History

Fact Explanation
Fullness of the neck with sometimes visible and palpable nodules. When the thyroid gland is unable to meet the metabolic demands of the body with sufficient hormone production, thyroid gland compensates by uniform follicular epithelial hyperplasia which results in diffuse enlargement. If the thyroid gland is then re-exposed to iodine, the area of follicular hyperplasia undergoes involution and fibrosis. This causes the thyroid gland to have hyperplastic areas as well as involuted areas which results in multiple nodules.[1,2]
Pain Haemorrhage into a nodule.[1,2]
Rapid enlargement Haemorrhage into a nodule or a malignant change.[1,2]
Positional and nocturnal dry cough, dyspnoea, dysphonia and stridor Narrowing of the the trachea by the compressive force caused by enlarged thyroid gland. [1,2]
Dysphagia for solid foods and pills. Compression of the oesophagus by the enlarging gland cause this but this is rare as the muscular esophagus merely relocates itself when compressed.[1,2]
Hoarseness of voice. Compression or invasion of the recurrent laryngeal nerve by a goiter or thyroid malignancy results in vocal cord dysfunction.[1,2]
Iodine intake Iodine deficiency can be the etiology.[1,2]
Any history of head and neck radiation exposure,during childhood, Increases the risk of nodular thyroid disease (benign and malignant) and thyroid dysfunction.[1,2]
Drug history Ex: amiodarone This could cause thyroid dysfunction and a goiter since it contains high iodine concentration.[1,2]
Family history Familial forms (familial medullary carcinoma of the thyroid and multiple endocrine neoplasia) and familial papillary carcinoma of the thyroid can present as a nodular goiter.[1,2]
Symptoms of hyperthyroidism: heat intolerance,increased appetite,loss of weight,diarrhoea,oligomenorrhoea,irritability,palpitations To exclude a toxic nodular goitre.[1,2]
Very young or advanced age (<30 or >60 yr old) Increases the risk of malignancy.[1,2]
Male gender Increases the risk of malignancy.[1,2]
References
  1. BAHN REBECCA S., CASTRO M. REGINA. Approach to the Patient with Nontoxic Multinodular Goiter. The Journal of Clinical Endocrinology & Metabolism [online] 2011 May, 96(5):1202-1212 [viewed 28 May 2014] Available from: doi:10.1210/jc.2010-2583
  2. Holzheimer RG. Benign nodular thyroid disease. In: Holzheimer RG, Mannick JA, editors. Surgical Treatment: Evidence-Based and Problem-Oriented. Munich: Zuckschwerdt; 2001. Available from: http://www.ncbi.nlm.nih.gov/books/NBK6893/

Examination

Fact Explanation
Pemberton maneuver by raising the patient’s arms above the head for 1 minute. Positive finding occurs with facial plethora or engorgement of the neck veins. If the goiter is enlarged retrosternally ,when the arms are raised thoracic inlet is further narrowed compressing the superior vena cava.[1]
Dull percussion note below the sternum Goitre has extended retrosternally.[1]
Butterfly shaped, midline neck mass which moves upwards with swallowing Indicates it's a mass arising from the thyroid gland.[1]
On palpation asymmetrical mass with nodules. Indicates it's a multinodular goiter.[1]
Cervical lymphadenopathy Indicates that it's more likely to be malignant.[1]
Tracheal deviation Indicates the goitre has compressed the trachea.[1]
Displaced and/absent carotid pulses Indicates the goiter has compressed and displaced the carotid artery.[1]
Irregularly, irregular pulse rate or increased pulse rate,palmar erythema,lid lag,brisk reflexes,tremor Most multinodular goitres are euthyroid but its useful to screen for these signs on examination which will Indicate it's a toxic goitre.[1]
Bruit over the goitre. Indicates increased vascularity.In a nodular goitre it's a sign which makes it malignant.[1]
Hard/soft consistency, fixed/ mobile nodules, nodule size Hard , fixed and nodules greater than 4cm are likely to be malignant whereas soft, mobile and nodules less than 4cm are likely to be benign.[1,2]
References
  1. BAHN REBECCA S., CASTRO M. REGINA. Approach to the Patient with Nontoxic Multinodular Goiter. The Journal of Clinical Endocrinology & Metabolism [online] 2011 May, 96(5):1202-1212 [viewed 28 May 2014] Available from: doi:10.1210/jc.2010-2583
  2. MARY JO WELKER, and DIANE ORLOV,, Ohio State University College of Medicine and Public Health, Columbus, Ohio,Thyroid Nodules,Am Fam Physician. 2003 Feb 1;67(3):559-567.

