Bone Analysis Using Trabecular Bone Score and Dual-Energy X-Ray Absorptiometry-Based 3-Dimensional Modeling in Postmenopausal Women With Primary Hyperparathyroidism

ObjectivePredominance of bone loss in cortical sites with relative preservation of trabecular bone, even in postmenopausal women, has been described in primary hyperparathyroidism (PHPT). The aim of this study was to evaluate bone microarchitectural differences using dual-energy x-ray absorptiometry (DXA), trabecular bone score (TBS), and DXA-based 3-dimensional (3D) modeling (3D-DXA) between postmenopausal women diagnosed with PHPT (PM-PHPT) and healthy postmenopausal controls.MethodsThis retrospective study included 44 women with PM-PHPT (9 of whom had fractures) and 48 healthy women matched by age, body mass index, and years since menopause treated at Hospital Universitario Fundación Jiménez Díaz between 2008 and 2017. The bone mineral density (BMD) of the lumbar spine (LS), femoral neck, total hip (TH), and 1/3 radius was assessed using DXA, and trabecular volumetric BMD (vBMD), cortical vBMD, integral vBMD, cortical thickness, and cortical surface BMD at TH were assessed using a 3D-DXA software and TBS at LS.ResultsThe mean adjusted BMD values at LS, the femoral neck, and TH; TBS at LS; and TH 3D-DXA parameters (trabecular vBMD, integral vBMD, cortical thickness, and cortical surface BMD) were significantly reduced in women with PM-PHPT compared with those in the controls. However, differences in mean cortical vBMD were not statistically significant (P = .078). There were no significant differences in mean BMD, TBS, or the 3D-DXA parameters between patients with fractures and those without fractures. The 25-hydroxyvitamin D level appeared to be associated with TBS but not with DXA and 3D-DXA measurements.ConclusionPM-PHPT has significant involvement of the trabecular and cortical compartments of the bone, as determined by DXA, TBS, and 3D-DXA.     

Differences in Primary Hyperparathyroidism Between Pre- and Postmenopausal Women in India

ObjectivePrimary hyperparathyroidism (PHPT) is a common endocrine disorder in women which becomes more prevalent after menopause. In this study, we compared the demographic, clinical, and biochemical variables between premenopausal (pre-M) and postmenopausal (post-M) women with PHPT.MethodsA retrospective analysis (from 2005 to 2019) of enrolled women PHPT patients from an online Indian PHPT registry.ResultsOf the women with PHPT, 232 and 122 were pre-M and post-M, respectively. The number of post-M PHPT cases registered had a 3.3-fold increase in 2015-2019 from 2005-2009 compared with only a 2.5-fold increase in pre-M cases in the same duration. The majority were symptomatic (90%), although pre-M had a higher proportion of symptomatic than post-M (92% vs 85%; P = .04). Pre-M women showed more prevalence of osteitis fibrosa cystica than post-M women (28% vs 13%; P = .03), although hypertension and gallstone disease were seen more frequently in post-M PHPT women. Pre-M women had a significantly higher median PTH (403 vs 246 pg/mL; P = .02) and median alkaline phosphatase (202 vs 145 pg/mL; P = .02) than post-M women, and vitamin D deficiency was more common in pre-M women (58% vs 45%; P = .03). Gland localization, tumor weight, and disease cure rates did not differ according to menopausal status.ConclusionPHPT was more prevalent in pre-M women, although the number of post-M cases had significantly increased in the last 10 years. Pre-M women had generally more severe clinical and biochemical variables than post-M PHPT women.     

Echocardiographic Findings in Patients With Normocalcemic Primary Hyperparathyroidism Compared With Findings in Hypercalcemic Primary Hyperparathyroid Patients and Control Subjects

