Ana E. Espinosa De Ycaza

Thyroid hormone treatment among pregnant women with subclinical hypothyroidism: US national assessment

Objective To estimate the effectiveness and safety of thyroid hormone treatment among pregnant women with subclinical hypothyroidism. Design Retrospective cohort study. Setting Large US administrative database between 1 January 2010 and 31 December 2014. Participants 5405 pregnant women with subclinical hypothyroidism, defined as untreated thyroid stimulating hormone (TSH) concentration 2.5-10 mIU/L. Exposure Thyroid hormone therapy. Main outcome measure Pregnancy loss and other pre-specified maternal and fetal pregnancy related adverse outcomes. Results Among 5405 pregnant women with subclinical hypothyroidism, 843 with a mean pre-treatment TSH concentration of 4.8 (SD 1.7) mIU/L were treated with thyroid hormone and 4562 with a mean baseline TSH concentration of 3.3 (SD 0.9) mIU/L were not treated (P<0.01). Pregnancy loss was significantly less common among treated women (n=89; 10.6%) than among untreated women (n=614; 13.5%) (P<0.01). Compared with the untreated group, treated women had lower adjusted odds of pregnancy loss (odds ratio 0.62, 95% confidence interval 0.48 to 0.82) but higher odds of preterm delivery (1.60, 1.14 to 2.24), gestational diabetes (1.37, 1.05 to 1.79), and pre-eclampsia (1.61, 1.10 to 2.37); other pregnancy related adverse outcomes were similar between the two groups. The adjusted odds of pregnancy loss were lower in treated women than in untreated women if their pre-treatment TSH concentration was 4.1-10 mIU/L (odds ratio 0.45, 0.30 to 0.65) but not if it was 2.5-4.0 mIU/L (0.91, 0.65 to 1.23) (P<0.01). Conclusion Thyroid hormone treatment was associated with decreased risk of pregnancy loss among women with subclinical hypothyroidism, especially those with pre-treatment TSH concentrations of 4.1-10 mIU/L. However, the increased risk of other pregnancy related adverse outcomes calls for additional studies evaluating the safety of thyroid hormone treatment in this patient population.

How to Measure Adipose Tissue Insulin Sensitivity

Context and Objective Adipose tissue insulin resistance may cause hepatic and skeletal muscle insulin resistance by releasing excess free fatty acids (FFAs). Because no consensus exists on how to quantify adipose tissue insulin sensitivity we compared three methods for measuring adipose tissue insulin sensitivity: the single step insulin clamp, the multistep pancreatic clamp, and the adipose tissue insulin resistance index (Adipo-IR). Design and Participants We studied insulin sensitivity in 25 adults by measuring the insulin concentration resulting in 50% suppression of palmitate flux (IC50) using both a multistep pancreatic clamp and a one-step hyperinsulinemic-euglycemic clamp. Palmitate kinetics were measured using a continuous infusion of [U-13C]palmitate. Adipo-IR was calculated from fasting insulin and fasting FFA concentrations. Results Adipo-IR was reproducible (sample coefficient of variability, 10.0%) and correlated with the IC50 measured by the multistep pancreatic clamp technique (r, 0.86; P < 0.001). Age and physical fitness were significant predictors of the residual variation between Adipo-IR and IC50, with a positive relationship with age (r, 0.47; P = 0.02) and a negative association with VO2 peak (r, -0.46; P = 0.02). Likewise, IC50 measured by the multistep pancreatic clamp technique correlated with IC50 measured using the one-step hyperinsulinemic-euglycemic clamp technique (r, 0.73; P < 0.001). Conclusion Adipo-IR and the one-step hyperinsulinemic-euglycemic clamp technique using a palmitate tracer are good predictors of a gold standard measure of adipose tissue insulin sensitivity. However, age and physical fitness systematically affect the predictive values. Although Adipo-IR is suitable for larger population studies, the multistep pancreatic clamp technique is probably needed for mechanistic studies of adipose tissue insulin action.

