ESPE Abstracts (2015) 84 P-3-602

The First Case of Primary Generalized Glucocorticoid Resistance in Serbia in an 8-Year-Old Boy with G679S Mutation of the NR3C1 Gene

Katarina Mitrovica, Rade Vukovica, Tatjana Milenkovica, Sladjana Todorovica, Ljiljana Plavsica & Dragan Zdravkovica,b

aMother and Child Healthcare Institute of Serbia, Belgrade, Serbia; bMedical Faculty University of Belgrade, Belgrade, Serbia

Background: Primary generalized glucocorticoid resistance (PGGR) is a rare genetic condition characterised by generalised, partial target-tissue insensitivity to glucocorticoids owing to inactivating mutations of the NR3C1 gene.

Case presentation: An 8.5-year-old boy was hospitalized because of precocious puberty and arterial hypertension. Over the last year, the appearance of pubic hair and gynecomastia were noted. At the local centre, high levels of ACTH, cortisol, testosterone and 24-h urinary free cortisol excretion were noted, as well as hypokalemia, alkalosis and pubertal response during LHRH test. Abdominal CT scan was normal, while head MRI showed pituitary microadenoma of 3 mm in diameter. Patient was started on dexamethason and GnRH agonist therapy. Hypertension was treated by spironolactone, propranolol and captopril therapy. On admission to our hospital he was tall (90th percentile) and obese (BMI 22.2 kg/m2 at 97th percentile) with arterial hypertension. No striae were noted and obesity was not centripetal in pattern. Serum cortisol levels were high with preserved diurnal variation. Morning serum cortisol was suppressed only after high-dose dexamethason test. Highly elevated ACTH level was noted, as well as elevated levels of 17-hydroxyprogesterone, DHEA, DHEAS, 11-deoxycorticosterone and testosterone. Urinary catecholamines, metanephrines and normetanephrines were normal. A boy and his parents undergo genetic investigation. The entire coding region, of the human glucocorticoid receptor gene (hGR, NR3C1) and the intron/exon junctions, were amplified by PCR and bi-directionally sequenced. Boy was found to be homozygote for the mutation G679S in exon 8 of the NR3C1 gene.

Conclusion: We are presenting a first case of PGGR diagnosed in Serbia. Despite the fact that PGGR is a very rare disease, it is associated with severe and refractory hypertension and must be considered in a child with precocious pubarche.

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