Gonadotropin Therapy Once a Week for Spermatogenesis in Hypogonadotropic Hypogonadism

ObjectiveHypogonadotropic hypogonadism (HH) can be caused by congenital HH (CHH), pituitary stalk interruption syndrome (PSIS), and pituitary injury (acquired HH). Gonadotropin therapy, typically administered every other day or twice a week, is commonly used to promote spermatogenesis. The aim of this retrospective study was to evaluate the efficacy of weekly gonadotropin therapy on spermatogenesis in patients with HH (n = 160).MethodsThe patients’ diagnoses include Kallmann syndrome (KS) (n = 61), normosmic CHH (nCHH) (n = 34), PSIS (n = 48), and acquired HH (n = 17). The rate of successful spermatogenesis and median time to achieve spermatogenesis among these 4 subgroups were compared as well as between a weekly group (n = 95) and a twice-a-week group (n = 223) of CHH patients.ResultsOnce-a-week gonadotropin therapy resulted in 74% (119/160) of HH patients achieving spermatogenesis with significantly increased testicular volume and total testosterone levels (P < .001). The median period of spermatogenesis was 13 (interquartile range[IQR] 11.4-14.6) months. Larger basal testicular volume (P = .0142) was an independent predictor for earlier sperm appearance. Six spontaneous pregnancies occurred. Compared with the twice-a-week regimen for spermatogenesis, the weekly injection group had a similar median time of sperm appearance (14 [IQR, 11.6-16.4] vs 15 [IQR, 13.5-16.5] months), success rate (78% [74/95] vs 64% [143/223]), sperm concentration (20.9 [IQR, 5.0-46.3] vs 11.7 [IQR, 2.1-24.4] million/mL), and progressive sperm motility (40.8 ± 27.3% vs 36.9% ± 20.2%).ConclusionWeekly gonadotropin therapy is effective in inducing spermatogenesis, similar to that of twice-a-week therapy. A larger basal testicular size was a favorable indicator for earlier spermatogenesis.     

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.     

Desmopressin Suppresses Gonadotropin-Induced Spermatogenesis in Patients With Pituitary Stalk Interruption Syndrome: A Retrospective,Single-Center Cohort Study

ObjectiveTo explore the influence of desmopressin on gonadotropin-induced spermatogenesis in patients with pituitary stalk interruption syndrome (PSIS).MethodsA single-center retrospective cohort study was conducted. All patients with PSIS had both gonadotropin and growth hormone (GH) deficiency. Patients were divided into desmopressin and nondesmopressin groups. The desmopressin and nondesmopressin groups were defined by the presence or absence of central diabetes insipidus, which determined whether the patient received desmopressin or not.ResultsThe average age of gonadotropin therapy was 24.3 and 26.1 in the desmopressin and nondesmopressin groups, respectively. The rate of successful spermatogenesis in the 2 groups was 31.58% and 77.27%, respectively. The period for first sperm appearance was 13.62 ± 5.95 and 13.48 ± 6.69 months, respectively. A multivariable Cox proportional hazards model found that the adjusted hazard ratio for desmopressin was 0.260, indicating a “possible” detrimental effect of desmopressin on spermatogenesis. Central diabetes insipidus would be expected to show a similar detrimental effect. The spermatogenesis rate decreased with increased dosage of desmopressin. In the nondesmopressin group, the rate of spermatogenesis was similar between the GH group and the non-GH subgroup. The GH group had higher sperm count and concentration than the non-GH group.ConclusionA minority of patients with PSIS had mild diabetes insipidus and received desmopressin therapy. The spermatogenesis rate decreased with increasing desmopressin dosage. In addition, GH supplementation did not affect the spermatogenesis rate.     

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.     

