Thyroid impairment and male fertility: a narrative review of literature.

PURPOSE: To evaluate the effect of thyroid function on male fertility, focusing on hypo- and hyperthyroidism. METHODS: A PubMed/MEDLINE, Web of Science, and Scopus research was performed. Original studies in English published online up to 31 May 2023 were selected and reviewed. The final reference list was defined based on the relevance of each paper to the scope of this review. RESULTS: The available data in animals (31 studies) and human (26 studies) showed conflicting results. However, thyroid dysfunction altered erection and ejaculation both in animal models than in men. CONCLUSION: Both hypothyroidism and hyperthyroidism seem to cause ejaculation and erectile dysfunction. Hence, Guidelines recommend against the systematic screening for thyroid disorders in the men in sub-fertile couples, but only in men with ejaculation and erectile dysfunction and/or altered semen parameters.

Myxedema coma secondary to levothyroxine malabsorption in a patient previously submitted to bariatric surgery

SUMMARY Treating hypothyroidism can be challenging in patients with malabsorption, as they require a higher daily dose of oral levothyroxine (L-T4). Oral L-T4 absorption occurs mainly in the jejunum and the ileum and is affected by gastric acidity. As a result, absorption can be impaired by bariatric surgery. This paper presents a case of myxedema in a young man who had previously undergone biliopancreatic diversion. He was referred to the Emergency Department with deteriorated mental state, hypotension, bradycardia and hypothermia. Laboratory tests revealed severe hypothyroidism and hypokalaemia. The clinical and biochemical profile of the patient suggested myxedema coma. The tablet-based L-T4 therapy was replaced with intravenous (iv) L-T4, oral liquid L-T4 and oral liothyronine (L-T3) and inotropic agents and supportive care were also administered, resulting in a gradual improvement in clinical condition. The patient reported taking L-T4 tablets as prescribed before hospitalization. In patients with malabsorption, impaired L-T4 absorption may lead to severe forms of hypothyroidism. This case outlines the need for more frequent monitoring of serum Thyroid Stimulating Hormone in patients submitted to bariatric surgery and suggests the benefit of using liquid L-T4 in the place of tablets in cases of malabsorption.

Autoimmune polyglandular syndrome type 4: experience from a single reference center.

Purpose: To characterize patients with APS type 4 among those affected by APS diagnosed and monitored at our local Reference Center for Autoimmune Polyglandular Syndromes. Methods: Monocentric observational retrospective study enrolling patients affected by APS diagnosed and monitored in a Reference Center. Clinical records were retrieved and analyzed. Results: 111 subjects (51 males) were affected by APS type 4, mean age at the onset was 23.1 ± 15.1 years. In 15 patients the diagnosis of APS was performed during the first clinical evaluation, in the other 96 after a latency of 11 years (range 1-46). The most frequent diseases were type I diabetes mellitus and celiac disease, equally distributed among sexes. Conclusions: The prevalence of APS type 4 is 9:100,000 people. Type I diabetes mellitus was the leading indicator of APS type 4 in 78% subjects and in 9% permitted the diagnosis occurring as second manifestation of the syndrome. Our data, showing that 50% of patients developed APS type 4 within the first ten years, don't suggest any particular follow-up time and, more importantly, don't specify any particular disease. It is important to emphasize that 5% of women developed premature ovarian failure.

Thyroid disease and autoimmunity in obese patients: a narrative review.

INTRODUCTION: The high prevalence of obesity and thyroid diseases worldwide justifies di per se their simultaneous coexistence. In recent decades, there has been a parallel and significant rise in obesity and thyroid diseases in industrialised countries, although the underlying mechanisms are complex and not well known. MATERIAL AND METHODS: The authors accomplished a comprehensive literature search of original articles concerning obesity and thyroid status. Original papers exploring the association between these two morbidities in children and adults were included. RESULTS: A total of 79 articles were included in the present analysis. A total of 12% of obese children (mean age 10.9 ± 1.4 years) showed a thyroid disease, and they were younger than healthy obese children (10.9 ± 1.2 vs. 11.0 ± 0.4 years, p < 0.001). Isolated hyperthyrotropinaemia was the most frequent finding in children (10.1%). Autoimmune thyroid disease was more frequent in puberal age. Thyroid antibodies and subclinical hypothyroidism were more frequent in obese that in non-obese patients (7% vs. 3%, p < 0.001; 10% vs. 6%, p < 0.001). Among obese adults, 62.2% displayed a thyroid disease; those affected were younger (35.3 ± 6.8 vs. 41.0 ± 1.9 years, p < 0.001), heavier [body mass index (BMI): 39.4 ± 6.3 vs. 36.1 ± 2.3 kg/m², p < 0.001], and more frequently female (13% vs. 8%, p < 0.001). The most frequent disease was overt hypothyroidism (29.9%). BMI appears to be correlated with TSH levels in obese adults. Overt hypothyroidism was significantly more frequent in obese patients (7% vs. 3%, p < 0.005), but no difference was found in thyroid antibodies (15% vs. 14%, p = 0.178). CONCLUSIONS: An undeniable relationship between obesity and thyroid impairments exists. Isolated hyperthyrotropinaemia is frequently seen in obese children, often followed by spontaneous resolution. Subclinical hypothyroidism should never be treated in children or adults with the aim of reducing body weight.

