Impact of age on tumor characteristics and treatment outcomes in pediatric Differentiated Thyroid Carcinoma.

PURPOSE: There is a tendency to use data generated for adults in the management of pediatric Differentiated Thyroid Carcinoma, neglecting the clinical peculiarities of this condition in childhood. This study aimed to assess and compare the clinical-epidemiological characteristics and their significance in the evolution of thyroid carcinoma diagnosed in childhood across different age groups. METHODS: Seventy-seven patients diagnosed with Differentiated Thyroid Carcinoma (DTC) up to 21 years old were selected and divided into different age groups: up to 10 years, 11 to 18 years, and 19 to 21 years old. Clinical-epidemiological data and their influence in the disease progression were analyzed and compared across age groups. RESULTS: Patients diagnosed below 10 years of age were associated with tumors showing extrathyroidal extension, metastasis in regional lymph nodes, higher levels of stimulated thyroglobulin in the diagnostic iodine-131 whole-body scan (WBS), and under TSH suppression in the last assessment. Additionally, pulmonary metastasis were associated in both diagnostic and post-radioiodine dose WBSs in these younger patients. Analysis of findings in the post-radioiodine therapy WBS revealed significant differences between all age groups (p = 0.0029). The time of diagnosis was identified as a factor associated with an excellent response in subgroups up to 18 years and up to 21 years. No factors associated with dynamic responses over the 1st, 3rd and 5th years of follow-up and the persistence/recurrence of the disease were identified in the subgroup up to 18 years. In the subgroup up to 21 years, having an incomplete structural response in the 3rd year of follow-up increased the chances of recurrent or persistent response by 5.5 times, and by 32.6 times if found in the 5th year of follow-up. CONCLUSIONS: Younger patients exhibited more aggressive tumor characteristics and underwent more rigorous treatment. However, treatment response and disease status in the last assessment, whether free or recurrent/persistence, were similar when comparing the age groups of 11 to 18 and 19 to 21 years. Nonetheless, responses obtained in the 3rd and 5th years post-treatment emerged as factors associated with the persistence/recurrence of the disease in the last assessment in the age group up to 21 years but not in patients diagnosed up to 18 years, a relevant distinction considering the tumor behavior in defining the pediatric age range in thyroid cancer.

Impact of the number of intermediate risk factors on outcome of papillary thyroid cancer.

PURPOSE: The 2015 American Thyroid Association risk stratification system (2015-RSS) is used to assess the tumor recurrence rate and guide the initial treatment. At the current moment, patients with one or multiple intermediate risk factors (IRF) have the same treatment. This study was conducted to evaluate the impact of the number of IRF characteristics on tumor persistence or recurrence rates. METHODS: Patients with intermediate risk papillary thyroid cancer (PTC) were selected and analyzed, furthermore, they were divided into two subgroups, one with 1-2 IRF and another with ≥3 IRF. Those data were analyzed in relation to response to therapy at the end of the first year and in last appointment, time to reach non evidence of disease (NED) state and time in NED state. RESULTS: A total of 257 patients were evaluated. Extrathyroidal invasion, vascular invasion, the total number of IRF and the subgroup of ≥3 IRF were associated with non-excellent response in last consultation; IRF lymph node metastasis was associated with non-excellent response in the first year and in last appointment and prolonged time in NED state; vascular invasion was associated with a shorter time in NED state; total number of IRF and aggressive histology were related to delay in the achievement of NED state. CONCLUSIONS: Higher number of IRF was a predictive factor of non-excellent response in the last visit and was associated with longer time to reach the NED state. Those data suggest a benefit from closer follow-up and more intensive treatment in these patients.

Ocular Surface Disease Related to the Inflammatory and Non-Inflammatory Phases of Thyroid Eye Disease.

Purpose: This study evaluated the ocular surface disease (OSD), especially dry eye disease (DED) parameters by combining qualitative and quantitative tools, including tear matrix metalloproteinase 9 (MMP-9), in patients with Graves' disease (GD) with and without Thyroid eye disease (TED). Patients and Methods: A total of 17 active TED, 16 inactive TED, 16 GD without ophthalmopathy, and 16 healthy controls were included. All patients were assessed with CAS, ophthalmometry, qualitative tear MMP-9, Ocular Surface Disease Index (OSDI), ocular surface staining, Schirmer test, meibography, tear meniscus height, conjunctival hyperemia, and non-invasive tear film break-up time. Patients were classified into three subtypes of DED: aqueous tear deficiency, meibomian gland dysfunction (MGD) and mixed dry eye. Results: Inactive TED was shown to be an associated factor with DED (odds ratio 14, confidence interval 2.24-87.24, p=0.0047), and presented more DED than healthy controls (87.5% versus 33.3%, p=0.0113). MGD was also more prevalent among these subjects than in healthy control (62.5% versus 6.7%; p=0.0273). No significant differences were found in other ophthalmological parameters, except for more intense conjunctival redness among active TED than GD without ophthalmopathy (p=0.0214). Qualitative MMP-9 test was more frequently positive in both eyes among active TED than in other groups (p < 0.0001). Conclusion: Patients with GD were symptomatic and presented a high prevalence of ocular surface changes and DED, particularly the subgroup with inactive TED. Tear MMP-9 detection was associated with active TED suggesting a relationship between ocular surface changes and the initial inflammatory phase of ophthalmopathy.

