Thyroid Disorders

Yulianto Kusnadi Endocrinology and Metabolism Division Department of Internal Medicine, Faculty of Medicine Sriwijaya University/Mohammad Hoesin Hospital

Introduction
The thyroid gland is small, buterfflyshaped gland located located just below the Adam apple The thyroid produces hormones (T4 and T3) that affect body's metabolism and energy level Thyroid problems are among the most common medical conditions but, because their symptoms often appear gradually, they are commonly misdiagnosed The three most common thyroid problems are the underactive thyroid, the overactive thyroid , and thyroid nodules

Thyroid gland

Structure of thyroid hormones (1)

Thyroid hormones are unique in that they contain 59-65% of trace element iodine Iodine enters the body in food or water in the form of iodide or iodate ion; the iodate ion being converted to iodide in the stomach Thyroid hormones are derivatives of the the amino acid tyrosine bound covalently to iodine. The two principal thyroid hormones are: - Thyroxine (also known as T4 or L-3,5,3',5'-tetraiodothyronine) - Triiodotyronine (T3 or L-3,5,3'-triiodothyronine) The thyroid hormones are basically two tyrosines linked together with the critical addition of iodine at three or four positions on the aromatic rings Several other iodinated molecules are generated that have little or no biological activity; so called "reverse T3" (3,3',5'-T3)

Structure of thyroid hormones (2)

Thyroid hormones are poorly soluble in water, and more than 99% of the T3 and T4 circulating in blood is bound to carrier proteins The principle carrier of thyroid hormones is thyroxinebinding globulin, a glycoprotein synthesized in the liver Two other carriers of import are transthyrein and albumin. Carrier proteins allow maintenance of a stable pool of thyroid hormones from which the active, free hormones are released for uptake by target cells

Thyroid hormones synthesis and secretion

The synthesis of T4 and T3 by the thyroid gland involves six major steps: 1. Active transport of I- across the basement membrane into the thyroid cell (trapping of iodide) 2. Oxidation of iodide and iodination of tyrosyl residues in thyroglobulin 3. Coupling of iodotyrosine molecules within thyroglobulin to form T3 and T4 4. Proteolysis of thyroglobulin, with release of free iodothyronines and iodothyrosines 5. Deiodination of iodothyrosines within the thyroid cell, with the conservation and reuse of the liberated iodide 6. Undercertain circumstances, intrathyroidal 5-deiodination of T4 to T3

Physiologic effects of thyroid hormones (1)

Metabolism
Thyroid hormones stimulate diverse metabolic activities most tissues, leading to an increase in basal metabolic rate. One consequence of this activity is to increase body heat production, which seems to result, at least in part, from increased oxygen consumption and rates of ATP hydrolysis A few examples of specific metabolic effects of thyroid hormones include: Lipid metabolism: fat mobilization, increased concentrations of fatty acids in plasma, enhance oxidation of fatty acids in many tissues. Finally, plasma concentrations of cholesterol and triglycerides are inversely correlated with thyroid hormone levels - one diagnostic indiction of hypothyroidism is increased blood cholesterol concentration

Carbohydrate metabolism: Thyroid hormones stimulate almost all aspects of carbohydrate metabolism, including enhancement of insulin-dependent entry of glucose into cells and increased gluconeogenesis and glycogenolysis to generate free glucose

Physiologic effects of thyroid hormones (2)

Growth Thyroid hormones are clearly necessary for normal growth in children and young animals, as evidenced by the growth-retardation observed in thyroid deficiency Not surprisingly, the growth-promoting effect of thyroid hormones is intimately intertwined with that of growth hormone, a clear indiction that complex physiologic processes like growth depend upon multiple endocrine controls Development Of critical importance in mammals is the fact that normal levels of thyroid hormone are essential to the development of the fetal and neonatal brain

Physiologic effects of thyroid hormones (3)

Other effects Cardiovascular system: increased heart rate, cardiac contractility and cardiac output. They also promote vasodilation, which leads to enhanced blood flow to many organs Central nervous system: both decreased and increased concentrations of thyroid hormones lead to alterations in mental state. Too little thyroid hormone, and the individual tends to feel mentally sluggish, while too much induces anxiety and nervousness Reproductive system: normal reproductive behavior and physiology is dependent on having essentially normal levels of thyroid hormone. Hypothyroidism in particular is commonly associated with infertility

