Thyroid dysfunction in COVID-19 patients.

PURPOSE: "Non thyroidal illness syndrome" (NTIS) or "euthyroid sick syndrome" (ESS) is a possible biochemical finding in euthyroid patients with severe diseases. It is characterized by a reduction of serum T3 (fT3), sometimes followed by reduction of serum T4 (fT4). The relationship between thyroid hormones levels and mortality is well known and different studies showed a direct association between NTIS and mortality. The sudden spread of the 2019 novel coronavirus (SARS-CoV 2) infection (COVID-19) and its high mortality become a world healthcare problem. Our aim in this paper was to investigate if patients affected by COVID-19 presented NTIS and the relationship between thyroid function and severity of this infection. METHODS: We evaluated the thyroid function in two different groups of consecutive patients affected by COVID-19 with respect to a control group of euthyroid patients. Group A included patients hospitalized for COVID-19 pneumonia while patients requiring intensive care unit (ICU) for acute respiratory syndrome formed the group B. Group C identified the control group of euthyroid patients. RESULTS: Patients from group A and group B showed a statistically significant reduction in fT3 and TSH compared to group C. In group B, compared to group A, a further statistically significant reduction of fT3 and TSH was found. CONCLUSIONS: COVID-19 in-patients can present NTIS. FT3 and TSH serum levels are lower in patients with more severe symptoms.

Source and symptoms of COVID-19 among hospital workers in Milan.

BACKGROUND: Healthcare workers (HCWs) are commonly infected by SARS-CoV-2 and represent one of the most vulnerable groups. Adequate prevention strategies are necessary to guarantee HCWs' safety, as well as to prevent dissemination of the infection among patients. AIMS: To describe a case series of SARS-CoV-2-positive HCWs in a large public healthcare organization in Milan (Italy) during the most devastating weeks of the epidemic and analyse the sources, symptoms and duration of SARS-CoV-2 infection. METHODS: This study included 172 SARS-CoV-2-positive HCWs who were infected between the 25th of February and the 7th of April 2020. A nasopharyngeal swab (NPS) and RT-PCR were used to indicate. RESULTS: Initially, the most common sources of infection were other positive HCWs (49%). Medical doctors and nursing assistants were most frequently infected, with infection rates of 53/1000 and 50/1000, respectively. COVID-19 departments were less affected than internal medicine, surgery, intensive care, or emergency room. The most commonly reported symptom was mild cough, while loss of smell (anosmia) and loss of taste (ageusia) were reported as moderate and severe by 30-40% of HCWs. The time necessary for 50% of workers to recover from the infection was 23 days, while it took 41 days for 95% of HCWs to become virus-free. CONCLUSIONS: HCWs are commonly infected due to close contacts with other positive HCWs, and non-COVID departments were most affected. Most HCWs were asymptomatic or subclinical but contact tracing and testing of asymptomatic HCWs help identify and isolate infected workers.

Everolimus is a new anti-cancer molecule: Metabolic side effects as lipid disorders and hyperglycemia.

In the last few years, molecular targeted therapies have replaced traditional cytotoxic chemotherapy in the fight against many cancers to the extent that our understanding of tumor biology has become more sophisticated. This shift has markedly changed adverse event profiles, compared to cytotoxic chemotherapy, affecting a diverse range of organ systems. Everolimus was approved by the FDA in 2011 for the treatment of progressive pancreatic NE tumors. It is an inhibitor of mammalian target of rapamycin (mTOR) and exhibits antitumor activity via disruption of various signaling pathways and it's used in the treatment of advanced renal cell cancer, breast cancer and neuroendocrine tumors (NET); it's used also as anti-rejection agent for transplantation but with lower doses for anti-rejection (1.5-3.0 mg/day) than for anti-cancer (5-10 mg/day) treatment. Metabolic side effects are the most frequent reported and will be discussed in this review.

Measuring calcitonin in washout of the needle in patients undergoing fine needle aspiration with suspicious medullary thyroid cancer.