PD-L1 and MCL-1 markers and the relationship with prognostic characteristics of differentiated thyroid carcinoma.

OBJECTIVES: MCL-1 and PD-L1 proteins are related to carcinogenesis mechanisms in differentiated thyroid carcinoma(DTC). Tumor antigens stimulate the expression of PD-1 in immune cells, which binds to PD-L1 of tumor cells, inducing immune escape from the tumor. MCL-1, an anti-apoptotic member of the BCL-2 family, is necessary for the survival of T and B lymphocytes and has a high oncogenic potential. We aim to evaluate the clinical utility and relevance of MCL-1 and PD-L1 in the long-term prognosis of DTC. METHODS: 120 DTC patients after total thyroidectomy and radioiodine therapy followed for a minimum of 2 years were included. Demographic features, tumor histopathology, persistence/recurrence risk, factors associated with outcome, initial response to therapy, persistence or disease-free at the follow-up were related to MCL-1 and PD-L1 immunohistochemical expression and BRAFV600E mutation. RESULTS: 100(83.3%) were women, 46.64 ± 16.73 years old at diagnosis; 37(30.8%) patients were at high, 45(37.5%) of intermediate and 38(31.7%) of low disease recurrence/persistence risk. At the end of follow-up of 124.86 ± 65.36 months, 48(42.5%) had persistent disease. 103(85.8%) patients had papillary thyroid carcinoma (PTC), 17(14.2%) follicular thyroid carcinoma (FTC). In PTC, moderate/strong PD-L1 and MCL-1 expressions were associated to BRAFV600E (p=0.0467; p=0.0044). PD-L1 was also associated with tall cell subtype (p=0.0274). In FTC, weak PD-L1 expression was associated to the largest nodule diameter (p=0.0100). Strong/moderate PD-L1 expression was associated to T2 and the weak expression with T3 in TNM classification (p=0.0490). Moderate MCL-1 expression was associated to smoking (p=0.0350). CONCLUSIONS: PDL-1, marker of progression of tumor cells and MCL-1, anti-apoptotic marker, were associated with PTC carrying BRAFV600E mutation, while PDL-1 was associated with more aggressive PTC subtype. MCL-1 and PD-L1 could be useful in composing a panel to assess the prognosis of PTC patients. On the other hand, both markers seemed to have lower relevance to FTC patients.

Computed tomography and magnetic resonance imaging approaches to Graves' ophthalmopathy: a narrative review.

Graves' ophthalmopathy (GO) affects up to 50% of patients with Graves' disease (GD) ranging from mild ocular irritation to vision loss. The initial diagnosis is based on clinical findings and laboratory tests. Orbital imaging, such as magnetic resonance imaging (MRI) and computed tomography (CT), is an important tool to assess orbital changes, being also useful for understanding disease progression and surgical planning. In this narrative review, we included 92 studies published from 1979 to 2020 that used either MRI and/or CT to diagnose and investigate GO, proposing new methods and techniques. Most of the methods used still need to be corroborated and validated, and, despite the different methods and approaches for thyroid eye disease (TED) evaluation, there is still a lack of standardization of measurements and outcome reports; therefore, additional studies should be performed to include these methods in clinical practice, facilitating the diagnosis and approach for the treatment of TED.

Childhood-Onset GH Deficiency versus Adult-Onset GH Deficiency: Relevant Differences Regarding Insulin Sensitivity.

