Concomitant Use of Levothyroxine and Proton Pump Inhibitors in Patients with Primary Hypothyroidism: a Systematic Review.

BACKGROUND: The aim of this study was to assess the effect of concomitant use of levothyroxine (LT4) and proton pump inhibitors (PPIs) on thyroid-stimulating hormone (TSH) levels in patients with primary hypothyroidism. METHODS: A systematic review of interventional and observational studies that compared the TSH levels before and after concomitant use of LT4 and PPI was performed. Articles published in English up to September 1, 2019, were included. PubMed, EMBASE, and Cochrane Library databases. Gray literature was also searched in repositories, websites OpenGrey and Google Scholar, and abstracts of major international congresses. Study quality was assessed with the Newcastle-Ottawa quality assessment scale for observational studies and the Risk Of Bias In Non-randomized Studies - of Interventions (ROBINS-I) tool was used. RESULTS: Five thousand twelve discrete articles were identified. Following assessment and application of eligibility criteria, seven studies were included. There was a considerable heterogeneity among the included studies in design, sample size, inclusion and exclusion criteria, treatment regimen, and baseline demographics. Each of the included studies showed an increase in TSH levels following LT4 and PPI consumption, and in the majority of these, the increase was statistically significant. DISCUSSION: The concomitant use of LT4 and PPI showed a significant increase in TSH concentration. However, given the small number of studies, further research is needed to clarify the interfering role of PPI on LT4 intestinal absorption. PROSPERO REGISTRATION NUMBER: CRD42020047084.

Biochemical features of eugonadal patients with idiopathic gynaecomastia: A retrospective cross-sectional study.

Patients with idiopathic gynaecomastia have greater BMI and an unfavourable lipid profile compared with age-matched controls. Twenty-five adult eugonadal patients with idiopathic gynaecomastia and 50 age- and BMI-matched controls were selected. Clinical and biochemical parameters and ultrasound testis volume were reviewed retrospectively. Patients and controls differed for no biochemical parameter, except for LH levels, which were 31% higher in patients (p = 0.019), although within the normal range. Compared with controls, patients had a threefold greater rate of elevated LDL-c (p = 0.025). Patients ≥ 25 years had higher levels of serum LDL-c compared with either patients < 25 years (p = 0.006) or controls ≥ 25 years (p = 0.012). In patients, both at bivariate analysis and at linear regression, age correlated positively with total cholesterol and LDL-c, the latter correlated inversely with total testosterone. Negative interactions were found for age and total testosterone with LDL-c, for LH and estradiol to testosterone ratio (E2:T) with LDL-c, and for age and E2:T with total cholesterol. Our data suggest inadequate local androgen action in patients with idiopathic gynaecomastia. This partial androgen resistance might blunt the beneficial effects of testosterone on lipid metabolism. Further studies are needed to verify whether this metabolic derangement impacts the cardiovascular health of these patients.

The increasing prevalence of chronic lymphocytic thyroiditis in papillary microcarcinoma.

Although the incidence of some malignancy has decreased over the recent years, this is not the case of papillary thyroid microcarcinoma (PTMC), whose incidence has increased worldwide. Most PTMC are found incidentally after histological examination of specimens from surgery for benign thyroid disease. Hashimoto's thyroiditis, whose incidence has also increased, coexists in about one in three PTMC patients. Three different mechanisms have been proposed to clarify the association between chronic lymphocytic thyroiditis and PTMC, namely tumor development/growth by: (i) TSH stimulation, (ii) expression of certain proto-oncogenes, (iii) chemokines and other molecules produced by the lymphocytic infiltrate. Whether Hashimoto's thyroiditis protects against lymph node metastasis is debated. Overall, autommune thyroiditis seems to contribute to the favorable prognosis of PTMC. Major limitations of the studies so far performed include: (i) retrospective design, (ii) limited statistical power, (iii) high risk of selection bias, (iv) and predominant Asian ethnicity of patients. Full genetic profiling of both diseases and identification of environmental factors capable to trigger them, as well as well-powered prospective studies on different ethnical groups, may help understand their causal association and why their frequencies are continuing raising.

