Pituitary morphology in the GH deficiency for mutation in the growth hormone-releasing hormone receptor gene

PITUITARY MORPHOLOGY IN THE GH DEFICIENCY FOR MUTATION IN THE GROWTH HORMONE-RELEASING HORMONE RECEPTOR GENE. (ABSTRACT)^*. DISSERTATION. ARACAJU, 2001.

HÉLIO ARAÚJO OLIVEIRA^**

The objectives of this study were: to evaluate the pituitary morphologic characteristics by NMR examinations, of the pituitary-hypothalamus region in affected homozygous adults and children individuals and in heterozygous adults individuals, all with a mutation (IVS1 + 1G ® A) in the receptor gene of the releasing hormone of the growth hormone (GHRH-R); to compare the values of the pituitary volume and the cranial volume of the affected homozygous adults individuals, with the values of a group of non-affected adults individuals of the same region; to verify the occurrence of pituitary hypoplasia, morphology of the pituitary stalk and neurohypophisis location in the affected adults and children group.

We studied 38 individuals from the community of Carretéis and surroundings ¾ Itabaianinha-SE. They were divided in 4 groups: Group I ¾ 9 adults (5M and 4F), normal homozygous (WT / WT), with age of 38 ± 11.7 years (Control Group); Group II ¾ 13 adults (6M and 7F), heterozygous (MUT / WT), with age of 42.33 ± 8.60 years; Group III ¾ 8 adults (3M and 5F), affected homozygous (MUT / MUT), with age of 41.37 ± 15.04 years; Group IV ¾ 8 children (3M and 5F), affected homozygous, with age of 11.87 ± 2.47 years.

The affected homozygous individuals (MUT / MUT) had a particular clinical phenotype: short stature, sharp voice timbre, cherubim facies, central obesity, thin and wrinkled skin, very reduced IGF-1 concentration and GH response to the clonidina and insulin hypoglycemic tests.

All individuals were evaluated regarding: anthropometric measures (stature, head circunference and cranial volume) and IGF-1 concentration. Pituitary-hypothalamus region was examined by NMR scans. Pituitary height, length and width were measured in order to build its volume by using the cubic (V= h . l . w ) and elliptical (V= h . l. w / 2) shapes. Pituitary volume and the cranial volume were compared through the following variations: Pituitary Volume Fraction (PVF), Cranial Volume Fraction (CVF) and Volume Ratio (VR). The statistical analysis was carried out through the SSPS.8.0 program (Statistical Packet for Social Science) and data expressed in average ± SD. It was considered statistical significance when p < 0.05.

In adults cephalic perimeter showed no difference between Groups I and II (54.66 ± 1.22 cm and 54.57 ± 1.63 cm respectively) and was reduced in Group III (50.42 ± 1.14 cm).

There was no difference is pituitary height between Groups I and II (4.41 ± 0.62 mm and 4.61 ± 1.55 mm respectively). In Group III, the pituitary height was 2.67 ± 0.87 mm and the pituitary height SDS, -1.95 ± 0.58; in Group IV, the pituitary height was 2.87 ± 0.79 mm and the pituitary height SDS, ¾2.84 ± 0.04. Pituitary hypoplasia was present in all Group IV individuals and in 5/8 of Group III patients.

The pituitary volume resulted normal in Groups I and II (414.56 ± 71.57 mm³ and 417.12 ± 140.86 mm³ respectively), meanwhile in Groups III and IV (124.13 ± 64.23 mm³ and 155.68 ± 39.79 mm³ respectively) they were reduced, characterizing the pituitary hypoplasia, it seems to be due to a presence decrease of the somatotrophs resulted from the genetic involvement in the GHRH-R gene that blocks GHRH action.

A comparative study was developed between the pituitary and the cranial volumes , through the PVF, the CVF and the VR. There was no difference between Groups I and II, in PVF (1/1) and CVF (1 / 0.99). When the comparison was done between Groups I and III, the PVF (1 / 0.29) has a difference of 71% while the CVF (1 / 0.78) has a difference of 22%.

Groups I and II VR had the same values (0.015 ± 0.040); in Groups III and IV, the values (0.006 ± 0.02) were 3 times lower than Groups I and II. The relation pituitary / cranial volume is 0.015% in Groups I and II and 0.006% in Groups III and IV.

In the affected homozygous treated children (Group IV), it was observed that pituitary hypoplasia was present for the entire group (the pituitary height SDS, ¾2.84 ± 0.79), when compared before and after treatment, an increase in both stature and a cephalic perimeter was found. The treatment of the affected children with recombining GH influences more the height bone growth and the cephalic perimeter.

We conclude that there is a pituitary hypoplasia in the homozygous adults and children individuals affected by the IVS1 + 1A ® G mutation. The decrease of the pituitary volume is higher than the decrease of the cranial volume in the affected homozygous individuals. The decrease of pituitary volume is not exclusively due to decrease of the cranial volume but on the reduction of the somatotrophs too.

Pituitary volume was similar in heterozygous and normal homozygous individuals.

All analyzed individuals had complete pituitary stalk and neurohipophisis in topical location.

The finding of hypoplasia isolated from the pituitary suggests the DIGH presence, especially by the GHRH-R mutation.

KEY WORDS: pituitary hypoplasia, nanism, GHRH-R mutation.

**Andress: Rua Reginaldo Passos Pina 261, 49040-720 Aracaju SE, Brasil. E-mail: [e-mail]

*

Morfologia da hipófise na deficiência de GH por mutação no receptor do hormônio liberador do GH (Resumo). Dissertação de Mestrado. Universidade Federal de Sergipe (Área: Medicina). Orientador: Manuel Hemínio de Aguiar Oliveira.

Publication Dates

• Publication in this collection
  10 Sept 2002
• Date of issue
  Sept 2002