Circadian rhythms at a central and peripheral level are operated by transcriptional/translational feedback loops involving a set of genes called ‘clock genes’ that have been implicated in the development of several diseases, including malignancies. Dysregulation of the Clock system can influence cancer susceptibility by regulating DNA damage and repair mechanisms, as well as apoptosis. A number of oncogenic pathways can be dysregulated via clock genes’ epigenetic alterations, including hypermethylation of clock genes’ promoters or variants of clock genes. Clock gene disruption has been studied in breast, lung and prostate cancer, and haematological malignancies. However, it is still not entirely clear whether clock gene disruption is the cause or the consequence of tumourigenesis and data in endocrine neoplasms are scarce. Recent findings suggest that clock genes are implicated in benign and malignant adrenocortical neoplasias. They have been also associated with follicular and papillary thyroid carcinomas and parathyroid adenomas, as well as pituitary adenomas and craniopharyngiomas. Dysregulation of clock genes is also encountered in ovarian and testicular tumours and may also be related with their susceptibility to chemotherapeutic agents. The most common clock genes that are implicated in endocrine neoplasms are PER1, CRY1; in most cases their expression is downregulated in tumoural compared to normal tissues. Although there is still a lot to be done for the better understanding of the role of clock genes in endocrine tumourigenenesis, existing evidence could guide research and help identify novel therapeutic targets aiming mainly at the peripheral components of the clock gene system.

Objective: The association between hypothyroidism and breast cancer has been described from very early on. Breast and thyroid tissue are interconnected on a molecular level mainly through activation of thyroid hormone receptors expressed on cells of the mammary gland as well as on the plasma membrane of breast cancer cells. Despite the experimental evidence the true value of hypothyroidism as a risk factor for breast cancer remains controversial.Methods: We searched the PubMed database through February 2011 to identify studies that evaluated the association between hypothyroidism and risk for breast cancer as well as the effect of thyroid hormone replacement therapy on breast cancer incidence.Results: A meta-analysis performed in 12 studies showed that hypothyroidism was not associated with risk for breast cancer (pooled risk ratio (RR)=1.06, 95% confidence intervals (CIs) 0.82–1.35, P=0.672). The effect of treatment was assessed in seven studies and no evidence for an association between thyroid hormone replacement and breast cancer was observed with an overall RR of 0.99 (95% CI 0.73–1.35, P=0.965).Conclusions: Our meta-analysis showed that hypothyroidism is not associated with increased risk for breast cancer and thyroid hormone replacement therapy does not reduce breast cancer prevalence; however, the heterogeneity of the studies analyzed precludes firm conclusions.

Endocrine organs are metastatic targets for several primary cancers, either through direct extension from nearby tumour cells or dissemination via the venous, arterial and lymphatic routes. Although any endocrine tissue can be affected, most clinically relevant metastases involve the pituitary and adrenal glands with the commonest manifestations being diabetes insipidus and adrenal insufficiency respectively. The most common primary tumours metastasing to the adrenals include melanomas, breast and lung carcinomas, which may lead to adrenal insufficiency in the presence of bilateral adrenal involvement. Breast and lung cancers are the most common primaries metastasing to the pituitary, leading to pituitary dysfunction in approximately 30% of cases. The thyroid gland can be affected by renal, colorectal, lung and breast carcinomas, and melanomas, but has rarely been associated with thyroid dysfunction. Pancreatic metastasis can lead to exo-/endocrine insufficiency with renal carcinoma being the most common primary. Most parathyroid metastases originate from breast and lung carcinomas and melanoma. Breast and colorectal cancers are the most frequent ovarian metastases; prostate cancer commonly affects the testes. In the presence of endocrine deficiencies, glucocorticoid replacement for adrenal and pituitary involvement can be life saving. As most metastases to endocrine organs develop in the context of disseminated disease, surgical resection or other local therapies should only be considered to ameliorate symptoms and reduce tumour volume. Although few consensus statements can be made regarding the management of metastases to endocrine tissues because of the heterogeneity of the variable therapies, it is important that clinicians are aware of their presence in diagnosis.