James W. Plonk

Growth hormone and prolactin secretion in the carcinoid syndrome.

We evaluated plasma growth hormone (GH) and plasma prolactin (PRL) levels in ten patients with metastatic carcinoid tumors and the carcinoid syndrome (“active tumors”) and seven patients with metastatic carcinoid tumors without the carcinoid syndrome (“inactive tumors”). The patients with active tumors had elevated serum serotonin levels and increased urinary 5-hydroxyindoleacetic acid (5-HIAA) while these values were normal in patients with inactive tumors. Forty-five per cent of patients with active tumors had elevated fasting plasma GH levels that were either not suppressed or showed a paradoxical increase in response to I.V. glucose. There was a positive correlation between the plasma GH levels and serotonin production by the tumor. Twenty-eight per cent of patients with inactive tumors had elevated fasting plasma GH levels. GH levels were decreased by the administration of serotonin antagonists in some but not all of the patients. Parachlorophenylalanine (PCPA) an inhibitor of serotonin synthesis caused a paradoxical rise in GH levels. GH release in response to insulin hypoglycemia was normal. Plasma prolactin levels were normal in most of the patients with metastatic carcinoid tumors. PCPA administration did not systematically alter plasma prolactin levels. We conclude that elevated plasma GH levels are frequently present in patients with the carcinoid syndrome. Both serotonin produced by the tumors and the tumor itself may be responsible for the elevated GH levels.

Inhibitory effect of serotonin antagonists on growth hormone release in acromegalic patients.

We evaluated the effect of the serotonin antagonists cyproheptadine (Cypro) and methysergide (Methy) on growth hormone secretion in six patients with acromegaly. Two days administration of Cypro deceased the plasma GH concentration during oral glucose tolerance tests in four of the six patients evaluated; 2 days administration of Methy reduced the plasma GH levels of only one of the four patients evaluated. The one patient whose palsma GH concentration was lowered by Methy, did not have a decerase in plasma GH concentration after Cypro administration. Acromegalic patients have normal serum serotonin concentration and normal 5‐hydroxyindoleacetic acid excretion. If Cypro lowers plasma GH by antagonizing serotonin, our data would suggest that serotoninergic neruonal pathways are important in the regulation of pituitary GH secretion in some patients with acromegaly.

Alterations of pituitary-gonadal function in the carcinoid syndrome.

The purpose of the present study was to determine if sexual function is altered in patients with carcinoid tumors. Fifteen men with carcinoid tumors underwent clinical and laboratory evaluation of gonadal function. Ten patients had active tumors (serotoninsecreting) and five had inactive tumors (normal serotonin). All of the patients had noted a decrease in libido since developing their tumors and eight of the patients had almost complete sexual impotence. Three of the patients with active carcinoid tumors developed Peyronies disease and two developed gynecomastia. After allowance for the serum testosterone concentration, the patients with active tumors had higher serum luteinizing hormone (LH) levels than patients with inactive tumors. Although the elevated serum LH concentration of patients with active tumors did not correlate with urinary 5-hydroxyindole acetic acid excretion or serum serotonin concentration, the serum LH levels were reduced by the serotonin antagonist, cyproheptadine. Further studies will be needed to substantiate the suspicion that serotonin may stimulate LH secretion in man.

Serum prostaglandin F2α concentration in the carcinoid syndrome

Abstract Using specific radioimmunoassay procedures we measured prostaglandin F2α (PGF2α) and 13, 14-dihydro-15-keto prostaglandin F2α (PGF2α metabolite) in 12 patients with carcinoid tumors. Although PGF2α and PGF2α metabolite were each modestly elevated in 17% of the patients the magnitude of the elevation did not correlate with the symptoms of the carcinoid syndrome. The 24 hour urinary 5-hydroxyindoleacetic acid excretion showed a good correlation with carcinoid symptoms while the serum serotonin concentration showed a fair correlation with carcinoid symptoms. We conclude that serum elevation of PGF2α is not a frequent occurrence in patients with the carcinoid syndrome.

Monoamine oxidase inhibition: Possible mechanism for cyproheptadine-induced alterations in insulin secretion

Summary Studies were carried out to determine the mechanism of cyproheptadine (CYPRO) inhibition of glucose-stimulated insulin secretion in the golden hamster. Following CYPRO injection, intact hamsters have an increase in serum glucose concentration and an inhibition of insulin secretion. Using homogenates of isolated pancreatic islets and of liver from hamsters and rabbits we found that CYPRO is a competitive inhibitor of monoamine oxidase (MAO). There is a significant correlation between the inhibitory potency of the serotonin antagonists CYPRO, cinanserin (CINAN), and methysergide (METHY) on in vitro insulin secretion from hamster pancreas and the MAO inhibitory effect of these compounds. The decreasing order of potency of the serotonin antagonists as inhibitors of MAO and insulin secretion is: CYPRO > CINAN > METHY. The antihistaminic agents diphenhydramine and chlorpheniramine also inhibit insulin secretion and MAO activity. Our studies suggest that the net effect of CYPRO on insulin secretion in different species may be the results of the interaction of its MAO inhibitory and its antiserotonin properties.

