Transcription
This module is about the surgical diseases of the thyroid and parathyroid gland. I am Dr. Ailio from the department of surgical URL. The objectives of this module are as follows: to describe and explain the evaluation and diagnostic workup of a patient with a thyroid disorder, which is lecture one; most common thyroid gland disorders of surgical importance and the therapeutic options, lecture two; and the most common parathyroid gland disorders and diagnosis and management in lecture three. Not included in this module are congenital anomalies, which could be discussed elsewhere.
The thyroid gland is composed of two lobes, left and right, in the middle of the isthmus. Sometimes there is an upward prolongation, which is your pyramidal lobe. If a patient presents you with a mass in the anterior neck, and you see a dental neck mass moves up with swallowing, then it is a thyroid gland nodule.
So, for such a patient where we suspect a thyroid gland disorder, the initial diagnostic modality to order will be TSH, FT4, and FT3 to determine the thyroid function of the patient, whether the patient is hypothyroid, euthyroid, or hyperthyroid. These are the three tests that are in order because they are the most accurate tests of thyroid function. TSH means your thyroid-stimulating hormone, which is the most sensitive and specific test for the diagnosis of thyroid function. Then, in terms of the thyroid hormone level, there are three forms: serum T3, T4, and T3, the biologically active hormone.
Proper interpretation of serum thyroid function testing will depend on your norms of the hypothalamic-pituitary-thyroid or HPT axis. Recall that the hypothalamus induces TRH, which stimulates the pituitary to release TSH, which in turn stimulates the thyroid gland to produce thyroid hormone. So, when the thyroid hormone levels are low, then what happens is that there is a positive feedback regulation to stimulate the pituitary to produce more TSH and the hypothalamus to produce more TRH. So, there's an inverse relationship between your thyroid hormone and your TSH.
So, for example, we have a patient where the thyroid hormone levels are high, then there is now negative feedback regulation that suppresses the pituitary from producing more TSH and the hypothalamus to produce more TRH. Note again the inverse relationship between thyroid hormone and TSH.
So, in the clinical survey, let's say you have a patient with high TSH, low FT4, and FT3, then clinically the patient is hypothyroid. If you have a patient wherein you have a low TSH, a high FT4 or FT3, then the patient is clinically hyperthyroid. Now, you may also have a patient who has a high TSH but a normal FT4 and FT3. The patient is subclinically hypothyroid. The TSH has been able to compensate to normalize your FT4 and your FT3 levels. And you have a patient with a normal FT4, FT3, but a low TSH, then you can say that the patient is subclinically hyperthyroid. Again, there is a compensatory mechanism normalizing the FT4 and the FT3 levels.
These are the following additional thyroid tests which may be ordered, but not on a routine basis, only if they are indicated. You have to order for your thyroid peroxidase or TPO antibodies if you're suspecting thyroiditis, or serum thyroglobulin for monitoring for cancer recurrence, serum calcitonin if you're suspecting medullary cancer, and TRH if there is a discrepancy between the usually inverse relationship between TSH and FT4/FT3 levels.
So, after ordering for your thyroid function tests, you now know whether the patient is hyper or hypothyroid. If the patient is hyperthyroid, then the next diagnostic to order would be your thyroid scan to determine what is causing the patient's hyperthyroidism. So, it could be a hot or warm or a toxic nodule. The scan involves using a radioactive tracer, usually it's iodine, whether iodine-123 or iodine-131, or technetium pertechnetate for thyroid imaging. Radioactive iodine because 3 to 8% of nodules may be they appear as cold. On technetium, you will have what are known as either cold areas or hot areas. Cold areas are zones that take up less of the radioactivity than the surrounding tissue, and hot areas are areas of demonstrated increased activity. This is an example of a scan. There are areas that are abnormally decreasing uptake ability to uptake substance. These are known as cold nodules. There are areas which are more intensive, which indicates abnormally increased uptake, or hot. Therefore, if the scan shows a hot or a warm nodule, then subsequently it is a toxic nodule. If there is a cold nodule, then you have to proceed with the next diagnostic modality.
Also, if the initial diagnostic function testing shows that the patient is not hyperthyroid, meaning is euthyroid or hypothyroid, then the next diagnostic modalities to order would be an ultrasound and an FNA of suspicious nodules. Fine needle aspiration biopsy, which brings us to your parathyroid neck group. So, ultrasound has several uses. It can aid in the diagnosis depending on what the characteristics of the thyroid nodule is. Then it can also be used as a guide to subsequent FNA. It can be used to monitor nodule size because it's very accurate in determining the size of the thyroid nodule. It can also be used to determine the presence of cervical lymph nodes because ultrasound also involves the neck, not just the thyroid, and can evaluate substernal goiters, determine the extent how far it has gone down into the thoracic cavity, or even the presence of tracheal compression.
And these are examples of ultrasound to show you the characteristics of the nodule based on ultrasound findings. Here we have a nodule that has a spongy form appearance, and they call it a phase three description, clustered and several nodes of similar size, microcystic spaces separated by thin echogenicity, etc. So, these are the nine features of a benign nodule. A nodule has no solid components whatsoever, meaning it's just a simple cyst appearing completely homogeneously black. Then again, these are ultrasound characteristics associated with a benign pathology. Conversely, if you have characteristics that are as follows: number one, it's hypoechoic, meaning it is a solid nodule. Secondly, the shape of the solid nodule is taller rather than wide, as seen in the first diagram. Or if the nodule has irregular margins or the presence of microcalcifications, then these are the ultrasound characteristics that are associated with thyroid cancer.
Most hospitals now employ what is known as a thyroid scoring system or TI-RADS, a thyroid imaging reporting and data system. And this is meant to determine the risk of cancer in the thyroid nodules. The higher the score, the more the chance that it is cancerous. Okay. So, TI-RADS 1 is a normal thyroid. TI-RADS 2, it's benign. There are benign features that are found in ultrasound, such as a cystic or spongyiform nodule. As I told you earlier, TI-RADS 3, probably benign. There are no suspicious features present. TI-RADS 4 and 5 are the ones which are suspicious. For TI-RADS 4, there is at least one suspicious feature, and for TI-RADS 5, all suspicious features are present.
