{"id":411,"date":"2012-03-01T00:00:06","date_gmt":"2012-03-01T07:00:06","guid":{"rendered":"http:\/\/rhochistj.org\/RCP_TEST\/?p=411"},"modified":"2014-02-17T16:22:56","modified_gmt":"2014-02-17T23:22:56","slug":"chf-a-rare-but-serious-presentation-of-graves-disease","status":"publish","type":"post","link":"https:\/\/rhochistj.org\/RhoChiPost\/chf-a-rare-but-serious-presentation-of-graves-disease\/","title":{"rendered":"CHF, a Rare but Serious Presentation of Graves\u2019 disease"},"content":{"rendered":"

By: James Schurr, Pharm.D. Candidate c\/o 2014<\/p>\n

–<\/p>\n

Graves\u2019 disease is an autoimmune disorder that results in a state of thyrotoxicosis, or a cause of hyperthyroidism, due to the Immunoglobulin G-mediated agonism of thyroid stimulating hormone (TSH) receptors located on the thyroid. \u00a0Stimulation of TSH receptors causes an increase in circulating thyroxine (T4<\/sub>) and triiodothyronine (T3<\/sub>) levels, leading to a hyperthyroid state.1<\/sup>\u00a0 This can lead to many adverse effects in the Graves\u2019 disease patient, including but not limited to cardiac complications. While not a common cause of congestive heart failure (CHF), Graves\u2019 disease can lead to CHF secondary to thyrotoxicosis.2-5<\/sup><\/p>\n

As defined in the American College of Cardiology \/ American Heart Association Practice Guidelines, CHF is \u201ca complex clinical syndrome that can result from any structural or functional cardiac disorder that impairs the ability of the ventricle to fill with or eject blood.\u201d6<\/sup> \u00a0The pathophysiological mechanism underlying the relationship between Graves\u2019 disease and CHF is increased cardiac function associated with a hyperthyroid state.4<\/sup>\u00a0 This includes an increased heart rate, cardiac output, cardiac contractility, and peripheral oxygen consumption.4<\/sup> \u00a0Additional cardiac complications could be due to activation of the renin-angiotensin-aldosterone system (RAAS), as a result of increased circulating T3<\/sub> levels.4<\/sup> \u00a0The primary treatment of Graves\u2019 disease typically consists of either antithyroid drugs, surgery, or radioactive iodine; secondary adjunctive treatments include iodides, \u03b2-blockers, calcium channel blockers, and corticosteroids.7<\/sup><\/p>\n

Thyroid hormone has profound effects on the cardiovascular system, particularly the myocardium and hemodynamics. \u00a0The autoimmune nature of Graves\u2019 disease is an interesting factor in the pathogenesis of this disorder, and allows for a multifaceted approach in its treatment (from immunologic, endocrinologic, and cardiologic perspectives). \u00a0The immune mechanism in Graves\u2019 disease involves the activation of thyroid-specific T helper cells, which recognize the endogenous TSH receptor.\u00a0 This leads to the stimulation of autoreactive B cells and anti-TSH receptor immunoglobulins. \u00a0The anti-TSH receptor immunoglobulins cause an activation of adenylyl cyclase in the thyrocyte.\u00a0 This leads to an increase in cyclic-adenosine monophosphate (cAMP) levels in the cell, and causes increased thyroid hormone secretion.1 <\/sup>\u00a0T3<\/sub> is the active cellular form of thyroid hormone, and is the key player in altering cardiac function in hyperthyroid states. \u00a0The direct effects of T3<\/sub> include increased tissue thermogenesis, decreased systemic vascular resistance (leading to a cascade of decreased effective arterial filling volume), increased renal sodium reabsorption, and increased blood volume.\u00a0 All of these culminate to increase cardiac inotropy and chronotropy, as well as cardiac output.4<\/sup> \u00a0Overall, the increase in heart rate and cardiac output, as well as widened pulse pressure, resemble an increased adrenergic state, which helps explain why thyrotoxicosis can lead to CHF.8<\/sup><\/p>\n

Patients with Graves\u2019 disease generally present with diffuse goiter, hyperthyroidism, exophthalmos, and dermopathy. \u00a0The onset of symptoms is gradual, beginning with nonspecific findings (including nervousness, emotional lability, and weight loss) and progressing to cardiac complications (such as tachycardia and exacerbation of cardiac complications in patients with preexisting heart disease).1<\/sup> \u00a0Heart failure is generally a rare occurrence (6%) in thyrotoxicosis patients, but requires attention because it can lead to death.2<\/sup><\/p>\n

