Graves’ disease following hypothyroidism due to Hashimoto’s thyroiditis in a black South African lady: a case report

Graves' disease and Hashimoto's thyroiditis are autoimmune thyroid disorders with distinct pathological and histopathological features. The conversion from Hashimoto's thyroiditis to Graves' disease has been rarely reported throughout the world with no reports in the African race to our knowledge. We here report an African lady who was initially diagnosed with primary hypothyroidism following Hashimoto's disease but later became thyrotoxic due to Graves' disease.


Introduction
There are few reports in the literature of hyperthyroidism after an initial period of hypothyroidism [1][2][3][4]. These have been mainly in Asian and Western populations. It is important to identify the rare patients who develop hyperthyroidism after initial treatment for hypothyroidism to enable prompt discontinuation of thyroxine and institution of appropriate treatment for hyperthyroidism. We found no reports in the English literature of hyperthyroidism following hypothyroidism in an African patient. We herein, report on a middle aged black South African female, who was initially diagnosed with hypothyroidism due to Hashimoto's thyroiditis but later developed Graves' disease after 5 years of thyroxine replacement.

Consent
Written informed consent for this case report was obtained from the patient. A copy of the written consent is available for review by the editorial board on request.

Discussion
Our patient initially had clinical and laboratory features of hypothyroidism due to Hashimoto's thyroiditis. When she became thyrotoxic and presented in heart failure after 5 years of 150 mcg daily thyroxine replacement for hypothyroidism, the initial thinking was that of thyroxine induced thyrotoxic heart failure. However, with the finding of elevated serum TSH receptor antibody titers and persistent thyrotoxicosis despite withdrawal of thyroxine, her diagnosis was revised from hypothyroidism due to Hashimoto's to hyperthyroidism due to Graves' disease. Chronic hypothyroidism with inadequate thyroxine replacement can result in pituitary hyperplasia and eventual thyrotoxicosis secondary to an autonomous secretion of TSH [5]. This is however, unlikely in our patient as an elevated and not suppressed TSH would be expected.
Although the transition from thyrotoxicosis to hypothyroidism is rare, it occurs in the setting of Hashitoxicosis where following thyroid follicular cells destruction an initial phase of thyrotoxicosis due to leakage of preformed thyroid hormones is followed by permanent hypothyroidism [6]. Thyrotoxicosis following hypothyroidism is also rare and is often described in Asian and western populations [1][2][3][4]. This scenario has been described predominantly in middle aged females [7]. It may occur up to 20 years after an initial period of hypothyroidism [8]. Our case is similar to other reports in literature in being a middle-aged female, Page number not for citation purposes 3 the exception is that she is of black race and we have not found reports describing it in the black ethnicity in the English language literature. The factors that have been associated with the transition from hypothyroid Hashimoto's to Graves' disease include thyroxine treatment which may promote the elaboration of TSH receptor stimulating antibodies [1]. Treatment with immunomodulatory agents such as interferon and alemtuzumab have also been implicated in the switch from hypothyroidism to thyrotoxicosis [9,10]. Our patient, however, neither received interferon nor alemtuzumab. She expectedly received thyroxine replacement for chronic primary hypothyroidism.
In all reports of transition from thyrotoxicosis to hypothyroidism and vice versa, it has been in the setting of autoimmune thyroid disease.
The postulated mechanism includes a switch from TSH receptor blocking to TSH receptor stimulating antibodies [11]. Indeed, circulating levels of TSH receptor inhibiting and stimulating antibodies have been reported in the same patient [12]. The clinical manifestation will be determined by which antibody predominates and this may vary with time with the same patient clinically manifesting as Hashimoto's thyroiditis or Graves' disease [13].
Alternating episodes of hypothyroidism and hyperthyroidism may be ultimately stopped with thyroidectomy or radioactive ablation of the thyroid [8,12].
This case report is not without limitations; we did not test our patient for TSH receptor antibodies when she was diagnosed with hypothyroidism as it is not the standard of care. Our practice is to perform thyroid peroxidase antibody testing in primary hypothyroidism when Hashimoto's is suspected. Thyroid peroxidase antibody; which is positive in 90-95% of patients with Hashimoto's is the preferred test in autoimmune primary hypothyroidism [14,15]. We also did not perform radionuclide imaging in our patient when she became thyrotoxic to demonstrate the expected pattern of diffusely increased uptake in Graves' disease because of the limited resources in our setting. We are aware that TSH receptor antibodies may be falsely positive in patients with thyrotoxicosis not due to Graves' disease [13]. However, we do not expect this to be the case in our patient.

Conclusion
In conclusion, our case extends the rare reports of Graves's disease following hypothyroidism to include the black African population.