ObjectiveThere are no data regarding echocardiographic parameters in patients with normocalcemic primary hyperparathyroidism (NCPHPT). We compared the echocardiographic findings in postmenopausal women with NCPHPT with those in patients with hypercalcemic primary hyperparathyroidism (PHPT) and controls.MethodsSeventeen consecutive Caucasian postmenopausal women with NCPHPT were compared with 20 women with hypercalcemic PHPT and 20 controls. Obesity, diabetes, kidney failure, and previous cardiovascular diseases were considered exclusion criteria. Each patient underwent biochemical evaluation, bone mineral density scan, and echocardiographic measurements. Patients with parathyroid disorders underwent kidney ultrasound evaluation.ResultsPatients with PHPT had significantly higher mean total serum calcium, ionized calcium, 24-hour urinary calcium, and parathyroid hormone and lower mean phosphorus levels compared with those in the controls (all P < .05). The only differences between patients with NCPHPT and PHPT were significantly lower mean total serum calcium, ionized calcium, and 24-hour urinary calcium and higher phosphorus levels in patients with NCPHPT (all P < .05). The only biochemical difference between patients with NCPHPT and the controls was a higher level of mean parathyroid hormone in patients with NCPHPT. There were no differences in cardiovascular risk factors between patients with NCPHPT and PHPT and the controls. Hypertension was the most frequent cardiovascular risk factor, diagnosed in 65% of patients with PHPT. This high prevalence was not statistically significant compared with that observed in patients with NCPHPT (59%) and in the controls (30%). Echocardiography parameters were not different between patients with NCPHPT and PHPT and the controls when subdivided according to the presence of hypertension (ANOVA followed by Bonferroni correction).ConclusionIn a population with a low cardiovascular risk, we found no differences in cardiovascular risk factors and echocardiographic parameters between patients with NCPHPT and PHPT and the controls.     

Aldosterone Secretion in Patients With Primary Hyperparathyroidism Without Arterial Hypertension

ObjectiveThere is a direct bidirectional link between parathyroid hormone (PTH) and the renin-angiotensin-aldosterone system (RAAS), but few studies evaluated the RAAS in patients with primary hyperparathyroidism (PHPT), mainly biased from concomitant antihypertensive treatment.MethodsWe retrospectively evaluated a consecutive series of 130 normotensive patients with PHPT comparing aldosterone (ALD) levels and plasma renin activity (PRA) with the demographic, biochemical, or clinical features of PHPT.ResultsNo correlation was found between ALD and PRA, and the demographic, biochemical, and bone densitometry parameters in patients with PHPT without hypertension, with the exception of a negative correlation between age and serum PRA. Moreover, there was no significant correlation between PTH and ALD levels even in patients whose PTH level was >100 ng/L (P = .088).ConclusionIn our normotensive patients with PHPT, the ALD, PRA, and aldosterone/renin ratio were not correlated to PTH and calcium levels. In addition, they were neither related to PHPT clinical presentation nor renal function, vitamin D status, bone mass loss, or the presence of comorbidities such as diabetes and obesity. Further studies are needed to clarify the complex interplay between PTH and the RAAS in the modern PHPT presentation.     

Association of Parathyroidectomy With 5-Year Clinically Significant Kidney Stone Events in Patients With Primary Hyperparathyroidism

ObjectivePatients with primary hyperparathyroidism (PHPT) are at increased risk of kidney stones. Guidelines recommend parathyroidectomy in patients with PHPT with a history of stone disease. This study aimed to compare the 5-year incidence of clinically significant kidney stone events in patients with PHPT treated with parathyroidectomy versus nonoperative management.MethodsWe performed a longitudinal cohort study of patients with PHPT in a national commercial insurance claims database (2006-2019). Propensity score inverse probability weighting-adjusted multivariable regression models were calculated.ResultsWe identified 7623 patients aged ≥35 years old with continuous enrollment >1 year before and >5 years after PHPT diagnosis. A total of 2933 patients (38.5%) were treated with parathyroidectomy. The cohort had a mean age of 66.5 years, 5953 (78.1%) were female, and 5520 (72.4%) were White. Over 5 years, the unadjusted incidence of ≥1 kidney stone event was higher in patients who were managed with parathyroidectomy compared with those who were managed nonoperatively overall (5.4% vs 4.1%, respectively) and among those with a history of kidney stones at PHPT diagnosis (17.9% vs 16.4%, respectively). On multivariable analysis, parathyroidectomy was associated with no statistically significant difference in the odds of a 5-year kidney stone event among patients with a history of kidney stones (odds ratio, 1.03; 95% CI, 0.71-1.50) or those without a history of kidney stones (odds ratio, 1.16; 95% CI, 0.84-1.60).ConclusionBased on this claim analysis, there was no difference in the odds of 5-year kidney stone events in patients with PHPT who were treated with parathyroidectomy versus nonoperative management. Time horizon for benefit should be considered when making treatment decisions for PHPT based on the risk of kidney stone events.     

