What is the initial work‑up for a patient with an elevated growth hormone (hGH) level?

Initial Work-Up for Elevated Growth Hormone

The initial work-up for elevated GH requires measuring serum IGF-1 levels (age-, sex-, and Tanner stage-matched), performing an oral glucose tolerance test (OGTT) to assess GH suppression, and obtaining pituitary MRI imaging if biochemical confirmation is established. 1

Biochemical Confirmation Strategy

Primary Diagnostic Tests

• Measure serum IGF-1 concentration using assays with established local Tanner stage-matched, sex-matched, and age-matched normal ranges to avoid inter-assay variability 1

  • IGF-1 elevation with apparently normal GH values may reflect early disease 1
  • IGF-1 levels correlate linearly with GH only up to 4 μg/l and plateau at approximately 10 μg/l 1

• Perform oral glucose tolerance test (OGTT) to assess GH suppression 1, 2

  • In adults: failure to suppress GH below 1 μg/l (or 0.4 μg/l with sensitive assays) confirms GH excess 1, 2
  • In children/adolescents: failure to suppress below 1 μg/l suggests GH excess, though complete suppression can be difficult in normal puberty 1
  • Pubertal-specific nadirs vary: highest in mid-puberty (Tanner 2-3), particularly in girls (mean ± 2 SD: 0.22 μg/l ± 0.03–1.57 in girls vs 0.21 μg/l ± 0.09–0.48 in boys) 1

• Obtain baseline random GH levels for prognostic purposes, as higher baseline GH predicts lower likelihood of surgical remission 1

Clinical Context Assessment

• Evaluate phenotypic features including height velocity, pubertal stage (Tanner staging), and bone age via left wrist radiograph 1
  • Approximately 30% of children with tall stature (+3.1 ± 0.8 height SDS) lack GH suppression, making diagnosis challenging in this group 1

Comprehensive Pituitary Hormone Assessment

Evaluate for Hypopituitarism

• Perform dynamic pituitary assessment for hypofunction of other anterior pituitary hormones, as 25-35% of somatotrophinomas cause compression-related deficiencies 1
  • Hypogonadism with bone age delay is particularly relevant as it extends the growth window 1

Screen for Hormone Co-Secretion

• Measure prolactin levels, as 65% of pediatric acromegaly cases and 34-36% of gigantism cases demonstrate hyperprolactinemia 1

  • Half of GH-secreting adenomas show both GH and prolactin immunostaining 1

• Assess thyroid function (TSH, free T4), as TSH co-secretion occurs less frequently than prolactin but remains clinically significant 1

Imaging and Syndromic Evaluation

Structural Assessment

• Obtain pituitary MRI once biochemical GH excess is confirmed to identify adenoma presence, size, and invasiveness 2, 3

Syndromic Screening

• Clinically evaluate for associated syndromes including McCune-Albright syndrome, Carney complex, MEN1, MEN4, MEN5, and pheochromocytoma-paraganglioma-related pituitary disease 1
  • In Carney complex, biochemical GH axis alterations may occur without overt clinical acromegaly 1
  • Consider GH-releasing hormone-secreting pancreatic tumors in MEN1 syndrome 1

Assessment of Complications

Metabolic Screening

• Evaluate for glucose intolerance with fasting glucose and HbA1c, as GH excess causes insulin resistance 1

• Measure blood pressure to detect hypertension, a common complication of GH hypersecretion 1

Critical Pitfalls to Avoid

• Do not rely on random GH measurements alone, as pulsatile secretion and short half-life create highly variable serum levels 2, 4

• Recognize conditions causing falsely abnormal IGF-1: severe hypothyroidism, malnutrition, severe infection (falsely low); poorly controlled diabetes, hepatic/renal failure, oral estrogens (falsely elevated) 1, 2

• Interpret OGTT results cautiously in tall children, as 30% may not suppress GH below 1 μg/l despite normal physiology 1

• Consider functional GH hypersecretion in malnutrition, anorexia nervosa, liver cirrhosis, renal failure, Type 1 diabetes, and hyperthyroidism before attributing elevation to pituitary pathology 2