Vascularity-Targeted Percutaneous Ethanol Injection of Toxic Thyroid Adenomas: Outcomes of A Feasibility Study Performed in the USA

Objective: The recommended treatment options for toxic adenoma (TA) in the USA are radioactive iodine ablation and surgical resection, with continued observation for pre-toxic adenoma (PTA). Percutaneous ethanol ablation (PEI) has proven efficacy in the treatment of TA and is widely available in Europe but not in the USA.Methods: Retrospective analysis was performed of all patients who underwent PEI for TA/PTA at the University of Utah, from January 2010 to 2018. Ultrasound-guided PEI, with injections targeting power Doppler–mapped blood vessels within the adenomas, was conducted. Functionality was confirmed using thyroid scintigraphy prior to PEI.Results: Eighteen adults (15 female) underwent PEI. Mean age was 41 ± 13.7 years. Baseline thyroid-stimulating hormone (TSH) was suppressed (0.06 ± 0.09 mU/L), with normal free thyroxine (FT4) 1.43 ± 0.39 ng/dL. Median nodule volume was 5.7 cm³ (interquartile range &lsqb;IQR], 4.8 to 7.7 cm³). Seventy-eight percent (n = 14) underwent two or less PEI sessions. Median volume of ethanol used was 0.46 mL/mL nodule volume (IQR, 0.3 to 0.6 mL). There was a significant increase in TSH concentrations within the first 3 months after PEI (0.06 ± 0.09 mU/L vs. 1.22 ± 1.88 mU/L; P = .02), with a concomitant significant decrease in FT4 concentrations (1.43 ± 0.39 ng/day vs. 1.13 ± 0.25 ng/day; P<.01). Significant nodular volume reduction was observed following PEI (median 5.7 cm³ &lsqb;IQR 4.8–7.7 cm³] vs. 2.5 cm³ &lsqb;IQR 2.0–7.8 cm³]; P<.01).Conclusion: Vascularity-targeted PEI is safe and effective for treating PTA and TA. This unique approach required lower injected alcohol volume and fewer injections for therapeutic success.Abbreviations: ATA = American Thyroid Association; FT4 = free thyroxine; IQR = interquartile range; PD = power Doppler; PEI = percutaneous ethanol injection; PTA = pre-toxic adenoma; RAI = radioactive iodine ablation; RFA = radiofrequency ablation; TA = toxic adenoma; TT3 = total triiodothyronine; US = ultrasound     

Health-Related Quality of Life After Percutaneous Radiofrequency Ablation of Cold,Solid, Benign Thyroid Nodules: A 2-Year Follow-Up Study in 40 Patients

Objective: We studied the impact of radiofrequency ablation (RFA) on health-related quality of life (HRQL) in patients with benign thyroid nodules (TN) in a 2-year follow-up.Methods: Forty patients (35 women and 5 men; age, 54.9 ± 14.3 years) with cold thyroid solitary nodules or a dominant nodule within a normofunctioning multi-nodular goiter (volume range, 6.5 to 90.0 mL) underwent RFA of thyroid nodular tissue under ultrasound real-time assistance.Results: Data are mean and standard deviation. Energy delivered was 37,154 ± 18,092 joules, with an output power of 37.4 ± 8.8 watts. Two years after RFA, nodule volume decreased from 30.0 ± 18.2 mL to 7.9 ± 9.8 mL (-80.1 ± 16.1% of initial volume; P<.0001). Thyroid-stimulating hormone, free triiodothyronine, and free thyroxine levels remained stable. Symptom score measured on a 0- to 10-cm visual analogue scale (VAS) declined from 5.6 ± 3.1 cm to 1.9 ± 1.3 cm (P<.0001). Cosmetic score (VAS 0–10 cm) declined from 5.7 ± 3.2 cm to 1.9 ± 1.5 cm (P<.0001). Two patients became anti-thyroglobulin antibody–positive. Physical Component Summary (PCS)-12 improved from 50.4 ± 8.9 to 54.5 ± 5.3, and the Mental Component Summary (MCS)-12 improved from 36.0 ± 13.3 to 50.3 ± 6.3 (P<.0001 for both score changes).Conclusion: Our 2-year follow-up study confirms that RFA of benign TNs is effective in reducing nodular volume and compressive and cosmetic symptoms, without causing thyroid dysfunction or life-threatening complications. Our data indicate that the achievement of these secondary endpoints is associated with HRQL improvement, measured both as PCS and MCS.Abbreviations: fT₃ = free triiodothyronine fT₄ = free thyroxine HRQL = health-related quality of life MCS-12 = Mental Component Summary-12 PLA = percutaneous laser ablation PCS-12 = Physical Component Summary-12 RF = radiofrequency RFA = radiofrequency ablation SF-12 = Short-Form 12 Health Survey TgAb = anti-thyroglobulin antibody TN = thyroid nodule TRAb = anti-TSH-receptor antibody TSH = thyroid-stimulating hormone US = ultrasound VAS = visual analogue scale     

Effectiveness of Percutaneous Ethanol Injection in Nodular Diseases of the Thyroid Gland: 10-Year Follow-Up

