Carmichael JD, Bonert VS, Mirocha JM, Melmed S.
Department of Medicine, Division of Endocrinology, Cedars-Sinai Medical Center, David Geffen School of Medicine at UCLA, Los Angeles, CA; Biostatistics, Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA.
Context: Growth hormone (GH) suppression after oral glucose load (OGTT) and normal age- and gender-matched IGF-I levels reflect biochemical control of acromegaly. OGTT is the gold standard for determining control of GH secretion at diagnosis and after surgical treatment, but the usefulness of performing an OGTT in patients treated with medical therapy has not been determined.
Objective: To assess relationships between basal GH levels (GH0), GH responses to OGTT (GHn), and IGF-I levels.
Design: Retrospective electronic database review
Setting: Tertiary outpatient Pituitary Center
Patients: 166 Patients with acromegaly (79F, 87M).
Four categories of testing: diagnosis (Dx), post-operative assessment without medication (POP-NM), testing during SRIF analog therapy (SA), and testing during dopamine agonist therapy (DA).
Main Outcome Measure: Basal serum GH and IGF-I levels and GH levels 2 hours after 75g OGTT.
Results: 482 simultaneous OGTT and IGF-I measurements were observed from 1985-2008. Discordant results of OGTT testing (GHn and IGF-I) were observed 33, 48, and 18% in POP-NM, SA, and DA categories, respectively. In the SA category 42% of tests were discordant with normal IGF-I and non-suppressed GHn. In contrast, 4% of tests were discordant with normal IGF-I and non-suppressed GH in those treated with DA. No significant differences in discordance were observed when GH0 was used.
Conclusions: Both basal and GH nadir levels are highly discordant with IGF-I levels during medical therapy with SRIF analogs. OGTT is not useful in assessing biochemical control in these subjects.
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I was planning on posting a review of the AACE guidelines, but that's proving to be a time-consuming effort since I'm trying to get it into a Powerpoint format. I was reading the section about diagnosis and monitoring after treatment, and started to wonder if there was any new data on the utility of the OGTT is in acromegalics after they've been diagnosed and are initiated on treatment, especially since I've never seen one done at county for diagnosis or otherwise. I came across this article in a literature search that's an e-publication from the Pituitary guru himself, Dr. Melmed. Their data shows that basal and GH nadir levels do not correlate with IGF-I levels in patients on SRIF (somatotropin release-inhibiting factor) analogs, with a discordance of 42%. The patients in their review who were post-op & not on medication also showed discordant tests in 33%. Those patients on DA (dopamine agonist) therapy had discordant tests in 18% of patients. They also mention the fact that GH nadir levels following suppression with OGTT to <0.4 mcg/L have not been associated with a decrease in morbidity and mortality, whereas suppression of basal GH levels to <2.5 mcg/L and achieving normal IGF-I levels have been shown to decrease morbidity and mortality. Makes me wonder if there's any utility in diagnosis as well since we the diagnosis is mainly clinical and IGF-I is a pretty good indicator of peripheral activity of GH. Just some food for thought...
Here's the link to the PDF:
http://jcem.endojournals.org/cgi/rapidpdf/jc.2008-1371v1
Thanks for that post. I agree with your comments for patient on therapy.
ReplyDeleteHowever, I have seen 2 cases so far (pre-diagnosis) where patients had mildly elevated IGF-1 levels with borderline clinical evidence of acromegaly. I went ahead and did the OGTT and these tests were clearly negative. It seemed the better thing to do than go down the road of directly obtaining an MRI, because there is some 10% who will have an adenoma anyways.
For both patients, I did no further workup, but recommended follow up IGF-1 six months later.
I have been diagnosed based on my IGF-1 value alone (>999). Subsequently, an MRI scan confirmed a macroadenoma. I was told an OGTT was irrelevant.
ReplyDeleteI would agree that IGF-1 would seem to be the best method to diagnose acromegaly since it is a better "average" of the otherwise pulsatory GH value. However, it does rely on liver function.
An MRI scan where acromegaly is 'suspected' despite marginal results of GH and/or IGF-1 could result in a false negative or false positive. A false negative - if in the case of a microadenoma between the resolution steps of the MRI (especially if without correct contrasting agent). A false positive - if indeed a microadenoma is found - a great number of people do have pituitary tumours with no adverse clinical consequences.
In which case, investigate pseudo-acromegaly.
A course of action for marginal cases would be of a follow up with an IGF-1.
Trys