Graves\u2019 disease is the most prevalent autoimmune disease in the United States.\u00a0 It affects women 7-10 times more than men, and generally, in the third and fourth decades of life.1<\/sup> \u00a0James Magner and colleagues described the significance of the rare complication of CHF in young women with Graves\u2019 disease.\u00a0 A 34-year-old woman diagnosed with Graves\u2019 disease presented with tremulousness, nervousness, heat intolerance, and diffuse headaches. \u00a0The patient had no history of heart disease, but physical examination and laboratory diagnostics confirmed a small goiter and immune-mediated hyperthyroidism consistent with Graves\u2019 disease. \u00a0Upon cardiac examination, she had a jugular venous pulse with prominent ventricular waves and 10-centimeter elevation, pedal edema, cardiomegaly on chest x-ray, pleural effusion, and ventricular hypertrophy.\u00a0 Her presentation was consistent with CHF. \u00a0Shortly after the patient died, an autopsy revealed a dilated heart with evidence of a chronic congestive cardiomyopathy.5<\/sup> The findings in this patient demonstrated a prime example of how detrimental CHF can be, even to a young, previously healthy Graves\u2019 disease patient.<\/p>\n

The initial treatment for Graves\u2019 disease involves one of three routes determined by patients and their providers, consisting of radioactive 131<\/sup>I therapy, antithyroid pharmacotherapy, or thyroidectomy.9<\/sup> \u00a0For treatment with antithyroid drugs, the thioamides (methimazole and propylthiouracil) are the drugs of choice.10<\/sup> \u00a0The American Thyroid Association and American Association of Clinical Endocrinologists recommend using methimazole when initiating antithyroid therapy in a Graves\u2019 disease patient, except for patients in their first trimester of pregnancy (where propylthiouracil is preferred). Methimazole is continued for 12-18 months; then, it is tapered off or discontinued if TSH levels return to normal.9<\/sup> \u00a0Methimazole and propylthiouracil are associated with toxicities in ><\/span>12% of treated patients.\u00a0 These toxicities include gastrointestinal distress, a maculopapular pruritic rash, hepatitis (more common with propylthiouracil), cholestatic jaundice (more common with methimazole), and agranulocytosis.10<\/sup> \u00a0Agranulocytosis is a rare but potentially fatal adverse effect of thioamides; therefore, prior to initiation of therapy, it is important to obtain baseline white blood cell counts with a white cell differential.9<\/sup> \u00a0131<\/sup>I (radioactive iodine) is the sole isotope available for treatment of Graves\u2019 disease. \u00a0Patients take it as an oral solution, and it is rapidly absorbed and concentrated in the thyroid.\u00a0 \u03b2 radiation emissions destroy the parenchyma, and abate the thyrotoxicosis.10<\/sup>\u00a0 Treatment recommendations also include considering a \u03b2-adrenoceptor blocker (such as metoprolol or atenolol) for patients with symptomatic thyrotoxicosis.9<\/sup>\u00a0 Propranolol is preferred because it reduces T3<\/sub> levels by 20% when given at doses of ><\/span>160mg daily.10<\/sup> \u00a0This therapeutic option overlaps treatment of CHF in patients who are not in acute decompensation, and therefore would appear to be a good choice of therapy.<\/p>\n

Cardiovascular effects of Graves\u2019 disease subside after appropriate management of thyrotoxicosis.11<\/sup>\u00a0 Therefore, it is imperative to treat the underlying autoimmune disorder in these patients and initiate appropriate CHF treatment based on patients\u2019 presentations.<\/p>\n