Objective: Percutaneous ethanol injection (PEI) of thyroid cysts is not considered to be the standard of care in Kazakhstan, although thyroid nodules are highly prevalent. Patients with cystic nodules >3 cm typically undergo surgery with high rate of disability due to postsurgical hypothyroidism. Adoption of PEI as a standard of care will help reduce the number of unnecessary surgical interventions. The objective of this study was to assess effectiveness of PEI in patients with thyroid cysts and colloid nodules with 10 years of follow-up.Methods: A total of 257 patients were treated with PEI and have been followed for 10 ± 1.2 years. All patients had baseline labs (thyroid-stimulating hormone [TSH] and free thyroxine [FT4] levels) and ultrasonography prior to the procedure. The Short Form Health Survey (SF-36) assessing quality of life (QoL) was performed 12 months after the last PEI procedure.Results: At baseline, all patients had normal levels of FT4 and TSH that remained within normal limits throughout the follow-up period. Ultrasound evaluation performed over 3 months after PEI demonstrated significant volumetric reduction from 18.4 to 0.2 mL (P<.001) in cystic nodules and from 10.2 to 1.1 cm³ (P<.001) in colloid nodules. Patients who underwent the procedure had better SF-36 survey scores compared to their baseline QoL scores.Conclusion: PEI for cystic and colloid thyroid nodules could be considered as an effective and safe procedure. It enables up to a 100% reduction of nodule volume and has a low rate of adverse effects.Abbreviations: FT4 = free thyroxine; PEI = percutaneous ethanol injection; QoL = quality of life; SF-36 = Short Form Health Survey; TSH = thyroid-stimulating hormone; US = ultrasound; VRR = volume reduction rate     

No Benefit of Dedicated Thyroid Nodule Screening in Patients with Acromegaly

Objective: Acromegaly results from the excessive production of growth hormone and insulin-like growth factor-1. While there is up to a 2-fold increased prevalence of thyroid nodules in patients with acromegaly, the incidence of thyroid cancer in this population varies from 1.6 to 10.6% in several European studies. The goal of our study was to determine the prevalence of thyroid nodules and thyroid cancer among patients with acromegaly at a large urban academic medical center in the United States (U.S.).Methods: A retrospective chart review was performed of all patients with acromegaly between 2006–2015 within the University of California, Los Angeles health system. Data were collected regarding patient demographics, thyroid ultrasounds, thyroid nodule fine needle aspiration (FNA) biopsy cytology, and thyroid surgical pathology.Results: In this cohort (n = 221, 49.3% women, mean age 53.8 ± 15.2 &lsqb;SD] years, 55.2% Caucasian), 102 patients (46.2%) underwent a thyroid ultrasound, from which 71 patients (52.1% women, mean age 52.9 ± 15.2 &lsqb;SD] years, 56.3% Caucasian) were found to have a thyroid nodule. Seventeen patients underwent a thyroid nodule FNA biopsy and the results revealed 12 benign biopsies, 1 follicular neoplasm, 3 suspicious for malignancy, and 1 papillary thyroid cancer (PTC), from which 6 underwent thyroidectomy; PTC was confirmed by surgical pathology for all cases (8.5% of all nodules observed).Conclusion: In this sample, the prevalence of thyroid cancer in patients with acromegaly and coexisting thyroid nodules is similar to that reported in the general U.S. population with thyroid nodules (7 to 15%). These findings suggest that there is no benefit of dedicated thyroid nodule screening in patients newly diagnosed with acromegaly.Abbreviations: AACE = American Association of Clinical Endocrinologists; ATA = American Thyroid Association; DTC = differentiated thyroid cancer; FNA = fine needle aspiration; GH = growth hormone; IGF-1 = insulin-like growth factor-1; PTC = papillary thyroid cancer; U.S. = United States     

Higher Serum Osteoprotegerin Levels In Subjects With Thyroid Nodules

Objective: A recent study demonstrated that osteoprotegerin (OPG) could be expressed both in benign and malignant thyroid tissue. However, epidemiologic studies investigating the association between serum OPG and thyroid nodules are not available. The objective of this study was to determine whether serum OPG is associated with thyroid nodules.Methods: We measured serum OPG, total triiodothyronine, total thyroxine, free triiodothyronine, free thyroxine, thyrotropin, antithyroid peroxidase antibodies, thyrotropin-receptor antibodies, antithyroglobulin antibodies, and thyroglobulin in 1,120 Chinese participants in a cross-sectional community-based study performed in downtown Shanghai. Thyroid nodule was diagnosed by thyroid ultrasonographic examination.Results: The serum OPG levels were significantly increased in nodule-positive subjects compared to nodule-negative subjects (2.8 ± 1.2 ng/mL versus 2.1 ± 1.0 ng/mL; P<.001). After multiple adjustments, the odds ratios were substantially higher for thyroid nodule (odds ratio, 3.09; 95% confidence interval, 1.60 to 5.97) in the highest OPG quartile compared with those in the lowest quartile. These associations remained significant after further adjustment for potential confounders. Multivariate linear regression analysis demonstrated that age (P = .015) and OPG (P = .003) were independently associated with thyroid nodule.Conclusion: Serum OPG is elevated significantly in subjects with thyroid nodules among middle-aged and elderly individuals.Abbreviations:BMI = body mass indexCI = confidence intervalDBP = diastolic blood pressureFT3 = free triiodothyronineFT4 = free thyroxineOPG = osteoprotegerinOR = odds ratioRANKL = receptor activator of nuclear factor kappa ligandSBP = systolic blood pressureTg = thyroglobulinTGAb = antithyroglobulin antibodyTPOAb = antithyroid peroxidase antibodyTRAb = thyrotropin-receptor antibodyTRAIL = Tumor necrosis factor–related apoptosis-inducing ligandTSH = thyrotropinTT3 = total triiodothyronineTT4 = total thyroxine     