The next diagnostic modality I will discuss is your FNA-cytology, fine needle aspiration biopsy cytology. FNA or FNAB. This is the most single most useful diagnostic modality for actually diagnosing thyroid nodules in non-hyperthyroid patients. It can be done with or without ultrasound guidance. If nodules appear suspicious on ultrasound, then FNAB should be the next diagnostic modality. FNA or FNAB can also be both diagnostic and therapeutic. Diagnostic because you're able to get cells from the nodule which can be subjected to cytopathologic diagnosis. Or it is a thyroid cyst, you actually aspirate a thyroid cyst itself, meaning not just diagnostic, but it is also therapeutic. However, the FNA also has its limitations. Firstly, it's dependent on the technical expertise of the one doing it. We have to be able to hit the nodule accurately and obtain cells from a representative area. Secondly, there may be difficulty in differentiating follicular neoplasms. It cannot differentiate between follicular cancer versus its benign counterpart, the benign follicular adenoma. Thirdly, if a nodule is very small, it becomes hard to get a sample, when an ultrasound-guided FNA becomes important. Fourthly, it is not recommended for hyperthyroid patients because there are drawbacks of doing FNAB in warm nodules. First, because the patient is hyperthyroid, the nodule is more vascular in nature, there could be increased bleeding. Secondly, if you do FNAB on a hyperthyroid nodule, then you can probably have an increased possibility of false positives because the cells in hyperthyroid patients may also be actively dividing, and these hypertrophic cells can be mistaken for cancer.
If you have a thyroid score for ultrasound findings, you also have the BETHESDA criteria for the diagnosis of the thyroid nodule after you have done the FNAB. So, this actually tells you what to do next after the FNAB. Okay. So, if it is BETHESDA 1, then non-diagnostic, then you repeat the FNAB under ultrasound guidance. If it is BETHESDA 2, it is benign, just observe. If it is BETHESDA 3, repeat the FNAB. If it is BETHESDA 4, 5, and 6, these are the criteria wherein surgery is indicated.
And let us now recap so far on how to evaluate a thyroid nodule patient with an anterior neck mass that moves up with swallowing. Okay. Initial diagnostic modality is serum TSH, FT4, FT3 to determine thyroid function or thyroid status of the patient. If this shows that the patient is hyperthyroid, then the next order would be a thyroid scan. If a hot or a warm nodule is found on the thyroid scan, then it is treated as a toxic nodule. In the next lecture, I will tell you what this means. If it is a cold nodule, then you do an FNAC. If the patient is not hyperthyroid, meaning hypo or euthyroid, then the next order would be an ultrasound. Okay. You will have a thyroid score, do an FNA, and then you go to the BETHESDA criteria to determine what to do next.
What are diagnostics to order only if they are indicated would be the following. Okay. Next, CT scan. CT scan is ordered only if you have lesions of borderline resectability. Clinically, it seems to be fixed and not movable, and there is evidence of infiltration of adjacent organs. Second is laryngoscopy. If the patient presents with hoarseness and other signs of compression in the neck, then laryngoscopy may be indicated. Thirdly is a workup for MEN syndrome. If you're suspecting medullary cancer, then you have to work up the patient to see if there are also concomitant lesions elsewhere. This is suspected if there is a family history of MEN or a medullary thyroid cancer in the family, or if there is a high basal serum calcium, which is virtually diagnostic for medullary thyroid cancer. And again, if you're suspecting a parathyroid tumor or adrenal pheochromocytoma, then further imaging may be used for this.
This ends Lecture One, Evaluation and Diagnostic Workup of Thyroid Disorders. Okay. Uh, after that, after that, let me not, let me just show you the, my synthesis of the first part. Okay. Okay. So, basically, what you have to remember here is this algorithm. Okay. This is how to diagnose, or the diagnostic workup in steps for a patient with a thyroid nodule. So, it's really not that hard because you know it's a thyroid disease. If you see a neck mass that moves up with swallowing. So, if you have a patient with this manifestation, then that is a thyroid nodule. And based on the lecture, the first diagnostic modalities would have to be to determine the thyroid function. Okay. So, TSH, FT4, FT3. The subsequent diagnostics will depend on the result of this one. If the patient is hyperthyroid, okay, low TSH. Then the next is a thyroid scan. If the patient is however not hyperthyroid, you do an ultrasound and or an FNA. So, in the exam, in the exams, you may come across these particular questions. Okay. Based on the lecture, let's go to this one. A 33-year-old female consults for an anterior neck mass. If it moves up with swallowing, what is the organ of origin? Moves up with swallowing. So, it is thyroid. And with this, what is the initial diagnostic test that you will order? [clears throat] And based on the lecture, it's first to determine the thyroid function. So, it's TSH. The patient has a low TSH, then what will you order next? Patient has low TSH. Is the patient what? Hyper or not hyperthyroid? Okay. Low T, inverse relationship, remember. So, low TSH means high thyroid hormone. So, the patient is hyperthyroid. Therefore, based on our algorithm, we order a thyroid scan. Conversely, if the patient has a normal TSH, FT4, FT3. Okay. What will you order next? Normal. So, it's ultrasound and FNA. Ultrasound and FNA. Okay. And then there may also be questions that deal with whether the thyroid nodule is cancer or not based on ultrasound findings. You have to remember this slide. Okay. These are the suspicious features. If there is at least one suspicious feature of these four, that makes it TI-RADS 4, meaning it's suspicious for cancer. And after you've done the FNAB, okay, so you now know you can use this BETHESDA criteria to determine what to do next. Okay. So, you have a question like this. Ultrasound of a patient with an anterior neck mass that moves up with swallowing, and the ultrasound shows a simple cyst. So, what's the diagnosis? A thyroid cyst. A simple cyst. And what's the treatment for a thyroid cyst? Uh, that will be in the next lecture. Okay. Or you may come across a question like, what is a test that is both diagnostic and therapeutic for a thyroid nodule? As the lecture mentioned, it's FNAB because it's diagnostic, you can get cells. At the same time, if it is a thyroid cyst, you can already aspirate the cyst, making it also therapeutic in character. Limitations of FNAB. [snorts] It cannot distinguish benign from malignant follicular neoplasms. Okay. More on this in lecture two. Okay. So, let's go to lecture two. If you have any questions, you can just reserve it for later or you can put it in the chat box later on. Okay. So, we go to lecture two. This lecture is about thyroid diseases of surgical importance. Objective is to describe and explain the most common thyroid gland disorders you will encounter in surgery and the therapeutic options for these disorders. Let's start with thyroid cysts. A cyst is diagnosed if on ultrasound you see a hypodense or homogeneously black nodule, such as what is found in this diagram. So, that is a thyroid cyst. Its exact cause is unknown. There are just theories, whether it's a lack of iodine in the diet, or autoimmune thing, a genetic disorder, or exposure to medication. As I mentioned previously, the diagnosis is made or confirmed by ultrasound, and treatment may need little aspiration. However, if the cyst recurs after three aspirations, or if the size is large, greater than 4 cm, then these are indications for outright thyroidectomy.
