Association Between Aldosterone and Parathyroid Hormone Levels in Patients With Adrenocortical Tumors

ObjectivePatients with primary aldosteronism (PA) can present with high PTH levels and negative calcium balance, with some studies speculating that aldosterone could directly stimulate PTH secretion. Either adrenalectomy or mineralocorticoid receptor blockers could reduce PTH levels in patients with PA. The aim of this study was to assess the relationship between aldosterone levels and parathyroid hormone (PTH)-vitamin D-calcium axis in a cohort of patients with PA, compared with patients with nonsecreting adrenocortical tumors in conditions of vitamin D sufficiency.MethodsWe enrolled a series of 243 patients retrospectively, of whom 66 had PA and 177 had nonsecreting adrenal tumors, and selected those with full mineral metabolism evaluation and 25(OH) vitamin D levels >20 ng/mL at the time of initial endocrine screening. The final cohort was composed of 26 patients with PA and 39 patients, used as controls, with nonsecreting adrenal tumors. The relationships between aldosterone, PTH levels, and biochemistries of mineral metabolism were assessed.ResultsAldosterone was positively associated with PTH levels (r = 0.260, P < .05) in the whole cohort and in the PA cohort alone (r = 0.450; P = .02). In the multivariate analysis, both aldosterone concentrations and urinary calcium excretion were significantly related to PTH levels, with no effect of 25(OH) vitamin D or other parameters of bone metabolism.ConclusionPTH level is associated with aldosterone, probably independent of 25(OH) vitamin D levels and urinary calcium. Whether aldosterone interacts directly with the parathyroid glands remains to be established.     

Association of Daily Growth Hormone Injection Adherence and Height Among Children With Growth Hormone Deficiency

ObjectiveRecombinant human growth hormone (somatropin) is recommended for children with growth hormone deficiency (GHD) to normalize adult height. Prior research has indicated an association between adherence to somatropin and height velocity. Further research is needed using real-world data to quantify this relationship; hence the objective of this study was to investigate the association between adherence to somatropin and change in height among children with GHD.MethodsThis retrospective cohort study included patients in the IQVIA PharMetrics Plus and Ambulatory Electronic Medical Records databases aged 3 to 15 years, with ≥1 GHD diagnosis code claim and newly initiated on somatropin between January 1, 2007 and November 30, 2019. Adherence was measured over the follow-up using the medication possession ratio (MPR); patients were classified as adherent (MPR ≥ 0.8) or nonadherent (MPR < 0.8).ResultsAmong 201 patients initiated on somatropin, 74.6% were male, mean age was 11.4 years, and the mean follow-up was 343.3 days. Approximately 76.6% of patients were adherent to somatropin over the follow-up period. Adjusted growth trajectories were similar between adherent and nonadherent patients pre-treatment initiation (P = .15). Growth trajectories post-initiation were significantly different (P = .001). On average, adherent patients gained an additional 1.8 cm over 1 year compared with nonadherent patients, adjusted for covariates.ConclusionGreater adherence to somatropin therapy is associated with improved height velocity. As suboptimal adherence to daily somatropin therapy is an issue for children with GHD, novel strategies to improve adherence may improve growth outcomes.     

Diagnostic Values of Intraoperative (1-84) Parathyroid Hormone Levels are Superior to Intact Parathyroid Hormone for Successful Parathyroidectomy in Patients With Chronic Kidney Disease

