Hypothyroidism conversion to hyperthyroidism: it’s never too late

Abstract

SummaryPrimary hypothyroidism is a common endocrine condition, most commonly caused by autoimmune thyroiditis (Hashimoto’s disease) while Graves’ disease is the most common cause of hyperthyroidism. Hypothyroidism is usually a permanent condition in most patients requiring lifelong levothyroxine treatment. Transformation from Hashimoto’s disease to Graves’ disease is considered rare but recently been increasingly recognised. We describe a case of a 61-year-old lady who was diagnosed with hypothyroidism approximately three decades ago and treated with levothyroxine replacement therapy. Approximately 27 years after the initial diagnosis of hypothyroidism, she started to become biochemically and clinically hyperthyroid. This was initially managed with gradual reduction in the dose of levothyroxine, followed by complete cessation of the medication, but she remained hyperthyroid, ultimately requiring anti-thyroid treatment with Carbimazole. This case highlights that there should be a high index of suspicion for a possible conversion of hypothyroidism to hyperthyroidism, even many years after the initial diagnosis of hypothyroidism. To our knowledge, this case illustrates the longest reported time interval between the diagnosis of hypothyroidism until the conversion to hyperthyroidism.Learning points:Occurrence of Graves’ disease after primary hypothyroidism is uncommon but possible.In this case, there was a time-lapse of almost 28 years and therefore this entity may not be as rare as previously thought.Diagnosis requires careful clinical and biochemical assessment. Otherwise, the case can be easily confused for over-replacement of levothyroxine.We suggest measuring both anti-thyroid peroxidase (TPO) antibodies and TSH receptor antibodies (TRAB) in suspected cases.The underlying aetiology for the conversion is not exactly known but probably involves autoimmune switch by an external stimulus in genetically susceptible individuals.

Hypothyroidism to hyperthyroidism: an immunological pendulum swing from two extreme poles – a case series

“…We report two cases of hypothyroidism converting to hyperthyroidism after almost two decades of being stably euthyroid on thyroid hormone replacement. The period of conversion from one extreme to the other has been reported to develop within a period of 12–24 months on average with one exception reported by Ahmad et al of 27 years 2–4…”

“…The causes of this conversion are not well understood, but different theories have been postulated. One possible mechanism is that an environmental infectious trigger in a genetically susceptible individual may alter the thyroid state by altering the balance in the activity of blocking and stimulating antibodies and the response of thyroid gland to these antibodies 4. A second theory is that thyroid damage from an autoimmune phenomenon initially causes thyroid hypofunction but once enough thyroid tissue has recovered, it is stimulated by the stimulating autoantibodies and hyperthyroidism develops 4.…”

“…One possible mechanism is that an environmental infectious trigger in a genetically susceptible individual may alter the thyroid state by altering the balance in the activity of blocking and stimulating antibodies and the response of thyroid gland to these antibodies 4. A second theory is that thyroid damage from an autoimmune phenomenon initially causes thyroid hypofunction but once enough thyroid tissue has recovered, it is stimulated by the stimulating autoantibodies and hyperthyroidism develops 4. Some suggested that this conversion between blocking and stimulating antibodies occurs in some patients after using antithyroid drug treatment for Graves’ disease and levothyroxine for hypothyroidism 9.…”

Development of Graves' Disease After SARS-CoV-2 mRNA Vaccination: A Case Report and Literature Review

“…In contrast to the previous case presentations, the manifestation in our case was a less common presentation—Graves' disease on longstanding background of hypothyroidism requiring thyroxine replacement. The switch from hypothyroid to hyperthyroid state is believed to be stimulated by an external trigger, such as infection, in genetically susceptible individuals ( 10 ). Moreover, the development of de novo Graves' disease after COVID-19 is believed to take around 6–8 weeks ( 11 ).…”

Fluctuating Hyperthyroidism and Hypothyroidism in Graves’ Disease: The Swinging Between Two Clinical Entities

“…Graves' disease is usually associated with hyperthyroidism, while Hashimoto's thyroiditis is usually associated with hypothyroidism. The fluctuation of hyperthyroidism and hypothyroidism is a rarer phenomenon with fewer published case reports [1][2][3]. Antibodies responsible for these two states are thyroid-stimulating antibodies and thyroid-blocking antibodies, respectively.…”