Nancy A Melville

September 26, 2016

DENVER – Diagnosis of congenital primary hypothyroidism (CPH) is delayed in an alarming percentage of newborns, leaving them inadequately treated and therefore potentially exposed to unnecessary neurocognitive losses, according to a new study of a large birth cohort in Utah.

"Utah has a very [well-run] infrastructure, and my concern is that if we are missing the diagnosis in this many babies in Utah, I think we have a significant problem nationwide, and it just hasn't been looked at," first author Joel Ehrenkranz, MD, director of diabetes and endocrinology in the department of medicine, Intermountain Healthcare, Salt Lake City, Utah, said when presenting the findings here at the American Thyroid Association (ATA) 2016 Annual Meeting.

His data show that almost half of the infants they identified as having CPH had delayed diagnosis and a similar number had potentially inadequate treatment in the first few weeks of life.

Alex Stagnaro-Green, MD, regional dean of the University of Illinois College of Medicine at Rockford, who comoderated the session at the ATA meeting, commented that Dr Ehrenkranz's findings were "disquieting."

"The whole idea for having the screening is to make sure the newborn will develop normally, especially in terms of their neurocognitive abilities," he told Medscape Medical News.

"So to hear that there are issues where the screening is identifying children later than should be expected and where the treatment may also not have been to the extent recommended is worrisome.

"Our goal as physicians is to treat patients to make sure they have the ability to live up to their potential, so this is clearly something that needs to be pursued so we can make sure that this screening is effective," he concluded.

CPH Is an "Endocrine Emergency"

Under the guidelines of the American Academy of Pediatrics (AAP), congenital primary hypothyroidism — defined as a serum thyroid-stimulating hormone (TSH) level of 20 mIU/L or higher — should be diagnosed no later than the 14th day of life, and by 6 weeks, children should be biochemically euthyroid, with a serum TSH level below 5 mIU/L.

To evaluate compliance with these guidelines, Dr Ehrenkranz and his colleagues analyzed data on serum TSH assays of 4394 children under the age of 2 who had been referred for such testing at Intermountain Healthcare in Utah between 2006 and 2015.

Among the infants in the study, 98 (2%) were identified as having serum TSH samples that were above 20 mIU/L, including 82 (84%) that represented the initial TSH samples taken.

Nearly half of the 82 (39; 48%) had delayed diagnoses, with initial TSH samples that had not been taken in the first 14 days of life.

In terms of treatment follow-up, 12 of the 82 (15%) infants were not retested and 28 (34%) achieved goals of TSH levels of 5 mIU/L or lower within 28 days of the initial test; however, 42 (51%) showed one or more subsequent TSH values higher than 5 mIU/L 1 month or more after the initial TSH, indicative of inadequate treatment.

The consequences of delayed or inadequately treated CPH are potentially significant, Dr Ehrenkranz said.

"CPH is an endocrine emergency, because if untreated, a newborn baby can have irreversible losses of up to one-half an IQ point a day," he said.

The data also showed that 16 infants with TSH levels below 20 mIU/L on initial screening subsequently went on to develop elevated levels after 1 month of age, between the ages of 92 and 690 days.

Dr Ehrenkranz said those findings were perplexing.

"I don't know what this represents, but I think this is a very interesting cohort of patients with congenital hypothyroidism, which I refer to as 'late onset,' " he observed. "It is notable that of the 16 patients, three had multiple TSH tests that were greater than 20 mIU/L."

"A Bigger Problem Than We Thought"

Dr Ehrenkranz said he was prompted to look into the issue after observing that anecdotal reports of CPH are common.

"If you talk to pediatricians and hospitalists, they will tell you that it is not at all uncommon to see an infant 6 months or 9 months of age with CPH, so that piqued my interest."

"In the course of looking at data for the US Food and Drug Administration [FDA] to establish normal thyroid levels in newborns, we observed that a lot of the newborns had elevated levels of TSH, so we realized this is a bigger problem than we thought."

He added that some hospitals have published results indicating that they missed diagnoses as much as 10% of the time, "and that's probably an underestimate."

With screening and treatment, severe CPH, previously known as cretinism and associated with severe mental retardation, has been eradicated in the developed world; however, newborns can still suffer effects from delayed diagnosis or treatment, Dr Ehrenkranz told Medscape Medical News.

"In the first 3 months of life, when most of the neurogenesis is going on, it's very important that children have the appropriate amount of thyroid hormone," he said.

"I think people just assume the process works perfectly because we don't see true cretinism anymore, but you do see children who may not have been able to reach their cognitive potential."

A separate study underscores the potential cognitive risks to infants who are not properly screened [Lancet Diabetes Endocrinol. 2016; 4:756–765], with its results, from an Australian cohort, showing poor educational and developmental outcomes among infants with neonatal TSH concentrations in the highest percentiles.

Dr Ehrenkranz is the inventor of a TSH point-of-care immunoassay and of smartphone/tablet point-of-care diagnostics. He notes that the study was subject to independent review of all data. Dr Stagnaro-Green had no relevant financial relationships.

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American Thyroid Association (ATA) 2016 Annual Meeting; September 22, 2106; Denver, Colorado. Abstract 19.

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