Interference or Noninterference Between Soy and Levothyroxine: That Is the Question. A Narrative Review of Literature.

OBJECTIVE: To evaluate the effect of soy intake on levothyroxine (L-T4) absorption among different L-T4 formulations. METHODS: A PubMed/MEDLINE, Web of Science, and Scopus research was performed. Case reports, case series, and original studies written in English and published online up to November 30, 2022, were selected and reviewed. The final reference list was defined based on the relevance of each study to the scope of this review. RESULTS: Few data, mainly case reports, seemed to suggest a possible interference of soy products on L-T4 tablets absorption. However, the only prospective randomized cross-over study showed no differences in L-T4 absorption when L-T4 and soy isoflavones were assumed concomitantly. The very little data available on liquid L-T4 formulations did not allow for any conclusions to be made, even if a double-blind placebo-controlled trial showed no impaired L-T4 absorption. CONCLUSION: The inference of soy products on L-T4 absorption, if present, seems to have little clinical impact. Considering this fact, the Hamlet-like question whether soy milk interferes with L-T4 absorption remains unanswered.

When and why patients drop out from benign thyroid nodules follow-up: a single centre experience.

PURPOSE: Drop-out in clinical long-term follow-up is a general problem that is potentially harmful to patients. No data about patients that drop out from thyroid ultrasound follow-up is available literature. The aim of the present retrospective study was to evaluate the characteristics of patients that dropped out from ultrasound thyroid nodule follow-up. PATIENTS AND METHODS: We reviewed medical records of all consecutive patients who underwent a fine needle aspiration from January 2007 to March 2009 in our department. All the patients with benign nodule(s) were recommended annual ultrasounds; patients who had dropped out from follow-up were included and a telephone interview was obtained to evaluate the reasons for dropping out. RESULTS: 289/966 (30%) of patients with benign nodules dropped out during follow-up; 94% of them within the first 5 years. Phone interviews were obtained from 201/289 (70%) of the patients. In the 57% of cases, the main declared reason for dropping out was nodular dimension stability during the first 2-3 years; 8.7% of them had forgotten about the appointment; 6.4% of subjects claimed to check only serum TSH, and 3.2% stated that they would undergo an ultrasound only if the nodule(s) were symptomatic. Finally, 10.7% patients continued follow-up in other centres. CONCLUSION: we showed that a third of patients miss their thyroid ultrasound follow-ups, and that the major cause is the low perceived threat coming from the disease. As a certain amount of drop-out is inevitable, attempting to reinforce our patients' awareness regarding their own health state is mandatory. TRIAL REGISTRATION: Trial registration: no. 4084.

Liquid levothyroxine formulations in patients taking drugs interfering with L-T4 absorption.

Purpose: To describe the current knowledge on thyroid hormonal profile in patients on liquid L-T4 therapy and drugs known to interfere with L-T4 absorption. Methods: A PubMed/MEDLINE, Web of Science, and Scopus research was performed. Case reports, case series, original studies and reviews written in English and published online up to 31 August 2022 were selected and reviewed. The final reference list was defined based on the relevance of each paper to the scope of this review. Results: The available data showed that novel levothyroxine formulations circumvent gastric pH impairment due to multiple interfering drugs such as proton pump inhibitors, calcium or iron supplements, sevelamer, aluminum/magnesium hydroxide and sodium alginate. Conclusion: New formulations can be taken simultaneously with drugs interfering with L-T4 absorption, in particular liquid formulations. Softgel capsules need more studies to support these data.

