Diagnosis and Treatment > Medication
Centre for Endocrine and Diabetes Sciences, University Hospital of Wales, Heath Park, Cardiff, UK
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Summary
Graves’ disease is associated with tachydysrythmia, cardiac ischaemia and cardiomyopathy – all uncommon in young adults without previous cardiac disease. We present three young individuals who developed cardiac complications after periods of uncontrolled Graves’ disease. Subject 1: A 34-year-old female had severe thyrotoxic symptoms for weeks. Investigations showed fT4: 98.4 (11–25 pmol/L), fT3: 46.9 (3.1–6.8 pmol/L), TSH <0.01 (0.27–4.2 mU/L) and thyrotrophin receptor antibody (TRAb): 34.8 (<0.9 U//l). She had appropriate treatment but several weeks later she became breathless despite improving thyroid function. Echocardiography showed a pericardial effusion of 2.9 cm. She responded well to steroids and NSAIDs but developed active severe Graves’ orbitopathy after early total thyroidectomy. Subject 2: A 28-year-old male developed thyrotoxic symptoms (fT4: 38 pmol/L, fT3: 13.9 pmol/L, TSH <0.01 (for over 6 months) and TRAb: 9.3 U/L). One month after starting carbimazole, he developed acute heart failure (HF) due to severe dilated cardiomyopathy – EF 10–15%. He partially recovered after treatment – EF 28% and had early radioiodine treatment. Subject 3: A 42-year-old woman who had been thyrotoxic for several months (fT4: 54.3; fT3 >46.1; TSH <0.01; TRAb: 4.5) developed atrial fibrillation (AF) and heart failure. Echocardiography showed cardiomegaly – EF 29%. She maintains sinus rhythm following early total thyroidectomy (EF 50%). Significant cardiac complications may occur in previously fit young adults, who have had uncontrolled Graves’ disease for weeks to months. Cardiac function recovers in the majority, but early definitive treatment should be discussed to avoid Graves’ disease relapse and further cardiac decompensation.
Learning points:
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Cardiac complications of Graves’ disease are uncommon in young adults without previous cardiac disease.
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These complications may however occur if Graves’ disease had been poorly controlled for several weeks or months prior to presentation.
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Persistent symptoms after adequate control should alert clinicians to the possibility of cardiac disease.
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Specific treatment of Graves’ disease and appropriate cardiac intervention results in complete recovery in the majority and carries a good prognosis.
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Early definitive treatment should be offered to them to prevent cardiac decompensation at times of further relapse.
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Summary
This case is the first to describe a patient who experienced concomitant agranulocytosis and anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis as an adverse effect of propylthiouracil treatment for Graves’ disease. A 42-year-old female with Graves’ disease presented to the emergency department (ED) with a 2-week history of fevers, night sweats, transient lower limb rash, arthralgia, myalgia and fatigue. She had been taking propylthiouracil for 18 months prior to presentation. On admission, agranulocytosis was evident with a neutrophil count of 0.36 × 109/L and immediately propylthiouracil was stopped. There was no evidence of active infection and the patient was treated with broad-spectrum antibodies and one dose of granulocyte colony-stimulation factor, resulting in a satisfactory response. On further investigation, ANCAs were positive with dual positivity for proteinase 3 and myeloperoxidase. There was no evidence of end-organ damage secondary to vasculitis, and the patient’s constitutional symptoms resolved completely on discontinuation of the drug precluding the need for immunosuppressive therapy.
Learning points:
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Continued vigilance and patient education regarding the risk of antithyroid drug-induced agranulocytosis is vital throughout the course of treatment.
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ANCA-associated vasculitis is a rare adverse effect of antithyroid drug use.
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Timely discontinuation of the offending drug is vital in reducing end-organ damage and the need for immunosuppressive therapy in drug-induced ANCA-associated vasculitis.
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Similarities in the pathogenesis of agranulocytosis and drug-induced ANCA-associated vasculitis may offer insight into an improved understanding of vasculitis and agranulocytosis.
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Summary
Thyroid storm with multi-organ failure limits the use of conventional treatment. A 44-year-old male presented with thyroid storm and experienced cardiovascular collapse after beta-blocker administration, with resultant fulminant multi-organ failure requiring inotropic support, mechanical ventilation, extracorporeal membrane oxygenation (ECMO) and continuous renal replacement therapy. Hepatic and renal failure precluded the use of conventional thyroid storm treatment and early plasma exchange was instituted. The patient underwent emergency thyroidectomy after four effective exchanges, with subsequent rapid reversal of multi-organ failure. The challenges of institution of plasma exchanges with ongoing ECMO support, dialysis and timing of thyroidectomy are discussed. This case highlights the important role of early therapeutic plasma exchange (TPE) as an effective salvage therapy for lowering circulating hormones and stabilization of patients in preparation for emergency thyroidectomy in patients with thyroid storm and fulminant multi-organ failure.