The next is goiter. Goiter is probably the most predominant surgical disease of the thyroid found here in the Philippines, a third world country. And goiter may be a six-letter word, but there are actually several subclassifications of goiter. Firstly, goiter can be classified as diffuse or nodular. Diffuse, meaning there are no nodules, a diffusely enlarged thyroid gland. Nodular, meaning that there are nodules within the particular thyroid or masses distinct from the rest of the gland, and can be subclassified further into toxic or non-toxic. Okay. So, there could be a diffuse toxic goiter if the patient is hyperthyroid, or a diffuse non-toxic goiter if the patient is not hyperthyroid, based on your thyroid function. Let's see. Nodular can also be classified similarly: toxic nodular goiter or a non-toxic nodular goiter. Nodular versus diffuse goiters can be distinguished by ultrasound or even clinically. For example, for these two patients in the diagram, you will note that the one on the left side, okay, the patient in red, there is an asymmetric enlargement of the thyroid gland. Only part of the thyroid seems to be enlarged, and that is a nodular form of goiter. Contrast it with the one on the right side where you see both left and right thyroid lobes are enlarged. So, this is indicative clinically of a diffuse type of goiter. Toxic versus non-toxic. Then you have to rely clinically on manifestations as well as ultrasound findings. For a non-toxic goiter, you have a low thyroid hormone level, and the pathophysiology is as follows: this low thyroid hormone level stimulates TSH to increase, and this now, the TSH now stimulates the thyroid to produce more thyroid hormone, leading to glandular hypertrophy or hyperplasia. So, enlargement, enlargement of the thyroid gland because of the hypertrophy is non-toxic goiter. Conversely, for toxic goiter, this usually starts as a normal thyroid hormone level, but because of increased TSH secretion, probably from a brain tumor or from an autonomously functioning thyroid nodule, the thyroid continues to produce excessive thyroid hormone, again causing glandular hypertrophy and hyperplasia. So, you have goiter that is toxic, non-toxic versus toxic goiter. Goiter can also be differentiated clinically. Okay. For non-toxic goiter, they are usually asymptomatic thyroid nodules. However, you may elicit signs of compression. Okay. Compression is possible because the neck is a closed space, and the thyroid can press on the trachea, which is underneath it, causing dysphagia or dyspnea, or even dysphonia if it is the recurrent laryngeal nerve that's compressed. Or you can also press on the esophagus, which can cause dysphagia. One other characteristic of the presence of your so-called Pemberton's sign, found in your textbooks. Pemberton's sign is elicited on physical exam. There is facial flushing and engorgement of the neck base, and the patient raises arms above the head. A positive Pemberton's sign is indicative of obstruction of venous return at the thoracic inlet, as indicative of a substernal form of goiter, as the diagram shows. So, there is a prolongation of the left lobe into the thoracic inlet, causing a positive Pemberton's sign.
As for toxic goiter, the manifestations you will look for are of course thyrotoxic manifestations, as follows. So, hyperthyroidism present with the root of clinical manifestations. Classically, you have this patient in the diagram where you have exophthalmos, but most patients with hyperthyroidism may not really have exophthalmos. There could be systemic manifestations like heat intolerance, sweating, thirst, weight loss; cardiac manifestations: palpitations, atrial fibrillation, resting tachycardia, which is the most reliable sign; as well as nervous system, eye signs, manifestations, even amenorrhea and decreased fertility. The most reliable sign is your tachycardia. If a patient, in the absence of the other manifestations of hyperthyroidism, presents with resting tachycardia, then you can actually say that clinically this patient is hyperthyroid. So, if you have a patient with such manifestations of hyperthyroid disease and there is toxic, there is diffuse goiter, and that is what is known as Graves' disease. Graves' disease has a familiar predisposition, usually occurring in females, 40 to 60 years old. The etiology is autoimmune. Antibodies are produced directed against the thyroid hormone receptor, which stimulates your thyroid cells to produce excessive thyroid hormone. Thus, the hypertrophy. It can be triggered by some states like postpartum, iodine excess, radioiodine therapy, and some forms of bacterial and viral infections. Diagnosis can be confirmed by, of course, hyperthyroidism from the high FT4, FT3, and low TSH levels, and a thyroid scan. It shows diffuse uptake, as found in letter B of this particular diagram. Note that both glands seem like hot, not nodules, but the entire gland appears warm or hot. A diffusely hot uptake indicative of Graves' disease. And you can confirm this by ordering for autoantibodies against thyroid-stimulating hormone receptor, thyroglobulin, and peroxidase. The treatment of Graves' disease involves the following. Okay. There are three modalities. The first is antithyroid drugs. Antithyroid drugs are used usually to prepare a patient for the definitive treatment. It cannot be used permanently because there's a high relapse rate if it is discontinued. Furthermore, long-term antithyroid drugs have been shown to produce serious adverse effects like blood dyscrasias, avascular necrosis, toxicity, and arthralgia. Usually, we give either propylthiouracil or methimazole. Effective treatment of Graves' disease involves either radioactive iodine ablation (RAI ablation) or surgery in the form of thyroidectomy.
