Author:  Kapre, Madan - Director, Neeti Clinics,  Nagpur, Maharashtra, India

Abstract:  A concise logical review of the evaluation of a patient with a thyroid nodule is presented.  Important items in the physical examination and history are presented along with the techniques of fine needle biopsy of the thyroid and thyroid ultrasonography.  Three cases are presented: One of a patient with a right true vocal cord paralysis due to papillary carcinoma, another with a thyroid nodule and a third with tubercular lymphadenitis presenting as a possible thyroid mass.  

Introduction:  One of the most challenging tasks a modern physician faces is judging the nature and thereby advocating precise and adequate management of a solitary thyroid nodule.  The magnitude of the problem is even further amplified by the plethora of available information and investigations.  Information through patient friendly website adds further to the woes of the clinician as these sites may have unavoidable bias.  The author himself has a rather underprivileged background and lays more stress on baseline clinical and investigatory techniques in the assessment of thyroid nodules.    The prevalence of thyroid nodules varies depending upon the diagnostic criterion applied and so does the incidence of true solitary thyroid nodules.  The author’s own experience working in tribal areas of Melghat (India) reveals that amongst 171 patients initially thought to have solitary nodules,  132 progressed to multinodular goiters and only 39 remained truly solitary.  Diagnostic algorithms are the same as they have always been since our early clerkship days – History, Clinical examination, bed-side maneuvers, along with laboratory and imaging studies.  

Patient Evaluation:      Download Dr Kapre PowerPoint PDF Presentation on Slides.   download pdf file

History:  A thorough patient history will reveal facts about their thyroid disease function, risk and patient satisfaction factors.  Inflammatory thyroid disease be it acute inflammatory condition, like DeQuervain thyroiditis, or more chronic variety like Hashimoto’s autoimmune thyroiditis will reveal fever, pain, malaise and local tenderness.

Tenderness on thyroid is usually exquisite in acute inflammatory conditions where as chronic lymphocytic thyroiditis would have minimal tenderness which is confined to one or the other thyroid lobes.  Such patients often recevie a clinical label of gastroesophageal reflux disease or styloid glossalgia.  Firm palpation of the gland with the flat of the fingers while having the patient swallow will demonstrate exquisite local tenderness and thereby establish the diagnosis.

Pain in a thyroid nodule may indicate one of the following:

1. Bleeding into a benign colloid cyst.
2. Malignant transformation in a benign nodule
3. A malignant nodule
4. An inflammatory nodule or abscess

Hoarseness of Voice can either be due to hypothyroidism which is often characterized by voice fatigue or involvement of the recurrent laryngeal nerve (RLN) which may cause either vocal cord paresis or palsy with a characteristic husky or weak voice.  Occasionally, the voice may be normal in unilateral RLN palsy as the insidious nature of the palsy gives ample time for compensatory mechanisms.  Bilateral palsy due to massive tumors may have near normal voice but shortness of breath on mild exertion will be evident.  Changes in voice in longstanding thyroid nodules indicate a sudden increase in size, likely to be due to malignant transformation.  Stridor is a very alarming symptom indicating advanced disease. 

This video is of a 70 year old patient with a vocal cord paralysis caused by a Stage III papillary carcinoma of the thyroid. The tumor was four centimeters and wrapped around the Recurrent Laryngeal Nerve.There was also invasion of the strap muscles and inferior nodal spread.

View Video

Dysphagia is rather sinister if it should occur in a thyroid nodule patient.  It indicates extrathyroidal spread and nerve involvements either motor or sensory.  However a benign thyroid nodule lying posteriorly in the tracheoesophageal groove may also cause dysphagia due to the interference in the swallow mechanism.

The size of the thyroid nodule may not be as relevant as its histopathological status but it is generally accepted that nodules greater than 2 cm should be considered with caution and those greater than 4 cm usually indicate that they may have broken the capsule at some location or site, hence they need a full work-up.  However, a recent increase in size could either mean bleeding into a colloidal cyst or malignant disease.

Multiplicity of nodule within the thyroid gland itself may favor a multinodular goiter but presence of another nodule or swelling away from the thyroid gland should ring an alarm of metastatic disease.  Recent onset of difficulty in breathing or hemoptysis or bone pains should be considered as local or distant spread of a malignant disease.

Retrosternality of the thyroid mass usually gives classical postural dyspnea and fullness of neck veins, information which the patient will usually volunteer.

