Measuring Pituitary Gland Hormone with BIPSS in Children Not as Accurate as Previously Thought, Study Finds

Joana Carvalho, PhD avatar

by Joana Carvalho, PhD |

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Bilateral inferior petrosal sinus sampling (BIPSS) — a diagnostic technique for Cushing’s disease that measures the levels of the adrenocorticotropic hormone (ACTH) hormone produced by the pituitary gland — is not as accurate as previously reported in children and adolescents with Cushing’s, a retrospective study shows.

However, BIPSS sensitivity improved following desmopressin stimulation, which makes the pituitary secrete more ACTH. This occurrence suggests the approach could be used to diagnose Cushing’s disease in younger patients.

The study, “The effects of sampling lateralization on bilateral inferior petrosal sinus sampling and desmopressin stimulation test for pediatric Cushing’s disease,” was published in Endocrine.

Cushing’s syndrome is a medical condition that can be caused by the excessive production of the hormone ACTH by a tumor in the pituitary gland (Cushing’s disease), or by other tumors outside the pituitary (ectopic ACTH syndrome, EAS), that then stimulate the production of cortisol by the adrenal glands, which sit atop the kidneys.

BIPSS is considered a gold standard diagnostic tool to distinguish whether ACTH is being produced and released by the pituitary gland, or by a tumor, in adult patients. Despite maintaining the same level of accuracy in children and adolescents, some studies reported BIPSS lacked sensitivity in these patients. However, the incidence and the factors behind these false-negative results never have been addressed.

Corticotropin-releasing hormone (CRH) stimulation is known to increase the levels of ACTH and has been shown to improve BIPSS’s sensitivity, both in adults and children. Interestingly, some studies using desmopressin as an alternative to CRH reported similar results in terms of sensitivity. However, the effectiveness of desmopressin stimulation had not been tested in pediatric patients.

So, for the first time, a group of Chinese researchers carried out a retrospective study designed to evaluate the accuracy and sensitivity of BIPSS following desmopressin stimulation in a group of 16 children and adolescents with Cushing’s disease.

From 2006 to 2017, all participants underwent 17 BIPSS procedures. Patients were diagnosed with Cushing’s disease when the ratio between the levels of ACTH in the blood of veins draining the pituitary gland and peripheral blood was higher than two at baseline, or higher than three following desmopressin stimulation.

Sampling lateralization was used to determine which side of the pituitary gland contained a tumor responsible for the over-production of ACTH. Tumor localization was confirmed by magnetic resonance imaging (MRI) and surgery in all patients.

Results revealed that BIPSS sensitivity was 64.7% at baseline (higher than two) and reached a maximum of 83.3% after three minutes of desmopressin stimulation (higher than three).

Sampling lateralization helped detect tumor side in 62.5% and 63.6% of the cases before and after desmopressin stimulation, but only 50.0% and 42.9% of these matched the MRI and surgical findings.

“The most prominent finding of our study is that BIPSS is not as accurate as reported previously for diagnosis and tumor lateralization in children and adolescents with CD [Cushing’s disease],” researchers wrote.

However, “[T]his study validated that desmopressin stimulation can increase the sensitivity of BIPSS in children and adolescents. Thus, desmopressin can be an effective and easily available alternative of CRH in pediatric BIPSS,” they concluded.