The role of human parvovirus B19 and hepatitis C virus in the development of thyroid disorders.

The presence of viruses in the thyroid has been shown, but whether they are implicated in thyroid diseases or are only spectators is under investigation. The most important candidate viruses for autoimmune thyroid disorders (AITD) are hepatitis C virus (HCV) and human parvovirus B19 (or Erythrovirus B19 or EVB19). Retrospective and prospective case-control studies conducted on pathology slides showed (by PCR, in situ hybridization or immunohistochemistry) EVB19 was present in thyroid tissues of patients with autoimmune thyroiditis (AT), Graves' disease and thyroid cancer. Though AITD can be associated with acute EVB19 infection, it is not clear whether EVB19 could have a pathogenetic role in autoimmune thyroid diseases pathophysiology. Many studies have shown that frequently, patients with HCV chronic infection (CHC) show elevated serum anti-thyroperoxidase (TPOAb) and/or anti-thyroglobulin autoantibodies levels, ultrasonographic signs of chronic AT, and subclinical hypothyroidism. In patients with HCV-associated mixed cryoglobulinemia (MC + HCV), AITD were more prevalent with respect to controls, and also vs HCV patients without cryoglobulinemia. Papillary thyroid cancer was more prevalent in MC + HCV or CHC patients than in controls, especially in patients with AT. Recently it has been shown an elevated incidence of new cases of AT and thyroid dysfunction in MC patients. These results suggest an attentive monitoring of thyroid function and nodules in HCV patients with risk factors (female gender, a borderline high initial thyrotropin, TPOAb positivity, a hypoechoic and small thyroid) for the development of thyroid disorders.

Thyroid nodules and thyroid autoimmunity in the context of environmental pollution.

Evidence suggests that in most industrialized countries autoimmune disorders, including chronic lymphocytic thyroiditis, are increasing. This increase parallels the one regarding differentiated thyroid cancer, the increment of which is mainly due to the papillary histotype. A number of studies have pointed to an association between chronic lymphocytic thyroiditis and differentiated thyroid cancer. The upward trend of these two thyroid diseases is sustained by certain environmental factors, such as polluting substances acting as endocrine disrupting chemicals. Herein we will review the experimental and clinical literature that highlights the effects of environmental and occupational exposure to polluting chemicals in the development of autoimmune thyroid disease or differentiated thyroid cancer. Stakeholders, starting from policymarkers, should become more sensitive to the consequences for the thyroid resulting from exposure to EDC. Indeed, the economic burden resulting from such consequences has not been quantified thus far.

New therapies for dedifferentiated papillary thyroid cancer.

The number of thyroid cancers is increasing. Standard treatment usually includes primary surgery, thyroid-stimulating hormone suppressive therapy, and ablation of the thyroid remnant with radioactive iodine (RAI). Despite the generally good prognosis of thyroid carcinoma, about 5% of patients will develop metastatic disease, which fails to respond to RAI, exhibiting a more aggressive behavior. The lack of specific, effective and well-tolerated drugs, the scarcity of data about the association of multi-targeting drugs, and the limited role of radioiodine for dedifferentiated thyroid cancer, call for further efforts in the field of new drugs development. Rearranged during transfection (RET)/papillary thyroid carcinoma gene rearrangements, BRAF (B-RAF proto-oncogene, serine/threonine kinase) gene mutations, RAS (rat sarcoma) mutations, and vascular endothelial growth factor receptor 2 angiogenesis pathways are some of the known pathways playing a crucial role in the development of thyroid cancer. Targeted novel compounds have been demonstrated to induce clinical responses and stabilization of disease. Sorafenib has been approved for differentiated thyroid cancer refractory to RAI.

Personalization of targeted therapy in advanced thyroid cancer.

