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Year : 2013  |  Volume : 2  |  Issue : 3  |  Page : 205-208

Graves' disease with high out-put failure

Department of General Medicine, Government Siddhartha Medical College, Vijayawada, Andhra Pradesh, India

Date of Web Publication29-Aug-2013

Correspondence Address:
Vijaya Sree Potluri
Department of General Medicine, Government Siddhartha Medical College, Vijayawada, Andhra Pradesh
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/2277-8632.117192

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A middle-aged female patient was admitted to our medical ward with the complaints suggestive of congestive heart failure. Her history revealed that she was diagnosed as having thyroid disease about 6 years back, but the patient did not use any medication despite medical advice. Now, she is having small goiter and moderate proptosis. Investigations showed increased thyroid hormone levels with suppressed thyroid stimulating hormone levels. Immunological assay showed increased thyroperoxidase antibodies. Nuclear uptake study confirmed increased diffuse uptake of technetium-99m. Echocardiogram showed dilatation of all chambers of the heart with increased ejection fraction. Pathophysiology, clinical features, and management of Graves' disease, in particular hyperthyroidism induced high out-put failure are discussed and literature is reviewed.

Keywords: Graves′ disease, high out-put failure, ophthalmopathy, radioactive iodine, thyroid stimulating hormone receptor antibody

How to cite this article:
Rao KS, Rao DS, Venkata SK, Potluri VS, Hari Kiran P. Graves' disease with high out-put failure. J NTR Univ Health Sci 2013;2:205-8

How to cite this URL:
Rao KS, Rao DS, Venkata SK, Potluri VS, Hari Kiran P. Graves' disease with high out-put failure. J NTR Univ Health Sci [serial online] 2013 [cited 2021 May 12];2:205-8. Available from: https://www.jdrntruhs.org/text.asp?2013/2/3/205/117192

  Introduction Top

Graves' disease (GD) is the most common cause of hyperthyroidism in iodine replete parts of the world and is characterized by diffuse toxic goiter, infiltrative ophthalmopathy, and infiltrative dermopathy. [1] Robert Graves' disease, although first described by Parry in 1825, is best known as Graves' disease in English-speaking world and as Von Basedow's disease in Europe. [2]

  Case Report Top

A 38-year-old female was admitted with the complaints of palpitations, breathlessness, swelling of both legs, and distention of abdomen of 3-week duration. Breathlessness initially of grade II progressed to grade IV in 2 months duration.

Patient was afebrile, with no history of chest pain, chronic respiratory disease, double vision or change of voice, but had irregular menstrual history for 6 months. Bowels and micturition were normal. She was diagnosed as having thyroid disease 6 years back, but did not take any treatment.

General examination revealed warmth body, anemia, icterus, staring look, proptosis, firm and small diffuse goiter, raised jugular venous pressure, bruit over thyroid, fine rapid tremor of both outstretched hands, mild distention of abdomen and pedal edema [Figure 1] and [Figure 2]. Vital signs were as follows: Pulse rate 120/min, with occasional missed beats; BP 130/70 mmHg; respiratory rate 22/min.
Figure 1: Photograph of the patient

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Figure 2: Exophthalmos in lateral view

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Cardiovascular examination showed hyperdynamic apical impulse with downward and outward shift, left parasternal pulsations, mitral and tricuspid pansystolic murmer with mitral thrill, loud P2, pulmonary ejection systolic murmur. Other findings were bilateral basal crepitations in lungs, mild hepatomegaly, and ascites. Central nervous system examination including fundus was unremarkable. Von Graefe's, Joffroy's, Dalrymple's, and Mobius signs were positive.

Hemogram showed Hb 8 gm%, normocytic normochromic anemia with occasional microcytes. Serum bilirubin was 2.6 mg%. Ascitic fluid was transudate. Renal, glycemic status and urine analysis were unremarkable. Viral markers were negative. Thyroid profile showed suppressed thyroid stimulating hormone (TSH) (0.007 μIU/ml), increased total T3, T4 (150 ng/dl; 15 μg/dl), and increased free T3, free T4 (5.1 pg/ml; 2.2 ng/dl). Other findings were diffuse thyromegaly on ultrasonogram, increased thyroperoxidase antibodies (131 U/ml), and negative thyroid stimulating hormone receptor (TSH-R) antibodies. Radioscan showed increased diffuse uptake of technetium-99m (tc-99m) (11%), which is the feature of Graves' hyperthyroidism [Figure 3]. Computed tomography of orbits showed upper normal measurements of extraocular muscles on both sides.
Figure 3: Tc-99m uptake scan

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Electrocardiography showed sinus tachycardia with occasional atrial ectopics. Cardiomegaly and pulmonary congestion were present in chest X-ray [Figure 4]. Two-dimensional echocardiogram revealed dilatation of all cardiac chambers, severe mitral regurgitation, moderate tricuspid regurgitation, and pulmonary arterial hypertension with ejection fraction of 65%.
Figure 4: Chest X-ray PA view

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Clinical, radiological, biochemical, and nuclear scan studies confirmed the diagnosis of GD with high out-put failure.

The patient was treated with carbimazole, propranolol, and diuretics. Patient had good symptomatic relief in 10 days. Patient was discharged with advice of bi-weekly review.

