This short review article aims to provide updated information on the diagnosis and management of hyperthymidism. A second article will focus on the management of hypothymidism.peer-reviewe

Caruana, Noel

OAR@UM

Thyroid Disease: Diagnosis and Management of Hyperthyroidism Dr Noel Caruana This short rcview article aims to pmvide L1pdated information on the diagnosis and management ofhyperthymidism. A second article will focus on the management of hypothymidism. The most appropriate management of hyperthyroidism depends to a large extent on the proper diagnosis based on recognition of symptoms and signs of the disease followed by detem1ination of the underlying pathology. Graves disease is the most common underlying pathology followed by thyroiditis, multinodular goitre, toxic adenomas and iatrogenic causes. Graves disease, toxic adenoma and toxic multinodular goitre may be treated by surgery, antithyroid drugs or radioactive iodine. Treatment for hyperthyroidism caused by thyroiditis is usually symptomatic as the condition is usually transient. Treatment is not always straightforward however, as in such cases of associated ophthalmopathy in Graves disease and in patients who are pregnan tor breastfeeding. I t is very importan t to plan appropriate treatment with the patient. Thyrotoxicosis or clinical hyperthyroidism is due to the effects of surplus thyroid hormone and can be caused by different Signs and SymptOillS Older Patients Younger patients <50 years % Tachycardia Fatigue Weight loss Goitre Tremor Apathy Anial fibrillation Anorexia Nervousness Hyperactive reflexes Depression Increased sweating Polydipsia Heat il1tolerance Increased appetite > 70 years % 7l 56 50 50 44 41 35 32 31 28 24 24 21 15 0 96 84 51 94 84 25 2 4 84 96 22 95 67 92 57 Tablci : 1I1cidcl1cc of Signs and Symptoms ofhyperthyroidism 76 VOlUME 14 ISSUE 02 DECEMBER 2005 disorders. Prevalence of hyperthyroid disease based on community studies has been estimated at 2% in females and 0.2% in males Thus a family practice of 2500 patients is expected to have a prevalence of ten thyroid cases with one new case annually. The clinical diagnosis of an over active thyroid can be difficult as the initial clinical deviations from normal can be minima!. Symptoms are caused by the thyroid hormone's stimulation of the enzymatic catabolic activity and increased sensitivity to cathecholamines. Symptoms are usual1y more flOlid in younger patients, elderly patients may present with only cardiovascular signs such as atrial fibrillation and tachycardia, or with unexplained weight loss. Common symptoms and signs are listed in Table 1 ,,~th an emphasis on the differences in presentation between old and young patients. Tests for thyroid disorders Thyroid function tests With the highly sensitive TSH assays it is now possible to distinguish suppressed TSH levels in hyperthyroid states from low but normal-10w TSH levels in the euthyroid state. lt should however be noted that tests on their own are not foolproof and should be interpreted vvith the clinical situation in mind. Serum tri-iodothyronine (13) and free thyroxine (14) measurements can be useful in suspected T4 toxicosis where serum T41evels may be nom1al. 13 and T 41evels are also useful for monitoring patients on treatment for thyroid dysfunction . Thyroid autoantibodies Raised antimicrosomal and antithyroid peroxidase antibodies are indicative of Hashimoto's autoimmune thyroiditis . Antithyroglobulin and antimicrosomal antibodies are characteristically elevated in Graves' disease. Thyroid stimulating antibody (Thyroid-stimulating hormone receptor antibodies) levels are also used to monitor the effects of treatment of Graves' disease with antithyroid drugs. Maltese Family Doctor It-Tabib tal-Familja Thyroid ultrasound A thyroid ultrasound is usually more sensitive at detecting thyroid nodules. With ultrasound it is easier to diagnose a multinodular goitre which was clinically thought to be a solitary nodule (other nodules not being palpable clinically). This finding has clinical and prognostic significance as a multinodular goitre is said to be less likel)' to be malignant than a single nodule. It can also differentiate a solid mass from a cystic one. Also, high resolution Ultrasound is better than CT in assessing glandular texture. CT sean This examination is particularly useful to determine if there is any compression of the trachea and if there is any retro stemal and retrotracheal extension as sometimes happens in Hashimoto thyroiditis. It will also show the presence of a calcified adenoma or cyst. Fine needle Biopsy This is the most cost-effective test in the diagnosis of thl'roid nodules, when the nature of the goitre is stil! in doubt. It is also the best wal' to assess a nodule for malignancy. Multiple biopsies may be taken under local anaesthetic, but it is to be remembered that with small biopsl' specimens, false negative result is a possibility. Cause Graves disease thyroid stimulating ab Pathophysiology Increased stimulation of gland Aet iology (see Table 2) Graves Disease This is the most common cause of hyperthyroidism, and accounts for up to 75% of all cases . It is classified as an autoimmune disease caused byan anti TSH receptor antibodl' which stimulates the gland to synthesize and secrete more thl'roxine. There is an increased prevalence of HLA-DR3 which thus appears to occur in a geneticalll' predisposed population, and mal' be associated with other autoimmune diseases. An infiltrative ophthalmopathl' accompanies Graves' disease in 50% of cases. 