Cardiovascular Risk and Mild Thyroid Hormone Deficiency: Are there some Differences in the Elderly?

Subclinical hypothyroidism (sHT) is a clinical condition defined as serum TSH concentration above the upper limit of the reference range in the face of normal free T4 (FT4) and free T3 (FT3) levels. Subclinical hypothyroidism, the prevalence of which increases with age, especially among women, up to almost 20%, encompasses several pathological entities, mainly represented by chronic autoimmune thyroiditis [1,2]. sHT is often associated to symptoms that resembles those of overt hypothyroidism, although to a lesser extent thus, the expression ‘mild thyroid impairment’ or ‘mild thyroid hormone deficiency’ would be more appropriate for defining such a condition [1]. Nonetheless, the term sHT is recognized worldwide and will be utilized in the present editorial. Since 90s, a relationship between sHT and increased cardio-vascular (CV) risk (both heart failure and coronary heart disease events) has been reported, although some experiences suggest that the risk may depend on the degree of TSH elevation [1,3-5]. Moreover, several reports from elderly population (>65 years old) showed that this relationship seems no longer evident in such individuals especially in the oldest old (>85 years old) [6-9]

The Use of Antipsychotic Drugs for Treating Behavioral Symptoms in Alzheimer’s Disease

According to the World Alzheimer’s report, dementia was estimated to affect 50 million worldwide in 2018, number expected to increase to more than 150 million within 30 years. Alzheimer’s disease is the most common type of dementia, accounting on its own for 2/3 of all dementia cases. The initial signs and symptoms of Alzheimer’s disease relate to progressive cognitive decline, inexorably progressing until the loss of independence. Neuropsychiatric and behavioral symptoms may occur during the progression of the disease; around 20% of patients without any behavioral symptoms at the diagnosis will experience some of them within 2 years. Consequences are early institutionalization, lower quality of life, of both patients and carers, and more severe cognitive impairment. Treatment options for behavioral symptoms include pharmacological and nonpharmacological approaches. The latter are usually preferred, since antipsychotic therapy is not free from several, and often serious, adverse events. However, behavioral symptoms are not always controllable with non-pharmacological intervention. The psychotropic class of medication more frequently prescribed for behavioral symptoms are atypical antipsychotics; among them, risperidone is the only one licensed for the treatment of aggression, in Europe but not in the USA. On that regard, the use of antipsychotic drugs should be limited, due to the increased risk of mortality, stroke, hallucination, and higher risk of relapse after discontinuation. Some new agents are under evaluation, such as pimavanserin and lumateperone. In this review, we are evaluating the current available pharmacological options to treat behavioral symptoms as well as the forthcoming new agents

Clarithromycin-induced rhabdomyolysis: a case report

Rhabdomyolysis is a clinical and laboratory syndrome that is caused by various etiologies, involving the skeletal muscle. Clarithromycin, like other macrolides, is an inhibitor of CYP450 3A4, the major enzyme responsible for the metabolism of several drugs, in particular some statins. Rhabdomyolysis related to macrolide–statin interaction has previously been described. To date, rhabdomyolysis induced by clarithromycin has been described in only one previous report. We describe the case of a 90-year-old Caucasian male, admitted to the University Hospital of Pisa for dyspnea, who developed rhabdomyolysis associated with clarithromycin administration

Subclinical Hypothyroidism: behavioral and psychophysiological characteristics.A pilot study

Background: Clinical hypothyroidism affects various aspects of cognitive and affective brain function. The most severe hypothyroidism may also mimic a picture of melancholic depression and dementia. Subclinical hypothyroidism (SHT) is characterized by elevated TSH levels despite normal thyroid hormone concentrations. The aim of this research is to verify the presence of a typical psychophysiological pattern in SHT patients. Methods: Since 1998 fifty patients who underwent surgeries at the Department of Endocrinology, University of Pisa, diagnosed with SHT, were subsequently recruited. Subjects underwent an inspection of the reported symptoms using the Crown & Crisp Experiential Index, and a psychophysiological assessment with a simultaneous recording of the parameters Skin Conductance Level/ Response (SCL/SCR), Surface Frontal Electromyogram (EMG), Peripheral Temperature (PT), Heart Rate (HR). As a control group, fifty subjects without endocrine disorders were subsequently recruited. Results: Data shows little difference in levels in hormonal assays except for TSH. There is also a significant elevation of some of the CCEI subscales: Anxiety, Depression, and Somatic Complaints. At the autonomic level, there is a general pattern of excessive arousal with significant differences in SCL/SCR, HR, and PT. Conclusions: A first data interpretation is that in sub-clinical hypothyroidism, the body tries to support and integrate the general lack of energy with an acceleration of the autonomic activity. This condition of initial arousal could be a useful indicator in order to monitor the treatment course and its effectiveness on the pathological evolution