Evaluation of Lipohypertrophy in Patients With Type 1 Diabetes Mellitus on Multiple Daily Insulin Injections or Continuous Subcutaneous Insulin Infusion

ObjectiveTo determine lipohypertrophy (LH) in patients with type 1 diabetes mellitus (T1DM) on multiple daily insulin injections (MDII) or continuous subcutaneous insulin infusion (CSII) and to reveal the factors associated with the development and severity of LH.MethodsSixty-six patients with T1DM treated with MDII (n = 35, 53%) or CSII (n = 31, 47%) for at least 1 year were included. LH localizations were detected with palpation and ultrasonography (USG).ResultsThe LH detection rate with USG was significantly higher than that by palpation in the whole group (P < .001). The LH was detected with USG in 30 (85.7%) patients in the MDII group and 22 (71.0%) patients in the CSII group (P = .144). Advanced LH was detected in 13 (37.1%) of the patients treated with MDII and in 3 (9.7%) of the patients treated with CSII. LH was more severe in the MDII group than in the CSII group (P = .013). Diabetes duration and length of infusion set use were significantly longer and body mass index, hypoglycemia, and complication rates were higher in patients with LH than those in patients without LH (P < .05). A positive correlation was found between LH severity and HbA1C and insulin dose (P < .05, for both). MDII as insulin administration method, incorrect rotation, and a history of ketosis were found to be the most related factors with LH severity in a multiple linear regression analysis (P < .05).ConclusionUSG might be an effective approach for detecting and evaluating the severity of LH. MDII might cause more severe LH than CSII in patients with T1DM. In this study, LH was found to be associated mostly with incorrect rotation technique and a history of ketosis.     

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.     

Management of Fully Pubertal Girls With Nonclassical Congenital Adrenal Hyperplasia: Glucocorticoids Versus Oral Contraceptives

ObjectiveTo compare clinical outcomes of 3 treatment regimens—glucocorticoids (GCs), oral contraceptives (OCs), or a combination of both—administered to adolescents and young women diagnosed in childhood with nonclassical congenital adrenal hyperplasia (NCCAH), who had been treated with GCs until their adult height was achieved.MethodsA retrospective study of medical records of 53 female patients with NCCAH followed in 3 tertiary pediatric endocrinology institutes. The 3 treatment groups were compared for the prevalence of hirsutism and acne, standardized body mass index (BMI)-standard deviation score (SDS), and androgen levels at the attainment of adult height (baseline), 1-year later, and at the last documented visit.ResultsAt baseline, there were no significant differences among groups in BMI-SDS, androgen levels, hirsutism prevalence, acne, or irregular menses. From baseline to the last visit, the rate of hirsutism declined significantly only in the OC group (37.5% vs 6.2%, respectively; P = .03). The rate of acne declined in the combined group (50% vs 9%, respectively; P = .03) with a similar tendency in the OC group (50% vs 12.5%, respectively; P = .05). No significant changes were observed in BMI-SDS for the entire cohort or any subgroup during follow-up. A significant rise in androstenedione (P < .001), testosterone (P < .01), and 17-hydroxyprogesterone (P < .01) levels was observed only in the OC group.ConclusionIn girls diagnosed in childhood with NCCAH, who require treatment for hyperandrogenism following completion of linear growth, management should be tailored individually using a patient-centered approach. Treatment with OCs might be better than that with GCs for regression of hirsutism and acne. The long-term effects of elevated levels of androgens associated with this treatment regimen should be further studied.     

Differences in Clinical Manifestations and Tumor Features Between Metastatic Pheochromocytoma/Paraganglioma Patients With and Without Germline SDHB Mutation

ObjectiveTo compare metastatic pheochromocytoma/paraganglioma (MPP) patients with germline SDHB mutations (SDHB MPP) and without SDHB mutations (non-SDHB MPP) in terms of baseline clinical manifestations, tumor characteristics, and outcomes.MethodsClinical data were retrospectively reviewed in 101 MPP patients, including 34 SDHB MPP patients and 61 non-SDHB MPP patients.ResultsSDHB MPP patients presented at a younger age at onset, diagnosis, or metastasis (25 ± 16 vs 36 ± 14, 28 ± 17 vs 38 ± 15, and 31 ± 17 vs 44 ± 14 years old, respectively, P < .01 for all) than non-SDHB patients. Compared with their non-SDHB counterparts, SDHB patients were more likely to have paragangliomas (83% vs 47%, P < .05), synchronous metastases (44% vs 23%, P < .05), bone metastases (80% vs 48%, P < .01), and a shorter progression-free survival (3 years vs 5 years, P < .01). The Ki-67 index was higher in SDHB tumors (P < .05). The 5- and 10-year survival rates were 79% and 74%, respectively, in all patients. Seventeen patients died from MPP, and the time from metastasis to death in patients who had received systemic therapy was significantly longer than in those who had not (3.1 ± 1.5 vs 1.4 ± 0.7 years, P < .01).ConclusionCompared with MPP patients without SDHB mutations, MPP patients with SDHB mutations were younger at onset, diagnosis, or metastasis; had a higher incidence of synchronous metastases, higher ratio of paraganglioma, and higher Ki-67 index; had a shorter postoperative progression-free survival; and were more likely to develop bone metastasis or sole liver metastasis. Our results suggest that patients with SDHB mutations should be identified early and monitored regularly to achieve optimal clinical outcomes.     

