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.     

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 Quality as Measured by Trabecular Bone Score in Normocalcemic Primary Hyperparathyroidism

ObjectiveThe impact of normocalcemic hyperparathyroidism (NHPT) on bone quality remains largely unexplored. We aimed to investigate the usefulness of trabecular bone score (TBS) assessment in NHPT and the accuracy of TBS in predicting vertebral fractures (VFs) in NHPT.MethodsIn this multicentric cross-sectional study, we assessed the TBS in 47 subjects with NHPT, 41 with primary hyperparathyroidism (PHPT), and 39 age- and sex-matched control subjects.ResultsTBS values did not differ among the 3 groups. The prevalence of low TBS (TBS < 1.2) was 23.4% in NHPT, 26.8% in PHPT, and 15.4% in controls, without statistically significant differences between groups. However, we found a lower lumbar spine Z-score adjusted for TBS (LS Z-score1TBS) in PHPT participants when compared with controls (-0.48 ± 1.06 vs 0.07 ± 0.93, P = .017). In NHPT group, LS Z-score1TBS did not detect patients with overall VFs (threshold, -0.15; area under the curve, 0.45; 95% CI, 0.253-0.648; accuracy, 55.3%). Instead, it was useful for moderate-severe VFs (threshold, 0.55; area under the curve, 0.81; 95% CI, 0.62-0.996; accuracy, 83%). In PHPT subjects also, TBS did not predict VFs.ConclusionIn NHPT, TBS is not reduced. When adjusted for TBS, the LS Z-score might predict moderate-to-severe VFs.     

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.     

Type 1 Diabetes Mellitus and Lipohypertrophy - Impact of the Intervention on Glycemic Control via Patient’s Examination and Retraining on Change of Infusion Set

ObjectiveLipohypertrophy (LH) is a common complication of insulin therapy in type 1 diabetes mellitus (T1DM). We examined whether an intervention consisting of LH assessment and retraining on insulin infusion set use improves glycemic control on subcutaneous insulin infusion (CSII) in patients with T1DM.MethodsThe intervention was conducted in 79 consecutive patients with T1DM. Data on glucose levels, glycated hemoglobin (HbA1c), and insulin doses were collected at baseline and after a median of 22 weeks (20-31.75 weeks).ResultsA total of 46 patients with T1DM (23 [50%] women) participating in the follow-up were characterized by a median age of 29 years (25-33.8 years), body mass index of 24.6 ± 3.3 kg/m², T1DM duration of 16.5 years (8.3-20 years), and subcutaneous insulin infusion duration of 7 years (4-10.8 years). Patients’ median HbA1c fell from 7.4% (6.7%-8.2%) to 7.05% (6.4%-7.6%) (P < .001), daily insulin dose/kg decreased (0.7 ± 0.20 vs 0.68 ± 0.15 IU/kg; P = .017) together with the total daily insulin dose (50.3 [40.5-62.7] vs 47.6 [39.8-62.1] IU; P = .019]. Furthermore, the percentage of basal insulin dose increased (43.0% [36-50] vs 44.0% [39.0-50.0]; P = .010], whereas the percentage of bolus dose decreased (57% [50-64] vs 56% [50-61], P = .010).ConclusionsThe structured LH-related intervention in patients with T1DM on insulin pumps resulted in better glycemic control and a decrease in total daily insulin dose.     

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.     

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.     

SARS-CoV-2 Seroprevalence in Individuals With Type 1 and Type 2 Diabetes Compared With Controls

