce this complication rate. There is discrepancy in the definition and treatment of persistent hypoparathyroidism, and use of uniform evidence-based treatment guidelines enables comparison of interventions.

Risk of Chronic Kidney Disease and Estimated Glomerular Filtration Rate Decline in Patients with Chronic Hypoparathyroidism: A Retrospective Cohort Study.

INTRODUCTION: Chronic hypoparathyroidism, treated with conventional therapy of oral calcium supplements and active vitamin D, may increase the risk of kidney complications. This study examined risks of development and progression of chronic kidney disease (CKD) and estimated glomerular filtration rate (eGFR) decline in patients with chronic hypoparathyroidism. METHODS: A retrospective cohort study using a managed care claims database in the United States from January 2007 to June 2017 included patients with chronic hypoparathyroidism (excluding those receiving parathyroid hormone) and randomly selected patients without hypoparathyroidism followed for up to 5 years. Main outcome measures were (1) development of CKD, defined as new diagnosis of CKD stage 3 and higher or ≥ 2 eGFR measurements < 60 ml/min/1.73 m2 ≥ 3 months apart, (2) progression of CKD, defined as increase in baseline CKD stage, (3) progression to end-stage kidney disease (ESKD), and (4) eGFR decline ≥ 30% from baseline. Time-to-event analyses included Kaplan-Meier analyses with log-rank tests, and both unadjusted and adjusted Cox proportional hazards models were used to compare outcomes between cohorts. RESULTS: The study included 8097 adults with and 40,485 without chronic hypoparathyroidism. In Kaplan-Meier analyses, patients with chronic hypoparathyroidism had higher risk of developing CKD and CKD progression and higher rates of eGFR decline (all P < 0.001). In multivariable Cox models adjusted for baseline characteristics, hazard ratios (95% confidence intervals [CIs]) were 2.91 (2.61-3.25) for developing CKD, 1.58 (1.23-2.01) for CKD stage progression, 2.14 (1.51-3.04) for progression to ESKD, and 2.56 (1.62-4.03) for eGFR decline (all P < 0.001) among patients with chronic hypoparathyroidism compared with those without hypoparathyroidism. CONCLUSION: Patients with chronic hypoparathyroidism have increased risk of development and progression of CKD and eGFR decline compared with those without hypoparathyroidism. Further studies are warranted to understand underlying mechanisms for the associations between chronic hypoparathyroidism and kidney disease.

What are the real rates of temporary hypoparathyroidism following thyroidectomy? It is a matter of definition: a systematic review.

INTRODUCTION: Post-operative hypoparathyroidism is the most encountered complication of thyroid surgery and is classified as temporary or permanent. However, its incidence varies greatly in the literature ranging from 0.5% to 65%. This can be mainly attributed to the different definition of hypoparathyroidism used in each study and especially to the different time cutoff applied to distinguish temporary from permanent hypoparathyroidism. METHODS: We conducted a systematic literature search in PubMed, Scopus, Cochrane and GoogleScholar databases, as well as grey literature. Ultimately, 45 articles with 23,164 patients in total were included in this review. These articles used either the cutoff of six or twelve post-operative months to distinguish temporary from permanent hypoparathyroidism. RESULTS: The overall incidence of permanent hypoparathyroidism diagnosed at 6 months post-operatively was 4.11% and 4.08% at 12 months post-operatively. There was no statistically significant difference between the two groups (p = 0.92). CONCLUSIONS: We suggest that adhering to the current guidelines that recommend diagnosing temporary hypoparathyroidism when recovery is made within 6 months after surgery is important when conducting future research in order to narrow the gap that exists currently in the literature, as well as when deciding to put patients on long-term calcium supplements.

[Modern problems of hyper- and hypoparathyroidism].

The parathyroid glands are the most important regulators of mineral metabolism. The parathyroid glands were first discovered only in 1880 and their function went the long way unrecognized. Even the term "parathyroid gland" itself speaks of the initial misconception of it as an underdeveloped part of the thyroid. To date, there is a large amount of data regarding the role of this endocrine gland in the human body and the significant changes associated with their dysfunction, including such widespread diseases such primary, secondary and tertiary hyperparathyroidism, hypoparathyroidism. This review covers the problem of the main disturbances in calcium-phosphorus metabolism, presents the results of databases of patients with primary hyperparathyroidism and hypoparathyroidism, as well as current epidemiological trends in Russia and in the world.

