Postglucose growth hormone nadir and insulin-like growth factor-1 in naïve-active acromegalic patients: do these parameters always correlate?

The diagnosis of acromegaly is based on clinical features and biochemical criteria. While clinical suspicion is of extreme importance, laboratory evaluation is mandatory to establish the diagnosis. Growth hormone (GH) is secreted in a pulsatile pattern. Normal individuals have undetectable levels during most of the daytime period. In contrast, GH is always detectable in acromegalic patients, promoting higher levels of insulin-like growth factor-1 (IGF-1) (1). Thus, even random GH levels < 1 μg/L do not rule out acromegaly. The two most used tests to assess biochemical activity in acromegaly are postglucose GH nadir (GHn) and IGF-1. GHn during an oral glucose tolerance test (OGTT) has been used as the standard method for acromegaly diagnosis (2), although we have recently reported suppression in low GH naïve-active acromegalic patients below the current consensus values (3,4). Furthermore, it has been reported that OGTT should ideally be evaluated in relation to age (5-8), gender (5,7) and body mass index (5,8). Actually, there has been several attempts to define GHn in normal patients using different assays, when cutoff values were lower than 0.3 (9,10). One report has suggested that random basal GH levels ≥ 5 μl in men, and ≥ 10 μl in women may possibly obviate the need of an OGTT suppression test, when IGF-1 is elevated (11). IGF-1 levels correlate with clinical features of acromegaly and are stable during the day (12). Studies have demonstrated that GHn and IGF-1 usually correlate well (13), although their relationship has not been tested in acromegalic populations with different GH outputs, and for different GHn thresholds. Thus, we aimed at evaluating the correlation between GHn and IGF-1 levels in two different populations of clinically and biochemically naïve-active acromegalic patients: one with clearly elevated, and the other with low mean 24-h GH concentrations. We studied thirty-eight adults with untreated acromegaly (22 males, 16 females), as defined by the presence of clinical symptoms and exam results showing elevated ageadjusted IGF-1 values. Their ages ranged from eighteen to seventy-three years old. All patients had been enrolled in other reported protocols at the University of Michigan. All patients underwent frequent blood sampling for GH followed by an OGTT, when a sample for IGF-1 was also collected. A mean 24-h GH value of 4.3 μg/L was used as the threshold value to distinguish “high” and “low” GH study groups. This cutoff value was chosen because it represented the highest mean 24-h GH level in our studies of normal, healthy control adults (14). Fourteen patients were defined as “high” GH acromegalic patients (9 males, 5 females; mean age 40.6 ± 3.8 years) and twenty-four as letter to the editor