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Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by progressive loss of motor neurons. However, ALS has been recognized to also involve non-motor systems. Subclinical involvement of the autonomic system in ALS has been described. The recently developed (13)C-octanoic acid breath test allows the noninvasive measurement of gastric emptying. With this new technique we investigated 18 patients with ALS and 14 healthy volunteers. None of the patients had diabetes mellitus or other disorders known to cause autonomic dysfunction. The participants received a solid standard test meal labeled with (13)C-octanoic acid. Breath samples were taken at 15-min intervals for 5 h and were analyzed for (13)CO(2) by isotope selective nondispersive infrared spectrometry. Gastric emptying peak time (t(peak)) and emptying half time (t(1/2)) were determined. All healthy volunteers displayed normal gastric emptying with a mean emptying t(1/2) of 138 +/- 34 (range 68-172) min. Gastric emptying was delayed (t(1/2) > 160 min) in 15 of 18 patients with ALS. Emptying t(1/2) in ALS patients was 218 +/- 48 (range 126-278) min (p < 0.001). These results are compatible with autonomic involvement in patients with ALS, causing delayed gastric emptying of solids and encouraging the theory that ALS is a multisystem disease rather than a disease of the motor neurons only.

Ceruletide, a cholecystokinin-8-like peptide, was recently reported to stimulate ACTH secretion in man. The aim of this study was to investigate the effect of the mu-opiate agonist, loperamide, and the opiate antagonist, naloxone, on ceruletide-induced ACTH secretion in man. In 6 normal subjects, basal ACTH and cortisol plasma levels were significantly suppressed 3 h after loperamide administration (16 mg, orally) from 5 +/- 0 to 2 +/- 0 pmol/l and from 356 +/- 44 to 154 +/- 16 nmol/l. After stimulation with 8 ng ceruletide/kg body weight/min over a period of 5 min, the maximum ACTH levels (at 7.5 min) were significantly reduced by loperamide from 26 +/- 7 to 6 +/- 1 pmol/l and the maximum cortisol levels (at 30 min) were significantly reduced from 676 +/- 47 to 392 +/- 58 nmol/l. Furthermore, the ACTH peak (delta = 7.5 min) was significantly blunted by loperamide from 21 +/- 7 to 5 +/- 1 pmol/l and the integrated area under the curve from 0 to 120 min (delta AUC) of ACTH was significantly reduced from 40 +/- 11 to 14 +/- 4 pmol x 120 min/l. The cortisol peak (delta = 30 min) and the AUC of cortisol were not significantly diminished. The suppressive effect of loperamide on basal and ceruletide-induced ACTH and cortisol secretion was completely reversed by the administration of 0.8 mg naloxone, 20 min before and during infusion of ceruletide. The administration of naloxone itself had no significant effect on ACTH or cortisol levels. In conclusion, ACTH is released by peripherally administered ceruletide within a short period.(ABSTRACT TRUNCATED AT 250 WORDS)