Calcitonin measurement in washout of the needle after aspiration (WO-Ct) has been rarely evaluated. Here we analyzed the role of WO-Ct in a series of subjects who underwent fine needle aspiration (FNA) with suspicious medullary thyroid cancer (MTC). Twenty-one patients referred following elevated serum calcitonin (S-Ct) or suspicious MTC by cytology. All patients underwent re-evaluation of S-Ct, FNA, and measurement of WO-Ct. S-Ct and WO-Ct were assessed by chemiluminescence assay (IMMULITE 2000, Diagnostic Products Corporation, USA). S-Ct showed elevated value in six subjects (mean 368.8 ± 373.9 pg/ml), of which three cases were cytologically classified as Class 5. WO-Ct obtained in this group (304.0 ± 309.3 pg/ml) was no different from S-Ct. After surgery MTC was confirmed in all patients. In the other 15 patients MTC was excluded by cytology or histology. Two subjects had moderately skewed S-Ct with nonmedullary histology. In the remaining 13 patients S-Ct resulted normal (6.2 ± 5.6 pg/ml) and WO-Ct low (2.9 ± 2.2 pg/ml). Significant (two-tailed P < 0.05, r(2) = 0.27, 95% confidence interval = 0.017-0.81) correlation was found between S-Ct and WO-Ct in nonmedullary patients but not in MTC patients. This study showed that WO-Ct can play a role in diagnosing primary and metastatic MTC. The procedure is easy, cost effective, and should be used in patients undergoing FNA with elevated S-Ct. Further studies and guidelines for the method are needed to use this technique in clinical routine. Until this any institute should use itself cut-off.

Thyroid incidentaloma identified by ¹8F-fluorodeoxyglucose positron emission tomography with CT (FDG-PET/CT): clinical and pathological relevance.

OBJECTIVE: The percentage of patients with thyroid cancer incidentally diagnosed during a (18) F-fluorodeoxyglucose Positron Emission Tomography with computed tomography (CT) (FDG-PET/CT) for nonthyroid diseases ranges between 26% and 50%. DESIGN: Retrospective assessment of the clinical and pathological features of thyroid incidentalomas at FDG-PET/CT, aiming to identify potential predictors of malignancy. PATIENTS: Fifty-two patients with incidental thyroid uptake at FDG-PET/CT were retrospectively included [38 W, age 64·1 ± 12·5 years (mean ± SD)]. An arbitrary cut-off level of 5·0 for the 'maximum standardized uptake value' (SUV max) was chosen to differentiate benign from malignant tumours. Complete thyroid function, neck ultrasonography (US) features, and cyto-histological results were reported for all cases. RESULTS: In our institution, the prevalence of incidental thyroid (18) F-fluorodeoxyglucose ((18) F-FDG) uptake was nearly 1·76%. The prevalence of focal uptake correlated with greater risk of malignancy (P < 0·01). In particular, the euthyroidism (P < 0·003) and a SUV max >5·0 (P < 0·0001) were associated with the diagnosis of thyroid cancer. Diffusely increased FDG-PET/CT uptake in the thyroid was related to benign conditions. CONCLUSIONS: The presence of focal uptake with high SUV max and euthyroidism correlate with high likelihood of malignancy. Performing a neck US would have to be recommended in all patients with euthyroidism and an incidental FDG-PET/CT focal thyroid uptake. We do not suggest to use FDG-PET/CT as a screening tool for thyroid cancer in the general population, because of both its high cost and low incidence of thyroid incidentaloma at FDG-PET/CT.

Canine leishmaniasis surveillance in a northern Italy kennel.

An epidemiological survey on canine leishmaniasis (CanL) was performed during a 3-year period (2007-2009) in a public kennel of the Bologna province. The presence of the disease was shown in the canine population for the first time in 2007 by indirect fluorescent antibody test (IFAT). The parasite circulation was confirmed also by direct diagnostic tools, as PCR, cytology and cultural method, performed on different bioptic materials. The parasite was isolated and identified as Leishmania infantum zymodeme MON 1. The serological monitoring was performed also in 2008 and 2009 on animals that previously showed negative or uncertain results. The incidence values calculated by significant seroconversions in IFAT titre ≥ 1/160, ranged between 4.9% and 6.6%, indicating a stable focus of leishmaniasis. The entomological survey, performed by sticky and CO(2)-baited traps in 2008, showed the presence of the vector Phlebotomus perfiliewi. This study allowed us to identify a stable focus of CanL in an area that was not considered eco-compatible with the presence of the vector and infection. Our results confirm the northward spread of CanL towards areas not previously affected by autochthonous foci.