Thyroid Hormone Replacement Reduces The Risk of Cardiovascular Diseases in Diabetic Nephropathy Patients With Subclinical Hypothyroidism

Objective: Patients with diabetic nephropathy (DMN) have an increased risk of cardiovascular disease (CVD). However, strategies to reduce this risk are limited. Thyroid hormone replacement therapy (THRT) in patients with hypothyroidism has been shown to reduce several surrogate markers of CVD. Therefore, we performed a study to determine if THRT would reduce CVD risk in patients with subclinical hypothyroidism (SCH) and DMN.Methods: This was a retrospective, nonrandomized study of patients with type 2 diabetes, DMN, and SCH. Those with known thyroid dysfunction or taking THRT at baseline were excluded. Patients receiving THRT for at least 180 days were included in the THRT group, while the remaining patients were assigned to the non-THRT group. The primary outcome was CVD events, which included coronary syndrome, cerebrovascular events, and peripheral artery diseases.Results: Among the 257 patients, 83 (32.3%) were in the THRT group. The mean ages were 62.7 ± 12.3 and 66.8 ± 12.4 years in the THRT and non-THRT groups, respectively. The corresponding numbers of male patients were 32 (40.0%) and 94 (53.1%). During a mean follow-up of 38.0 ± 29.2 months, 98 CVD events were observed. Acute coronary syndrome and cerebrovascular event prevalence rates were lower in the THRT group than the non-THRT group, but there was no difference for peripheral artery diseases. Multivariate Cox analysis revealed that THRT was independently associated with a decreased CVD event risk.Conclusion: THRT may decrease the risk of CVD in DMN patients with SCH. Randomized trials are needed to verify this finding.Abbreviations:CV = cardiovascularDMN = diabetic nephropathyeGFR = estimated glomerular filtration ratefT4 = free thyroxineHbA1c = glycosylated hemoglobinHR = hazard ratiohs-CRP = high-sensitivity C-reactive proteinLDL-C = low-density lipoprotein cholesterolSCH = subclinical hypothyroidismT2DM = type 2 diabetesTHRT = thyroid hormone replacement therapyTSH = thyroid-stimulating hormone     

Alterations In Thyroid Hormone Levels Following Growth Hormone Replacement Exert Complex Biological Effects

Objective: Alterations in the thyroid axis are frequently observed following growth hormone (GH) replacement, but uncertainty exists regarding their clinical significance. We aimed to compare fluctuations in circulating thyroid hormone levels, induced by GH, to changes in sensitive biological markers of thyroid hormone action.Methods: This was a prospective observational clinical study. Twenty hypopituitary men were studied before and after GH replacement. Serum thyroid-stimulating hormone (TSH), thyroid hormones, and insulin-like growth factor 1 were measured. Changes in thyroid hormone concentrations were compared to alterations in resting metabolic rate and cardiac time intervals. Health-related quality of life (QOL) was assessed by disease-sensitive and generic questionnaires.Results: Following GH replacement, free thyroxine concentration declined and free triiodothyronine level increased. Resting energy expenditure increased, particularly in subjects with profound hypopituitarism, including TSH deficiency (16.73 ± 1.75 kcal/kg/min vs. 17.96 ± 2.26 kcal/kg/min; P = .01). Alterations in the thyroid axis were more pronounced in subjects with a low/normal baseline respiratory quotient (RQ) who experienced a paradoxical rise in RQ (0.81 vs. 0.86; P = .01). Subjects with a high baseline RQ experienced a slight but nonsignificant fall in RQ without alteration in thyroid axis. The isovolumetric contraction time was shortened during the study; however, this did not reach statistical significance. Improvements in QOL were observed despite alterations in thyroid axis.Conclusion: Changes in the thyroid axis following GH replacement are associated with complex tissue-specific effects. These fluctuations may induce a hypothyroid phenotype in some tissues while appearing to improve the biological action of thyroid hormone in other organs.Abbreviations: AGHDA = Assessment of Growth Hormone Deficiency in Adulthood; CHOox = carbohydrate oxidation; ET = ejection time; fT3 = free triiodothyronine; fT4 = free thyroxine; GH = growth hormone; GHD = growth hormone deficiency; HB-RQ = high baseline respiratory quotient; HPT = hypothalamic-pituitary-thyroid; ICT = isovolumetric contraction time; IGF-1 = insulin-like growth factor 1; IRT = isovolumetric relaxation time; LB-RQ = low baseline respiratory quotient; LV = left ventricular; NHP = Nottingham Health Profile; QOL = quality of life; REE = resting energy expenditure; RQ = respiratory quotient; rT3 = reverse triiodothyronine; SF-36 = Short Form 36; TSH = thyroid-stimulating hormone; T3 = triiodothyronine; T4 = thyroxine; TT3 = total triiodothyronine; TT4 = total thyroxine     

