abnormalities of the hypothalamic-pituitary axis, as detected by
cerebral magnetic resonance imaging (MRI) in children with isolated
growth hormone deficiency (GHD) or multiple pituitary hormone
deficiencies (MPHD) are a landmark of a group of patients with
hypopituitarism. Leger et al reported a prospective study of a group
of such 18 patients who had in common MRI markers of ectopic
neurohypophysis with defects of the pituitary stalk. The researchers
followed the patients until adulthood, after completion of GH
treatment. The initial diagnosis of GHD was based on a GH peak of <10
µg/L after provocative stimuli. At retesting, the same criteria
were applied, but GHD was considered as severe if the peak value was
<5 µg/L. The important finding at reevaluation was the
presence of normal or only partially deficient GH secretion with a
peak value of >5 µg/L in 7 patients; 6 out of whom had
isolated GHD. Among the 11 patients with severe GHD at retesting,
only one had isolated GHD. Therefore, MPHD, regardless of etiology,
was a strong predictor of permanent GHD after adolescence.
structure of the hypothalamic-pituitary axis differed among both
groups. It should therefore be recalled that the main anatomical
finding in the so-called pituitary stalk interruption syndrome is the
ectopic location of the bright spot of the neurohypophysis. This spot
may be located in its upper position at the median eminence or at a
lower level along the pituitary stalk with a hypoplastic anterior
pituitary. The ectopic neurohypophysis was found at the median
eminence level in 10 out of 11 patients with permanent, severe GHD.
In contrast, it was located along the stalk in all but one of the
patients with normal or partially reduced GH response at retesting.
Cerebral MRI (T1-weighted images). A, Sagittal slice; B, coronal slice; normal morphology of anterior
pituitary and pituitary stalk is seen. The hyperintense signal of the posterior pituitary is in the normal
location. C, Sagittal slice; D, Coronal slice; a normal anterior pituitary with a thin pituitary stalk is
seen. The ectopic posterior pituitary hyperintense signal is located along the stalk (at a proximal
level of the pituitary stalk; arrow). E, Sagittal slice; F, coronal slice; hypoplastic anterior pituitary
with no visible pituitary stalk after gadolinium injection. The ectopic pituitary hyperintense signal is
at the median eminence (arrow). Reprinted with permission Leger J, et al. J Clin Endocrinal Metab.
2005;90:650-656. Copyright ©2005. The Endocrine Society. All rights reserved.
concluded that increased GH secretion may be observed in adult
patients with less severe MRI anatomical defects. These individuals
need to be retested at the completion of GH treatment. In contrast,
the patients who persisted with severe GHD formed a subgroup with
their neurohypophysis at the median eminence with lack of or poor
visibility of the pituitary stalk. Retesting may not be necessary in
these patients, especially if there is MHPD.
Leger J, Danner S, Simon D, Garel C, Czernichow P. Do all patients with
childhood-onset growth hormone deficiency (GHD) and ectopic
neurohypophysis have persistent GHD in adulthood? J Clin
Endocrinol Metab. 2005;90:650−656.
Comment: The authors studied a group of non-acquired GHD patients
identified by MRI-detectable anatomical defects of the
hypothalamic-pituitary axis. This type of patient is of theoretical
as well as practical interest. It was first hypothesized that all
patients with such MRI-detectable defects would show permanent GHD
and eventually be candidates for life-long GH therapy. It is now
shown that a subgroup (approximately 40%) with isolated GHD in
childhood may appear as normal, or moderately affected, at retesting
after growth is completed. Furthermore, the patients with GHD appear
to present an anatomical defect detectable in the MRI which can be
considered as less severe: the pituitary stalk is eventually visible
and the neurohypophysis has partly “migrated” downward.
These findings may help predict a more favorable outcome. In
contrast, those presenting with MPHD with an ectopic neurohypophysis
located in the median eminence usually present persistent GHD into
adulthood. However, a word of caution is necessary as some of the
patients with isolated GHD may develop other pituitary defects at any
age. They require a lifetime follow-up, even if GH secretion has
apparently returned to normal. These data should be considered for
future guidelines of GH treatment.
pathogenesis of the pituitary stalk interruption syndrome with
pituitary insufficiency remains unknown in most cases. This defect
has been reported in some patients with identified molecular defects
of transcription factors controlling the early pituitary
development.1-3 Although it was not the scope of this
study, it seems important to not consider pituitary dysfunction as a
stable condition. As also shown in other studies, the switch from
isolated GHD to multiple defects remains possible at any age.4,5
It will be of great interest to follow the patients who had an
apparent recovery reported by Leger et al to document their
reproductive function. Finally, patients with this illness are
candidates for genetic studies and long-term follow-up to provide a
more complete and eventually significant description of their
hypothalamic-pituitary function throughout life.
Raphaël Rappaport, MD
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