A corticotroph pituitary adenoma as the initial presentation of familial glucocorticoid deficiency

Abstract

Context: Familial glucocorticoid deficiency (FGD) is a rare autosomal recessive ACTH-resistance syndrome characterized by glucocorticoid deficiency in the absence of mineralocorticoid deficiency. Here, we report the case of a young woman with a corticotroph pituitary adenoma as the initial presentation of FGD. Case report: A 15-year-old girl was referred to our institution for a 16 mm pituitary adenoma associated with glucocorticoid deficiency. Clinical and biological features were evocative of FGD. DNA sequencing did not identify mutations in either the melanocortin 2 receptor (MC2R) or the MC2R accessory protein genes, indicating type 3 FGD. Despite adequate glucocorticoid replacement, plasma ACTH levels remained increased and pituitary magnetic resonance imaging (MRI) showed a progression of the tumour size resulting in optic chiasm compression with intra-tumoural haemorrhaging. When the patient was 26 years old, it was decided that she would undergo transsphenoidal surgery. The histomorphological analysis identified a well-individualized pituitary adenoma immunoreactive for ACTH. The proband's sister also exhibited type 3 FGD associated with pituitary hyperplasia upon MRI. Conclusion: This case highlights the relationship between FGD and hyperplasia of ACTH-producing cells, potentially leading to histologically proven pituitary corticotroph adenomas. This observation raises the question of the pituitary MRI's significance in the follow-up of FGD.

Predicted Benign and Synonymous Variants in CYP11A1 Cause Primary Adrenal Insufficiency Through Missplicing

“…The main focus of the present study was to assess CYP11A1 in subjects with PAI of unknown etiology. The inclusion criteria included evidence of low cortisol, an attenuated cortisol response on cosyntropin stimulation testing, and elevated ACTH, with clinical signs of cortisol insufficiency and hyperpigmentation [15, 16] (Table 1). Some subjects also had elevated plasma renin activity and low aldosterone and/or electrolyte disturbances (hyponatremia, hyperkalemia) consistent with mineralocorticoid insufficiency.…”

The Glucocorticoid Receptor and its Expression in the Anterior Pituitary and the Adrenal Cortex: A Source of Variation in Hypothalamic-Pituitary-Adrenal Axis Function; Implications for Pituitary and Adrenal Tumors

“…To date, few other patients with CD have been found to have either somatic or germline GR-inactivating mutations (8,24). The important role of an intact HPA axis function and the normal expression of the GR in preventing corticotroph adenoma expansion (if not formation) is demonstrated by the cases of ACTH-producing tumors in patients with familial glucocorticoid deficiency (25), as well as the relatively frequent loss of heterozygosity, leading to hemizygosity and, thus, haploinsufficiency of the GR gene ( NR3C1 ) (26). …”

The molecular pathogenesis of corticotroph tumours

“…Cushing’s disease because of pituitary corticotroph hyperplasia has been described in a paediatric patient [106]. A corticotroph pituitary adenoma has also been reported as the initial presentation of familial glucocorticoid deficiency [107]. The combination of an ACTH‐producing microadenoma and corticotroph cell hyperplasia in the same patient has also been reported [108].…”