MON-885 - IGF-1 Elevation without Growth Hormone Excess in A Patient Receiving Testosterone Therapy

Background

Elevated IGF-1 is typically associated with growth hormone excess from pituitary adenoma.
Testosterone therapy may increase IGF-1, occasionally mimicking acromegaly without GH
excess.

Case Presentation

A 71-year-old male with hypogonadism on testosterone replacement therapy presented with
intermittent elevation of IGF-1 and acromegaloid features, including coarse facial changes,
prognathism, large feet, also joint pain, obstructive sleep apnea, prediabetes, hypertension
and erythrocytosis.
Longitudinal laboratory evaluation demonstrated a temporal correlation between
supraphysiologic testosterone levels (peak 1124 ng/dL) and elevated IGF-1 (302 ng/mL),
while lower testosterone levels were associated with lower IGF-1 values. Oral glucose
tolerance testing showed appropriate growth hormone suppression, excluding biochemical
acromegaly. Pituitary MRI revealed no adenoma, and other pituitary hormones were within
normal limits.

Discussion

In this context, patients may present with elevated IGF-1 despite preserved GH suppression
and the causes could be metabolic, pharmacological, and physiological influences, including
testosterone therapy, dopamine agonist use, chronic kidney disease, pregnancy and
hyperthyroidism.
Testosterone therapy is an important modulator of the GH–IGF-1 axis and may increase
circulating IGF-1 through androgen receptor–mediated transcription, stimulation of GH
secretion, and direct hepatic effects independent of pathological GH excess, causing positive
hormonal feedback.
Nevertheless, sustained IGF-1 elevation itself may be associated with the development of
acromegaloid features and, consequently, a higher risk of acromegaly-related comorbidities,
such as obstructive sleep apnea, erythrocytosis, hypertension and benign colon polyps. These
observations highlight that peripheral hormonal modulation can influence both biochemical
markers and clinical phenotype independently of pituitary tumor activity.

Conclusion

Testosterone replacement therapy can elevate IGF-1 through GH-dependent and independent
mechanisms and produce acromegaloid features. Awareness of this association, combined
with confirmatory GH suppression testing, allows accurate diagnosis, prevents
misclassification as acromegaly, and guides appropriate surveillance.

*Unless otherwise noted, all abstracts presented at ENDO must not be released to the press or the public until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.*