The results of the studies on the pattern of insulin sensitivity (IS) are contradictory in patients with GH deficiency (GHD); however, the interference of the GHD onset stage, childhood or adulthood in the IS has not been assessed by euglycemic hyperinsulinemic clamp (EHC), a gold-standard method for the assessment of insulin sensitivity. In a prospective cross-sectional study, we assessed IS and body composition in 17 adults with hypopituitarism without GH replacement, ten with childhood-onset (COGHD) and seven with adulthood-onset (AOGHD) and compared them to paired control groups. COGHD presented higher IS (p = 0.0395) and a similar percentage of fat mass (PFM) to AOGHD. COGHD showed higher IS than the control group (0.0235), despite a higher PFM (0.0022). No differences were found between AODGH and the control group. In AOGHD and the control group, IS was negatively correlated with PFM (rs: −0.8214, p = 0.0234 and rs: −0.3639, p < 0.0344), while this correlation was not observed with COGHD (rs: −0.1152, p = 0.7514). Despite the higher PFM, patients with COGHD were more sensitive to insulin than paired healthy individuals, while patients with AOGHD showed similar IS compared to controls. The lack of GH early in life could modify the metabolic characteristics of tissues related to the glucose metabolism, inducing beneficial effects on IS that persist into adulthood. Thus, the glycometabolic findings in patients with COGHD seems to be not applicable to AOGHD.

Higher systemic inflammatory status and cardiovascular risk associated with Charcot arthropathy unrelated to infection or extremity amputation.

Purpose: People with diabetes and Charcot arthropathy have higher mortality than people with diabetes without this complication. Are the causes of this higher mortality exclusively infectious or of a cardiovascular origin? We aimed to study aspects related to cardiovascular risk and inflammation in a population of people with type 2 diabetes with and without Charcot arthropathy. Methods: A cross-sectional study was performed in people with diabetes and Charcot Eickenholtz III arthropathy, matched for sex and age, with two groups of people with diabetes without Charcot arthropathy with and without peripheral sensory-motor neuropathy, in the absence of active infection. All participants underwent clinical and laboratory evaluation at the time of the interview, and their cardiovascular risk was calculated according to the United Kingdom Prospective Diabetes Study (UKPDS) calculator. Results: We evaluated 69 people with type 2 diabetes (21 with Charcot arthropathy, 24 with diabetic peripheral neuropathy and 24 without this neuropathy), with a mean age between 57 and 61 years and with a diabetes duration of more than 10 years. Patients with Charcot arthropathy had a longer duration of diabetes; more frequency of dyslipidemia; and higher levels of uric acid, microalbuminuria and C-reactive protein than the other two groups. A total of 73.9% of the people evaluated had high or very high cardiovascular risk according to the UKPDS score. Conclusion: The people with type 2 diabetes presenting Charcot arthropathy had greater values of systemic inflammatory parameters, even in the chronic phase of the complication, with a higher risk of mortality unrelated to infections.

Impact of the use of illicit and licit substances and anxiety disorders on the academic performance of medical students: a pilot study.

BACKGROUND: Medical students have a considerable prevalence of anxiety and substance use disorders. Our aim was to assess the presence of anxiety disorders and the use of alcohol and licit and illicit substances, and their influence on the academic performance of medical students. METHODS: This is a cross-sectional, non-experimental pilot study, with quantitative analyses, in which 67 medical students at the Federal University of Rondonópolis, Mato Grosso, Brazil (UFR), were evaluated through the application of non-invasive anxiety assessment instruments, screening for involvement with tobacco, alcohol and other substances, related to school performance coefficient, between June 2019 and March 2020. RESULTS: Worse academic performance was associated with frequent use of tobacco and its derivatives (p = 0.0022), marijuana (p = 0.0020), hypnotics and sedatives (p = 0.0138). Also, the performance was negatively correlated with the use of tobacco (p = 0.0004), alcoholic beverages (p = 0.0261), cannabis (p = 0.0075), sedatives (p = 0.0116) and trait anxiety (p = 0.0036). Greater trait anxiety intensity was associated with previous use of tobacco (p = 0.0276), marijuana (p = 0.0466), amphetamines/ecstasy (p = 0.0151), and hypnotics/sedatives (p = 0.0103). State anxiety was positively correlated with heavy alcohol use (p = 0.0434). Higher state anxiety intensity was related to needing intervention due to the use of amphetamines/ecstasy (p = 0.00379). Students from the intermediate classes of the course (3rd and 4th years) had a higher frequency and intensity of use of tobacco and its derivatives (p = 0.0133), amphetamines or ecstasy (p = 0.0006), and inhalants (p = 0.0256). CONCLUSIONS: Worse academic performance in medical students was correlated with licit and illicit substances use and anxiety disorders. Mid-course students had a higher frequency and intensity of substance use.

Cardiovascular Autonomic Reflex Tests and 7 Heart Rate Variability Indices for Early Diagnosis of Cardiovascular Autonomic Neuropathy in Type 2 Diabetes Individuals.