This slide compares the two definitive treatments I mentioned previously: surgery versus RAI. Surgery affords the advantage of immediate ablation, or the patient becomes euthyroid after the surgery. RAI usually takes time for ablation, causes return to euthyroid status gradually. There's a 50% decrease in 6 to 12 months, and the relief of most toxic symptoms may take 3 to 6 months. For surgery, there's a need, of course, to render the patient euthyroid first, because to operate on a patient with thyrotoxic storm. RAI is not necessary. For surgery, you have surgical risks. RAI, however, you also have radiation effects, so it's not for pregnant or breastfeeding persons. Surgery also affords the advantage of a definitive histologic diagnosis because once you do a thyroidectomy, this can be pathologically determined to see what disease is causing it or to confirm the diagnosis of Graves' disease. This is not possible for RAI because there is no tissue that is obtained from the biopsy. So, this slide shows a comparison of when surgery versus RAI is indicated. Surgery is usually indicated for those with compressive symptoms, for large goiters which will require too high amounts of RAI, or RAI resistant, also for those where immediate resolution of the hyperthyroidism is needed, and if it is suspicious for cancer. RAI, on the other hand, is indicated for smaller goiters, volume less than 100 ml, without any suspected malignant potential, or if the patient already underwent surgery and then recurrence, or if the patient is a high surgical risk.
So, from diffuse toxic goiter or Graves', now go to your toxic multinodular goiter. This usually affects patients who are older than 50 years of age. They also have a prior history of non-toxic multinodular goiter, and over several years, these nodules become autonomous, and they become hyperthyroid. Usually, in the clinic, you have a patient who has a previous history of a non-toxic multinodular goiter, then suddenly develops hyperthyroidism. This is because there is an escape from the negative feedback mechanism over time, and this may be precipitated by excess exogenous iodine intake in the form of other iodinated drugs, maybe a contrast material was injected with this radioiodine-containing during a particular diagnostic procedure, but only in the form of dietary supplements. A previously non-toxic becomes toxic goiter in patients, and this iodine-induced hyperthyroidism is known as your Jod-Basedow phenomenon. Diagnosis is made by TSH, FT4, FT3, which shows hyperthyroidism, and a thyroid scan. Now, look at this scan. It shows multiple nodules, the ones which appear black, indicative of a toxic multinodular goiter. Now, the treatment of toxic multinodular goiter is thyroidectomy.
So, from toxic goiter, let's now go to your non-toxic goiter. And this can also be either diffuse or nodular. The causes are either iodine deficiency, or there is TSH stimulation secondary to thyroid hormone resistance. Most of the time, it's idiopathic. Special types of non-toxic goiter would be either familial or endemic goiters. Familial goiters result from inherited deficiencies in enzymes that are called normal thyroid hormone synthesis. Endemic term refers to the occurrence of goiter in a significant proportion of individuals in a particular geographic region. Physical examination of a thyroid will help differentiate whether it is diffuse or nodular. You also should also look for signs of compression on physical exam, history in the form of either dysphagia, dyspnea, dysphagia, a foreign body sensation in the throat, or hoarseness. And diagnosis is established by the usual means: thyroid function testing, which shows the patient is not hyperthyroid, and then ultrasonography, which confirms the diagnosis. For non-toxic nodular goiter, then an FNA may be indicated if it is suspicious. Treatment of non-toxic goiter will involve either of these two modalities. The first is non-surgical TSH suppression, which involves giving the patient a high dose of exogenous thyroid hormone at levels that suppress the serum TSH, thus the term TSH suppression. And the second is in the form of surgery. This suppression is indicated for patients of endemic goiters, young patients, small thyroid nodules, and no evidence of functional autonomy. Thyroidectomy or surgery is indicated for large goiters, those with compressive symptoms, those that are suspicious for cancer. All of these are contraindications to TSH suppression, like the patient is postmenopausal or more than 60 years old, making them at risk for osteoporosis and cardiovascular disease. Also, failure of medical treatment or failure of previous TSH suppression is an indication for surgery.
And to recap what I have explained to you regarding goiter: a toxic goiter patient has hyperthyroid manifestations; non-toxic, no hyperthyroid manifestations and normal serum thyroid function. So, for toxic goiter, it's either diffuse, meaning it's Graves' disease, or nodular, so toxic multinodular goiter. Hyperthyroid. Toxic goiter can be diagnosed mainly by thyroid scan, and for Graves' disease, thyroid antibodies. So, antithyroid drugs are important for toxic goiter, whether it's multinodular or diffuse, and then the definitive modality for Graves' disease is surgery versus RAI. For toxic multinodular goiter, it is surgery. Antithyroid drugs are given before surgery to prevent thyroid storm, rendering the patient first euthyroid before proceeding to surgery. As for non-toxic goiter, either diffuse or nodular, then ultrasound is the modality that will aid in the diagnosis. If it is diffuse, no need for FNA. If it is nodular, then ultrasound and FNA are indicated. Treatment is the same. It's either TSH suppression versus a thyroidectomy for large or compressive manifestations or suspicion of malignancy.
The last disease is thyroiditis, meaning it's some form of inflammation of the thyroid. It is either acute, subacute, or chronic. It is not very common, but it is often mistaken for other more common diseases like goiter and tumors. What's characteristic about thyroiditis is that it may cause initial hyperthyroidism and thus be mistaken for a toxic goiter, but over time it may progress to hypothyroidism. The first type is your acute. So, acute thyroiditis is an inflammation secondary to an actual infection. Okay. Usually, the cause is an acute bacterial infection, and the treatment is similar to other types of infections, which is antibiotics. Or if there is frank suppuration, then the treatment or drainage should be there. As for subacute thyroiditis, there are four stages. Patient comes in initially as hyperthyroid, then later on becomes euthyroid, and then hypothyroid until it finally resolves. Recovery usually takes two to four months. There are two other subtypes: the painful type versus your painless type. Your painful, both of them occur in females around 30 to 60, 40 or 60 years old. For the painful type, it is usually secondary to viral or postviral inflammatory response, and as such, it is known as your granulomatous or de Quervain's thyroiditis. In contrast, your painless type is secondary to an autoimmune response. Usually, the most classic example of this is your postpartum thyroiditis. Now, treatment for subacute thyroiditis is basically symptomatic in nature. So, pain control by giving analgesics, and if the patient is in the hypothyroid state, then thyroid hormone replacement. In the hyperthyroid phase, then short-term antithyroid drugs.