The Role of Surgeon-Performed Office and Preincision Ultrasounds in Localization of Parathyroid Adenomas in Primary Hyperparathyroidism

ObjectiveWe studied the use of surgeon-performed office ultrasound (OU) and preincision ultrasound (PIU) in preoperatively localizing parathyroid adenomas in primary hyperparathyroidism (PHPT).MethodsA retrospective chart review was performed for patients with PHPT who underwent parathyroidectomy between 2013 and 2015. The results of OU and PIU were recorded and compared with the final surgical pathology.ResultsOf 348 patients with PHPT, 285 (81.9%) had single-lesion disease, 49 (14.1%) had double-lesion disease, and 14 (4.0%) had multigland disease with 3 or more lesions. For single-lesion disease, the overall sensitivity and specificity of OU to correctly lateralize the lesion were 64.2% and 91.2%, while those of PIU were 89.4% and 93.6%, respectively. The sensitivity and specificity of PIU were comparable to those of 4-dimensional computed tomography (87.1% and 90.7%, respectively) and ^99mTc-sestamibi scintigraphy (70.4% and 95.9%, respectively). While the majority of PIU cases were preceded by other imaging studies, the accuracy in localizing lesions was not largely affected by the presence of prior computed tomography and/or ^99mTc-sestamibi scintigraphy, as opposed to ultrasounds only. For detecting the presence of multigland disease, the sensitivity and specificity of OU were 26% and 92.2%, while those of PIU were 64.3% and 94.7%, respectively.ConclusionSurgeon-performed OU and PIU are valuable tools in preoperatively localizing the parathyroid adenoma in single-lesion disease, while their utility may be limited for double-lesion or multigland disease. PIU in particular yields high accuracy in detecting parathyroid lesions in combination with other imaging modalities.     

Comparison of Profile of Primary Hyperparathyroidism With and Without Type 2 Diabetes Mellitus: Retrospective Analysis From the Indian Primary Hyperparathyroidism Registry

ObjectiveTo describe the prevalence and compare the clinicobiochemical profile of patients with primary hyperparathyroidism (PHPT) with and without type 2 diabetes mellitus (T2DM).MethodsWe conducted a retrospective observational study wherein the details of patients with PHPT with T2DM (PHPT-T2DM) and without T2DM were retrieved from the Indian PHPT Registry (www.indianphptregistry.com) between 2005 and 2019. We compared the clinical, biochemical, and postoperative findings of patients with PHPT-T2DM with age-, sex-, and body mass index–matched patients with PHPT without T2DM (in 1:2 ratio).ResultsOf the 464 patients with PHPT, 54 (11.6%) had T2DM. We observed an increase in the prevalence of PHPT-T2DM cases over time; only 7 (7.1%) of the total patients with PHPT had T2DM between 2005 and 2009 that increased to 31 (12.8%) in the last half decade (2015-2019). Patients with PHPT-T2DM had a significantly lower prevalence of nephrolithiasis (18.5% vs 36.1%, respectively; P = .03) and a higher prevalence of pancreatitis (22.2% vs 5.6%, respectively; P = .007) than those without T2DM. Furthermore, intact parathyroid hormone (203 pg/mL [139.8-437.3 pg/mL] vs 285 pg/mL [166-692 pg/mL], respectively; P = .04) and serum creatinine (0.90 mg/dL [0.67-1.25 mg/dL] vs 1.10 mg/dL [0.73-1.68 mg/dL], respectively; P = .03) levels were significantly lower in patients with PHPT-T2DM than those without T2DM. Also, tumor weight tended to be lower in patients with PHPT-T2DM than in the non-T2DM counterparts (1.05 g [0.5-2.93 g] vs 2.16 g [0.81-7.0 g], respectively; P = .06).ConclusionThe prevalence of T2DM in Asian Indians with PHPT is 11.6%. Patients with PHPT-T2DM are characterized by a higher prevalence of pancreatitis, a lower prevalence of nephrolithiasis, and lower levels of intact parathyroid hormone/creatinine. Part of the clinical picture can possibly be explained by early detection of PHPT in patients with T2DM consequent to more frequent screening.     