Effect of Age on Intravenous Glucose Tolerance and Insulin Secretion

ABSTRACT: Twenty‐seven normal volunteers whose ages ranged from 22 to 67 (mean, 37 years) were given intravenous glucose tolerance tests (IVGTT). Age was not correlated with the glucose disposal rate constant (KG), incremental insulin secretion (ΔI), or the “insulinogenic index (ΔI/ΔG). The volunteers were divided into three age groups: 1) mean age 25 years, 2) mean age 42 years, and 3) mean age 62 years. Groups 2 and 3 did not differ from Group 1 with respect to the mean level of fasting plasma glucose, KG, or ΔI/AG. Group 2 (but not Group 3) had a greater mean ΔI than Group 1, and Group 3 (but not Group 2) had a higher mean fasting insulin concentration than Group 1. No significant deterioration was detected in the intravenous glucose tolerance of healthy volunteers up to age 67. This may be attributable to the previously described feed‐back system that calibrates the pancreatic beta‐cell response according to the insulin sensitivity of the peripheral tissues.

Carcinoembryonic Antigen and Carcinoid Tumors

Excerpt Carcinoembryonic antigen is a cancer-specific antigen that is present in the plasma of 82% of patients with malignant tumors arising from structures of entodermal origin (1). The tumors inc...

Effect of hyperprolactinemia on pituitary-adrenal function.

Three patients with hyperprolactinemia (2 with pituitary tumors and 1 with a hypothalamic disturbance) underwent evaluation of their hypothalamic-pituitary-adrenal axis using ACTH, metyrapone and in one case repetitive insulin tolerance tests. With the exception of a suggestion of a slight increase in adrenal responsiveness to pharmacological doses of ACTH in one of the patients, there was no alteration in the adrenal responsiveness of the 3 patients evaluated. We conclude that hyperprolactinemia probably does not systematically modify the responsiveness of the hypothalamic-pituitary-adrenal axis.

Effect of intravenous glucose and insulin on plasma tryptophan and tyrosine concentrations in normal subjects and patients with carcinoid tumors

We evaluated the effect of intravenous (i.v.) glucose on the plasma tryptophan (TRP) and tyrosine (TYR) concentration of 12 normal subjects, six patients with carcinoid tumors and the carcinoid syndrome (carcinoid syndrome), and five patients with carcinoid tumors without the carcinoid syndrome (tumor.) Following i.v. glucose administration, the plasma Trp concentration of the normal subjects and the tumor patients incresed, while the plasma Trp concentration of the carcinoid syndrome patients decreased. Following i.v. glucose administration, the plasma Tyr concentration of the normal subjects and the tumor patients decreased, while the plasma Tyr concentration of the carcinoid syndrome patients did not change. The response to i.v. insulin differed in some respects from the response to i.v. glucose: the plasma Trp of normal subjects did not change while the plasma Trp of carcinoid syndrome patients decreased; the plasma Tyr of the normal subjects increased while the plasma Tyr concentration of the carcinoid syndrome patients did not change. The carcinoid syndrome patients had high serum serotonin concentrations and impaired glucose tolerance and insulin secretion as compared to both normal subjects and tumor patients. We conclude that under appropriate experimental conditions, glucose administration can increase the plasma Trp concentration of normal human subjects.

Plasma amino acids in patients with the carcinoid syndrome.

Plasma tryptophan (Trp) is reported to be decreased in some patients with the carcinoid syndrome. To determine if the plasma levels of other amino acids are also altered in the carcinoid syndrome, we used a gas‐liquid chromatographic method to determine the plasma amino acid concentration of nine patients with the carcinoid syndrome and nine age‐matched healthy control subjects. In comparison to the control subjects, the patients with the carcinoid syndrome had decreased plasma concentrations of valine (Val), isoleucine (Ile), lysine (Lys), and ornithine (Orn), and an increased plasma concentration of methionine (Met). With the exception of a decrease in urinary excretion of proline (Pro) and hydroxyproline (Hyp), the patients with the carcinoid syndrome had normal quantities of amino acids in their urine. Plasma Met returned to normal when serotonin production by the tumor was reduced 60% by parachlorophenylalanine (PCPA); the other amino acid abnormalities persisted. Further studies are needed to determine the significance of these amino acid abnormalities.