Congenital central hypothyroidism plusminus ACTH or growth hormone deficiency: etiology and outcome

Congenital hypothyroidism (CH) can be of thyroidal or central origin. Central
CH (CH-C) can be isolated or occur within the framework of multiple anterior
pituitary hormone deficiency (MPHD). In the Netherlands from 1994 onwards CH-C
is effectively detected by way of a unique neonatal screening strategy. This
has led to a cohort of early treated children with CH-C in the Netherlands.
Such a cohort of early treated children with CH-C has never been reported on
and many questions still remain regarding mortality, morbidity of early treated
CH-C and etiology.
By collecting data on mortality and morbidity we will provide further insight
in the benefit of screening for CH-C which may lead to changes in neonatal
screening programs worldwide. Most screening programs worldwide do not detect
CH-C. Recently,a high percentage of developmental delay was reported in a
retrospective study of late diagnosed CH-C patients (56% developmental delay)
In this study also the genetic/molecular physiological background may be
further unraveled.

In this predominantly observational study all patients diagnosed with CH-C in
the Netherlands between 1-1-1995 and 1-1-2015 will be traced and the following
research questions will be addressed:
1) What is the mortality rate associated with early diagnosed CH-C within the
framework of MPHD?
2) What is the developmental and psychosocial outcome of children with early
diagnosed and treated CH-C?
3) What is the genetic/molecular physiologic background of isolated CH-C and
CH-C within the framework of MPHD?

The whole cohort of children diagnosed with permanent congenital CH-C between
1-1-1995 and 1-1-2015 will be traced. The names of the pediatric
endocrinologists and pediatricians caring for these children are registered by
TNO Leiden. All children and their parents will be contacted through their
treating doctor. The details of the Medical charts will be reviewed with
respect to medical/treatment history, and growth/pubertal development. Cause of
death will be well documented.
As a measure of cognitive outcome we will use school results, results of
intelligence tests and results of questionnaires regarding psychosocial
functioning. Permission will also be asked to retrieve school results of
siblings. Siblings will also be asked to fill in questionnaires regarding
psychosocial functioning. These questionnaires may be filled in at home online.

Children and their parents will be invited to visit the Academic Medical Center
for an interview, physical examination and an intelligence test. A single
venous blood collection will be performed for genetic analysis and, if
necessary, additional endocrine laboratory investigations. Intelligence testing
will also be performed in siblings. A single venous blood collection will be
performed for genetic analysis and, if necessary, additional endocrine
laboratory investigations.

The burden to the subjects is minimal and consists of filling in online
questionnaires, one visit to the Academic Medical Center in Amsterdam for a
structured interview, physical examination, intelligence test and one venous
blood collection to obtain 4-10 ml blood.