Global Adrenal Insufficiency in Two Independent Patients Carrying the Same Homozygous c.172A&gt;G, p.(Thr58Ala) Mutation in the <i>TBX19</i> Gene

Author:

Holterhus Paul-Martin,Roll Claudia,Gaida Barbara,Richter-Unruh Annette,Kulle Alexandra E.ORCID,Kaschta Daniel,Hartmann Michaela F.,Wudy Stefan A.,Reinehr ThomasORCID

Abstract

<b><i>Introduction:</i></b> <i>TBX19</i> mutations cause isolated ACTH-deficiency. While this classically results in severe hypocortisolism, potential consequences for mineralocorticoid biosynthesis have not been described to date. Liquid chromatography mass spectrometry (LC-MS/MS) and gas chromatography mass spectrometry (GC-MS) allow novel insights into the steroid metabolism of pediatric endocrine diseases. <b><i>Case Presentation:</i></b> Patient 1 (female) presented right after birth with hypoglycemia and hyponatremia (minimum sodium 126 mmol/L). She recovered under therapy with hydrocortisone, fludrocortisone and initial NaCl. Patient 2 (male) presented after birth with prolonged cholestatic jaundice. Only at the age of 3.5 months, repeated episodes of hypoglycemia occurred. Both patients showed severely reduced ACTH. LC-MS/MS analyses on plasma samples demonstrated combined reduced glucocorticoid- and mineralocorticoid biosynthesis confirmed by GC-MS analyses on spot urine. In contrast to patient 1, patient 2 (currently 8 years old) never suffered from hyponatremia. Both patients carry the same homozygous c.172A&gt;G, p.(Thr58Ala) mutation in the <i>TBX19</i> gene proving isolated ACTH-deficiency. <b><i>Conclusion:</i></b> Isolated ACTH-deficiency can be associated with reduced mineralocorticoids and hyponatremia. We hypothesize that sufficient pituitary ACTH secretion is an important predisposition for regular adrenal mineralocorticoid biosynthesis.

Publisher

S. Karger AG

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