BACKGROUND: Cardiovascular autonomic neuropathy (CAN) is a common complication of type 2 Diabetes mellitus (T2D), and prevalence varies according to the methodology used. CAN should be diagnosed in the subclinical stage when an intensive treatment of T2D could avoid the progression to irreversible phases. OBJECTIVE: Determine the prevalence of early involvement (EI) of CAN in T2D individuals comparing two methodologies. METHODS: This was a cross-sectional study that included 183 T2D individuals who were monitored in a Tertiary centre. The diagnosis of CAN was based on the results of four cardiovascular autonomic reflex tests (CARTs: expiration-inspiration index, Valsalva maneuver, orthostatic test, and changes in blood pressure after standing) and of seven heart rate variability (7HRV) indices (CARTs plus the spectral analysis). The findings were validated in an independent cohort comprised of 562 T2D individuals followed in a Primary care setting. RESULTS: With the use of 7HRV, 30.6% and 77.8% of individuals in the Tertiary and in the Primary centers, respectively, were classified as without CAN; 25.1% and 15.3% as EI and 44.3% and 6.9% as definitive CAN, respectively. The use of CARTs decreased the proportion of individuals without CAN in both centers (7.1% and 47%) and increased the frequency of EI (30.6% and 36.6%) and definitive CAN (62.3% and 16.4%), respectively. The concordance between both evaluated methodologies was weak. CONCLUSION: Higher proportions of T2D individuals were diagnosed with EI and with definitive CAN with the use of CARTs.

Influence of thyroid hormone in the expression of the marker pro-apoptosis BID, in spite of the predominance of anti-apoptosis activation in intratiroidal lymphocytic infiltration in Hashimoto's thyroiditis.

Cell destruction in Hashimoto's thyroiditis (HT) involves autoantibodies and cytotoxic T lymphocytes. Thyrocytes maintenance occurs by pro-apoptotic, anti-apoptotic and cell proliferation balance. OBJECTIVES: To characterize factors related to the mechanisms of apoptosis and cell proliferation in thyroid cells and intrathyroid lymphocytic infiltrate in HT. METHODS: We assessed lymphocytic infiltrate and thyroid cells from HT and normal thyroid by immunohistochemical analysis of cell proliferation (Ki-67), antiproliferation (p27Kip1), pro-apoptosis (Fas, Fas-ligand, BID) and anti-apoptosis (MCL-1, BCL2) markers. RESULTS: Lymphocytic infiltrate presented BCL2 and MCL-1 higher expression, Ki-67 and p27kip1 balance. Thyrocytes exhibited Fas and FasL balance, higher BID expression; MCL-1, BCL-2, Ki-67 similar to the normal thyroid. T4 and higher lymphocytes BID expression were associated. CONCLUSIONS: In lymphocytic infiltrate predominated anti-apoptosis in relation to pro-apoptosis except for BID. Thyrocytes presented pro-apoptosis and anti-apoptosis balance and cell proliferation similar to normal thyroid. T4-associated BID expression in HT lymphocytes suggests the influence of thyroid hormone as a signal to up-regulate the BID pro-apoptotic protein and thus increase lymphocytic apoptosis rates.

Usefulness of pre-thyroidectomy neutrophil-lymphocyte, platelet-lymphocyte, and monocyte-lymphocyte ratios for discriminating lymph node and distant metastases in differentiated thyroid cancer.

OBJECTIVE: This study aimed to analyze the relationship of neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and monocyte-lymphocyte ratio (MLR) with clinicopathological characteristics of patients with differentiated thyroid cancer (DTC). METHODS: This retrospective study included 390 patients with DTC who had complete blood cell counts available at the time of surgery. NLR, PLR, and MLR were calculated, and the risk of cancer-related death, structural recurrence, and response to therapy were assessed using the eighth edition of the tumor-node-metastasis classification, American Thyroid Association (ATA) Risk Stratification System, and ATA Response to Therapy Reclassification, respectively. RESULTS: PLR was higher in patients with distant metastasis than in those without (133.15±43.95 versus 119.24±45.69, p=0.0345) and lower in patients with disease-free status (117.72±44.70 versus 131.07±47.85, p=0.0089) than in those who experienced persistent disease or death. Patients aged ≥55 years had a higher MLR than those aged <55 years (0.26±0.10 versus 0.24±0.12, p=0.0379). Higher MLR (odds ratio [OR]: 8.775, 95% confidence interval [CI]: 1.532-50.273, p=0.0147), intermediate ATA risk (OR: 4.892, 95% CI: 2.492-9.605, p≤0.0001), and high ATA risk (OR: 5.998, 95% CI: 3.126-11.505, p≤0.0001) were risk factors associated with active disease. NLR was not significantly different among the studied variables. Receiver operating characteristic curve cut-off values for NLR, PLR, and MLR were able to differentiate distant metastasis from lymph node metastasis (NLR>1.93: 73.3% sensitivity and 58.7% specificity, PLR>124.34: 86.7% sensitivity and 69.2% specificity, MLR>0.21: 80% sensitivity and 45.2% specificity). CONCLUSION: Cut-off values of NLR, PLR, and MLR differentiated distant metastasis from lymph node metastasis with good sensitivity and accuracy. PLR was associated with disease-free status and it was higher in DTC patients with distant metastasis, persistent disease, and disease-related death. MLR was a risk factor for active disease.

