Which of these patients has acromegaly?

In this blog post, I present three cases involving patients suspected of having possible acromegaly and discuss follow up. After reading, please share your thoughts.

Case #1

Case #1 is a 51-year-old man who was first referred to me for primary hypothyroidism. However, at our first visit, I was struck by his large hands. Upon further questioning, he reported a history of snoring, sleep apnea and excessive sweating. He no longer was able to wear his wedding ring.

His initial baseline insulin-like growth factor I (IGF-I) was 359 ng/mL, with the upper limits of normal for that lab for age and gender being 252 ng/mL. We performed an oral glucose growth hormone suppression study, however, and his growth hormone suppressed to 0.4 ng/mL.

An MRI of the pituitary showed a 4 mm or 5 mm with decreased enhancement in the right pituitary, which was suggestive of a possible microadenoma. We repeated IGF-I and found levels of 339 ng/mL and 346 ng/mL, respectively.

Does case #1 have acromegaly?

Case #2

Case #2 had already been seen by three other endocrinologists before seeing me. My opinion is the fourth on her case. She is a 34-year-old woman who was found to have possible pituitary microincidentaloma on MRI.

This patient did not have any of the classic symptoms or physical exam findings of acromegaly. However, her initial IGF-I was 432 ng/mL in July 2010. The patient had an oral glucose GH suppression study. The GH did not suppress; the lowest value was 1.02 ng/mL.

The oral glucose GH suppression study was repeated, however, and the GH then did suppress down to 0.05 ng/mL.

A follow-up IGF-I in August 2010 was 283 ng/mL, which was within the normal range. Nevertheless, since then, case #2 has had IGF-I levels slightly higher than predicted for age and gender, although lower than the initial value.

She went to a tertiary referral canter for a third opinion. Repeat MRIs failed to confirm the presence of a pituitary microadenoma. Repeat oral glucose GH suppression studies showed suppression of GH less than 0.4 ng/mL.

When I saw this patient as a new consult, she did not have any of the physical exam findings of acromegaly and did not report any of the classic symptoms. Her IGF-I is now 367 ng/mL (132 ng/mL-333 ng/mL). Another MRI shows no pituitary abnormality. I repeated the oral glucose GH suppression study yet again. Her GH suppressed down to 0.13 ng/mL.

What do you think of case #2’s slightly high IGF-I levels with normal GH suppression and lack of clear clinical features of GH excess?
Do you think the slightly high IGF-I is simply an abnormal lab result of uncertain significance or do you think case #2 might have early acromegaly?

Case #3

Case #3 was a 29-year-old woman referred to me by an astute primary care physician who noted that she had somewhat coarse facial features.

Her initial IGF-I was 1342 ng/mL and a repeat IGF-I was 1,258 ng/mL, with the upper limits of normal for age/gender being 321 ng/mL or less. Her baseline GH was also markedly elevated at 25 ng/mL, with upper limits of normal being 3.61 ng/mL. A pituitary MRI revealed a 2.2-cm macroadenoma.

This patient definitely had acromegaly. She was referred to a neurosurgeon and underwent a transphenoidal resection in September 2011. After her surgery, her IGF-I levels decreased markedly. Shortly, post-op IGF-I was 342 ng/mL, which is barely above the normal range.

However, since then her IGF-I levels have increased slightly. Her most recent IGF-I was 449 ng/mL (upper limit of normal <321 ng/mL).

We repeated the oral glucose GH suppression study twice. The GH suppressed to 0.21 ng/mL in May 2012.

Most recently, a second oral glucose study suppressed the GH to 0.08 ng/mL.

Does case #3 still have acromegaly?

Discussion

A patient’s clinical features and serum IGF-I level are important in the initial evaluation of patients suspected of having acromegaly. Oral glucose GH suppression testing is done to confirm or rule out the diagnosis and to follow up on cases post-operatively. The inability to suppress GH to less than 1 ng/mL after oral glucose has traditionally been considered the gold standard criteria for diagnosis of acromegaly. However, more recent guidelines have suggested using a lower nadir GH after oral glucose of less than 0.4 ng/mL.

Follow up of the above cases:

Case #1’s IGF-I levels slowly continued to increase. His symptoms appeared to be progressing. He was referred to a neurosurgeon who agreed that he likely had acromegaly. He underwent transphenoidal pituitary resection; pathology confirmed GH-secreting microadenoma. Post-operatively, his IGF-I decreased and many of his symptoms improved. It appears that case #1 did have early subclinical acromegaly successfully treated with surgery. We will continue to follow him, however, to detect any recurrence.

Case #2 is more challenging. I agree with all of her previous endocrinologists. At present, the slightly high IGF-I without symptoms is only an abnormal lab result of unknown clinical significance. Without more definite clinical features and without abnormal GH suppression, we cannot confirm a diagnosis of acromegaly. The patient understands that is possible she could have very early disease and may require more definitive intervention in the future. Case #2 will be followed closely to identify if/when this occurs.

Case #3 definitely had acromegaly. The persistence of slightly high IGF-I after surgery concerns me for residual disease. However, with normal suppression of GH on oral glucose suppression testing, treatment with pharmacotherapy or repeat surgery is presently not indicated. I have a very strong suspicion that case #3 has residual disease and eventually will need further intervention. She will also be followed closely in the future.

Readers: I encourage you to add your comments and to share your past experiences with similar patients. I appreciate your thoughts regarding these cases.

For more information:

American Association of Clinical Endocrinologists Medical Guidelines for Clinical Practice for the Diagnosis and Treatment of Acromegaly -2011. Available at: https://www.aace.com/files/acromegaly-guidelines.pdf