Non-endocrine tumors causing endocrine syndromes: a brief review

In the early decades of the 20th century it was established that some non neuro-endocrine malignant tumors and their metastasis, were secreting substances with biologic properties and causing clinical syndromes similar to the ones caused by naturally occurring hormones. The most known syndromes are caused by substances mimicking the biologic properties of ACTH, erythropoietin, insulin and PTH. Many theories have been postulated in an attempt to explain the synthesis process of hormone mimetic substances. Ectopic secretion of ACTH syndrome comprises 10%-20% of all cases presenting with Cushing's syndrome. The clinical picture manifests in a variable way. The increased plasma levels of cortisol in these cases, cause symptoms distinct from the ones of true Cushing's syndrome. In general these patients have an ominous prognosis. Survival is limited to 6-12 months and is attributed to hypercortisolemia that is known to increase the risk of metastasis. Hypercalcemia syndrome from ectopic secretion of hypercalcemic factors is a severe complication of cancer patients with an incidence of 5-10%. Increased serum calcium is caused either by the osteolytic metastasis of malignant tumors or by their secretions. The clinical picture caused is similar to the findings of primary hyperparathyroidism. Treatment options in case of acute and severe hypercalcemia in patients with malignancy are limited. The endocrine syndromes produced by non-endocrine tumors not only affect patient's quality of life but also occasionally cause severe complications and can disrupt surgical or medical treatment of the primary tumor. Searching for the occurrence of such syndromes demands a high index of suspicion. This paper brings the spotlight back to the clinical syndromes of hypercortisolemia and hypercalcemia caused by ectopic ACTH and hypercalcemic factors respectively, re-iterating the need for early diagnosis and prompt management in such cases.