Acute portal vein thrombosis precipitated by indomethacin in a HCV-positive elderly patient

BACKGROUND: An increased risk of venous thromboembolism has been reported in patients treated with non-steroidal anti-inflammatory drugs (NSAIDs). We describe a case of acute portal vein thrombosis (PVT) in a hepatitis C virus (HCV)-positive elderly patient following administration of indomethacin. CASE PRESENTATION: A 79-year-old HCV-positive man was hospitalized for severe abdominal pain, nausea and vomiting, 15 days after starting indomethacin for back pain. Clinical signs and imaging evaluations disclosed a picture of PVT. Indomethacin was discontinued, and the patient was started on fondaparinux and antithrombin. He was discharged 15 days later due to improvement of his clinical conditions. Thirty days later, a follow-up ultrasound did not show appreciable signs of PVT. The time elapsing between the start of analgesic therapy and PVT onset suggests a role of indomethacin as the triggering agent. Indomethacin could have precipitated PVT by a combination of at least two detrimental mechanisms: 1) direct action on liver vascular endothelium by inhibition of prostacyclin biosynthesis; 2) damage to the intestinal mucosa, followed by inflammatory and pro-coagulant activation of portal endothelium upon exposure to bacterial endotoxins. CONCLUSIONS: This case can be of interest to physicians, who should exert caution when prescribing NSAIDs for inflammatory pain in patients with background inflammatory dysfunctions of the portal vein endothelium

Exploring Cost-Effectiveness of the Comprehensive Geriatric Assessment in Geriatric Oncology: A Narrative Review

: The Comprehensive Geriatric Assessment (CGA) and the corresponding geriatric interventions are beneficial for community-dwelling older persons in terms of reduced mortality, disability, institutionalisation and healthcare utilisation. However, the value of CGA in the management of older cancer patients both in terms of clinical outcomes and in cost-effectiveness remains to be fully established, and CGA is still far from being routinely implemented in geriatric oncology. This narrative review aims to analyse the available evidence on the cost-effectiveness of CGA adopted in geriatric oncology, identify the relevant parameters used in the literature and provide recommendations for future research. The review was conducted using the PubMed and Cochrane databases, covering published studies without selection by the publication year. The extracted data were categorised according to the study design, participants and measures of cost-effectiveness, and the results are summarised to state the levels of evidence. The review conforms to the SANRA guidelines for quality assessment. Twenty-nine studies out of the thirty-seven assessed for eligibility met the inclusion criteria. Although there is a large heterogeneity, the overall evidence is consistent with the measurable benefits of CGA in terms of reducing the in-hospital length of stay and treatment toxicity, leaning toward a positive cost-effectiveness of the interventions and supporting CGA implementation in geriatric oncology clinical practice. More research employing full economic evaluations is needed to confirm this evidence and should focus on CGA implications both from patient-centred and healthcare system perspectives

Hypothyroidism in the Elderly: Who Should Be Treated and How?

Hypothyroidism is among the most frequent chronic diseases in the elderly, and levothyroxine (l-T4) is worldwide within the 10 drugs more prescribed in the general population. Hypothyroidism is defined by increased serum thyroid-stimulating hormone (TSH) values and reduced circulating free thyroid hormones, whereas subclinical hypothyroidism (sHT) is characterized by free hormone fractions within the normal ranges and has been divided into two classes, depending on circulating TSH levels (above or below 10 mIU/L). Given that during aging, a natural trend toward higher values of circulating TSH has been reported, it is necessary to verify carefully the diagnosis of sHT to tailor an appropriate follow-up and ad hoc therapy, avoiding unnecessary or excessive treatment. In the current review, we evaluate the state of the art on hypothyroidism in the elderly with special focus on the effect of sHT on cognition and the cardiovascular system function. We also summarize the recommendations for a correct diagnostic workup and therapeutic approach to older people with an elevated TSH value, with special attention to the presence of frailty, comorbidities, and poly therapy. In conclusion, personalized therapy is crucial in good clinical practice, and in the management of older patients with sHT, multiple factors must be considered, including age-dependent TSH cutoffs, thyroid autoimmunity, the burden of comorbidities, and the possible presence of frailty. l-T4 is the drug of choice for the treatment of hypothyroid older people, but the risk of overtreatment, potential adverse drug reactions, and patient compliance should always be considered and thyroid status periodically reassessed

