Continuation of amiodarone delays restoration of euthyroidism in patients with type 2 amiodarone-induced thyrotoxicosis treated with prednisone: a pilot study

Context: Type 2 amiodarone-induced thyrotoxicosis (AIT) is a destructive thyroiditis usually re- sponsive to glucocorticoids. Whether continuation of amiodarone affects treatment outcome is unsettled. Objective: The objective of the study was to compare the outcome of glucocorticoid treatment in type 2 AIT patients who continued or withdrew amiodarone. Design: This was a matched retrospective cohort study. Setting: The study was conducted at a university center. Patients: Eighty-three consecutive patients with untreated type 2 AIT participated in the study. After matching with patients continuing amiodarone (AMIO-ON, n 8), patients interrupting amiodarone were randomly selected in a 4:1 ratio (AMIO-OFF, n 32). Intervention: All patients were treated with oral prednisone. Patients whose thyrotoxicosis re- curred after glucocorticoid withdrawal were treated with a second course of prednisone. Main Outcome Measure: Time and rate of cure were measured. Results: Median time to the first normalization of serum thyroid hormone levels did not signifi- cantly differ in AMIO-ON and AMIO-OFF patients (24 and 31 d, respectively; P 0.326). Conversely, median time for stably restoring euthyroidism was 140 d in AMIO-ON patients and 47 d in AMIO- OFF patients (log rank, P 0.011). In fact, AIT recurred in five of seven AMIO-ON patients (71.4%) and in only three of 32 AMIO-OFF patients (9.4%, P 0.002), requiring readministration of pred- nisone. One AMIO-ON patient never reached thyroid hormone normalization during the study period. Factors associated with glucocorticoid failure were thyroid volume and amiodarone continuation. Conclusions: Prednisone restores euthyroidism in most type 2 AIT patients, irrespective of amio- darone continuation or withdrawal. However, continuing amiodarone increases the recurrence rate of thyrotoxicosis, causing a delay in the stable restoration of euthyroidism and a longer exposure of the heart to thyroid hormone exces

Steroid treatment in the management of destructive thyrotoxicosis induced by PD1 blockade

Objective: Destructive thyroiditis is the most common endocrine immune related adverse event (iRAEs) in patients treated with anti-PD1/PD-L1 agents. Given its self-limited course, current guidelines recommend no treatment for this iRAE. Nevertheless in patients with enlarged thyroid volume and a poor performance status, thyrotoxicosis may be particularly severe and harmful. Aim of the study is to evaluate if steroid treatment might be useful in improving thyrotoxicosis in subjects with a poor performance status. Methods: We conducted a retrospective study, comparing the course of thyrotoxicosis of 4 patients treated with oral prednisone at the dosage of 25 mg/d (tapered to discontinuation in three weeks) and an enlarged thyroid volume to that of 8 patients with similar thyroid volume who were left untreated. Results: The levels of thyroid hormones were lower in subjects treated compared to those untreated at time 7, 14, 21, 28, 35, 42, 60 and 90 days (P<0.05 at each time). The time to remission of thyrotoxicosis was 24 days in patients treated with steroids and 120 days in untreated patients (P<0.001). At 6 months, the rate of evolution to hypothyroidism was similar in the 2 groups (4/4 in steroid group vs 7/8 in untreated group, P=0.74) and no difference was found in tumor progression (P=0.89). Conclusions: Our preliminary data suggest that in patients with a poor performance status experiencing a severe destructive thyrotoxicosis induced by PD-1 blockade, a short period of administration of oral prednisone is effective in obtaining a quick reduction of the levels of thyroid hormones

Active surveillance in differentiated thyroid cancer: a strategy applicable to all treatment categories response

Currently, the differentiated thyroid cancer (DTC) management is shifted toward a tailored approach based on the estimated risks of recurrence and disease-specific mortality. While the current recommendations on the management of metastatic and progressive DTC are clear and unambiguous, the management of slowly progressive or indeterminate disease varies according to different centers and different physicians. In this context, active surveillance (AS) becomes the main tool for clinicians, allowing them to plan a personalized therapeutic strategy, based on the risk of an unfavorable prognosis, and to avoid unnecessary treatment. This review analyzes the main possible scenarios in treated DTC patients who could take advantage of AS

