General Surgery Sheet #8 By Moh'd Bustani

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Lecture # 8 ((10.4.2012))
بسم الله الرحمن الرحيم
The Approach To a Thyroid Nodule
Thyroid is the most important endocrine gland.
Position: found in the anterior triangle of the neck, anterior to the trachea, larynx and cricoid which is above C1. So, It starts cranially at the oblique line on the thyroid cartilage (just below the laryngeal prominence, or 'Adam's Apple'), and extends inferiorly to approximately the fifth or sixth tracheal ring.
Structure: Anatomically; thyroid is consisted of 2 main loops; right and left loop, isthmus in between and the pyramidal lobe ((which is the third lobe, conical in shape, frequently arises from the upper part of the isthmus, or from the adjacent portion of either lobe, but most commonly the left)). There are 2 important structures next to the thyroid; the recurrent laryngeal nerve (at the lateral & posterior border) and the parathyroid glands which are 4 in number usually but may reach up to 7.
The histology: of the thyroid; it consists of cells arranged in a follicular pattern (follicular cells). Inside the follicles there is the colloid which is rich in a protein called thyroglobulin which serves as a reservoir of materials for thyroid hormone production and, to a lesser extent, acts as a reservoir for the hormones themselves. And there is, the parafollicular cells (or "C cells") which secrete calcitonin.

So .. Follicles: the functional units of the thyroid gland. Follicles are the sites where key thyroid elements function: Thyroglobulin (Tg), Tyrosine, Iodine, Thyroxine (T4) and Triiodotyrosine (T3).
Physiology of the thyroid gland; thyroid hormones:
- Thyroid pro-hormone is stored as thyroglobulin as an extracellular colloid.
- T3 and T4 can cross lipid membranes readily (secretion and uptake).
- T3 and T4 are small and hydrophobic; that is why they circulate in the blood bounded to a globulin called TBG (Thyroxine-binding globulin).
The most important hormone is T4, because T3 results from the peripheral conversion of T4 in the blood stream and it is more potent than T4.So, T4 is found in 4 times higher concentration in the circulation than T3.
Hypothalamus – Anterior Pituitary -Thyroid Axis.
It is an important regulatory mechanism (negative feedback mechanism) and it consists of short loop and long loop inhibition.
TRH > thyrotropin-releasing hormone, produced by the hypothalamus.
TSH > thyroid-stimulating hormone, produced by the anterior pituitary.
Now how to approach a thyroid nodule?? We have 4 approaches; Clinical, Biochemical, Radiological and Histopathological.
Clinical approach consists of History taking and physical examination. The history should include; the profile, present illness, reviews of the body systems, family history, drug history, and social history. Then we evaluate the mass in the anterior neck in terms of: onset, duration, pain, course, and trauma. Then we assess the function of the thyroid by checking the symptoms of thyrotxicosis or hypothyroidism. Then we try to identify any risk factors of malignancy (classify the mass as a malignant or benign) and this is the main factor in prognosis and possibility to live normally.
The main function of Thyroxine is to maintain the metabolic rate. So, symptoms of thyrotoxicosis are either because of increased basal metabolic rate or increased thyroid cells reactivity. And, the symptoms of hypothyroidism are because of decrease basal metabolic rate.
Symptoms of thyrotoxicosis: nervousness, tremors, sweating, heat intolerance, palpitations, weight loss despite normal or increased appetite, amenorrhea, and weakness.
Symptoms of hypothyroidism: lethargy, hoarseness, hearing loss, thick and dry skin, constipation, cold intolerance, stiff gate, and weight gain.
So we should ask about these symptoms during history taking.
Another thing that we should pay attention to is the risk factors of malignancy, which means increased possibility that the mass is malignant, and these are:
- Age > extremes of age is a risk factor.
- Sex > males are higher risk than females.
- Occupation > like people working in irradiation or nuclear reactors.
- Family history > some tumors has +ve family history factor.
- Hoarseness > which means that there is invasion for the recurrent laryngeal nerve.
- Residency > if the patient is living in a place with background radiation.
- Painless > if the mass is painless, this increases the risk of malignancy.
- Hx of irradiation
- Hard
- LN enlargement
Now we will start with the physical examination; there should be a mass or swelling in the anatomical site of the thyroid (anterior triangle of the neck but may be found in any part of the neck except the sublingual). The second and the most important feature in the diagnosis of thyroid nodule that it moves with swallowing.
We refer to thyroid swelling as Goitre or Goiter. It could be diffuse, which means that the mass involves all the loops and the isthmus or it could be nodular, which could be solitary or multinodular.
Now, in physical examintion we should evaluate the anatomical dx (diagnosis) by the extension whether it is a retrosternal extension or it exteneds below the sternocledomastoid.
If we have a solitary nodule, this nodule could be neoplastic (which could be malignant or benign) or non-neoplastic. Starting with the non-neoplastic type, it is either cystic or solid. The solid type is almost always a part of multinodular goiter the multinodular goiter is mainly a degenerative changes in the thyroid gland and it is of unknown cause exactly but it maybe because of growth in the thyroid gland that overcomes its blood supply which will result in nodules formation)). The cystic type, the cyst could be degenerative, haemorrhogic or because of hydatid disease. The cystic type could be simple or complex, in the complex there is a solid part and another cystic part. In the simple cystic type; the surgery is indicated after second recurrence – the first time it is diagnosed we treat either by radiology or by inspiriting all the cyst contents. In the first recurrence (the patient is coming for the 2nd time) we do the same management, but if he came for the 3rd time (2nd recurrence) surgery is indicated.
Now the neoplastic nodule, it could be malignant or benign as we said. The only benign form is called Follicular adenoma, while the malignant nodules has very wide spectrum of behavior, ranging from very benignish (with very good prognosis) to the most nasty tumors in the body – (deadly within 6 months). Theses malignant types are:

