Neurological manifestations following clonidine test for growth hormone reserve in children: case report and review of the literature

Abstract

Introduction administration of a single dose of clonidine 4 μg/kg or 0.15 mg/m2.[6] However, the use of clonidine for this Clonidine is an α2-adrenergic agonist usually used for purpose is not authorised in the manufacturer’s prescribing treatment of hypertension, phaeochromocytoma, pain and information. other disorders. α2-Adrenergic agonists modulate growth hormone secretion by inhibiting the release of Case report somatostatin by the hypothalamus and also by stimulating growth hormone releasing factor secretion.[1-3] Due to its An 11-year-old girl with short stature (1.25m) and agonist action in the CNS, clonidine is used in the delayed puberty was referred to the Paediatric diagnosis of delayed growth in adults and children with Endocrinology Department at the Severo Ochoa Hospital lack of growth hormone (somatotropin).[1,4] in Madrid, Spain to have her growth hormone reserve Growth hormone has a direct effect on growth, but assessed. Levels of thyroid stimulating hormone (TSH) most of its effect is mediated by an insulin-like growth and IGFBP-3 were normal, while levels of IGF-1 were factor (IGF) and other peptides, such as somatomedin. low (89 ng/mL; normal range 117–771 ng/mL). The IGF is closely linked to six specific plasmatic proteins following month, the IGF-1 level test was repeated, giving referred to as IGF binding protein (IGFBP). The levels of results of 51 ng/mL. The growth hormone insulin IGF and IGFBP-3 depend on growth hormone secretion, stimulation test was considered negative (i.e. growth which increases in patients with acromegaly and decreases hormone levels were <5 ng/mL after insulin stimulation). in patients with hypopituitarism or growth hormone Consequently, it was decided to use the clonidine deficiency. At high levels, insulin also stimulates growth stimulation test to assess her growth hormone levels. She due to its anabolic action.[5] received 0.11mg of clonidine. During the test, she suffered The growth disorders are diagnosed by physical from hypotension, loss of consciousness and hypertonia. examination, bone age measurement, thyroid function She was initially diagnosed as having syncope. Two hours tests, and indirect (IGF-I and IGFBP-3 later, she was admitted to the Paediatric Emergency radioimmunoassays) and direct (growth hormone release Department with hallucinations, psychomotor agitation, stimulation test) growth hormone tests. The randomised pallor and sphincter relaxation. IGF-I and IGFBP-3 quantifications accurately reflect the That evening, after being discharged, she presented average growth hormone blood levels, as they have a long with dysarthria, drowsiness, paraesthesia and carpopedal half life. When IGF-I and IGFBP-3 levels are low, direct spasm. She returned to the Paediatric Emergency determinations of growth hormone levels are required. As Department and was kept under medical observation for the secretion of growth hormone is episodic, the 24 hours. Blood ion tests and physical and neurological measurement of this hormone is determined after explorations were normal. stimulation by various substances, such as insulin or clonidine.[5] If adequate increments in growth hormone This adverse reaction was communicated to the levels do not occur after stimulation by at least two Pharmacovigilance Surveillance Programme. The results substances, the stimulation test is considered negative and, of the clonidine stimulation test were considered positive, therefore, the patient has a growth hormone deficiency. with growth hormone levels of 6.90, 7.90, 11.10 and 13.50 Using the clonidine test, growth hormone levels are ng/mL at 0, 60, 90 and 120 minutes, respectively, after measured at 60, 90 and 120 minutes after the clonidine administration.