Thyroid cancer can be largely classified as well-differentiated, poorly differentiated, medullary and anaplastic. Differentiated thyroid cancer (DTC) includes follicular and papillary subtypes, with the incidence of papillary thyroid cancer (PTC) on the rise. The mainstay of treatment for DTC includes a combination of surgery, radioactive iodine (RAI) and levothyroxine suppression. DTC portends a favorable prognosis, even in the presence of distant metastases, with a 50% rate of 5-year survival largely due to tumor cell's sensitivity to RAI therapy influencing disease outcome. In radioactive iodine refractory differentiated thyroid cancer (RAI-refractory DTC) there is a lower survival rate prompting the use of other therapeutic options available. RAI refractoriness is more common in older patients (age >40), large metastases and lesions that are fluorodeoxyglucose (FDG) avid on position emission tomography (PET). Over the past decade, Identification of genetic mutations in the signaling pathway involved in thyroid tumorigenesis has led to the approval of tyrosine kinase inhibitors (TKIs); Sorafenib and Lenvatinib in RAI-refractory DTC. Similarly, metastatic medullary thyroid cancer (MTC) implies an unfavorable 10-year survival rate of only 20% as the principal treatment options focuses on loco regional control via surgical and/or non-surgical options. The approval of TKIs such as Cabozantinib and Vandetanib has introduced an encouraging, novel, systemic therapeutic option for metastatic MTC. Lastly, anaplastic thyroid cancer (ATC) carries the worst prognosis with high recurrence rates. Treatment includes surgery, chemotherapy and external beam radiation. The FDA recently approved Dabrafenib plus trametinib for BRAF V600E mutated ATC. Considering the modality of chemotherapy and the expanding field of targeted therapies, the role of the oncologist and interaction with endocrinologist in the management of thyroid cancer needs further clarification aiming at collaborative management plans more than ever. This review summarizes the key phase III trials that led to the approval of TKIs in the treatment of DTC and metastatic MTC. Additionally, the review aims to clarify the patient selection criteria for initiation of TKIs and examine the implications, considerations and adverse effects prior to utilizing targeted therapy. Clinical trials are ongoing with promising results and may contribute to the addition of several targeted molecules and immune check point inhibitors to the therapeutic armamentarium for RAI-refractory DTC, medullary and anaplastic thyroid cancer.
Background: Ovarian hyperstimulation syndrome (OHSS) is a rare but serious complication of ovarian stimulation occurring during assisted reproduction technologies (ART). It is characterized by increased vascular permeability and hypercoagulable states resulting in strokes and peripheral ischemia. Acute myocardial infarction and cardiac thrombosis, however, have been rarely reported complications of OHSS.
Methods: A literature search was performed for reports on myocardial infarction and cardiac thrombosis associated with ovarian stimulation with a summary of their clinical characteristics.
Results: A total of twelve published cases were reviewed with 5 out of 12 (41.67%) of the reported cases were 35 years of age or older. Myocardial infarction was reported in 10 out of the 12 cases (83.3%). Two of the cases were pregnant at presentation (16.67%). The mean duration between starting ovarian stimulation medications and clinical presentation was 23 days. Chest pain was the most common presenting symptom (66.67%), 2 cases presented with stroke (16.67%) and 2 cases presented with abdominal distention (16.67%). A total of 8 patients underwent coronary angiography with 2 of these cases were treated with percutaneous coronary intervention. No mortality reported in any of the twelve cases.
Conclusion: Women of a relatively younger age undergoing ovarian stimulation may be at risk for developing myocardial infarction and cardiac thrombosis. Once thrombosis is suspected, initiating appropriate therapy in a timely manner is crucial.