ObjectiveData for the association between diabetes and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) susceptibility are conflicting. We aimed to evaluate this association using an analytical cross-sectional study design.MethodsStudy participants were recruited from endocrine clinics of our hospital and belonged to 3 groups: group 1 (type 1 diabetes mellitus [T1DM]), group 2 (type 2 diabetes mellitus [T2DM]), and group 3 (controls). All participants submitted blood samples for SARS-CoV-2 S1/S2 immunoglobulin G antibody test (LIAISON; DiaSorin) and were interviewed for a history of documented infection.ResultsWe evaluated a total of 643 participants (T1DM, 149; T2DM, 160; control, 334; mean age, 37.9 ± 11.5 years). A total of 324 (50.4%) participants were seropositive for SARS-CoV-2. The seropositivity rate was significantly higher in the T1DM (55.7% vs 44.9%, P = .028) and T2DM (56.9% vs 44.9%, P = .013) groups than in the control group. The antibody levels in seropositive participants with T1DM and T2DM were not significantly different from those in seropositive controls. On multivariable analysis, low education status (odds ratio [OR], 1.41 [95% CI, 1.03-1.94]; P = .035), diabetes (OR, 1.68 [95% CI, 1.20-2.34]; P = .002), and overweight/obesity (OR, 1.52 [95% CI, 1.10-2.10]; P = .012) showed a significant association with SARS-CoV-2 seropositivity. The association between diabetes and SARS-CoV-2 seropositivity was found to further increase in participants with coexisting overweight/obesity (adjusted OR, 2.63 [95% CI, 1.54-4.47]; P < .001).ConclusionSARS-CoV-2 seropositivity, assessed before the onset of the national vaccination program, was significantly higher in participants with T1DM and T2DM than in controls. The antibody response did not differ between seropositive participants with and without diabetes. These findings point toward an increased SARS-CoV-2 susceptibility for patients with diabetes, in general, without any differential effect of the diabetes type.     

A Parathyroid Hormone–Guided Calcium and Calcitriol Supplementation Protocol Reduces Hypocalcemia-Related Readmissions Following Total Thyroidectomy

ObjectiveTo determine the effect of a 4-hour postoperative serum parathyroid hormone (PTH)–guided calcium (Ca) and calcitriol supplementation protocol on the incidence of hypocalcemia and hospital readmissions in patients undergoing total thyroidectomy.MethodsThis was a single-institution, retrospective chart review of patients who underwent total thyroidectomy; 148 and 389 of the patients underwent surgery prior to and after the protocol implementation, respectively. The risk of hypocalcemia was stratified as low (PTH level of >30 pg/mL), medium (15-30 pg/mL), and high (<15 pg/mL), using serum PTH values obtained 4 hours postoperatively. Hypocalcemia was defined as a total serum Ca level of <8 mg/dL. Baseline demographic and operative characteristics and postoperative outcome were recorded for both groups. The Fisher exact test and Wilcoxon rank sum test were used to compare the characteristics of the 2 groups. A multivariate logistic regression model was applied to account for potentially confounding variables.ResultsPostoperative hypocalcemia occurred significantly less frequently in the protocol group compared with that in the preprotocol group (10.3% vs 20.9%, P = .002). The reduction in hypocalcemia in the protocol group was observed in both patients with (16.3% vs 25.6%) and without (8.4% vs 19.3%) cervical lymph node dissection. The protocol group had a significantly lower incidence of hospital readmission events than the preprotocol group (1.0% vs 4.7%, P = .013).ConclusionCompared with a historical cohort, a PTH-guided protocol for Ca and calcitriol supplementation significantly reduces the postoperative hypocalcemia and hospital readmission rates in patients undergoing total thyroidectomy.     

Anemia in Patients With Diabetes and Prediabetes With Normal Kidney Function: Prevalence and Clinical Outcomes

ObjectiveAnemia is a known complication of diabetes mellitus (DM); however, its prevalence and prognostic relevance in patients with DM and pre-DM with normal kidney function have not been well defined. This study assessed the prevalence of anemia in patients with DM and pre-DM and evaluated its association with clinical outcomes during a 4-year follow-up period.MethodsThis retrospective analysis included patients with DM and pre-DM referred to the Meir Medical Center Endocrine Institute in 2015. Patients with an estimated glomerular filtration rate (eGFR) of <60 mL/min or any other recognized cause of anemia were excluded. The risk of developing microvascular or macrovascular complications or of death during the 4-year follow-up period was determined.ResultsA total of 622 patients (408 with DM and 214 with pre-DM) were included. The mean age of the patients was 64 ± 10.6 years, and 70% were women. The baseline hemoglobin A1C level was 7.1% ± 1.7% (54 mmol/mol), and the eGFR was 86.1 ± 15.3 mL/min. At the time of inclusion, 77 patients (19%) with DM and 23 (11%) with pre-DM had anemia (hemoglobin level 11.9 ± 0.8 and 11.8 ± 0.8 g/dL, respectively), compared with normal hemoglobin levels of 13.8 ± 0.9 and 13.7± 0.9 g/dL, respectively, in the others. A multivariable analysis demonstrated an inverse correlation between baseline hemoglobin (as a continuous variable) and mortality (P = .035), microvascular complications (P = .003), and eGFR decline (P < .001) but not between baseline hemoglobin and macrovascular complications (P = .567).ConclusionThis study found a significant prevalence of anemia unrelated to renal failure, both in patients with DM and pre-DM. Anemia in these patients is associated with the development of microvascular complications, eGFR decline, and mortality. These results underscore the need for intensive lifestyle and pharmacologic interventions in these patients.     