Ocular Manifestations and Neuropathy in Type 2 Diabetes Patients With Charcot Arthropathy.

Objective: Diabetes can affect the eye in many ways beyond retinopathy. This study sought to evaluate ocular disease and determine any associations with peripheral neuropathy (PN) or cardiac autonomic neuropathy (CAN) in type 2 diabetes (T2D) and Charcot arthropathy (CA) patients. Design: A total of 60 participants were included, 16 of whom were individuals with T2D/CA, 21 of whom were individuals with T2D who did not have CA, and 23 of whom were healthy controls. Ocular surface evaluations were performed, and cases of dry eye disease (DED) were determined using the Ocular Surface Disease Index (OSDI) questionnaire, ocular surface staining, Schirmer test, and Oculus Keratograph 5M exams. All variables were used to classify DED and ocular surface disorders such as aqueous deficiency, lipid deficiency, inflammation, and ocular surface damage. Pupillary and retinal nerve fiber measurements were added to the protocol in order to broaden the scope of the neurosensory ocular evaluation. PN and CAN were ascertained by clinical examinations involving the Neuropathy Disability Score (for PN) and Ewing's battery (for CAN). Results: Most ocular variables evaluated herein differed significantly between T2D patients and controls. When the controls were respectively compared to patients with T2D and to patients with both T2D and CA, they differed substantially in terms of visual acuity (0.92 ± 0.11, 0.73 ± 0.27, and 0.47 ± 0.26, p=0.001), retinal nerve fiber layer thickness (96.83 ± 6.91, 89.25 ± 10.44, and 80.37 ± 11.67 µm, p=0.03), pupillometry results (4.10 ± 0.61, 3.48 ± 0.88, and 2.75 ± 0.81 mm, p=0.0001), and dry eye symptoms (9.19 ± 11.71, 19.83 ± 19.08, and 24.82 ± 24.40, p=0.03). DED and ocular surface damage also differed between individuals with and without CA, and were associated with PN and CAN. Conclusion: CA was found to be significantly associated with the severity of ocular findings. DED in cases of CA was also associated with PN and CAN. These findings suggest that intrinsic and complex neurosensory impairment in the eyes, peripheral sensory nerves, and the autonomic nervous system are somehow connected. Thus, a thorough ocular evaluation may be useful to highlight neurological complications and the impact of diabetes on ocular and systemic functions and structures.

Fixed 30 mCi (1110 MBq) 131I-iodine therapy in autonomously functioning nodules: Single toxic nodule as a predictive factor of success.

AIMS: The aim of this study is to evaluate the efficacy of a fixed 30 mCi (1110 MBq) 131I-iodine dose for the treatment of hyperthyroidism due to uninodular or multinodular toxic goiter and identify predictors of success. MATERIALS AND METHODS: Fifty-nine patients diagnosed with nonautoimmune toxic goiter were treated with a fixed 30 mCi dose of 131I-iodine and were followed at a tertiary service between 2000 and 2016. The therapy was considered successful if the patient reached euthyroidism or hypothyroidism without needing an extra 131I-iodine dose or antithyroid drugs for at least 1 year after the radioiodine therapy (RIT). RESULTS: Patients with a single toxic nodule were younger at diagnosis (52 vs. 63 years; P = 0.007), presented a shorter disease duration until RIT (2 vs. 3.5 years; P = 0.007), smaller total thyroid volume (20 vs. 82 cm3; P = 0.044), and lower pre-RIT thyroid uptake (P = 0.043) than patients with multinodular goiter. No significant difference was seen with antithyroid drug use, thyroid-stimulating hormone and free thyroxine level, and follow-up after RIT. After RIT, 47 patients (79.66%) met the success criteria, and 12 (20.33%) remained hyperthyroid. Among the success group, 32 (68.08%) reached euthyroidism, while 31.92% developed hypothyroidism after 1 year. Patients with single toxic nodules who achieved success after RIT presented smaller nodules (2.8 vs. 5.75 cm; P = 0.043), while the pre-RIT thyroid uptake was higher among patients with multinodular toxic goiter who achieved success after RIT (5.5% vs. 1.5%; P = 0.007). A higher success rate was observed among patients with a single toxic nodule than those with a toxic multinodular goiter (92.3% vs. 55%; P = 0.001), and a single toxic nodule presentation was found to be an independent predictor of success (P = 0.009). CONCLUSIONS: The fixed 30 mCi 131I-iodine dose was particularly effective in the group of patients with single autonomously functioning nodule rather than the group with multiple nodules. A single toxic nodule was an independent predictor of treatment success.