Trends in Pediatric Thyroid Cancer Incidence, Treatment, and Clinical Course in Korea During 2004-2016: A Nationwide Population-Based Study.

Background: The incidence of thyroid cancer has increased worldwide. We investigated nationwide trends in the incidence and treatment course of pediatric thyroid cancer in South Korea. Methods: Using the National Health Information Database, we analyzed 1580 patients (324 males) <20 years of age diagnosed with thyroid cancer during 2004-2016 in South Korea. The annual percentage change (APC) in the age-standardized incidence rate (ASR) was calculated by joinpoint regression analysis. The initial treatment modality was categorized as either surgery only or surgery with radioactive-iodine treatment (surgery+RAIT), and we defined new treatment events as reoperations or additional RAITs among 1464 patients followed up for ≥12 months. Results: During 2004-2016, the mean ASR per 100,000 person-years increased from 0.6 [confidence interval; CI 0.5-0.8] to 0.9 [CI 0.8-1.1], with a mean APC of 4.0% [CI 1.8-6.2]. The ASRs (APCs) among 0-9-, 10-14-, 15-17-, and 18-19-year olds were 0.07 (9.9% [CI 0.08-20.7]), 0.6 (4.6% [CI 0.2-9.2]), 2.2 (3.9 [CI 1.7-6.0]), and 4.2 (3.5% [CI 0.9-6.2]), respectively. The lobectomy and lymph-node-dissection rates increased (from 18.5% to 33.6%, p = 0.0014; and from 29.6% to 84.5%, p < 0.001; respectively), but the RAIT rate decreased (67.9-39.7%, p < 0.001) during the study period. During a median 6.3-year follow-up, two patients died. New treatment events occurred in 56 (10.7%) of patients in the initial surgery-only group (n = 523). In the initial surgery+RAIT group (n = 941), 316 patients received two or more RAITs within 2 years, and 80 (12.8%) of the remaining 625 patients underwent new treatment events. In the surgery+RAIT subgroup, the event-free survival rate was lower in 0-14-year olds than in 18-19-year olds (hazard ratio 2.5 [CI 1.4-4.4]). Conclusions: The pediatric thyroid cancer incidence increased from 2004 to 2012 in South Korea. The lobectomy and lymph-node-dissection rates increased, but the RAIT rate decreased. The higher risk for new treatment events in patients younger than 15 years requiring initial RAIT may be linked to advanced stage at diagnosis, and it needs to be further evaluated.

What is the experience of our patients with transient hypoparathyroidism after total thyroidectomy?

BACKGROUND: We sought to better understand the experience of patients with transient hypoparathyroidism using patient interviews and quality of life surveys. METHODS: This is a prospective analysis of 62 patients after total thyroidectomy at a high-volume institution. Semistructured patient interviews and quality of life surveys were conducted preoperatively and postoperatively at 2 weeks, 6 weeks, 6 months, and 1 year and compared based on postoperative parathyroid hormone levels. RESULTS: Postoperative parathyroid hormone levels were <10 pg/mL in 32% of patients (n = 20), 10 to 20 pg/mL in 19% (n = 12), and >20 pg/mL in 48% (n = 30). Hypocalcemic symptoms at 2 weeks were reported in 28 of 55 patients (51%), but patients felt "well prepared" and reported it "wasn't a big deal." If symptoms persisted at 6 weeks, they became more bothersome. At 6 months and 1 year, patients reported calcium supplementation prevented most symptoms and did not interfere with daily activities. Quality of life as measured by the European Organization for Research and Treatment of Cancer and the 12-Item Short Form Survey demonstrated a slight improvement at 1 year postoperatively regardless of parathyroid hormone level. CONCLUSION: Early postoperative transient hypoparathyroidism is common but when appropriately managed did not have a substantial negative impact on the overall quality of life.

The predictive factors for postoperative hypoparathyroidism and its severity on the first postoperative day after papillary thyroid carcinoma surgery.