  Discussion Top

Being spectral part of autoimmune thyroid disease, peak presentation of GD occurs in third and fourth decades with rarity in adolescents and elderly. Female:male ratio is 7–10:1 in western world, but in India it was reported as 2–3:1. [1]

Immunopathogenesis involves formation of autoantibodies that stimulate the TSH-R and activate adenylate cyclase as TSH agonists. High concordance rate in monozygotic twins indicates genetic susceptibility. [1] There is increased association with HLA-DR3 and DQA 10501 haplotypes in Caucasians and CTLA4 gene that codes for a modulator of the second signal to T cells. Perhaps it is the X chromosome or fetal microchimerism rather than sex steroids that is the responsible element in female susceptibility. [2] Immune response directed against an antigen, common to the thyroid and orbital tissue or skin, can be responsible for ophthalmopathy and dermopathy, respectively. There is no unequivocal evidence for infection and stress as etiological factors. In patients and their relatives there is an increased frequency of other autoimmune diseases such as insulin-dependent diabetes and pernicious anemia. [1]

The most common symptoms are nervousness, fatigue, palpitations, heat intolerance, and weight loss. Atrial fibrillation is uncommon in younger people, but seen in 20% of elderly. Unique clinical features of thyrotoxicosis in Indian population are severe weight loss, dyspnea, proximal muscle weakness, diarrhea, anemia, cardiac failure, hepatic dysfunction, and cortisol deficiency. [3]

Thyrotoxicosis is confirmed by suppressed TSH (<0.05 μIU/ml) and elevated total or free T4 and T3 levels. [3] Thyroperoxidase antibodies and TSH-R antibodies are present in 80% of cases. TSH-R antibodies are very low or undetectable in a few patients; reasons being assay insensitivity, exclusively intrathyroidal production of the antibodies, and gain mutations of TSH-R. [4] Evaluation for TSH-R antibodies is generally recommended for prediction of postpartum GD, neonatal thyrotoxicosis, relapse in medically treated patients, identifying orbitopathy in the absence of obvious features of thyrotoxicosis. Computed tomography/magnetic resonance imaging of orbits may reveal thickening of extraocular muscles, with sparing of tendons. In Doppler flow assessment, thyroid blood flow area of 8% or greater has a sensitivity of 95% and specificity of 90% for prediction of GD. Tc-99m and radioactive iodine (RAI) uptake is diffusely increased. Advantages with Tc-99m are quick scanning (20–30 min) and lower degree of radioactivity. [3]

One-third of the patients become hypothyroid within 20 years of treatment with antithyroid drugs. Sometimes GD begins with orbitopathy, and may later be followed by thyrotoxic component. [2]

Thyrotoxicosis and heart

Action of thyroid hormone on the cardiovascular system leads to increase in blood volume, decrease in systemic vascular resistance, and shortened circulation time, leading to hyperdynamic circulation, resulting in increased preload and decreased afterload. Increased heart rate and preload result in high cardiac output state. Ionotropic actions of thyroid hormone include increased left ventricular end diastolic volume, rate of ventricular diastolic relaxation, and left ventricular contractility. All these changes result in high out-put failure, with normal or high ejection fraction, which is interpreted as thyrotoxic cardiomyopathy with complete reversibility on antithyroid treatment. [5] Six percent thyrotoxic individuals develop symptoms of heart failure, but <1% develop dilated cardiomyopathy with impaired left ventricular systolic function. [6]

Treatment consists of medical RAI ablation and surgery. Thionamides (methimazole, carbimazole, and propylthiouracil [PTU]) are preferred drugs. Methimazole is the active form of carbimazole. Carbimazole is given as 30–45 mg in three divided doses with maintenance dose of 10 mg/day. PTU is given as 50–100 mg every 8 hours. PTU also inhibits peripheral conversion of T4 to T3. Major side effects of thionamides are agranulocytosis and hepatotoxicity, which may need discontinuation of the drug. [1]

RAI ablation is the definitive treatment, but contraindicated in pregnancy and lactation. RAI may induce or worsen ophthalmopathy particularly in smokers, but may be prevented by prior glucocorticoid therapy. [4] Permanent hypothyroidism occurs in 40% of patients within 10 years of treatment with RAI. [1]

Subtotal thyroidectomy is indicated in large goiters, compressive symptoms, suspicious nodules, and significant ophthalmopathy. [7]

Adjuvant agents are lithium, dexamethasone, beta-blockers, Lugol's iodine, and saturated solution of potassium iodide. [3]

Spontaneous remission in hyperthyroidism is seen in pregnancy because of natural immunosuppression. [2] PTU is preferred in pregnancy because of the risk of aplasia cutis with methimazole. [7] Antithyroid drugs may be continued during lactation, but the baby's thyroid status should be evaluated periodically. [2]

  References Top

1.Munjal Y. API Textbook of Medicine. 9 th ed. Mumbai: Association of Physicians of India; 2012. p. 421-5.  Back to cited text no. 1
2.Kronenberg HM, Melmed S, Polonsky KS, Larsen PR. Williams Textbook of Endocrinology. 11 th ed. Philadelphia: Saunders Elsevier; 2008. p. 337-60.  Back to cited text no. 2
3.Shah SN, Joshi SR. Indian thyroid guidelines. J Assoc Physicians India 2011;59:26-31.  Back to cited text no. 3
4.Weetman AP. Graves' disease. N Engl J Med 2000;343:1236-48.  Back to cited text no. 4
5.Woeber KA. Thyrotoxicosis and the heart. N Engl J Med 1992;327:94-8.  Back to cited text no. 5
6.Dahl P, Danzi S, Klein I. Thyrotoxic cardiac disease. Curr Heart Fail Rep 2008;5:170-6.  Back to cited text no. 6
7.Brent GA. Clinical practice. Graves' disease. N Engl J Med 2008;358:2594-605.  Back to cited text no. 7


  [Figure 1], [Figure 2], [Figure 3], [Figure 4]


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