A nationwide, registry-based study found that the real-world prevalence of hypothyroidism in patients with autoimmune Addison disease (AAD) was lower than had been reported in the literature. These findings were published in the Journal of Clinical Endocrinology & Metabolism.

All patients with both AAD and autoimmune thyroid disorder in The Norwegian Registry for Organ-Specific Autoimmune Diseases between 1996 and 2021 were identified. Comprehensive epidemiologic and clinical patterns of AAD with autoimmune thyroid disorder were evaluated. Overt hypothyroidism was defined as thyroid-stimulating hormone (TSH; thyrotropin) level greater than the reference range.

A total of 912 patients with AAD were identified; 42% (n=380) had hypothyroidism and 8.6% (n=78) had Graves disease.  The median age of the hypothyroidism and Graves disease cohorts was 38.0 (range, 2-87) and 33.0 (range, 9-89) years at onset of autoimmune disease, 36.0 (range, 3-85) and 33.5 (range, 14-64) years at onset of AAD. At least 1 associated disease was reported in 49% and 56% of patients, respectively.


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The most common (≥5%) autoimmune conditions in patients with hypothyroidism were type 1 diabetes, vitiligo, vitamin B12 deficiency, gonadal insufficiency, and alopecia, and the most common autoimmune conditions in patients with Graves disease were  vitiligo, type 1 diabetes, vitamin B12 deficiency, celiac disease, gonadal insufficiency, and alopecia.

Most patients (n=98) with ADD and hypothyroidism had subclinical hypothyroidism with TSH levels ranging from 4.1 to 10 mU/L, subclinical hypothyroidism with TSH levels greater than 10 mU/L (n=50), or overt hypothyroidism (n=41); few had TSH levels within the reference range (n=14). The onset of hypothyroidism tended to occur simultaneously with AAD among patients with overt hypothyroidism and those with TSH levels >10 mU/L or after AAD among patients with TSH levels in the reference range or TSH levels ranging from 4.1 to 10 mU/L.

Testing for thyroid peroxidase autoantibodies (TPOAb) was reported as negative in 35.7% patients with onset of hypothyroidism before AAD (35.7%), in 27.3% of patients with simultaneous onset, and in 30.6% of patients who experienced onset of AAD prior to hypothyroidism.

Regardless of TPOAb positivity, more patients had subclinical hypothyroidism at onset (48%), followed by subclinical hypothyroidism (25%), overt hypothyroidism (20%), and normal TSH levels (7%).

Most patients were given levothyroxine monotherapy, 4% used combination levothyroxine therapies, and 1% used thyroid extracts.

Remission was achieved by 33% of patients with Graves disease. The remaining patients had either a single episode of Graves disease (49%) or multiple episodes (27%).

This study was limited by missing data, such as about autoantibodies.

The study authors concluded, “In summary, even if autoimmune thyroid disease is the most common autoimmune comorbidity in AAD, overt hypothyroidism was seen in only about 20% and [Graves disease] in about 9% of cases. It is likely that a significant portion of patients are treated with levothyroxine without having autoimmune thyroid disease. Careful consideration of the indication to start thyroxin therapy is warranted, especially in patients with mild subclinical disease or negative TPOAb. Finally, we recommend careful monitoring of AAD patients with thyroid disease, in order to detect co-occurring autoimmunity.”

Reference

Stokland A-E, Ueland G, Lima K, et al. Autoimmune thyroid disorders in autoimmune Addison’s disease. J Clin Endocrinol Metab. Published online February 28, 2022. doi:10.1210/clinem/dgac089