National Center for Advancing and Translational Sciences Genetic and Rare Diseases Information Center, a program of the National Center for Advancing and Translational Sciences

Congenital hypopituitarism



Other Names:
Congenital combined pituitary hormone deficiency; Non-acquired combined pituitary hormone deficiency

The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.
orphanet

Orpha Number: 467

Definition
Congenital hypopituitarism is characterized by multiple pituitary hormone deficiency, including somatotroph, thyrotroph, lactotroph, corticotroph or gonadotroph deficiencies, due to mutations of pituitary transcription factors involved in pituitary ontogenesis.

Epidemiology
Congenital hypopituitarism is rare compared with the high incidence of hypopituitarism induced by pituitary adenomas, transsphenoidal surgery or radiotherapy. The incidence of congenital hypopituitarism is estimated to be between 1:3000 and 1:4000 births.

Clinical description
Clinical presentation is variable, depending on the type and severity of deficiencies and on the age at diagnosis. If untreated, main symptoms include short stature, cognitive alterations or delayed puberty.

Etiology
Congenital hypopituitarism is due to mutations of several genes encoding pituitary transcription factors. Phenotype varies with the factor involved: PROP1 (somatolactotroph, thyrotroph, gonadotroph and sometimes corticotroph deficiencies; pituitary hyper and hypoplasia), POU1F1 (somatolactotroph and thyrotroph deficiencies, pituitary hypoplasia), HESX1 (variable pituitary deficiencies, septo-optic dysplasia), and less frequently LHX3 (somatolactotroph, thyrotroph and gonadotroph deficiencies, limited head and neck rotation) and LHX4 (variable pituitary deficiencies, ectopic neurohypophysis, cerebral abnormalities).

Diagnostic methods
A diagnosis of combined pituitary hormone deficiency (CPHD) must be suspected when evident causes of hypopituitarism (sellar tumor, postsurgical or radioinduced hypopituitarism. . .) have been ruled out. Clinical, biological and radiological work-up is very important to better determine which transcription factor should be screened. Confirmation is provided by direct sequencing of the transcription factor genes.

Genetic counseling
Type of transmission varies with the factor and the mutation involved (recessive transmission for PROP1 and LHX3, dominant for LHX4, autosomal or recessive for POU1F1 and HESX1).

Management and treatment
An appropriate replacement of hormone deficiencies is required. Strict follow-up is necessary because patients develop new deficiencies (for example late onset corticotroph deficiency in patients with PROP1 mutations).

Prognosis
Prognosis is equivalent to patients without pituitary deficiencies if treatment is started immediately when diagnosis is confirmed, and if a specialized follow-up is performed.

Visit the Orphanet disease page for more resources.
Last updated: 3/1/2008

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Healthcare Resources


These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

In-Depth Information

  • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
  • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.

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