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]

Mild Thyroid Deficiency in the Elderly

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Potential drug–drug interactions in alzheimer patients with behavioral symptoms

The use of multi drug regimens among the elderly population has increased tremendously over the last decade although the benefits of medications are always accompanied by potential harm, even when prescribed at recommended doses. The elderly populations are particularly at an increased risk of adverse drug reactions considering comorbidity, poly-therapy, physiological changes affecting the pharmacokinetics and pharmacodynamics of many drugs and, in some cases, poor compliance due to cognitive impairment and/or depression. In this setting, drug-drug interaction may represent a serious and even life-threatening clinical condition. Moreover, the inability to distinguish drug-induced symptoms from a definitive medical diagnosis often results in addition of yet another drug to treat the symptoms, which in turn increases drug-drug interactions. Cognitive enhancers, including acetylcholinesterase inhibitors and memantine, are the most widely prescribed agents for Alzheimer's disease (AD) patients. Behavioral and psychological symptoms of dementia, including psychotic symptoms and behavioral disorders, represent noncognitive disturbances frequently observed in AD patients. Antipsychotic drugs are at high risk of adverse events, even at modest doses, and may interfere with the progression of cognitive impairment and interact with several drugs including anti-arrhythmics and acetylcholinesterase inhibitors. Other medications often used in AD patients are represented by anxiolytic, like benzodiazepine, or antidepressant agents. These agents also might interfere with other concomitant drugs through both pharmacokinetic and pharmacodynamic mechanisms. In this review we focus on the most frequent drug-drug interactions, potentially harmful, in AD patients with behavioral symptoms considering both physiological and pathological changes in AD patients, and potential pharmacodynamic/pharmacokinetic drug interaction mechanisms

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

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

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

Surgical management of adult Brainstem Gliomas: a systematic review and meta-analysis

The present review aims to investigate the survival and functional outcomes in adult high-grade brainstem gliomas (BGSs) by comparing data from resective surgery and biopsy. MEDLINE, EMBASE and Cochrane Library were screened to conduct a systematic review of the literature, according to the PRISMA statement. Analysis was limited to articles including patients older than 18 years of age and those published from 1990 to September 2022. Case reports, review articles, meta-analyses, abstracts, reports of aggregated data, and reports on multimodal therapy where surgery was not the primary treatment were excluded. The ROBINS-I tool was applied to evaluate the risk of bias. Six studies were ultimately considered for the meta-analysis. The resective group was composed of 213 subjects and the bioptic group comprised 125. The analysis demonstrated a survival benefit in those patients in which an extensive resection was possible (STR HR 0.59 (95% CI 0.42, 0.82)) (GTR HR 0.63 (95% CI 0.43, 0.92)). Although surgical resection is associated with increased survival, the significantly higher complication rate makes it difficult to recommend surgery instead of biopsy for BSGs. Future investigations combining volumetric data and molecular profiles could add important data to better define the proper indication between resection and biopsy

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