ObjectivePersistent secondary hyperparathyroidism (SHPT) may occur because of residual cervicothoracic parathyroids in parathyroidectomy (PTX) patients with chronic kidney disease. We prospectively compared the predictive values of intraoperative plasma (1-84) parathyroid hormone (PTH) and intact PTH (iPTH) levels to improve the safety and efficacy of PTX.MethodsWe included 100 healthy controls, 162 stage 5 chronic kidney disease patients without SHPT, and 214 patients who underwent PTX because of SHPT. Plasma iPTH and (1-84) PTH levels were measured before incision (io-iPTH0 and io-[1-84]PTH0, respectively) and 10 minutes (io-iPTH10 and io-[1-84]PTH10, respectively) and 20 minutes (io-iPTH20 and io-[1-84]PTH20, respectively) after removing all parathyroids. The percentage reduction of iPTH and (1-84) PTH at 10 minutes (io-iPTH10% and io-[1-84]PTH10%, respectively) and 20 minutes (io-iPTH20%, and io-[1-84]PTH20%, respectively) was calculated. iPTH and (1-84) PTH were measured using second- and third-generation PTH assays, respectively.ResultsCompared with the controls and non-PTX patients, the PTX group had more obvious mineral metabolism disorders. There were 187 successful PTXs, 19 patients with persistent SHPT, and 8 patients lost to follow-up. The receiver operating characteristic curves revealed that io-(1-84)PTH10% >86.6% and io-(1-84)PTH20% >87.5% suggested successful PTX. The sensitivity of io-iPTH20% and io-(1-84)PTH20% were higher than those at the timepoint of 10 minutes. Moreover, the specificity and sensitivity of the (1-84) PTH reduction percentage were superior to that of iPTH.ConclusionIntraoperative reduction percentages of plasma (1-84) PTH levels are superior to iPTH for accurately predicting successful PTX, especially at 20 minutes after all cervicothoracic parathyroids had been resected.     

High Prevalence of Nonalcoholic Fatty Liver Disease Among Adolescents and Young Adults With Hypopituitarism due to Growth Hormone Deficiency

ObjectiveTo investigate the prevalence of nonalcoholic fatty liver disease (NAFLD) in adolescents and young adults with hypopituitarism and to examine the associations of growth hormone (GH) deficiency with the occurrence of NAFLD.MethodsA cross-sectional study for the determination of NAFLD prevalence included 76 patients with childhood-onset hypopituitarism and 74 controls matched by age and body mass index (BMI). We investigated the prevalence of NAFLD in adolescent and young adult patients with hypopituitarism as well as the age- and BMI-matched controls. Among patients with hypopituitarism, anthropometric, clinical, and biochemical assessments using transient elastography and magnetic resonance imaging were performed. Logistic regression was used to identify the factors associated with NAFLD.ResultsThe adolescents and young adults with hypopituitarism exhibited higher prevalence of NAFLD than the age- and BMI-matched controls. Among patients with hypopituitarism, obesity and obesity-related metabolic derangements were significantly associated with liver steatosis and fibrosis, whereas lower insulin-like growth factor (IGF)-I standard deviation score (SDS) and IGF-I/IGF-binding protein 3 molar ratios were associated with steatosis. In regression analyses adjusted for BMI SDS, steatosis was found to be associated with a lower IGF-I SDS and IGF-I/IGF-binding protein 3 molar ratios, whereas liver fibrosis was found to be associated with a lower IGF-I SDS.ConclusionOur results suggest that GH deficiency contributes to the occurrence of NAFLD, along with obesity and obesity-related metabolic changes. Because NAFLD occurs early in patients with hypopituitarism, the surveillance, weight control, and timely replacement of deficit hormones, including GH, are essential.     

Decreased Mortality After Long-Term Treatment With Dipeptidyl Peptidase-4 Inhibitors: A Retrospective Study of U.S. Veterans With Type 2 Diabetes