Drivers of the Decision to Biopsy and Follow-Up of Small Suspicious Thyroid Nodules

Objective: In 2015, the updated American Thyroid Association (ATA) guidelines recommended observation for suspicious subcentimeter thyroid nodules, based on their indolent course. We aimed to evaluate the frequency of biopsy in suspicious thyroid nodules since the introduction of these guidelines, including factors contributing to clinical decision-making in a tertiary care center.Methods: We conducted a retrospective study of patients in the Mayo Clinic, Rochester, Minnesota, with new, subcentimeter suspicious thyroid nodules (by report or by sonographic features) between March, 2015, and November, 2017, not previously biopsied.Results: We identified 141 nodules in 129 patients: mean age 58.1 ± 14.1 years, 74% female, 87% Caucasian. The frequency of biopsy in suspicious thyroid nodules was 39%. Ultrasound features that were the strongest predictors for biopsy on multivariate analysis included: nodule volume (odds ratio [OR] 37.3 [7.5–188.7]), radiology recommendation for biopsy (OR 2.6 [1.8–3.9]) and radiology report of the nodule as “suspicious” (OR 2.1 [1.4–3.2]). Patient’s age and degree of comorbidities did not change the likelihood for biopsy, nor did it vary by clinician type or how the nodule was initially found (incidentally or not incidentally). Among 86 nodules that were not biopsied, 41% had no specific follow-up recommendations.Conclusion: One third of suspicious thyroid nodules underwent biopsy since the release of updated ATA guidelines. Factors driving thyroid biopsy seem to be associated with nodule characteristics but not with patient factors including age and comorbidities. Further studies and development of decision aides may be helpful in providing individualized approaches for suspicious thyroid nodules.Abbreviations: ATA = American Thyroid Association; OR = odds ratio     

Autoimmune Thyroid Disease: A Risk Factor for Thyroid Cancer

ObjectiveTo examine the relationship between clinical markers of autoimmune thyroid disease and the risk of thyroid cancer in patients with thyroid nodules.MethodsA retrospective cohort analysis was performed in a single clinical practice. In 2, 500 consecutive patients, fine-needle aspiration biopsy (FNAB) was performed on all 3, 658 ultrasonography-positive thyroid nodules that were ≥ 1.0 cm in diameter or ≥ 0.5 cm in diameter with ultrasound features suspicious for thyroid cancer. Serum concentrations of thyroglobulin antibodies (TgAb), thyroid peroxidase antibodies, and thyroid-stimulating hormone were measured before FNAB. Diagnosis of thyroid cancer was based on pathologic analysis of thyroidectomy tissue. Associations of thyroid cancer with the independent variables were determined by multivariate logistic regression analysis and reported as the adjusted odds ratio (OR) with the 95% confidence interval (CI).ResultsThere were 202 patients with malignant thyroid nodules, 51 patients with microscopic unsuspected thyroid cancer distal to the nodule under investigation (found at thyroidectomy), and 2, 247 patients with benign thyroid nodules. To evaluate the association of clinical markers for autoimmune thyroid disease with thyroid cancer, we included all 253 patients with thyroid cancer in the malignant cohort. Thyroid cancer was associated with elevated levels of TgAb (OR = 1.57; CI = 1.11 to 2.23) and age < 55 years (OR = 2.01; CI = 1.45 to 2.78), and a strong trend was demonstrated for association with male sex (OR = 1.45; CI = 0.99 to 2.12). Thyroid cancer was not associated with elevated levels of thyroid peroxidase antibodies.ConclusionIn patients who have thyroid nodules with indications for FNAB, elevated levels of TgAb are associated with thyroid cancer. (Endocr Pract. 2011;17: 201-209)     

Assay of Free Thyroxine and Free Triiodothyronine in Fine-Needle Aspiration of Thyroid Nodules: a Useful and Low-Cost Assessment

ObjectiveTo evaluate whether analysis of thyroid hormones in fine-needle aspiration (FNA) of thyroid nodules can provide information about the functional status and the nature of the nodules.MethodsWe studied 4 groups of patients: group 1, 17 patients with autonomous hyperfunctioning thyroid nodules; group 2, 52 patients with cold nonfunctioning thyroid nodules; group 3, 12 patients with malignant thyroid nodules; and group 4 (control group), 10 patients with nonthyroid nodular lesions (enlarged parathyroid glands or lymph nodes). The assay of thyroid hormones was performed in FNA after the washing of needles and, with patient consent, also in normal thyroid parenchyma.ResultsThe free thyroxine (FT₄) and free triiodothyronine (FT₃) values were remarkably high in group 1 (mean, 5.5 ± 0.53 ng/dL and 27.6 ± 3.1 pg/mL, respectively; P < 0.05 versus group 2 and group 4, the control group). The levels of FT₄ and FT₃ were very low in group 3 (< 0.2 ng/dL and < 1.0 pg/mL, respectively; P < 0.05 versus group 2). Thyroglobulin values in FNA specimens were much higher than the normal range in human serum, but no significant differences were found between the various groups. The control group had low levels of FT₄ and FT₃ (< 0.2 ng/dL and < 1.0 pg/mL, respectively) in conjunction with low levels of thyroglobulin, whereas parathyroid hormone levels were high in parathyroid nodules.ConclusionThese results show that assay of FT₄ and FT₃ in FNA can yield information about the functional status of thyroid nodules and, indirectly, about the nature of nodules. In this era of sophisticated new molecular markers in FNA cytology, this low-cost diagnostic method can be readily performed in every laboratory. (Endocr Pract. 2004;10:311-316)     

