Pegylated interferon-α stimulates pituitary hormone secretion during long-term therapy

Abstract

In vitro and in vivo data indicate multiple possible effects of interferon on pituitary hormone secretion. We therefore investigated pituitary hormone secretion in twenty-one patients with chronic hepatitis C before and during therapy with pegylated interferon-α (IFN). Patients: N=21, age (mean±SE) 48.1±2.3 ys, 18m, 3f, IFN therapy for 5.2±0.2 mo (mean±SE). All patients received a combination of IFN and a nucleosid analogon (ribavirin or levovirin) for the treatment of chronic hepatitis C. No patient had signs or symptoms of liver cirrhosis. Patients with transaminases above three times the upper limit were excluded, as were all patients with endocrine diseases. Of the 21 patients seventeen were investigated before and during IFN. Methods: Insulin induced hypoglycemia (0.1 IU/kg), LHRH-TRH test (LHRH 200µg and TRH 100µg iv). Determination of IGF-I, fT3, fT4, testosterone and/or estrogen. All data are median concentration and range. Results: IHG: The glucose nadir was below 40mg% in all patients. Basal and stimulated cortisol (nmol/l) concentration was 584 [184–979] and 664 [331–979] before and 453 [218–795] and 604 [218–819]) during IFN. Cortisol was above 200 nmol/l (basal) and 500 nmol/l (stimulated) in 20/21 (95%) and 16/21 (76%) patients before and 17/17 (100%) and 14/17 (82%) during IFN. Thus, the adrenal axis was normal in 16 and partially insufficient in 5 patients. Before therapy the GH (µg/l) concentration (basal and stimulated, 0.75 [0.5–6.9] and 1.1 [0.5–29.3]) increased to above 10µg/l in only 2/21 (10%) patients. In contrast, GH increased significantly (p<0.006 and p<0.002, for the basal and stimulated GH concentration, respectively) during therapy (basal: 1.7 [0.5–14.6], stimulated 6.45 [0.5–35.6], p<0.003 basal vs. stimulated GH) compared to before therapy. Neither the stimulated cortisol nor GH concentration was correlated to the nadir glucose concentration during IHG. The IGF-I (ng/l) concentration was 99 [44–173] and 87 [45–312], before and during IFN. IGF-I was below age and sex matched normal values in 11/21 (52%) and 9/17 (53%) patients before and during IFN, respectively. LHRH-TRH test: GH was significantly higher during IFN compared to before therapy basal and 30 minutes after LHRH-TRH injection (p<0.006 and p<0.002, respectively). PRL (µg/l) concentration was significantly higher during than before IFN, basal and 30 minutes after the LHRH-TRH injection: basal 5.5 [3–8.6], and at 30min 31.6 [17.2–86.7] before, 6.0 [4.0–11.8] and 45.7 [23.5–151.0] during IFN, p<0.001 and p<0.0006, before versus during IFN, basal and stimulated concentrations, respectively). Basal TSH, fT3 and ft4 concentrations were within the normal range and did not change during IFN, while TSH increase was significantly (p<0.05) more pronounced during IFN. The concentrations of LH, FSH, and testosterone were normal before therapy and not significantly different during IFN. In conclusion Ninety percent of the patients with chronic hepatitis C demonstrated pituitary GH insufficiency that was attenuated during IFN therapy, while IGF-I remained subnormal, indicating a persistent resistance of the liver to GH. In addition PRL increased during IFN therapy and the stimulated TSH response was increased as well indicating a profound effect of IFN on somatotrop, lactotrop and thyrotrop cells.