Gene variants associated to malignant thyroid disease in familial adenomatous polyposis: a novel APC germline mutation.

BACKGROUND AND AIM: Familial adenomatous polyposis (FAP) is an autosomal inherited syndrome characterized by hundreds to thousands colorectal adenomatous polyps with oncological transformation lifetime risk of 100%. FAP is mainly associated with mutations in APC (autosomal dominant inheritance) or MUTYH (autosomal recessive inheritance) genes. Affected individuals are at increased risk of developing extra-intestinal tumors. Lifetime risk of developing thyroid carcinoma has been described in previous reports of about 2-12%, mainly in females, and the mean age is below 30 yr. About 95% of cancers are papillary thyroid carcinomas (PTC), mostly multifocal. The aim of this study was to evaluate the frequency of PTC among our series of FAP patients and to assess the type of gene mutation associated with the disease. METHODS: Fifty-four subjects from 36 FAP families were selected (29 females/25 males) and the mean age (±SD) at diagnosis was 28.8±10.8 yr. All patients underwent blood examination for thyroid hormones and antibodies, germline mutational analysis of APC and/or MUTYH genes, thyroid ultrasound, and endocrinological evaluation. RESULTS: In 13/54 (24.1%) subjects, an eumetabolic thyroid disease was found: plurinodular disease in 7/54 (13.0%); single nodule in 4/54 (7.4%); in 2/54 patients (3.7%), we found a malignant nodule characterized after total thyroidectomy as a classical PTC. Both patients were female and showed a classic FAP phenotype. Mutational analysis revealed in the first patient the APC germline mutation 3183_87del ACAAA and in the second patient the del9-10 (del9080dup11) novel APC variant; the first mutation has been already reported in association with PTC; to our knowledge the second mutation has never been previously reported in association with FAP. CONCLUSIONS: In the population examined, the estimated prevalence of thyroid malignant diseases was 3.7%. In both patients, the identified APC gene pathogenetic variants mapped within the 5' region of the gene, previously reported as a PTC-associated mutational hot spot. Both patients had classic FAP phenotype and genetic analysis revealed two pathogenetic APC mutations: c.3183_87delACAAA, a recurrent pathogenetic variant and del9-10 (del9080dup11), a novel, not previously described genomic rearrangement. In agreement with previous studies, the morpho-functional surveillance of thyroid in FAP series should be recommended. A better insight into the overall genotype-phenotype correlation of APC gene mutations would be helpful for the identification of at-risk individuals.

Transition process of patients with type 1 diabetes (T1DM) from paediatric to the adult health care service: a hospital-based approach.

INTRODUCTION: The outcomes of different types of transitions of young people with chronic diseases have been poorly investigated. OBJECTIVE: To evaluate and compare a structured transition from the paediatric diabetes services (PDS) into the adult diabetic services (ADS) with an unstructured one. DESIGN: We retrospectively investigated 62 adolescents and young adults with type 1 diabetes discharged from the PDS from 1 January 1994 to 31 December 2004. Thirty-two patients (group A) were transferred to the ADS of the same hospital with an unstructured method (letter) and 30 patients after a structured transfer planned with adult physicians (group B). We analysed the date of the first admission in ADS, the glycated haemoglobin (HbA1c), the clinic attendance rate in PDS and in the first year in ADS, and a phone questionnaire on the transition experience. RESULTS: The duration of the transfer was longer in A than in B with a lack of medical assistance during the unstructured transition (P < 0.001). At the first visit in ADS, before any medical intervention, HbA1c was improved in B compared to the last in PDS (P < 0.01), and had a trend in worsening in A. After 1 year in the ADS there was a better clinical attendance, and a lower HbA1c in B than in A (P < 0.05). All the subjects of group B reported a favourable opinion for the structured transition (P < 0.0001). CONCLUSION: The transition process plays an important role in diabetic care and a structured plan is mandatory to avoid to lose the patients and to get worse their health.