A Retrospective Study of Ultrasonography in the Investigation of Primary Hyperparathyroidism: A New Perspective for Ultrasound Echogenicity Features of Parathyroid Nodules

ObjectiveTo identify and understand parathyroid lesions of patients with primary hyperparathyroidism (PHPT) more accurately under ultrasound.MethodsThis retrospective study involved 423 adult patients with PHPT with a single parathyroid nodule and positive parathyroid ultrasonography between 2018 and 2019. The clinical characteristics of the study patients and histopathologic sections were reviewed.ResultsAccording to the main grayscale echogenicity features of parathyroid nodules, 423 cases were divided into groups: iso-hyperechogenicity solid (61/423), hypoechogenicity solid (304/423), and mixed-echogenicity cyst-solid (58/423) groups. Comparison among the 3 groups showed that the iso-hyperechogenicity group included more asymptomatic patients with PHPT and fewer patients with severe symptoms like bone fractures (P < .05). The mixed-echogenicity group showed higher median serum parathyroid hormone (PTH) and serum calcium levels and larger lesion sizes (P < .05), and the iso-hyperechogenicity group showed the lowest median serum PTH level. No difference in lesion size was noted between the 2 solid groups, but the median serum PTH level in the hypoechogenicity group was higher than that in the iso-hyperechogenicity group (P < .05). According to histopathology, the hypoechogenic area of the samples may contain more functional components (chief cells), whereas the iso-hyperechogenic area has more nonfunctional components (eg, lipocytes and connective tissues).ConclusionThe PHPT nodules distinguished by ultrasound echogenicity features showed different histopathologic components, reflected by different clinical characteristics of the patients with PHPT.     

A Comparison of Bone Mineral Density and Its Predictors in HIV-Infected and HIV-Uninfected Older Men

ObjectiveBone health in older individuals with HIV infection has not been well studied. This study aimed to compare bone mineral density (BMD), trabecular bone score (TBS), and bone markers between HIV-infected men and age- and body mass index (BMI)-matched HIV-uninfected men aged ≥60 years. We investigated the associations of risk factors related to fracture with BMD, TBS, and bone markers in HIV-infected men.MethodsThis cross-sectional study included 45 HIV-infected men receiving antiretroviral therapy and 42 HIV-uninfected men. Medical history, BMD and TBS measurements, and laboratory tests related to bone health were assessed in all the participants. HIV-related factors known to be associated with bone loss were assessed in the HIV-infected men.ResultsThe mean BMD, TBS, and osteopenia or osteoporosis prevalence were similar among the cases and controls. The HIV-infected men had significantly higher mean N-terminal propeptide of type 1 procollagen and C-terminal cross-linking telopeptide of type I collagen levels. Stepwise multiple linear regression analysis demonstrated that low BMI (lumbar spine, P = .015; femoral neck, P = .018; and total hip, P = .005), high C-terminal cross-linking telopeptide of type I collagen concentration (total hip, P = .042; and TBS, P = .010), and low vitamin D supplementation (TBS, P = .035) were independently associated with low BMD and TBS.ConclusionIn older HIV-infected men with a low fracture risk, the mean BMD and TBS were similar to those of the age- and BMI-matched controls. The mean bone marker levels were higher in the HIV group. Traditional risk factors for fracture, including low BMI, high C-terminal cross-linking telopeptide of type I collagen level, and low vitamin D supplementation, were significant predictors of low BMD and TBS.     

Cystic Parathyroid Adenomas: An Enigmatic Entity and Role of Tc-99 m Sestamibi Scintigraphy

ObjectiveFunctional cystic lesion of the parathyroid gland is a rare cause of primary hyperparathyroidism (PHPT). They have been postulated to arise from the hemorrhage and cystic degeneration in the parathyroid adenoma (PA). We intended to analyze their scintigraphic and histopathological findings since available literature is sparse.MethodsDual-phase ^{99 m}Tc-sestamibi planar and SPECT/CT scans performed from January 2014 to January 2020 in patients presenting with PHPT were retrospectively analyzed. The clinical, biochemical, and ultrasound features were collected. Planar and SPECT/CT imaging parameters were analyzed. Detailed histopathological analysis, along with post-surgical clinical and biochemical features of the patients who underwent surgery, was reviewed with a mean follow-up of 21.8 ± 20.1 months.ResultsOf the 979 scans analyzed, 10 showed cystic parathyroid lesions (M:F- 3:7, mean age 45.6 ± 15 years, range: 23-66). The predominant presenting features in patients were abdominal pain and renal stone disease, present in 60% of the patients. On planar scintigraphy, 90% of the patients had tracer avid distinct lesions, whereas tracer activity was seen in the solid part of the cystic lesions in all 10 patients on SPECT/CT, with cystic areas showing an attenuation of 23.1 ± 7.6 HU. Eight of these patients underwent surgery, with all showing PA with cystic changes on histopathology. Two of these patients also showed hemorrhage within the cystic spaces.ConclusionHemorrhage within a PA may give rise to cystic parathyroid lesions with PHPT. ^{99 m}Tc-sestamibi scintigraphy with dual-phase imaging and SPECT/CT may help in detecting this rare entity.     