4 Toxie Multinodular Goitre This usualll' has a more insidious onset, and typicalll' occurs in patients over the age of 50 years who have a longstanding historl' of goitre. The nodules are usualll' tender. Toxie Adenoma These are usualll' found in younger individuals especially in iodine deficient areas. There is a single autonomously functioning nodule which is not tender to palpation. Thyroiditis Typically is abrupt in onset and usually follows a vi ral infection. The symptoms may be quite severe and are due to Gland size Nodularity Increased None Toxic multinodular goitre Autonomous honnone production lncreased Multiple nodules " Subacute thyroiditis Toxic adenoma Lymphocytic thyroiditis Iodine-induced (iodide, amiodarone contrast media) Functioning pituitary adenoma (TSH; trophoblastic tumour hCG Factitial hyperthyroidism Metastatic thyroid cancer ' Tencln gla nd Table 2: Aetiology \I altcsc Famih- Dacto r 'l-llhb (:l, . F,l'''''''' Leakage of hormone from gland Increased None* Autonomous hormone production Decreased Single nodule Leakage of hormone from gland Increased None Substance causing stimulation of gland Increased Multiple or None lncreased glandular stimulation lncreased None Exogenous hormone intake Decreased None Extraglandular hormone production Decreased None , l "" 4 '<;Sll" C? ~I'CEM'l~1'I 'ors 77 hormone leaking from an inflamed gland. Symptoms usually resolve within a few months. Postpartum thyroiditis can occur in up to 10% of women in the first six months after delivery The hyperthyroid state may lead to a transient hypothyroid state before resolution 5 Tumours It is indeed quite rare to have a tumour as a cause of hyperthyroidism. Such tumours include: metastatic thyroid cancer, ovarian tumours that produce thyroid hormones and trophoblastic tumours that produce human chorionic gonadotrophin which activate TSH receptors. Pituitary tumours also produce TSH. I nvestigation The initial most significam test to be done in a patient with signs and symptoms of hyperthyroidism is TSH estimation. A very low TSH level is diagnostic ofhyperthyroidism. An algorithm for investigating suspected hyperthyroidism is illustrated in figure 1. An elevated TSH warrants the estimation of freeT4 levels, which if high, indicate secondary hyperthyroidism and necessitate pituitary gland imaging. characteristically elevated in Graves disease. Thyroid stimulating antibody levels are also used to monitor the effects of treatment of Graves disease with antithyroid drugs. Management of hyperthyroidism Main principles of management: 1. Establish precisely the cause for the hyperthyroidism before starting treatment (Figure 1) 2. Educate your patient and emphasise the need for lifelong monitoring due to possibility of relapse 3. Monitor for cardiovascular complications and osteoporosis The aim of treatment is to correct the hypermetabolic - state with the least possible side effects including hypothyroidism. The main treatment options are; antithyroid drugs, radioiodine and surgery. The choice depends on the patient's age, size of goitre, co morbidity and patient's desires. Anti-thyroid drugs This class of drugs works by interfering with the organification of iodine thus suppressing thyroxine levels. Carbimazole is used locally with a dose of 10-45 mg daily (Methimazole and propylthiouracil are two agents used in the United States) Relapse Antibody studies can occurin up to 50% of patients hence the importance of regular Raised antimicrosomal and antithyroid peroxidase follow-up. A recent RCT6 showed that patients with a large goitre, antibodies are indicative of Hashimoto's autoimmune thyroiditis. who smoked and had high thyroid-stimulating antibody levels at Antithyroglobulin and antimicrosomal an tibodies are end of treatment had higher relapse rates. LowTSH ( High 14 Measure 13 H Normal14 Normal13 Primary hyperthyroidism I J Measure 13 Antibody studies High 13 Thyroid uptake Radionucleotide scan Resolving 13 toxicosis hyperthyroidism ( l High uptake Low uptake 1 ) Exogenous hormone l. Graves diffuse uptake (Low thyroglobulin level) 2. Nodular Toxic multi nodular OR Thyroiditis (high thyroglobulin) OR toxic Adeneoma (hot spot) Figure 1: AIgorithl11 for investigating low TSH level in suspected l1yperthymidisl11 J 78 VOLUME 14 ISSUE 02 DECEMBER 2005 Maltese Family Doctor !t-Tabib tal-Familja Carbimazole is usually the drug of choice( Propylthiouracil 100-200mg daily is used in pregnancy) , with a starting dose of 10mg daily and can be given in combination with Propranolol 10-40 mg 6-8 hourly. 