Complexities of Cushing’s Syndrome

Richard Auchus, MD, Professor of Medicine at the University of Michigan in Ann Arbor, also emphasized that underdiagnosis of Cushing’s syndrome needs to be addressed. Even so, he also said that because the condition is so rare, pharmaceutical companies do not have a great deal of interest in developing diagnostic tools.

“It is hard to diagnose in the early stages because there is no simple blood or saliva test that distinguishes these patients,” Dr. Auchus said in an interview with Endocrinology Advisor.

Elizabeth J. Murphy, MD, Chief of Endocrinology at San Francisco General Hospital, said this is a controversial area, as there is a lack of conclusive evidence when it comes to underdiagnosis of Cushing’s syndrome and subclinical Cushing’s syndrome.

“The issue of how much clinically relevant increased cortisol secretion is undiagnosed remains an open and unanswered question. There are many new drugs to treat Cushing’s syndrome on the market. True Cushing’s syndrome is a very rare disease and thus there is a clear agenda on the part of the pharmaceutical companies to generate a new market by increasing those diagnosed with ‘subclinical Cushing’s syndrome,’” she said.

“We will need well done studies to determine the true impact of subclinical disease and also the value, if any, of these newer medical therapies that do not come without risks,” said Dr. Murphy.

Unanswered Questions

Laurence Katznelson, MD, Medical Director of the Pituitary Center at Stanford University School of Medicine in California, said that while significant advances are occurring, there is still a lot unknown about Cushing’s syndrome.

For example, he cautioned that significant numbers of patients with Cushing’s syndrome may have a form of the illness with no genetic link.

“Cushing’s syndrome refers to a group of disorders that result in hypercortisolism. These disorders include a pituitary tumor, neuroendocrine tumors and adrenal disorders, including tumors and hyperplasia syndromes. Of the pituitary tumors, less than 5% appear to have a clearly defined genetic basis and most cases are sporadic,” Dr. Katznelson told Endocrinology Advisor. “Of the adrenal disorders, genetic disorders, including Carney syndrome, a genetic basis can be present in a minority of cases.”

Pituitary endocrinologist Lewis Blevins Jr., MD, Clinical Professor of Neurological Surgery and Medicine and Medical Director of the California Center for Pituitary Disorders at the University of California San Francisco, agrees with Dr. Katznelson.

He noted that newer forms of radiotherapy and better surgical approaches have reduced morbidity and mortality in recent years. Endocrinologists now have many more tools for medically managing this syndrome and there are many other novel agents in the pipeline, according to Dr. Blevins.

“I am finding this to be a very exciting time,” he told Endocrinology Advisor. “The new genetic research will help certain families and should help achieve a greater understanding of the disorder.”


  1. Beuschlein F et al. N Engl J Med. 2014;370:1019-1028.
  2. Assié G et al. N Engl J Med. 2013;369:2105-2114.
  3. Fein HG et al. Abstract MON-0663. Presented at: ICE/ENDO 2014; June 21-24, 2014; Chicago.