Abstract
Congenital isolated adrenocorticotropic hormone (ACTH) deficiency (IAD) is a rarely seen disease characterized by low serum ACTH and cortisol levels accompanied by normal levels of the other anterior pituitary hormones. In these patients, severe hypoglycemia, convulsions, and prolonged cholestatic jaundice are expected findings in the neonatal period. In this paper, we present two siblings with TBX19 gene mutation. The first case was investigated at the age of 2 months for severe hypoglycemia, recurrent convulsions, and prolonged cholestatic jaundice persisting since the neonatal period. The second sibling presented with hypoglycemia in the neonatal period. In both cases, baseline cortisol and ACTH levels were low and cortisol response to the low-dose ACTH test was inadequate, while all other anterior pituitary hormones were normal. Thus, IAD was suspected. Genetic analysis of the TBX19 gene was performed. Both cases were homozygous for c.856 C>T (p.R286*), and hydrocortisone treatment was initiated. The first patient did not attend the clinic regularly. On attendance at another hospital, hydrocortisone treatment was discontinued and antiepileptic treatment was initiated because of suspected epilepsy. This led to developmental delay, measured with the Denver Developmental Screening Test II (DDST-II), because of cessation of the hydrocortisone therapy. The second sibling had normal development, as measured with the DDST. In conclusion, TBX19 gene analysis must be performed if adrenal insufficiency is associated with isolated ACTH deficiency. Delay in diagnosis may lead to inappropriate diagnoses, such as epilepsy, and thus inappropriate therapy, which may result in neonatal mortality.
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References
Lamolet B, Pulichino AM, Lamonerie T et al (2001) A pituitary cell-restricted T-box factor, Tpit, activates POMC transcription in cooperation with Pitx homeoproteins. Cell 104:849–859
Couture C, Saveanu A, Barlier A et al (2012) Phenotypic homogeneity and genotypic variability in a large series of congenital isolated ACTH-deficiency patients with TPIT gene mutations. J Clin Endocrinol Metab 97:486–495
Vallette-Kasic S, Figarella-Branger D, Grino M, et al (2003) Differential regulation of proopiomelanocortin and pituitary-restricted transcription factor (TPIT), a new marker of normal and adenomatous human corticotrophs. J Clin Endocrinol Metab 88: -3056
Pulichino AM, Vallette-Kasic S, Couture C et al (2003) Human and mouse Tpit gene mutations cause early onset pituitary ACTH deficiency. Genes Dev 17:711–716
Akcan N, Serakıncı N, Turkgenc B, Bundak R, Bahceciler N, Temel SG, 2017 A Novel TBX19 gene mutation in a case of congenital isolated adrenocorticotropic hormone deficiency presenting with recurrent respiratory tract infections. Front Endocrinol 18;8:64
Krude H, Biebermann H, Gruters A (2003) Mutations in the human proopiomelanocortin gene. Ann N Y Acad Sci 994:233–239
Farooqi IS, Volders K, Stanhope R et al (2007) Hyperphagia and early-onset obesity due to a novel homozygous missense mutation in prohormone convertase 1/3. J Clin Endocrinol Metab 92:3369–3373
Thompson-Branch A, Havranek T (2017) Neonatal hypoglycemia. Pediatr Rev 38:147–157
Dennis EC (1985) Isolated ACTH deficiency in childhood: lack of response to corticotropin-releasing hormone alone and in combination with arginine vasopressin. J Pediatr 107:925–928
Metherell LA, Savage MO, Dattani M et al (2004) TPIT mutations are associated with early onset, but not late-onset isolated ACTH deficiency. Eur J Endocrinol 151:463–465
Vallette-Kasic S, Brue T, Pulichino AM et al (2005) Congenital isolated adrenocorticotropin deficiency: an underestimated cause of neonatal death, explained by TPIT gene mutations. J Clin Endocrinol Metab 90:1323–1331
Weintrob N, Drouin J, Vallette-Kasic S et al (2006) Low estriol levels in the maternal triple-marker screen as a predictor of isolated ACTH deficiency caused by a new mutation in the TPIT gene. Pediatrics 117:322–327
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Unal, E., Yıldırım, R., Taş, F.F. et al. A rare cause of neonatal hypoglycemia in two siblings: TBX19 gene mutation. Hormones 17, 269–273 (2018). https://doi.org/10.1007/s42000-018-0028-2
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DOI: https://doi.org/10.1007/s42000-018-0028-2