SOURCES:<\/span><\/b><\/p>\n

    \n
  1. Rubin, R. Rubin\u2019s Pathology: Clincopathic Foundations of Medicine. 5th Edition. Lipincott Williams & Wilkins. Philadelphia PA. 2008<\/li>\n
  2. Hong JY, Park DG, Yoo JJ, et al<\/i>. The Correlation Between Left Ventricular Failure and Right Ventricular Systolic Dysfunction Occuring in Thytotoxicosis. Korean Circ J.<\/i> 2010;40:266-271<\/li>\n
  3. Berlin T, Lubina A, Levy Y, Shoenfeld Y. Graves\u2019 disease Presenting as Right Heart Failure. IMAJ.<\/i> 2008;7:217-218<\/li>\n
  4. Epstein FH, Klein I, Ojamaa K. Thyroid Hormone and the Cardiovascular System. N Engl J Med.<\/i> 2001; 344,7:501-509<\/li>\n
  5. Magner JA, Clark W, Allenby P. Congestive Heart Failure and Sudden Death in a Young Woman with Thyrotoxicosis. West J Med.<\/i> 1988; 149: 86-91<\/li>\n
  6. Hunt SA, et al. ACC\/AHA guidelines in the evaluation and management of chronic heart failure in the adult: a report of the American College of Cardiology\/American Heart Association Task Force on Practice Guidelines. Circulation.<\/i> 2001; 104: 2996<\/li>\n
  7. Koda-Kimble MA. Applied Therapeutics: The Clinical use of Drugs. 9th edition. Lipincott Williams & Wilkins. Philadelphia PA. 2009<\/li>\n
  8. Levey GS, Klein I. Catecholamine-thyroid hormone interactions and the cardiovascular manifestations of hyperthyroidism. Am J Med.<\/i> 1990; 88: 642-6<\/li>\n
  9. Bahn, RS, Burch HB, Cooper, DS, et al.<\/i> Hyperthyoidism and other causes of thyrotoxicosis: management guidelines of the American Thyroid Association and American Association of Clinical Endocrinologists<\/li>\n
  10. Katzung BG, Masters SB, Trevor AJ. Basic and Clinical Pharmacology. 11th edition. McGraw-Hill. New York NY. 2009<\/li>\n
  11. Nakchbandi IA, Wirth JA, Inzucchi SE. Pulmonary hypertension caused Graves\u2019 thyrotoxicosis: normal pulmonary hemodynamics restored by 131I treatment. Chest.<\/i> 1999; 116: 1483-5<\/li>\n<\/ol>\n","protected":false},"excerpt":{"rendered":"

    By: James Schurr, Pharm.D. Candidate c\/o 2014 – Graves\u2019 disease is an autoimmune disorder that results in a state of thyrotoxicosis, or a cause of hyperthyroidism, due to the Immunoglobulin G-mediated agonism of thyroid stimulating hormone (TSH) receptors located on the thyroid. \u00a0Stimulation of TSH receptors causes an increase in circulating thyroxine (T4) and triiodothyronine…<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[7,4],"tags":[1971,343,261,22,61,52,2269,1218,198,15,60,2229,2227,420,314,2251,39,18,2253,291,363,968,1625,657,19,2244,2260,298,671,55,628,240,350,2252,149,453,1161,16,59,1061,1370],"class_list":["post-411","post","type-post","status-publish","format-standard","hentry","category-clinical","category-featured","tag-absorbed","tag-and","tag-atenolol","tag-blood","tag-calcium","tag-cardiac","tag-chest","tag-complex","tag-daily","tag-disease","tag-disorder","tag-drugs","tag-ebola-virus-disease","tag-factor","tag-for","tag-guidelines","tag-heart","tag-hepatitis","tag-hypertension","tag-metoprolol","tag-of","tag-one","tag-or","tag-oral","tag-patient","tag-pharmacology","tag-pressure","tag-propranolol","tag-r","tag-renal","tag-right","tag-sodium","tag-solution","tag-symptoms","tag-syndrome","tag-system","tag-therapy","tag-treatment","tag-weight","tag-with","tag-women"],"views":2684,"_links":{"self":[{"href":"https:\/\/rhochistj.org\/RhoChiPost\/wp-json\/wp\/v2\/posts\/411","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/rhochistj.org\/RhoChiPost\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/rhochistj.org\/RhoChiPost\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/rhochistj.org\/RhoChiPost\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/rhochistj.org\/RhoChiPost\/wp-json\/wp\/v2\/comments?post=411"}],"version-history":[{"count":0,"href":"https:\/\/rhochistj.org\/RhoChiPost\/wp-json\/wp\/v2\/posts\/411\/revisions"}],"wp:attachment":[{"href":"https:\/\/rhochistj.org\/RhoChiPost\/wp-json\/wp\/v2\/media?parent=411"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/rhochistj.org\/RhoChiPost\/wp-json\/wp\/v2\/categories?post=411"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/rhochistj.org\/RhoChiPost\/wp-json\/wp\/v2\/tags?post=411"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}