Although generally the prognosis of differentiated thyroid carcinoma (DTC) is good, approximately 5% of people are likely to develop metastases which fail to respond to radioactive iodine, and other traditional therapies, exhibiting a more aggressive behavior. Nowadays, therapy is chosen and implemented on a watch-and-wait basis for most DTC patients. Which regimen is likely to work best is decided on the basis of an individual's clinical information, but only data referring to outcomes of groups of patients are employed. To predict the best course of therapy, an individual patient's biologic data is rarely employed in a systematic way. Anyway, the use of not expensive individual genomic analysis could lead us to a new era of patient-specific and personalized care. Recently, key targets that are now being evaluated in the clinical setting have been evidenced in the pathogenesis of these diseases. Some of the known genetic alterations playing a crucial role in the development of thyroid cancer include B-Raf gene mutations, rearranged during transfection/ papillary thyroid carcinoma gene rearrangements, and vascular endothelial growth factor receptor-2 angiogenesis pathways. The development of targeted novel compounds able to induce clinical responses and stabilization of disease has overcome the lack of effective therapies for DTC, which are resistant to radioiodine and thyroid stimulating hormone-suppressive therapy. Interestingly, the best responses have been demonstrated in patients treated with anti-angiogenic inhibitors such as vandetanib and XL184 in medullary thyroid cancer, and sorafenib in papillary and follicular DTC.

Drug-induced TINU syndrome and genetic characterization.

Tubulointerstitial nephritis and uveitis (TINU) syndrome is due to a disregulation of cell-mediated immunity and genetical predisposition due a particular molecular characterization. We report the case of a 50-year-old woman who was admitted for acute renal failure. She had recently taken flurbiprofen for 10 d for recurrent bronchitis. A renal biopsy revealed acute tubulointerstitial nephritis. Prednisone was started and prognosis was favorable. Three months later the patient developed transitory blurred vision. The diagnosis was bilateral uveitis and she received topic and systemic corticosteroid therapy, with resolution of ocular symptoms. Recurrent episodes of uveitis experienced during the next 12 months were treated with same therapy. Genomic haplotype in our patients was HLA A*0278/2631,-B*1517/3802,- Cw*0701/1202, -DRB1*0101/1359 (DRB3* 52), -DQA1*0102/0102, DQB1*0603/0603. TINU syndrome is characterized by tubulointerstitial nephritis that tends to be selflimiting, whereas uveitis tends to relapse. HLA-DQA1*01 and -DQB1*06 haplotypes are strongly associated with TINU syndrome. This is the first report of TINU syndrome induced by flubiprofen intake. Our case emphasizes the importance of the association between drug exposure and strong susceptibility to TINU syndrome giving the molecular characterization.

Intratumoral Heterogeneity in Differentiated Thyroid Tumors: An Intriguing Reappraisal in the Era of Personalized Medicine.

Differentiated thyroid tumors (DTTs) are characterized by significant molecular variability in both spatial and temporal intra-tumoral heterogeneity (ITH), that could influence the therapeutic management. ITH phenomenon appears to have a relevant role in tumor growth, aggressive behavior and drug resistance. Accordingly, characteristics and consequences of ITH in DTTs should be better analyzed and understood in order to guide clinical practice, improving survival. Consequently, in the present review, we investigated morphological and molecular ITH of DTTs in benign, borderline neoplasms and in malignant entities, summarizing the most significant data. Molecular testing in DTTs documents a high risk for recurrence of cancer associated with BRAFV600E, RET/PTC 1/3, ALK and NTRK fusions, while the intermediate risk may be related to BRAFK601E, H/K/N RAS and PAX8/PPARγ. In addition, it may be suggested that tumor genotype is associated with peculiar phenotype.

Conservative Management of Gestational Hypercalcemia Due to Primary Hyperparathyroidism with Lack of Complications.