Interplay Between Thyroid Hormone Status and Pulmonary Hypertension in Graves' Disease: Relevance of the Assessment in Thyrotoxic and Euthyroid Patients.

Background: Graves' disease (GD) is the most common cause of hyperthyroidism and can cause cardiac changes, such as pulmonary hypertension. Methods: This is a prospective study in which we obtained demographic, clinical, laboratory data and characteristics of the GD, in addition to investigating cardiorespiratory function, focusing on the detection of pulmonary hypertension. Patients were separated into two groups: thyrotoxicosis and euthyroidism. Ninety patients with GD of both sexes, over 18 years of age, were included. The cardiorespiratory assessment included an echocardiographic evaluation, a questionnaire of specific symptoms, spirometry and a six-minute walk test. Results: The hyperthyroid group included 42 patients (47.73%) and the euthyroid group 46 patients (52.27%); 78 were women (86.67%). The prevalence of pulmonary hypertension between the hyperthyroidism (48.57%) and the euthyroidism (29.41%) groups was not different. Free thyroxine levels (FT4) (OR 1.266), higher left atrium volume (OR 1.113) and right ventricle diameter were associated with pulmonary hypertension. A direct correlation between FT4 with forced vital capacity (FVC) and forced expiratory volume in the first second (FEV1), as also an inverse correlation between initial oxygen saturation (SpO2) with diagnostic time and drop SpO2 with the ratio between the diastolic velocity E of the mitral flow and the diastolic velocity of the mitral ring (E/e') were observed in the euthyroid group. An inverse correlation between FT4 levels with walked distance as % of predicted value, and a direct correlation between E/e' ratio and walked distance as % of predicted value were observed in the hyperthyroid group. Conclusion: We emphasize the importance of a cardiorespiratory reassessment in GD, even after a long-term control of the thyrotoxic state, as we demonstrate that about 30% of these patients remain with PH and are subject to specific treatment.

Usefulness of pre-thyroidectomy neutrophil-lymphocyte, platelet-lymphocyte, and monocyte-lymphocyte ratios for discriminating lymph node and distant metastases in differentiated thyroid cancer

OBJECTIVE: This study aimed to analyze the relationship of neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and monocyte-lymphocyte ratio (MLR) with clinicopathological characteristics of patients with differentiated thyroid cancer (DTC). METHODS: This retrospective study included 390 patients with DTC who had complete blood cell counts available at the time of surgery. NLR, PLR, and MLR were calculated, and the risk of cancer-related death, structural recurrence, and response to therapy were assessed using the eighth edition of the tumor-node-metastasis classification, American Thyroid Association (ATA) Risk Stratification System, and ATA Response to Therapy Reclassification, respectively. RESULTS: PLR was higher in patients with distant metastasis than in those without (133.15±43.95 versus 119.24±45.69, p=0.0345) and lower in patients with disease-free status (117.72±44.70 versus 131.07±47.85, p=0.0089) than in those who experienced persistent disease or death. Patients aged ≥55 years had a higher MLR than those aged <55 years (0.26±0.10 versus 0.24±0.12, p=0.0379). Higher MLR (odds ratio [OR]: 8.775, 95% confidence interval [CI]: 1.532-50.273, p=0.0147), intermediate ATA risk (OR: 4.892, 95% CI: 2.492-9.605, p≤0.0001), and high ATA risk (OR: 5.998, 95% CI: 3.126-11.505, p≤0.0001) were risk factors associated with active disease. NLR was not significantly different among the studied variables. Receiver operating characteristic curve cut-off values for NLR, PLR, and MLR were able to differentiate distant metastasis from lymph node metastasis (NLR>1.93: 73.3% sensitivity and 58.7% specificity, PLR>124.34: 86.7% sensitivity and 69.2% specificity, MLR>0.21: 80% sensitivity and 45.2% specificity). CONCLUSION: Cut-off values of NLR, PLR, and MLR differentiated distant metastasis from lymph node metastasis with good sensitivity and accuracy. PLR was associated with disease-free status and it was higher in DTC patients with distant metastasis, persistent disease, and disease-related death. MLR was a risk factor for active disease.

