Case Presentation: A 28 year old man presented to the ED with hypotension and tachycardia. Laboratory evaluation showed hyponatremia, hyperkalemia, hematocrit of 47.4, cortisol level<0.5, ACTH elevated at 886, TSH 11.91, Free T4 1.0 and negative anti TPO antibody.

On admission, the patient had orthostatic hypotension and ashen grey skin tone. Cosyntropin stimulation test resulted in a peak cortisol level<0.5. Imaging revealed markedly atrophic adrenal glands bilaterally with no organomegaly. Further testing was significant for a 21 hydroxylase (21-OHA) antibody level of 3.8 (normal 0-1), ferritin of 650 and homozygous H63D hemochromatosis mutations.

The patient was discharged and started on hydrocortisone and fludrocortisone therapy and referred to outpatient endocrinology for management of Addison’s disease and to hematology for management of hereditary hemochromatosis (HH).

Discussion: The patient likely has autoimmune polyendocrine syndrome type 2 given the elevated 21-OHA antibody and subclinical hypothyroidism, despite absence of anti TPO antibody1. The picture is complicated by the presence of HH. The presentation of Addison’s with HH is not well reported in the literature. An extensive literature review resulted in one case report2 and one study looking at mineralocorticoid and glucocorticoid status in hemochromatosis for which they did not find an association3.

Treatment for patients with Addison’s and HH should focus first on steroid replacement for adrenal insufficiency, which in this case resulted in significant improvement in symptoms. Management of HH should include close follow up to monitor for complications of iron overload and treatment with phlebotomy or iron chelation, recommended if patients are symptomatic from iron overload or have a ferritin level>300ug/L in men and >200ug/L in women4. In this case, given the ferritin level of 650ug/L, phlebotomy will be considered even in the absence of symptoms from iron overload.

Conclusions: When differentiating the possible causes of Addison’s it is important to test for the most common etiologies (autoimmune)1as well as rare etiologies such as HH. In patients presenting with both Addison’s and HH, treatment should be focused first on management of adrenal insufficiency and then on close follow up for secondary complications from HH and subsequent treatment when indicated.

References

  1. Ten, S., New, M., & Maclaren, N. (2001). Addison’s disease 2001. The Journal of Clinical Endocrinology & Metabolism, 86(7), 2909-2922.
  2. Wood, W, et al. (1950). Hemochromatosis versus Addison’s Disease. American Journal of Medicine, 9(3), 383-393.
  3. Salgia, R. J., & Brown, K. (2015). Diagnosis and management of hereditary hemochromatosis. Clinics in liver disease, 19(1), 187-198.
  4. Barton JC, McDonnell SM, Adams PC, et al. Management of hemochromatosis. Hemochromatosis Management Working Group. Ann Intern Med 1998; 129:932.