As for chronic thyroiditis, it is also known as your Hashimoto's thyroiditis. The cause is usually autoimmune. They have a lymphocytic form of thyroiditis, and later on, it predisposes the patient to developing thyroid lymphoma. So, autoimmune, there are antibodies that develop against thyroid antigens. You have your anti-TPO antibodies. You have your anti-thyroglobulin antibodies, which can be detected by serum assay. Others would include your TSH receptor antibodies, stimulating antibodies, or cytotoxic antibodies. Treatment of Hashimoto's thyroiditis is again just thyroid hormone replacement if this is indicated.
The next is your Riedel's thyroiditis, also known as your invasive fibrous thyroiditis. This type of thyroiditis is a chronic inflammatory disease that causes a dense fibrosis. It is again probably autoimmune. Now, what is characteristic is you see a patient with a thyroid that is hard, woody, and fibrotic. So, it's often mistaken for thyroid cancer. So, as such, the treatment is surgery because it might really be cancer and not thyroiditis, and thyroid hormone replacement if it is indicated. So, at this point, let us recap what I have discussed on thyroiditis. Usually, patients present with a history of function spectrum that may range from hyper to euthyroid to hypothyroid. Serial monitoring of thyroid function may be indicated. Secondary medical treatment is usually the first line of treatment, except for Riedel's. Indications for surgery for thyroiditis will be to rule out malignancy, as in Riedel's thyroiditis, or if there are significant signs of compression, or failure of medical treatment, or for acute type of thyroiditis, abscess formation.
Now, go to tumors of the thyroid gland. So, we have benign and malignant tumors. Let's start with benign tumors. The benign tumor of the thyroid is your adenoma. There are two types of thyroid adenomas. These are either your follicular adenoma, Hurthle cell adenoma, versus your toxic adenoma. Your follicular adenoma and Hurthle cell adenomas are usually in a euthyroid patient. Now, the characteristic of follicular adenoma and Hurthle cell adenoma is the fact that they are hard to differentiate from follicular carcinoma, which is the malignant counterpart, pre-operatively, because the only histologic difference between the benign and the malignant counterpart is the absence of capsular and blood vessel invasion. The architecture is similar. It's very hard to diagnose this pre-operatively by FNA alone, and diagnosis is usually established after surgery. The second issue is toxic adenoma. In the patient, it is hyperthyroid with an adenoma. So, also known as Plummer's disease, toxic adenoma is a hyperthyroid patient from a single hyperfunctioning warm nodule. This typically occurs in younger patients versus in toxic. Diagnosis is established by thyroid scan showing a single hot nodule. Treatment is by thyroidectomy after controlling the hyperthyroidism. And this is a thyroid scan of a patient with toxic adenoma or Plummer's disease. You can see the single hot nodule found in the right lobe of the thyroid.
So, from the benign tumors, we now go to malignant thyroid tumors. The thyroid carcinoma. The very different types of thyroid carcinoma are as follows. Note that 80% of all thyroid cancers is in the form of papillary CA, 10% is follicular, and the rest are Hurthle cell, anaplastic, and others like sarcoma, lymphoma, metastatic tumors represent only a small proportion. So, virtually 90% are either papillary or follicular cancers. Together, these two cancers are known as well-differentiated thyroid carcinoma. Papillary carcinoma or your PTC. It's actually an indolent form of cancer. It has a relatively benign course, compatible with long life, and there is a very high cure rate of 90 to 95%. The main spread of this cancer is to the lymph nodes, 30 to 45%. And only 1 to 2% present with distant metastasis. There are several subtypes of PTC. The first bullet represents the more common ones: pure papillary, papillary-follicular, and follicular, which are also the ones which are least aggressive. And the second bullet: cribriform, columnar, insular, Hurthle cell, and solid, which are fully differentiated, represent a minority of these particular cancers and are the ones which are more aggressive. Histologically, PTC is characterized by cells with intranuclear cytoplasmic inclusions, which are known as your Orphan Annie nuclei, and calcification deposits, which form what are known as psammoma bodies.
Papillary thyroid cancer has a relatively benign course, associated with goiter, around 10-15%. 5 to 20% metastasize to the lymph nodes, and there's a higher risk of bloodstream invasion compared to your papillary thyroid cancer. Only 2 to 5% distant metastasis, and you also have a relatively indolent tumor like your PTC, and has a 70 to 80% cure rate. Histologically, the diagnosis of follicular CA is based on the presence of capsular and vascular invasion. It's very hard to diagnose follicular carcinoma by FNA alone. It's very hard to see the invasion in an FNA smear. Because of these similar behaviors, both your papillary and follicular cancers have been lumped together into what is known as well-differentiated thyroid carcinoma. 85 to 90% of these cancers are indolent and slow-growing and associated with an excellent prognosis with more than 90% survival rate. There's also a high response to your adjuvant radioactive iodine treatment. However, having said this, there are still around 5 to 10% of your well-differentiated cancers that are aggressive with a poor prognosis. The challenge is identifying, differentiating the two.