Effect of Bisphosphonates on Fracture Incidence in Young Adults With Low Bone Density

ObjectiveTo assess the effect of bisphosphonates on fracture incidence in young adults over a 5-year follow-up period.MethodsBased on the Kaiser Permanente electronic health record, this retrospective study investigated patients aged 19 to 40 years with abnormal bone density (either any Z-score of ≤−2 standard deviation [SD] or any T-score of ≤−2.5 SD). The incidence and time to fracture between the control (patients with <6 months of bisphosphonate exposure) and treatment (patients with ≥6 months of bisphosphonate use within 4 years of their first dual energy x-ray absorptiometry scan) groups were compared. Comparisons were analyzed with Χ² test for categorical variables and Wilcoxon rank sum test for continuous variables.ResultsA total of 422 patients met the inclusion and exclusion criteria. Fractures occurred in 18 patients (5.0%) of the control group (n = 358) and 5 patients (7.8%) of the treatment group (n = 64; P = .37). T-scores were significantly lower in the treatment group (−2.53 ± 0.58 SD) than those in the control group (−2.30 ± 0.80 SD; P = .002) but did not correlate with fracture risk. No significant differences were found in total fracture incidence (hazard ratio = 1.54; 95% confidence interval, 0.26-6.26). Similarly, no correlation was noted between the length of bisphosphonate therapy and fracture incidence (odds ratio = 0.99; 95% confidence interval, 0.966-1.026).ConclusionIn summary, we did not find a clear correlation of fracture incidence with the use of bisphosphonates in young adults. Further research into the pathophysiology, specific etiologies, and treatment options in this population is needed.     

Quality of Life in Patients With Asymptomatic Primary Hyperparathyroidism After Parathyroidectomy: A 3-Year Longitudinal Study

ObjectiveImpaired quality of life (QoL) is considered as a nonclassical manifestation of primary hyperparathyroidism (PHPT). This study aimed to detect and compare changes in the QoL of patients with asymptomatic PHPT who had successful curative parathyroidectomy (PTX) 3 months and 3 years after the procedure.MethodsPatients with diagnosed PHPT were eligible for the study. There were 2 groups: the PTX group, with patients who underwent PTX, and the non-PTX group, with patients who were treated conservatively. QoL was assessed using Pasieka’s Parathyroid Assessment of Symptoms Questionnaire (PAS-Q) at baseline, 3 months, and 3 years.ResultsThirty-eight patients were included in the study: 18 in the PTX group and 20 in the non-PTX group. In the PTX group, the mean PAS-Q total score before PTX was 518, which was reduced significantly at the 3-month (P = .003) and 3-year assessments (P = .001). However, in the non-PTX group, the mean PAS-Q total score was 326 at baseline and increased continuously for 3 years (P = .019). At the 3-year evaluation, the mean total score was significantly higher compared to that of the PTX group (P = .021). Finally, there was a positive correlation between total serum calcium and PAS-Q score in the non-PTX group (r = 0.524, P = .018).ConclusionQoL of patients with PHPT improved significantly compared to that in conservative surveillance as early as 3 months after successful, curative PTX, and remained improved for 3 years. This finding strengthens, even more, the hypothesis that PTX contributes to better QoL, suggesting that the derangement of QoL may be considered as an individual indication for surgery.     

The Added Value of Second-Look Ultrasound in Patients With Primary Hyperparathyroidism With Discordant or Negative Previous Imaging Findings

ObjectiveThe preoperative localization for patients with primary hyperparathyroidism with negative or discordant previous imaging results has always been a difficult problem to be solved in clinical practice. Second-look ultrasound (US) is a viable but underestimated method. This study aimed to assess the added value of second-look US and explore the attributing factors.MethodsAmong 711 surgically confirmed patients with primary hyperparathyroidism, 63 patients with negative or discordant first-time US and ^99mTc-MIBI imaging results were retrospectively studied. All 63 patients underwent second-look US, and the results were compared with intraoperative findings and histopathologic diagnosis. The diagnostic value of second-look US was calculated, and the reasons for changed second-look US results were analyzed.ResultsSixty-three parathyroid lesions were found in 63 patients. The sensitivity, positive predictive value, and accuracy of second-look US were 92.1%, 95.1%, and 88.1%, respectively. Comparing the results of first-time and second-look US, we found that 54.0% of the patients got benefits from second-look US because 34 patients with negative results in the first-time US revealed localization with second-look US. Second-look US was more likely to produce changes in results for lesions with a lower location (OR, 3.23; 95% CI, 1.11-9.43, P < .05) and larger length-to-thickness ratio (3.0 vs 2.4, P < .05).ConclusionSecond-look US is a promising method to determine preoperative localization in patients with negative or discordant results of previous imaging findings. Lesions with elongated shape and lower location are more expected to be detected in second-look US when missed at the first time.     