ObjectiveThe prevalence of chronic kidney disease (CKD) in the United States is 13% of the general population. Among those with CKD, diabetic nephropathy is the leading cause of end-stage renal disease. This is a retrospective study examining the effect of long-term use of dipeptidyl peptidase-4 (DPP-4) inhibitors on all-cause mortality and progression of renal disease in the veteran population.MethodsData was extracted using the Veterans Administration Informatics and Computing Infrastructure. A large cohort of veterans diagnosed with type 2 diabetes mellitus were used to identify patients on DPP-4 inhibitors and without DPP-4 inhibitors. Groups were compared to determine the effect of DPP-4 inhibitors on the progression of CKD and all-cause mortality. Data were analyzed using SAS.ResultsSubjects in the treatment group (n = 40 558) had baseline variables (age, body mass index, race) similar to the control group (n = 40 558). Diabetes control improved in the treatment group (HgbA1c, 8.3% [67 mmol/mol] to 7.8% [62 mmol/mol]; P < .001) but not in the control group (HgbA1c, 7.4% [57 mmol/mol] to 7.3% [56 mmol/mol]). New diagnoses of heart failure and coronary artery bypass grafts were clinically significant (odds ratios = 0.66 and 0.52). No change in progression of CKD was seen in either group. All-cause mortality was reduced by 59%.ConclusionWe conclude that DPP-4 inhibitors are associated with a significant reduction in all-cause mortality independent of glucose control, albeit with no clear cause, including obtainable cardiovascular outcomes. Our data is consistent with prior trials in that DPP-4 inhibitors did not show a significant change in serum creatinine or microalbuminuria.     

Associations of Urinary Polycyclic Aromatic Hydrocarbons With Bone Mineral Density at Specific Body Sites in U.S. Adults,National Health and Nutrition Examination Survey 2001 to 2004

ObjectiveWe aimed to analyze the association between certain types of urinary polycyclic aromatic hydrocarbons (PAHs) and bone mineral density (BMD) at specific sites of the body.MethodsA total of 2978 eligible participants from the National Health and Nutrition Examination Survey 2001 to 2004 were included in this study. Data of 8 urinary PAHs and BMDs of 3 skeleton sites and the total body were analyzed. Univariate and multivariate linear regression analyses were performed to explore the association between urinary PAHs and BMDs. Subgroup analyses stratified by sex and body mass index were also performed.ResultsAfter adjustment for all confounders, elevated 3-fluorene (β = 0.046; 95% confidence intervals [CIs], 0.007-0.084) and 2-fluorene (β = 0.054; 95% CI, 0.007-0.100) levels were associated with greater left arm BMD, whereas no statistical differences were observed in the relationship between other PAHs and BMDs (all P > .05). Higher 3-fluorene and 2-fluorene levels were still associated with increased left arm BMD in men (P < .05), whereas the higher 2-phenanthrene level was related to decreased left arm BMD (β = ?0.062; 95% CI, ?0.105 to ?0.019), right arm BMD (β = ?0.059; 95% CI, ?0.091 to ?0.027), and total BMD (β = ?0.065; 95% CI, ?0.119 to ?0.012) in women. Similar results were also found in different body mass index populations (all P < .05).ConclusionCertain urinary PAHs are associated with BMDs at specific body sites. Future studies are needed to illustrate the mechanisms behind the association to establish a causal relationship.     

Decreased Serum Wnt Antagonist Levels in Patients With Active Acromegaly

ObjectiveThe Wnt signaling pathway is an important modulator of bone metabolism. This study aims to clarify the changes in Wnt antagonists in active and biochemically controlled acromegalic patients.MethodsWe recruited 77 patients recently diagnosed with acromegaly. Of those, 41 patients with complete follow-up data were included. Thirty healthy patients matched for age, sex, and body mass index served as controls. At baseline and posttreatment, Wnt antagonists (sclerostin [SOST], dickkopf-related protein 1 [DKK-1], and Wnt inhibitory factor 1 [WIF-1]), bone turnover markers (osteocalcin, procollagen type 1 N-terminal propeptide [P1NP], and C-terminal telopeptide of type 1 collagen [CTX]) and the bone remodeling index were investigated.ResultsAcromegalic patients had higher serum osteocalcin, P1NP, and CTX and a higher bone remodeling index than controls (P < .01). Serum SOST, DKK-1, and WIF-1 levels were significantly decreased in patients compared to controls (all P < .01). Serum SOST and WIF-1 levels were negatively correlated with growth hormone levels; SOST levels were positively correlated with WIF-1. After treatment, serum bone turnover markers and the bone remodeling index decreased, while SOST and WIF-1 significantly increased (P < .05). DKK-1 levels did not change compared to baseline (P > .05). In biochemically controlled patients, SOST and WIF-1 levels and bone turnover markers were restored and did not differ from those of the control participants (all P > .05).ConclusionPatients with active acromegaly exhibited significantly decreased Wnt antagonist levels. The reduction in Wnt antagonists is a compensatory mechanism to counteract increased bone fragility in active acromegaly.     

