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Genetic evaluation for new mutation urged for patients with central hypothyroidism
Genetic evaluation for IGSF1 deficiency syndrome is recommended for all patients with central hypothyroidism without a known cause, according to study findings.
“Despite having been discovered only recently, this syndrome already encompasses more unique mutations and patients than all other known genetic causes of isolated central hypothyroidism combined,” the researchers wrote.
Wilma Oostdijk, MD, PhD, of Leiden University in the Netherlands, and colleagues evaluated 34 men, 35 boys, 53 women and three girls who are carriers of the IGSF1 gene mutation from 30 unrelated families to form recommendations for clinical management. Levothyroxine was used in 89% of boys, 44% of men and in 5% of the female cases.
Central hypothyroidism was present in all males and additional symptoms included small thyroid gland volume (74%), high birth weight (25%) and large head circumference (20%). Although there was a late rise in testosterone levels, timing of pubertal testicular growth was normal or premature.
Patients with prolactin deficiency experienced late adrenarche.
Six of 28 newborns who were evaluated had hypocortisolism; however, cortisol levels were normal later in life.
Eighteen percent of female carriers had low free thyroxine and 60% had low-normal free T4. Thirty-one percent experience menarche later than normal, 22% had mild prolactin deficiency and 57% had increase waist circumference.
“We advise genetic evaluation of all patients with central hypothyroidism of unknown cause for IGSF1 mutations, especially when accompanied by an X-linked inheritance pattern, prolactin or [growth hormone] deficiency, disharmonious pubertal development, macroorchidism or delayed adrenarche,” the researchers wrote. “As asymptomatic adult carriers are likely to benefit from treatment with levothyroxine, family members should be evaluated based on the X-linked inheritance pattern. All children or female carriers (and female children of male patients) should be screened at birth with [thyroid-stimulating hormone] and T4.” – by Amber Cox
Disclosure: The researchers report no relevant financial disclosures.