Comparison of Clinical Tests for Peripheral Diabetic Neuropathy in a Type 1 Diabetes Cohort

ObjectiveTo examine the performance and agreement of 5 modalities for testing sensory neuropathy against a neurothesiometer among Hispanic patients with type 1 diabetes (T1D) in an outpatient setting.MethodsA cross-sectional study was conducted at a tertiary reference center in Mexico City. Sensitivity, specificity, predictive values, and likelihood ratios were calculated using a VibraTip device, 128 Hz tuning fork, and the Semmes-Weinstein 5.07/10 g monofilament test, Ipswich touch test (IpTT), and pinprick test (PPT). The VPT obtained using a neurothesiometer was used as the standard. Agreement between tests was calculated using kappa coefficients.ResultsOur study included 78 patients (156 examinations), of whom 56.4% were females. The mean age was 38.2 ± 13.0 years, and the mean body mass index was 24.6 ± 4.8 kg/m². The best sensitivity was found for IpTT and VibraTip (89.7% and 79.3%, respectively), while the PPT and IpTT had the highest positive predictive values (94.4% and 92.9%, respectively). The highest kappa coefficients were obtained for the IpTT vs neurothesiometer (kappa coefficient [κ] = 0.893, P < .001), followed by VibraTip vs neurothesiometer (κ = 0.782, P < .001). The VibraTip vs IpTT also had a substantial agreement (κ= 0.713, P < .001).ConclusionOur findings demonstrated that the IpTT had the best diagnostic performance and agreement compared with the standard in this cohort of Hispanic patients with T1D. The IpTT is a useful, simple test for diabetic neuropathy screening. These findings support its inclusion in future guidelines for diabetic foot examination.     

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.     

COVID-19 May Increase the Risk of Insulin Resistance in Adult Patients Without Diabetes: A 6-Month Prospective Study

ObjectiveDuring the coronavirus disease 2019 (COVID-19) pandemic, exploring insulin resistance and beta-cell activity is important for understanding COVID-19‒associated new-onset diabetes. We assessed insulin sensitivity and fasting insulin secretion in patients with COVID-19 without diabetes on admission and at 3 and 6 months after discharge.MethodsThis 6-month prospective study assessed data from the records of 64 patients without diabetes diagnosed with COVID-19 at Wenzhou Central Hospital, China. Each patient was followed up at 3 and 6 months after discharge. Repeated measures analysis of variance was used to investigate differences in multiple measurements of the same variable at different times. Linear regression analysis was performed to analyze the contributor for changes in the triglyceride-glucose (TyG) index.ResultsFasting C-peptide levels in patients at baseline were lower than the normal range. Compared with the baseline results, patients had significantly elevated fasting C-peptide levels (0.35 ± 0.24 vs 2.36 ± 0.98 vs 2.52 ± 1.11 μg/L; P < .001), homeostasis model assessment for beta-cell function (0.42, interquartile range [IQR] 0.36-0.62 vs 2.54, IQR 1.95-3.42 vs 2.90, IQR 2.02-4.23; P < .001), and TyG indices (8.57 ± 0.47 vs 8.73 ± 0.60 vs 8.82 ± 0.62; P = .006) and decreased fasting glucose levels (5.84 ± 1.21 vs 4.95 ± 0.76 vs 5.40 ± 0.68 mmol/L; P = .003) at the 3- and 6-month follow-up. Male gender, age, interferon-alfa treatment during hospitalization, and changes in total cholesterol and high-density lipoprotein levels were significantly associated with changes in the TyG index.ConclusionOur study provided the first evidence that COVID-19 may increase the risk of insulin resistance in patients without diabetes.     