Fixed 30 mCi 131I-iodine therapy without recombinant human thyroid-stimulating hormone stimulation as an attractive therapeutic alternative in nontoxic nodular goiter.

OBJECTIVE: To analyze outcomes of patients with compressive nontoxic multinodular goiter after 131I-iodine 30 mCi treatment without previous use of recombinant human thyroid-stimulating hormone or methimazole. METHODS: We evaluated fixed-dose radioiodine therapy outcomes in patients with nontoxic multinodular goiter who did not accept thyroidectomy as a therapeutic option. Laboratory thyroid function and thyroid volume estimated by ultrasound were assessed before and one year after radioiodine therapy. RESULTS: Twenty euthyroid female patients received 30 mCi of 131I-iodine without recombinant human thyroid-stimulating hormone or methimazole pretreatment. Median thyroid volume and Tc-99m sodium pertechnetate thyroid uptake before radioiodine therapy were 68.05 cm (31.3-295.3) and 0.5% (0.1%-1.2%), respectively. One year after radioiodine therapy, thyroid volume decreased to 55.4 cm (19.8-149.9), and merely 4 patients (20%) developed hypothyroidism. Thyroid volume decreased significantly after radioiodine therapy, presenting a variation of -21.1 cm (-161.3 to -0.8) and -30.61% (-73.88 to -1.02), both with P < 0.0001. Thyroid volume variation was positively correlated with thyroid uptake in Spearman's correlation (r = 0.4730; P = 0.0352). The group satisfied with radioiodine therapy (85%, n = 17) showed a significant reduction in thyroid volume, -25.8 cm (-161.3 to -6.2) and -36.74% (-73.88 to -9.95). The dissatisfied group (15%, n = 3) showed -1.0 cm (-2.0 to -0.8) and -1.67% (-3.38 to -1.02) in thyroid volume, P = 0.0081. Patients that complained about dysphagia presented a lower percentage of thyroid volume decrease after radioiodine therapy, -21.97% (-70.12 to -1.02, P = 0.0430). CONCLUSIONS: A substantial reduction in thyroid volume associated with a low incidence of hypothyroidism and a high satisfaction rate support the use of conventional radioiodine therapy with a fixed dose of 30 mCi. This therapy is an attractive and cheaper therapeutic alternative in selected patients with nontoxic multinodular goiter.

Head-to-head comparison of F-18 FDG PET/CT in radioidine refractory thyroid cancer patients with elevated versus suppressed TSH levels a pilot study.

INTRODUCTION: To perform a head-to-head comparison of the uptake pattern of F-18 fluorodeoxyglucose in positron emission computed tomography (FDG PET/CT) in radioiodine refractory thyroid carcinomas (RAIR) in the same patient under elevated TSH levels (eTSH) and suppressed TSH levels (sTSH). METHODS: FDG PET/CT studies were performed under two conditions: levothyroxine intake (sTSH) and 30 days after hormonal withdrawal (eTSH). SUVmax values and the number of lesions detected (local recurrence and metastases in cervical and distant lymph nodes, lungs and bone) where blindly evaluated. Blood serum TSH and Tg levels were obtained prior to both studies. FDG PET/CT imaging, neck ultrasound, biopsy and follow-up were considered the reference standard. RESULTS: Fifteen patients performed both eTSH and sTSH FDG PET/CT studies. Both were positive for metastases in 80% of the patients. eTSH FDG PET/CT studies did not reveal increased uptake (p = 0.0640) and did not demonstrate a higher number of lesions (p = 0.320) when compared to sTSH FDG PET/CT studies. There was no change in the clinical management of these patients. CONCLUSIONS: eTSH FDG PET/CT in patients with RAIR did not show more metastases in comparison to sTSH FDG PET/CT and there was no impact in clinical management of patients. Elevating TSH levels (whether by hormonal withdrawal or recombinant TSH) in patients being submitted to FDG PET/CT may not be necessary.

Type 1 diabetes mellitus associated or not with primary hypothyroidism and women's fertility.