- Papillary Ca
Most common, best prognosis.
10 year survival around 85 % (and in favorable group about 99%).
At younger age group.
Spreads by lymphatics (in case of metastases).
Can be multifocal.
Can be familial.
Usually sensitive to RAI (radio-active Iodine as a treatment).
- Follicular Ca
10 year survival around 60 % (maybe less in advanced age group).
Associated with iodine deficiency (like in areas lacking iodine in their diet – in Jordan, we started using iodized salt since 1991).
Usually monofocal.
Haematogenous spread (to the lung or any place in the body).
Diagnosed by capsular and vascular infiltration (to be sure of the presence of invasion – cannot be diagnosed by cytology (just examining cells under the microscope) and you need both capsular and vascular infiltration).
Sensitive to RAI.
- Medullary Ca
From Parafollicular cells.
10 year survival 25-30%.
Can be Familial or Sporadic.
Can be part of MEN 2 (multiple endocrine neoplasia 2, which is a collection of tumors and associated with hereditary background).
Does not uptake RAI.
- Anaplastic
Around 1 % (very rare).
Very aggressive tumor.
The worst prognosis.
Survival is usually less than 6 months.
Can not be treated at all, this is the nastiest tumor in body.
+ Fibrolymphovasclar tumors: which result from metastases, like; Haemangioma, Lymphoma, Fibroma…
Now the third approach > Biochemical evaluation, includes;

Thyroid function tests: T3, T4, TSH.
>> evaluate if the thyroid is functioning or not, whether the patient has thyrotoxicosis or hypothyroidism. And TSH is the most important; because T3 result from peripheral conversion of T4 and T4 has a wide range [9-20 nanograms per deciliter] so it is not sensetive, so we depend mainly on TSH in evaluating the physiological function of thyroid.

Antithyroid Antibodies: antithyroglobulin, antimicrosomal antibodies.
>> Some diseases affecting the thyroid cause chronic inflammation state in the thyroid, such as; Hashimoto thyroiditis. In this disease the anti-thyroid antibodies level is high and these antibodies work against the thyroid and causes hypothyroidism. While in Gravis disease; the antibodies stimulates the thyroid and causes thyrotoxicosis.
The 4th approach > Imaging studies, such as;
- Ultrasound: it is the most useful study for us. And it is considered now as a part of the physical examination and it is found in all medical faculties. It is very effective, cheap and non-invasive. In the ultrasound, we can differentiate whether we have solitary nodule or multinodular and if this nodules is cystic or solid. Moreover, we can see if we have any features of malignancy on the ultrasound. You can see if there is cervical LN enlargement as well.
Features of malignancy in U/S:
Microcalcification, hypoechoeic nodules, increased vascularity and interupted hallo sign. [But the dr said that these are not important]

U/S guided FNA is preferred if:
- > 50 % cystic leision.
- located posteriorly.
[These are found in the slides but the dr did not mention them]
- Computerized tomographic scan (CT scan): usually we do not use it as an initial diagnostic measure; we use it in a very big thyroid nodule with retrosternal extension; because when there is a retrosternal extension, the nodule will result in compression of the surrounding structures such as trachea and esophegus. So we have diagnostic features >> shortness of breath (respiratory distress) and difficulty in swallowing (dysphagia). So the CT scan is important to assess the size of the nodule since we cannot reach it by physical examination and to assess if there is destruction to any adjacent structures.

- MRI (Magnetic resonance scan): we use it in case of recurrent thyroid goiter.
- Radioactive Iodine scan: in the past, it was widely used. But in present time, it is only used in case of suppressed TSH (to assess if the whole thyroid is working but with deficiency or only 1 nodule is working – in the follicular adenoma).


The 5th approach > Histopathological Dx. either by;
Fine Needle Aspiration (FNA) Or surgery for definitive biopsy.
- In FNA: we insert a needle into the mass, take some cells and examine them under microscope looking for any changes that suggest malignancy, such as:
** Orphan Annie eye nuclear inclusions (nuclei with uniform staining, which appear empty) and psammoma bodies >> papillary tumor.
** Very big and dense nucleus (like a ball) >> follicular neoplasm, but we cannot differentiate by FNA alone if it is carcinoma or adenoma. So we need surgery of definitive diagnosis. Frozen sectioning cannot differentiate between them as well.
** Medullary cancer we use Congo red stain to differentiate it, because we have big amounts of amyloid depositions.
** Anaplastic type contains cells with odd appearance with vesicular appearance of the nuclei.
Now, Serum Thyroglobulin is increasesd in most thyroid pathologies, so it is not specific as a diagnostic tool. But is important in follow up, to know if there is recurrence and/or metastesis. In surgery, usually we do not remove the whole thyroid, so in follow up after 6 months if serum thyroglobulin is increased again we should consider recurrence.
The dr stopped here and said that this is enough for us as dentists, and considered the material in slide 31 till the end is a little bit advanced. Soo, good luck :D


CORRECTIONS ARE WELCOMED
Written by: Mohammad H. Bustani
GS lect. # 8 on 10.4.2012