The functioning of thyroid gland needs to be determined.   A baseline evaluation also needs to be made.   Weight loss, sweating, tremors, anxiety state, sleeplessness and wet palms would point to a hyperactive state.  Weight gain, apathy, sleepiness would point to a hypothyroid state.   Risk assessment for malignancy could be further made by
enquirying into the patient’s age, sex, duration of the disease, familial occurrence, exposure to radiation or treatment with radioactive iodine for hyperthyroidism.

The author feels the last, but not the least, of enquiry into the reason for the patient’s visit to the surgeon should be documented and weighted on its own merit.
  

Clinical Examination:  A brief general examination will go a long way to assess the function of the thyroid and the status of the patient in general.  It is important to note the patient's pulse, weight, hair, skin texture, edema of feet, etc.  A sweaty palm and anxious looking eyes would tell a tale of hundred words.

The examiner is encouraged to examine and palpate the thyroid gland from standing behind the patient and asking the patient to relax and swallow frequently to accurately assess the size, tenderness, mobility and the lower edge of the tumor.

1. Pemberton’s Maneuver: The patient is asked to raise his arms above the shoulder and watched for breathlessness and fullness of neck veins. Occurrence of these signs would mean a retrosternal significant extension and compression of the vascular compartment of the superior mediastinum.
 
2. Patient is asked to lie supine and head extended with a pillow under the shoulder, upon swallowing if one is able to slip a finger under the lower border of the swelling it is very easily postulated that the help of the thoracic surgeon will not be required and the so called retrosternal goiter could be delivered per neck. (Please note CT are usually performed in supine position).

Importance of assessment of the mobility of the vocal cord either by mirror examination or by a Hopkin’s Rod rigid fiberoptic laryngoscoy is mandatory. It will not only forewarn of the malignancy but also it may also provide a medicolegal defense, since quite often RLN palsy is slow in onset and the patient may not have change in voice. This occurs most often, if both the vocal cords are paralyzed and in cadaveric position, resulting in a voice which may be normal at rest.

The picture on the far right is of a normal larynx with symmetrical vocal cords.  The picture on the left shows a larynx with a right true vocal cord paralysis from a laryngeal cancer.  The right true vocal cord is shorter than the left.
 

Talk to the patient and the history will guide your management

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Once the anatomical diagnosis is confirmed,  the next issue ahead is to establish a pathological diagnosis. There could be a battery of investigations available and are often misused. The scope of this script does not allow detailed discussion on all of them but in our practice we take help of ultrasonograpy (USG) and Fine Needle Aspiration Cytology (FNAC) as minimal tools.

Ultrasonography:     Although an operator-dependent investigation, USG for neck is rapidly proving to be an imaging technique of primary choice, there is lot to be said if surgeon trains himself in this imaging modality.  USG can also be used to aid in the differentiation between benign and malignant nodules.1,2   The following criteria can be used by USG, and favor a diagnosis of malignancy:

1)  Absence of a halo sign
2)  Uniformly solid tumor with occasional central necrosis
3)  Irregular margins
4)  Fine calcifications
5)  Heterogenous echos and large size
6)  Surrounding tissue invasion

Below are Pictures from a Patient with tubercular lymphadenitis next to the thyroid gland.  The thyroid gland is normal on ultrasound and the pathology is between the left thyroid lobe and the carotid artery.   Click on Pictures to Enlarge  

      

Picture 1 (left):  The patient presents with a neck mass which on physical exam mimics a thyroid nodule.
Picture 2 (middle):  The thyroid ultrasonography demonstrates that the mass is separate from the thyroid.  (mouse over to label the ultrasound.) 
Picture 3 (right):  Needle biopsy produces a white granular fluid, characteristic of tubercular lymphadenitis.  

The scope of USG is obvious as it can help to identify and objectively document the nature of the thyroid nodule.  The size, number and identifying the non-palpable nodules can change solitary status of the nodule instantly.  USG is a very useful tool for evaluating nodules which are either managed medically or are observed for indeterminate cytology report.  Above all, FNAC coupled with USG has not only optimized the cytological yield but increased accuracy to aid the clinician in following his cases.  In fact, the author insists upon his pathologist to work with the sonologist and even primary FNAC is done under USG patients.3,4  In summary, diagnostic USG aids in confirming or disproving the solitary status of the nodule, solid or cystic or mixed consistency of the nodule, size of the nodule and guides the physician in making the correct management decisions and diagnosis.  
   
