By: Damian McNamara | May 31, 2024 | 6 min. read |
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Summary of the article
- Dr Roy Weiss was part of a research team that discovered the genetic explanation for the inherited condition, resistance to TSH.
- The researchers found that genetic changes in the non-coding region of chromosome 15 lead to resistance to TSH.
- Dr. Weiss believes that a greater understanding of these non-coding regions could lead to increased knowledge about other genetic diseases.
Miami cardiologist Cintia Cuperman’s first born son tested positive for congenital hypothyroidism in 2002. Her family doctor initially thought it was a false positive. Only one in about 4,000 babies is born with a malfunction of the thyroid gland that produces low levels of thyroid hormone and results in high levels of thyroid-stimulating hormone (TSH).
“We read some ourselves,” said Dr. Cuperman. “My husband and I are both doctors, and we could tell something was going on that we should be concerned about.”
In the first few weeks, before they were referred to an endocrinologist, “we were terrified,” added Dr. Cuperman.
More thyroid exam abnormalities
When the couple had twins, both children also had abnormal thyroid tests. They underwent thyroid hormone treatment for years to avoid associated health risks, including poor growth and neurological and cognitive impairments.
Children of Dr. The Cupermans are adults now and recently discovered they no longer need therapy. Roy E. Weiss, MD, Ph.D., professor and chairman of the Department of Medicine at the University of Miami Miller School of Medicine, delivered the good news.
“I was able to convince them and their doctors not to treat them because otherwise they would have been inappropriately treated with thyroid hormones for the rest of their lives,” said Dr. Weiss, also Rabbi Morris I. Esformes Endowed Chair in Medicine and Endocrinology and the Kathleen & Stanley Glaser Distinguished Chair in Medicine. “Their thyroid tests were not consistent with the type of congenital hypothyroidism that needed treatment.”
In some cases, newborns screened for congenital hypothyroidism have high TSH but normal thyroxine hormone levels. Children of Dr. Cupermans have this rare, congenital thyroid condition known as TSH resistance.
“The important clinical implication is to make the correct diagnosis, as most of these patients do not need any treatment and are misdiagnosed as hypothyroid,” said Dr. Weiss. “Misdiagnosis forces them into a lifetime of thyroid hormone treatment and unnecessary blood tests.”
The Mystery of TSH Resistance
Resistance to TSH at birth has been a long-standing mystery, until now.
Dr. Weiss and fellow researchers Samuel Refetoff, MD, from the University of Chicago Medicine, Helmut Grasberger, MD, from the University of Michigan and others found a genetic explanation in an unexpected place. They knew for years that the genetic variants associated with TSH resistance were on chromosome 15. They recently identified genetic changes in the non-coding region of this chromosome, a discovery published in the prestigious journal. Genetics of Nature.
As we better understand the function of the majority of the genome, the non-coding regions, we will learn more not only about thyroid function, but also about the genetics of other diseases.
— Dr. Roy Weiss
Importantly, they discovered how non-coding regions resulted in the clinical syndrome. A separate team of researchers in Japan made a similar discovery about the molecular mechanism behind this condition and published their work in the same issue of the journal.
Their discovery could lead to finding more genetic changes and helping people with other inherited or Mendelian genetic conditions. Dr. Weiss and researchers identified noncoding mutations in a short tandem repeat as the underlying cause of the condition in all affected individuals.
These mutations occur in primate-specific DNA known as the Alu retrotransposon, also found in gorillas. Previous studies have shown that some gorillas also have high TSH and normal thyroid hormone thyroid tests, which are similar to TSH resistance.
“This is the exciting part, as we don’t know how often disease is caused by the 98% of total DNA that is non-coding,” said Dr. Weiss. “As we better understand the function of the majority of the genome, the non-coding regions, we will learn more not only about thyroid function, but also about the genetics of other diseases.”
Much of the genetic discovery took place in the laboratory of Dr. identify affected children and families.
One of the families was that of Dr. Cuperman, which Dr. Weiss first met him in 2012. Two years later, they became his patients in Miami and continue to this day.
As groundbreaking as this genetic discovery is, questions about treatment persist, said Dr. Weiss. But the sons of Dr. The Cupermans are doing well and are no longer on thyroid hormone replacement.
“They’re super, super healthy,” she said. “They’re both playing college football—you know, thriving.”
Label: Division of Endocrinology, Diabetes and Metabolism, Dr. Roy Weiss, hypothyroidism, TSH resistance
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Image Source : news.med.miami.edu
