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Changes in ACTH and catecholamines in response to arecoline in patients with autonomic failure
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Changes in ACTH and catecholamines in response to arecoline in patients with autonomic failure R.J. Polinsky, R.T. B r o w n , M.T. C u r r a s , S.M. Baser, C.E. B a u c o m , D . R . H o o p e r and A.M. Marini N.LN.D.S., Bethesda, MD, U.S.A.
Anterior pituitary hormones are released mainly under the control of hypothalamic releasing factors; however, pituitary responses are modulated by neurotransmitters [1,3]. Patients with autonomic failure accompanied by multiple system atrophy (MSA) have a reduced ACTH and beta-endorphin response to insulin-induced hypoglycemia, whereas the response is normal in patients with pure autonomic failure (PAF) [2]. To investigate the role of cholinergic and adrenergic mechanisms in the release of ACTH, plasma levels of adrenaline, noradrenaline and ACTH were measured in 15 MSA and 6 PAF patients and 10 controls, after administration of the cholinomimetic drug arecoline. Peripheral muscarinic effects were blocked with glycopyrrolate, which raised baseline plasma adrenaline levels. ACTH levels were similar in the three groups, but they increased significantly after arecoline injection only in control subjects. Adrenaline levels increased in controls and in MSA patients; in controls the adrenaline increase preceded ACTH increase and there was a significant correlation between ACTH and adrenaline responses. Noradrenaline plasma levels did not change in any subject. Our results show an impaired ACTH response to cholinergic stimulation in autonomic failure patients. The increase in adrenaline level after stimulation, in controls and in MSA patients, may be due to nicotinic stimulation of adrenal glands; the lack of this response in PAF patients is consistent with peripheral sympathetic damage. The failure of ACTH secretion to rise in response to arecoline in MSA patients probably reflects dysfunction of the cholinergic mediation of hypothalamic corticotropin releasing factor. Hypothalamic cholinergic neurone degeneration is suggested by the fall in acetylcholinesterase [4]. The failure of ACTH secretion to rise in response to arecoline in PAF patients might be due to the lack of plasma adrenaline level increase which may be required to elicit this response. 1 2 3 4
Mezey et al., Proc. Natl. Acad. Sci. USA 80 (1983) 6728-6731. Polinsky et al., Ann. Neurol. 22 (1987) 573-577. Risch et al., Peptides 2 (1981) 95-97. Spokes et al., J. Neurol. Sci. 43 (1979) 59-82.
Evoked potentials in multiple system atrophy I. E a r d l e y , R.S. K i r b y , N.P. Q u i n n , C . D . M a r s d e n , R. B a n n i s t e r a n d C.J. F o w l e r St. Bartholomew's Hospital and The National Hospital for Nervous Diseases, Queen Square, London, U.K.
Electromyography of the striated musculature of the external sphincter of the urethra in patients with multiple system atrophy often shows evidence of denervation and reinnervation. These changes are interpreted as a sign of nerve cell loss within the nucleus of Onuf in the spinal cord, supplying the motor innervation to the muscle. There are, however, no other reports on neurophysiological tests in these patients. We studied a group of patients with probable multiple system atrophy, and carried out tests which included assessment of the sacral reflex arc, measurement of the pudendal somatosensory evoked
Changes in ACTH and catecholamines in response to arecoline in patients with autonomic failure R.J. Polinsky, R.T. B r o w n , M.T. C u r r a s , S.M. Baser, C.E. B a u c o m , D . R . H o o p e r and A.M. Marini N.LN.D.S., Bethesda, MD, U.S.A.
Anterior pituitary hormones are released mainly under the control of hypothalamic releasing factors; however, pituitary responses are modulated by neurotransmitters [1,3]. Patients with autonomic failure accompanied by multiple system atrophy (MSA) have a reduced ACTH and beta-endorphin response to insulin-induced hypoglycemia, whereas the response is normal in patients with pure autonomic failure (PAF) [2]. To investigate the role of cholinergic and adrenergic mechanisms in the release of ACTH, plasma levels of adrenaline, noradrenaline and ACTH were measured in 15 MSA and 6 PAF patients and 10 controls, after administration of the cholinomimetic drug arecoline. Peripheral muscarinic effects were blocked with glycopyrrolate, which raised baseline plasma adrenaline levels. ACTH levels were similar in the three groups, but they increased significantly after arecoline injection only in control subjects. Adrenaline levels increased in controls and in MSA patients; in controls the adrenaline increase preceded ACTH increase and there was a significant correlation between ACTH and adrenaline responses. Noradrenaline plasma levels did not change in any subject. Our results show an impaired ACTH response to cholinergic stimulation in autonomic failure patients. The increase in adrenaline level after stimulation, in controls and in MSA patients, may be due to nicotinic stimulation of adrenal glands; the lack of this response in PAF patients is consistent with peripheral sympathetic damage. The failure of ACTH secretion to rise in response to arecoline in MSA patients probably reflects dysfunction of the cholinergic mediation of hypothalamic corticotropin releasing factor. Hypothalamic cholinergic neurone degeneration is suggested by the fall in acetylcholinesterase [4]. The failure of ACTH secretion to rise in response to arecoline in PAF patients might be due to the lack of plasma adrenaline level increase which may be required to elicit this response. 1 2 3 4
Mezey et al., Proc. Natl. Acad. Sci. USA 80 (1983) 6728-6731. Polinsky et al., Ann. Neurol. 22 (1987) 573-577. Risch et al., Peptides 2 (1981) 95-97. Spokes et al., J. Neurol. Sci. 43 (1979) 59-82.
Evoked potentials in multiple system atrophy I. E a r d l e y , R.S. K i r b y , N.P. Q u i n n , C . D . M a r s d e n , R. B a n n i s t e r a n d C.J. F o w l e r St. Bartholomew's Hospital and The National Hospital for Nervous Diseases, Queen Square, London, U.K.
Electromyography of the striated musculature of the external sphincter of the urethra in patients with multiple system atrophy often shows evidence of denervation and reinnervation. These changes are interpreted as a sign of nerve cell loss within the nucleus of Onuf in the spinal cord, supplying the motor innervation to the muscle. There are, however, no other reports on neurophysiological tests in these patients. We studied a group of patients with probable multiple system atrophy, and carried out tests which included assessment of the sacral reflex arc, measurement of the pudendal somatosensory evoked