Discordant growth hormone and IGF-1 levels post pituitary surgery in patients with acromegaly naïve to medical therapy and radiation: what to follow, GH or IGF-1 values?

New criteria that define acromegaly remission are more stringent: normal (age/sex-adjusted) insulin-like growth factor type 1 (IGF-1), growth hormone (GH) random (GHr) <1 µg/L, and a GH nadir (GHn) during oral glucose tolerance test (OGTT) of <0.4 µg/L. Discordance between GH and IGF-1 values is often attributed to somatostatin receptor ligands (SRLs) or radiation. The purpose of this study was to evaluate rates of discordant IGF-1 and GH levels in patients with GH secreting adenomas (after pituitary surgery), who were naïve to any other treatment. We retrospectively analyzed data over a 5 year time period (2006-2010), in post-surgery acromegaly patients who had elevated IGF-1 but normal GH levels (per the new cure criteria). Symptoms of acromegaly were scored according to a 4-point scale. Fifty-four patients had post-operative GHr and IGF-1 measurements, 28 patients had GHn during OGTT, and 16 patients had 5-point 2-h GH day curve tests. Thirteen of 54 (24%) patients were found to have intermittent persistent discordant values; high IGF-1 and normal GH at final evaluation (77% of these patients were women). Patients had a median number of IGF-1 evaluations of 7.5 (range: 2-15) over a median of 22 months (range: 3-47 months). Mean elevated IGF-1 in the discordant population was 1.25 × upper limit of normal (ULN) ± 0.17 (range: 1.01-1.6 × ULN). Twelve of the 13 (92%) patients had macroadenomas; 10 of the 13 (69%) patients had mammosomatotroph, mixed lacto/somatotroph tumors or prolactin staining. No patient in the discordant population was on estrogen replacement therapy or had overt cardiac disease. When the relatively asymptomatic discordant population was compared with 35 patients from the concordant population (six were excluded because of preoperative medical treatment for acromegaly), no significant difference between age, gender distribution, body mass index (BMI), presence of diabetes mellitus (DM) or glucose intolerance and adrenal insufficiency between groups was noted. In our study of postoperative patients with acromegaly naïve to both SRLs and radiation, using new GH cut-off levels, 24% had intermittent or persistent discordant values. Our results highlight that relying on IGF-1 or GH measurements alone is not adequate for assessing disease control in surgically treated acromegaly patients. Management of such patients needs to be individualized and long-term studies evaluating morbidity and mortality incorporated into treatment decisions. Further studies with larger patient populations and longer follow-up are required to determine the long-term implications of discordant GH and IGF-1 value patterns.

Serum IGF-1 in the diagnosis of acromegaly and the profile of patients with elevated IGF-1 but normal glucose-suppressed growth hormone.

OBJECTIVE: To report the utility of insulin-like growth factor-1 (IGF-1) as a single biomarker for establishing the diagnosis of acromegaly and to examine the clinical and biochemical profile of patients with an elevated IGF-1 in whom a diagnosis of acromegaly could not be confirmed by means of the oral glucose tolerance test (OGTT). METHODS: Between the years 1999 and 2010, we identified 101 patients who underwent pituitary surgery and had histologically proven somatotroph adenomas (Group 1, Gr 1). We selected 149 patients with non-growth hormone (GH) secreting pituitary macroadenomas (Gr 2, n = 97) and microadenomas (Gr 3, n = 52) to serve as control subjects. In addition, we identified 34 patients with elevated IGF-1values in whom acromegaly could not subsequently be proven by the OGTT (Gr 4). RESULTS: IGF-1 was elevated in all patients with acromegaly prior to therapy with a median (range) standard deviation score (SDS) of +9.52 (+2.34 to +9.2), compared to SDS -1.46 (-2.91 to +2.17) and -1.22 (-2.8 to +1.58) in Gr 2 and 3, respectively (P<0.001). IGF-1 SDS values were +3.28 (+2.05 to +6.1), and IGF-1 was less than twice the upper limit of normal in all patients in Gr 4. OGTT was performed in 51 of the 101 acromegalic patients. The nadir GH in these patients was 4.01 (0.2 to 46.7) in comparison with 0.2 (<0.05 to 0.6) in Gr 4 (P<0.001). CONCLUSION: Elevated IGF-1 levels, alone, are sufficient to establish a diagnosis of acromegaly in the majority of clinically suspected cases. The OGTT may be useful to obtain corroborative evidence when there is modest elevation of IGF-1 with absent or equivocal clinical features.