Tailored management of advanced thyroid cancer patients treated with lenvatinib or vandetanib: the role of a multimodal approach.

BACKGROUND: In differentiated/poorly differentiated (DTC/PDTC) or medullary thyroid cancer (MTC) treated with kinase inhibitors (KIs), additional treatments (ATs) can be performed in selected cases. METHODS: We retrospectively analysed all the ATs performed in our center in KI-treated TC patients, evaluating the subsequent KI modulation, the local PD in case of loco-regional procedure (LRP) and the AT-related complications. DTC/PDTC patients with or without progressive disease before the first AT (PD and NO PD GROUP, respectively) were analysed separately. RESULTS: In our center, 32 ATs (30 LRPs and 2 radioactive iodine treatments) were performed in 14 DTC/PDTC patients and 4 MTC subjects after the start of systemic therapy with lenvatinib or vandetanib (27 and 5 ATs, respectively). Brain was the most treated site (11/30 LRPs) and external beam radiation was the most employed LRP (18/30 LRPs). KIs dose reduction or discontinuation of KI therapy (at least transient) was performed after 50% of ATs in DTC/PDTC NO PD GROUP. The KI was maintained at the same dosage after 75% and 50% of the ATs performed in DTC/PDTC PD GROUP and MTC, respectively. During the follow-up, local PD was detected after 14 LRPs. Local progression-free survival (LPFS) was significantly shorter in DTC/PDTC PD GROUP in comparison to NO PD GROUP (12 month-LPFS 91.7% versus 15.2%); in patients with MTC, 12 month-LPFS was 50%. AT-related AEs were mostly G1-G2. CONCLUSIONS: In selected DTC/PDTC without previous PD and treated with a multimodal strategy, local disease control is generally maintained regardless the KI dose modulation. In DTC/PDTC patients with previous limited PD and in MTC subjects, the choice of performing a LRP and continue the ongoing KI therapy must consider the risk of early local progression. AT-related AEs in KI treated patients were mild in most cases.

Pituitary Hyperplasia Due to Longstanding Primary Hypothyroidism: A Case Report and Comprehensive Review of the Literature.

Hypothyroidism is a frequently diagnosed endocrine disorder. Common signs and symptoms include fatigue, cold intolerance, hoarseness, dry skin, constipation, a slow relaxation phase of deep tendon reflexes, and bradycardia. However, some patients may exhibit atypical signs and symptoms, which can result in diagnostic confusion. Pituitary hyperplasia resulting from longstanding primary hypothyroidism was first described by Niepce in 1851. It is usually asymptomatic, but sometimes, in addition to symptoms of overt hypothyroidism, patients may complain of headaches, hypopituitarism, visual field impairment, and hyperprolactinemia. Furthermore, on imaging, pituitary hyperplasia can be mistaken for a pituitary adenoma. Distinguishing between the two is crucial, as their management differs; the former often responds to thyroid hormone replacement therapy, while the latter might need treatment with surgery and/or radiotherapy. Here we describe a patient who developed pituitary hyperplasia in the setting of longstanding uncompensated primary hypothyroidism due to a lack of compliance with levothyroxine replacement therapy. We also review the clinical, laboratory, and radiologic findings of the case reports available in the literature up to now in order to improve the knowledge and the care of the disease.

Increased cardiometabolic risk and prevalence of ascending aorta dilation in patients with nonfunctioning adrenal incidentaloma: a retrospective propensity score-matched study.

The cardiometabolic implications of Non-Functioning Adrenal Incidentaloma (NFAI) is still matter of debate. This study takes a novel approach to analyze this association, accounting for the influence of various confounding factors. We present the findings of a retrospective, cross-sectional, and case-control study. Data from all NFAI patients in primary prevention, referred to the University of Turin between 2000 and 2023, were collected and compared with subjects without adrenal disease, using propensity score matching analysis. A total of 1997 patients were included (906 patients with NFAI; 1091 controls). Adrenal tumor group was associated with high levels of cardiovascular risk scores in both univariate and multiple linear regression analyses (Progetto CUORE: EC 11.00, 95% CI 2.72-44.46, p = 0.001; SCORE: EC 1.97, 95% CI 1.01-3.81, p = 0.046). Regarding cardiometabolic complications, multivariable logistic regression revealed an independent association between NFAI and ascending aorta dilation (OR 4.64, 95% CI 2.24-9.63, p = 0.000), after adjusting for age, sex, smoking status, metabolic syndrome, number of antihypertensive drugs, estimated glomerular filtration rate (eGFR), and normetanephrine levels. Propensity score matching analysis (1:1 matching ratio), based on the same logistic regression model, confirmed the association of NFAI with aortic dilation (ß = 0.083, 95% CI 0.008-0.157, p = 0.030). No significant associations were found with metabolic syndrome, type II diabetes, eGFR <60 mL/min/1.73 m2, microalbuminuria, atrial fibrillation, or hypertensive heart disease. This study suggests that patients with NFAI face increased cardiometabolic risk and high prevalence of ascending aorta dilation. Routine evaluation of NFAI patients should include thorough cardiovascular assessment and consideration of treatments aimed at reducing cardiovascular risk.

Immune-related thyroid dysfunctions during anti PD-1/PD-L1 inhibitors: new evidence from a single centre experience.

The role of anti-thyroid peroxidase antibodies (anti-TPO Abs) in the development of abnormal thyroid function tests (DYSTHYR) during treatment with immune checkpoint inhibitors (ICIs) is not fully understood; moreover, controversial data exist about the relationship between ICI-related thyroid dysfunction (TD) and survival. We retrospectively analyzed the onset or the worsening of DYSTHYR in patients treated with programmed cell death protein-1 (PD-1) or its ligand (PD-L1) inhibitors between 2017 and 2020. In patients without previous TD, we focused on the association between baseline anti-TPO Abs level and DYSTHYR. Furthermore, the relationship between DYSTHYR and progression-free survival (PFS) or overall survival (OS) was explored. We included 324 patients treated with anti PD-1 (95.4%) or anti PD-L1 inhibitors. After a median of 3.3 months, DYSTHYR was registered in 24.7%, mostly hypothyroidism alone (17%). Patients with pre-existing TD (14.5% of the sample) were at higher risk of DYSTHYR compared to patients without previous TD (adjusted OR 2.44; 95% IC 1.26-4.74). In patients without known previous TD, high anti-TPO Abs level, even below the positivity cut-off, was a risk factor for developing DYSTHYR (adjusted OR 5.52; 95% IC 1.47-20.74). DYSTHYR was associated with a longer 12-month OS (87.3% vs 73.5%, p = 0.03); no statistically significant difference in terms of PFS was observed between the DYSTHYR+ and DYSTHYR- group. DYSTHYR is common during anti PD-1/anti PD-L1 treatment, especially in patients with pre-existing TD. In subjects without known previous TD, high anti-TPO Abs level at baseline can be a predictive biomarker of DYSTHYR. An improved OS is observed in patients with anti PD-1/anti PD-L1-induced DYSTHYR.