A new test for the diagnosis of growth hormone deficiency due to primary pituitary impairment: combined administration of pyridostigmine and growth hormone-releasing hormone

• Published in: Journal of endocrinological investigation Vol. 13; no. 4; p. 307
• Main Authors: Ghigo, E, Imperiale, E, Boffano, G M, Mazza, E, Bellone, J, Arvat, E, Procopio, M, Goffi, S, Barreca, A, Chiabotto, P
• Format: Journal Article
• Language: English
• Published: Italy 01.04.1990
• Subjects: Administration, Oral; Adolescent; Body Height; Child; Child, Preschool; Drug Therapy, Combination; Female; Growth Disorders - diagnosis; Growth Disorders - drug therapy; Growth Disorders - etiology; Growth Hormone - blood; Growth Hormone - deficiency; Growth Hormone-Releasing Hormone - administration & dosage; Humans; Infusions, Intravenous; Male; Pituitary Gland - drug effects; Pituitary Gland - pathology; Pituitary Gland - physiopathology; Pyridostigmine Bromide - administration & dosage
• ISSN: 0391-4097; 1720-8386
• DOI: 10.1007/BF03349569

The diagnosis of growth hormone (GH) deficiency (GHD) is currently based on failure to increase plasma GH levels to an arbitrary cutoff point of 7 or 10 micrograms/l in response to two provocative stimuli. False negative responses to these tests, however, frequently occur thus reducing their diagnostic reliability. The aim of this study was to assess a combination of pyridostigmine (PD) and GH-releasing hormone (GHRH) (60 mg oral PD 60 min before 1 microgram/Kg GHRH iv) as a reliable test probing pituitary somatotropic function. In fact PD, an acetylcholinesterase inhibitor, strikingly potentiates GH response to GHRH likely by inhibiting somatostatin release. The combination PD + GHRH was tested in normal children and adolescents (NS, n = 27) and in a large group of short children classified as having familial short stature (FSS, n = 24), constitutional growth delay (CGD, n = 34) and GH deficiency (organic, oGHD, n = 6; idiopathic, iGHD, n = 10). In all groups results obtained by PD + GHRH were compared with those obtained by testing with GHRH, clonidine (CLON) and PD alone and by studying spontaneous nocturnal GH secretion over 8 hours. Assuming 7 micrograms/l as minimum normal GH peak, a positive response occurred in only 18/24, 11/12 and 12/13 NS for GHRH, CLON, and PD, respectively. In contrast even assuming a minimum normal GH peak as high as 20 micrograms/l, PD + GHRH induced a positive response in 27/27 NS all having a nocturnal GH mean concentration (MC) greater than or equal to 3 micrograms/l. Therefore PD + GHRH test gave no false negative responses and this was true not only in NS but even in all FSS and CGD having a GH MC greater than or equal to 3 micrograms/l. On the other hand, PD + GHRH induced a negative GH response in all oGHD and in 8/10 iGHD patients. In the remaining two iGHD patients, PD + GHRH demonstrated a normal pituitary GH reserve in spite of a GH MC less than 3 micrograms/l and low IGF-I level, thus pointing to a hypothalamic pathogenesis for the GHD. Considering FSS and CGD children having a GH MC less than 3 micrograms/l, PD + GHRH showed a primary pituitary GH deficiency in 3/12 CGD with low plasma IGF-I levels. In conclusion, in slowly growing children PD + GHRH test is the most reliable provocative test for the diagnosis of primary pituitary GH deficiency being capable to discriminate between an unequivocally normal and impaired somatotropic function.