Cushing Syndrome: Implications for the Science of Obesity and Overweight

Researchers have long recognized that Cushing Syndrome predisposes patients to obesity.

1. Consider this article from the New England Journal of Medicine (1994): "Cushing's syndrome in children and adolescents – presentation, diagnosis, and therapy."[1]

The authors reviewed the treatment and case histories of 59 patients and concluded that "weight gain and growth retardation are common clinical characteristics of Cushing's syndrome."

So, assuming this weight gain is clinically well established, how might it inform our national debate about healthy diets and good nutrition?

The Caloric Balance Hypothesis says that "Calories In" and "Calories Out" control our weight. So people who gain weight as a result of this syndrome must be doing so because they're overeating or under exercising relative to healthy populations.

The Lipophilia Hypothesis says that calories don't "matter." We get fat when insulin deranges our fat tissue. This theory tells us that Cushing Syndrome weight gain must stem from physiological effects at the level of the fat tissue itself.

Okay, we have our two hypotheses and our two predictions. What does the evidence say?

2. Consider this paper from the journal Clinical Endocrinology and Metabolism from 1983: "Insulin resistance in Cushing's syndrome."[2]

The authors stipulate:

"It is well established that cortisol excess causes insulin resistance in man, but the mechanisms responsible for this insulin resistance are poorly understood."

They compared patients with Cushing's Syndrome with "normal subjects" to find out how these subjects differed in response to glucose tolerance tests. They found that:

"In Cushing Syndrome, the dose-response curve was shifted to the right in comparison with normal subjects, with a significantly lower M [rate of glucose disposal]... during the highest insulin infusion rate."

If patients with this syndrome metabolize glucose and secrete insulin differently than "normal subjects" do, doesn't that support Lipophilia's point of view?

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1. Maria Alexandra Magiakou, George Mastorakos, Edward H. Oldfield, M. Teresa Gomez, John L. Doppman, Gordon B. Cutler, Lynnette K. Nieman, and George P. Chrousos"Cushing's syndrome in children and adolescents – presentation, diagnosis, and therapy." NEJM Volume 331:629-636 September 8, 1994 Number 10.

2. Nosadini R, Del Prato S, Tiengo A, Valerio A, Muggeo M, Opocher G, Mantero F, Duner E, Marescotti C, Mollo F, Belloni F. "Insulin resistance in Cushing's syndrome." J Clin Endocrinol Metab. 1983 Sep;57(3):529-36.

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