Diagnosing Growth Hormone Deficiency: Can a Combined Arginine and Clonidine Stimulation Test Replace 2 Separate Tests?

ObjectiveGiven the large number of false-positive growth hormone deficiency (GHD) diagnoses from a single growth hormone (GH) stimulation test in children, 2 different pharmacologic tests, performed on separate days or sequentially, are required. This study aimed to assess the reliability and safety of a combined arginine-clonidine stimulation test (CACST).MethodsThis was a retrospective, single-center, observational study. During 2017-2019, 515 children aged >8 years underwent GH stimulation tests (CACST: n = 362 or clonidine stimulation test [CST]: n = 153). The main outcome measures used to compare the tests were GH response (sufficiency/deficiency) and amplitude and timing of peak GH and safety parameters.ResultsPopulation characteristics were as follows: median age of 12.2 years (interquartile range [IQR]: 10.7, 13.4), 331 boys (64%), and 282 prepubertal children (54.8%). The GHD rate was comparable with 12.7% for CACST and 14.4% for CST followed by a confirmatory test (glucagon or arginine) (P = .609). Peak GH was higher and occurred later in response to CACST compared with CST (14.6 ng/mL [IQR: 10.6, 19.4] vs 11.4 ng/mL [IQR: 7.0, 15.8], respectively, P < .001; 90 minutes [IQR: 60, 90] vs 60 minutes [IQR: 60, 90], respectively, P < .001). No serious adverse events occurred following CACST.ConclusionOur findings demonstrate the reliability and safety of CACST in detecting GHD in late childhood and adolescence, suggesting that it may replace separate or sequential GH stimulation tests. By diminishing the need for the second GH stimulation test, CACST saves time, is more cost-effective, and reduces discomfort for children, caregivers, and medical staff.     

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.     

Parathyroidectomy Is Associated With Reversed Nondipping Heart Rate That Impacts Mortality in Chronic Kidney Disease Patients

ObjectiveNondipping heart rate (HR), defined as a night/day HR ratio >0.90, has been associated with increased mortality in epidemiologic studies. However, its prognostic value in stage 5 chronic kidney disease (CKD5) patients and the effects of parathyroidectomy (PTX) on nondipping HR remain unknown.MethodsThis case-control study of 162 healthy controls and 502 CKD5 patients was performed between 2011 and 2018, in which CKD5 patients were further divided into non-PTX (n = 186) and severe secondary hyperparathyroidism (SHPT) with PTX (n = 316) subgroups. Each participant underwent 24-hour Holter monitoring for HR ratio. Mortality was followed up in CKD5 patients (median time: 46.0 months).ResultsThe HR ratio in CKD5 patients was higher than in controls (0.92 ± 0.08 vs 0.81 ± 0.08, P <.001), associated with a 44% increase in mortality risk per 0.1 increment (hazard ratio, 1.44; 95% CI: 1.02-2.03; P =.04), and was positively related to serum intact parathyroid hormone levels (P <.001). PTX reversed nondipping HR in SHPT patients (n = 50, median time: 6.3 months, P <.001). Survival probabilities for PTX (n = 294) were better than non-PTX (n = 47) (hazard ratio, 0.31; 95% CI: 0.14-0.67; P <.01) in SHPT patients (serum intact parathyroid hormone >500.0 pg/mL).ConclusionCKD5 patients displayed a nondipping HR pattern, which is a prognostic marker of all-cause mortality. PTX for SHPT patients was associated with a reversal in nondipping HR ratio, which may mediate a better outcome.     

