Poster Presentation ESA-SRB 2023 in conjunction with ENSA

Phaeochromocytoma resection unmasking Addison’s disease in a case of Autoimmune Polyglandular Syndrome type 2 (#350)

Alexander Yao 1 , Michael Christie 2 , Julie Miller 3 , Christopher Yates 1
  1. Diabetes and Endocrinology, Royal Melbourne Hospital, Melbourne, Victoria, Australia
  2. Anatomical Pathology, Royal Melbourne Hospital, Melbourne, Victoria, Australia
  3. Endocrine and Breast Surgery, Royal Melbourne Hospital, Melbourne, Victoria, Australia

Case Report

A 33-year old man with Hashimoto’s disease was incidentally found to have a 4.1cm heterogeneously enhancing left adrenal mass on a CT performed to investigate right flank pain. There was no family history of endocrinopathies.

He reported 6 months of paroxysmal palpitations, headaches and agitation. Blood pressure and heart rate were 110/60mmHg and 70bpm, respectively. Adrenal hormone testing confirmed a phaeochromocytoma: secreting normetanephrine (10,524pmol/L) and 3-methoxytyramine (460pmol/L) (Table 1). Phenoxybenzamine and later propranolol were uptitrated before posterior laparoscopic retroperitoneal adrenalectomy. Histopathology confirmed typical phaeochromocytoma features with intact SDHA/B immunohistochemistry, however the adjacent adrenal cortex demonstrated lymphocytic infiltration and cortical cell destruction.

Post-operatively he developed symptomatic hyponatraemia. Short-synacthen testing confirmed primary adrenal insufficiency (Table 2), with elevated ACTH, low aldosterone and positive adrenal cortex antibodies (Table 3). Retrospective imaging review demonstrated right adrenal atrophy. Symptoms and hyponatraemia resolved with hydrocortisone and fludrocortisone commencement. Plasma metanephrines normalised post-operatively.

Genetic testing was declined due to anxiety, however evaluation for other endocrinopathies and MEN2-related diseases was unremarkable.

Discussion

Autoimmune polyglandular syndrome-type 2 (APS-2) has a prevalence of 1:1000-1:20,000 and is characterised by two of Addison’s disease, autoimmune thyroid disease and type 1 diabetes with typical age of onset 20-40 years.1 APS-2 is a polygenic disease, with significant heterogeneity due to multiple genetic loci and environmental factors responsible. Major histocompatibility complex (MHC) genes located on chromosome 6 have been implicated. It appears that HLA-DR3 and HLA-DR4 haplotypes and the class 2 HLA alleles DQ2 and DQ8 increase predisposition.2

There have been 4 reported cases of phaeochromocytoma with APS-2.3-6 This is the first where Addison’s disease was unmasked by postoperative normalisation of catecholamines.

 64f0bf8d45535-KB+Table+1.png

64f0bf8d45535-KB+Table+2.png

64f0bf8d45535-KB+Table+3.png

 

  1. Förster G et al. Dtsch Med Wochenschr. 1999;124(49):1476-1481.
  2. Weinstock C, Matheis N, Barkia S, et al. Autoimmune polyglandular syndrome type 2 shows the same HLA class II pattern as type 1 diabetes. Tissue Antigens. 2011;77(4):317-324.
  3. Toni García M, Anda Apiñániz E, Pablo J, et al. An unusual association: pheochromocytoma on an atrophied adrenal gland due to addison's disease. Endocrinol Nutr. 2008;55(10):510-513.
  4. Manso J, Censi S, Iacobone M, et al. First proof of association between autoimmune polyglandular syndrome and multiple endocrine neoplasia in humans. Endocr J. 2020;67(9):929-934.
  5. Park E, Kim MS, Noh ES, et al. Multiple endocrine neoplasia type 2 and autoimmune polyendocrine syndromes (type 1 diabetes mellitus and Graves' disease) in a 16-year-old male with Kabuki syndrome. Endocr J. 2022;69(10):1211-1216.
  6. Murao K, Imachi H, Sato M, et al. A case of pheochromocytoma complicated with slowly progressive type 1 diabetes mellitus and chronic thyroiditis. Endocrine. 2007;32(3):350-353.