Association of Vitamin D Status With Hospital Morbidity and Mortality in Adult Hospitalized Patients With COVID-19

ObjectiveTo determine the association between vitamin D status and morbidity and mortality in adult hospitalized coronavirus disease 2019 (COVID-19) patientsMethodsWe performed a retrospective chart review study in COVID-19 patients aged ≥18 year hospitalized at Boston University Medical Center between March 1 and August 4, 2020. All studied patients tested positive for COVID-19 and had serum levels of 25-hydroxyvitamin D (25[OH]D) results measured within 1 year prior to the date of positive tests. Medical information was retrieved from the electronic medical record and was analyzed to determine the association between vitamin D status and hospital morbidity and mortality.ResultsAmong the 287 patients, 100 (36%) were vitamin D sufficient (25[OH]D >30 ng/mL) and 41 (14%) died during hospitalization. Multivariate analysis in patients aged ≥65 years revealed that vitamin D sufficiency (25[OH]D ≥30 ng/mL) was statistically significantly associated with decreased odds of death (adjusted OR 0.33, 95% CI, 0.12-0.94), acute respiratory distress syndrome (adjusted OR 0.22, 95% CI, 0.05-0.96), and severe sepsis/septic shock (adjusted OR 0.26, 95% CI, 0.08-0.88), after adjustment for potential confounders. Among patients with body mass index <30 kg/m², vitamin D sufficiency was statistically significantly associated with a decreased odds of death (adjusted OR 0.18, 95% CI, 0.04-0.84). No significant association was found in the subgroups of patients aged <65 years or with body mass index ≥30 kg/m².ConclusionWe revealed an independent association between vitamin D sufficiency defined by serum 25(OH)D ≥30 ng/mL and decreased risk of mortality from COVID-19 in elderly patients and patients without obesity.     

Serum Selenium Levels in Patients With Graves Disease With or Without Thyroid Ophthalmopathy

BackgroundGraves disease is one of the most common autoimmune thyroid diseases. Thyroid has the highest concentration of selenium (Se) in the body. Se plays a crucial role in the functioning of some thyroid enzymes; however, there are controversial results regarding the administration of serum Se levels in patients with Graves disease.MethodsIn this study, patients with Graves disease with orbitopathy (GO group) or without orbitopathy (GD group) were recruited. Healthy individuals without a history of any disease were enrolled as the control group. Serum Se and thyroid hormone levels, including T3, T4, and thyroid-stimulating hormone (TSH), were measured using atomic absorption and radioimmunoassay techniques, respectively.ResultsIn this cross-sectional study, 60 and 56 patients and 58 healthy subjects were included in the GO, GD, and control groups. Serum Se levels in the GO, GD, and control groups were 94.53 ± 25.36 μg/dL, 96.82 ± 30.3 μg/dL, and 102.55 ± 16.53 μg/dL, respectively (P = .193). There was a reverse association between the serum Se level and thyroid hormones, including T3, T4, and TSH, in the GO group. However, serum Se levels exhibited a significant reverse association with T4 and TSH hormones but not with T3 in the GD group.ConclusionOur results showed no significant differences in the serum Se levels in the GO and GD groups compared with that in the control group. In addition, we did not detect any significant difference in the serum Se levels between the GO and GD groups.     

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.     

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.     

The Optimal Parathyroid Hormone Cut-Off Threshold for Early and Safe Management of Hypocalcemia After Total Thyroidectomy

ObjectiveTo define optimal intact parathyroid hormone (iPTH) cut-off threshold predictive of hypocalcemia after total thyroidectomy for safe and effective postoperative management.MethodsThis prospective single center study was done in 2 phases. In phase I, predictors of symptomatic hypocalcemia were analyzed and the receiver operating characteristic curve was used to define the optimal iPTH cut-off threshold predictive of hypocalcemia. Phase II studied giving prompt prophylactic supplemental calcium and vitamin D to all patients who had iPTH levels below the calculated threshold, while phase I patients were given prompt selective supplementation if they had postoperative hypocalcemia or symptoms.ResultsUnivariate analysis of patients in phase I showed that postoperative iPTH was the only significant variable that can predict symptomatic hypocalcemia. Using receiver operating characteristic curve and Youden index, the confirmed optimal cut-off threshold predictive of hypocalcemia was iPTH 19.95 pg/mL, with area under the curve of 0.903, 100% sensitivity, negative predictive value, and highest Youden index, while iPTH 15 pg/mL and iPTH 10 pg/mL were less optimal. Symptomatic hypocalcemia occurred in 30% of the phase I cohort who received selective supplementation versus 3% of those in the phase II cohort who received prophylactic supplementation. Return to emergency department and need for intravenous calcium were also significantly better in phase II.ConclusioniPTH cut-off for post-thyroidectomy hypocalcemia was 19.95 pg/mL. Low-risk patients were discharged with no supplementation while all high-risk patients received prompt calcium and vitamin D supplementation, which led to effective hypocalcemia management and safe 24-hour discharge.     

Embryo Quality May Be Associated With Serum Inhibin B Levels but Not With Serum or Follicular Fluid Levels of Other Components of the Activin–Follistatin–Inhibin Axis

ObjectiveWe investigated the potential associations of embryo quality with serum and/or follicular fluid (FF) concentrations of the molecules of the activin–follistatin–inhibin (AFI) axis and antimüllerian hormone and aimed to identify molecules that could predict a positive assisted reproductive technology (ART) outcome.MethodsIn this cross-sectional study, we measured AFI hormone and antimüllerian hormone levels in the serum and FF of follicles (n = 101) obtained from healthy oocyte donors who underwent an assisted reproductive technology course (n = 32). After egg retrieval, embryos were characterized as good or bad quality according to the European Society of Human Reproduction and Embryology criteria. Women were divided into 3 groups (<50%; 50%-66.7%; and >66.7%) according to the percentage of good quality embryos obtained.ResultsThere was no difference between good and bad quality embryos in any of the molecules measured in FF. Moreover, there was no difference in the parameters measured in the serum among women according to the percentage of good quality embryos (ie, suitable for transfer or freezing) except for inhibin B, which tended to increase along with a good quality embryo rate (55.6 ± 7.9 vs 95.3 ± 14.3 vs 113.9 ± 36.9; P = .045).ConclusionsAmong the molecules of the AFI axis, only serum but not FF inhibin B levels were marginally associated with good quality embryo rates.     

Parathyroid Hormone Level Changes Following Radioiodine Therapy for Thyroid Cancer: A Prospective Observational Study

