Bone Abstracts

Background: Congenital multiple hormone deficiency (CMHD) is a rare condition caused by mutations in transcription factors involved in pituitary ontogenesis¹. Incidence of mutations in POU1F1 gene in results between 3.8 and 7.7%². POU1F1 gene mutations lead to somatolactotroph and thryotroph deficiencies. Brain MRI can be normal or shows pituitary hypoplasia without extrapituitary anomalies.

Presenting problem: We describe the growth, the sexual development and the bone metabolism of a patient with CMHD due to a de novo Q167K mutation in POU1F1 gene at the heterozygous level³.

Clinical management: After investigations for hypoglycemic hypotonia, deficit of growth and cranio-facial dismorfism in a 8 months patient already in replacement therapy for a congenital hypothyroidism we found TSH, FT4, basal PRL, IGF1 and IGFBP3 under normal range. GH and TSH stimulating tests showed total unresponsiveness, so substitutive GH therapy was begun. The anterior pituitary gland was hypoplasic at brain MRI. The patient underwent periodic clinical, biochemical and radiological controls. Replacement therapy was adjusted with the patient’s weight, speed of growth and blood exams. At 7 years old the patient presented precocious puberty so she started Gonadotropin-releasing hormone agonists until 11 years old. At 10 years old vomiting and weakness expecially during stressfull events happened: ACTH was undetectable so we started hydrocortisone with disappearance of symptoms. Parameters of bone metabolism showed hypovitaminosis D, for which we gave supplementation with low compliance of the patient. The quantitative bone ultrasonometry showed normal Z Score of BTT and AD-SoS. The patient reached the height of 157.4 cm (−0.75 SDS) inside her target zone and the weight of 57.4 kg (0.20 SDS).

Discussion: There are no informations in litterature about bone metabolism in CHMD, besides the prematurity, the lack of endogenous hormones, the chronic use of drug (L-thyroxine at high doses, glucocorticoids, gonadotropin releasing hormone analogue) associated with this condition could interfere with bone metabolism. A good management of substitutive therapy could guarantee a normal growth, sexual development and bone densitometry together with supplementation of vitamin D. The lack of hypogonadism in POU1F1 mutation could be a protective factor for bone density. However an annual evalutation of bone metabolism could be useful in these patients.

Disclosure: The authors declared no competing interests.

References

1. Romero CJ et al., Novel mutations associated with combined pituitary hormone deficiency, Journal of molecular endocrinology (201), 46, 93-102.

2. Turton JP et al., Two novel mutations in the POU1F1 gene generate null alleles through different mechanisms leading to combined pituitary hormone deficiency, Clinical Endocrinology (2012), 76, 387–393.

3. Malvagia S et al., The De Novo Q167K mutation in the PU1F1 gene leads to combined pituitary hormone deficiency in an Italian patient, Pediatric research (2003), 54, 5, 635–640.

4. Stagi S et al., Bone health in children and adolescents: the avalaible imaging techiques, Clinical cases in mineral and bone metabolism, 2013, 10(3), 66–171.