7 The beta blocker is tapered down over a period of one to two months, and the carbimazole is titrated according to clinical response and monthly free T4 towards a normal T} and T , level. lt is important to note that the TSH levels may remain very low despite the patient having retumed to the normal state with treatment, and should not be used to gauge treatment. After one year of treatment, if the anti-TSH-receptor antibodies are not detectable one can stop the anti-thyroid treatment 4 The patient should be monitored every three momhs during the first year as relapse on stopping treatment is common. Once a relapse occurs it is usually recommended that radioactive iodine (illI) therapy or subtotaV total thyroidectomy be considered. The risk of agranulocytosis is the most serious complication of antithyroid treatment and patiems should be warned to stop treatment if they develop sudden fever or sore throat. Arthralgia and polyarticular arthritis may also occur, although to a minor extent. Surgery A subtotal thyroidectomy is the most common performed procedure; it preserves some thyroid tissue and hence reduces the risk of hypothyroidism. Total thyroidectomy is reserved for very large goitres and those with very severe symptoms, in whom recurrences are !ikely. This procedure however carries a high risk of hyper parathyroidism and laryngeal nerve damage8 Radioactive therapy Radioactive iodine is gradually replacing surgery, and in the United States it is the preferred mode of treatment for Graves' disease and toxic nodular goitre. There is stil! much debate about the treatment regime of radioiodine. Gland-specific dosage , based on the estimated weight of the thyroid gland, allows a lower dosage to be given and is associated with lower incidence of hypothyroidism, but may have a higher recurrence rate. There is stil! reluctance to use radio therapy in women of child bearing age because of the possibility of cancer of thyroid, genetic damage to offspring and leukaemia, however long term study of these patients has failed to support these fears9 Patients with toxic adenomas and toxic nodular goitre are more radio resistant and need higher dose regimen to achieve remission. lt is important to note that up to 15 % of patients treated with radioiodine, may develop Graves' ophthalmopathy. Opthalmopathy may be controlled or its incidence reduced with the use of 40 to 80mg of Prednisolone dailyI° Maltese Family Doeror lt-Tabib tal-Familja Precautions on radioactivity hazards. Most radioactive sodium iodide is excreted via saliva, urine and feaces within 48 hours of receiving the dose. Close contact with persons should be avoided for up to three days, especially children and pregnant women. lt is also recommended to double flush toilet and repeat hand washing for 12 weeks 9 Outcome and follow-up Patients receiving appropriate management have a good prognosis. Some extra-thyroid manifestations of the disease , notably ophthalmopathy, and cardiac complications are resistant to all forms treatment. In view of increased morbidity, patients who have been treated for hyperthyroidism should be screened annually, with special emphasis to atherosclerosis, osteoporosis, diabetes and insidious hypothyroidism 11 . References l. Turnbridge W M, Evered DC, Clark Fer al. The spectrum of thyroid disease in a community: the Whickham survey. C1in Endocrinol (Oxf) 1977; 7: 481-93. 2. Trivalle C, DoueetJ Chassagne Pet al. Differenees in the signs and symptoms of hyperrhyroidism in older and younger patients. J Am Geriarr Soc 1996; 44:51. 3. Weetman AP Graves Disease. New England J Med 2000; 343:1236-48. 4. Woeber KA. Update on the management of hyperrhyroidism and hypothyroidism. Areh Intern Med 2000;160:1067-71. 5. Slatosky j , Shipton B, Wahba H. Thyroidiris: differential diagnosis and management. Am Fam Physician 2000; 6l:l047-52. 6. Nedrebo BG, Holm PA, Uhlving Set al. Predietors of omeome and comparison of different drug regimes for the prevention of relapse in patients with Graves' disease. EurJ Endoerino12002; 147:583-9. 7. Cooper DS. Antithyroid drugs. N Englj Med 2005; 352:905-17. 8. Alsanea 0, C!ark OH. Trearment of Graves' disease: the advantages of surgery. Endoerinol Metab Clin North Am 2000; 29:321-37. 9. Meier DA, Brill DR, Beeker DV et al. Society of Nuclear Medicine Proeedure guideline for therapy of thyroid disease lvith sodium iodide. htrp:// interaetive.snm.orgldoes/p&... eh26 _ 0403. pdf. 10. Bartalena L, Maloeei C, Bogazzi F et al. Relation between therapy for hyperthyroidism and the eourse of Graves' ophrhalmopathy. N Englj Mecl1998; 338:73-8. 11.Tene C, Zarate A Basuno L et al. COITeetion of insulin resisranee in merhimazo\e-treared patients \vith Graves' disease. Rev lnvest C1in 2001;53:531-5. Noel CARUANA MD MSc General Practitioner Email: noekaruana@gmail.com VOLUME 14 ISSUE 02 DECEMBER 2005 79 

Thyroid disease : diagnosis and management of Hyperthyroidism

https://www.um.edu.mt/library/oar//bitstream/123456789/21383/1/Maltese%20Family%20Doctor%2014%282%29%20-%20A8.pdf

Thyroid disease : diagnosis and management of Hyperthyroidism

Abstract

Similar works

Full text

Available Versions

OAR@UM