INTRODUCTION: Primary hyperparathyroidism (PHPT) is rare in pregnancy. PHPT and hypercalcemia are associated with negative maternofetal outcomes. Therefore, an early diagnosis and adequate treatment are essential. CASE PRESENTATION: We described the case of a pregnant woman complaining of nausea, vomiting and weight loss. Diagnosis of gestational PHPT (GPHPT) was made based on elevated serum calcium and parathyroid hormone levels (3.4 mmol/L and 41.6 pmol/L). Neck ultrasound documented a nodule suggestive of enlarged parathyroid, whereas the abdomen ultrasound revealed renal microlithiasis. Conservative treatment was started with oral hydration and a low-calcium diet. Clinical and biochemical monitoring was weekly and multidisciplinary. Despite our suggestion, the patient refused parathyroidectomy in the second trimester. Additional intravenous fluid rehydration from the 15th to the 25th week of gestation ameliorated the symptoms rapidly, and reduced calcium levels progressively from the 23rd week. At week 40, the woman gave birth to a healthy girl. At month 8 postpartum, calcemia and PTH were still elevated, and accompanied by osteoporosis and nephrocalcinosis. Surgery was accepted, and a parathyroid adenoma was removed. CONCLUSION: In the absence of guidelines for GPHPT management, its treatment should be individualized. In our case, despite high calcium levels, conservative treatment with strict monitoring led to a positive outcome of pregnancy.

Alexithymia, Emotional Distress, and Perceived Quality of Life in Patients With Hashimoto's Thyroiditis.

Emotion-processing impairment represents a risk factor for the development of somatic illness, affecting negatively both health-related quality of life (HRQoL) and disease management in several chronic diseases. The present pilot study aims at (i) investigating the associations between alexithymia and depression, anxiety, and HRQoL in patients with Hashimoto's thyroiditis (HT); (ii) examining the association between these three psychological conditions together with HRQoL, and thyroid autoantibodies status as well as thyroid echotexture in patients with HT; and (iii) comparing the intensity of all these clinical psychological features in patients with HT versus controls. Twenty-one patients with serologically or ultrasonographically verified HT and 16 controls with non-toxic goiter or postsurgical hypothyroidism were recruited for this study. Serum thyrotropin (TSH) and free thyroxine, as well as thyroid autoantibodies (thyroglobulin antibodies and thyroid peroxidase antibodies), were assayed. Alexithymia, depression, anxiety, and HRQoL were assessed with Toronto Alexithymia Scale; Beck Depression Inventory, second edition; Hamilton Anxiety Rating Scale; and Health Survey Short-Form 36, respectively. A negative relationship between the difficulty to describe feelings and the cognitive component of depression was found (r = -0.46, p = 0.04). Besides, patients with seronegative HT had lower somatic anxiety than patients with HT who tested positive (r = -0.68, p = 0.01 and r = -0.59, p = 0.04, respectively). Besides, no statistically significant difference was found between patients with HT and controls with regard to somatic anxiety. The present study suggests the relevance of alexithymia in patients suffering from HT, which may be intertwined with a possible state of underreported depression that is mainly expressed through physical complaints. Promoting the capability to describe and communicate feelings could contribute to psychological elaboration and coping with the disease and, consequently, to the improvement of self-management and perceived HRQoL.

Rates of lymphocytic thyroiditis and ultrasound features of citologically-interrogated thyroid nodules based on the area of residence in a Sicily province.

PURPOSE: To verify the prevalence of autoimmune thyroiditis (AIT) and the ultrasound characteristics (composition and volume) of thyroid nodules with respect to the area of residence in the province of Messina, some areas having environmental issues. METHODS: Fine-needle aspiration-interrogated nodules (n = 902) of 809 patients were evaluated upon stratification into 8 areas of residence. RESULTS: Overall, women were younger than men (55.3 ± 14.0 vs. 58.6 ± 12.6 years, P = 0.0083). Patients residing in three areas (one hosting two garbage dumps, one hosting a petrochemical complex and a thermoelectrical power plant, and one hosting several ceramic factories [CFA]) were younger than those residing in the city of Messina (MEA) (52.9 ± 13.4 vs. 57.7 ± 13.6 years, P < 0.0001). Also, patients residing in those three areas had a greater rate of AIT, diagnosed either ultrasonographically/serologically (22.2% of patients) or cytologically (26.3% of nodules), compared with MEA (11.7% of patients, P = 0.0007 or 20.2% of nodules, P = 0.0815). Rates of AIT ranged 12.5-28.6% in the remaining four areas. Overall, nodules in women were smaller than in men (3.6 ± 5.7 vs. 6.1 ± 9.4 ml, P = 0.0006). Compared with the other seven areas, patients living in CFA had the largest nodules (6.8 ± 6.8 ml, P = 0.0040-0.0291), with the nodule volume being inversely correlated to patient's age (r = -0.4955, P = 0.0431). CONCLUSION: Rates of AIT and associated ultrasound features of thyroid nodules vary in different areas of our province. Further studies correlating these rates and features with exposure to specific toxicants are warranted.