Chlamydia trachomatis serovar distribution and other concurrent sexually transmitted infections in heterosexual men with urethritis in Italy.

The distribution of Chlamydia trachomatis serovars among 157 heterosexual male patients with urethritis and the presence of coinfections with other sexually transmitted infections were studied. One hundred seventeen (74.5%) patients, with a mean age of 33.7 years, were Italians, whereas 40 (25.5%) were immigrants coming from eastern European countries, Africa, and South America. All the immigrants and 82 (70.0%) Italian patients reported sex with prostitutes. Out of 157 patients, 73 (46.5%) were found positive for C. trachomatis in urethral secretions and eight different C. trachomatis serovars were identified. The most common serovars were E (n = 18; 24.7%), D (n = 15; 20.5%), G (n = 14;19.2%), and F (n = 12; 16.4%). The sequencing data showed a high degree of conservation of the omp1 gene. Thirty-six (46.7%) out of the 73 C. trachomatis-positive patients were coinfected with another sexually transmitted infection. The most common coinfection was gonorrhoea detected in 22 (30.1%) patients, followed by condyloma in eight (8.2%) patients, syphilis in five (6.8%), and HIV in three (4.1%).

Hurthle cell tumours of the thyroid. Personal experience and review of the literature.

Hurthle cell carcinoma represents about 5% of differentiated thyroid carcinomas. The prognosis of the malignant type of the tumour is still under debate as some Authors have reported that Hurthle cell adenoma occasionally behaves like Hurthle cell carcinoma. Aim of the present study was to evaluate previously reported data and personal experience on the clinical and pathological features of patients affected by Hurthle cell tumour that may predict disease progression and death. In the literature, factors potentially associated with decreased survival were identified and include: age, disease stage, tumour size, extra-glandular invasion, lymph node disease, distant metastases, extensive surgery, radioiodine treatment. From 1992 to 2003, the Authors identified 28 patients affected by Hurthle cell tumour, 9 with Hurthle cell adenoma and 19 with Hurthle cell carcinoma. Of these, 22 were females and 6 males. Mean age of patients affected by adenoma was 49.7 years (range 30-72) vs. 49.3 years (range 15-72) in Hurthle cell carcinoma patients. In all patients, total thyroidectomy was performed. At histology, 9 adenomas, 5 "minimally invasive" and 14 invasive carcinomas were found. Post-operatively, in Hurthle cell carcinoma patients, TNM staging showed 9 patients with stage I, 5 stage II, 4 stage III and one stage IVa (UICC, 2002). All invasive carcinomas underwent (131)I therapy (91-585 mCi). One Hurthle cell carcinoma patient received external beam radiotherapy. The mean follow-up period was 62 months (range 6-324). Relapse was not observed in any of the cases with adenoma. Only one Hurthle cell carcinoma patient showed distant lung metastases at 60 months' follow-up. In conclusion, Hurthle cell carcinoma was not found to present a more aggressive behaviour than follicular carcinoma, when risk factors, including extent of tumour invasion, were taken into account. None of the patients with Hurthle cell adenoma showed a relapse or death caused by the tumour.

Fertility and hypopituitarism.

Fertility outcomes in hypopituitaric women are about half of those reported in isolated hypogonadotropic hypogonadism; GH deficiency (GHD) is a major contributor to poor pregnancy rate. GH seems to play a physiological role in the control of male sexual maturation and adult reproductive functions. In males, GH regulates gonadal differentiation, steroidogenesis, and gametogenesis, as well as gonadotropin secretion and responsiveness. In females, GH has a role not only as a modulator on gonadotropins, mediated by the property of IGF-I to amplify the action of both LH and FSH on granulosa, but also, through a direct GH action, on follicular maturation. GH treatment seems to play an important role in the sensibilization of ovary responsivity and uterine morpholgy in GHD patients. Since GH, directly or indirectly via IGF-I, regulates reproductive functions at all levels of the hyophyseal-pituitary-gonadal, it should always be tested as a possible cause of unexplained infertility.