Disorders of the thyroid

Patients with thyroid disease will usually complain of: 1. Thyroid enlargement, which may be diffuse or nodular 2. Symptoms of thyroid deficiency or hypothyroidism 3. Symptoms of thyroid hormones excess or hyperthyroidism 4. Complications of specific form of hypo- or hyperthyroidism - Graves ophthalmopathy - Graves dermopathy

Simple goiter (1)

Definition A goiter is an enlargement of the thyroid gland. It is not cancer
Causes

A simple goiter usually occurs when the thyroid gland is not able to produce enough thyroid hormone to meet the body's needs The thyroid gland makes up for this by becoming larger, which usually overcomes mild deficiencies of thyroid hormone A simple goiter may be classified as either an endemic (colloid) goiter or a sporadic (nontoxic) goiter Endemic goiters occur within groups of people living in geographical areas with iodine-depleted soil, usually regions away from the sea coast People in these communities might not get enough iodine in their diet (iodine is vital to the formation of thyroid hormone) The modern use of iodized table salt in the United States prevents this deficiency. However, inadequate iodine is still common in central Asia, the Andes region of South America, and central Africa In most cases of sporadic goiter the cause is unknown. Occasionally, certain medications such as lithium or aminoglutethimide can cause a nontoxic goiter Hereditary factors may cause goiters. Risk factors for the development of a goiter include female sex, age over 40 years, inadequate dietary intake of iodine, living in an endemic area, and a family history of goiter

Simple goiter (2)

Symptoms The main symptom is a swollen thyroid gland. The size may range from a single small nodule to large neck lump The swollen thyroid can put pressure on the windpipe and esophagus, which can lead to: - Breathing difficulties - Cough - Swallowing difficulties - Wheezing - There may be neck vein swelling and dizziness when the arms are raised above the head

Simple goiter (3)

Exams and Tests Thyroid stimulating hormone (TSH) Free thyroxine (T4) Thyroid scan and uptake Ultrasound of thyroid -- if nodules are present, a biopsy should be done to check for thyroid cancer Treatment A goiter only needs to be treated if it is causing symptoms Treatments for an enlarged thyroid include: - Radioactive iodine to shrink the gland - Surgery (thyroidectomy) to remove all or part of the gland - Small doses of Lugol's iodine or potassium iodine solution if the goiter is due to iodine deficiency

Simple goiter (4)

Prognosis A simple goiter may disappear on its own, or may become large. Over time, destruction to the thyroid may cause the gland to stop making enough thyroid hormone. This condition is called hypothyroidism Occasionally, a goiter may become toxic and produce thyroid hormone on its own. This can cause high levels of thyroid hormone, a condition called hyperthyroidism

Possible Complications Hypothyroidism Hyperthyroidism Thyroid cancer Toxic nodular goiter

Prevention The use of iodized table salt prevents endemic colloid goiter

Hypothyroidism (1)
Causes
Insufficient thyroid tissue Developmental disorders, radiation and surgical injury , thyroiditis (e.g., Hashimoto's) with destruction of tissue Inhibition of hormone synthesis Idiopathic primary hypothyroidism (autoimmune TSH receptor blockade?), inborn errors of metabolism, iodine deficiency, drugs (lithium, iodides and others), thyroiditis (e.g., Hashimoto's) In elderly patients, may be confused with "senility" Cretinism In children, retarded mental and physical growth, classic appearance: dry, rough skin, periorbital puffiness, wide-set eyes, broad nose, protuberant tongue, may occur with developmental failure of the thyroid, inborn errors of metabolism affecting thyroid hormone synthesis, or iodine deficiency during fetal development

Hypothyroidism (2)
Central Loss of pituitary tissue with decreased TSH secretion Hypothalamic lesions with decreased TRH secretion Clinical sequelae Myxedema In adults Lethargy, cold intolerance, apathy, slow speech and mentation Periorbital edema, dry coarse skin, thickened tongue, constipation Flabby enlarged heart with pericardial effusion (hypothyroid cardiomyopathy)

Hypothyroidism (underactive thyroid) (1)

The most common cause of hypothyroidism is Hashimoto's thyroiditis. In this condition, the body's immune system mistakenly attacks the thyroid gland. Common symptoms of hypothyroidism are: Fatigue or lack of energy Weight gain Feeling cold Dry skin and hair Heavy menstrual periods Constipation Slowed thinking

Hypothyroidism (underactive thyroid) (2)