Differential Diagnoses

Fact Explanation
Thyroid Carcinoma (Follicular,medullary,papillary) Hard fixed nodules,cervical lymphadenopathy,malignant findings from the US and FNA investigations can differentiate malignancy from a benign non toxic MNG.[1,2]
Inherited defects in thyroid hormone synthesis This could cause a MNG with hypothyroidism.[2]
Endemic goiter This could also cause a MNG with hypothyroidism.[2]
Toxic multinodular goiter (Plummer's disease) TSH and T4 assay can differentiate between a toxic and a non toxic MNG.[2]
Benign follicular goitre. FNA can't exclude a malignancy.Therefore a biopsy has to be done after the surgery to exclude a malignancy.[2]
Hashimoto's thyroiditis It may present with a high-normal to elevated TSH and apparent nodularity, which may represent focal lymphocytic infiltration (pseudonodules). US evaluation is often helpful in distinguishing these findings from true thyroid nodules. The measurement of serum thyroid peroxidase antibody levels may be helpful because moderate to high levels are indicative of coexisting autoimmune thyroid disease.[2]
References
  1. David S. Cooper, Gerard M. Doherty, Bryan R. Haugen, Richard T. Kloos, Stephanie L. Lee, , Susan J. Mandel, Ernest L. Mazzaferri, Bryan McIver, Furio Pacini, Martin Schlumberger, Steven I. Sherman,David L. Steward and R. Michael Tuttle, Revised American Thyroid Association Management Guidelines for Patients with Thyroid Nodules and Differentiated Thyroid Cancer, November 2009,
  2. BAHN REBECCA S., CASTRO M. REGINA. Approach to the Patient with Nontoxic Multinodular Goiter. The Journal of Clinical Endocrinology & Metabolism [online] 2011 May, 96(5):1202-1212 [viewed 28 May 2014] Available from: doi:10.1210/jc.2010-2583

Investigations - for Diagnosis

Fact Explanation
Serum TSH and T4 assay. Normal TSH and T4 level will exclude toxic goitre.[1]
Ultrasound (US) All ultrasound examinations for thyroid nodule should include a malignancy risk assessment based on the markedly hypoechoic nature of the nodule, presence of microcalcifications, ill-defined margins, nodule with shape taller than wide,absent halo and intranodular hyper vascularity at color Doppler. On the other hand, if each of the nodules has benign sonographic appearance (i.e. well-defined borders, a peripheral halo, iso- or hyperechogenicity) These features also assist in the selection of nodules that may need fine-needle aspiration biopsy. The main US features for malignant adenopathy include: rounded lymph node, loss of normal echogenic fatty hilum, and loss of normal hilar vascularization. Several patterns are highly suggestive of thyroid cancer metastasis: microcalcifications, cystic components, hyperechoic nodes, mimicking thyroid tissue.[1]
X-ray of the neck To see the retrosternal extension and tracheal deviation.It can also visualize calcification in the thyroid cartilages in long standing goiters.
Fine-needle aspiration biopsy of the nodule, with or without ultrasound (US) guidance. In US if only benign features are present only the largest or “dominant” nodule(s) should be aspirated, and the rest should be observed with serial US. Whereas in the other hand malignant looking nodules from the US should be aspirated. Interpretations are reported as benign, malignant, suspicious for a follicular or Hürthle cell tumor, insufficient.[1]
thyroid scintigraphy (using either technetium 99mTc pertechnetate or 123I) If low serum levels of TSH is found it suggest an overt or subclinical hyperthyroidism and indicates the presence of hyperfunctioning (“hot”) nodules which is unlikely malignant.Therefore FNA is not usually done. Results of scintigraphy should be compared with the US images, and FNA should be considered only for iso- or nonfunctioning nodules, particularly those with suspicious sonographic features.[1]
Computed tomography (CT) and magnetic resonance imaging(MRI) These investigations are helpful in the assessment of patients with large goiters, those with suspected substernal extension, and/or those with obstructive or pressure symptoms because they provide a good assessment of goiter size and its positional relationship to surrounding structures . Since these imaging modalities are expensive and CT imaging of patients with MNG may require iodine-containing contrast agents for better definition, they are not recommended for routine evaluation of patients with thyroid nodules.[1]
References
  1. BAHN REBECCA S., CASTRO M. REGINA. Approach to the Patient with Nontoxic Multinodular Goiter. The Journal of Clinical Endocrinology & Metabolism [online] 2011 May, 96(5):1202-1212 [viewed 28 May 2014] Available from: doi:10.1210/jc.2010-2583