Case Report: Hypothalamic Amenorrhea Following COVID-19 Infection and Review of Literatures.

SARS-CoV-2 infection, responsible for the coronavirus disease 2019 (COVID-19), can impair any organ system including endocrine glands. However, hypothalamic-pituitary dysfunctions following SARS-CoV-2 infection remain largely unexplored. We described a case of hypothalamic amenorrhea following SARS-CoV-2 infection in a 36-year-old healthy woman. The diagnostic workup excluded all the causes of secondary amenorrhea, in agreement to the current guidelines, whereas the gonadotropin increase in response to GnRH analogue tests was suggestive for hypothalamic impairment. Therefore, since our patient did not present any organic cause of hypothalamic-pituitary disorder, we hypothesized that her hypothalamic deficiency may have been a consequence of SARS-CoV-2 infection. This assumption, besides on the temporal consecutio, is strengthened by the fact that SARS-CoV-2 infection can impair the hypothalamic circuits, altering the endocrine axes, given that angiotensin-converting enzyme 2 receptors have also been observed in the hypothalamus. We reviewed the literature regarding hypothalamic-pituitary dysfunction in patients with SARS-CoV-2 infection. No study has previously described female hypogonadotropic hypogonadism with secondary amenorrhea following COVID-19. We suggest clinicians focusing greater attention on this possible endocrine disorder.

Graves' disease treated by complementary medicine leading to thyroid storm: A case report.

BACKGROUND: Thyroid storm is a rare, life-threatening condition characterized by severe clinical manifestations of thyrotoxicosis and can be precipitated by several factors. We described a thyroid storm precipitated by a long-term treatment using homeopathic medicine containing iodine. CASE PRESENTATION: A 55-year-old Italian woman was admitted to our Sub-Intensive Care Unit with the diagnosis of congestive heart failure and thyrotoxicosis. She has been diagnosed with Graves' disease two years before; she refused conventional therapy and in the preceding six months had been using phytotherapeutic and homeopathic medicine. We found serum and urine iodine levels consistent with severe intoxication by iodine (serum iodine: 42100 mcg/L and urinary iodine: 4223 mcg/L, respectively). After a few hours, the patient went into cardiac arrest. She was subjected to invasive ventilation, dialyzed with continuous veno-venous hemofiltration and treated with vasoactive amines. CONCLUSION: The high level of iodemia manifested in our patient - around a thousand times greater than the normal range and itself associated with fatal outcomes - was caused by long-term homeopathic treatment. This long-term treatment has two consequences: first, iodine load-precipitated hyperthyroidism in thyroid storm, and secondly, it prevents us from treating patients with inorganic iodide.

Incidence of De Quervain's thyroiditis during the COVID-19 pandemic in an area heavily affected by Sars-CoV-2 infection.

PURPOSE: To evaluate the possible association between Covid-19 infection and subacute thyroiditis. METHODS: We reviewed the medical and imaging records of patients referred to our Department's outpatient setting dedicated to 'thyroid emergency' (records with a 'bollino verde'-green sticker, classifed as urgent) from April 2020 to October 2020. This outpatient clinic is devoted to patients requiring evaluation for severe hypothyroidism, thyrotoxicosis and neck discomfort or pain. All patients with a newly-diagnosed subacute thyroiditis were selected. The data of all patients receiving a diagnosis of subacute thyroiditis was collected retrospectively, taking into account the same period of time (April-October) and starting from 2016. RESULTS: During the COVID-19 outbreak in our region (April 2020 to October 2020) 396 patients attended the outpatient emergency clinic. Among them, 10 (2.5%) patients received a diagnosis of subacute thyroiditis. In a single patient, a 44-year-old man, a COVID-19 pulmonary infection had been diagnosed 7 weeks before the diagnosis of subacute thyroiditis. All of the remaining patients were and remain COVID-19 free as confirmed by telephone interview. The percentage of patients who received a diagnosis of subacute thyroiditis in the same period starting from 2016 was very similar (2.9%, 2.9%, 2.6% and 3.0% in 2016, 2017, 2018 and 2019, respectively). CONCLUSIONS: Our data do not show an increase in the incidence of subacute thyroiditis in the Brescia area, a region with the highest prevalence of COVID-19 in Italy during the period of the pandemic outbreak.

Ultrasound of benign thyroid nodules: A 120 months follow-up study.

