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Hepatomegaly and fatty liver disease secondary to central hypothyroidism in combination with macrosomia as initial presentation of IGSF1 deficiency syndrome

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Abstract

Purpose

IGSF1 deficiency syndrome (immunoglobulin superfamily member 1) is considered the most common sex-linked cause of secondary congenital hypothyroidism and is characterized by a wide variety of other clinical and biochemical features, including hypoprolactinemia, transient and partial growth hormone deficiency, early/normal timing of testicular enlargement but delayed testosterone rise in puberty, and adult macro-orchidism. Congenital central hypothyroidism is a rare disease (1:65,000 births); the detection of which may be delayed and missed by neonatal screening programs since most neonatal screening programs are based on TSH determination in dried blood spots only. Untreated hypothyroidism may cause abnormal liver biochemistry and non-alcoholic fatty liver disease. Our aim is to report a case of secondary hypothyroidism in an infant with an uncommon initial presentation.

Case presentation (methods/results)

A 3-month-old male baby was referred to our hospital due to elevated alpha-fetoprotein levels, hypercholesterolemia, and macrosomia. Initial investigations revealed enlarged fatty liver and central hypothyroidism. Pituitary insufficiency was biochemically excluded and a pituitary MRI showed normal findings. Upon genetic analysis, a hemizygous variant NM_001170961.1:c.2422dup, p.(His808Profs*14), in IGSF1 gene was detected, establishing the diagnosis of the IGSF1 deficiency syndrome. In our patient, no other clinical findings were identified. Treatment with levothyroxine led to the remission of liver disease.

Conclusion

Liver disease may be the initial presentation of secondary hypothyroidism in neonates and infants. Macrosomia in patients with isolated secondary central hypothyroidism is a strong indicator of IGSF1 syndrome.

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Data availability

The datasets generated during and/or analyzed during the current study are not publicly available due to patient confidentiality agreements but are available from the corresponding author upon reasonable request.

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Authors and Affiliations

  1. Division of Endocrinology, Metabolism, and Diabetes, First Department of Pediatrics of the Medical School of Athens, National and Kapodistrian University of Athens, “Aghia Sophia” Children’s Hospital, Athens, Greece

    Michaela Nikolaou, Ioannis-Anargyros Vasilakis & Christina Kanaka-Gantenbein

  2. Laboratory of Medical Genetics, National and Kapodistrian University of Athens, “Aghia Sophia” Children’s Hospital, Athens, Greece

    Nikolaos M. Marinakis, Faidon-Nikolaos Tilemis & Joanne Traeger-Synodinos

  3. Research University Institute for the Study and Prevention of Genetic and Malignant Diseases of Childhood, National and Kapodistrian University of Athens, “Aghia Sophia” Children’s Hospital, Athens, Greece

    Nikolaos M. Marinakis

  4. First Department of Pediatrics of the Medical School of Athens, National and Kapodistrian University of Athens, “Aghia Sophia” Children’s Hospital, Athens, Greece

    Aglaia Zellos, Evangelia Lykopoulou & Christina Kanaka-Gantenbein

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  1. Michaela Nikolaou
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  8. Christina Kanaka-Gantenbein
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Correspondence to Michaela Nikolaou.

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Ethical approval

This study was obtained from Aghia Sophia Children’s Hospital Scientific and Ethics Committee (Approval number: 3669/12-02-18) and the parents of the proband provided their written informed consent for the participation of their child in the present study and the publication of the details of their medical case.

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Nikolaou, M., Vasilakis, IA., Marinakis, N.M. et al. Hepatomegaly and fatty liver disease secondary to central hypothyroidism in combination with macrosomia as initial presentation of IGSF1 deficiency syndrome. Hormones 22, 515–520 (2023). https://doi.org/10.1007/s42000-023-00468-0

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