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U500 insulin screening of diabetic patients uncovers large amount of
undiagnosed hypercorticolismconsistent with Cushing’s syndrome
Fifty percent of patients screened
using concentrated U500 insulin
were found to suffer from underlying
hypercortisolism consistent with
Cushing’s syndrome, reports a
community-based, randomized
screening study.
J
oseph Wolfgang Mathews, MD, of Palmetto Endocrinology, Summerville, South Caro-
lina, explained, “Studies screening patients with diabetes for hypercortisolism indicate
that 2–10% of patients suffer from undiagnosed Cushing’s syndrome. These authors
concluded that such a low percentage prevents screening of all diabetic patients Cush-
ing’s syndrome.
“The Centers for Disease Control and Prevention estimate that in 2014, 29.1 million Amer-
icans suffered from diabetes. So we tried to identify a more at-risk population to screen
those with severe insulin resistance requiring high doses of insulin.”
Patients with type 2 diabetes requiring concentrated insulin (Humulin R U500, Lilly), how-
ever, suffer severe insulin resistance and hyperglycemia that result from undiagnosed
and uncontrolled hypercortisolism.
This was the first report on screening patients for Cushing’s syndrome using U500 insulin.
“U500 insulin is used commonly in patients who require more than 200 units of insulin
daily,” Dr Mathews said.
“Identifying patients with hypercortisolism is important,” Dr Mathews said, “but not easy.
Patients can present a wide range of phenotypes with mild symptoms easily attributed
to other conditions.”
He continued, “Excess cortisol contributes to dysfunction in multiple organ systems includ-
ing muscle weakness and atrophy, osteoporosis, dermatologic manifestations, menstrual
irregularities, insomnia, mood disturbances, recurrent infection, obesity, hypertension,
dyslipidemia, and insulin resistance. These metabolic disturbances increase the risk of
heart attack, stroke, and death. So we wanted to determine the prevalence of hypercor-
tisolism in our patient population.”
“In our community endocrine practice,” Dr Mathews said, “we screened 34 patients using
concentrated U500 insulin. Twenty-one patients (62%) had a biochemical indicator of
hypercortisolism consistent with Cushing’s syndrome. Of those 21 patients, 13 underwent
imaging at the time of publication, and nine showed radiologically confirmed hyperplasia
or adenoma. The remaining patients are anticipated to complete imaging soon.”
Dr Mathews concluded that in this community practice, 50% of patients screened by using
concentrated U500 insulin were found to suffer from underlying hypercortisolism con-
sistent with Cushing’s syndrome. These patients likely represent a population enriched
in undiagnosed Cushing’s syndrome who would benefit from testing and treatment.
“Results of our study,” he added, “demon-
strated that hypercortisolism appears to
be prevalent in the population of patients
requiring concentrated U500 insulin. The
majority of these patients appear to have
an adrenal etiology of hypercortisolism.”
He continued, “Based on this data, it
would make sense to consider screen-
ing patients requiring U500 insulin for
Cushing’s syndrome. Once such patients
are identified, they can receive more tar-
geted therapy to improve their morbidity
and mortality.”
Paras Mehta, MD, of Baylor College of
Medicine, Houston, Texas, highlighted
the difficulty of diagnosing and manag-
ing Cushing’s syndrome in a case series.
Individualized treatment of
Cushing’s syndrome
He explained that while the diagnosis
of Cushing’s syndrome is often une-
quivocal, determining its etiology and
managing the syndrome effectively
remain a challenge.
It would make sense to
consider screening patients
requiring U500 insulin for
Cushing’s syndrome. Once
such patients are identified,
they can receive more
targeted therapy to improve
their morbidity and
mortality.
© Photo by Jean Whiteside/AACE 2017
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