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      Hypothyroidism conversion to hyperthyroidism: it’s never too late

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          Summary

          Primary 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.

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          Most cited references9

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          Changes of TSH-Stimulation Blocking Antibody (TSBAb) and Thyroid Stimulating Antibody (TSAb) Over 10 Years in 34 TSBAb-Positive Patients with Hypothyroidism and in 98 TSAb-Positive Graves' Patients with Hyperthyroidism: Reevaluation of TSBAb and TSAb in TSH-Receptor-Antibody (TRAb)-Positive Patients

          Two TRAbs: TSBAb and TSAb. TSBAb causes hypothyroidism. TSAb causes Graves' hyperthyroidism. TSBAb and TSAb block TSH-binding to cells as TRAb, measured as TSH-binding inhibitory immunoglobulin (TBII). We reevaluate TSBAb and TSAb. We studied TSBAb, TSAb, and TBII over 10 years in 34 TSBAb-positives with hypothyroidism and in 98 TSAb-positives with hyperthyroidism. Half of the 34 TSBAb-positives with hypothyroidism continued to have persistently positive TSBAb, continued to have hypothyroidism, and did not recover from hypothyroidism. Ten of the 98 TSAb-positives with hyperthyroidism continued to have positive TSAb and continued to have hyperthyroidism. TSBAb had disappeared in 15 of the 34 TSBAb-positives with hypothyroidism. With the disappearance of TSBAb, recovery from hypothyroidism was noted in 13 (87%) of the 15 patients. TSAb had disappeared in 73 of the 98 TSAb-positives with hyperthyroidism. With the disappearance of TSAb, remissions of hyperthyroidism were noted in 60 (82%) of the 73. Two of the 34 TSBAb-positives with hypothyroidism developed TSAb-positive Graves' hyperthyroidism. Two of the 98 TSAb-positive Graves' patients with hyperthyroidism developed TSBAb-positive hypothyroidism. TSBAb and TSAb are TRAbs. TSBAb-hypothyroidism and TSAb-hyperthyroidism may be two aspects of one disease (TRAb disease). Two forms of autoimmune thyroiditis: atrophic and goitrous. We followed 34 TSBAb-positive patients with hypothyroidism (24 atrophic and 10 goitrous) over 10 years. All of the 10 TSBAb-positive goitrous patients recovered from hypothyroidism and 19 (79%) of the 24 TSBAb-positive atrophic patients continued to have hypothyroidism.
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            Graves' disease following hypothyroidism due to Hashimoto's disease: studies of eight cases.

            Hashimoto's and Graves' diseases represent the main two types of autoimmune thyroid disease. The combination of these two is well known. However, occurrence of Graves' disease after primary hypothyroidism is rare. We report seven patients with hypothyroidism due to Hashimoto's disease, who developed Graves' disease with hyperthyroidism. We also report one patient with hypothyroidism due to Hashimoto's disease, who continued to be hypothyroid even in the presence of TSAb (thyroid stimulating antibody). These patients were divided into three groups according to the changes in thyroid function and clinical course: (1) transient hyperthyroidism due to Graves' disease following hypothyroidism; (2) persistent hyperthyroidism due to Graves' disease following hypothyroidism; and (3) persistent hypothyroidism with positive TSAb. Such changes in thyroid function and clinical course seem to be decided by three factors: (1) TSAb and (2) TSBAb (thyroid stimulation blocking antibody) activities in the blood and (3) the responsiveness of the thyroid gland to TSAb. Seven patients had hyperthyroidism, when they had TSAb, which stimulated the thyroid gland; one of these seven patients had TSBAb during the hypothyroid state and TSAb during the hyperthyroid state, indicating that the alterations in the thyroid state related to the balance between the activities of TSAB and TSBAb. Another patient continued to be hypothyroid despite the presence of TSAb; his thyroid gland was not palpable and could not respond to TSAb.
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              Conversion of autoimmune hypothyroidism to hyperthyroidism

              Background Graves’ disease and Hashimoto’s thyroiditis are the two autoimmune spectrum of thyroid disease. Cases of conversion from hyperthyroidism to hypothyroidism have been reported but conversion from hypothyroidism to hyperthyroidism is very rare. Although such cases have been reported rarely in the past we are now seeing such conversions from hypothyroidism to hyperthyroidism more frequently in clinical practice. Case presentation We are reporting three cases of middle aged Asian females who presented with classical symptoms of hypothyroidism and the investigations showed elevated thyroid stimulating hormone with positive thyroid antibodies. Diagnosis of autoimmune hypothyroidism was made and thyroxine replacement therapy was initiated. Patients became asymptomatic with normalization of thyroid stimulating hormone level. After few years they developed symptoms of hyperthyroidism with suppressed thyroid stimulating hormone level. Over replacement of thyroxine was considered and the dose of thyroxine was decreased, but they remain symptomatic. After gradual decrease in the dose of thyroxine it was stopped finally. Even after few months of stopping thyroxine, the symptoms of hyperthyroidism did not improve and the biochemical and imaging modalities confirmed that the patients have developed hyperthyroidism. Anti-thyroid treatment was then started and the patients became symptom free. Conclusion High index of suspicion should be there for possible conversion of hypothyroidism to hyperthyroidism if a patient with primary hypothyroidism develops persistent symptoms of hyperthyroidism. Otherwise it can be missed easily considering it as an over replacement with thyroid hormone.

                Author and article information

                Journal
                Endocrinol Diabetes Metab Case Rep
                Endocrinol Diabetes Metab Case Rep
                EDM
                Endocrinology, Diabetes & Metabolism Case Reports
                Bioscientifica Ltd (Bristol )
                2052-0573
                03 August 2018
                2018
                : 2018
                : 18-0047
                Affiliations
                [1 ]Endocrinology and Diabetes , Queen Elizabeth the Queen Mother Hospital, Margate, UK
                [2 ]Endocrinology and Diabetes , Tunbridge Wells Hospital, Tunbridge Wells, UK
                [3 ]Endocrinology and Diabetes , Sheffield Teaching Hospitals, Sheffield, UK
                [4 ]Tunbridge Wells Hospital , Tunbridge Wells, UK
                [5 ]St George’s University of London Medical School , London, UK
                Author notes
                Correspondence should be addressed to E Ahmad Email ehtasham.ahmad@ 123456nhs.net

                *(E Ahmad and M F Arshad contributed equally and are joint first authors)

                Article
                EDM180047
                10.1530/EDM-18-0047
                6075370
                79cad838-e3c3-4e15-bc0c-a65a912c4028
                © 2018 The authors

                This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License.

                History
                : 17 June 2018
                : 16 July 2018
                Categories
                Unique/Unexpected Symptoms or Presentations of a Disease

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