ObjectiveOur objective was to analyze the effect of radioiodine (RAI) therapy on parathyroid hormone (PTH) secretion.MethodsA total of 137 patients were included and divided into 2 groups based on pretherapy PTH levels. The residual thyroid tissue volume was classified into 4 grades (0-3), and a value of 0 indicated that there was no apparent residual tissue. We analyzed the PTH level changes among different time points in each group and the factors that could predict the PTH level changes.ResultsIn 113 patients with normal parathyroid gland function, the PTH level at baseline, 1 day, 7 days, 1 month, 3 months, and 6 months after RAI therapy did not show any significant difference; in 24 patients with decreased parathyroid gland function, the level of PTH immediately decreased after the implementation of RAI therapy but gradually returned to a pre-RAI therapy level within 6 months. On the seventh day after therapy, the mean value of PTH in patients with a residual thyroid tissue volume of extent of 0/1 was 8.0 ± 2.3 pg/mL, which was significantly higher than that in patients with a residual thyroid tissue volume of extent of 2/3 (P = .011). Similar phenomena were observed 1 month, 3 months, and 6 months after therapy.ConclusionRAI therapy had a significant transient adverse effect on parathyroid gland function in patients with decreased PTH secretion pretherapy, and the extent was associated with the amount of residual thyroid tissue.     

The Effect of Gender-Affirming Hormone Therapy on Serum Creatinine in Transgender Individuals

ObjectiveTo describe the changes in serum creatinine (Cr) levels after the initiation of gender-affirming hormone therapy (GAHT) in transgender individuals to better understand the expected changes and interpretation of laboratory values in this population.MethodsA retrospective chart review of all adult transgender patients initiated on GAHT at Mayo Clinic from January 2011 to October 2019 was completed. Laboratory values were obtained prior to initiating GAHT and at 3, 6, and 12 months after initiating GAHT. Baseline Cr values were compared with Cr values at 3, 6, and 12 months after initiating GAHT in transgender men (TM) on testosterone and transgender women (TW) on estradiol and antiandrogens.ResultsA total of 84 TW (median age of 30 years) and 24 TM (median age of 23 years) were included for analysis. Following a matched pair analysis of TW, Cr values were found to be significantly decreased by ?0.03 at 3 months (P = .04), ?0.10 at 6 months (P < .01), and ?0.07 at 12 months (P < .01) compared with baseline values. Following a matched pair analysis of TM, Cr values were found to be significantly increased, on average, by 0.14 at 3 months (P = .04), 0.21 at 6 months (P = .016), and 0.15 at 12 months (P = .003) compared with baseline values.ConclusionIn TW and TM, a change in Cr level was seen as early as 3 months toward their affirmed gender after initiating GAHT. Clinicians can use Cr levels established at 6 months as new baseline values, as these changes continue to persist up to 12 months.     

Hyperglycemia is Associated With Increased Mortality in Critically Ill Patients With COVID-19

ObjectiveTo explore the relationship between hyperglycemia in the presence and absence of diabetes mellitus (DM) and adverse outcomes in critically ill patients with coronavirus disease 2019 (COVID-19).MethodsThe study included 133 patients with COVID-19 admitted to an intensive care unit (ICU) at an urban academic quaternary-care center between March 10 and April 8, 2020. Patients were categorized based on the presence or absence of DM and early-onset hyperglycemia (EHG), defined as a blood glucose >180 mg/dL during the first 2 days after ICU admission. The primary outcome was 14-day all-cause in-hospital mortality; also examined were 60-day all-cause in-hospital mortality and the levels of C-reactive protein, interleukin 6, procalcitonin, and lactate.ResultsCompared to non-DM patients without EHG, non-DM patients with EHG exhibited higher adjusted hazard ratios (HRs) for mortality at 14 days (HR 7.51, CI 1.70-33.24) and 60 days (HR 6.97, CI 1.86-26.13). Non-DM patients with EHG also featured higher levels of median C-reactive protein (306.3 mg/L, P = .036), procalcitonin (1.26 ng/mL, P = .028), and lactate (2.2 mmol/L, P = .023).ConclusionAmong critically ill COVID-19 patients, those without DM with EHG were at greatest risk of 14-day and 60-day in-hospital mortality. Our study was limited by its retrospective design and relatively small cohort. However, our results suggest the combination of elevated glucose and lactate may identify a specific cohort of individuals at high risk for mortality from COVID-19. Glucose testing and control are important in individuals with COVID-19, even those without preexisting diabetes.     

