Do All Patients with Childhood-Onset Growth Hormone Deficiency (GHD) and Ectopic Neurohypophysis Have Persistent GHD in Adulthood?

Abstract

Cerebral magnetic resonance imaging findings are of great value for the diagnosis of nonacquired GH deficiency (GHD), and ectopic posterior pituitary hyperintense signal (EPPHS) is a sensitive and specific indicator of hypopituitarism. It has been suggested that patients with childhood-onset GHD and EPPHS do not require additional investigation of GH secretion and should not be retested when adult height is achieved. This recommendation has never been validated through a systematic study. This study aimed to characterize the anterior pituitary function status of patients with EPPHS treated for GHD during childhood after completion of GH therapy when adult height had been achieved. Patients (n = 18; 15 males and three females) with childhood-onset GHD associated with ectopic neurohypophysis were treated with hGH (0.20 ± 0.05 mg/kg·wk) for 9.9 ± 4.0 yr (from 6.8 ± 4.7 to 17.7 ± 1.3 yr of age) with a mean height gain of 2.6 ± 1.4 sd score. GH secretion was reevaluated by arginine insulin (n = 15) or propanolol glucagon (n = 3) test after 0.5 ± 0.6 yr of GH withdrawal. At reevaluation, peak GH was more than 10 μg/liter in four patients (22%; range, 11.7–19.5 μg/liter; group I), between 5 and 10 μg/liter in three patients (17%; range, 7.3–9 μg/liter; group II), and less than 5 μg/liter in 11 patients (61%; range, 0–4.7 μg/liter; group III). A positive correlation was found between serum IGF-I and peak GH levels after attainment of adult height (P = 0.007). Only one of the seven patients who showed increased GH secretion ability in adulthood (groups I and II) demonstrated other hormonal deficiencies (gonadotropin and adrenal insufficiencies). Among the 11 patients with persistent severe GHD (group III), 10 (91%) of the 11 subjects were shown to have multiple pituitary hormone deficits after attainment of adult height. The structure of the hypothalamo-pituitary axis differs among groups [i.e. patients who showed increased GH secretion ability in adulthood (groups I and II) vs. those who remained severely GHD (group III)]. The location of the EPPHS was significantly different among groups (P < 0.003). The EPPHS was found at the median eminence in all but one of group III patients and along the pituitary stalk (proximal stalk) in all but one of group I and II patients. The pituitary stalk was visible and described as normal (n = 1) or thin (n = 6) in all group I and II patients, whereas the pituitary stalk was not visible even after enhancement in seven of the 11 group III patients (P < 0.02). The prevalence of anterior pituitary hypoplasia and the mean height gain sd score were similar in each group. In conclusion, only 61% of patients with childhood-onset GHD and EPPHS remained severely GHD, and thus suitable for GH therapy, in adulthood. Although the pathogenesis of anterior pituitary dysfunction remains unclear in patients with ectopic neurohypophysis, isolated GHD, location of EPPHS along the stalk, and visibility of the pituitary stalk on magnetic resonance imaging findings clearly represent important markers to predict a less severe form of the disease.