IMAGE-GUIDED THERMAL ABLATION OF ADRENAL METASTASES: HEMODYNAMIC AND ENDOCRINE OUTCOMES

OBJECTIVE Image-guided thermal ablation of adrenal metastases has been increasingly used for local tumor control. This procedure has been associated with hypertensive urgency; however, endocrine complications have not been clearly described. Our objective was to assess the hemodynamic behavior and risk for adrenal insufficiency related to adrenal ablation. Additionally, we sought to understand the utility of preprocedural α-blockade to prevent periprocedural hemodynamic complications. METHODS This was a retrospective study of patients undergoing image-guided ablation of adrenal metastases between 2003 and 2015 at our institution. We reviewed electronic medical records to obtain clinical information, including α-blockade preparation, periprocedural hemodynamic parameters, interventions, and postablation adrenal function. RESULTS Thermal ablation was performed in 58 patients (46 men [79%]; median age, 66 years) with 60 adrenal metastases ablated in 62 sessions. Alpha-blockade was used pre-ablation in 49 (79%) sessions; it was associated with less hypertensive urgency (23 [47%] for α-blockade vs. 10 [77%] for no α-blockade; P = .048) but higher need for vasopressors (22 [45%] for α-blockade vs. 1 [8%] for no α-blockade; P = .02) during ablation. Adrenal insufficiency occurred in 13 (22%) patients, of whom 10 had history of contralateral adrenalectomy or metastases, and only 3 of 13 had a normal-appearing contralateral adrenal gland. CONCLUSION Hemodynamic changes during ablation of adrenal metastases are common. Pre-ablation α-blockade decreases the severity of the hypertensive episode, at the expense of higher need for vasopressors periprocedurally. Adrenal function should be assessed after adrenal metastasis ablation, as adrenal insufficiency may occur after such treatment. ABBREVIATIONS ACTH = adrenocorticotropic hormone BP = blood pressure CT = computed tomography DBP = diastolic blood pressure HR = heart rate IQR = interquartile range IV = intravenous MAP = mean arterial pressure MWA = microwave ablation RFA = radiofrequency ablation SBP = systolic blood pressure.

Comparison of Methods for Analyzing Human Adipose Tissue Macrophage Content: Analysis of Adipose Tissue Inflammation

The relationship between inflammation, obesity, and adverse metabolic conditions is associated with adipose tissue macrophages (ATM). This study compared the measurements of human ATM using flow cytometry, immunohistochemistry (IHC), and real‐time polymerase chain reaction (RT‐PCR) of ATM markers.

Effects of Increasing Levothyroxine on Pregnancy Outcomes in Women with Uncontrolled Hypothyroidism

Uncontrolled hypothyroidism has been associated with an increased risk of adverse pregnancy outcomes. We aimed to assess the effectiveness of increasing levothyroxine (LT4) dose on reducing the risk of adverse outcomes for pregnant women with TSH level greater than the recommended 1st trimester limit.

Physical exam in asymptomatic people drivers the detection of thyroid nodules undergoing ultrasound guided fine needle aspiration biopsy

Understanding epidemiology and the factors leading to thyroid nodule diagnosis might help alter the course of the thyroid cancer epidemic. Population-based study using the Rochester Epidemiology Project database between 2003 and 2006. Patients with thyroid nodules who underwent ultrasound guided fine needle aspiration biopsy were included. We identified 453 patients with 520 thyroid nodules undergoing ultrasound guided fine needle aspiration. Patients were mostly women (n: 349, 77 %) with a mean age of 52 (standard deviation 17) years. The age-adjusted and sex-adjusted incidence of ultrasound guided fine needle aspiration-thyroid nodules between 2003 and 2006 was 89 (95 % confidence interval, 80–97) per 100,000 person-years; the incidence in women was 130 (95 % confidence interval, 117–144), and for men 43 (95 % confidence interval, 35–52) per 100,000 person-years. The incidence of ultrasound guided fine needle aspiration-thyroid nodules increased by 42 %, from 68 (95 % confidence interval, 54–82) in 2003 to 97 (95 % confidence interval, 80–113) per 100,000 person-years in 2006. The group with the highest incidence was patients between 70 and 79 years of age, 258 per 100,000 person-years. Most ultrasound guided fine needle aspiration-thyroid nodules were found in asymptomatic patients (n: 371, 82 %) by physical examination (n: 197, 43 %) or on imaging studies performed for non-thyroid issues (n: 108, 24 %). Women were more likely to have nodules detected by palpation (45 %), whereas imaging and physical examination contributed similarly in men (39 and 38 %). There is a large and rapid increase in the ultrasound guided fine needle aspiration-thyroid nodules, particularly among women and elderly patients which mirrors the trends observed in thyroid cancer. Most thyroid nodules were found in asymptomatic patients as a result of routine physical examination or imaging.

