Bleeding in Pituitary May Complicate Diagnosis of Cushing’s Disease

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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Children and adolescents with Cushing’s disease who have subclinical bleeding near their disease-driving tumors may respond differently to tests used to diagnose the disease, compared with patients without this bleeding, according to a new study.

These differences may complicate the diagnostic workup of these patients and “should be incorporated in their evaluation,” researchers say.

The study, “Subclinical Hemorrhage of ACTH-secreting Pituitary Adenomas in Children and Adolescents Changes Their Biochemical Profile,” was published in the Journal of the Endocrine Society.

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In Cushing’s disease, a tumor in the brain’s pituitary gland causes excessive production of the signaling molecule ACTH, which drives the overproduction of the stress hormone cortisol that causes disease symptoms. A common test used to diagnose Cushing’s disease is the dexamethasone suppression test, which measures how cortisol levels change in response to a steroid medication that lowers ACTH levels.

Subclinical pituitary hemorrhage, or SPH, refers to bleeding or unusual tissue death in the pituitary gland. By definition, SPH is subclinical and does not cause overt problems, which is usually noted incidentally during assessments of pituitary tumors, particularly larger ones.

Here, scientists at the National Institutes of Health in the U.S. analyzed data for 170 children and adolescents with Cushing’s disease participating in a clinical study (NCT00001595). All patients were younger than 21 years at diagnosis, and all underwent surgery to remove the disease-driving tumor.

From the 170 patients, 12 (7.1%) had evidence of SPH on MRI scans of their brains taken before surgery. Compared with the rest of the patients, those with SPH were similar in terms of age and sex, but had a markedly shorter median disease duration (1.0 vs. 2.5 years), as well as larger median tumor size (8.5 vs. 5.4 mm).

Cortisol levels did not differ significantly between patients with or without SPH. However, patients with SPH had significantly higher levels of morning ACTH (60.8 vs. 39.4 picograms per milliliter, pg/mL).

Additionally, among eight patients with SPH and 120 without who underwent the dexamethasone test, the average extent of cortisol reduction was significantly lower for patients with SPH (58% vs. 86%). The researchers noted that patients with SPH were markedly less likely to have a reduction in cortisol levels of at least 69%, which is often used as a cutoff for diagnosing Cushing’s disease.

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Rates of remission and relapse following surgery did not differ significantly between patients with or without SPH.

“SPH is often an incidental finding in the imaging evaluation of patients with [pituitary tumors]. The frequency of SPH in patients with [Cushing’s disease] is low (7.1% in our study) but these patients may differ in terms of their history of shorter duration of symptoms and the biochemical evaluation,” the researchers wrote.

“More specifically, patients with [Cushing’s disease] and SPH showed higher ACTH levels and lower suppression of cortisol to high-dose dexamethasone. This, however, did not affect their prognosis in terms of immediate postoperative remission and long-term risk of recurrence,“ they wrote.