medwireNews: Italian researchers have determined a glucagon stimulation test (GST) threshold that can predict whether a teenager with growth hormone deficiency (GHD) has or has not experienced normalisation of GH levels at the time of transition to adult care.
The insulin tolerance test (ITT) is the “gold standard” for confirmation of GHD after adult stature is reached and a GH threshold of 6 μg/L or less is recommended to determine whether GHD continues at time of transition to adult care, say Mohamad Maghnie (University of Genoa, Italy) and co-workers.
However, the ITT is unsuitable for patients with seizures, epilepsy or cerebrovascular or cardiovascular disease. While the GST offers an alternative form of GH stimulation for determining the need for ongoing GH therapy into adulthood, the diagnostic cutoffs for this test have not been confirmed in clinical practice, the team says.
To investigate the accuracy of the GST versus the ITT for determining GHD at time of transition, the team assessed 97 people (64% male) with childhood-onset GHD at a median age of 11.4 years using the ITT (intravenous bolus 0.1 IU/kg insulin) and GST (1 mg intramuscular) on different days. The participants were then retested at a median age of 17.4 years, at least 1 month after they had discontinued GH therapy on reaching adult height (growth velocity <2 cm/year) and pubertal maturity (Tanner stage 4–5).
The patients were divided into three groups based on magnetic resonance imaging findings at GHD diagnosis and the number of pituitary deficiencies diagnosed, the researchers explain in The Journal of Clinical Endocrinology & Metabolism.
Forty-four patients had idiopathic GHD, defined as normal imaging, no malignancy and isolated GHD, and this group was considered to have a low probability of permanent GHD. A further 35 patients were classified as having organic moderate GHD with one or two pituitary hormone defects caused by either malignancy leading to organic hypothalamic–pituitary disease after brain surgery, radiation therapy or infiltrative disease (n=27), or pituitary stalk interruption syndrome (n=8). These patients were considered to have a high likelihood of permanent GHD.
Finally, 18 patients had three or more pituitary hormone deficiencies and organic severe GHD from central nervous system malignancy (n=14), or from pituitary stalk interruption syndrome (n=3) or Rathke’s cleft cyst (n=1). These patients formed a comparison group in the study as, under current recommendations, they are unlikely to experience GH normalisation and do not need further testing, the researchers say.
ITT confirmed GHD in 47.4% of the cohort, including 94.4% of the organic severe and 71.4% of the organic moderate GHD patients and 9.0% of those with idiopathic GHD, whereas a GST peak of less than 5.8 ug/L confirmed the diagnosis in 48.5%, 94.4%, 74.3% and 9.0% of these groups, respectively.
There was a “strong positive” and significant correlation between ITT and GST for peak GH, with an intraclass correlation coefficient of 92.4%. There were also significant correlations between GH peak, measured by either the ITT or GST test, with serum inulin-like growth factor (IGF)-1 standard deviation score (SDS). The optimal cutoff for IGF-1 was –1.4 SDS, being 75.0% sensitive and 94.0% specific and correctly classifying GHD status in 85.1% of the full cohort.
Receiver operating characteristic curve analysis denoted that for GST a GH cutoff of 7.3 ug/L was optimal for the diagnosis of GHD during transition, regardless of the origin of the GH defect, with a sensitivity of 95.7% and a specificity of 88.2%, resulting in 91.8% of the cohort being correctly classified for GHD status.
However, the best GH cutoff for patients with organic moderate GHD – who the researchers describe as being the “most challenging” group due to their high likelihood of permanent GHD – was 5.8 μg/L, being 91.4% accurate for diagnosing GHD in this cohort at transition, with a sensitivity of 96.0% and a specificity of 80.0%. And this threshold retained accuracy, sensitivity and specificity when applied to the whole patient cohort (89.4%, 91.3% and 90.2%, respectively), the researchers emphasize.
“Our data confirm that GST is a safe alternative to ITT for assessing GH secretion in young adults with [childhood onset]-GHD after attainment of adult height and that patients who demonstrated peak GH <5.8 μg/L can restart [recombinant human] GH therapy”, the authors conclude.
They now “propose to retest with GST all [childhood onset]-GHD patients with organic GHD (brain tumors, congenital anomalies, irradiation to the hypothalamic/pituitary region) with 0, 1, or 2 pituitary hormone defects with IGF-1 ≥ –2SDS, and patients with idiopathic GHD with IGF-1 <0 SDS.”
By Lynda Williams
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