Abnormalities of growth hormone release in response to human pancreatic growth hormone releasing factor (GRF (1-44) ) in acromegaly and hypopituitarism.

Abstract

Human pancreatic growth hormone releasing factor ) is the parent molecule of several peptides recently extracted from pancreatic tumours associated with acromegaly. A study was conducted to examine its effects on the release of growth hormone in normal volunteers and in patients with hypopituitarism and acromegaly.GRF (1-44) dose dependently stimulated the release of growth hormone in normal people and produced no appreciable side effect. This response was grossly impaired in patients with hypopituitarism and, although similar to the growth hormone response to hypoglycaemia, was of quicker onset and a more sensitive test of residual growth hormone function. Patients with acromegaly appeared to fall into (a) those with a normal response to GRF, whose growth hormone suppressed significantly with oral glucose, and (b) those who had an exaggerated response to GRF (1-44), whose growth hormone had not suppressed previously after oral glucose.Present methods for testing growth hormone deficiency entail using the insulin stress test, which is time consuming, unpleasant, and sometimes dangerous. A single intravenous injection of GRF now offers the possibility of an easier, safer, and more reliable routine test for growth hormone deficiency. It has the further

Comparative in vivo and in vitro Studies on Abnormal GH Secretion in Patients with Acromegaly.

“…An increase in GH either to the same or a greater extent as in the normal has been reported in the majority of acromegalics. In our patients the frequency of decreased or no response to GRF was higher than those reported previously (Wood et al, 1983, Shibasaki et al, 1984, von Werder et al, 1984, Pieters et al, 1984b, Gelato et al, 1985, Arosio et al, 1985.…”

“…Decreased response of plasma GH or no response to GRF administered iv is frequently reported, though GH is increased either to the same as, or to a greater extent than the normal in the majority of the acromegalics (Wood et al, 1983, Shibasaki et al, 1984, von Werder et al, 1984, Pieters et al, 1984b, Gelato et al, 1985, Arosio et al, 1985. These abnormalities in GH secretion could be due to either a change in the hypothalamic regulatory mechanism (hypothalamic hor-mones and/or amines) for GH secretion, the disappearance of, or aberrant appearance of, receptors for these hypothalamic hormones at the pituitary level, and/or a change in the postreceptor mechanism.…”

GHRF test in acromegalic patients for the evaluation of therapeutic results.

“…Plasma GH in case 1 did not respond to TRH, arginine, and to GHRF 11 years after the pituitary irradiation, while it responded to the former two agents before the therapy. It is reported that TRH and GHRF act on tumor somatotrophs directly to release GH (Ishibashi and Yamaj i 1978 ; Adams et al 1979 ;Lambert et al 1984 ;Nakagawa et al 1985), and maximum OH responses to GHRF usually exceed 5 ng/ml (Wood et al 1983 ;Takano et al 1984 ;Gelato et al 1985). Therefore, case 1 would have severe posttherapeutic pituitary damage not only in tumor but also in normal somatotrophs.…”

“…GHRF acts directly on pituitary gland and selectively stimulates growth hormone secretion (Guillemin et al 1982 ; Rivier et al 1982 ; Thorner et al 1983). Although, acromegalic patients often show responses in plasma GH following GHRF administration, the magnitude of the responses is reported to be variable (Wood et al 1983 ; Shibasaki et al 1984). Therefore, Gelato et al (1985) suggested that GHRF test for diagnostic use in acromegalic patients is less valuable than TRH test.…”

An Acromegalic Patient with Pulsatile Secretion of Growth Hormone (GH) Coincident with the Slow-Wave Sleep.

“…ACROMEGALY is characterized by a typical clinical appearance associated with hypersecretion of GH for 24 h,abnormal responses of plasma GH including incomplete suppression by glucose administration or a paradoxical increase after TRH [1][2][3]and/or LHRH [4],hyperresponse to GHRH [5] and a decrease after dopaminergic stimulation [6].In normal subjects,GH is secreted in a pulsatile manner under the hypothalamic regulation via GHRH and somatotropin release inhibiting factor (SRIF),with a close relationship to the slow-wave sleep during the night.The GH pulse is more frequent,and plasma GH levels at both the interpulse and the nadir were much higher in acromegalic patients than in normal subjects [7]. Furthermore,it has been reported that GH secretion during the night is not related to the slow-wave sleep in acromegaly [8,9].There has not been any report on the detection of pulsatile GH secretion associated with slow-wave sleep in acromegalic patients.When a GH secreting pituitary tumor was removed,plasma GH levels were improved but the pattern of secretion was not completely normalized [10].Paradoxical GH responses to a number of GH stimuli were recognized in many patients with acromegaly.The relationship between the spontaneous pulsatile GH secretion and such paradoxical responses of GH has not been fully elucidated.…”