PURPOSE: The purpose of the study was to investigate the predictive factors for hypoparathyroidism and its severity on the first postoperative day (POD1) after total thyroidectomy (TT) with or without central neck dissection (CND) in patients with papillary thyroid carcinoma (PTC). METHODS: From February 2014 to February 2019, 2550 PTC patients were admitted to our department. PTC patients who underwent TT were enrolled in this study. A parathyroid hormone (PTH) level lower than 15 pg/mL on POD1 was defined as hypoparathyroidism, and the severity of hypoparathyroidism was classified into three categories according to the level of PTH on POD1: mild hypoparathyroidism (10 pg/mL ≤ PTH < 15 pg/mL), moderate hypoparathyroidism (5 g/mL ≤ PTH < 10 pg/mL), and severe hypoparathyroidism (PTH < 5 pg/mL). Multiple clinical, pathological and surgical parameters of these two different groups were compared and analyzed to demonstrate the possible causes of hypoparathyroidism. Furthermore, patients who developed postoperative hypoparathyroidism were also included in a subgroup analysis according to the severity of their hypoparathyroidism. The underlying factors affecting different severities of hypoparathyroidism were also illustrated with univariate and multivariate analyses. RESULTS: Ultimately, 690 patients who underwent TT were enrolled in this retrospective study. Through the univariate analysis, different surgeons (P < 0.001), extent of CND (P = 0.009), prophylactic calcium supplementation (PCS) (P < 0.001), preoperative (pre-op) PTH level (P < 0.001), and pre-op phosphorus concentration (P = 0.022) were found to be significantly correlated with postoperative hypoparathyroidism. According to the multivariate analysis, PCS was the only independent high-risk factor for hypoparathyroidism. In the univariate analysis of patient subgroups with different severities of hypoparathyroidism, we demonstrated that the tumor T stage (P = 0.021) and pre-op PTH level (P < 0.001) were associated with the severity of hypoparathyroidism. Furthermore, after the multivariate analysis, hypertension (P < 0.001) and pre-op PTH (P < 0.001) were the two independent predictive factors for the severity of hypoparathyroidism after surgery. CONCLUSIONS: Postoperative PCS could increase the risk for PTC patients developing hypoparathyroidism after thyroid surgery. Patients with a history of hypertension and a relatively high pre-op PTH level may not develop severe hypoparathyroidism after TT with CND.

Postoperative Hypoparathyroidism After Total Thyroidectomy in Children.

BACKGROUND: Postoperative hypocalcemia because of hypoparathyroidism is the most common complication of total thyroidectomy in children. We hypothesized that most children with postoperative hypocalcemia would be eucalcemic by 12 mo and sought to define risk factors for permanent hypoparathyroidism. METHODS: We retrospectively reviewed children who underwent total thyroidectomy at a single children's hospital from 2012 to 2019. Patients with prior neck surgery were excluded. Indication for operation, final pathologic diagnosis, and postoperative serum calcium up to 12 mo were recorded. Permanent hypoparathyroidism was defined as supplemental calcium requirement beyond 1 y postoperatively. RESULTS: Sixty-eight patients underwent total thyroidectomy. Graves' disease was the most common benign indication for surgery (38 patients). Twenty-six patients (38%) had cancer on final pathology. Central lymph node dissection (CLND) was performed in 12 cancer patients. Twenty-eight patients (41%) had postoperative hypocalcemia. Eight patients (12%) had hypocalcemia at 6 mo. Risk factors for hypoparathyroidism at 6 mo were a cancer diagnosis (odds ratio [OR] 6.7; P = 0.02), CLND (OR 12.6; P < 0.01), and parathyroid tissue in the surgical specimen on pathologic analysis (OR 19.5; P < 0.01). Only two patients (3%) developed permanent hypoparathyroidism, both of whom had thyroidectomy for cancer and underwent CLND. CONCLUSIONS: Children with thyroid cancer are at high risk for postoperative hypocalcemia after total thyroidectomy. The risk is further increased by CLND, which should be performed selectively. A majority of patients with hypoparathyroidism at 6 mo postoperatively regain normal parathyroid function by 1 y. Permanent hypoparathyroidism in children after total thyroidectomy at a pediatric endocrine surgery center is rare.