Endocrine, Metabolic & Immune Disorders-Drug Targets (Formerly Current Drug Targets - Immune, Endocrine & Metabolic Disorders) - Volume 25, Issue 10, 2025

Thyroid hormone deficiencies can disrupt organ functions, significantly impacting the cardiovascular system. Recently, the effects of thyroid hormones on the heart have garnered increased attention. However, most studies are conducted on humans using clinical data, while cellular-level and experimental studies remain limited.

This study aimed to investigate the cardiovascular implications of hypothyroidism and evaluate the impact of caffeine on cardiac health in rats induced with hypothyroidism using propylthiouracil (PTU).

The study involved 60 rats divided into six groups. Group 1 served as the untreated control. Group 2 received PTU for two months to induce hypothyroidism. Group 3 received PTU for one month, followed by caffeine for one month. Group 4 received caffeine for two months. Group 5 received both PTU and caffeine simultaneously for two months. Group 6 received PTU for one month, followed by one month under normal conditions.

During necropsy, normal thyroid glands were observed in Groups 1, 4, and 6, enlarged thyroids in Group 2, and smaller thyroids in Groups 3 and 5. Microscopic examination revealed varying thyroid histologies: Group 2 showed significant epithelial cell proliferation and absent colloid, while Groups 3, 5, and 6 had altered yet colloid-containing acini. Macroscopic inspection of hearts appeared normal across all groups. However, histopathological examination revealed significant hyperemia and microhemorrhages in Group 2, contrasting with normal findings in other groups. Immunohistochemical analysis indicated reduced cardiac troponin expression in Group 2, while other groups maintained prominent expression. Additionally, Group 2 displayed increased serum TSH levels and decreased T3 and T4 levels.

The findings suggest that administering caffeine alongside or after PTU treatment in rats with experimentally induced hypothyroidism may ameliorate thyroid and cardiac irregularities. This study indicates caffeine's potential in mitigating the adverse effects of hypothyroidism on thyroid and heart health.

Depression is a common mental illness that has become a major economic burden worldwide. Recently, increasing evidence has highlighted the inflammatory mechanism of depression. In order to understand the research status of this field, this study used the bibliometric analysis method to overview the research content and progress, as well as analyze the development trend and limitations.

In this study, articles and reviews were included in the specific search strategy. The matched papers were exported from the Web of Science database. CiteSpace 6.3 R1 and Bibliometrix (R package) were utilized to generate bibliometric and knowledge maps.

A total of 25,063 articles were included in this study. The number of publications in this field has gradually increased, especially in recent years. These papers come from 156 countries, led by the United States and China mainland. The leading research institution is the University of Toronto (Canada). Brain Behavior and Immunity is the journal with the most publications and the most frequently co-cited journals. Among 91,100 authors, Maes M has the most publications and co-citations. According to the keywords burst and co-cited reference analysis, the hotspots in the field in recent years include kynurenine, c-reactive protein, neuroinflammation, and gut microbiota.

Although abundant academic achievements have been made on the inflammatory mechanism of depression, there is still a long way to go before these research results can be applied to clinical practice. Strengthening international academic exchanges and cooperation may promote breakthroughs in this field.

Papillary Thyroid Carcinoma (PTC) is the most common thyroid cancer, with an etiology and progression that are not fully understood. Research suggests a link between cathepsins and PTC, but the causal nature of this link is unclear. This study uses Mendelian Randomization (MR) to investigate if cathepsins causally influence PTC risk.

We applied univariable and multivariable MR analyses using genetic variants as proxies for cathepsin levels. Genetic data for cathepsins were sourced from the INTERVAL study, while PTC data came from the Finnish Genome-Wide Association Study database. Our analysis employed several MR methods, including the Inverse Variance Weighted (IVW) approach, MR-Egger, and the Weighted Median method, to provide comprehensive insights and address possible pleiotropy.

MR findings suggest a significant causal association between higher cathepsin levels and increased PTC risk. Notably, genetic variants indicating higher cathepsin Z expression were positively causal associated with PTC risk (OR:1.1190, 95% CI: 1.0029-1.2486), multivariable analysis confirmed significant carcinogenesis role of cathepsin Z in PTC (OR: 1.1593, 95% CI: 1.0137-1.3258), with results consistent across various tests, indicating a robust relationship.

This study established a causal link between cathepsin levels and PTC risk, emphasizing the roles of cathepsin Z in its progression. These insights could lead to new therapeutic strategies targeting these enzymes. Further research is necessary to understand the underlying biological mechanisms and their clinical implications.

Patients with permanent hypoparathyroidism experience an impaired quality of life, due to acute and chronic complications that may affect several organs, with an increased risk of hospitalisation and death. Adequate and continuous replacement therapy with calcium and calcitriol is necessary to avoid symptoms and long-term complications related to hypocalcemia.

A 63 years old male, affected by permanent post-surgical hypoparathyroidism, was hospitalized in the cardiology department because of a dehiscence of the subcutaneous housing of the double-chambered implantable cardioverter-defibrillator. Chronic replacement therapy for hypoparathyroidism was poorly controlled and, during hospitalization, severe hypocalcemia occurred together with electrocardiographic and echocardiogram life-threatening alterations.

Constant and targeted long-term replacement therapy with calcium and particularly calcitriol is necessary to avoid major consequences on patients’ health, especially during acute events and in the presence of other comorbidities.

The possibility of sustained disease remission in functioning pituitary adenomas after drug withdrawal is well-known for prolactinomas and it has also been described in a subset of acromegalic patients. On the contrary, medical treatment for Cushing’s Disease (CD) is generally considered a life-long measure except for previously radio-treated patients. Sparse evidence of spontaneous remissions in CD has been reported, mainly related to a possible pituitary tumor apoplexy. To the best of our knowledge, none of these cases has included the use of a pituitary targeting agent.

Herein, we have reported the case of a radiotherapy-naïve patient with persistent CD after pituitary surgery who participated in the CSOMG230 trials, presenting sustained remission after Long-acting Release (LAR) pasireotide withdrawal. Under monthly pasireotide LAR 40 mg, the patient achieved urinary hormone control and clinical signs of cortisol excess normalization. After 8 years of treatment, the patient completed the study protocol and had to withdraw the drug as it was no longer available for CD in Italy. Before starting new therapies, we reassessed hormone levels that were surprisingly within normal ranges. At 24 months after the last dose of pasireotide, the patient was still in clinical and biochemical full remission. We have also briefly reviewed previous cases of sustained remission after somatostatin analogues withdrawal in other functioning pituitary adenomas.

Far from the general rule, this case suggests that prolonged treatment with pasireotide LAR might induce a durable CD remission. A dose down-titration/suspension might be considered in patients well-controlled on long-term therapy and with negative pituitary imaging. However, close monitoring is recommended given the high rate of complications in untreated patients.