Diagnosis and management of treatment-refractory hypothyroidism: an expert consensus report

There is a frequently encountered subset of hypothyroid patients who are refractory to standard thyroid hormone replacement treatment and require unexpectedly high doses of levothyroxine. In addition to clinical situations where hypothyroid patients are non-compliant, or where there is the possibility of excipient-induced disease exacerbation (gluten/celiac disease), therapeutic failure may be due to impaired absorption of the administered drug. The common approach to managing patients with unusual thyroxine needs is to escalate the dose of levothyroxine until targeted TSH levels are achieved. This approach can increase the risk for prolonged exposure to supratherapeutic doses of levothyroxine, which increase the chances of adverse outcomes. Repeated adjustments of levothyroxine can also escalate the costs of treatment, as frequent office visits and laboratory tests are required to determine and maintain the desired dose. Clinicians should take a systematic approach to managing patients whom they suspect of having treatment-refractory hypothyroidism. This may include searching for, and adjusting, occult medical conditions and/or other factors that may affect the absorption of levothyroxine, before up-titrating the dose of traditional levothyroxine therapy. Depending on the underlying pathology, another approach that may be considered is to try alternative formulations of levothyroxine that are less susceptible to intolerance issues related to excipients, or, in some cases, to malabsorption. The early discovery of these factors via a thoughtful patient work-up may avoid unnecessary thyroid medication adjustments and their consequences for both patients and clinicians

Bronchoscopic sampling techniques in the era of technological bronchoscopy

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The unmet need for pertussis prevention in patients with chronic obstructive pulmonary disease in the Italian context

Despite high rates of vaccination, pertussis resurgence has been reported worldwide in recent years, including in Italy, especially in older adults. Chronic obstructive pulmonary disease (COPD) is a respiratory disease associated with progressive inflammation of the respiratory tract. Regional population studies have shown the prevalence of COPD in Italy to be approximately 15% with an age-dependent increase in proportion of COPD cases. Emerging data shows that individuals with COPD are at high risk of contracting pertussis. Furthermore, those who develop pertussis could experience exacerbation of their pre-existent COPD and further susceptibility to other infections. Immunization programs in Italy currently recommend a decennial reduced-antigen-content diphtheria-tetanus-acellular pertussis booster vaccine dose for adults. Active measures to encourage booster vaccination, especially for high-risk adults such as those with COPD, could positively impact pertussis morbidity and the associated healthcare burden

Seeking optimization of LT4 treatment in patients with differentiated thyroid cancer

: Levothyroxine sodium (LT4) is the mainstay treatment to replace thyroid hormonal production in thyroidectomized patients, but, depending on the aggressiveness of the cancer and on the risk of recurrence, patients with differentiated thyroid cancer may also be treated in a TSH-suppressive or semi-suppressive mode. The pathophysiological rationale for this LT4 treatment stems from the role of TSH, considered to be a growth factor for follicular cells, potentially inducing initiation or progression of follicular cell-derived thyroid cancer. Therefore, accurate tailoring of treatment, taking into account both patient characteristics (age and comorbidities) and risk of persistent/recurrent disease, is highly recommended. Furthermore, adjustments to traditional LT4 treatment should be made in thyroidectomized patients due to the lack of thyroidal contribution to whole body triiodothyronine (T3) concentration. Since LT4 exhibits a narrow therapeutic index and the side effects of over- and under-treatment could be deleterious, particularly in this category of patients, caution is required in dose individualization, in the mode of ingestion, and in potential pharmacological and other types of interference as well. Our aim was to analyze the current knowledge concerning LT4 dose requirements in patients with thyroid cancer according to different therapeutic approaches, taking into account a number of factors causing interference with LT4 efficacy. Specific mention is also made about the use of the novel LT4 formulations

The relationship between thyroid disorders and vitamin A. A narrative minireview

: The terms "vitamin A" and "retinoids" encompass a group of fat-soluble compounds essential for human nutrition. Some of them (retinol, retinal, 9-cis-retinoic acid, tretinoin, and 13-cis-retinoic acid) are fully natural, while others are synthetic compounds used mostly for therapeutic purposes. Some evidence indicates that the nutritional status of these retinoids (i.e., the presence or absence of deficiency) is able to modulate thyroid gland metabolism. Vitamin A deficiency is tightly correlated with structural and functional impairment of the thyroid gland and is often associated with iodine deficiency. Furthermore, retinoids are involved in different immune functions, as well as in the process of activation, proliferation, and differentiation of regulatory T cells (Treg). This is particularly significant given the high prevalence of thyroid autoimmune disorders, whose pathogenesis seems to be related to the altered homeostasis of regulatory T cells. Retinoids are also involved in the modulation of gene expression via their interaction with nuclear receptors, and they also act as cofactors in cell growth and differentiation. The ability of retinoic acid to increase iodine uptake and sodium-iodine symporter activity in human thyroid cancer cell lines suggests that some retinoids and their derivatives may be of use in the treatment of different thyroid tumors. This minireview summarizes the current knowledge on the link between nutritional intake of vitamin A and various thyroid disorders

