Neonatal screening required for prompt central congenital hypothyroidism detection

medwireNews: The diagnosis of central congenital hypothyroidism (CH) with or without multiple pituitary hormone deficiencies (MPHD) is frequently missed in children, even among those admitted to hospital, say Dutch researchers.

Nitash Zwaveling-Soonawala (University of Amsterdam) and co-workers say their study of patients identified through a neonatal screening programme “illustrates the importance of a [thyroxine] T4-based neonatal screening program to ensure early diagnosis of central CH.”

“It also highlights the need to improve awareness of this rare disorder among clinicians since most patients, especially in [the] case of MPHD, were not recognized despite the presence of classic symptoms such as hypoglycemia, jaundice and micropenis”, they emphasise.

Overall, 154 children were diagnosed with central CH following screening between 1995 and 2015. Of these, permanent central CH was recorded in 148 patients, giving an incidence of one case per 25,642 children, the authors report in the European Journal of Endocrinology.

After excluding patients who had died, had a severe syndrome, or a transient diagnosis of central CH, 126 patients were eligible for medical chart review; 92 patients from 89 families gave permission for this process, the majority of whom were male (79%) and had MPHD (62%).

Most of the isolated central CH (86%) and MPHD (63%) patients were born from mothers without health issues or medication.

Sixty-one of the children were admitted to hospital before their screening results were available, including 50 patients with MPHD, but central CH was diagnosed from clinical findings in just three (5%) of these cases.

Nevertheless, 86% of patients began treatment within a month of birth, with thyroxine commenced by MPHD patients at a median age of 17 days, say the researchers, who note that without neonatal screening the average age of endocrine assessment for central CH has been reported to be 16 months.

Patients with MPHD were more likely than those with isolated central CH to have hypoglycaemia, with a significantly lower glucose concentration during an episode (average difference –0.9 mmol/L), as well be diagnosed with hyperbilirubinaemia and sepsis-like illness.

MPHD patients also had significantly lower free T4 levels before treatment than those with isolated central CH (average difference –1.7 pmol/L).

Among the MPHD patients, the most common pituitary hormone deficiency was a combination of TSH, adrenocorticotropic hormone (ACTH) and growth hormone (GH), which affected 47% of the cohort. A further 35% were deficient in TSH, ACTH, GH and luteinising hormone/follicle-stimulating hormone, while 14% were deficient in TSH and GH, and 4% in TSH and ACTH.

Gonadotrophin deficiency occurred in 74% of the 20 MPHD patients old enough for pubertal assessment, but five boys had no evidence of micropenis or cryptorchidism, “implying that normal male genitalia early in life does not exclude [gonadotrophic deficiency]”, Zwaveling-Soonawala et al remark.

Brain magnetic resonance imaging findings were assessed for 73 patients. None of the 19 patients with isolated central CH had abnormalities detected whereas 50 of the 54 MPHD patients had an ectopic posterior pituitary, anterior pituitary hypoplasia and/or pituitary stalk abnormalities. One patient with pituitary stalk interruption syndrome and another patient with septo-optic dysplasia also had optic nerve hypoplasia.

“This is the largest group of early-detected central CH patients reported on to date, providing insight into the yield of a central CH screening program”, say Zwaveling-Soonawala and co-authors.

Acknowledging an earlier study of Dutch children, the team believes the incidence of central CH has remained stable in the Netherlands but notes that it is higher than reported for screening programmes Buenos Aires, Argentina, and Indiana, USA.

This is likely related to the use of a fixed T4 cutoff in these countries, whereas the Dutch programme recommends immediate referral for a T4 concentration less than –3.0 standard deviations (SD) of the daily mean, with an additional TSH measurement for a concentration of less than –0.8 SD of the daily mean, and TSH and thyroxine-binding globulin measurement for a T4 concentration below –1.6 SD.

“As a result of this unique program a higher number of central CH patients is detected, including milder cases with T4 concentrations which are on average higher compared to cases from Buenos Aires and Indiana”, the team concludes.

By Lynda Williams

medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2020 Springer Healthcare Ltd, part of the Springer Nature Group

Eur J Endocrinol 2020; doi:10.1530/EJE-20-0833
Martin Savage
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