The Risk Factors for Developing Clustered Vertebral Compression Fractures: A Single-Center Study

ObjectiveVertebral compression fractures (VCFs) are common among elderly individuals, but clustered VCFs (C-VCFs) are rare and more severe. The risk factors for C-VCFs remain unclear. Thus, we investigated the clinical characteristics of C-VCFs to identify the imminent fracture risk and improve the treatment for such patients.MethodsWe reviewed the records of patients with VCF at a single medical center between January 2011 and September 2020. Patients who had 4 or more VCFs within 1 year were categorized into the C-VCF group, and the remaining patients were paired into the control group at a ratio of 2:1. We collected demographic, clinical, laboratory, and radiologic information regarding these patients. Univariate analyses, stratified analyses, and multivariate logistic regression were performed to identify the risk factors for C-VCFs.ResultsA total of 156 patients were enrolled, of whom 52 were patients with C-VCF. Patients with C-VCF had more severe fractures and pain, with fractures occurring at uncommon sites of the spine. The independent risk factors for C-VCFs included glucocorticoid (GC) treatment (P < .001; hazard ratio [HR], 12.7), recent fracture history (P = .021; HR, 5.5), and lower trabecular bone score (TBS) (P = .044; HR, 1.6). TBS and bone mineral density had greater predictive values in patients without GC treatment (P < .001). Sex, age, and bone turnover biomarkers were not independent risk factors for C-VCFs.ConclusionC-VCFs are rare adverse consequences of severe osteoporosis, for which GC treatment, recent fracture history, and lower TBS are unique risk factors that are valuable for the early identification and prevention of C-VCFs.     

Increased Bone Mineral Density in Male Patients With Idiopathic Hypogonadotropic Hypogonadism Who Undergo Sex Hormone Therapy: Findings From Cross-Sectional and Longitudinal Studies

ObjectiveThis retrospective observational study assessed the long-term impact of pulsatile gonadotropin-releasing hormone, combined gonadotropin, or testosterone replacement therapy on total hip, femoral, and lumbar bone mineral density (BMD) and Z-scores in adult men with idiopathic hypogonadotropic hypogonadism (IHH).MethodsIn the cross-sectional study, 69 patients were allocated to untreated (n = 42) and treated (n = 27) groups. The untreated group included IHH patients without hormone therapy history, while the treated group included age- and body mass index-matched patients who had received hormone therapy for at least 5 years. The longitudinal study included 53 IHH patients, and their hip and lumbar BMDs were measured several times during hormone therapy. We then evaluated the changes in their BMD.ResultsOur cross-sectional study showed that the treated group had a significantly higher BMD and Z-score for total hip, femoral neck, and lumbar spine (P < 0.001 for all) than the untreated group, and the average bone mass even reached the age-matched normal range. The prevalence of low BMD was 80.95% and 11.11% in untreated and treated groups, respectively. In the longitudinal study (N = 53), the total hip, femoral neck, and lumbar spine BMD gradually increased during treatment. The lumbar spine showed a greater increment in BMD compared with the total hip and femoral neck (P < 0.05).ConclusionSex hormone therapy improved hip and lumbar spine BMD and Z-scores in patients with IHH. The lumbar spine showed a greater improvement in BMD compared with the total hip and femoral neck.     

