What do the glucagon stimulation test results (cortisol rising to 506 nmol/L and growth hormone peaking at 20 µg/L) indicate about adrenal and growth‑hormone function in a 13‑year‑old boy?

Glucagon Stimulation Test Results Analysis in a 13-Year-Old Boy

Overall Interpretation

This glucagon stimulation test demonstrates normal adrenal function and normal growth hormone secretion in this 13-year-old boy. Both the cortisol and growth hormone responses meet established diagnostic thresholds for sufficiency 1, 2.

---

Adrenal Function Assessment

Cortisol Response Analysis

The peak cortisol of 506 nmol/L (approximately 18.3 µg/dL) indicates adequate adrenal reserve. 2, 3

• The cortisol rose appropriately from baseline values of 178-212 nmol/L to a peak of 506 nmol/L at 150 minutes 2
• Using validated thresholds from prospective studies, a peak cortisol >599 nmol/L (>21.7 µg/dL) provides 100% specificity for adrenal sufficiency, while a peak <277 nmol/L (<10 µg/dL) indicates adrenal insufficiency with >95% specificity 2
• This patient's result of 506 nmol/L falls in the intermediate zone but is closer to the sufficiency threshold 2
• In pediatric populations specifically, a peak cortisol cutoff of 14.6 µg/dL (403 nmol/L) during glucagon stimulation provides 100% specificity for diagnosing adrenal sufficiency, and this patient exceeds that threshold 3

Clinical Context for Adrenal Assessment

• The cortisol peak occurred at 150 minutes, which is within the expected timeframe for glucagon stimulation testing 2, 3
• No further adrenal testing is indicated based on these results 1
• The Lancet Diabetes & Endocrinology guidelines note that in children with Cushing's syndrome, using insulin tolerance or glucagon stimulation test, severe growth hormone deficiency is defined as <9 mU/L (approximately <3 µg/L) and partial deficiency as <30 mU/L (approximately <10 µg/L), but this patient is being evaluated for sufficiency, not deficiency 1

---

Growth Hormone Function Assessment

GH Response Analysis

The peak growth hormone of 20.0 µg/L at 120 minutes confirms normal GH secretion. 4, 2, 3

• The GH rose from baseline values of 0.14-0.18 µg/L to a robust peak of 20.0 µg/L 4
• Using modern assay thresholds, a peak GH >10 µg/L (10 ng/mL) during glucagon stimulation indicates sufficient GH secretion in children 4
• A peak GH of 2.5 ng/mL (2.5 µg/L) provides 95% sensitivity and 79% specificity for diagnosing GH deficiency when compared to insulin tolerance testing, and this patient far exceeds this threshold 2
• The timing of the GH peak at 120 minutes is considered "typical" and reassuring 4

Importance of Peak Timing

• GH typically peaks at 90 or 120 minutes during glucagon stimulation 4
• Atypical timing (peaks at times other than 90 or 120 minutes) may indicate abnormal GH secretion even when absolute values appear sufficient 4
• In one pediatric study, 75% of patients with atypical deficient glucagon tests showed atypical timing on confirmatory clonidine testing, suggesting underlying pituitary dysfunction 4
• This patient's peak at 120 minutes is reassuringly typical and supports normal GH axis function 4

Technical Considerations

• Two samples were noted as "grossly hemolyzed" (at -20 minutes with GH 0.14 µg/L and at 90 minutes with GH 5.59 µg/L) 4
• Hemolysis can artificially affect hormone measurements, but the clear peak at 120 minutes (20.0 µg/L) in a non-hemolyzed sample provides reliable diagnostic information 4
• The test can be safely terminated at 150 minutes without sacrificing sensitivity, as only 1.3% of peaks occur at 180 minutes 4

---

Glucose Response Pattern

Glycemic Changes During Testing

• Baseline glucose was 4.4-4.6 mmol/L, rose to 5.8 mmol/L at 30 minutes, then declined to a nadir of 3.8 mmol/L at 120 minutes 5, 6
• This pattern is consistent with expected glucagon-induced glycemic changes: initial rise followed by reactive decline 5
• The mean glycemic nadir in adult studies occurs around 30 minutes post-injection at approximately 4.34 mmol/L, though this patient's nadir occurred later 5
• No hypoglycemic symptoms were documented, and glucose values remained in a safe range throughout 5, 6

---

Clinical Implications and Next Steps

What These Results Rule Out

• Growth hormone deficiency is excluded by the robust GH peak of 20.0 µg/L with typical timing 4, 2
• Central adrenal insufficiency is unlikely given the cortisol peak of 506 nmol/L, though it falls in an intermediate diagnostic zone 2, 3
• If there were clinical suspicion for adrenal insufficiency (unexplained fatigue, hypotension, hypoglycemia), consider confirmatory testing with insulin tolerance test or early-morning ACTH and cortisol during wellness and illness 1

Adolescent-Specific Considerations

• In a 13-year-old, pubertal status (Tanner stage) is critical for interpreting GH dynamics 1, 7, 8
• Standard GH suppression testing (oral glucose tolerance test) is unreliable in adolescents, with approximately 30% of normally growing tall adolescents failing to suppress GH below 1 µg/L despite being completely normal 1, 7, 8
• IGF-1 levels should be interpreted using Tanner stage-matched, sex-matched, and age-matched reference ranges, as marginal elevation during mid-puberty (Tanner 2-3) requires cautious interpretation 1, 7, 8
• IGF-1 may be falsely low with concurrent hypothyroidism, malnutrition, or severe infection, and falsely elevated with poorly controlled diabetes or hepatic/renal failure 1, 7, 8

Recommended Follow-Up

• Document Tanner stage to contextualize these results 1, 7, 8
• Measure serum IGF-1 with local age-matched and Tanner-matched reference ranges 1, 7, 8
• Check thyroid function (TSH, free T4) to exclude hypothyroidism 7, 8
• Obtain left wrist radiograph for bone age assessment if growth concerns persist 7, 8
• Plot serial heights and calculate mid-parental target height to assess growth velocity over 6-12 months 7, 8

---

Common Pitfalls to Avoid

• Do not dismiss hemolyzed samples without considering the overall pattern: this patient had a clear non-hemolyzed peak that provides diagnostic certainty 4
• Do not apply adult cortisol cutoffs rigidly to pediatric patients: use age-appropriate thresholds (>14.6 µg/dL or >403 nmol/L for sufficiency in children) 3
• Do not interpret GH results without considering peak timing: atypical timing may indicate dysfunction even with apparently adequate peak values 4
• Do not use glucagon stimulation as the sole test for adrenal insufficiency in borderline cases: if clinical suspicion remains high, proceed to insulin tolerance testing 2, 3
• Do not overlook the importance of Tanner staging in adolescents: GH and IGF-1 interpretation is highly dependent on pubertal status 1, 7, 8