Chest pain and a left parasternal soft tissue swelling in an immunocompetent refugee with disseminated tuberculosis

An immunocompetent migrant with chest pain was admitted to an Italian hospital. CT scan showed a left pectoral abscess and osteomyelitis of the sternum. The infection spread into the anterior mediastinum near to the pericardium and the heart, where an atrial mass was confirmed by echocardiography. Disseminated tuberculosis was diagnosed

Effect of inhaled bronchodilators on inspiratory capacity and dyspnoea at rest in COPD

It has been shown that patients with chronic obstructive pulmonary disease (COPD) develop dynamic hyperinflation (DH), which contributes to dyspnoea and exercise intolerance. Formoterol, salmeterol and oxitropium have been recommended for maintenance therapy in COPD patients, but their effect on DH has only been assessed for salmeterol. The aim of the present study was to compare the acute effect of four inhaled bronchodilators (salbutamol, formoterol, salmeterol and oxitropium) and placebo on forced expiratory volume in one second, inspiratory capacity, forced vital capacity and dyspnoea in COPD patients. A cross-over, randomised, double-blind, placebo-controlled study was carried out on 20 COPD patients. Patients underwent pulmonary function testing and dyspnoea evaluation, in basal condition and 5, 15, 30, 60 and 120 min after bronchodilator or placebo administration. The results indicate that in chronic obstructive pulmonary disease patients with decreased baseline inspiratory capacity, there was a much greater increase of inspiratory capacity after bronchodilator administration, which correlated closely with the improvement of dyspnoea sensation at rest. For all bronchodilators used, inspiratory capacity reversibility should be tested at 30 min following the bronchodilator. On average, formoterol elicited the greatest increase in inspiratory capacity than the other bronchodilators used, though the difference was significant only with salmeterol and oxitropium. The potential advantage of formoterol needs to be tested in a larger patient population

Overcoming barriers to the effective management of severe asthma in Italy

Introduction: People with severe asthma (SA) often have poor disease control and quality of life, and are at high risk of exacerbations, lung function decline and asthma-related death. The present expert opinion article aimed to identify unmet needs in the management of SA in Italy, and propose possible solutions to address these needs. Methods: At five multidisciplinary events in Italy, attendees identified factors that interfered with the effective management of SA and suggested how these barriers could be overcome. A core group of 12 Italian experts (pulmonologists, general practitioners, allergists, payers and patients) identified the main issues and proposed possible solutions based on the results from the meetings and relevant articles from the literature. Results and Conclusions: We reviewed the gap between real-world practice and guide-lines, oral corticosteroid overuse, SA-related mortality, and barriers to effective SA treat-ment. Common themes were lack of awareness about SA among both patients and clinicians, and lack of networking/information exchange between those involved in the treatment of SA. Participants agreed on the need to implement patient education and create multidisciplinary groups of specialists to improve SA management through multidisciplinary educational initiatives, meetings with local experts, development of a flow chart for referral/connection with local experts and specialized centers. Clinical instruments that might help specialists improve SA management included referral networks, integrated care pathways, phenotyping and treatment algorithms, exacerbation tracking, and examination of electronic medical records for patients with uncontrolled asthma. The following actions need to be implemented in Italy: i) maximize the use of advanced therapies, eg, biologics; ii) increase/improve education for physicians and patients; iii) improve multidisciplinary communication and care coordination; iv) introduce regional and local protocols for SA diagnosis and treatment; and v) change the structure of healthcare services to reduce specialist waiting times and facilitate access to biologic therapies

Imposex levels and concentrations of organotin compounds (TBT and its metabolites) in Nassarius nitidus from the Lagoon of Venice

Specimens of Nassarius nitiduswere collected in seven stations of the Venice Lagoon to assess the levels of tributyltin (TBT) and its metabolites monobutyltin and dibutyltin in the tissues and monitor their effect on organisms, in particular the phenomenon of imposex (superimposition of male sexual characteristics on females). The following values of population indices were found: vas deferens sequence: 1.2 ± 0.7–4.0 ± 0.5; relative penis length: 6–47%. The least impacted station was situated in the northern part of the Lagoon, where females without imposex were found and Butyltin (BuTs) concentrations in the organisms (average sum of BuTs = 43 ± 14 ng Sn g-1 w.) were significantly lower than in the other stations (range of average sum of BuTs: 101 ± 22–217 ± 27 ng Sn g-1 d.w.). Population indices were found to be related to the TBT content in the tissues. In particular VDSI had a significant logarithmic correlation: r = 0.95,n =8, p < 0.05