Prolonged Intracranial Hypertension after Recombinant Growth Hormone Therapy due to Impaired CSF Absorption

Abstract

We experienced a case of a Japanese boy who developed intractable idiopathic intracranial hypertension (IIH) during growth hormone (GH) treatment. At the age of 4 yr, the boy was diagnosed with idiopathic growth hormone deficiency, and recombinant human GH replacement was initiated. Nine months after initiation of the GH therapy, he began to complain of headache, but papilledema was not observed. His headache persisted thereafter, and right esotropia occurred 10 mo after the initiation of GH therapy, at which time papilledema was detected. No other neurological abnormalities were detected, and the findings of computed tomography and magnetic resonance imaging were normal. In a cerebrospinal fluid (CSF) examination, the pressure was markedly elevated to 450 mmH2O, but no other abnormality was recognized. Impaired CSF absorption was detected using the pressure-volume index technique. The CSF levels of GH and insulin-like growth factor I were not increased. GH therapy was withdrawn after it was suggested that the IIH was associated with the GH therapy, but the headache persisted. The intracranial hypertension did not respond to diuretics, and prednisolone was only transiently effective. Although the funduscopic findings were normalized, increased CSF pressure was still observed. For over 2 yr, repeated lumbar puncture was necessary to protect against visual defect. IIH is an uncommon adverse event during GH therapy, but it must be considered carefully.

Long-Term Safety of Growth Hormone Treatment in Childhood: Two Large Observational Studies: NordiNet IOS and ANSWER

“…Patients experiencing SCFE also received a higher average GH dose up to the AE onset (43.7 µg/kg/day) compared with the whole patient population (30.9-38.6 µg/kg/day), which may have contributed to the rapid height velocity associated with SCFE ( 34 ), or to acute joint changes. Edema and increased ICP are likely related to the water retention and temporary imbalance of cerebrospinal fluid production and resorption associated with GH treatment ( 20 , 37 ), and thus possibly related to GH dose. Patients experiencing edema or ICP increase received a higher average GH dose (39.0-39.8 µg/kg/day) than the whole patient population, although this difference was less pronounced than in the patients with SCFE.…”

New-Onset Isolated Asymptomatic Papilledema in Two Patients Treated With Recombinant Growth Hormone

“…Early screening may reduce morbidity associated with growth hormone induced IIH due to early recognition. 2…”

“…1 IIH developed anywhere between 2 weeks to 8 years after initiating GH therapy at a dose of 0.18 to 0.33 mg/kg/wk. 1,2 IIH is characterized by elevated intracranial pressure, papilledema, and symptoms including headache, vision changes, nausea, and vomiting.…”