Hormone Substitution after Gastric Bypass Surgery in Patients with Hypopituitarism Secondary to Craniopharyngioma

Objective: Craniopharyngiomas (CPs) are benign brain tumors presenting frequently in childhood and are treated by surgery with or without radiotherapy. About 50% of cured patients suffer from eating disorders and obesity due to hypothalamic damage, as well as hypopituitarism, necessitating subsequent hormone substitution therapy. Gastric bypass surgery has been reported to be an efficient treatment strategy for morbid hypothalamic obesity. However, so far it is unknown whether oral hormone substitution is affected by impaired intestinal drug absorption, potentially leading to severe hypopituitarism or pituitary crisis.Methods: Four morbidly obese CP patients with panhypopituitarism treated by gastric bypass surgery were included in this retrospective analysis. Dosages of hormone substitution therapy, blood concentrations of hormones, potential complications of impaired drug absorption, and anthropometric characteristics were investigated pre- and postoperatively after 6 to 14 months and 13 to 65 months.Results: In all CP patients (3 female/1 male; baseline body mass index, 49 ± 7 kg/m²), gastric bypass resulted in distinct weight loss (-35 ± 27 kg). In follow-up examinations, mean daily dosage of thyroid hormone (levothyroxine_baseline 156 ± 44 μg/day versus levothyroxine_follow-up 150 ± 30 μg/day), hydrocortisone (hydrocortisone_baseline 29 ± 12 mg/day versus hydrocortisone_follow-up 26 ± 2 mg/day), growth-hormone (somatotropin_baseline 0.9 ± 0.5 mg/day versus somatotropin_follow-up 1.0 ± 0.4 mg/day), and desmopressin (desmopressin_baseline 222 ± 96 μg/day versus desmopressin_follow-up 222 ± 96 μg/day) substitution was unchanged. No patient developed adrenal insufficiency. Oral thyroid/hydrocortisone absorption testing performed in 1 patient indicated sufficient gastrointestinal drug absorption after bariatric surgery.Conclusion: Our preliminary results suggest that oral hormone substitution therapy is not impaired following gastric bypass operation in CP patients with morbid obesity, indicating that it might be a safe and effective treatment strategy.Abbreviations:BMI = body mass indexCP = craniopharyngiomafT4 = free thyroxineGH = growth hormoneIGF-1 = insulin-like growth factor 1     

Markedly Delayed Insulin Secretion and a High Rate of Undetected Overt Diabetes Characterize Glucose Metabolism in Adult Patients with Cystic Fibrosis After Lung Transplantation

Objective: Cystic fibrosis–related diabetes (CFRD) is associated with adverse clinical outcomes and should be screened for by an annual oral glucose tolerance test (OGTT). Since pathophysiologic studies have mainly been performed in a pediatric/adolescent, nontransplanted collective, we aimed to assess parameters of insulin secretion and sensitivity in adult cystic fibrosis (CF) patients after lung transplantation (LT).Methods: Twelve adult CF patients after LT without known diabetes (33.3 ± 11.5 years; body mass index &lsqb;BMI] 21.5 ± 3.3 kg/m²) and 8 control subjects matched by age (36.0 ± 6.6 years; P>.05), BMI (22.3 ± 1.5 kg/m²; P>.05), and gender (CON group) underwent a 3-hour OGTT with glucose, insulin, and C-peptide measurements. Parameters of insulin secretion and sensitivity as well as lipid profiles were assessed.Results: In the CF group, 4 patients were diagnosed with overt diabetes (CFRD) compared to CF patients without diabetes (CF-noDM), of whom 6 had indeterminate glycemia with 1-h glucose values >200 mg/dL. The insulin peak after glucose load occurred after 30 minutes in CON, after 90 minutes in CF-noDM, and was missing in CFRD. Insulin sensitivity was comparable between the groups. Beta-cell glucose sensitivity was markedly reduced in CFRD (10.7 ± 5.8 pmol/min*m²*mM), higher in CF-noDM (39.9 ± 23.4 pmol/min*m²*mM), but still significantly lower compared to CON (108.3 ± 53.9 pmol/min*m²*mM; P = .0008). CFRD patients exhibited increased triglyceride levels and decreased high-density lipoprotein levels.Conclusion: Adult CF patients after LT have profound disturbances in glucose metabolism, with a high rate of undetected diabetes and markedly delayed insulin secretion. Curbed beta-cell glucose sensitivity rather than insulin resistance explains postprandial hyperglycemia and is accompanied by abnormalities in lipid metabolism.Abbreviations: AUC = area under the curve; BMI = body mass index; CF = cystic fibrosis; CFRD = cystic fibrosis–related diabetes; CFTR = cystic fibrosis transmembrane-conductance regulator; CF-TX = cystic fibrosis patients who underwent lung transplantation; CGM = continuous glucose monitoring; HbA1c = glycated hemoglobin; HDL = high-density lipoprotein; INDET = indeterminate glycemia; LDL = low-density lipoprotein; LT = lung transplantation; OGIS = oral glucose sensitivity index; OGTT = oral glucose tolerance test; QUICKI = quantitative insulin sensitivity check index     