OBJECTIVE: Some evidence suggests that most benign nodules exhibit no significant size increase during 5 years of follow-up, although conflicting results have emerged. The aim of the present study is to evaluate the frequency and the magnitude of growth in benign nodules during 120 months of follow-up. DESIGN: We reviewed the medical and imaging records of patients who were submitted to ultrasound-guided FNA of thyroid nodules at our hospital from January 2007 to March 2009. We selected only patients with benign nodules who underwent annual ultrasound evaluation in our Department. RESULTS: Among 966 selected patients, 289 were lost during follow-up, meaning that the total number of patients analysed was 677 (474 women and 203 men), with a mean age of 45.6 (16-71) years. In 559/677 patients (82.7%), the size of the nodule remained stable during follow-up; 42 (6.2%) patients experienced spontaneous nodule shrinkage, and 75 (11.1%) patients showed nodule growth. Patients with or without nodule growth during follow-up were superimposable at baseline for age, gender, TSH values, number of patients on levothyroxine treatment and nodule characteristics. All baseline variables in predicting nodular growth were entered to an adjusted multivariate logistic regression model. None of the parameters taken into account was associated with nodular growth. CONCLUSIONS: In conclusion, the majority of benign nodules remained stable over the period of monitoring. On the basis of our experience, we recommend ultrasound examination at a distance of 2 and 5 years following cytological evaluation, then every 4-5 years from then on.

Thyroid scintigraphy in the era of fine-needle aspiration cytology.

PURPOSE: To evaluate whether thyroid scintigraphy would alter the clinical management of patients referred for fine-needle aspiration cytology (FNA). METHODS: We reviewed the medical and imaging records of patients referred to our Department between 2016 and 2019. All the patients had to take a serum thyrotropin test administered in our hospital at least two months before the FNA; where the TSH level was ≤1.5 mIU/L, the patients were subjected to a scan and subsequently to FNA, where indicated. We selected only healthy patients with no previous history of thyroid disease, who were not taking any drugs and who had a TSH level of ≤1.5 mIU/L. We excluded patients with multinodular goitre. RESULTS: A total of 176 patients were analysed. A total of 67/176 patients (38%) showed a serum of TSH ≤ 0.27 mIU/L. Scintigraphy identified a hot nodule in 142 lesions (80.7%), a warm nodule in 8 lesions (4.5%) and a cold nodule in 26 lesions (14.8%). The ROC curve analysis indicated that a TSH value of ≤0.42 mIU/L identified patients with hyperfunctioning nodules with a sensitivity of 65% and a specificity of 77%. All patients with cold and warm nodules were submitted to FNA: 22/26 (85%) and 5/8 (63%) lesions showed suspected malignancy or were compatible with malignancy, respectively. CONCLUSION: Speculating on our data, if we had subjected our patients to FNA as indicated by the 2015 ATA guidelines, we would have subjected 117 patients to cytology, from whom 83 had undetected hot nodules. Conversely, by adopting scintigraphy for all patients with TSH ≤ 1.5 mIU/L, 109 patients have avoided FNA. However, our study was performed in a region with a history of mild iodine deficiency. Therefore, we cannot claim that our observation is valid for patients born and living in areas with sufficient iodine uptake. We recommend thyroid scintigraphy for treating single thyroid nodules in euthyroid patients born and living in regions with an iodine deficiency, when TSH levels are below 1.5 mIU/L before FNA.

Liquid Levothyroxine Formulation Taken during Lunch in Italy: A Case Report and Review of the Literature.

Levothyroxine (L-T4) is among the most widely prescribed medications in the world, and it is considered by the World Health Organization an essential medicine for basic health care. Replacement therapy has always been considered straightforward although different factors may interfere with intestinal absorption of L-T4, including food, dietary fibre, coffee, drugs, and gastrointestinal diseases. For these reasons, current guidelines recommend that L-T4 should be taken in a fasting state because its absorption is maximised when it is taken on an empty stomach, reflecting the importance of gastric acidity in the absorption process. In addition to sodium L-T4 in tablet form, various formulations (soft-gel capsules and liquid solutions) have become available for clinical use in the last years promising improved absorption. We described a 31-year-old Italian man who took liquid levothyroxine formulation during lunch. He was under replacement therapy with liquid levothyroxine 75 mcg daily for hypothyroidism due to Hashimoto thyroiditis for three years. During confirmation of the L-T4 replacement therapy, the patient stated that he was going to continue to "take liquid levothyroxine during (his) lunch every day." We recommended taking the medication correctly in the morning at least thirty minutes before breakfast and repeating TSH, fT4, and fT3 after three months. The thyroid hormonal profiles taken after 3 and 6 months were comparable to those when the patient was taking the medication during lunch. In conclusion, liquid levothyroxine formulation should be preferred in case of malabsorption or potential malabsorption. Liquid formulation should be preferred due to the possibility of taking it during breakfast, which significantly improves the compliance of patients. Further studies are needed to evaluate the possibility of taking liquid L-T4 during lunch.