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.     

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.     

Low Diagnostic Utility of Overnight High-Dose Dexamethasone Suppression Test in ACTH-Dependent Cushing’s Syndrome

ObjectiveOvernight high-dose dexamethasone suppression test (ON-HDDST) is a simple test to localize the source of ACTH in patients with ACTH-dependent Cushing’s syndrome (CS). However, previous studies have reported its varying accuracy. We studied the utility of ON-HDDST in diagnosing Cushing’s disease (CD) in a series of patients with CD and ectopic ACTH syndrome (EAS).MethodsWe conducted a retrospective study of 88 patients with ACTH-dependent CS (plasma ACTH > 20.0 pg/mL), who underwent an ON-HDDST. CD and EAS were diagnosed in 68 and 20 patients, respectively. Patients were investigated using MRI of the sellar region, CT of the thorax/abdomen, Gallium-68-DOTANOC PET scan, and bilateral inferior petrosal sinus sampling as required.ResultsPatients with EAS had a significantly higher serum cortisol after ON-HDDST than patients with CD (median [IQR], 19.9 [12.4-31.1] μg/dL vs 9.9 [5.1-25.0] μg/dL, P <.01). A suppressed ON-HDDST (≥50% fall from baseline) was noted in 44 (65%) patients with CD and 3 (15%) patients with EAS (P <.0001). Among patients with CD, cortisol suppression >50% was noted in 35 (76%) of patients with microadenoma and 7 (44%) with macroadenoma. Among patients with EAS, ON-HDDST was suppressed in 1 of 6 patients (17%) with an occult tumor and 2 of 14 patients (14%) with a localized tumor. The ROC curve plotted for the percentage suppression of cortisol had an area under the curve (AUC) of 0.72 (P =.01). The best test parameters, with 65% sensitivity, 85% specificity, 94% positive predictive value, 42% negative predictive value, and 69% accuracy, were at 50% cutoff level.ConclusionThe ON-HDDST had a poor diagnostic value in differentiating CD and EAS.     

Nordic Walking Improves Cardiometabolic Parameters,Fitness Performance,and Quality of Life in Older Adults With Type 2 Diabetes

ObjectiveTo assess the effect of Nordic walking (NW) on cardiometabolic health, physical performance, and well-being in sedentary older adults with type 2 diabetes (T2D).MethodsFifteen subjects with T2D (female, 5; male, 10; age, 65 ± 6.2 years [mean ± standard deviation]; body mass index, 27.3 ± 4.9 kg/m² [mean ± standard deviation]) were enrolled in a 6-month NW training program. The fasting glucose and glycosylated hemoglobin levels, lipid profile (total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides), systolic blood pressure (SBP), and diastolic blood pressures were measured before and after the intervention. Participants’ quality of life (Short-Form Health Survey) and physical fitness (6-minute walking test) were also evaluated.ResultsCompared with baseline, NW significantly improved the fasting glucose level (103.5 ± 18.5 vs 168.7 ± 37.7 mg/dL, P = .01), SBP (121.8 ± 12.2 vs 133 ± 14.4 mm Hg, P = .02), physical fitness (759.88 ± 69 vs 615.5 ± 62.6 m, P < .001), and both mental health (54.5 ± 4.4 vs 45.7 ± 5.6, P < .01) and physical health (49.8 ± 4.7 vs 40.3 ± 5.9, P < .01). The levels of glycosylated hemoglobin (6.15% ± 0.8% vs 6.4% ± 1%, P = .46), total cholesterol (162.2 ± 31.2 vs 175.5 ± 28.8 mg/dL, P = .13), low-density lipoprotein cholesterol (95.2 ± 24.2 vs 106.3 ± 32.3 mg/dL, P = .43), and triglycerides (135.5 ± 60.8 vs 127.6 ± 57.4 mg/dL, P = 0.26) improved without reaching significance.ConclusionNW training improved the glycemic levels, SBP, physical fitness, and perception of quality of life in older adults with T2D. NW represents a suitable complementary strategy to improve the global health status in this population.     

