Serum leptin levels in patients with acromegaly before and after correction of hypersomatotropism by trans-sphenoidal surgery.

It has been shown that GH excess is associated with decreased leptin levels and decreased body fat mass. Reports regarding the effect of GH on serum leptin levels are inconsistent. We studied leptin secretion in 20 acromegalics before and 2 months after trans-sphenoidal surgery and in 20 gender-, age-, and body mass index (BMI)-matched control subjects. The mean 8-h leptin concentration for each subject was measured from a pool formed of samples collected hourly beginning at 2200 h until 0600 h the next morning. In a subgroup of 10 acromegalics, leptin pulsatility was assessed for the same period of time in 10-min sampling intervals. Basal GH, insulin-like growth factor-I (IGF-I), insulin, glucose, and lipids levels were measured. Area under the curve for insulin (AUCins) during oral glucose tolerance test was calculated. Control subjects and acromegalics had similar BMI, but patients with active acromegaly had significantly lower mean leptin level (mean +/- SEM; in men, 2.6+/-0.4 vs. 7.1+/-1.1 microg/L, P = 0.003; in women, 16.0+/-3.4 vs. 23.5+/-3.1 microg/L; P = 0.036). Mean 8-h leptin correlated with BMI (r = 0.57, P = 0.007, in controls; r = 0.70, P = 0.001, in patients). In stepwise regression analysis with mean 8-h leptin as a dependent variable, BMI (P<0.001) and gender (P = 0.01) in acromegalics entered the equation, whereas in control subjects gender, free fatty acids, insulin, and age accounted for 99.3% in leptin variability. After surgery, BMI did not change significantly; and glucose (P = 0.014), GH (P<0.001), and IGF-I (P<0.001) levels together with AUCins (P = 0.002) decreased, whereas mean leptin concentration rose significantly and attained normal levels (4.1+/-0.8 microg/L, P = 0.028) in acromegalic men and (23.6+/-4.7 microg/L, P = 0.003) in acromegalic women. Correlation between leptin level and BMI was preserved after surgery (r = 0.62, P = 0.005). In stepwise regression analysis, free fatty acids (P = 0.04) contributed to 26.8% of the variance in corrected-leptin (for BMI and gender). Leptin concentration peak height and interpeak nadir level rose significantly (P = 0.033 and P = 0.037) after surgery by Cluster analysis, without significant changes in leptin pulse frequency and incremental peak amplitude. Nocturnal rise of leptin (mathematically described by a cubic curve) was characterized by an acrophase just after midnight, before and after surgery. The amplitude and the average leptin concentration of the cubic fit increased significantly after surgery (P = 0.028 and P< 0.001). In conclusion in acromegalic patients: 1) leptin secretion maintains the pulsatility and nocturnal rise; 2) the gender-based leptin differences are preserved; 3) GH-IGF-I normalization leads to a rise in leptin that is not related to changes in BMI; and 4) the possible role of rise in leptin levels when assessing clinical and metabolic outcome of therapy in acromegalic patients deserves additional studies.

Pituitary adenomas secreting large amounts of prolactin may give false low values in immunoradiometric assays. The hook effect.

Immunoradiometric assay (IRMA) for serum prolactin (PRL) measurement can give falsely low values, leading to unnecessary surgery in patients with prolactinomas. We studied clinical and biochemical features of patients with pituitary macroprolactinomas in whom plasma PRL levels had been underestimated due to the so-called "high dose PRL hook effect". This phenomenon was observed in four (14.2%) out of 28 patients with pituitary macroadenomas (13 macroadenomas) and 15 non-functioning macroadenomas) reffer during one-year period. Undiluted median (range) PRL levels were 11.3 (3.0-48.7), 983.9 (194.4-1959.4), and 96.9 (66.6-147.7) micrograms/l in patients with non-functioning macroadenomas, macroprolactinomas and the hook effect adenomas, respectively. In all patients assay was performed after serum dilution, and only in patients with the hook effect the median PRL levels increased significantly to 5795.0 (2097.2-12722.2) micrograms/l. The mean age at diagnosis was 38 +/- 6.5, 45 +/- 6, and 53 +/- 3 yr, for the patients with the hook effect, macroprolactinoma and non-functioning adenoma, respectively. Males were predominant (75%) in the hook effect adenoma group. Patients with the hook effect macroprolactinomas were all treated successfully with dopamine agonists, and all patients had significant shrinkage of the tumor mass (more than 50% shrinkage). In conclusion, this study suggests that patients with high dose PRL hook effect are generally younger, more frequently males with very large pituitary adenomas (grade III-IV according to Hardy). It is necessary, whenever performing IRMA for serum prolactin measurement, to dilute samples routinely (1:1 and 1:10 dilutions) in every patient with pituitary tumor.

Gonadotrophin and free alpha-subunit secretion in patients with acromegaly and clinically non-functioning pituitary tumors: anterior pituitary function and the effect of thyrotrophin-releasing hormone.

The effect of the tumor size on the anterior pituitary hypofunction is analyzed in 29 patients with acromegaly and 34 patients with clinically non-functioning pituitary tumor (NFPA). Gonadotrophin and free alpha-subunit (SU) concentrations during daytime variations (samples were taken hourly for 24 h) and after stimulation with TRH were measured as well. Patients with NFPA had a higher prevalence of isolated secondary hypogonadism (20.6% vs 10.3%) and more severe pituitary failure (52.9% vs 6.9%) in comparison with acromegalic patients (p < 0.0001). However, there was no association between the tumor size and the anterior pituitary hypofunction (p = 0.1 and p = 0.9) in patients with NFPA and acromegaly respectively. In premenopausal women and in men with normal/low gonadotrophin levels, mean daytime levels of LH (0.75 +/- 0.6 vs 1.5 +/- 1.9 mlU/ml; p = 0.002) and FSH (2.1 +/- 2.7 vs 4.1 +/- 4.9 mlU/ml; p = 0.009) were higher in patients with acromegaly. There was no difference in the alpha-SU level (p = 0.9). Women with gonadotrophin levels compatible with menopause and men with elevated gonadotrophin levels had the same degree of gonadotrophin and alpha-SU elevation regardless of the tumor type. TRH induced significant rise of LH in 8 (23.5%), FSH in 5 (14.7%) and alpha-SU in 10 (29.4%) patients with NFPA. Among 29 patients with acromegaly LH rose in 6 (20.7%), FSH in 5 (17.2%) and alpha-SU in 3 (10.3%) patients. In conclusion, the anterior pituitary function is better preserved in patients with acromegaly than in patients with NFPA. It seems that the size of pituitary tumor is not the major factor in the pathogenesis of hypopituitarism in patients with macroadenomas. Gonadotrophin and possibly alpha-SU response to TRH exists not only in some patients with clinically non functioning pituitary tumors but also in some patients with acromegaly. Further investigations are need to explain if it represents a biochemical marker of a plurihormonal pituitary tumor in these patients.