The challenge for this particular type of cancer is to be able to determine which of the cancers are low risk, meaning indolent, as compared to your high risk or aggressive ones, in order to determine the proper type of treatment. So, originally, there have been several scoring systems that have been developed by various authors to differentiate between these two. We have the AJCC classification or scoring system, wherein what are used to differentiate are age, grade, extrathyroidal extension, and size. Another one by the same author is your MACIS score. It's factors are metastasis, age, completeness of resection, invasion, and size. ADL Ross, C also has your ANS classification, consisting of your age, metastasis, extrathyroidal spread, and size. Of these different factors, the AJCC, or the American Joint Committee on Cancer, classifies age as the most important factor to distinguish low risk from high risk. Thus, in their classification, absolutely, you would see that patients who are under 55 years old, even if the tumor has already distant metastasis, are still classified as stage two. Unlike for cancers which occur in 55 years old and above, wherein distant metastasis is classified already as stage four. Another way of differentiating between low versus high risk should be the type of cell variant. So, there are now what are known as aggressive variants of your well-differentiated cancer. This include your tall cell variant, your diffuse sclerosing variant, insular, solid variant, NHV. For these particular variants, they tend to be more aggressive compared to the usual types of well-differentiated cancer. And probably the best way to differentiate between low risk versus high risk are through molecular or genetic markers, which are still however under development at present. Presently, we have these four markers to determine whether the well-differentiated cancer is aggressive or not. The most is your BRAF V600E gene mutation, followed by your RET/PTC rearrangements, your RAS mutation, and your TERT promoter mutations.
So, to recap what I have discussed about low-risk versus high-risk well-differentiated cancer, you see that the following. If the patient is young, the tumor is small, there are no extrathyroidal spread or metastasis, there are negative molecular and genetic markers, and it is not an aggressive variant type, then the patient can be classified as low risk. On the other hand, when the patient is older, more than 55, the tumor is large, there is frank local invasion or distant mets, and molecular genetic markers are positive, and it is of the aggressive variant type, then these patients can be classified as high risk. And the treatment would depend on whether the patient is low risk or high risk. So, for a low-risk patient, meaning that the tumor is less than or equal to 1 cm and solitary, minimal or occult or microcarcinoma, then a less than total thyroidectomy may be sufficient. A total thyroidectomy alone plus an isthmusectomy. However, if the patient's tumor is more than 1 cm and or is multifocal, then total thyroidectomy is the minimum procedure. If there is already extrathyroidal spread, the capsule, and the adjacent structures, then in addition to the total thyroidectomy, some form of neck dissection, the central neck dissection, must also be done. And if there are already frank lymph node metastasis, then a total thyroidectomy and a comprehensive modified radical neck dissection is indicated. Adjuvant treatment after surgery for well-differentiated cancer consists of TSH suppression with a target serum TSH which is very low, close to zero. And if it is a high-risk treatment type of cancer, radioactive iodine ablation. Unlike most other cancers elsewhere, there is no proven role for chemotherapy or radiation therapy for well-differentiated thyroid cancer. Monitoring or follow-up after treatment also depends whether it is a low-risk or a high-risk cancer. Low-risk, symptom-directed follow-up is sufficient, meaning just clinical PE, ultrasound to see if there is evidence of any recurrence. However, for high-risk, after doing the surgery and the RAI, you have to monitor using your serum thyroglobulin. Remember, serum thyroglobulin is produced solely by thyroid cells. So, we expect that after a total thyroidectomy, the serum thyroglobulin should be zero or low. If during the course of follow-up, you find that the serum thyroglobulin is increasing, then that's evidence that there could be recurrence of a thyroid cancer. So, serum thyroglobulin is first obtained baseline, 3 to 6 months after treatment, and every 6 to 12 months. Then, after it is negative, you continue the monitoring. If it's equivocal, then you repeat it by first withdrawing your exogenous thyroxine. If it's consistently positive, then further imaging is indicated in the form of a total body scan or CT scan. Here's an example of a patient who underwent a total body scan after developing thyroid cancer. The I-131 scan shows very high, initially showed very high thyroglobulin levels, which means the cancer may have recurred. So, the red arrow shows increased uptake in a bone in the lower spine, less uptake in the bones of the mid-pelvis. So, this is one indication that the cancer has metastasized based on your total body scan.
Let's now go to the other types of cancers aside from well-differentiated cancer. We have your Hurthle cell carcinoma, considered as a subtype of your follicular carcinoma. It is derived from the oxyphilic cells of the thyroid, characterized by large cells, small irregular nuclei, and dense acidophilic granules with the presence of abundant mitochondria in the cells. Now, unlike your follicular carcinoma, Hurthle cell carcinoma is more often multifocal and bilateral and does not respond to RAI imaging. They are also more likely to metastasize. Thus, they are more aggressive with a higher mortality rate compared to your follicular type. Therefore, surgical treatment should also be more aggressive compared to your usual well-differentiated carcinoma. The minimum procedure is a total thyroidectomy with or without a neck dissection, depending on the findings.
And the next type is your medullary carcinoma. Again, this is more aggressive than the usual well-differentiated types. It arises from the parafollicular or C cells of the thyroid, and these C cells of the thyroid secrete calcitonin. That's the reason why serum calcitonin levels can be used to actually diagnose medullary carcinoma. A raised or a high serum calcitonin level may be diagnostic for medullary carcinoma in a patient with a thyroid. Secondly, 25% occur within the spectrum of your MEN syndrome or hereditary syndromes because of a germline mutation in the RET proto-oncogene. Your familial medullary thyroid cancer is part of your MEN 2A and MEN 2B syndromes. So, diagnosis, aside from raised serum calcitonin, by FNA cytology. Remember also, all new patients with this type of cancer should be screened for cancers in other organs based on your MEN syndrome. So, there could be a concomitant tumor in the adrenal causing pheochromocytoma, or in the parathyroid, which may cause hyperparathyroidism.
And of all the types of thyroid cancer, it is your anaplastic carcinoma which is the most aggressive of all. These are rapidly enlarging. We had a patient once in the ward who we could not operate on yet because of financial problems, and every day that we were going on rounds with that patient, every week the tumor seems to be growing right before our eyes. That's how aggressive anaplastic carcinoma can be. Treatment here consists usually of palliative surgery or tracheotomy in order to alleviate or palliate airway obstruction because of the rapidly expanding tumor. External beam radiation can also be tried, or debulking total thyroidectomy if resectable, and experimental treatments like chemotherapy and radiation therapy. Most of the time, these patients present late, and we are left with nothing more to do but palliation.
Other rare cancers of the thyroid constitute only around 1% of all thyroid cancers. This can be in the form of sarcomas, lymphomas, or metastatic cancer, usually from the kidney, breast, lung, and melanoma.