Effects of Thyroid Dysfunction and the Thyroid-Stimulating Hormone Levels on the Risk of Atrial Fibrillation: A Systematic Review and Dose-Response Meta-Analysis from Cohort Studies

ObjectiveTo explore the relationship between thyroid dysfunction, thyroid-stimulating hormone (TSH) levels, and risks of atrial fibrillation (AF) in studies and conduct a dose-response meta-analysis on the correlation between the TSH levels and risk of AF.MethodsThirteen studies from 5 databases with 649 293 subjects (mean age, 65.1 years) were included. The dose-response meta-analysis was conducted by comparing the risk ratios (RRs) and 95% confidence intervals (CIs) for incident AF associated with different levels of TSH (vs TSH level of 0 mU/L) across studies. Data were collected until October 25, 2021.ResultsSubclinical hyperthyroidism, subclinical hypothyroidism, and clinical hyperthyroidism were associated with an increased risk of AF (RR, 1.70; 95% CI, 1.11-2.62; RR, 1.23; 95% CI, 1.05-1.44; and RR, 2.35; 95% CI, 1.07-5.16, respectively), whereas clinical hypothyroidism was not associated with the significantly increased risk of AF (RR, 1.20; 95% CI, 0.72-1.99). A nonlinear relationship was observed in 2 models (crude model, P_nonlinear < .001; adjusted model, P_nonlinear = .0391) between the TSH levels and risks of AF.ConclusionsOur study indicated that subclinical hyperthyroidism, subclinical hypothyroidism, clinical hyperthyroidism were associated with the risk of AF, and the results for the TSH levels and risk of AF were mixed, which showed a U-shaped relationship.     

Calcium Challenge to Confirm Secondary Hyperparathyroidism Caused by Decreased Calcium Intake

ObjectiveSecondary hyperparathyroidism commonly occurs in the setting of mid-to low-normal serum calcium levels, often in the setting of chronic kidney disease, phosphate loading, vitamin D deficiency, or insufficient calcium intake or absorption. In this article, we report 9 patients who had adequate kidney function (estimated glomerular filtration rate >60 mL/min/1.73 m²) and normal 25-hydroxy vitamin D level (≥30 ng/dL) and whose secondary hyperparathyroidism resolved after starting adequate oral calcium intake.MethodsOur retrospective case series included 8 women and 1 man; the mean age was 69.0 ± 12.2 years (mean ± standard deviation). The initial intact parathyroid hormone (iPTH) level was 80.6 ± 13.4 pg/mL (reference range [ref], 10-65 pg/mL), corrected serum calcium level was 9.2 ± 0.2 mg/dL (ref, 8.5-10.5 mg/dL), serum phosphate level was 3.6 ± 0.4 mg/dL (ref, 2.5-4.9 mg/dL), 25-hydroxy vitamin D level was 42.2 ± 10.5 mg/dL (ref, 20-50 ng/mL), and estimated glomerular filtration rate was 72.6 ± 14.4 mL/min/1.73 m². Patients were treated clinically with oral calcium 600 mg twice a day.ResultsiPTH was retested after a mean duration of 17.6 ± 12.7 days of calcium supplementation; the iPTH level decreased to 51.0 ± 10.6 pg/mL, with all patients achieving iPTH in the normal range with normocalcemia, consistent with hyperparathyroidism being because of insufficient calcium intake or absorption. All patients were normocalcemic after supplementation.ConclusionSecondary hyperparathyroidism can result from insufficient oral calcium intake. Calcium challenge is an efficacious and cost-effective tool for confirming and treating secondary hyperparathyroidism in the setting of normal vitamin D levels and kidney function.     

Bone Mineral Density in Pituitary Stalk Interruption Syndrome: The Role of Insulin-Like Growth Factor-1 and Testosterone at Different Skeletal Sites

ObjectiveThis study aimed to determine the clinical indicators influencing bone mineral density (BMD) of the lumbar spine and femoral neck in patients with pituitary stalk interruption syndrome (PSIS) who underwent multiple hormone replacement therapy (MHRT).MethodsMale patients with PSIS (n = 51) who underwent MHRT for at least 1 year were enrolled in this study. Their BMD parameters were recorded and compared with age-, weight-, and height-matched control adults. In addition, we performed multiple linear regression analysis to correlate clinical parameters with BMD parameters at 2 different sites.ResultsFifty-one patients with PSIS had a mean age of 30.39 ± 5.50 years. After 36 months of treatment, patients with PSIS who underwent MHRT had slightly lower BMD than those in the control group. Multiple linear regression models revealed a positive association between the Z-score values for the lumbar spine with treatment duration (r = 0.453, P < .001), insulin-like growth factor-1 (IGF-1) standard deviation score (SDS) values (r = 0.248, P = .038), and total testosterone level (r = 0.260, P = .036) and a positive association between the Z-score values for the femoral neck with treatment duration (r = 0.425, P < .001) and IGF-1 SDS values (r = 0.338, P = .009).ConclusionCollectively, long-term MHRT improves bone density in patients with PSIS to the normal range. A combination of recombinant human growth hormone replacement is more beneficial to the BMD than non–recombinant human growth hormone treatment. Moreover, serum IGF-1 contributes to femoral and lumbar mineralization, whereas serum testosterone plays a role in lumbar mineralization.     