Investigations - Fitness for Management

Fact Explanation
Indirect laryngoscopy If thyroidectomy is performed as a treatment option this could damage the recurrent laryngeal nerve and result in dysfunction of the vocal cords.Therefore to assess the baseline vocal cord function indirect laryngoscopy is done. [1]
Serum Ca2+ level If thyroidectomy is performed as a treatment option this could cause a transient hypoparathyroidism or a permanent hypoparathyroidism if the parathyroid gland gets damaged.Therefore to get an idea about the baseline Ca2+ level is done.[1]
Direct laryngoscopy This is done to ascertain the difficulty of intubation and to calculate the Malampati/ Cormack Lehane score.
References
  1. Holzheimer RG. Benign nodular thyroid disease. In: Holzheimer RG, Mannick JA, editors. Surgical Treatment: Evidence-Based and Problem-Oriented. Munich: Zuckschwerdt; 2001. Available from: http://www.ncbi.nlm.nih.gov/books/NBK6893/

Investigations - Followup

Fact Explanation
Ultrasound Since a false-negative rate of up to 5% has been reported in patients with previous benign cytology , patients with MNG should be followed with US within 6 to 18 months of initial FNA and periodically thereafter (every 3–5 yr) to evaluate for nodule growth.[1]
Repeat biopsy This should be done if significant growth of a nodule (when there is at least a 50% increase in nodule volume within the first 6–18 months after initial FNA) or other worrisome clinical (persistent hoarseness, dysphagia, lymphadenopathy, etc.) or sonographic features develop on follow-up[1]
Serum calcitonin Routine measurement of serum calcitonin as a means to screen for medullary thyroid cancer in patients with thyroid nodules is for early detection of C-cell hyperplasia and medullary thyroid cancer.[1]
References
  1. BAHN REBECCA S., CASTRO M. REGINA. Approach to the Patient with Nontoxic Multinodular Goiter. The Journal of Clinical Endocrinology & Metabolism [online] 2011 May, 96(5):1202-1212 [viewed 28 May 2014] Available from: doi:10.1210/jc.2010-2583

Management - General Measures

Fact Explanation
Follow up without any treatment Unless there is compression of the trachea or esophagus, venous-outflow obstruction,malignant change,neck discomfort or cosmetic issues no treatment is needed.[1]
References
  1. BAHN REBECCA S., CASTRO M. REGINA. Approach to the Patient with Nontoxic Multinodular Goiter. The Journal of Clinical Endocrinology & Metabolism [online] 2011 May, 96(5):1202-1212 [viewed 28 May 2014] Available from: doi:10.1210/jc.2010-2583