Diagnosis Diagnosis of hypothyroidism is usually straightforward, once it is suspected Patients with hypothyroidism due to Hashimoto's thyroiditis have an elevated level of serum TSH (thyroid stimulating hormone) However, the rare patient with hypothyroidism due to a pituitary or hypothalamic condition may have a normal or low serum TSH Treatment Treatment of hypothyroidism consists of taking thyroid hormone in pill form on a daily basis Symptoms of hypothyroidism should clear up within a few months of starting treatment Adjustment of the dose of thyroid pills is based upon measurements of serum TSH. Most patients need to take thyroid hormone for life

Hyperthyroidism
Causes
Graves disease (autoimmune stimulation of the TSH receptor) Toxic multinodular goiter (toxic refers to excess thyroid hormone production) Toxic thyroid adenoma Other thyroid, ovarian, or placental tumors are uncommon causes Iatrogenic (exogenous thyroxine)

Clinical presentation: Thyrotoxicosis

Hypermetabolic state Tachycardia, palpitations, tremor, diarrhea Heat intolerance, warm skin, perspiration, nervousness Thyrotoxicosis + hyperfunction of the thyroid gland = hyperthyroidism Thyrotoxicosis can also result from intermittent release of excess thyroid hormone from a thyroid gland that is not hyperfunctional. For example, destruction of thyroid tissue in thyroiditis (e.g., Hashimoto's) occasionally causes release of excess thyroid hormone from colloid as follicles break down. This produces transient symptoms of thyrotoxicosis, but is not classified as hyperthyroidism.

Laboratory measurement of thyroid hormones

Measurement of the TSH/T4 relationship
- Hyperthyroidism is almost always caused by a hyperactive thyroid gland which is producing too much thyroid hormone (hypothalamic causes for hyperthyroidism are extremely rare) - In the typical case, excess free thyroid hormone feeds back on the hypothalamus and pituitary, resulting in very low TSH levels (low TSH is a very good diagnostic indicator for hyperthyroidism) - The opposite happens in thyroid-related hypothyroidism: low free thyroid hormone decreases negative feedback resulting in very high TSH - If TSH is low in the setting of low thyroid hormone, the problem lies in the pituitary or hypothalamus - At present, most authorities recommend that the initial workup of thyroid status should be done by measuring TSH or TSH in combination with assay of free T4

Hyperthyroidism (overactive thyroid) (1)

The most common cause of hyperthyroidism is Graves' disease. This occurs when the body's immune system overstimulates the thyroid. Common symptoms of hyperthyroidism are: Jitteriness, shaking, increased nervousness, irritability Rapid heart beat or palpitations Feeling hot Weight loss Fatigue, feeling exhausted More frequent bowel movements Shorter or lighter menstrual periods

In addition to symptoms of hyperthyroidism, some patients with Graves disease develop eye symptoms such as a stare, eye irritation, bulging of the eyes and, occasionally, double vision or loss of vision. Involvement of the eyes is called Graves' Ophthalmopathy.

Hyperthyroidism (overactive thyroid) (2)

Diagnosis
Diagnosis is straightforward if suspected Patients are sometimes evaluated for other conditions, such as cancer or heart problems, if the doctor doesn't think of hyperthyroidism The diagnosis is best made by finding an elevated level of free T4 and low level of TSH in the blood A thyroid scan should then be performed to determine whether the hyperthyroidism is due to Graves' disease or another condition such as toxic multinodular goiter, hot nodule, subacute thyroiditis, or silent thyroiditis There are other, rare, cases of hyperthyroidism that usually require the expertise of an endocrinologist for diagnosis

Hyperthyroidism (overactive thyroid) (3)

Treatment
Radioactive iodine Because the thyroid is the only organ in the body that takes up and uses iodine, when a dose of radioactive iodine is given the radiation enters the thyroid and destroys part of it The main side effect is the development of an underactive thyroid which is treated Medications These drugs slow down the working of thyroid and restore normal levels However, they usually need to be taken for 6-12 months and 60-80% of patients have a relapse when they stop taking them These drugs are associated with serious side effects in a small percentage of patients taking them Surgical removal Surgical removal of part of the thyroid is occasionally used as a treatment Consultation with a thyroid specialist is highly recommended to determine which treatment is best for you!