The aim of this study is to evaluate the prevalence of infertility and other reproductive parameters in women with type 1 diabetes mellitus (DM1) with and without primary hypothyroidism (PH). This is a cross-sectional study conducted at Division of Endocrinology. We evaluated 110 female, aged over 18 years, 79 had DM1 and 31 had DM1 plus PH. They were interviewed to obtain data on their gynecological and obstetric history; medical charts were reviewed to determine the characteristics of the diseases and to assess clinical/laboratory data. Infertility was defined as 12 months of unprotected sexual intercourse without conception. We used the chi-square and Mann-Whitney's tests, and logistic regression analysis. The prevalence of infertility in the total sample was 24.5%, no differences were found between groups regarding obstetric outcomes and gynecologic variables. Factors associated with infertility were microvascular complication (OR: 11.36; 95% CI: 2.488-52.632; p = .029), polycystic ovary syndrome (OR: 9.80; 95% CI: 2.247-43.478; p = .016), PH (OR: 3.38; 95% CI: 1.078-10.638; p = .047), and older age at onset of DM1 (OR: 1.12; 95% CI: 1.029-1.215; p = .019). The presence of PH in women with DM1 was a predictive factor for infertility. Women with DM1 showed poorer reproductive outcomes compared to the general population.

Insulin Sensitivity Is Not Decreased in Adult Patients With Hypopituitarism Without Growth Hormone Replacement.

Decreased insulin sensitivity in patients with hypopituitarism without GH replacement (pHP-WGHR) remains conflicting in literature. It is known that these patients present a decrease in free fat mass and an increase in fat mass. Typically, these kinds of alterations in body composition are associated with a decrease in insulin sensitivity; however, there is no consensus if this association is found in pHP-WGHR. Thus, we investigated pHP-WGHR regarding insulin sensitivity by euglycemic hyperinsulinemic clamp, the gold standard method, and body composition. In a cross-sectional study, we evaluated 15 pHP-WGHR followed up in a Service of Neuroendocrinology and 15 individuals with normal pituitary function as a control group with similar age, gender and body mass index. Insulin sensitivity was evaluated by euglycemic hyperinsulinemic clamp and homeostatic model assessment insulin resistance (HOMA-IR). Kappa coefficient evaluated the agreement between these two methods. Percentage of fat mass, percentage of free fat mass, fat mass weight and free fat mass weight were assessed by electrical bioimpedance. The pHP-WGHR presented similar insulin sensitivity to control group by euglycemic hyperinsulinemic clamp, both by the M-value, (p = 0.0913) and by the area under the glucose infusion rate curve, (p = 0.0628). These patients showed lower levels of fasting glycemia (p = 0.0128), insulin (p = 0.0007), HOMA-IR (p = 0.009). HOMA-IR shows poor concordance with euglycemic hyperinsulinemic clamp (Kappa = 0.16) in pHP-WGHR, while in the control group the agreement was good (Kappa = 0.53). The pHP-WGHR presented higher values of percentage of fat mass (p = 0.0381) and lower values of percentage of free fat mass (p = 0.0464) and free fat mass weight (0.0421) than the control group. This study demonstrated that the insulin sensitivity evaluated by euglycemic hyperinsulinemic clamp in pHP-WGHR was similar to individuals with normal pituitary function, despite the pHP-WGHR presenting higher fat mass percentage. HOMA-IR was not a good method for assessing insulin sensitivity in pHP-WGHR.

Value of Infrared Thermography Camera Attached to a Smartphone for Evaluation and Follow-up of Patients with Graves' Ophthalmopathy.

PURPOSE: Graves' ophthalmopathy (GO) is the most common extra-thyroid manifestation of Graves' disease (GD). The Clinical Activity Score (CAS) has been widely used to evaluate GO inflammation severity and response to treatment; however, it is quite subjective. Infrared thermography (IRT) is a portable and low-cost device to evaluate local temperature and assess inflammation. The aim was to evaluate ocular temperature by IRT as an instrument for measuring inflammatory activity in GO and its correlation with CAS. METHODS: This is a cross-sectional study involving 136 consecutive GD patients (12 with CAS ≥ 3/7, 62 with CAS < 3 and 62 without apparent GO) with 62 healthy controls. Patients with active ophthalmopathy were prospectively evaluated. Exophthalmometry, CAS, and thermal images from caruncles and upper eyelids were acquired from all subjects. RESULTS: All eye areas of thermal evaluation had higher temperatures in GD patients with active ophthalmopathy (caruncles, p<0.0001; upper eyelids, p<0.0001), and it was positively correlated with CAS (r=0.60 and p<0.0001 at caruncles; r=0.58 and p<0.0001 at upper eyelids). No difference in temperature was found between other groups. Patients with active ophthalmopathy were prospectively evaluated after 6 or 12 months of the treatment and a significant difference was found in ophthalmometry (p=0.0188), CAS (p=0.0205), temperature of caruncles (p=0.0120), and upper eyelids (p=0.0066). CONCLUSIONS: IRT was an objective and simple tool for evaluation and follow-up of inflammation in GO, allowed evidencing patients with significant inflammatory activity, and had a good correlation with the CAS score.