An Unusual Case of Hypercortisolemia

Presentation Number: MON 414
Date of Presentation: April 3rd, 2017

Ji Wei Yang*, Maria Daniela D'Agostino and Juan Andres Rivera
McGill University Health Center, Montreal, QC, Canada

Abstract

Background: Chrousos syndrome is a rare condition characterized by tissue insensitivity to glucocorticoids (GC). Patients may have manifestations of mineralocorticoid and/or androgen excess due to compensatory high ACTH. Clinical case: A 56-year-old woman was referred to endocrinology for assessment post-adrenalectomy. Her past medical history was significant for severe acne, hirsutism, infertility and osteoporosis. Family history was significant for infertility in her mother, maternal uncle and aunt, as well as SLE in her mother, sister and maternal grandmother. In January 2010, a 3.7 cm suspicious left adrenal nodule was found on CT abdomen, requested for the follow up of an ovarian mass. Investigations by surgery showed an 11 AM cortisol 790 nmol/L (ref 120-535), 24h urinary free cortisol (UFC) 126-159 nmol/day (ref 55-330) and normal urinary metanephrines. ACTH was not available preoperatively. In June 2010, the patient underwent hysterectomy, bilateral salpingo-oophorectomy and left adrenalectomy. Histopathology showed a 3.5 x 1.8 x 1.6 cm benign multinodular adrenal mass. The patient was seen in endocrinology 2 month post-op because of complaints of fatigue, weakness and weight loss. On exam, she was a petite woman with BMI 15 kg/m2, BP 140/70 mmHg, and no signs of cortisol excess. She did have oily skin and mild hirsutism. Hormonal profile showed ACTH 9 pmol/L (ref ≤ 10), late morning cortisol 364 nmol/L with a peak of 819 nmol/L after 1 mcg cosyntropin stimulation. The patient was reassured and followed yearly. In 2013, she complained again of fatigue and inability to gain weight. AM cortisol ranged 677-806 nmol/L (24.5-29.2 ug/dL), ACTH 11-17 pmol/L and 24h UFC 1-1.9 times normal. Cortisol after dexamethasone 1 mg was 127 nmol/L (4.6 ug/dL) and suppressed to 28 nmol/L (1.0 ug/dL) with dexamethasone 8 mg. MRI of the sella was normal. Additional findings included a nodular right adrenal gland, a 1.7 cm right vertebral artery aneurysm, hepatic hemangiomas, a left renal hemorrhagic cyst and profound osteoporosis. The patient remained well, slim, with no classical signs of cortisol excess. The combination of hypercortisolemia, high ACTH, clinical hyperandrogenism without clinical Cushing’s, and intermittent symptoms of adrenal insufficiency lead to the suspicion of glucocorticoid resistance syndrome (GRS). GC receptor NR3C1 gene sequencing exposed a novel heterozygous variant with c.1392 deletion in exon 4. Interestingly, our patient never exhibited signs of mineralocorticoid excess. Multiple vascular anomalies and osteoporosis have not been previously described with GRS. Conclusion: This case exemplifies the heterogeneous tissue sensitivity to GC and wide clinical spectrum of GRS. It questions the wisdom of recommending treatment with dexamethasone for all GRS patients. An individualized approach to treatment of individuals with Chrousos syndrome seems more appropriate.

 

Nothing to Disclose: JWY, MDD, JAR