Impact of Lifestyle Changes During Ramadan on Thyroid Function Tests in Hypothyroid Patients Taking Levothyroxine

Objective: The holy month of Ramadan poses a challenge for levothyroxine-treated patients due to altered eating habits and time restrictions. The aim of this study was to examine the impact of lifestyle changes during Ramadan on thyroid function tests in hypothyroid patients taking levothyroxine in the United Arab Emirates.Methods: Retrospective design whereby levothyroxine-treated hypothyroid patients who had thyroid function tests within 3 months pre-Ramadan and within 2 months post-Ramadan were included. We looked at adherence to levothyroxine, eating pattern, and levothyroxine administration in relation to meal times during Ramadan. Pre- and post-Ramadan thyroid function tests and the potential impact of independent variables using a random-intercept mixed effects linear model were examined.Results: A total of 112 patients (89 females) were recruited in the study, with a mean age ± standard error (SE) of 44.70 ± 1.36 years (range, 19.0 to 79.0 years). The mean thyroid-stimulating hormone (TSH) within 3 months before Ramadan was 1.809 ± 0.094 mIU/L (median, 41.5 days; interquartile range &lsqb;IQR], 25.0 to 73.0 days), while the mean TSH within 2 months post-Ramadan was higher at 3.072 ± 0.312 mIU/L (median, 27.5 days; IQR, 14.0 to 42.0 days). Post-Ramadan, 36 out of 112 patients had a plasma TSH outside of the normal reference range. The independent variable outcomes model showed that older patients and males were more likely to have an increased plasma TSH post-Ramadan. There was no relationship between the time of levothyroxine administration and change in TSH level.Conclusion: Levothyroxine-treated hypothyroid patients showed a significant increase in plasma TSH post-Ramadan, amounting to 2.525 standard deviations, with older patients and males more likely to be affected.Abbreviations: IQR = interquartile range; T4 = thyroxine; TSH = thyroid-stimulating hormone     

Metformin-Sustained Weight Loss and Reduced Android Fat Tissue At 12 Months In Empowir (Enhance The Metabolic Profile Of Women With Insulin Resistance): A Double Blind,Placebo-Controlled,Randomized Trial of Normoglycemic Women with Midlife Weight Gain

Objective: To assess 12-month body weight (BW) and body composition changes in normoglycemic women with midlife weight gain, after dietary and pharmacologic interventions targeting hyperinsulinemia.Methods: EMPOWIR (Enhance the Metabolic Profile of Women With Insulin Resistance; NCT00618072) was a double-blind, placebo-controlled, 12-month trial of women with >20-pound weight gain, normal glucose tolerance test, and increased area-under-the-curve insulin. Subjects (mean ± SD, 46.7 ± 6.5 years of age; body mass index, 30.8 ± 2.8 kg/m²; 50% white) attended 4 nutrition workshops to introduce a novel carbohydrate-modified diet (CMD) and were then randomized to one of three arms for 6 months (phase 1): CMD alone (D), or in combination with metformin (M), or metformin + rosiglitazone (MR), with rerandomization of the D group to one of the active treatment arms (phase 2, months 7 through 12). Repeated measure analysis of variance was used to assess BW at baseline, 6 months, and 12 months in 32 subjects with 12-month data; paired t tests compared baseline and 12-month dual-energy X-ray absorptiometry–derived body composition.Results: Mean (±SD) BW decreased significantly at 12 months in the M arm: 85.1 ± 8.5 kg to 79.8 ± 9.0 kg (P = .0003), with 54% of variance in weight over time explained by M treatment. Mean (±SD) percent android fat decreased significantly in the M and D arms: 53.5 ± 4.8% to 49.3 ± 7.6% (P = .010) and 52.9 ± 6.2% to 48.1 ± 8.7% (P = .021).Conclusion: In combination with a novel carbohydrate modified diet, metformin enhanced 12-month weight loss and improved body composition in ethnically diverse normoglycemic, hyperinsulinemic women with midlife weight gain. These findings suggest that EMPOWIR's easily implemented dietary interventions, alone and in combination with pharmacotherapies that target hyperinsulinemia, merit additional investigation in larger, long-term studies.Abbreviations:ANOVA = analysis of varianceBC = body compositionBW = body weightCMD = carbohydrate-modified dietD = diet alone groupDXA = dual-energy X-ray absorptiometryEMPOWIR = Enhance the Metabolic Profile of Women With Insulin ResistanceM = metformin groupMR = metformin + rosiglitazone group     

Maternal thyroid hormone trajectories during pregnancy and child behavioral problems

