medwireNews: A collaborative study details the symptoms of patients with immunoglobulin superfamily, member 1 (IGSF1) deficiency and offers guidance for their management.

“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”, say researcher Wilma Oostdijk (Leiden University Medical Center, the Netherlands) and colleagues.

Their study includes 69 affected males (including 35 children) and 56 female mutation carriers (including three children) from 30 unrelated families.

All male patients had central hypothyroidism, as did 18% of female carriers, so the researchers advise testing for IGSF1 mutations in all patients with otherwise unexplained central hypothyroidism.

Patients should especially be tested if there is an X-linked inheritance pattern, they say, and also if the patient has macroorchidism (detected in 88% of adult males) and “disharmonious” pubertal development (75% of males; 31% of female carriers). Other key symptoms are prolactin deficiency (61% of males; 22% of female carriers), childhood growth hormone deficiency (16% of males) and delayed adrenarche (50% of males).

Other common symptoms in male patients are low–normal testosterone levels in adulthood (88%), mild problems with attentional control (75%), a small thyroid gland (74%) and an increased waist circumference in both adults and children (57–59%).

The researchers advise screening family members of patients with IGSF1 mutations. They detail their recommended tests for males and females found to have mutations and advise levothyroxine treatment for all boys. And they add: “As asymptomatic adult carriers are likely to benefit from treatment with levothyroxine, family members should be evaluated based on the X-linked inheritance pattern.”

The team suggests trying levothyroxine treatment in all adult male patients and in female carriers with low T4 levels if they also show evidence of tissue hypothyroidism. Patients experienced many benefits of treatment, they say, including correction of jaundice and growth delay and major improvements in energy levels.

“On the other hand, untreated adults were generally well-functioning, well-educated, of normal height, rarely showed dyslipidemia or cardiovascular disease, and were not more obese than their treated peers”, say Oostdijk et al.

The team recommends genetic testing at birth for female children of IGSF1 deficiency patients and all children of carriers, and provision of hydrocortisone for neonates with an impaired cortisol response. They also advise testosterone in boys with delayed pubertal development and recombinant human growth hormone (rhGH) treatment in children, as indicated.

“As GH [deficiency] proved transient in most, but not all, patients treated with rhGH, GH stimulation tests should be repeated after reaching adult height”, they add.

By Eleanor McDermid, Senior medwireNews Reporter

J Clin Endocrinol Metab 2016; Advance online publication

medwireNews is an independent medical news service provided by Springer Healthcare Limited. © Springer Healthcare Ltd; 2016

Free abstract