Postpartum Thyroiditis in Women With Euthyroid and Hypothyroid Hashimoto's Thyroiditis Antedating Pregnancy.

CONTEXT: Postpartum thyroiditis (PPT) is defined as the occurrence of de novo autoimmune thyroid disease accompanied by thyroid dysfunction in the first year postpartum. However, hormonal changes resembling the typical pattern of PPT have been reported to occur even in women with pregestational Hashimoto's thyroiditis (HT) on levothyroxine (LT4). OBJECTIVE: To evaluate the risk of PPT in women with HT antedating pregnancy. DESIGN/SETTING: Retrospective chart review of pregnant women with HT antedating pregnancy seen in a university hospital (2008-2017), who were followed from preconception up to 1 year after delivery. PATIENTS: 167 women preconceptionally diagnosed with HT and classified as hypothyroid HT (hypo-HT; n = 98) or euthyroid HT (eu-HT; n = 69), according to their thyroid status at the time of diagnosis. OUTCOME MEASURES: PPT occurrence and associated clinical characteristics/risk factors. RESULTS: PPT occurred in 65/167 women, with a rate statistically greater in the eu-HT than in the hypo-HT group (68.1% vs 18.4%; odds ratio [OR] 9.49, 95% confidence interval [CI] 4.62-19.49). Most of the women experiencing PPT in both groups were euthyroid at the time of first-trimester evaluation (39/47 eu-HT [83%] and 16/18 hypo-HT [88.9%]). Multivariate regression analysis showed eu-HT group and first-trimester euthyroidism to be positively associated with PPT occurrence (ORs 10.71 and 3.89, respectively). CONCLUSION: PPT may occur in hypo-HT women on LT4 therapy, although significantly less frequently than in eu-HT women. The 4-fold higher risk of PPT in HT women maintaining euthyroidism at first -trimester of gestation suggests that the risk of PPT could be related to the amount of unaffected thyroid tissue.

RAS inhibition modulates kynurenine levels in a CKD population with and without type 2 diabetes mellitus.

Kynurenine pathway of tryptophan metabolism is involved in the pathophysiology of chronic kidney disease (CKD) and diabetes mellitus, mainly through the inflammation-induced activity of indoleamine 2,3-dioxygenase (IDO), and few studies have investigated its potential link with proteinuria. Renin-angiotensin system inhibitors (RASis) are recommended in these patients to decrease proteinuria, slow CKD progression and reduce cardiovascular risk, but whether these drugs influence kynurenine levels in humans is unknown. We evaluated serum tryptophan and kynurenine in patients suffering from CKD with or without type 2 diabetes mellitus, their correlations with markers of reduced kidney function, and their relationship with RAS-inhibiting therapy. Of 72 adult patients enrolled, 55 were receiving RASis, whereas 17 were not. Tryptophan was assessed by HPLC (high-performance liquid chromatography); kynurenine was measured using an enzyme-linked immunosorbent assay kit; IDO activity (%) was calculated with the formula (kynurenine/tryptophan) × 100. Kynurenine levels were significantly lower in the group under RASis compared to the untreated group (1.56 ± 0.79 vs 2.16 ± 1.51 µmol/l; P = 0.0378). In patients not receiving RASis, kynurenine was inversely related to estimated glomerular filtration rate (eGFR) (r = - 0.4862; P = 0.0478) and directly related to both proteinuria (ρ = 0.493; P = 0.0444) and albuminuria (ρ = 0.542; P = 0.0247). IDO activity was higher in patients with history of cardiovascular disease compared to patients with no such history, and it negatively correlated with eGFR (ρ = - 0.554; P = 0.0210) in the same group. These findings may contribute to explain the well-known beneficial effects of RAS inhibition in CKD population, especially considering that kynurenine is emerging as a potential new biomarker of CKD.

