Presentation: Child with multiple pituitary deficiency

A three-year-old girl is referred to the paediatric clinic by her GP because of short stature. She is tracking below the 0.4th centile, with no cause yet identified. There are no developmental concerns, and there is no family history of short stature. Biochemical tests have revealed growth hormone deficiency and thyroid stimulating hormone deficiency.

Genomic testing for combined pituitary hormone deficiency should be considered if endocrine investigations for short stature reveal deficiency in at least two pituitary hormones of neonatal or childhood onset, and no acquired cause is identified.

• Consult the National Genomic Test Directory. From here you can access the rare and inherited disease eligibility criteria, which provides information about individual tests and their associated eligibility criteria. You can also access a spreadsheet containing details of all available tests.
  • For information about how to arrange testing in Wales, Scotland or Northern Ireland, see our dedicated Knowledge Hub resource.
• To find out which genes are included on different gene panels, see the NHS Genomic Medicine Service (GMS) Signed Off Panels Resource.
• Decide which of the panels best suits the needs of your patient or family. For investigation of multiple pituitary deficiency, the appropriate test is:
  • R159 Pituitary hormone deficiency: This includes analysis of a small number of genes associated with pituitary hormone deficiency via a whole exome sequencing or gene panel test for the detection of small variants, and multiplex ligation-dependent probe amplification (MLPA) for the detection of copy number variants in DNA.
    • As this test does not include whole genome sequencing (WGS):
      • you can use your local Genomic Laboratory Hub test order and consent (record of discussion) forms; and
      • parental samples may be needed for interpretation of the child’s result. Parental samples can be taken alongside that of the proband, and their DNA stored, or can be requested at a later date if needed.
  • The majority of tests are DNA-based, and an EDTA sample (purple-topped tube) is required. Exceptions include karyotype testing and DNA repair defect testing (for chromosome breakage), which require lithium heparin (green-topped tube).
• Information about patient eligibility and test indications was correct at the time of writing. When requesting a test, please refer to the National Genomic Test Directory to confirm the right test for your patient.

For clinicians

• Genomics England: NHS Genomic Medicine Service (GMS) Signed Off Panels Resource
• Medline Plus: Combined pituitary hormone deficiency
• NHS England: National Genomic Test Directory

References:

• Castinetti F, Reynaud R, Quentien MH and others. ‘Combined pituitary hormone deficiency: Current and future status’. Journal of Endocrinological Investigation 2014: volume 38, pages 1–12 . DOI: 10.1007/s40618-014-0141-2

For patients

• British Society for Paediatric Endocrinology and Diabetes: Hypopituitarism (multiple pituitary hormone deficiency) (PDF, three pages)
• Child Growth Foundation
• The Pituitary Foundation