Conversion of Hypothyroidism to Hyperthyroidism: A Rare Clinical Phenomenon

Abstract

Objective: We present a patient with long standing hypothyroidism that developed hyperthyroidism secondary to Graves’ disease. Recognition of this disease phenomenon is crucial to ensure prompt diagnosis and close follow-up. Methods: The patient was evaluated with thyroid function testing and thyroid antibody testing. Further evaluation included ophthalmologic examination and radioactive iodine uptake imaging. Results: A 56-year-old female with past medical history of human immunodeficiency virus (HIV), hepatitis C infection, and hypothyroidism presented for evaluation of thyroid disease. She had been off of levothyroxine for the last 8 months due to biochemical findings of thyrotoxicosis. Family history was significant for hyperthyroidism and hypothyroidism. Labs were consistent with hypothyroidism so levothyroxine was restarted. Exam showed lid lag and proptosis. Ophthalmologic evaluation found bilateral 23 mm proptosis. Additional lab testing was positive for thyroid peroxidase antibody and thyroid stimulating immunoglobulin. Following levothyroxine use, the patient developed subclinical hyperthyroidism and thyroid replacement was stopped. The patient remained euthyroid for one year off of levothyroxine. Following one year, she developed mild hyperthyroidism with increased radioactive iodine uptake. She was placed on propranolol for symptomatic relief. Months later, thyroid function testing normalized. Conclusion: In Graves’ disease, hypothyroidism and conversion of hypothyroidism to hyperthyroidism are rare, yet important to recognize, clinical phenomenon. The stimulatory and inhibitory properties of thyroid-stimulating hormone receptor antibodies are speculated to play a role in individuals with alternating hypothyroidism and hyperthyroidism. These individuals can present a diagnostic and therapeutic challenge. Clinicians must maintain a high clinical suspicion for this disease entity.

Autoimmune Thyroiditis Shifting from Hashimoto’s Thyroiditis to Graves’ Disease

“…We used the keywords "transition from HT to GD or "GD following HT" or "HT converting to GD" or "HT to GD". To date, 50 cases regarding conversion from HT to GD have been reported [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21], including this case (Table 1). The male-to-female ratio was 1:9, median age was 44 years (range, 23-82 years), and the most common age group was 36-55 years.…”

Conversion From Hypothyroidism to Hyperthyroidism and Back After Anti-SARS-CoV-2 Vaccination

“…Researchers predominantly focused on the search and confirmation of immune molecular mechanisms triggering Graves' disease [15,16]. Such mechanisms, in their opinion, were possible because of the cross effect of autoimmune processes [17], human immunodeficiency virus (HIV) infection, hepatitis C [18], genetic predisposition [27], and medications [28]. However, these hypotheses have weak evidence and remain as assumptions.…”

“…However, these hypotheses have weak evidence and remain as assumptions. This is the reason why some authors, aside from considering these hypotheses, express the view that the actual mechanism of hormonal metabolism alteration is not known, and the proposed theories are speculative [17,18,26, . However, some observations indicate that in some cases of diffuse hyperthyroidism the level of stimulating TSHR antibodies does not increase [30,31], and in some hypothyroidism cases the level of blocking TSHR antibodies is normal [32].…”

“…This patient had been receiving hormone replacement therapy with levothyroxine for several years. Hypothyroidism conversion to hyperthyroidism (Graves' disease) is known to be a rare phenomenon associated hypothetically with immune changes [15][16][17][18][19]. For instance, this is observed in cases in which the physicians switch between blocking and stimulating thyroid-stimulating hormone receptor (TSHR) antibodies "in nonstandard patients" [15].…”