Magnetic resonance imaging of the hypothalamuspituitary unit in children suspected of hypopituitarism: Who, how and when to investigate

Abstract

The magnetic resonance (MR) identification of pituitary hyperintensity in the posterior part of the sella has been the most striking recent finding contributing to the diagnosis of "idiopathic" and permanent GH deficiency (GHD). Moreover, advancements in DNA technology have shed new light on the study of the genetic causes of hypopituitarism. Abnormalities in two genes, the GH-N encoding the GH and the GHRH receptor (GHRH-R), have been identified, while mutations in five other gene-encoding transcription factors such as Pit-1, Prop-1, Hesx-1, Lhx-3 and Lhx-4 involved in anterior pituitary development, have also been described. MR imaging shows marked differences in pituitary morphology indicating different GHD etiologies and different prognoses. Ectopic posterior pituitary is a specific marker of permanent GHD. These patients do not have Pit-1, Prop-1, or Lhx-3 mutations and should be carefully monitored for evolving pituitary hormone defects, though they do not require GH re-evaluation in adulthood; selected cases may have Hesx-1 or Lhx-4 mutations. MR evidence of normal or small anterior pituitary gland, enlarged empty sella, pituitary hyperplasia and/or intrasellar or suprasellar mass when associated with combined pituitary hormone deficiency call for molecular analysis of Pit-1, Prop-1, Hesx-1, or Lhx-3. Limitation of neck rotation and Chiari-I malformation may suggest Lhx-3 or Lhx-4 mutations (exceedingly rare). In "idiopathic" isolated GHD, evidence of normal anterior or small anterior pituitary size with normal location of posterior pituitary and normal connection between the hypothalamus and pituitary gland is suggestive of "transitory" or false positive GHD; patients with such characteristics should be re-evaluated well before reaching adult height. In selected cases, anterior pituitary height that is 2 SD below age-adjusted normal pituitary height could be suggestive of GHRH-R gene defect; it is worth pointing out that normal pituitary MR together with severe GHD has been observed, though rarely, in subjects with a genetic origin of GHD.

Magnetic resonance imaging of CNS in 15 043 children with GH deficiency in KIGS (Pfizer International Growth Database)

“…Indeed, the first report about the latter MRI findings in children with GHD was published in 1987 (1), and since then, MRI has become a standard diagnostic technique used to identify anatomical causes of GHD, which was previously diagnosed by anthropometrical and biochemical methods alone (20,22,25).…”

“…In fact, the neuroimaging findings in GHD mainly include the following: first, normal or hypoplastic pituitary gland/empty sella (ES) without anatomical abnormalities of the hypothalamus or pituitary stalk and secondly, moderate-to-severe (pituitary height %3 mm) hypoplastic pituitary gland with ectopic posterior pituitary located anywhere from the median eminence to the distal stalk (1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25). Isolated GHD is more commonly observed in the first category while multiple pituitary hormone deficiencies (MPHD) occur more frequently in the second.…”

“…An ES occurs in 10% of idiopathic GHD (IGHD) (12). MPHD may be associated with a variety of cerebral malformations such as Arnold-Chiari I and II, agenesis of the septum pellucidum, septo-optic dysplasia, vermis dysplasia, syringomyelia, absence of the internal carotid artery, dysgenesis of the corpus callosum, arachnoid cysts and tentorium anomalies with basilar impression (11,20,22,25). The frequency of these radiological findings and their endocrine spectrum is variable.…”

“…The frequency of these radiological findings and their endocrine spectrum is variable. In particular, MPHD is more frequently associated with ectopic posterior pituitary and anterior pituitary hypoplasia than isolated GHD (2,3,5,13,14,15,17,18,20,21,22,23,24,25). The variability between different studies can be ascribed to the degree of restriction in the studies' diagnostic criteria, to the diagnostic limits of GHD itself (transitory deficits, recovery, false positives, etc.)…”

Evaluation of pituitary imaging in patients with PROP-1 gene mutation

“…Literatūros duomenimis, radiologiniai pokyčiai hi-pofizės srityje gali būti labai įvairūs: nuo hipofizės tūrio padidėjimo (hiperplazija, pseudonavikas "turkiš-kojo balno" srityje, imituojantis kraniofaringeomą arba Ratkės pluošto cistą) iki hipofizės hipoplazijos ("tuščio turkiškojo balno" sindromo); kartais hipofizė būna normalių matmenų (6,7,(11)(12)(13)(14)(15)(16). Kartojant vaizdinius tyrimus po kiek laiko, kartais būna hipofizės regresija (6,11,12,16).…”