Thyroid cancer

Thyroid cancers are the most common endocrine malignancies and their incidence is rising globally, largely due to significant increases in small, incidentally detected low-risk tumours. Follicular epithelial cell cancer is the commonest type; this usually presents with usually well differentiated tumours and has an excellent prognosis, but occasionally highly undifferentiated; it may be induced by exposure to ionizing radiation. Medullary thyroid carcinoma arises from parafollicular C cells; it comprises 3–5% of all thyroid cancers; usually hereditary autosomal dominant forms associated with germline point mutations in the RET proto-oncogene. Rare thyroid tumours include anaplastic carcinomas, which present as a rapidly enlarging and fixed thyroid masses, sometimes with local pain; they are rapidly fatal; sarcomas; and primary lymphomas—these usually present as a rapidly enlarging thyroid mass in a patient with Hashimoto’s thyroiditis.

Basal Autophagy Deficiency Causes Thyroid Follicular Epithelial Cell Death in Mice

Autophagy is a catabolic process that involves the degradation of cellular components through the lysosomal machinery, relocating nutrients from unnecessary processes to more pivotal processes required for survival. It has been reported that systemic disruption of the Atg5 or Atg7 gene, a component of autophagy, is lethal and that its tissue-specific disruption causes tissue degeneration in several organs. However, the functional significance of autophagy in the thyroid glands remains unknown. Our preliminary data imply the possible involvement of dysfunctional autophagy in radiation-induced thyroid carcinogenesis. Therefore, we evaluated the effect of Atg5 gene knockout (KO) on thyroid morphology and function. To this end, Atg5flox/flox mice were crossed with TPO-Cre mice, yielding the thyroid follicular epithelial cell (thyrocyte)‒specific ATG5-deficient mice (Atg5thyr-KO/KO). Atg5 gene KO was confirmed by a lack of ATG5 expression, and disruption of autophagy was demonstrated by a decrease in microtubule-associated protein 1 light chain 3–II puncta and an increase in p62. Atg5thyr-KO/KO mice were born normally, and thyroid morphology, thyroid weights, and serum T4 and TSH levels were almost normal at 4 months. However, at 8 and 12 months, a decrease in the number of thyrocytes and an increase in TUNEL+-thyrocytes were observed in Atg5thyr-KO/KO mice even though thyroid function was still normal. The number of irregularly shaped (gourd-shaped) follicles was also increased. Excess oxidative stress was indicated by increased 8-hydroxy-2′-deoxyguanosine and 53BP1 foci in Atg5thyr-KO/KO mice. These data demonstrate that thyrocytes gradually undergo degradation/cell death in the absence of basal levels of autophagy, indicating that autophagy is critical for the quality control of thyrocytes.

Thyroid cancer

Thyroid cancers account for less than 1% of all malignancies but are much the most frequent cancers of endocrine organs. Follicular epithelial cell cancer—the commonest type; may be induced by exposure to radiation; can be highly undifferentiated or differentiate into recognizable follicular cells, sometimes with retention of hormone biosynthesis; typically present with an asymptomatic thyroid nodule; usually diagnosed by fine needle aspiration biopsy; treatment is typically by total or near total thyroidectomy, with radio-iodine then administered to remove any remaining thyroid tissue (followed by long-term thyroid replacement therapy)....