Primary adrenal insufficiency due to hereditary apolipoprotein AI amyloidosis: endocrine involvement beyond hypogonadism

Abstract

Several mutations in the gene encoding apolipoprotein AI (apoAI) have been described as a cause of familial amyloidosis. Individuals with apoAI-derived (AApoAI) amyloidosis frequently manifest with liver, kidney, laryngeal, skin and myocardial involvement. Although primary hypogonadism (PH) is considered almost pathognomonic of this disease, until now, primary adrenal insufficiency (PAI) has not been described as a common clinical feature. Here, we report the first kindred with AApoAI amyloidosis in which PAI is well-documented. All family members with the Leu60_Phe71delins60Val_61Thr heterozygous mutation who were regularly followed-up at our centre were considered. Nineteen individuals had the confirmed APOA1 deletion/insertion mutation, with detailed medical records available in 11 cases. Of these, 6 had PAI and 3 (all males) had PH. Among them, one 47-year-old man, not previously diagnosed with PAI, developed adrenal crisis after liver transplantation, precipitated by an opportunistic infection. Transplantation due to organ failure, which necessitates use of immunosuppressive medication such as corticosteroids, is frequently required during the course of hereditary amyloidosis. Consequently, PAI can remain masked, being discovered only when an adrenal crisis develops. Therefore, according to the present evidence, patients with AApoAI amyloidosis should be submitted to regular testing of corticotrophin and cortisol levels in order to avoid delaying corticosteroid replacement.

Keywords:

• Hereditary amyloidosis
• apolipoprotein AI
• endocrine dysfunction
• adrenal insufficiency’ primary hypogonadism

Acknowledgements

The authors would like to express their most sincere gratitude to David R. Booth, Si-Yen Tan, Susanne E. Booth, Glenys A. Tennet, Winston L. Hutchinson, J. Justin Hsuan, Nicholas F. Totty, Oanh Truong, Anne K. Soutar, Philip N. Hwakins, Miquel Bruguera, Manel Solé, Josep M. Campistol and Joan Rodés for their meticulous investigation regarding AApoAI amyloidosis due to Leu60_Phe71delins60Val_61Thr (published for the first time in the Journal of Clinical Investigation in 1996 and later extended in the American Journal of Gastroenterology in 2001), which provided excellent information to complete the present study. We are also immensely grateful to Joan Minguet and Helen Sims (Koonec Medical, Terassa, Spain) for their helping in writing and editing the manuscript. Finally, we wish to thank Josep Oriola for his valuable guidance on genetic nomenclature and Sara Caelles for her assistance with digital image processing.

Disclosure statement

The authors affirm that there are no conflicts of interest concerning the information contained in the manuscript.

Additional information

Funding

This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors.