Unexpected insulin resistance exposes rare Cushing’s disease diagnosis
Case highlights need to look beyond diabetes when control worsens
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A woman with type 1 diabetes was diagnosed with Cushing’s disease after her daily insulin needs rose sharply and no longer controlled her blood sugar levels, a case study reports.
“This case underscores the importance of regular review of automated insulin delivery data and consideration of [hormonal] causes of insulin resistance and increased insulin requirements in those with type 1 diabetes,” the researchers wrote.
The case was detailed in the study, “Insulin Resistance Unveiled: Cushing’s Disease in a Patient with Type 1 Diabetes Mellitus and Worsening Glycemic Control,” published in AACE Endocrinology and Diabetes.
When rising insulin needs signal more than diabetes
Type 1 diabetes mellitus is an autoimmune disease in which the immune system attacks pancreatic beta cells, the cells that produce insulin — a hormone needed to regulate blood sugar (glucose). Because of this, people with type 1 diabetes cannot make enough insulin on their own and require daily insulin delivery, often through an automated pump.
In Cushing’s disease, tumors in the pituitary gland cause the release of excess adrenocorticotropic hormone (ACTH). This hormone stimulates the adrenal glands, located above the kidneys, to produce abnormally high levels of cortisol. Over time, excess cortisol can interfere with how the body uses insulin, leading to a range of symptoms, including insulin resistance and worsening blood sugar control.
This report describes a 21-year-old woman with type 1 diabetes who noticed that her automated insulin pump was running out of insulin earlier than expected because of increasing insulin demands.
Over the following 16 months, she gained weight and developed higher blood pressure and blood sugar levels. A review of her insulin pump data showed a gradual rise of about 30% in her total daily insulin dose, along with an increase in hemoglobin A1c (HbA1c), a measure of average blood glucose levels over the previous two to three months.
A physical examination revealed signs consistent with elevated blood cortisol levels, known as hypercortisolism. This included cystic acne (a severe form of inflammatory acne), swelling in the feet and ankles, and purple stretch marks on her abdomen, hips, and thighs. Doctors found no evidence that her symptoms were caused by prior corticosteroid use, which can also raise cortisol levels.
Testing points to excess cortisol as the cause
Further testing revealed elevated salivary cortisol, high blood levels of ACTH, and persistently elevated blood cortisol after exposure to dexamethasone — a medication that normally suppresses cortisol production. In healthy individuals, cortisol levels fall after dexamethasone treatment. She also had low bone mineral density for her age, a finding consistent with both type 1 diabetes and excess cortisol.
With Cushing’s disease suspected, doctors ordered a pituitary MRI, which revealed a large tumor. She then underwent a transsphenoidal adenomectomy, a surgery used to remove pituitary tumors. Testing confirmed that the tumor was producing ACTH, establishing the diagnosis of Cushing’s disease.
Despite surgery, cortisol levels remained high even after intraoperative dexamethasone, raising concern that part of the tumor remained. During hospitalization, her cortisol and ACTH levels fluctuated, and follow-up testing showed markedly elevated urinary cortisol levels, confirming persistent hypercortisolism. A repeat MRI revealed residual tumor tissue, which was treated with radiation therapy.
She was started on Isturisa (osilodrostat), an approved treatment for Cushing’s disease that lowers cortisol production by the adrenal glands. Over two years, her dose was gradually increased to 7 mg twice daily, alongside temporary increases in insulin pump settings. With ongoing treatment, her urinary cortisol levels normalized, she lost weight, and her total daily insulin needs declined.
“This case emphasizes the importance of considering secondary [hormone-related] disorders in those living with diabetes mellitus who experience sudden or unexplained changes in [blood sugar] control and insulin requirements,” the team wrote.
