Search

Growth hormone (GH) secretion has been studied in two patients with the carcinoid syndrome during glucose loading and growth hormone-release inhibiting hormone (GHRIH, somatostatin) infusion. Both patients had elevated fasting GH levels which were not suppressed by glucose; GH levels fell rapidly during GHRIH infusion. One patient also had hyperprolactinaemia with galactorrhoea and the prolactin (PRL) levels were unaltered by GHRIH. The association between carcinoid tumours and abnormalities of GH and PRL secretion is discussed.

Bradykinin and structurally related peptides are potent vasodilators and a role for these kinins in the aetiology of the carcinoid flush has been proposed. Using an antiserum directed against the COOH-terminal region of bradykinin in radioimmunoassay, the concentrations of bradykinin-like immunoreactivity in extracts of peripheral blood were compared in patients with carcinoid syndrome (n = 11) and healthy subjects (n = 6). In the fasted state, the concentrations of bradykinin-like immunoreactivity in the patients (10 +/- 5 ng/l) were not significantly different from the concentrations in healthy subjects (6 +/- 3 ng/l). An intravenous injection of pentagastrin (0.6 micrograms/kg) provoked a flush of differing degrees of severity in all patients. In four patients, the flush was concurrent with large rises (277-, 26-, 11- and 10-fold over mean basal values) in bradykinin-like immunoreactivity that was resolved by high performance liquid chromatography into lysyl-bradykinin and bradykinin (approximate ratio 1:2). In two patients, small rises in immunoreactivity (2.4- and 1.7-fold) occurred after the flush and in the remaining five patients no rise in bradykinin-like immunoreactivity was measured. In the healthy subjects, the pentagastrin injection did not provoke a flush and no rises in bradykinin-like immunoreactivity were observed. The data support earlier results obtained using bioassays that the carcinoid flush in some patients is associated with the appearance in blood of bradykinin-related peptides. It has been shown, however, that these kinins cannot be the sole causative agent of the flush. It is suggested, therefore, that the aetiology of the flush is probably multi-factorial.

To determine if patients with chronic hyperserotoninaemia from the carcinoid syndrome have increased basal adrenocortical function, I have determined the urinary free cortisol excretion of seventeen patients with carcinoid tumours and the carcinoid syndrome, twelve patients with carcinoid tumours without the carcinoid syndrome and seventeen normal subjects. There was no significant difference in the urinary free cortisol excretion of the patients with carcinoid tumours and the carcinoid syndrome (133 +/- 20.0 nmoles/24 h), patients with carcinoid tumours without the carcinoid syndrome (115 +/- 29 nmoles/24 h) and the normal subjects (96 +/- 9 nmoles/24 h). There was no correlation between the urinary free cortisol secretion and urinary 5-hydroxyindoleacetic acid or serum serotonin concentration in the patients with the carcinoid syndrome. There was a suggestion that patients with 5-hydroxytryptophan (5-HTP) secreting carcinoid tumours had higher urinary free cortisol excretion than patients with predominantly serotonin (5-HT) secreting carcinoid tumours. This may be due to the fact that the non-polar 5-HTP molecule penetrates the blood-brain barrier more effectively than the polar 5-HT molecule. 5-HTP is then converted to 5-HT within the brain. None of the twenty-nine patients with carcinoid tumours had clinical or laboratory evidence of the ectopic ACTH syndrome.

Intravenous injection of pentagastrin (0.6 microgram/kg body wt) into two patients with metastatic carcinoid tumours evoked a severe carcinoid flush. Analysis by reverse-phase HPLC of acetone-extracts of peripheral blood taken from the patients during the flush indicated the presence of a peptide identified as the residues (1-33) fragment of the alpha-chain of haemoglobin. The peptide was not detected in blood taken from the patients immediately before stimulation of the flush or in the blood of healthy subjects after pentagastrin injection. The observation is interpreted as evidence that the pentagastrin-induce carcinoid flush is associated with the activation and possible release of a tumour protease that result in damage to erythrocytes.