The role of IGF-1 and growth hormone assay in the evaluation of acromegaly. Various conditions may lead to spurious lowering of growth hormone and IGF-1, even in patients with acromegaly.

IGF-1 testing

The best screening test for acromegaly (growth hormone excess) is serum insulin-like growth factor 1 (IGF-1). IGF-1 has a sensitivity and specificity for acromegaly of 97% and 90%, respectively.

Causes of low IGF-1 in patients with acromegaly

In normal physiology, the production of IGF-1 (both hepatic and extra-hepatic) sites is facilitated by thyroxine, testosterone, insulin, and estrogen (low levels). Conversely, IGF-1 production is inhibited by inflammatory cytokines. When the clinical features do not match biochemical testing, these conditions should be considered and excluded.

  • Uncontrolled diabetes mellitus
  • Hypothyroidism (both primary and secondary hypothyroidism)
  • Male Hypogonadism
  • Chronic liver disease
  • Chronic renal failure
  • Malnutrition
  • Systemic illness
  • Oral estrogen therapy

Causes of elevated IGF-1 without acromegaly

  • Preclinical disease (acromegaly)
  • Hyperthyroidism
  • Immediately after surgery (for acromegaly). Due to the long-circulating half-life of IGF-1 (12 to 15 hours)
  • After surgery (for acromegaly)

Glucose suppression testing

The gold standard confirmatory test for acromegaly is the glucose suppression test. An inability to appropriately suppress serum growth hormone (GH) below 1ng/ml after a 75g oral glucose load.

These are causes of elevated (non-suppressible) GH after a glucose tolerance test

  • Uncontrolled diabetes mellitus
  • Hypothyroidism
  • Pubertal growth spurt
  • Pregnancy
  • Depression
  • Chronic liver disease
  • Chronic kidney disease
  • Anorexia nervosa.

Clinical Question

Acromegaly IGF1 and GH discrepancy Mind Map

A patient with clinical features of acromegaly, elevated IGF-1, and a non-suppressed growth hormone (after an oral glucose load) has no demonstrable adenoma on pituitary imaging. What are the possible differential diagnoses?

  • Silent apoplexy of a somatotroph tumor
  • An ectopic source of Growth hormone-releasing hormone (GHRH) neuroendocrine tumor
  • An ectopic source of Growth hormone (GH) neuroendocrine tumor
  • McCune-Albright syndrome
  • An ectopic pituitary adenoma (sphenoid sinus)


Laurence Katznelson, Edward R. Laws, Jr, Shlomo Melmed, Mark E. Molitch, Mohammad Hassan Murad, Andrea Utz, John A. H. Wass, Acromegaly: An Endocrine Society Clinical Practice Guideline, The Journal of Clinical Endocrinology & Metabolism, Volume 99, Issue 11, 1 November 2014, Pages 3933–3951

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