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EditorialEDITORIAL

Etiology of Congenital Growth Hormone Deficiency

Walter Kucharczyk
American Journal of Neuroradiology June 2000, 21 (6) 1000;
Walter Kucharczyk
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Growth hormone deficiency (GHD) comprises a spectrum of diseases. The disorder may consist of an isolated deficiency of GH, or it may be part of a syndrome of multiple pituitary hormone deficiencies (MPHD). Morphologic changes in the pituitary gland and stalk have been observed in a large percentage of these cases on MR images. Since the late 1980s, when these morphologic changes were first reported, there have been a large number of reports describing this disease in both the radiology and endocrinology literature. Some of these reports had large cohorts with series of over 100 patients. In the numerous publications that now exist on this topic, two hypotheses have been proposed about the etiology of this disease: perinatal head trauma and dysgenesis.

The earliest reports on the MR imaging findings in children with GHD documented a striking association between adverse perinatal events and breech delivery, leading to the hypothesis that birth or perinatal trauma might be the cause of the pituitary stalk transection that is observed so frequently in this disease. In 1990, Maghnie et al reported 37 cases of MPHD and GHD (1). Adverse perinatal events were present in 80% of those cases in which morphologic lesions were observable on MR images, but the incidence of perinatal events was much lower in those with normal-appearing MR images or isolated GHD. The authors speculated that the disease was a congenital syndrome worsened by breech delivery.

In the middle 1990s, reports appeared documenting an association of GHD and MPHD with midline anomalies of the brain, including lesions of the corpus callosum, septum pellucidum, and optic chiasm and nerves (2–4). A familial association also became recognized. Authors began to favor more strongly a genetic etiology for this disorder.

Triulzi et al published an important study with a series of 101 patients in 1994 (2). Only 32% of the patients in this series had a breech delivery. He concluded that the disease in the other 68% had to have a different cause. He also reported that 12% of the patients in his series had anomalies of the brain. He concluded that dysgenesis was the probable etiology of GHD and MPHD in the majority of cases, and he implied that breech presentation was the result of a fetal endocrinopathy, rather than breech presentation (with perinatal head trauma) being the cause of the endocrinopathy. Many subsequent papers, including the paper by Maintz et al in this issue of the AJNR (page 1116), have documented further familial occurrences of this disorder, lending more weight to the hypothesis that dysgenesis is the etiology of many, or even most, cases of GHD.

It seems reasonable to conclude that GHD and MPHD are genetically determined diseases in most cases, and that breech delivery has the potential to worsen the severity of the pituitary endocrinopathy. Although breech presentation is strongly associated with fetal hypopituitarism, breech presentation probably causes very few cases. That does not indicate that dysgenesis is the only cause of GHD and MPHD. It is well recognized that blunt head trauma can transect the stalk, and cases of stalk transection can result in GHD in children (4).

References

  1. ↵
    Maghnie M, Larizza D, Triulzi F, Sampaolo P, Scotti G, Severi F. Hypopituitarism and stalk agenesis: a congenital syndrome worsened by breech delivery? Horm Res 1991;35:104-108
    PubMed
  2. ↵
    Triulzi F, Scotti G, di Natale B, et al. Evidence of a congenital midline brain anomaly in pituitary dwarfs: a magnetic resonance imaging study in 101 patients. Pediatrics 1994;93:409-416
    Abstract/FREE Full Text
  3. Hellstrom A, Wiklund LM, Svensson E, Stromland K, Albertsson-Wikland K. Midline brain lesions in children with hormone insufficiency indicate early prenatal damage. Acta Paediatr 1998;87:528-536
    CrossRefPubMed
  4. ↵
    Yamanaka C, Momoi T, Fujisawa I, et al. Acquired growth hormone deficiency due to pituitary stalk transection after head trauma in childhood. Eur J Pediatr 1993;152:99-101
    CrossRefPubMed
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American Journal of Neuroradiology
Vol. 21, Issue 6
1 Jun 2000
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Etiology of Congenital Growth Hormone Deficiency
Walter Kucharczyk
American Journal of Neuroradiology Jun 2000, 21 (6) 1000;

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Etiology of Congenital Growth Hormone Deficiency
Walter Kucharczyk
American Journal of Neuroradiology Jun 2000, 21 (6) 1000;
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