Tocilizumab for the treatment of severe COVID-19 pneumonia with hyperinflammatory syndrome and acute respiratory failure: A single center study of 100 patients in Brescia, Italy.

A hyperinflammatory syndrome (HIS) may cause a life-threatening acute respiratory distress syndrome (ARDS) in patients with COVID-19 pneumonia. A prospective series of 100 consecutive patients admitted to the Spedali Civili University Hospital in Brescia (Italy) between March 9th and March 20th with confirmed COVID-19 pneumonia and ARDS requiring ventilatory support was analyzed to determine whether intravenous administration of tocilizumab (TCZ), a monoclonal antibody that targets the interleukin 6 (IL-6) receptor, was associated with improved outcome. Tocilizumab was administered at a dosage of 8 mg/kg by two consecutive intravenous infusions 12 h apart. A third infusion was optional based on clinical response. The outcome measure was an improvement in acute respiratory failure assessed by means of the Brescia COVID Respiratory Severity Score (BCRSS 0 to 8, with higher scores indicating higher severity) at 24-72 h and 10 days after tocilizumab administration. Out of 100 treated patients (88 M, 12 F; median age: 62 years), 43 received TCZ in the intensive care unit (ICU), while 57 in the general ward as no ICU beds were available. Of these 57 patients, 37 (65%) improved and suspended noninvasive ventilation (NIV) (median BCRSS: 1 [IQR 0-2]), 7 (12%) patients remained stable in NIV, and 13 (23%) patients worsened (10 died, 3 were admitted to ICU). Of the 43 patients treated in the ICU, 32 (74%) improved (17 of them were taken off the ventilator and were discharged to the ward), 1 (2%) remained stable (BCRSS: 5) and 10 (24%) died (all of them had BCRSS≥7 before TCZ). Overall at 10 days, the respiratory condition was improved or stabilized in 77 (77%) patients, of whom 61 showed a significant clearing of diffuse bilateral opacities on chest x-ray and 15 were discharged from the hospital. Respiratory condition worsened in 23 (23%) patients, of whom 20 (20%) died. All the patients presented with lymphopenia and high levels of C-reactive protein (CRP), fibrinogen, ferritin and IL-6 indicating a HIS. During the 10-day follow-up, three cases of severe adverse events were recorded: two patients developed septic shock and died, one had gastrointestinal perforation requiring urgent surgery and was alive at day 10. In conclusion, our series showed that COVID-19 pneumonia with ARDS was characterized by HIS. The response to TCZ was rapid, sustained, and associated with significant clinical improvement.

Could Serum TSH Levels Predict Malignancy in Euthyroid Patients Affected by Thyroid Nodules with Indeterminate Cytology?

BACKGROUND: Serum TSH levels in the upper-normal range were reported to be associated with increased risk of thyroid malignancy. However, measurement of TSH levels is currently not recommended for assessing the risk of malignancy in patients with newly diagnosed thyroid nodules. OBJECTIVE: To evaluate a possible relationship between the serum levels of TSH and the histological outcome of patients undergoing thyroidectomy for thyroid nodules with indeterminate cytology. MATERIALS AND METHODS: We collected the clinical data of all patients who had performed ultrasound-guided FNA of thyroid nodules with cytological diagnosis of indeterminate lesions (TIR3A and TIR3B) and serum TSH levels within the normal range. All patients had been submitted to thyroid surgery (hemi or thyroidectomy, as appropriate), and histological diagnosis had been performed. RESULTS: A histological diagnosis of thyroid malignancy was rendered in 74/378 (19.6%) nodules. Patients with histologically proven thyroid malignancy were characterized by higher serum levels of TSH as compared to patients with histologically proven benign nodules (3.03 ± 1.16 vs. 2.37 ± 1.19 mIU/L, p < 0.001). To further analyze the role of serum TSH in predicting thyroid cancer, patients were stratified in 4 groups according to quartiles of TSH concentrations. The prevalence of malignancy was 12.2% for the first quartile and 50.0% for the last quartile. ROC curve analysis identified that a serum TSH level of ≥2.7 mIU/L predicted thyroid malignancy with a sensitivity of 61% and a specificity of 65%. CONCLUSIONS: TSH levels in the upper-normal range are associated with an increased risk of thyroid malignancy in patients affected by thyroid nodules with indeterminate cytology at FNA. The measurement of serum TSH levels represents an easily performed additional tool for decision-making in patients with indeterminate cytological findings.