Serum Hormone Concentrations in Transgender Individuals Receiving Gender-Affirming Hormone Therapy: A Longitudinal Retrospective Cohort Study

ObjectiveTo examine the association of various gender-affirming hormone therapy regimens with blood sex hormone concentrations in transgender individuals.MethodsThis retrospective study included transgender people receiving gender-affirming hormone therapy between January 2000 and September 2018. Data on patient demographics, laboratory values, and hormone dose and frequency were collected. Nonparametric tests and linear regression analyses were used to identify factors associated with serum hormone concentrations.ResultsOverall, 196 subjects (134 transgender women and 62 transgender men), with a total of 941 clinical visits, were included in this study. Transgender men receiving transdermal testosterone had a significantly lower median concentration of serum total testosterone when compared with those receiving injectable preparations (326.0 ng/dL vs 524.5 ng/dL, respectively, P = .018). Serum total estradiol concentrations in the transgender women were higher in those receiving intramuscular estrogen compared with those receiving oral and transdermal estrogen (366.0 pg/mL vs 102.0 pg/mL vs 70.8 pg/mL, respectively, P < .001). A dose-dependent increase in the hormone levels was observed for oral estradiol (P < .001) and injectable testosterone (P = .018) but not for intramuscular and transdermal estradiol. Older age and a history of gonadectomy in both the transgender men and women were associated with significantly higher concentrations of serum gender-affirming sex hormones.ConclusionIn the transgender men, all routes and formulations of testosterone appeared to be equally effective in achieving concentrations in the male range. The intramuscular injections of estradiol resulted in the highest serum concentrations of estradiol, whereas transdermal estradiol resulted in the lowest concentration. There was positive relationship between both oral estradiol and injectable testosterone dose and serum sex hormone concentrations in transgender people receiving GAHT.     

Preoperative Calcium and Parathyroid Hormone Values Are Poor Predictors of Gland Volume and Multigland Disease in Primary Hyperparathyroidism: A Review of 2000 Consecutive Patients

ObjectiveCalcium and parathyroid hormone (PTH) values are believed to have a linear relationship in patients with primary hyperparathyroidism and correlate with parathyroid gland size, with higher values predicting single-gland disease. In this modern series, these preoperative values were correlated with operative findings to determine their utility in predicting the gland involvement at parathyroid exploration.MethodsTwo thousand consecutive patients who underwent initial surgery for sporadic primary hyperparathyroidism from 2000 to 2014 were reviewed. All patients underwent a 4-gland exploration. Relationships between preoperative calcium and PTH values with the total gland volume of each patient were examined and stratified using the number of involved glands: single adenoma (SA), double adenoma (DA), and hyperplasia (H).ResultsThere were 1274 (64%) SA, 359 (18%) DA, and 367 (18%) H cases. There was a poor correlation between preoperative calcium and PTH values (R = 0.37) and both poorly correlated with the total gland volume (R < 0.40). Similarly, subgroup analysis using the number of involved glands showed poor correlation. The mean total gland volume was similar among all subgroups (SA = 1.28 cm³, DA = 1.43 cm³, and H = 1.27 cm³; P = .52), implying that individual glands were smaller in multigland disease. SA was found in 271 (53%) of patients with calcium levels of ≤10.5 mg/dL and 122 (78%) with levels of ≥12 mg/dL (P < .001).ConclusionThis is the largest series correlating preoperative calcium and PTH values with operative findings of gland size and number of diseased glands. Although a lower calcium value predicts somewhat more multigland disease, the overall poor correlation should make the parathyroid surgeon aware that gland size and multigland disease cannot be predicted by preoperative laboratory testing.     

Seated Saline Suppression Test Is Comparable With Captopril Challenge Test for the Diagnosis of Primary Aldosteronism: A Prospective Study

