Meeting News CoveragePerspective

Shorter test for GH deficiency as accurate as traditional protocol

HALIFAX, Nova Scotia — Clinicians can safely revise their growth hormone stimulation protocols to reduce the amount of sampling they perform when determining if children have growth hormone deficiency, retrospective research presented here suggests.

“It is a very long test [testing for growth hormone deficiency],” Reem Al Khalifah, MD, FRCPC, ABP, said.

Al Khalifah led the growth hormone stimulation protocols study as part of a pediatric endocrinology fellowship at McGill University/Montreal Children's Hospital in Montreal, Quebec.

“Children are in hospital typically from 8 am until 12 pm for sequential Clonidine and Arginine testing. They have to fast before the test, and they go without food for about 12 to 16 hours,” Khalifah said.

Al Khalifah and colleagues reviewed charts of 243 children (mean age 11 years) who had been tested for GH deficiency from 2008 to 2014. Specificity of standard testing duration, which involved 120 minutes of clonidine and 90 minutes of arginine, was compared with an abbreviated clonidine and arginine test in which clonidine testing was reduced to 90 minutes and arginine testing was reduced to 60 minutes. Additionally, they compared the combined standard test results with the abbreviated combined test results, to simulate the clinical interpretation of the results. Traditionally, growth hormone deficiency is diagnosed based on the results of two stimulation tests.

Among 159 children tested with both agents, the investigators found 29 children were diagnosed with GH deficiency using standard testing while 30 were diagnosed with the shortened combined test. This shortened combined test yielded a false positive rate of 0.8% and a specificity of 99.2%. The individual clonidine shortened test yielded a specificity of 98.1% and a false positive rate of 1.9% while the individual arginine shortened test produced a specificity of 97.9% and a false positive rate of 2.1%.

Investigators concluded that the combined shortened test did not significantly affect specificity and had the same sensitivity in diagnosing growth hormone deficiency, and have since adopted the protocols that are shorter in duration, Al Khalifah said.

“Children have to be available for 2.5 hours [with the combined test] instead of 3.5 hours that is required with the other protocol," Al Khalifah said. She described the revised protocol as more practical and added that by limiting the timed samples, children are able to eat sooner and do not have to stay in the hospital as long, and health care dollars are being saved with fewer samples being drawn. “Patients, their families, and health professionals all prefer this [protocol].”

These results are generalizable to children up to 18 years old. Future studies should explore if similar testing specificity can be obtained in the adult population to diagnose adult growth hormone deficiency.

Al Khalifah and colleagues conducted a survey prior to beginning their retrospective research and found variation and inconsistency in growth stimulation protocols across Canadian centers. “There is a lot of heterogeneity in protocols,” said Al Khalifah said. – by Louise Gagnon

Reference:

Al Khalifah R, et al. Oral Abstract 11. Presented at: Canadian Pediatric Endocrine Group Scientific Meeting; Feb. 19-21, 2015; Halifax, Nova Scotia, Canada.

Disclosure: Al Khalifah reports no relevant financial disclosures.   

HALIFAX, Nova Scotia — Clinicians can safely revise their growth hormone stimulation protocols to reduce the amount of sampling they perform when determining if children have growth hormone deficiency, retrospective research presented here suggests.

“It is a very long test [testing for growth hormone deficiency],” Reem Al Khalifah, MD, FRCPC, ABP, said.

Al Khalifah led the growth hormone stimulation protocols study as part of a pediatric endocrinology fellowship at McGill University/Montreal Children's Hospital in Montreal, Quebec.

“Children are in hospital typically from 8 am until 12 pm for sequential Clonidine and Arginine testing. They have to fast before the test, and they go without food for about 12 to 16 hours,” Khalifah said.

Al Khalifah and colleagues reviewed charts of 243 children (mean age 11 years) who had been tested for GH deficiency from 2008 to 2014. Specificity of standard testing duration, which involved 120 minutes of clonidine and 90 minutes of arginine, was compared with an abbreviated clonidine and arginine test in which clonidine testing was reduced to 90 minutes and arginine testing was reduced to 60 minutes. Additionally, they compared the combined standard test results with the abbreviated combined test results, to simulate the clinical interpretation of the results. Traditionally, growth hormone deficiency is diagnosed based on the results of two stimulation tests.

Among 159 children tested with both agents, the investigators found 29 children were diagnosed with GH deficiency using standard testing while 30 were diagnosed with the shortened combined test. This shortened combined test yielded a false positive rate of 0.8% and a specificity of 99.2%. The individual clonidine shortened test yielded a specificity of 98.1% and a false positive rate of 1.9% while the individual arginine shortened test produced a specificity of 97.9% and a false positive rate of 2.1%.

Investigators concluded that the combined shortened test did not significantly affect specificity and had the same sensitivity in diagnosing growth hormone deficiency, and have since adopted the protocols that are shorter in duration, Al Khalifah said.

“Children have to be available for 2.5 hours [with the combined test] instead of 3.5 hours that is required with the other protocol," Al Khalifah said. She described the revised protocol as more practical and added that by limiting the timed samples, children are able to eat sooner and do not have to stay in the hospital as long, and health care dollars are being saved with fewer samples being drawn. “Patients, their families, and health professionals all prefer this [protocol].”

These results are generalizable to children up to 18 years old. Future studies should explore if similar testing specificity can be obtained in the adult population to diagnose adult growth hormone deficiency.

Al Khalifah and colleagues conducted a survey prior to beginning their retrospective research and found variation and inconsistency in growth stimulation protocols across Canadian centers. “There is a lot of heterogeneity in protocols,” said Al Khalifah said. – by Louise Gagnon

Reference:

Al Khalifah R, et al. Oral Abstract 11. Presented at: Canadian Pediatric Endocrine Group Scientific Meeting; Feb. 19-21, 2015; Halifax, Nova Scotia, Canada.

Disclosure: Al Khalifah reports no relevant financial disclosures.   

    Perspective

    The authors tackled the longstanding question of the optimal timing and sampling for growth hormone stimulation testing. Despite its limitations as a nonphysiologic stress, GH stimulation testing remains the gold standard for diagnosing GH deficiency. GH testing is a prolonged, resource-heavy, expensive procedure for many centers, and a burden for many families. Clonidine is thought to work through the stimulation of GH-releasing hormone and arginine through inhibition of hypothalamic somatostatin release. These authors analyzed whether the arginine test could be shortened from 90 to 60 minutes and/or the clonidine test from 120 to 90 minutes, without losing specificity and sensitivity; this amounts to the deletion of one final sample for each test protocol. Using retrospective results from their classical, combined protocol as the comparator, the authors were able to demonstrate that shortening the tests resulted in a specificity of 98.1% and a false-positive rate of 1.9% for the clonidine test, and a specificity of 98.6% and a false-positive rate of 1.4% for arginine. This provides further evidence that a shortened, combined arginine–clonidine test can be substituted for the longer test without losing significant test performance. This should hopefully save on system resources and improve patient satisfaction with GH stimulation testing.

    • Daniel L. Metzger , MD, FAAP, FRCPC
    • Pediatric Endocrinologist, BC Children’s Hospital Clinical Professor of Pediatrics, University of British Columbia Vancouver, British Columbia

    Disclosures: Metzger reports no relevant financial disclosures.