This slide recaps what I have said regarding the diagnosis and treatment of follicular, Hurthle cell, medullary, and anaplastic carcinoma. So, in terms of aggressiveness, the most benign or indolent is your well-differentiated PTC, and the most aggressive is your anaplastic cancer. In terms of diagnosis, most of them can be diagnosed by your ultrasound and FNA, except follicular. And for medullary CA, calcitonin may be important in arriving at the correct diagnosis. And for medullary, also a workup for your MEN syndrome should be conducted. For surgical treatment, since the well-differentiated is the most indolent, then you may get away with just doing a less than total thyroidectomy. But for the others, the minimum is a total thyroidectomy and a neck dissection. Because of its very aggressive nature, sometimes just palliation of the patient's signs and symptoms may be the only one that is possible. In terms of adjuvant therapy for well-differentiated CA, it's TSH suppression, RAI for high-risk. For anaplastic CA, experimental chemo or radiation therapy. Follow-up thyroglobulin can be used for following up patients with WDC, and for medullary CA, calcitonin may be used for follow-up.
And since thyroidectomy is the mainstay of treatment for thyroid cancer, let me just tell you the possible complications after a thyroidectomy. Postoperative hemorrhage. Remember, the neck is a very vascular area. So, postoperative hemorrhage can occur after a thyroidectomy, 1%. Okay. Or, of course, like other operations, surgical site infection. The second is nerve injury, and there are two nerves at risk: your recurrent laryngeal nerve and your superior laryngeal nerve. The recurrent nerve usually is found in the tracheoesophageal groove, and any injury, if it is unilateral injury, will produce hoarseness of voice. However, since if you're going to do a total thyroidectomy, if there is a bilateral damage to the recurrent laryngeal nerve, the patient will present with airway obstruction, which may necessitate tracheostomy. As for the superior laryngeal nerve, usually found adjacent to the superior thyroid artery and other vessels in that area, then any injury to this will cause a decrease in voice strength. And the third is your parathyroid injury. Remember that the parathyroid glands may be in close or even intimate contact with the thyroid lobe. So, injury in this case, which occurs in 3 to 5% of cases, may result in postoperative hypocalcemia.
Okay. So, let's go back now to your correlation, but it's still fresh in your minds. Uh, so again, to recap goiter. Okay. There are four subtypes. You have your diffuse toxic goiter or Graves' disease, your diffuse nodular toxic goiter, which is your toxic multinodular goiter, and then for non-toxic goiter, you have your diffuse non-toxic goiter and your nodular non-toxic goiter. Non-toxic usually ultrasound plus or minus FNA, and treatment is the same. Graves' disease, thyroid antibodies. Otherwise, they're more or less similar. Of course, RAI. So, in the exam, you might have some questions like this. Let's say a [clears throat] thyroid scan shows a diffuse reduced hot uptake in the entire gland. What is the most probable diagnosis? Toxic, hot, and it's diffuse. So, it's most probably your Graves' disease.
Have a patient with a 5 cm nodular non-toxic goiter presents with dysphagia and dyspnea. Okay. Treatment. Okay. This is a non-toxic nodular goiter with signs of compression. Therefore, it's thyroidectomy. Okay. Thyroiditis. Well, as I mentioned earlier, spectrum from hyper to hypothyroid. Usually medical, except if you cannot rule out malignancy or there are signs of compression, etc. Okay. Tumors. As I mentioned, there are two benign tumors. It's a non-toxic follicular adenoma. Toxic, it's Plummer's disease. And CA. For well-differentiated CA, first step is to classify whether it's low risk, meaning it's indolent or less aggressive, or high risk, meaning it's more of the aggressive type. So, young, small, no invasion, negative molecular genetic markers, not an aggressive variant type, then it's indolent. Otherwise, it's a high-risk or more aggressive form. So, low risk, then you can get away with just doing a less than total thyroidectomy. If it's high risk, then you really have to do a total thyroidectomy. As this slide shows you. Okay. So, total thyroidectomy. You of course have to include neck dissection if there is already spread beyond the thyroid or frank lymph node metastasis. Yeah, this is a very important slide. It shows you that the behavior of the tumor determines the treatment. You have a less aggressive tumor, more conservative thyroidectomy. To the more aggressive forms, wherein a total thyroidectomy and neck dissection may be indicated. And the only one wherein chemo or radiation plays a role is anaplastic, because this is an experimental form, no other form of treatment available. So, they try chemo or radiation. CA where there's an increased calcitonin level, medullary. So, have an exam. A 40-year-old male with a 1.2 cm well-differentiated carcinoma. Okay. Pure papillary type. No lymph node enlargement. No evidence of distant metastasis. Negative for BRAF. 1 cm. Okay. A 40-year-old male presents with a 1 cm well-differentiated cancer. Okay. So, that makes it not that large, pure papillary type. It's not the type that is aggressive. No lymph node enlargement. So, no lymph node metastasis. No evidence of distant mets. Negative for tumor markers. So, is this low risk or high risk? Low risk. Then you do a lobectomy, isthmusectomy. Okay. The second question is a 60-year-old male. Okay. So, relatively older already with more than 1 cm cancer. Frank cervical lymph node metastasis, and it is a more aggressive variant. So, the most appropriate treatment is total thyroidectomy. But there are enlarged cervical lymph nodes. So, aside from the total thyroidectomy, you have to also do a neck dissection. Okay. That means the answer here would be letter C. Okay. You complications already mentioned earlier, and there can be some questions like this. So, after thyroidectomy, patient is noted to be hoarse voice. Hoarse in voice. Okay. What is the most probable diagnosis? Okay. So, hoarseness is a nerve injury. So, recurrent nerve injury. Unilateral. After thyroidectomy, a patient is positive Chvostek's sign. Most probable diagnosis. Lecture three. After thyroidectomy, the patient is pale, hypotensive with a bulging neck. Most probable diagnosis and not a nerve injury, not a parathyroid injury. It's more of a postoperative hemorrhage. Okay. So, which brings us to your last lecture. This is the shortest of the three. So, it's around 15 minutes. Uh, eight. This lecture is about the parathyroid disorders of surgical importance, and the objective is to describe to you and explain the most common parathyroid gland disorders, diagnosis, and management of these disorders. In order to understand parathyroid gland diseases, let us first review calcium homeostasis. In order to maintain calcium balance in the blood, there are two opposing forces. The
Horses that tend to increase serum calcium are your parathyroid hormone, which is secreted by the parathyroid. Blood and vitamin D, which stimulates the absorption of calcium and phosphate from the GI tract.