Positive Thyroid Peroxidase Antibody and Thyroglobulin Antibody are Associated With Better Clinicopathologic Features of Papillary Thyroid Cancer

ObjectiveTo compare the thyroid autoantibody status of patients with papillary thyroid cancer (PTC) and benign nodular goiter as well as possible associations between thyroid autoantibodies and clinicopathologic features of PTC.MethodsA total of 3934 participants who underwent thyroidectomy were enrolled in this retrospective study. Patients were divided into PTC and benign nodule groups according to pathological diagnosis. Based on the preoperative serum antibody results, PTC patients were divided into thyroid peroxidase antibody (TPOAb)-positive, thyroglobulin antibody (TgAb)-positive, dual TPOAb- and TgAb-positive, or antibody-negative groups.ResultsOf the 3934 enrolled patients, 2926 (74.4%) were diagnosed with PTC. Multivariate regression analyses suggested that high thyroid-stimulating hormone levels (adjusted odds ratio [OR] = 1.732, 95% CI [1.485-2.021], P < .001), positive TgAb (adjusted OR = 1.768, 95% CI [1.436-2.178], P < .001), and positive TPOAb (adjusted OR = 1.452, 95% CI [1.148-1.836], P = .002) were independent risk factors for predicting malignancy of thyroid nodules. Multinomial multiple logistic regression analyses indicated that positive TPOAb alone was an independent predictor of less central lymph node metastasis in PTC patients (adjusted OR = 0.643, 95% CI [0.448-0.923], P = .017), whereas positive TgAb alone was significantly associated with less extrathyroidal extension (adjusted OR = 0.778, 95% CI [0.622-0.974], P = .028). PTC patients with dual-positive TPOAb and TgAb displayed a decreased incidence of extrathyroidal extension (adjusted OR = 0.767, 95% CI [0.623-0.944], P = .012) and central lymph node metastasis (adjusted OR = 0.784, 95% CI [0.624-0.986], P = .037).ConclusionAlthough preoperative positive TPOAb and TgAb are independent predictive markers for PTC, they are also associated with better clinicopathologic features of PTC.     

Albumin-Corrected Calcium and the Prevalence and Categories of Hypercalcemia in Hospitalized Patients With 1-Year Follow-Up of Undiagnosed Cases

ObjectiveTo assess the impact of using corrected calcium versus total calcium on hypercalcemia case detection in hospitalized patients.MethodsPatients hospitalized from June 2012 to June 2017 with a corrected calcium level of ≥10.5 mg/dL were identified by medical record review. One-year follow-up data through June 2018 were acquired. Albumin-corrected calcium level was calculated: (4 − albumin concentration in g/dL) × 0.8 + total serum calcium in mg/dL.ResultsA group of 1067 patients had a corrected calcium level of ≥10.5 mg/dL. The prevalence of hypercalcemia was 0.73% with total calcium and 1.09% with corrected calcium, respectively, with a 49% relative increase. Most patients (62%) had mild hypercalcemia (10.5-11.9 mg/dL); 3.7% had severe hypercalcemia (>14 mg/dL). With corrected calcium, the most common categories of hypercalcemia were malignancy (35.4%), hypercalcemia that was not further evaluated (31.1%), and hyperparathyroidism (22.4%). All patients in the unidentified category had albumin levels <2.8 g/dL. At the 1-year follow–up, 63% of the unidentified cases had normal calcium levels, and 26.8% had mild persistent hypercalcemia. Of those with persisting hypercalcemia at 1 year, 16.8% were diagnosed with hyperparathyroidism.ConclusionUsing albumin-corrected calcium resulted in an ∼50% increase in the detection of hypercalcemia cases. Although hypercalcemia resolved in majority of the undiagnosed cases at 1 year, a number of these remained abnormal. Detecting hypercalcemic disorders by correcting for low albumin level can help identify conditions such as hyperparathyroidism. Adding auto-calculated albumin-corrected calcium to routine laboratory tests could be a cost-effective intervention to improve the detection of hypercalcemic disorders.