Learning points:
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Administration of beta-blockers in thyroid storm presenting with congestive cardiac failure may precipitate cardiovascular collapse due to inhibition of thyroid-induced hyperadrenergic compensation which maintains cardiac output.
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TPE can be an effective bridging therapy to emergency total thyroidectomy when conventional thyroid storm treatment is contraindicated.
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End-organ support using ECMO and CRRT can be combined with TPE effectively in the management of critically ill cases of thyroid storm.
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The effectiveness of plasma exchange in lowering thyroid hormones appears to wane after 44–48 h of therapy in this case, highlighting the importance early thyroidectomy.
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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:
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Occurrence of Graves’ disease after primary hypothyroidism is uncommon but possible.
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In this case, there was a time-lapse of almost 28 years and therefore this entity may not be as rare as previously thought.
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Diagnosis requires careful clinical and biochemical assessment. Otherwise, the case can be easily confused for over-replacement of levothyroxine.
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We suggest measuring both anti-thyroid peroxidase (TPO) antibodies and TSH receptor antibodies (TRAB) in suspected cases.
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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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Summary
We report a patient with Graves’ disease who remained persistently hyperthyroid after a total thyroidectomy and also developed de novo Graves’ ophthalmopathy 5 months after surgery. She was subsequently found to have a mature cystic teratoma containing struma ovarii after undergoing a total hysterectomy and salpingo-oophorectomy for an incidental ovarian lesion.
Learning points:
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It is important to investigate for other causes of primary hyperthyroidism when thyrotoxicosis persists after total thyroidectomy.
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TSH receptor antibody may persist after total thyroidectomy and may potentially contribute to the development of de novo Graves’ ophthalmopathy.
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Thyroid Research Group, Institute of Molecular and Experimental Medicine, Cardiff University School of Medicine, Cardiff, UK
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Thyroid Research Group, Institute of Molecular and Experimental Medicine, Cardiff University School of Medicine, Cardiff, UK
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Summary
TSH receptor antibodies (TRAbs) are the pathological hallmark of Graves’ disease, present in nearly all patients with the disease. Euthyroid Graves’ ophthalmopathy (EGO) is a well-recognized clinical entity, but its occurrence in patients with negative TRAbs is a potential source of diagnostic confusion. A 66-year-old female presented to our endocrinology clinic with right eye pain and diplopia in the absence of thyroid dysfunction. TRAbs were negative, as measured with a highly sensitive third-generation thyrotropin-binding inhibitory immunoglobulin (TBII) ELISA assay. CT and MRI scans of the orbit showed asymmetrical thickening of the inferior rectus muscles but no other inflammatory or malignant orbital pathology. Graves’ ophthalmopathy (GO) was diagnosed on the basis of the clinical and radiological features, and she underwent surgical recession of the inferior rectus muscle with complete resolution of the diplopia and orbital pain. She remained euthyroid over the course of follow-up but ultimately developed overt clinical and biochemical hyperthyroidism, 24 months after the initial presentation. By this time, she had developed positive TRAb as well as thyroid peroxidase antibodies. She responded to treatment with thionamides and remains euthyroid. This case highlights the potential for negative thyroid-specific autoantibodies in the presentation of EGO and underscores the variable temporal relationship between the clinical expression of thyroid dysfunction and orbital disease in the natural evolution of Graves’ disease.
Learning points
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Euthyroid Graves’ ophthalmopathy can present initially with negative thyroid-specific autoantibodies.
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Patients with suggestive symptoms of ophthalmopathy should be carefully evaluated for GO with imaging studies even when thyroid function and autoantibodies are normal.
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Patients with EGO can develop thyroid dysfunction within 4 years of follow-up underpinning the need for long-term follow-up and continued patient and physician vigilance in patients who have been treated for EGO.
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Summary
A 55-year-old female patient presented to the endocrine clinic with Grave's disease. She was initially treated with carbimazole. After an early relapse, a decision was made to proceed with radioactive iodine therapy. Four days after radioiodine administration, she presented to the emergency department with chest tightness and dyspnea due to heart failure. Biochemistry revealed thyrotoxicosis and significantly elevated Troponin-T. There was ST segment elevation on electrocardiography. However, coronary angiography was normal. Ventricular function was fully restored after 6 weeks of supportive medical management. A diagnosis of stress cardiomyopathy following radioactive iodine therapy was made. This is the second case reported in the literature so far to the best of our knowledge.
Learning points
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Stress cardiomyopathy in the context of radiation thyroiditis is a rare complication following radioiodine therapy.
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A degree of awareness is essential because the approach is multidisciplinary. Management is mainly supportive and cardiac dysfunction is completely reversible in most cases.
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The pathogenesis of this condition remains unclear. Post-menopausal women and susceptible individuals appear to be pre-disposed.