Selenium supplementation in patients with subclinical hypothyroidism affected by autoimmune thyroiditis: Results of the SETI study.

OBJECTIVE: The purpose of this prospective study was to assess the effects of selenium supplementation on TSH and interferon-γ inducible chemokines (CXCL9, CXCL10 and CXCL11) levels in patients with subclinical hypothyroidism due to Hashimoto's thyroiditis. PATIENTS AND METHODS: Patients with subclinical hypothyroidism due to Hashimoto thyroiditis were prospectively enrolled in the SETI study. They received 83mcg of selenomethionine/day orally in a soft gel capsule for 4 months with water after a meal. No further treatment was given. All patients were measured thyroid hormone, TPOAb, CXCL9, CXCL10, CXCL11, iodine, and selenium levels at baseline and at study end. RESULTS: 50 patients (43/7 female/male, median age 43.9±11.8 years) were enrolled, of which five withdrew from the study. At the end of the study, euthyroidism was restored in 22/45 (48.9%) participants (responders), while 23 patients remained hypothyroid (non-responders). There were no significant changes in TPOAb, CXCL9, CXCL10, CXCL11, and iodine levels from baseline to the end of the study in both responders and non-responders. TSH levels were re-tested six months after selenomethionine withdrawal: 83.3% of responding patients remained euthyroid, while only 14.2% of non-responders became euthyroid. CONCLUSIONS: The SETI study shows that short-course supplementation with selenomethionine is associated to a normalization of serum TSH levels which is maintained 6 months after selenium withdrawal in 50% of patients with subclinical hypothyroidism due to chronic autoimmune thyroiditis. This TSH-lowering effect of selenium supplementation is unlikely to be related to changes in humoral markers of autoimmunity and/or circulating CXCL9.

Ultrasound Microvascular Blood Flow Evaluation: A New Tool for the Management of Thyroid Nodule?

BACKGROUND: Toshiba Medical System has developed a new Doppler technique [Superb Microvascular Imaging (SMI)] that has improved microvascular flow imaging. SMI depicts perinodular and intranodular thyroid microvascular flow in higher detail compared to standard colour Doppler (CD) and power Doppler (PD) imaging. OBJECTIVE: Assess the nodular microvascular architecture by SMI compared to CD and PD features in a series of thyroid nodules submitted to fine needle aspiration cytology, in order to evaluate the potential of SMI in detecting thyroid cancer. MATERIALS AND METHODS: From April 2016 to July 2017, 254 patients with thyroid nodules, evaluated as at high risk for malignancy in agreement with AACE/ACE/AME guidelines, were submitted to cytology. All nodules were previously submitted to ultrasound grayscale, CD, PD, and SMI evaluation. Benign and malignant nodules were stratified in accordance to the number of vessels visualised by SMI: score 1 with a maximum of two blood vessels and score 2 with three or more vessels. RESULTS: Score 1 was found in 59.6% of benign nodules and in 17.9% of malignant nodules, whereas score 2 was found in 40.4% and in 82.1%, respectively (sensitivity 81.7%; specificity 60.5%, p < 0.001). Variables significantly associated with malignancy in the univariate analysis were gender (OR, 0.18; 95% CI, 0.08-0.37; p < 0.001), vascularity (OR, 1.91; 95% CI, 1.65-3.89; p < 0.001), and SMI (OR, 6.72; 95% CI, 3.89-11.59; p < 0.001); multivariate logistic model confirmed SMI score 2 as an independent risk factor for malignancy (OR, 6.99; 95% CI, 3.46-12.09; p < 0.001). CONCLUSIONS: This prospective pilot study showed that SMI can depict intranodular flow in higher detail compared to CDI and PDI, thus improving thyroid cancer detection.

p.Ser891Ala RET gene mutations in medullary thyroid cancer: Phenotypical and genealogical characterization of 28 apparently unrelated kindreds and founder effect uncovering in Northern Italy.