ObjectiveThe saline suppression test (SST) and captopril challenge test (CCT) are commonly used confirmatory tests for primary aldosteronism (PA). Seated SST (SSST) has been reported to be superior to recumbent SST. Whether SSST is better than CCT remains unclear. We aimed to compare the diagnostic accuracy of SSST and CCT in a prospective study.MethodsHypertensive patients at a high risk of PA were consecutively included. Patients with an aldosterone-renin ratio of ≥1.0 ng/dL/μIU/mL were asked to complete SSST, CCT, and the fludrocortisone suppression test (FST). Using FST as a reference standard (plasma aldosterone concentration [PAC] post FST ≥ 6.0 ng/dL), area under the receiver-operating characteristic curve (AUC), sensitivity, and specificity of SSST and CCT were calculated, and multiple regression analyses were performed to identify potential factors leading to false diagnosis.ResultsA total of 196 patients diagnosed with PA and 73 with essential hypertension completed the study. Using PAC post SSST and PAC post CCT to confirm PA, SSST and CCT had comparable AUCs (AUC_SSST 0.87 [95% CI 0.82-0.91] vs AUC_CCT 0.88 [0.83-0.95], P = .646). When PAC post SSST and post CCT were set at 8.5 and 11 ng/dL, respectively, the sensitivity and specificity of SSST (0.72 [0.65, 0.78] and 0.86 [0.76, 0.93]) and CCT (0.73 [0.67, 0.80] and 0.85 [0.75, 0.92]) were not significantly different. In the multiple regression analyses, 1-SD increment of sodium intake resulted in a 40% lower risk of false diagnosis with SSST.ConclusionSSST and CCT have comparable diagnostic accuracy. Insufficient sodium intake decreases the diagnostic efficiency of SSST but not of CCT. Since CCT is simpler and cheaper, it is preferred over SSST.     

Ultra Rapid-Acting Inhaled Insulin Improves Glucose Control in Patients With Type 2 Diabetes Mellitus

ObjectiveTo determine whether the use of an inhaled insulin would improve HbA1c.MethodsThis study was performed in 20 type 2 diabetes mellitus (T2DM) participants with HbA1c values ≥7.5 (58) to ≤11.5% (102 mmol/mol) on a variety of glucose-lowering regimens. Prandial Technosphere insulin (TI) was rapidly titrated based on a treatment algorithm using postprandial blood glucose to calculate premeal doses. A 2-week baseline period was followed by 12 weeks of active treatment with TI. The primary outcome was change in HbA1c. Secondary outcomes included glucose time in range (time in range: 70-180 mg/dL) obtained by a blinded continuous glucose monitoring during the baseline period and at the end of 12 weeks. Goals were to assess how to rapidly and safely initiate TI intensification, determine dosing requirements, and establish an effective dose range in uncontrolled T2DM.ResultsMean HbA1c decreased by −1.6% (−17 mmol/mol) from 9.0% (75 mmol/mol) at baseline to 7.4% (57 mmol/mol) at 12 weeks (P < .0001). Mean time in range increased from 42.2% to 65.7% (P < .0002). Mean prandial doses of TI were 18 or 19 units for all meals. Time below range was 1.1% baseline and 2.6% post treatment (P = .01).ConclusionTreatment with inhaled TI dosed using a simple algorithm improved glycemic control measured by both HbA1c and time in range, with low rates of hypoglycemia. These data add significantly to understanding TI in the management of T2DM patients for whom prandial insulin is a consideration.     

Correlation of Body Mass Index and Age with Osteoporosis Probability in Patients with Primary Hyperparathyroidism

ObjectiveCurrently, there are limited markers to predict the osteoporosis probability in patients with primary hyperparathyroidism. We studied the relationship between various parameters and results of DXAs at various skeletal sites.MethodsRetrospective review of data for 218 patients with primary hyperparathyroidism was performed. Age, BMI, bone mineral density, serum total calcium, ionized calcium, intact parathyroid hormone, albumin, alkaline phosphatase, phosphate, 25-hydroxy vitamin D, 1,25-dihydroxy vitamin D, 24-hour urinary calcium levels and parathyroid tumor weight were analyzed. Two different statistical models- linear regression and multivariate logistic regression were performed.ResultsAt the lumbar spine, with the linear model, BMI (P < .001), alkaline phosphatase (P < .001), and ionized calcium (P < .001) significantly correlated with T scores; whereas with the logistic model, BMI was the only variable predicting osteoporosis probability.At the femoral neck, BMI (P < .022), 25-hydroxy vitamin D (P < .001), 1,25-dihydroxy vitamin D (P < .034) correlated with T scores; whereas both BMI (P < .029) and age (P < .051) were the significant variables that predicted osteoporosis.At the total hip, BMI (P < .001) and age (P < .001) correlated with T scores; whereas with the logistic model, only BMI (P < .016) predicted osteoporosis. At the forearm, a model could not be generated due to limited number.ConclusionIn patients with primary hyperparathyroidism, BMI strongly correlated with T scores and probability of osteoporosis.     

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.