Because acromegaly produces slow changes over time, diagnosis is often significantly delayed. In fact, the characteristic coarsening of the facial features is often not recognized by family members, friends, or long-time family physicians. Often, the diagnosis is suspected by a new physician who sees the patient for the first time and is struck by the patient's characteristic facial appearance. Comparing old photographs from a number of different time periods will often increase suspicion of the disease.

Because the quantity of GH produced varies widely under normal conditions, demonstrating high levels of GH in the blood is not sufficient to merit a diagnosis of acromegaly. Instead, laboratory tests measuring an increase of IGF-1 (3-10 times above the normal level) are useful. These results, however, must be carefully interpreted because normal laboratory values for IGF-1 vary when the patient is pregnant, undergoing puberty, elderly, or severely malnourished. Normal patients will show a decrease in GH production when given a large dose of sugar (glucose). Patients with acromegaly will not show this decrease, and will often show an increase in GH production. Magnetic resonance imaging (MRI) is useful for viewing the pituitary, and for identifying and locating an adenoma. When no adenoma can be located, the search for a GHRH-producing tumor in another location begins.