There is ample evidence demonstrating the importance of maternal thyroid hormones, assessed at single trimesters in pregnancy, for child cognition. Less is known, however, about the course of maternal thyroid hormone concentrations during pregnancy in relation to child behavioral development. Child sex might be an important moderator, because there are sex differences in externalizing and internalizing behavioral problems. The current study examined the associations between maternal thyroid hormone trajectories versus thyroid assessments at separate trimesters of pregnancy and child behavioral problems, as well as sex differences in these associations. In 442 pregnant mothers, serum levels of TSH and free T4 (fT4) were measured at 12, 24, and 36 weeks gestation. Both mothers and fathers reported on their children's behavioral problems, between 23 and 60 months of age. Latent growth mixture modeling was used to determine the number of different thyroid hormone trajectories. Three trajectory groups were discerned: 1) highest and non-increasing TSH with lowest fT4 that decreased least of the three trajectories; 2) increasing TSH and decreasing fT4 at intermediate levels; 3) lowest and increasing TSH with highest and decreasing fT4. Children of mothers with the most flattened thyroid hormone trajectories (trajectory 1) showed the most anxiety/depression symptoms. The following trimester-specific associations were found: 1) lower first-trimester fT4 was associated with more child anxiety/depression, 2) higher first-trimester TSH levels were related to more attention problems in boys only. A flattened course of maternal thyroid hormone concentrations during pregnancy was a better predictor of child anxiety/depression than first-trimester fT4 levels.     

Does Unilateral Lobectomy Suffice to Manage Unilateral Nontoxic Goiter?

ObjectiveTo evaluate the effectiveness of ipsilateral lobectomy to treat unilateral, nontoxic, benign nodular goiter and to define predictive factors for recurrence.MethodsPatients undergoing thyroid lobectomy for unilateral, nontoxic, benign nodular goiter between 2002 and 2007 were included. Patients were excluded if coincidental thyroid cancer was detected at histopathologic examination and completion thyroidectomy was performed. Potential predictors of recurrence including age; sex; family history; preoperative volume of the thyroid gland; preoperative number, size, and ultrasonography characteristics of the nodules; duration of postoperative follow-up; postoperative use of thyroxine; and histopathologic diagnoses were recorded at baseline. Follow-up visits were scheduled every 3 months during the first year and every 6 months thereafter. Recurrent disease was defined as a hypoechogenic or hyperechogenic nodule larger than or equal to 3 mm detected in the remaining contralateral lobe during ultrasonography. Patients with a thyrotropin value greater than 5 mIU/L received thyroxine. Fineneedle aspiration biopsy was performed for nodules greater than 10 mm or for nodules with characteristics suggestive of malignancy. Reoperation was indicated if a nodule was greater than 3 cm in diameter, posed a risk of malignancy, or caused compression signs or symptoms.ResultsA total of 104 patients were included. Histopathologic diagnoses at initial operation were adenoma in 45 patients, colloidal nodular goiter in 45 patients, and chronic lymphocytic thyroiditis in 14 patients. Average duration of follow-up was 39.75 ± 21.75 months (range, 5-87 months). Recurrence was seen in 63 patients (60.6%). Histopathologic characteristics of the lobectomy material (P <.001), preoperative volume of the thyroid gland (P <.006), and multinodularity (P <.011) were significant predictors of recurrence.ConclusionsHigher preoperative thyroid volume, histopathologic characteristics of nodules, and multinodular disease are associated with an increased risk of recurrence in patients with unilateral nodular goiter. Unilateral lobectomy is an effective therapeutic option with low reoperation rates in unilateral benign thyroid disease. (Endocr Pract. 2010;16:36-41)     

Quality of Life in Patients with Low-Risk Papillary Thyroid Microcarcinoma: Active Surveillance Versus Immediate Surgery

Objective: This study aimed to compare the quality of life (QoL) and psychological issues of patients with papillary thyroid microcarcinoma (PMC) who were under active surveillance (AS) and those who underwent immediate surgery (OP).Methods: This was a cross-sectional study conducted on 347 patients with low-risk PMC who were under AS (n = 298) or who underwent OP (n = 49). They were asked to complete two questionnaires (thyroid cancer–specific health-related QoL [THYCA-QoL] and the Hospital Anxiety and Depression Scale [HADS]). The results between the AS and OP groups were compared.Results: The mean ages of patients in the AS and OP groups were 58.6 ± 12.5 and 58.4 ± 13.1 years (P =.94), respectively, and the male ratios were 34/298 (11%) and 2/49 (4.1%) (P =.14), respectively. The median follow-up periods from diagnosis in the AS and OP groups were 56.5 months (interquartile range [IQR], 32 to 88 months) and 84 months (IQR, 64 to 130 months) (P<.001), respectively. In the THYCA-QoL questionnaire, the OP group had more complaints about “voice” (P<.001), “psychological” (P =.025), “problems with scar” (P<.001), and “gained weight” (P =.047) than the AS group. Other scales of the THYCA-QoL were comparable in the two groups. In the HADS questionnaire, the AS group had significantly better anxiety (P =.020), depression (P =.027), and total scores (P =.014) than the OP group.Conclusion: PMC patients in the OP group had more complaints and were more anxious and depressed than the AS group. These findings suggest that AS is a reasonable alternative to surgery for patients with low-risk PMC from the point of view of QoL and psychology.Abbreviations: AS = active surveillance; CI = confidence interval; HADS = Hospital Anxiety and Depression Scale; LT4 = levothyroxine; OP = immediate surgery; PMC = papillary microcarcinoma; PTC = papillary thyroid carcinoma; QoL = quality of life; STAI = State-Trait Anxiety Inventory; THYCA-QoL = thyroid cancer–specific health-related quality of life; TSH = thyrotropin     