REGULATION OF CARDIAC FATTY ACID METABOLISM IN TRANSGENIC MICE OVEREXPRESSING BOVINE GROWTH HORMONE

Cardiac energy metabolism depends mainly on fatty acid (FA) oxidation; however, regulation of FA metabolism in acromegalic (Acro) heart is unknown. The aim of the study was to evaluate cardiac expression of key proteins of FA metabolism in young and elder transgenic mice overexpressing bovine GH Acro. Expression of proteins regulating FA entry into the cells, their uptake by mitochondria and b-oxidation were evaluated by western blot, while FA content by Fourier transform infrared microspectrometry. Regulatory mechanisms of key steps of FA metabolism were also studied. The expression of plasma-membrane FA carriers (fatty acid-binding protein and fatty acid transport protein-1) and acylCoA synthetase was higher in young and lower in elder Acro than in corresponding controls; likewise, expression of cytoplasm to mitochondria-1 (CPT-1), the key enzyme of mitochondrial FA uptake, and that of medium-chain acyl-CoA dehydrogenase and long-chain acyl-CoA dehydrogenase, two regulatory b-oxidation dehydrogenases, followed a similar pattern. FA content was lower in young and higher in elder Acro than in wild-type, suggesting an increased utilisation in young animals. GH regulated expression of key proteins of FA metabolism through changes in peroxisome proliferator-activated receptor a (PPARa) expression, which varied accordingly. GH effect was confirmed by treatment of Acro mice with a receptor antagonist, which abolished changes in key proteins of FA metabolism in young Acro. GH increased phosphorylation of AMP-activated protein kinase and antiacetyl- CoA-carboxylase, two regulatory kinases, leading to lower CPT-1 inhibition by malonyl-CoA, and intervened in regulating PPARa expression through the ERK 1/2 pathway. In conclusion, chronic GH excess increased FA metabolism in the young age, whereas its action was overwhelmed in elder ages likely by GH-independent mechanisms, leading to reduced expression of key enzyme of FA metabolis

Graves' Disease Induced by Immune Checkpoint Inhibitors: A case report and Review of the literature

Introduction: In the last few years, immune checkpoint inhibitors (ICPis) have become a common treatment of cancer. ICPis are associated with peculiar immune side effects, termed immune-related adverse events (irAEs). Thyroid disfunction is a common irAE, but clinical manifestation, severity, and pathogenesis can be variable. While destructive thyroiditis and hypothyroidism are the most common thyroid irAEs induced by ICPis, autoimmune hyperthyroidism (Graves' disease) is rare. We describe a case of a Graves' disease induced by anti-PD-1 therapy and we review the previous reports on this issue. Case presentation: A 51-year-old man developed an overt autoimmune hyperthyroidism 2 months after he had started nivolumab (anti-PD-1) therapy for a metastatic non-small cell lung cancer. Although TSH-receptor autoantibodies (TRAb) were negative, the persistence of hyperthyroidism, the hypervascular pattern at thyroid ultrasound, and the high uptake at thyroid scintigraphy were all features suggestive of Graves' disease. Methimazole was started with the prompt restoration of euthyroidism. TRAb remained undetectable during the entire follow-up. Conclusions: Autoimmune hyperthyroidism can be induced by anti-PD-1 treatment. TRAb were negative in both cases of nivolumab-induced Graves' disease described to date. A correct differential diagnosis between destructive thyroiditis and autoimmune hyperthyroidism is crucial for the appropriate treatment

Identification, treatment and management of cardiovascular risks patients with acromegaly

Acromegaly, a syndrome related to growth hormone/IGF-1 excess, is frequently complicated by cardiovascular abnormalities (acromegalic cardiomyopathy). Extremely frequent are left ventricular hypertrophy and alterations of diastolic filling, which may progress to systolic dysfunction and eventually heart failure. Cardiac abnormalities may normalize after successful medical or surgical treatment of acromegaly, particularly in young patients with short-lasting disease, but this is less likely to occur in elderly patients. Both hypertension and cardiac valve disease are frequently encountered in acromegaly, but neither seems to be favorably influenced by disease control. The prevalence of coronary heart disease (CHD) is controversial but is probably not increased in acromegaly. Arrhythmias are relatively common in untreated acromegalic patients, although their clinical relevance is unknown. A cardiac evaluation of acromegalic patients should include echocardiography, basal electrocardiogram and blood pressure measurement, and evaluation of common risk factors for CHD. Appropriate and prompt treatment allowing a rapid control of growth hormone/IGF-1 hypersecretion is warranted because many features of acromegalic cardiomyopathy may be reverted, particularly in younger patients. In view of the lack of association with acromegaly, common risk factors for CHD, hypertension, arrhythmias or valve disease should be managed independently, irrespective of control of disease activity. © 2008 Expert Reviews Ltd