Refractory thyrotoxicosis induced by iodinated contrast agents treated with therapeutic plasma exchange. A case report.

Excess free iodide in the blood (ingested or injected) may cause thyrotoxicosis in patients at risk. Iodinated contrast solutions contain small amounts of free iodide and may be of significance for patients affected by Graves' disease, multinodular goiter or living in areas of iodine deficiency. Herein, we report a 57 elderly woman with a clinical history of multinodular goiter presented with a thyrotoxicosis induced by an iodinate contrast agent used during computed tomography scan. Because of the patient's resistance to conventional antithyroid drugs, she was treated with therapeutic plasma exchange (TPE). TPE is used in the treatment of several immunologic and nonimmunologic disorders. Temporary improvement after TPE in cases with thyrotoxicosis has been reported. In our patient's case, we observed an improvement in the thyroid hormone laboratory values as well as clinical findings. TPE can be an addition treatment when standard therapies for thyrotoxicosis fail providing the clinician with an adjuvant tool for rapid preparation of such a patient for thyroidectomy surgery.

Telecare for teenagers with type 1 diabetes: a trial.

AIM: The aim of this paper was to test in teenagers with type 1 diabetes mellitus (T1DM) the Glucobeeb (Gb), a web based tool to support the diabetes care. METHODS: Gb transfers glucometer's data by phone and Internet to the PC of practitioner in files dedicated to each patient; the response returns to patient as 1-min vocal message. From outpatients paediatric clinic 28 teenagers (mean 14.8 years, range 10-20, male 14) with T1DM on multiple daily injections insulin therapy, with glicated haemoglobin (HbA1c) over 7% and >2 years' duration of the disease (9.1 years, range 2-15), were consequently randomized to telecare (glucometer transmission with feedback, group A) or control (standard communication by phone and face-to-face visits, group B). Glycaemia was tested four times per day and data transmitted every 2 weeks; clinician feedback returned within the following week. Two controls were excluded after randomization. Outcomes of 14 patients of A were compared with 12 of B. RESULTS: In intervention group average HbA1c% decreased from baseline at 3 and 6 months in comparison with controls (9.5, 9.0, 9.1, vs 9.1, 9.4, 9.4 respectively). Controls after 6 months were introduced to Gb, and similar trend of HbA1c was observed in the following examinations at 3 and 6 month (9.4, 8.9, 8.7). Then, in both groups HbA1c after 12 months of Gb increased, and after 18 reduced (A: 9.2, and 8.8, B 9.1 and 8.5 respectively). The enhancement of HbA1c from baseline to end was significant (P=0.01). CONCLUSION: The tool improves metabolic control in teenagers with T1DM.

Malignant insulinoma presenting as metastatic liver tumor. Case report and review of the literature.

Insulin-secreting tumors are the commonest hormone-producing neoplasm of the gastrointestinal tract. They occur with an incidence of 4 cases per million per year. About 10% of them are metastatic and malignant insulinomas very rarely observed in children and in elderly. We report a rare case of very large malignant insulinoma in a 71-year-old woman admitted in our Oncological Institute on October 2005. She presented with fasting hypoglicemia (blood glucose 35 mg/dl) and high serum insulin levels (insulin 115.9 microU/ml). A computerized tomographic scan showed a pancreatic tail lesion of about 6 cm in max diameter and multiple liver metastases. A whole body scintiscan using 111In-DTPA-D-Phe1-octreotide was made and an increased uptake in the tail of the pancreas has been found. The patient was submitted to liver biopsy and the diagnosis of a metastatic insulin-secreting tumor was immunoistochemically confirmed. Due to the presence of some hypoglicemic episodes uncontrolled by medical treatment, on December 2005 the patient was admitted to surgical intervention with a body and tail pancreatic resection. Post-operatively the patient experienced again syncope with hypoglycemia and hyperinsulinemia. It was then decided to start a schedule of treatment with somatostatin analog (octreotide subcutaneously 500 microg three times a day) with a good control of blood glucose levels (101 mg/dl). A trans-arterial chemioembolization was planned but the patient died for pancreatic and cardiovascular complications before this treatment started.