In contrast, what produces a decrease in calcium in the body is your calcitonin, which decreases serum calcium. So, to maintain a calcium balance in the body is an interplay of these three forces: PTH and vitamin D versus your calcitonin.
Let us go first to your hyperparathyroidism. There are three types: primary, secondary, or tertiary. Your primary hyperparathyroidism (PHP) is due to abnormal parathyroid glands. Secondary is actually a compensatory response to diseases that cause hypocalcemia, like chronic renal failure or GI problems in absorption. Tertiary is some form of secondary where in the chronically civic glands become autonomous, resulting in persistence or recurrence of the hypercalcemia. This is most commonly a result of renal transplantation and chronic renal failure. But for the purpose of this lecture, we will deal solely with your primary type of hyperparathyroidism.
Primary hyperparathyroidism is due to an abnormal parathyroid. The causes of primary hyperparathyroid disease are either a parathyroid hyperplasia, adenoma, or carcinoma. Clinically, since you expect that this patient has a high calcium state, you will find signs and symptoms that are indicative of hypercalcemia, where what is known as the classic pentad of symptoms. We have kidney stones, painful bones, abdominal groans, psychic moans, and fatigue. So, a patient has requests for kidney stones, complaints of bone pains, abdominal pain, or even some mental problems and fatigue. However, it's very rare to see patients with this classic pentad of symptoms. They may just be minimally symptomatic with nonspecific symptoms like weakness, fatigue, polyuria, polydipsia, nocturia, and so forth. Most of the time, however, most of these patients may be asymptomatic.
For diagnosis, a high serum calcium is usually the first thing that will be detected. This is especially important for patients who are minimally or who are asymptomatic. Some of these patients, the parathyroid problem just manifests once they have taken a serum calcium and incidentally find that the serum calcium level is elevated. So, in such cases with the high serum calcium, then you have to order for a PTH or parathyroid hormone assay to confirm if there is an increase in parathyroid hormone. Then it is a parathyroid gland problem. To localize which parathyroid is causing the hyperparathyroidism, it is a parathyroid scan that may be done in order to find this. Remember, there are four parathyroid glands, but usually around two to more than six. It's a little variable.
So, once a parathyroid problem is confirmed, it's either hyperplasia, adenoma, or carcinoma. The treatment is parathyroidectomy. If it is parathyroid hyperplasia, then correct surgical procedures would be a subtotal parathyroidectomy, which involves removal of three and a half glands. Okay. Just one half of a normal gland is usually sufficient to be able to maintain calcium homeostasis. Or we can do a total parathyroidectomy, but you auto-transplant one of the parathyroids in the neck or a forearm muscle. Now, if the diagnosis is a tumor or an adenoma or carcinoma, then frank excision of the enlarged gland is the treatment of choice.
As for hypoparathyroidism, defined as low calcium, usually causes are either the DiGeorge syndrome, which is congenital absent parathyroid, or neonatal hypoparathyroid disease. However, the most common cause encountered is thyroid surgery injury to the parathyroid, usually after a total thyroidectomy, can produce hypoparathyroidism. So, clinically, the signs and symptoms you would expect would be those that are related to hypocalcemia. The hypocalcemia may cause usually increased neuromuscular excitability. So, you have circumoral and fingertip numbness or tingling sensation in those areas, or there may be some mental symptoms like anxiety, confusion, or depression. On physical exam, you will have your positive Chvostek's sign, which is contraction of the facial muscles elicited by tapping on the facial nerve anterior to the ear, or Trousseau's sign, which is carpal spasm elicited by occluding blood flow to the extremity with a blood pressure cuff for two to three minutes to around 20 mm Hg over their systolic blood pressure, or maybe frank tetany.
So, we have a patient who is posted off after a thyroid surgery. We have to monitor these patients for these particular signs and symptoms to see if they're developing hypocalcemia secondary to parathyroid injury during the surgery. The diagnosis is achieved or confirmed by decreased serum ionized calcium levels. Once confirmed, the treatment is calcium supplementation, either calcium tablets, or if there is frank tetany, then an IV infusion of calcium gluconate may be indicated. In the long term, vitamin D supplements may also be used for these patients.
Okay. So, uh, last part. [sighs] The correlations. So, uh, so this one. So, you have a question like this: After thyroidectomy, a patient has a positive Chvostek's sign. Okay. What is the most probable diagnosis? So, as mentioned, this is a sign of hypocalcemia post-thyroidectomy. Okay. So, you suspect a parathyroid injury to the patient. Most of these injuries are actually transient. Okay. But, uh, it meaning it's either transient or permanent. The risk of a permanent hypocalcemia is usually low. Most of the time, it's transient, and there's recovery after a few months. Okay.
So, for parathyroid, as I mentioned, it's either hypo or hyper. Hypo has your Chvostek's and Trousseau's signs. These are the things you have to monitor for in a patient who just underwent a thyroidectomy. So, since hypocalcemia diagnosis is established by determining the serum ionized calcium, and the treatment, of course, is calcium. Or hyper, there's really a parathyroid lesion here. It's either hyperplasia or a tumor, and it's diagnosed by a high serum calcium. There may be manifestations, the classic pentad, or actually no minimal to no manifestations at all, just a high serum calcium. So, after confirming it by a high serum calcium, then you know it's a parathyroid problem. So, you do a parathyroid scan to identify which of the parathyroid glands are causing the hypercalcemia. Hyperplasia meaning all of the glands are abnormal. You do a three and a half parathyroidectomy or a total with re-implantation. For an adenoma or cancer, it's usually less than four, just one or two. So, just excise the enlarged or abnormal parathyroid gland. Okay.
What else did I not cover? Um, I think that's it. So, are there any questions?