Combined pituitary hormone deficiency diagnosis often delayed

medwireNews: Childhood-onset combined pituitary hormone deficiency (CPHD) occurs in around one in 16,000 children, but its diagnosis is often delayed due to nonspecific presenting symptoms, say researchers.

Taneli Raivio (University of Helsinki, Finland) and study colleagues identified 124 children with CPHD treated at Helsinki University Hospital between 1985 and 2018. Based on the total number of children born in the hospital’s catchment area during this period, they calculated an estimated CPHD incidence of one in 16,000 live-born children.

The majority (61%) of these cases were acquired, mostly due to brain tumours, and presenting symptoms in these children were often related to the underlying pathology (71%). Nearly a third had symptoms of hypopituitarism at presentation, but some developed these only after treatment for a tumour.

Of the 48 children with congenital CPHD, 15% had a conclusive genetic diagnosis – a diagnosis rate the researchers say is in line with previous studies.

However, they found presenting symptoms to be frequently nonspecific, contributing to diagnostic delay. Of the 35 children with relevant data, 74% had signs of hypopituitarism during the neonatal period, including hypoglycaemia in 23, jaundice in 17 and micropenis and/or bilateral cryptorchidism in eight boys.

Nonetheless, five children with neonatal features of hypopituitarism did not undergo endocrine investigations within the first year of life. The age of congenital CPHD diagnosis ranged from early infancy to 11–12 years, say Raivio and team in eClinicalMedicine.

Nearly three-quarters of the congenital CPHD group had extra-pituitary phenotypic features, most frequently developmental delay or epilepsy (38%), craniofacial differences (27%) or abnormalities of the eyes (33%) or genitals (21%). And of the 26 assessed for growth, impaired velocity was seen in 46% by the age of 6 months and in 42% between 6 months and 4 years.

“While neonatal phenotypic features of CPHD led to investigations of CPHD in many patients with early growth retardation, 25% of them presented due to reduced growth only, which highlights the importance of growth monitoring in the early identification of CPHD”, say the researchers.

They also note that the children had a “remarkably long” median delay of 2.2 years between first evidence of impaired growth and start of recombinant human growth hormone treatment.

Reasons for this included choosing a watchful waiting approach, investigating more common causes of growth impairment and sometimes already having a “plausible explanation” such as an existing condition or treatment, say Raivio and colleagues.

“However, in some patients, the early diagnostic opportunity of CPHD based on growth retardation was indeed missed”, they stress.

All of the 41 congenital CPHD patients who underwent brain magnetic resonance imaging had abnormalities – 90% involving the pituitary and 61% other brain abnormalities.

“Persistent neonatal hypoglycemia, jaundice, and genital hypoplasia are important cues to early diagnosis of congenital CPHD”, conclude the researchers.

And they emphasise that “height growth deviation during the first six months of life should not go unnoticed in any patient since this is a manifestation of severe CPHD phenotype.”

By Eleanor McDermid

medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2022 Springer Healthcare Ltd, part of the Springer Nature Group

EClinicalMedicine 2022; doi:10.1016/j.eclinm.2022.101556
Martin Savage
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