Percutaneous ethanol injection in treatment of benign nonfunctional and hyperfunctional thyroid nodules

In recent years a new method of treatment of thyroid disorders, percutaneous ethanol injection (PEI), has been successfully used as an alternative to surgery for the management of benign nodules. In this study 103 females and 5 males (34.4 +/- 11.3 yrs) with nonfunctional cystic (23) or solid (38) nodules, and also 47 with hyperfunctional solid nodules, were treated with single or repeated ethanol injections. In all patients, the cytological studies, ultrasound evaluation and the levels of free triiodothyronine (fT3), free thyroxine (fT4), and thyrotropin or thyroids-stimulating hormone (TSH) before and after ethanol administration, were determined. The patients were followed up for 12-36 months. The size of the benign nonfunctional nodules was totally reduced in 49.9% of cases with solid and in 60.9% of patients with cystic nodules. Hyperthyroidism was cured in 91.5% of patients. The PEI procedure was connected with a few significant complications only, in relation to the localization of nodules. It was cheap, possible on an outpatient basis, easy to perform and acceptable to patients. Since the cost of thyroidectomy is high and the complication rate significant, PEI is a suitable substitute treatment especially for some patients with small toxic benign nodules of the thyroid gland.     

Aromatase Inhibitor Increases the Height of Patients with Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency

Objective: Patients with 21-hydroxylase deficiency (21OHD) typically suffer from short stature due to early exposure to adrenal-derived androgen. The aim of this study was to investigate whether adding aromatase inhibitor (AI) to gonadotropin-releasing hormone (GnRH) analogue (GnRHa) and recombinant human growth hormone (rhGH) therapy would increase the height of patients with 21OHD.Methods: This retrospective study included 15 patients with 21OHD. The AI/GnRHa/rhGH group consisted of 9 patients, who were treated with AI for at least 12 months in addition to GnRHa/rhGH therapy. The other 6 patients, who received GnRHa/rhGH therapy only, were defined as the GnRHa/rhGH group.Results: Patients were 6.3 ± 1.7 years old, and 7/15 of patients were male. Among them, 12 patients exhibited simple virilization type, and 3 patients were salt-wasting type. In the AI/GnRHa/rhGH group, patients were 6.6 ± 2.0 years old when AI therapy was initiated. Their bone age was 5.9 ± 2.2 years ahead of their chronological age. They received the AI letrizole for an average of 25.1 months (range, 12 to 37 months). In the GnRHa/rhGH group, the patients were 5.9 ± 0.9 years old when they started GnRHa/rhGH therapy, and their bone age was 6.2 ± 1.7 years ahead of their chronological age. Patients received GnRHa/rhGH therapy for an average of 24.5 months (range, 12 to 41 months). The predicted final height increased from 145.9 ± 7.9 to 158.0 ± 8.4 cm in the AI/GnRHa/rhGH group (P = .001, compared with the baseline) and from 141.7 ± 2.7 to 150.7 ± 4.7 cm in the GnRHa/rhGH group (P = .001, compared with the baseline). Bone age progression was 0.15 ± 0.05 per year versus 0.44 ± 0.13 per year in the two groups, respectively (P = .032).Conclusion: Addition of letrizole to GnRHa/rhGH therapy significantly delays bone maturation and may increase the final height.     

Fine-Needle Aspiration Biopsy of Thyroid Nodules: Comparison of Diagnostic Performance of Experienced and Inexperienced Physicians

ObjectiveTo determine whether a difference exists in terms of obtaining adequate cytologic samples from ultrasound-guided fine-needle aspiration cytology (US-FNAC) between experienced and inexperienced physicians in a tertiary referral center.MethodsIn a prospective design, all patients with thyroid nodules of at least 10 mm in diameter were referred for US-FNAC tissue sampling as a part of their diagnostic work-up. Between May 2006 and September 2009, 997 euthyroid patients with 1, 320 thyroid nodules were referred for US-FNAC by the attending endocrinologist (experienced physician) or 1 of 2 endocrinology fellows (inexperienced physicians).ResultsOf the 1, 320 nodules, 713 biopsy specimens were obtained by the experienced physician and 607 were obtained by the inexperienced physicians. Nodule size was significantly larger in the endocrinologist’s group of patients than in the fellows’ group of patients (17 mm versus 14 mm, respectively; P < .001). The inadequacy rate of the US-FNAC procedures performed by the experienced physician (22 of 713 thyroid nodules or 3.1%) was significantly lower than for those performed by the inexperienced physicians (102 of 607 thyroid nodules or 16.8%) (P < .001).ConclusionWe conclude that, with increasing operator experience, the number of inadequate cytologic specimens generated by US-FNAC procedures is substantially reduced. This limits both direct and indirect costs and also minimizes the risks of possibly unnecessary surgical procedures. (Endocr Pract. 2010;16:986-991)