Management - Specific Treatments

Fact Explanation
Thyroxine therapy Since TSH has been regarded as a growth factor for thyroid epithelial cells , treatment with levothyroxine in doses sufficient to suppress TSH has long been used to prevent or reduce growth of thyroid nodules. However, the effectiveness of this practice remains controversial. Although some studies have shown efficacy, others have failed to show a clear benefit. Before treatment with thyroxine serum thyrotrophin should be measured because patients may have autonomous thyroid hormone production and subclinical hyperthyroidism Because of the known deleterious effects on the skeleton associated with subclinical hyperthyroidism resulting from levothyroxine suppressive therapy and the increased risk of atrial fibrillation and other cardiovascular complications, this treatment modality is not recommended by the ATA(american thyroid association). It should be particularly avoided in postmenopausal women with evidence of low bone mass, in the elderly, and in those with cardiac disease, in whom the risk of this therapy generally outweighs its uncertain benefits .[2,3]
Radio iodine therapy(RAI) It resulted in significant goiter size reduction when compared with levothyroxine suppressive therapy, which offered no benefit, and improvement in obstructive symptoms (dyspnea, dysphagia) in the majority of patients. Some patients develop transient hyperthyroidism in the first 2 wk after RAI, and up to 45% become permanently hypothyroid and require lifelong thyroid hormone replacement (58). pretreatment with a single dose of 0.1 mg of recombinant human TSH (rhTSH) has been occasionally used successfully for carefully selected patients in some centers in Europe as adjuvant to RAI. It improves the efficacy of RAI by enhancing uptake in nontoxic thyroid tissue and allowing the use of lower doses of RAI, while still resulting in greater reduction of goiter size Painful transient thyroiditis and transient mild thyrotoxicosis may occur within the first month after treatment, and there is an increased incidence of subsequent hypothyroidism. Development of Graves' hyperthyroidism in patients with preexisting high thyroid peroxidase antibody concentrations has also been described after treatment of euthyroid MNG with RAI .[1,2]
Surgery This is the preferred treatment modality for patients with euthyroid,benign, large, obstructive, and substernal nontoxic MNG and those with continued growth. Near-total or total thyroidectomy is the procedure of choice for these patients. Complications of surgery such as injury to the recurrent laryngeal nerve, trachea, and parathyroid glands are more common in patients with large and substernal goiters. In long standing goiters pressure atrophy of the thyroid cartilages can result in tracheal collapse just after extubation.This is managed by tracheostomy or by inserting a tracheal stent. In suspicion of a malignancy total thyroidectomy with/ without cervical lymph node dissection and radiotherapy followed by supraphysiological doses of levo-thyroxine is given.[2,4,5]
References
  1. NYGAARD B, HEGEDüS L, GERVIL M, HJALGRIM H, SøE-JENSEN P, HANSEN JM. Radioiodine treatment of multinodular non-toxic goitre. BMJ [online] 1993 Oct 2, 307(6908):828-832 [viewed 28 May 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1678858
  2. BAHN REBECCA S., CASTRO M. REGINA. Approach to the Patient with Nontoxic Multinodular Goiter. The Journal of Clinical Endocrinology & Metabolism [online] 2011 May, 96(5):1202-1212 [viewed 28 May 2014] Available from: doi:10.1210/jc.2010-2583
  3. BANERJEE A, COOPER J. Nonsurgical treatment of multinodular nontoxic goitre. Postgrad Med J [online] 1995 Nov, 71(841):643 [viewed 28 May 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2398344
  4. Holzheimer RG. Benign nodular thyroid disease. In: Holzheimer RG, Mannick JA, editors. Surgical Treatment: Evidence-Based and Problem-Oriented. Munich: Zuckschwerdt; 2001. Available from: http://www.ncbi.nlm.nih.gov/books/NBK6893/
  5. FINDLAY J. M., SADLER G. P., BRIDGE H., MIHAI R.. Post-thyroidectomy tracheomalacia: minimal risk despite significant tracheal compression. British Journal of Anaesthesia [online] December, 106(6):903-906 [viewed 30 May 2014] Available from: doi:10.1093/bja/aer062