Other imaging modalities like CT, MRI or PET coupled with CT and radionucleide scans are reserved for further assessing the nodule regarding its anatomical extent but rarely used for diagnosing its pathological status.  For this reason the author does not recommend the use of these modalities as primary diagnostic tools.  It should always be remembered that Iodine contrast material used in CT scans may interfere with I-131 therapy and have an adverse effect on patient treatment in the event the nodule is found to be a thyroid cancer.

Fine Needle Aspiration Cytology:    Click On Pictures To Enlarge

Initial skepticism by pathologists and clinicians with regards to Fine Needle Aspiration Cytology has gradually diminished and this technique has gained acceptance in USA and UK by the mid 1980’s.  Today it is practiced worldwide.  A large body of world literature attests to the accuracy and advantages of the cytological techniques for screening of thyroid nodules.   With experience and meticulous attention to technique, clinical correlation and caution in interpretation, it has been possible to reduce the false positive and false negative cytological diagnosis to 5 %.

The sensitivity and accuracy is as high as 95% in experienced hands.  Positive predictive values of 90-98% and negative predictive value of 94 to 99% have established FNAC as an invaluable diagnostic modality.
5

Papillary carcinomas, medullary carcinomas, anaplastic carcinomas, lymphomas and metastasis can be accurately diagnosed with 90-95% accuracy.    However, if a follicular neoplasm is reported, some studies have found one in four patients to have a carcinoma.
6

Cytology is an excellent method for study of inflammatory and autoimmune thyroid lesions.  The natural history of the disease may be better understood by sequential cytological monitoring.  Association of lymphoma in Hashimoto’s Thyroiditis is well-known and can be picked up early, by cytological monitoring.

Some dare credit this investigation as a desert island choice amongst all others.  Issues about dry vs wet preparations and who actually performs the test can best be settled by mutual convenience between the surgeon and the pathologist. Undeniably, logistics of patient comforts and economics cannot be overruled by the desires of the clinician.  However, the number of false negatives or indeterminate reports can be significantly reduced by a healthy mutual trust and frequent feedbacks.

Summary:

Author has made an attempt to put forward a simple diagnostic philosophy in assessing the thyroid nodules.  It is quite obvious that the clinical behavior of all nodules can be predicted with this scheme.  Unreservedly, the author accepts the limitations of arriving at the diagnosis of a thyroid nodule with these three clinical methods alone.

It only resonates the old saying: “How Much Can Be Done With How Little”.

References:

1)  Nóbrega LH, Paiva FJ, Nóbrega ML, Mello LE, Fonseca HA, Costa SO, et al.  Predicting malignant involvement in a thyroid nodule: role of ultrasonography.  Endocr Pract. 2007 May-Jun;13(3):219-24.   View Abstract

2)  Wong KT &  Ahuja AT.  Ultrasound of thyroid cancer   Cancer Imaging. 2005; 5(1): 157–166.    Published online 2005 December 9.   View Article

3)  Izquierdo R, Arekat MR, Knudson PE, Kartun KF, Khurana K, Kort K & Numann PJ.   Comparison of palpation-guided versus ultrasound-guided fine-needle aspiration biopsies of thyroid nodules in an outpatient endocrinology practice.  Endocr Pract. 2006 Nov-Dec;12(6):609-14.   View Abstract

4)  Bhatki AM, Brewer B, Robinson-Smith T, Nikiforov Y & Steward DL.  Adequacy of surgeon-performed ultrasound-guided thyroid fine-needle aspiration biopsy.  Otolaryngol Head Neck Surg. 2008 Jul;139(1):27-31.  View Abstract

5)  Kim DW, Lee EJ, Kim SH, Kim TH, Lee SH, Kim DH & Rho MH.   Ultrasound-guided fine-needle aspiration biopsy of thyroid nodules: comparison in efficacy according to nodule size.   Thyroid. 2009 Jan;19(1):27-31.   View Abstract

6)  Mihai R, Parker AJ, Roskell D & Sadler GP.  One in four patients with follicular thyroid cytology (THY3) has a thyroid carcinoma.  Thyroid. 2009 Jan;19(1):33-7.  View Abstract

Editors Note:  To learn more about the parable "The Seven Blind Men and an Elephant" go to:
http://www.cs.princeton.edu/~rywang/berkeley/258/parable.html 


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