Frequency of Thyroid Hormone Replacement After Lobectomy for Differentiated Thyroid Cancer

ObjectiveTo determine the frequency of levothyroxine (LT4) supplementation after therapeutic lobectomy for low-risk differentiated thyroid cancer (DTC).MethodsThis retrospective cohort study enrolled adult patients with low-risk DTC confirmed using surgical pathology who underwent therapeutic lobectomy at a single institution from January 2016 through May 2020. The outcome measures were postoperative serum thyroid-stimulating hormone (TSH) levels and the initiation of LT4. The predictors of a postoperative TSH level of >2 mU/L and initiation of LT4 were evaluated using Cox proportional hazards models.ResultsPostoperative TSH levels were available for 115 patients (91%), of whom 97 (84%) had TSH levels >2 mU/L after thyroid lobectomy. Over a median follow-up of 2.6 years, a postoperative TSH level of >2 mU/L was associated with older age (median 52 vs 37 years; P = .01), higher preoperative TSH level (1.7 vs 0.85 mU/L; P < .001), and primary tumor size of <1 cm (38% vs 11%, P = .03). Multivariate analysis revealed that only preoperative TSH level was an independent predictor of a postoperative TSH level of >2 mU/L (hazard ratio [HR] 1.53, P = .003). Among patients with a postoperative TSH level of >2 mU/L, 66 (68%) were started on LT4 at a median of 74 days (interquartile range 41-126) after lobectomy, with 51 (77%) undergoing at least 1 subsequent dose adjustment to maintain compliance with current guidelines.ConclusionMore than 80% of the patients who underwent therapeutic lobectomy for DTC developed TSH levels that were elevated beyond the recommended range, and most of these patients were prescribed LT4 soon after the surgery.     

A Novel Monoclonal Antibody Degrades the Thyrotropin Receptor Autoantibodies in Graves' Disease

ObjectiveAutoantibodies against the thyrotropin receptor (TSH-R-Ab) are key mediators for the pathogenesis of Graves' disease (GD). TSH-R-Ab degradation was evaluated using several immunoassays within an exploratory, controlled trial in patients with GD receiving a monoclonal antibody (mAb) targeting the neonatal crystallizable fragment receptor (FcRn).MethodsSerial measurements of TSH-R-Ab serum levels were performed using 3 different binding and cell-based assays in patients with GD either on medication or on placebo.ResultsIn contrast to the placebo group, in which no changes were observed, a 12-week mAb therapy led to an early and significant decrease (>60%) in the serum TSH-R-Ab levels in patients with thyroidal and extrathyroidal GD, as unanimously shown in all 3 assays. These marked changes were noted already at week 7 post baseline (P <.0001 for the binding immunoassay and for the luciferase (readout) bioassay). The 3 TSH-R-Ab binding and bioassays were highly correlated in the samples of both study groups (binding immunoassay vs luciferase bioassay, r =.91, P <.001, binding vs cyclic adenosine monophosphate (cAMP) bioassay, r = 0.86, P <.001, and luciferase vs cAMP bioassay, r = 0.71, P =.006). The serological results correlated with the course of the extrathyroidal clinical parameters of GD, that is, clinical activity score and proptosis.ConclusionTargeting the FcRn markedly reduces the disease-specific TSH-R-Ab in patients with GD. The novel and rapid TSH-R-Ab bioassay improves diagnosis and management of patients with GD.     

The Effects of Chronic Lymphocytic Thyroiditis on Clinicopathologic Factors in Papillary Thyroid Cancer

ObjectiveThis study evaluated the impact of chronic lymphocytic thyroiditis (CLT) on clinicopathologic parameters, prognostic outcome, and initial treatment responses in patients with papillary thyroid cancer (PTC).MethodsA retrospective review was conducted of 1409 patients with PTC, comprising 443 patients with pathology-proven PTC with CLT and 447 patients with PTC without CLT.ResultsThe median follow-up time was 58 months (range, 8-380 months), and the median age at the time of diagnosis was 43 years. The age at diagnosis was significantly lower in patients with CLT than in those without CLT (42 years vs 45 years, respectively; P = .001). The preoperative thyroid-stimulating hormone level was found to be significantly higher in patients with CLT than in those without CLT (1.71 mIU/L vs 1.28 mIU/L, respectively; P < .001). Multifocality and capsular, lymphovascular, and perineural invasion were detected at a higher rate in the group with CLT than in the group without CLT (P = .015, P = .024, P = .004, and P = .039, respectively). No difference was found between the 2 groups in terms of tumor size, bilaterality, extrathyroidal invasion, lymph node metastasis, disease stage, or response to treatment (P > .05).ConclusionThe results of the present study demonstrated that the coexistence of PTC and CLT is very frequent. Patients with the coexistence of PTC and CLT were diagnosed at a younger age, and the thyroid-stimulating hormone level was higher in these patients. Contrary to previous studies, no positive effect of the CLT and PTC combination was detected on any clinicopathologic factor. In addition, lymphovascular and perineural invasions, which had negative effects on prognosis, were more common in the group with CLT.     

