To the best of our knowledge, hypoplastic adenohypophysis in GSDIa has not been described previously. Melis et al. previously investigated brain MRI findings in patients with GSDI, and showed that 57.1% of the patients had an altered brain MRI pattern . There was no mention in their study of pituitary abnormality or a hypothalamopituitary imaging pattern .
Kuemmerle et al. showed that sustained metabolic acidosis causes growth inhibition in rats by decreasing the amplitude and mean mass of GH pulses . As metabolic (hypoxic) injuries of the hypothalamus are also known to cause hypoplasia of the anterior pituitary, the hypoplastic adenohypophysis in the woman described in this case report is considered to be related to growth hormone neurosecretory dysfunction (GHNSD) . GHNSD is an abnormality characterized by short stature, growth retardation and abnormal spontaneous GH secretion despite normal GH response to provocative testing . Our case would formally have satisfied the diagnostic criteria for GHNSD, with a further finding of hypoplastic adenohypophysis. While prepubertal dynamic testing revealed a subnormal GH response, but not severe GH deficiency (that is, stimulated GH response <3 ng/ml), a normal peak GH response was obtained in her re-evaluation using an insulin-tolerance test when she was 20 years old. Such a discrepancy between childhood and adulthood peak GH responses have already been reported in GHNSD . A more frequent sampling than the limited 2-hour intervals undertaken in our case may have detected significant peaks, especially overnight. Spontaneous GH secretion may have been underestimated here.
On the other hand, the existence of GHNSD as a separate entity has been questioned recently in one paper . In this study, which was entirely focused on GH abnormalities following cranial irradiation, it was concluded that a reduced somatotroph reserve might mimic or seemingly present as GHNSD when hypothalamic compensation fails to restore GH secretion in the case of increased demands such as puberty . As growth hormone-releasing hormone (GHRH) also functions as a trophic factor for the pituitary gland, an atrophic or hypoplastic pituitary associated with discordant spontaneous and stimulated GH secretion patterns is generally considered as GHRH deficiency due to GHNSD.
A normal stimulated GH response in an insulin-tolerance test is defined as a peak of above 5.0 ng/ml . Although the stimulated GH level of 5.18 ng/ml in our case was just above the cut-off level, it could still be considered as a relatively low response due to lack of normative data for GSDIa. If so, the reduction in both the spontaneous and stimulated GH secretion, which is proportional to somatotroph volume, may be a reflection of primary pituitary hypoplasia rather than GHNSD.
As described and demonstrated by Darzy et al. in cranial irradiation, the possibility of primary loss in the somatotroph mass, rather than secondary atrophy due to a neurosecretory defect in GHRH secretion, should also be considered, especially in patients with an underlying injury which is potentially harmful to the pituitary gland itself . Although there is a lack of evidence, it is possible that GSDIa may have an associated genetic involvement of the pituitary gland which has not yet been defined.