Are We Restoring Thyroid Hormone Signaling in Levothyroxine-Treated Patients With Residual Symptoms of Hypothyroidism?

IntroductionLevothyroxine (LT4) at doses that maintain the serum thyroid-stimulating hormone levels within the normal range constitutes the standard of care for the treatment of hypothyroidism. After a few months, this eliminates the signs and symptoms of overt hypothyroidism in the majority of patients, owing to the endogenous activation of thyroxine to triiodothyronine, the biologically active thyroid hormone. Still, a small percentage of the patients (10%-20%) exhibit residual symptoms, despite having normal serum thyroid-stimulating hormone levels. These symptoms include cognitive, mood, and metabolic deficits, with a significant impairment in psychological well-being and quality of life.ObjectiveTo provide a summary of progress in the approach of patients with hypothyroidism that exhibit residual symptoms despite treatment.MethodsWe reviewed the current literature and here we focused on the mechanisms leading to a deficiency of T3 in some LT4-treated patients, the role of residual thyroid tissue and the rationale for combination therapy with LT4 + liothyronine (LT3).ResultsA score of clinical trials comparing therapy with LT4 versus LT4 + LT3 concluded that both are safe and equally effective (neither is superior); however, these trials failed to recruit a sufficiently large number of patients with residual symptoms. New clinical trials that considered LT4-treated symptomatic patients revealed that such patients benefit from and prefer therapy containing LT4 + LT3; desiccated thyroid extract has also been used with similar results. A practical approach to patients with residual symptoms and on initiation of combination therapy with LT4 + LT3 is provided.ConclusionA recent joint statement of the American, British, and European Thyroid Associations recommends that a trial with combination therapy be offered to patients with hypothyroidism that do not fully benefit from therapy with LT4.     

Parathyroid Cystic Adenoma: A Systematic Review and Meta-Analysis

ObjectiveTo review diagnostic imaging modalities for parathyroid cystic adenomas (PCA). Since PCAs are a rare (0.5%-1%) subclass of parathyroid adenomas, and due to their cystic component, imaging modalities known to be efficient for diagnosing solid adenomas might fail in localizing them.MethodsWe conducted a systematic review using the PubMed and Cochrane databases for English articles on PCAs published between 1995 and 2020. A meta-analysis of the retrieved data was performed.ResultsOverall, 39 studies, reporting on a total of 160 patients, were included in the analysis. Two thirds (68%) of the patients were female, with a mean age of 53.9 years. A single cystic adenoma was detected in 98.1% of cases. The mean blood calcium corrected for albumin level was 12.6 ± 2.7 mg/dL, and the mean parathyroid hormone level was 565.5 ± 523.8 pg/mL. The mean PCA sizes as measured by ultrasound (US), computed tomography (CT), and ex vivo measurement were 4.8 ± 3.6, 5.2 ± 3.2, and 3.5 cm, respectively. The median weight was 8.1 g. PCA was detected in 86% of US examinations; 100% of US-guided fine needle aspiration, 4-dimensional computed tomography (4D-CT), or magnetic resonance imaging examinations; and 61% of 99m-technetium sestamibi scan with single-photon emission computed tomography ((99m)Tc-SPECT). (99m)Tc-SPECT showed a significantly lower diagnostic rate than US (odds ratio, 3.589), US-guided fine needle aspiration, CT combined with 4D-CT, and the combination of US, CT, 4D-CT, and magnetic resonance imaging (P < .001).ConclusionAlthough US and 4D-CT showed a significantly high rate in diagnosing PCA, (99m)Tc-SPECT showed a lower PCA diagnostic rate. These findings suggest that larger cystic lesions suspected as PCAs should be further evaluated using 4D-CT rather than (99m)Tc-SPECT.