0021-972X/79/4805-0784S02.00/0 Journal of Clinical Endocrinology and Metabolism Copyright © 1979 by The Endocrine Society

Vol. 48, No. 5 Printed in U.S.A.

Abnormal Plasma Catecholamine Responses in Acromegalics GLEN R. VAN LOON Division of Endocrinology and Metabolism, Department of Medicine, University of Toronto, Toronto, Ontario, Canada M5S 1A8

ABSTRACT. Plasma dopamine, norepinephrine, and epinephrine responses to bromocriptine (2.5 mg orally) or to LRH (100 /xg iv) were studied in seven acromegalic patients. In contrast to normal men, in whom plasma concentrations of catecholamines decrease markedly, acromegalic subjects fail to show decreases in plasma dopamine, norepinephrine, or epinephrine in response to bromocriptine (four of four studied) or LRH (three of four studied). Mean basal plasma catecholamine concentrations do

not differ in acromegalic patients, normal men, and a group of nonacromegalic endocrine control patients. Since it appears that bromocriptine and LRH suppress plasma catecholamine concentrations through mechanisms at brain catecholamine neurons, these data are compatible with disordered catecholamine neurons in the brain of patients with acromegaly. (JClin Endocrinol Metab 48: 784, 1979)

I

N ACROMEGALY, the excess secretion of GH results from either eosinophilic adenoma or hyperplasia of eosinophilic cells of the anterior pituitary. Several reports have suggested that GH secretion in both of these situations is not autonomous and remains, in part, under hypothalamic control (1-3). Furthermore, these reports suggest the possibility that adenomatous hyperplasia of pituitary somatotrophs in acromegaly may result from chronic excessive secretion of hypothalamic GH-releasing factors (GHRF). The more recent identification of somatostatin (SRIF) raises another possibility, namely that such eosinophilic adenomatous hyperplasia may result from deficient SRIF secretion. Proof for either of these hypotheses has not yet been provided. In any case, there remains no explanation for the possibly disordered secretion of GHRF or SRIF by the hypothalamus. Abnormalities of neurons regulating the secretion of these factors have not been described. Neurotransmitter regulation of GH secretion probably acting through regulation of GHRF or SRIF secretion, has received considerable attention in recent years, but a unifying hypothesis has not yet emerged. Perhaps the best evidence supports stimulatory roles for dopamine and a-adrenergic receptors in the normal regulation of GH secretion (4). In marked contrast to their effects in normal man, dopaminergic agonists decrease serum GH in acromegalics (5).

The above data raise the possibility that excessive GH secretion (and perhaps even the earlier development of adenomatous hyperplasia) results from defective catecholaminergic regulation of the neurons secreting GHRF or SRIF. No previous studies have defined a defect in the function of catecholamine neurons in acromegaly. Recently, we reported that bromocriptine, a dopaminergic agonist, suppresses plasma dopamine, norepinephrine, and epinephrine in normal men (6, 7). LRH produces a similar suppressive effect on plasma concentrations of all three catecholamines in normal men (8). We hypothesized that these effects were mediated on presynaptic dopamine receptors, probably in the brain. In the present study, these observations have been applied as tests of normal presynaptic catecholamine receptor mechanisms in searching for a possible defect in such mechanisms in patients with acromegaly. Some of these data have been reported previously in abstract form (9). Materials and Methods Eleven acromegalic patients, aged 25-80 yr, were studied. Relevant medical history is recorded in Table 1. Three different studies were carried out. Study I Basal plasma catecholamine concentrations. To avoid the possibility of differences resulting from interassay variation, basal plasma concentrations of dopamine, norepinephrine, and epinephrine in six acromegalics and nine control subjects were compared in one assay. Control subjects were hospitalized patients with various endocrine disorders not thought to involve catecholamine mechanisms.

Received October 11,1978. Address requests for reprints to: Dr. Glen R. Van Loon, University of Toronto, Medical Sciences Building, Room 6265, Toronto, Ontario, Canada M5S 1A8. 784

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A CATECHOLAMINE DEFECT IN ACROMEGALICS TABLE 1. Clinical data on 11 patients with acromegaly Patient

Sex

Age (yr)

A

F

48

B

M

52

Previous treatment Transphenoidal pituitary surgery 8 yr previously Transphenoidal pituitary surgery

Serum GH (ng/ ml) 7-12

Carpel tunnel syndrome

15-22

Diabetes mellitus, peripheral neuropathy, hypogonadism Sleep apnea, angina, hypogonadism Osteoarthritis, severe Depression, hypogo nad ism Nil Major seizures, personality disorder, hypogonadism

C

M

49

Nil

6-12

D

F

80

7-12

E

M

40

F G

F M

45 34

H

M

47

Pituitary irradiation 12 yr previously Proton beam irradiation 5 yr previously Nil Transfrontal pituitary surgery 7 yr previously and cobalt irradiation to pituitary 5 yr previously Nil

J K

F F

25 71

L

M

24

Nil Transfrontal pituitary surgery and postoperative cobalt irradiation to pituitary 39 yr previously Nil

Signs and symptoms

39-75 9-14 9-12

6-12

14-43

Abnormal plasma catecholamine responses in acromegalics.

0021-972X/79/4805-0784S02.00/0 Journal of Clinical Endocrinology and Metabolism Copyright © 1979 by The Endocrine Society Vol. 48, No. 5 Printed in U...
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