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A Comprehensive Endocrine Description of Kennedy’s Disease Revealing Androgen Insensitivity Linked to CAG Repeat Length

Department of Endocrinology (S.D., H.B.-G., E.B., R.C., P.G., G.T.), Hôpital de La Pitié-Salpétrière, Assistance Publique-Hôpitaux de Paris; Department of Neurology (B.E., F.S.), Myological Institute, Hôpital de La Salpétrière; and Institut National de la Santé et de la Recherche Médicale U 289 and Department of Genetics, Cytogenetics, and Embryology (E.L., S.T.), Hôpital de La Salpétrière, 75 013 Paris, France

Address all correspondence and requests for reprints to: Sylvie Dejager, M.D., Ph.D., Department of Endocrinology, Hôpital de La Pitié-Salpétrière, 83 Bd de L’Hôpital, 75 013 Paris, France. E-mail: . sylvie.dejager{at}wanadoo.fr

Abstract

Our study aims to provide a comprehensive view of the endocrine features in Kennedy’s disease (KD). Twenty-two men with KD underwent detailed endocrine investigations. Clinical signs of partial androgen resistance were present in more than 80% of the patients, with gynecomastia being the most prominent. Gynecomastia was postpubertal but appeared before muscular weakness in most cases. Thirteen patients had alteration of testicular exocrine function. Hormonal profile of partial androgen resistance was present in 86% of the patients, with an elevated testosterone level in 68%. Androgen insensitivity seems to appear later in life in KD, similar to the development of neurological signs.

Although we confirm the previously reported correlation between the CAG repeat length and the early onset of the neurological disease, we describe a significant correlation between repeat length and the age of onset of gynecomastia as well as biological indexes of androgen insensitivity. This is supported by numerous in vitro data correlating variations in the CAG tract with androgen receptor activity; the longer the CAG repeats, the weaker the receptor transactivation. Ours is the first study to show such a clear and prominent pattern of androgen insensitivity in KD. In clinical practice, KD patients are often misdiagnosed as having amyotrophic lateral sclerosis. Careful examination of the endocrine component could avoid such a deleterious misdiagnosis.

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