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Nancy D Perrier, Andrew Arnold, Jessica Costa-Guda, Naifa L Busaidy, Ha Nguyen, Hubert H Chuang, and Maria Luisa Brandi

This report summarizes published data on parathyroid cancer, with the inclusion of topics discussed at MEN2019: 16th International Workshop on Multiple Endocrine Neoplasia, 27–29 March 2019, Houston, TX, USA. An expert panel on parathyroid cancer was constituted by the Steering Committee to address key questions in the field. The objectives were to recap open forum discussion of interested parties from multiple disciplines. The expert panel met in a closed session to consult on the data to be highlighted on the evidence-based results and on the future directions. Preceding the Conference, members of the expert panel conducted an extensive literature search. All presentations were based upon the best peer-reviewed information taking into account the historical and current literature. Questions were developed by the expert panel on parathyroid carcinoma. A comprehensive literature search for relevant studies was undertaken. This report represents the expert panel’s synthesis of the conference material placed in a context designed to be relevant to clinicians and those engaged in cutting-edge studies of parathyroid carcinoma. This document not only provides a summary of our current knowledge but also places recent advances in its management into a context that should enhance future advances in our understanding of parathyroid carcinoma.

Free access

Marie-Claude Hofmann, Muthusamy Kunnimalaiyaan, Jennifer R Wang, Naifa L Busaidy, Steven I Sherman, Stephen Y Lai, Mark Zafereo, and Maria E Cabanillas

Protein kinases play critical roles in cell survival, proliferation, and motility. Their dysregulation is therefore a common feature in the pathogenesis of a number of solid tumors, including thyroid cancers. Inhibiting activated protein kinases has revolutionized thyroid cancer therapy, offering a promising strategy in treating tumors refractory to radioactive iodine treatment or cytotoxic chemotherapies. However, despite satisfactory early responses, these drugs are not curative and most patients inevitably progress due to drug resistance. This review summarizes up-to-date knowledge on various mechanisms that thyroid cancer cells develop to bypass protein kinase inhibition and outlines strategies that are being explored to overcome drug resistance. Understanding how cancer cells respond to drugs and identifying novel molecular targets for therapy still represents a major challenge for the treatment of these patients.

Open access

Ha Nguyen, Komal Shah, Steven G Waguespack, Mimi I Hu, Mouhammed Amir Habra, Maria E Cabanillas, Naifa L Busaidy, Roland Bassett, Shouhao Zhou, Priyanka C Iyer, Garrett Simmons, Diana Kaya, Marie Pitteloud, Sumit K Subudhi, Adi Diab, and Ramona Dadu

Data on the diagnosis, natural course and management of immune checkpoint inhibitor (ICI)-related hypophysitis (irH) are limited. We propose this study to validate the diagnostic criteria, describe characteristics and hormonal recovery and investigate factors associated with the occurrence and recovery of irH. A retrospective study including patients with suspected irH at the University of Texas MD Anderson Cancer Center from 5/2003 to 8/2017 was conducted. IrH was defined as: (1) ACTH or TSH deficiency plus MRI changes or (2) ACTH and TSH deficiencies plus headache/fatigue in the absence of MRI findings. We found that of 83 patients followed for a median of 1.75 years (range 0.6–3), the proposed criteria used at initial evaluation accurately identified 61/62 (98%) irH cases. In the irH group (n = 62), the most common presentation was headache (60%), fatigue (66%), central hypothyroidism (94%), central adrenal insufficiency (69%) and MRI changes (77%). Compared with non-ipilimumab (ipi) regimens, ipi has a stronger association with irH occurrence (P = 0.004) and a shorter time to irH development (P < 0.01). Thyroid, gonadal and adrenal axis recovery occurred in 24, 58 and 0% patients, respectively. High-dose steroids (HDS) or ICI discontinuation was not associated with hormonal recovery. In the non-irH group (n = 19), one patient had isolated central hypothyroidism and six had isolated central adrenal insufficiency. All remained on hormone therapy at the last follow-up. We propose a strict definition of irH that identifies the vast majority of patients. HDS and ICI discontinuation is not always beneficial. Long-term follow-up to assess recovery is needed.