Novel treatments for anaplastic thyroid carcinoma.

Anaplastic thyroid cancer (ATC) is one of the deadliest human cancers and it is less than 2% of thyroid carcinomas (TCs). The standard treatment of ATC includes surgical debulking, accelerated hyperfractionated external beam radiation therapy (EBRT), and chemotherapy, in particular with cisplatin or doxorubicin, achieving about 10 months of median survival. Since ATC is a rare and aggressive tumor, it is still challenging to predict the patient clinical therapy responsiveness. Several genetic mutations have been described in ATC, involved in different molecular pathways linked to tumor progression, and novel therapies acting on these molecular pathways have been investigated, to improve the quality of life in these patients. Here we review the new targeted therapy of ATC. We report interesting results obtained with molecules targeting different pathways: angiogenesis (vandetanib, combretastatin, sorafenib, lenvatinib, sunitinib, CLM94, CLM3, etc.); EGFR (gefitinib, docetaxel); BRAF (dabrafenib/trametinib, vemurafenib); PPARγ agonists (rosiglitazone, pioglitazone, efatutazone); PD-1 and PD-L1 (pembrolizumab); TERT. To escape resistance to monotherapies, the evaluation of combination strategies with radiotherapy, chemotherapy, or targeted drugs is ongoing. The results of clinical trials with dabrafenib and trametinib led to the approval from FDA of this combination for patients with BRAF V600E mutated ATC with locally advanced, unresectable, or metastatic ATC. The anti-PD-L1 antibody immunotherapy, alone or combined with a BRAF inhibitor, has been shown also promising in the treatment of ATC. Furthermore, to increase the therapeutic success and not to use ineffective or even harmful treatments, a real tailored therapy should be pursued, and this can be achieved thanks to the new available genomic analysis methods and to the possibility to test in vitro novel treatments directly in primary cells from each ATC patient. Exploring new treatment strategies is mandatory to improve the survival of these patients, guaranteeing a good quality of life.

A patient with stress-related onset and exacerbations of Graves disease.

BACKGROUND: An 18-year-old, nonsmoking woman presented to her general practitioner with a 1-week history of weakness, fatigue, palpitations, nervousness, tremors, insomnia, heat intolerance, and sudden enlargement of a thyroid goiter that had been detected 2 years earlier. The patient's symptoms had started shortly after she experienced emotional stress. Diagnostic work-up disclosed an avid radioactive iodine uptake by the goiter. On ultrasound examination, the thyroid gland was enlarged with a diffusely hypoechogenic structure and intense vascularization. INVESTIGATIONS: Thyroid scintigraphy with (131)I; ultrasonography of the thyroid gland; and measurements of serum free T(3), free T(4), TSH levels and thyroid autoantibodies, including autoantibodies against thyroglobulin (TgAb), thyroperoxidase (TPOAb) and TSH receptor (TRAb). DIAGNOSIS: Graves disease, with stress-related onset and subsequent stress-related exacerbations. MANAGEMENT: The patient was treated with methimazole to normalize levels of thyroid hormone and thyroid autoantibodies, and with bromazepam to help her cope with stress. The daily dose of methimazole was kept low during pregnancy. Over the 4 year period when the patient was taking methimazole, exacerbations of hyperthyroidism occurred twice: during her first pregnancy and 9 months after her first delivery. On all three occasions, symptoms were preceded by stressful life events. Further exacerbations were avoided by starting bromazepam treatment soon after the patient experienced stressful events.

Stress-induced hashitoxicosis: case report and relative HLA serotype and genotype.