The Role of Medical Management for Nodular Hyperthyroidism

Toxic multinodular goiter (TMNG) and autonomously functioning thyroid nodules (AFTN) are common causes of hyperthyroidism. We discuss the nonsurgical management of TMNG and AFTN.

Effect of Dehydroepiandrosterone and Testosterone Supplementation on Systemic Lipolysis

CONTEXT Dehydroepiandrosterone (DHEA) and T hormones are advertised as antiaging, antiobesity products. However, the evidence that these hormones have beneficial effects on adipose tissue metabolism is limited. OBJECTIVE The objective of the study was to determine the effect of DHEA and T supplementation on systemic lipolysis during a mixed-meal tolerance test (MMTT) and an iv glucose tolerance test (IVGTT). DESIGN This was a 2-year randomized, double-blind, placebo-controlled trial. SETTING The study was conducted at a general clinical research center. PARTICIPANTS Sixty elderly women with low DHEA concentrations and 92 elderly men with low DHEA and bioavailable T concentrations participated in the study. INTERVENTIONS Elderly women received 50 mg DHEA (n = 30) or placebo (n = 30). Elderly men received 75 mg DHEA (n = 30), 5 mg T (n = 30), or placebo (n = 32). MAIN OUTCOME MEASURES In vivo measures of systemic lipolysis (palmitate rate of appearance) during a MMTT or IVGTT. RESULTS At baseline there was no difference in insulin suppression of lipolysis measured during MMTT and IVGTT between the treatment groups and placebo. For both sexes, a univariate analysis showed no difference in changes in systemic lipolysis during the MMTT or IVGTT in the DHEA group and T group when compared with placebo. There was no change in the results after adjusting for the resting energy expenditure, except for a small, but significant (P = .03) lowering of MMTT nadir palmitate rate of appearance in women who received DHEA. CONCLUSION In elderly individuals with concentrations of DHEA (men and women) or T (men) below the normal range for young adults, supplementation of these hormones has no effect on insulin suppression of systemic lipolysis.

Approach to the management of rare clinical presentations of macroprolactinomas in reproductive-aged women

Objective To describe 2 cases of macroprolactinomas with atypical presentation in women desiring pregnancy that illustrate important considerations in the management approach for macroprolactinomas in reproductive-aged women. Patient(s) Case 1 was a 26-year-old woman referred to our institution for possible tumor resection after pituitary apoplexy during her first pregnancy. Instead, she underwent treatment with cabergoline for a year with goals of normalization of prolactin and decrease in tumor size to < 1 cm before trying to conceive. Case 2 was an 18-year-old woman with a macroprolactinoma intolerant to dopamine agonists. She underwent stereotactic radiosurgery, with marked reduction in tumor size and normalization of prolactin levels. She conceived and delivered a healthy infant 3 years after radiosurgery. Conclusion Management of macroprolactinomas in women desiring pregnancy requires careful consideration of alternatives to surgery which could impair pituitary function and fertility and awareness of treatment goals that can minimize the risks for pituitary apoplexy and vision loss during pregnancy. It is important to increase awareness of these options prior to initiation of treatment and conception.