Applying genetic screening in medullary thyroid cancer (MTC) patients we identified an unexpectedly high frequency of c.2671T>G, p.Ser891Ala RET mutation carriers. Our aim was to: (a) deeply characterize the clinical expression of this mutation, (b) identify the presence of a founder effect in our region. Genetic analysis was performed in 251 relatives from 28 Ser891Ala kindreds, among 108 p.Ser891Ala asymptomatic carriers, 64 were submitted to thyroidectomy: mean age for 10 subjects presenting C-cells hyperplasia was 30.2 ± 13.7 years, raising to 37.9 ± 10.3 in 14 subjects with micro-MTC and to 55.0 ± 14.7 years in 39 subjects with MTC. Age-related progression across histopathological groups CCH/microMTC and MTC were statistically significant: genetic screening in Ser891Ala families could be safely postponed at the age of 14. To investigate the hypothesis of a common ancestor for Ser891Ala mutation we genotyped for 18 polymorphic microsatellite markers encompassing RET locus all subjects belonging to Ser891Ala families and we identified a founder effect, estimating the age of a common ancestor, dating back to 1493 AD. Ethnographic data collected in historical archives support laboratory results; the high prevalence of this mutation in our region could suggest the hypothesis of a population study to realize a preventive intervention in a rare neoplastic disease.

Adherence to Levothyroxine Treatment Among Patients With Hypothyroidism: A Northeastern Italian Survey.

Background: A significant number of patients show sub-optimal adherence to levothyroxine (LT4) therapy, mainly because they have to postpone their breakfast by at least 30 min. The aim of this observational cross-sectional study was to assess the therapeutic compliance of patients on LT4 treatment and to verify the preference of a lifetime treatment in tablet or liquid form. Patients and Methods: Ambulatory care patients aged 18 years or older, affected by hypothyroidism and on LT4 treatment (in tablet or liquid form) were administered the eight-item Morisky Medication Adherence Scale (MMAS-8). The MMAS-8 questionnaire was supplemented with 3 further items to specifically evaluate preference between tablet and liquid forms of LT4 for lifetime treatment. Results: A total of 320 patients (272 female), median age 47.9 ± 15.6 years (range, 20-78 years), completed the MMAS-8 questionnaire. Eighty-seven percent of the participants were adhering to their treatment for both tablet and liquid LT4 formulations, although significant differences emerged. Patients on LT4 tablets forgot to take their medication more frequently (p < 0.001), felt hassled about sticking to their treatment plan (p < 0.001), and had difficulty remembering to take all their medication(s) (p < 0.001) than those on liquid LT4 treatment. Conclusions: Adherence to LT4 treatment was high for both tablet and liquid formulations. Taking LT4 at breakfast was the most convenient option for most patients.

TSH Variability of Patients Affected by Differentiated Thyroid Cancer Treated with Levothyroxine Liquid Solution or Tablet Form.

BACKGROUND: Recent guidelines from the American Thyroid Association (ATA) indicate that, in many patients affected by differentiated thyroid cancer (DTC), the serum TSH should be maintained between 0.1 and 0.5 mU/L. The purpose of this study was to evaluate the TSH variability of patients affected by DTC treated with liquid L-T4 formulation or in tablet form. PATIENTS AND METHODS: Patients were eligible if (a) they were submitted to a total thyroidectomy and 131I remnant ablation for DTC in our institution and (b) they were classified low-risk patients according to ATA guidelines 2009. Patients were randomized (1 : 1) to receive treatment of hypothyroidism with liquid L-T4 or tablet form. The first check-up evaluation was made from 8 to 12 months after 131I remnant ablation. TSH values were established again after further 12 months. RESULTS: A significant increase in TSH values (median) was observed in patients taking tablets [TSH (min-max): 0.28 (0.1-0.45) versus 0.34 (0.01-0.78) mIU/L, p = 0.041] as compared to those taking liquid formulation [TSH (min-max): 0.28 (0.1-0.47) versus 0.30 (0.1-0.55) mIU/L, p = 0.345]. CONCLUSIONS: The use of L-T4 liquid formulation, as compared to that of tablets, resulted in a significantly higher number of DTC patients maintaining TSH values in range for the ATA risk score, reducing TSH variability over the time.