OBJECTIVE: Even though stress has been long known as a provocative factor for Graves' disease, its relationship with Hashimoto's thyroiditis is more controversial. Studies on this topic are scanty. This paper aims to report a case of stress-induced Hashitoxicosis. RESULTS: Here we report a case of Hashitoxicosis induced by a psychological stressful event in a 28-year-old woman with Hashimoto's thyroiditis. She had remained stably euthyroid for 12 years. She was first observed in April 2016, while euthyroid. She came back after 11 months because of fatigue and palpitations, in the absence of neck pain. Thyroid function tests revealed moderate thyrotoxicosis (undetectable TSH; FT4 36.94 pmol/L, normal values 9.0-24.46; FT3 13.50 pmol/L, normal values 3.07-6.14) with negative TSH-receptor antibodies. In the previous three months, she had experienced a psychological stressful event. Inflammatory markers were negative, and the white cell count was normal. Thyroid ultrasound revealed a modest increase in vascularization. Transient subclinical hypothyroidism ensued after seven weeks and spontaneously recovered. On the last visit, the patient was still on euthyroidism. (TSH 1.01 mU/L; FT4 9.22 pmol/L; FT3 3.98 pmol/L). We also performed HLA serotyping and genotyping. CONCLUSION: This case demonstrates that, similarly to Graves' disease, Hashitoxicosis can also be triggered by stressful life events.

Determinants of Early Response to Low-Intensity Extracorporeal Shockwaves for the Treatment of Vasculogenic Erectile Dysfunction: An Open-Label, Prospective Study.

The aim of this study was to expand existing literature on the effects of cardiovascular risk factors on the outcome of low-intensity extracorporeal shockwaves therapy (LIESWT), and to evaluate the role of hormone concentrations. Twenty patients with long-standing, PDE5i-resistant, vasculogenic erectile dysfunction (VED) were treated with six weekly sessions of LIESWT (9000 pulses). After a three-week break, four poor responders underwent another six weekly sessions. Rigidity score (RS) questionnaire was administered at baseline (T0), last session (T1), and three months after LIESWT (T2), while the Improvement component of the Clinical Global Impression of Change (CGIC-I) and the International Index of Erectile Function-5 (IIEF-5) questionnaires were administered at T1 and T2, and at T0 and T2, respectively. At T0 serum luteinizing hormone (LH), testosterone, sex hormone binding globulin (SHBG), calculated free testosterone, and prolactin levels were also recorded. At T1 and T2, 12/20 (60%) and 11/20 (55%) patients reached a RS ≥ 3; 16/20 (80%) and 13/20 (65%) improved their erections variably. Testosterone levels correlated positively with CGIC-I at T1. Patients < 65 years and those nonhypercholesterolemic had higher RS at T1 and T2. Age correlated negatively with RS at T1 and T2. At T0, diabetic patients had lower IIEF-5 scores, but those with RS ≥ 3 at T1 had higher IIEF-5 compared to those with RS < 3. Also, diabetes duration correlated inversely with IIEF-5 at T0. At T2, IIEF-5 improved significantly by an average of 2.8-points. We confirm safety and effectiveness of LIESWT for the treatment of VED. Age ≥ 65 years, diabetes, and hypercholesterolemia influence early and negatively the outcome of LIESWT.

BRAF Status in Papillary Microcarcinomas of the Thyroid Gland: a Brief Review.

Papillary thyroid microcarcinoma (PTMC) is defined by the World Health Organization as papillary cancer measuring 10 mm or less in diameter. Generally, PTMC shows an indolent clinical behavior with a good prognosis, although a minority of PTMC is characterized by an aggressive course. However, efforts to identify this aggressive subset of PTMC after surgery remain inconclusive. Several oncogenic pathways have been identified in thyroid cancer and have been applied translationally to improve prognosis and clinical management. In particular, the BRAFV600E mutation was found more frequently in large, aggressive, recurrent and advanced tumors. We aimed at reviewing studies on BRAFV600E mutation as a prognostic factor in PTMC.