Hormone Secretion, Diabetes, Cortisol Levels Linked to Worse Prognosis in Ectopic Cushing’s Syndrome, Study Finds

Hormone Secretion, Diabetes, Cortisol Levels Linked to Worse Prognosis in Ectopic Cushing’s Syndrome, Study Finds
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Secretion of multiple hormones, high morning cortisol levels, higher tumor grade, and diabetes are all significantly associated with a worse prognosis for people with ectopic Cushing’s syndrome (ECS) caused by a neuroendocrine tumor, a new study found.

The study, “Multiple hormone secretion may indicate worse prognosis in patients with ectopic Cushing’s syndrome,” was published in Hormones – International Journal of Endocrinology and Metabolism.

Cushing’s syndrome is a condition characterized by high levels of the hormone cortisol in the blood stream. The causes of Cushing’s can be classified into two groups: exogenous and endogenous. Exogenous cases, or those relating to external factors, are often caused by prolonged use of medications that have corticosteroids, a form of cortisol.

Endogenous cases, or those relating to factors within the body, are often caused by tumors — either benign or malignant — that produce excess levels of certain hormones. The majority of endogenous Cushing’s cases are caused by a tumor in the pituitary gland that produces too much of the adrenocorticotrophic hormone (ACTH). That, in turn, makes the adrenal glands — which sit atop the kidneys — secrete excess cortisol.

However, roughly 5-10% of endogenous Cushing’s syndrome cases are attributed to tumors in other locations that also produce excess ACTH. These cases are referred to as ectopic Cushing’s syndrome, which means in an unexpected location.

The most prevalent and well-described cause of ectopic Cushing’s syndrome is small cell lung carcinoma.

The second most prevalent cause is a neuroendocrine neoplasm, which is a tumor that develops from cells of the endocrine, or hormonal system. These tumors normally originate in the lungs, pancreas, and thymus.

The rarity of ectopic Cushing’s syndrome caused by a neuroendocrine tumor has all but prevented any large studies examining its features and prognostic factors. To learn more, researchers at Uppsala University in Sweden now examined the records of 886 patients with neuroendocrine tumors referred to their center in the 28-year period between 1986 and 2014.

Among these 886 patients, just 51 (6%) were found to have ectopic Cushing’s syndrome. They included 18 men and 31 women, with an average age at tumor diagnosis of 51 years, and an average age at Cushing’s diagnosis of 52 years. The tumor itself was located in the pancreas for 15 patients and in the thorax for 28 individuals. The cause of Cushing’s was unknown in the remaining eight patients.

The majority of these individuals (30 patients; 59%) received a diagnosis of tumor and Cushing’s simultaneously. In 12 patients, the tumor diagnosis preceded Cushing’s development, with a median time of 43.5 months (about 3.5 years). The remaining eight were initially diagnosed with ectopic Cushing’s without a detectable tumor — in five of them, a tumor was never found.

Most of the patients had low potassium levels (75%), very high ACTH levels (91%), diabetes mellitus (71%), and high blood pressure (71%). A large proportion (41%) had tumors producing at least one more hormone other than ACTH — including 10% with the simultaneous production of two or more additional hormones.

The researchers then compared the symptoms experienced by the patients to their overall survival rates, to determine which symptoms resulted in worse prognoses. The results showed that those with multiple hormone secretion had significantly shorter survival (32 months), compared with the individuals who only had ectopic Cushing’s syndrome (95 months).

Statistical analysis confirmed this was the stronger predictor of worse survival in people with ectopic Cushing’s syndrome, increasing by nearly 4-fold their risk of death. Other predictors of worse survival included high levels of cortisol in the morning, a higher graded tumor, and diabetes.

“Patients with multiple hormone secretion as well as high morning cortisol levels and diabetes have worse prognosis,” the researchers said.

“These patients should be monitored carefully and probably treated more aggressively,” they added.

The study did concede, however, that the specific cause of death in these cases was often difficult to identify due to numerous complications. Thus, a larger sample group ultimately will be needed to confirm these results. Nevertheless, the data provide an important insight into ectopic Cushing’s syndrome prognosis.

David earned a PhD in Biological Sciences from Columbia University in New York, NY, where he studied how Drosophila ovarian adult stem cells respond to cell signaling pathway manipulations. This work helped to redefine the organizational principles underlying adult stem cell growth models. He is currently a Science Writer, as part of the BioNews Services writing team.
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Inês holds a PhD in Biomedical Sciences from the University of Lisbon, Portugal, where she specialized in blood vessel biology, blood stem cells, and cancer. Before that, she studied Cell and Molecular Biology at Universidade Nova de Lisboa and worked as a research fellow at Faculdade de Ciências e Tecnologias and Instituto Gulbenkian de Ciência. Inês currently works as a Managing Science Editor, striving to deliver the latest scientific advances to patient communities in a clear and accurate manner.
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David earned a PhD in Biological Sciences from Columbia University in New York, NY, where he studied how Drosophila ovarian adult stem cells respond to cell signaling pathway manipulations. This work helped to redefine the organizational principles underlying adult stem cell growth models. He is currently a Science Writer, as part of the BioNews Services writing team.
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