Clinical Aggressiveness and Long-Term Outcome in Patients with Papillary Thyroid Cancer and Circulating Anti-Thyroglobulin Autoantibodies

Objective: The association between papillary thyroid cancer (PTC) and Hashimoto's thyroiditis is widely recognized, but less is known about the possible link between circulating anti-thyroglobulin antibody (TgAb) titers and PTC aggressiveness. To shed light on this issue, we retrospectively examined a large series of PTC patients with and without positive TgAb. Methods: Data on 220 TgAb-positive PTC patients (study cohort) were retrospectively collected in 10 hospital-based referral centers. All the patients had undergone near-total thyroidectomy with or without radioiodine remnant ablation. Tumor characteristics and long-term outcomes (follow-up range: 2.5-24.8 years) were compared with those recently reported in 1020 TgAb-negative PTC patients with similar demographic characteristics. We also assessed the impact on clinical outcome of early titer disappearance in the TgAb-positive group. Results: At baseline, the study cohort (mean age 45.9 years, range 12.5-84.1 years; 85% female) had a significantly higher prevalence of high-risk patients (6.9% vs. 3.2%, p < 0.05) and extrathyroidal tumor extension (28.2% vs. 24%; p < 0.0001) than TgAb-negative controls. Study cohort patients were also more likely than controls to have persistent disease at the 1-year visit (13.6% vs. 7.0%, p = 0.001) or recurrence during subsequent follow-up (5.8% vs. 1.4%, p = 0.0001). At the final follow-up visit, the percentage of patients with either persistent or recurrent disease in the two cohorts was significantly different (6.4% of TgAb-positive patients vs. 1.7% in the TgAb-negative group, p < 0.0001). At the 1-year visit, titer normalization was observed in 85 of the 220 TgAb-positive individuals. These patients had a significantly lower rate of persistent disease than those who were still TgAb positive (8.2% vs. 17.3%. p = 0.05), and no relapses were observed among patients with no evidence of disease during subsequent follow-up. Conclusions: PTC patients with positive serum TgAb titer during the first year after primary treatment were more likely to have persistent/recurrent disease than those who were consistently TgAb-negative. Negative titers at 1 year may be associated with more favorable outcomes

Is There a Crucial Link Between Vitamin D Status and Inflammatory Response in Patients With COVID-19?

Background: Hypovitaminosis D has been suggested to play a possible role in coronavirus disease 2019 (COVID-19) infection. Methods: The aim of this study is to analyze the relationship between vitamin D status and a biochemical panel of inflammatory markers in a cohort of patients with COVID-19. A secondary endpoint was to evaluate the correlation between 25OHD levels and the severity of the disease. Ninety-three consecutive patients with COVID-19-related pneumonia were evaluated from March to May 2020 in two hospital units in Pisa, in whom biochemical inflammatory markers, 25OHD levels, P/F ratio at nadir during hospitalization, and complete clinical data were available. Results: Sixty-five percent of patients presented hypovitaminosis D (25OHD ≤ 20 ng/ml) and showed significantly higher IL-6 [20.8 (10.9–45.6) vs. 12.9 (8.7–21.1) pg/ml, p = 0.02], CRP [10.7 (4.2–19.2) vs. 5.9 (1.6–8.1) mg/dl, p = 0.003], TNF-a [8.9 (6.0–14.8) vs. 4.4 (1.5–10.6) pg/ml, p = 0.01], D-dimer [0.53 (0.25–0.72) vs. 0.22 (0.17–0.35) mg/l, p = 0.002], and IL-10 [3.7 (1.8–6.9) vs. 2.3 (0.5–5.8) pg/ml, p = 0.03]. A significant inverse correlation was found between 25OHD and all these markers, even adjusted for age and sex. Hypovitaminosis D was prevalent in patients with severe ARDS, compared with the other groups (75% vs. 68% vs. 55%, p &lt; 0.001), and 25OHD levels were lower in nonsurvivor patients. Conclusions: The relationship between 25OHD levels and inflammatory markers suggests that vitamin D status needs to be taken into account in the management of these patients. If vitamin D is a marker of poor prognosis or a possible risk factor with beneficial effects from supplementation, this still needs to be elucidated