Cushings' syndrome in an adult patient with McCune Albright syndrome

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: MON 1-36-Adrenal Incidentaloma & Carcinoma
Clinical
Monday, June 17, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board MON-13
Monica Graciela Loto*1, Maria Fernanda Bueno2, Carlos Vigovich2, Maria Rosa Mongitore3, Mariana Dicugno3, Marcos Manavela4 and Karina Danilowicz4
1Hospital Británico de Buenos Aires, Ciudad Autonoma de Buenos Aires, Argentina, 2Hospital de Clinicas de Buenos Aires, Ciudad Autonoma de Buenos Aires, Argentina, 3Hospital Britanico de Buenos Aires, Ciudad Autonoma de Buenos Aires, Argentina, 4Hospital de Clínicas, Argentina
Background

McCune Albright syndrome (MAS) is a rare genetic disorder caused by postzygotic activating mutations of the GNSA1 gene leading to a constitutive activation of the stimulatory G protein´s α-subunit. Clinical manifestations in MAS are quite different due to the mosaicism in the distribution of affected tissues. Beyond the classic triad (café-au-lait spots, precocious puberty and fibrous dysplasia), many other non-endocrine and endocrinopathies have been added.

In the adrenal glands this mutation can produce ACTH-independent macronodular adrenal hyperplasia (AIMAH) with Cushing´s syndrome (CS). Hypercortisolism affects only a minority of patients with MAS, with a prevalence of 7.1 % according to the largest published series from NIH. About 30 patients with CS in MAS have been published, and all of them were under 4 years old.

We report a case with adulthood onset of CS in a patient with fibrous dysplasia (FD).

Case report

A 24 year-old man was referred for evaluation due to arterial hypertension, progressive increase in weight of 10 kg for the last two years, asthenia and dyspnea. In addition, he had monostotic FD diagnosed through temporal bone biopsy when he was 12 years old, with facial paralysis as sequelae. It´s aggressive behavior required three surgeries and intravenous high doses of bisphosphonates with unsuccessful evolution. No precocious puberty was associated.

Physical examination was remarkable for arterial hypertension, overweight with centripetal fat distribution, thin skin with no café-au-lait spots, scarce purple striae and muscular hypotrophia. 

Biochemical evaluation showed elevated 24-h urinary free cortisol (UFC): 624 mcg/24 h (normal value up to 120mcg/24 h).  The standard low dose dexamethasone suppression test revealed no suppression (serum cortisol 17.3 mcg/dl), confirming CS. Plasma ACTH level was <5 pg/ml, so an adrenal source was suspected and an abdominal TC was performed. Bilateral AIMAH was evident, and MAS was diagnosed because of the association with FD. Other hyperfunctioning endocrinopathies were ruled out.

Ketoconazole treatment was started, with a good initial response but after a few months the patient complained of dyspnea, asthenia, loose of weight and a very poor quality of life. The UFC values were again elevated; a new abdominal TC revealed an increase in adrenals’ size. So, surgical treatment was decided and a laparoscopic bilateral adrenalectomy on two times was performed. Histological exam confirmed adrenal hyperplasia. After surgery, hydrocortisone and fludrocortisone replacement was started.

Conclusion

To the best of our knowledge, there is no case reported where the diagnoses of CS had been done in adulthood, like in our patient. In patients with MAS, CS can still be expected in adulthood.

Nothing to Disclose: MGL, MFB, CV, MRM, MD, MM, KD

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm

Sources of Research Support: Dumitrescu C, Collins MT. Review: McCune- Albright syndrome. Orphanet Journal of Rare Disease, 3:12, 2008Brown R, Kelly M, Collins MT. Cushing syndrome in McCune-Albright syndrome. J Clin Endocrinol Metab 95: 1508-15, 2010 Lumbroso S, Paris F, sultan Ch. Activating Gsa mutations : Analysis of 113 patients with signs of McCune-Algright Syndrome: An European collaborative study. J Clin Endocrinol Metab 89 (5): 2107-13, 2004 Collins MT, Singer F, Eugster E. McCune-Albright syndrome and the extraesqueletal manifestations of fibrous dysplasia. Orphanet Journal of Rare Disease, 7 (Supl 1):54, 2012.Chapurlat R. Fibrous dysplasia of bone and McCune-Albright syndrome. Best Practice and Research Clinical Reumatology 22 (1): 55-69, 2008.