Phenotype Prevalence and Health-Related Quality of Life of Lebanese Women With Polycystic Ovary Syndrome

ObjectivePolycystic ovary syndrome (PCOS) is one of the most common endocrine disorders. Our study aimed to assess, for the first time, the phenotype prevalence and the health-related quality of life of Lebanese women with PCOS.MethodsThis was a cross-sectional study conducted on 322 Lebanese women with PCOS, using a questionnaire containing sociodemographic data, comorbidities, disease-related clinical questions, and the validated PCOS questionnaire (PCOSQ). The quality of life mean scores and phenotypes were compared and correlated among the different sociodemographic data, comorbidities, and disease-related questions.ResultsPhenotype A (67%) was the most common phenotype. High waist circumference and higher Body Mass Index (BMI) were reported mostly in classic phenotypes in comparison with nonclassic (P < .05). The mean total score of all PCOSQ domains was 3.61 ± 1.60. The mean score for each domain (from the greatest to the least serious concern) was menstrual problems (3.31 ± 1.26), emotion (3.33 ± 1.22), weight (3.41 ± 2.12), body hair (3.86 ± 1.79), and infertility (4.15 ± 1.61). Age was negatively correlated only to weight domain score (r = ?0.17, P = .002). BMI was associated only with emotion and weight domain scores (P = .017 and P < .001, respectively). A bigger impairment in nearly all subscales of the PCOSQ in patients presenting with abdominal obesity, glucose intolerance, and increased blood pressure was noted (P < .05).ConclusionMost Lebanese women with PCOS present phenotype A and have a serious impairment in their health-related quality of life, particularly in the menstrual and emotional domains. This highlights the need for community and individual support.     

Thyroid-Associated Ophthalmopathy: Preliminary Study Using T2 Mapping to Characterize Intraorbital Optic Nerve Changes Before Dysthyroid Optic Neuropathy

ObjectiveTo evaluate the performance of T2 mapping in detecting intraorbital optic nerve (ON) changes in patients with thyroid-associated ophthalmopathy (TAO) before the onset of dysthyroid optic neuropathy (DON).MethodsThirty-five patients with TAO and without DON (21 active, 14 inactive) and 21 healthy controls (HCs) were enrolled. Magnetic resonance imaging-derived parameters of T2 relaxation time (T2RT) at the intraorbital ON, extraocular muscle (EOM), orbital fat, exophthalmos, summed thickness of EOMs, orbital fat thickness, and clinical variables were compared. Correlations between T2RT at the ON and other variables were assessed.ResultsPatients with TAO showed significantly higher T2RTs at the intraorbital ON than HCs (P < .001). Patients with active TAO had significantly higher T2RTs than those with inactive TAO and HCs (P < .001). Differences between patients with inactive TAO and HCs were insignificant (P > .05/3). T2RT at the intraorbital ON was positively correlated with clinical activity score, modified NOSPECS score, T2RT at EOM, exophthalmos, and summed thickness of EOMs in the TAO group (P ≤ .003) and negatively correlated with visual acuity (P = .033) and visual field indices (P = .030) in patients with active TAO. A T2RT cutoff of 82.9 ms for the intraorbital ON distinguished active TAO and healthy eyes optimally (area under the curve, 0.800; sensitivity, 85.7%; specificity, 64.3%).ConclusionT2RT detects disturbance in the intraorbital ON in patients with TAO, especially active TAO, before DON develops. T2 mapping has a potential for noninvasive evaluation of ON changes in patients with TAO.