Graves disease
Definition Diffuse hyperplastic goiter with symmetric enlargement of the gland (goiter is a generic term that refers to enlargement of the thyroid gland). Characteristic ophthalmopathy (proptosis, upper lid lag and retraction, periorbital edema) in most patients Characteristic dermopathy (10-15% of cases), appearing as plaque-like or nodular areas of edema on the backs of the legs and feet Because the orbital and skin changes are not present in all cases, symmetric goiters with hyperthyroidism (as measured by increased iodine uptake) and thyrotoxicosis are generally presumed to indicate Grave's disease Occurs in 1-2% of women, less often in men, more common with certain HLA haplotypes, autoimmune mechanism (also accounts for the ophthalmopathy and dermopathy) Thyroid-stimulating antibodies produced as a part of the autoimmune reaction, bind to the TSH receptor and mimic the action of TSH

Case Study
A 27 year old female presented with a history of nervousness, palpitations and heat intolerance. Her heart rate was 105 and bowel sounds were hyperactive. The skin was moist. TSH was undetectable in a 3rd-generation immunoassay. Free T4 was 7.5 ng/dl (0.8-2.3) Thyroid uptake of radioactive iodine was substantially increased overall (172% of normal), but there is also a "cold nodule" (a localized area of decreased iodine uptake) in the lower right pole of the gland. The thyroid gland was removed and pathologic examination showed diffuse hyperplasia with folded follicles and hypermetabolic cells. Note the white bubbly appearance of the edge of the colloid that borders the cells. This indicates active colloid resorption. Sections in the area of the lower right pole showed a discrete mass that was determined to be a follicular adenoma on microscopic exam. Final Diagnosis: Grave's Disease with a hyperplastic thyroid gland and an incidental Follicular Adenoma

Thyroid nodules (Lumps)

Thyroid nodules are fairly common and usually harmless However, about 4% of nodules are cancerous, so further testing needs to be done This is usually best accomplished by fine needle aspiration biopsy This is a quick and simple test that takes just a few minutes to perform in the doctor's office If the biopsy does not raise any suspicion of cancer, the nodule is usually observed Some thyroid specialists recommend treatment with thyroid hormone to try to decrease the size of the nodule A second biopsy is usually recommended 6-12 months later, to make sure there continues to be no evidence of cancer If a nodule is cancerous, suspicious for cancer, or grows large enough to interfere with swallowing or breathing, surgical removal is advised

Terminology (1)
Goiters ~ A thyroid goiter is a dramatic enlargement of the thyroid gland. Goiters are often removed because of cosmetic reasons or, more commonly, because they compress other vital structures of the neck including the trachea and the esophagus making breathing and swallowing difficult. Sometimes goiters will actually grow into the chest where they can cause trouble as well. Several nice x-rays will help explain all types of thyroid goiter problems

Thyroid Cancer ~ Thyroid cancer is a fairly common malignancy, however, the vast majority have excellent long term survival. We now include a separate page on the characteristics of each type of thyroid cancer and its typical treatment, follow-up, and prognosis. Over 30 pages thyroid cancer
Solitary Thyroid Nodules ~ There are several characteristics of solitary nodules of the thyroid which make them suspicious for malignancy. Although as many as 50% of the population will have a nodule somewhere in their thyroid, the overwhelming majority of these are benign. Occasionally, thyroid nodules can take on characteristics of malignancy and require either a needle biopsy or surgical excision. Now includes risks of radiation exposure and the role of Needle Biopsy for evaluating a thyroid nodule. Also a new page on the role of ultrasound in diagnosing thyroid nodules and masses

Terminology (2)
Hyperthyroidism ~ Hyperthyroidism means too much thyroid hormone. Current methods used for treating a hyperthyroid patient are radioactive iodine, anti-thyroid drugs, or surgery. Each method has advantages and disadvantages and is selected for individual patients. Many times the situation will suggest that all three methods are appropriate, while other circumstances will dictate a single best therapeutic option. Surgery is the least common treatment selected for hyperthyroidism. The different causes of hyperthyroidism are covered in detail Hypothyroidism ~ Hypothyroidism means too little thyroid hormone and is a common problem. In fact, hypothyroidism is often present for a number of years before it is recognized and treated. There are several common causes, each of which are covered in detail. Hypothyroidism can even be associated with pregnancy. Treatment for all types of hypothyroidism is usually straightforward Thyroiditis ~ Thyroiditis is an inflammatory process ongoing within the thyroid gland. Thyroiditis can present with a number of symptoms such as fever and pain, but it can also present as subtle findings of hypo or hyper-thyroidism. There are a number of causes, some more common than others. Each is covered on this site

Approach to diagnose hyperthyroidism

Technique 1. The location of the thyroid is identified by inspection 2. Using the anterior or posterior approach, palpate the thyroid to identify nodules 3. Note the size and number of nodules 4. Note the consistency of the nodule 5. Palpate regional lymph nodes for consistency and mobility

Inspection: lateral approach - After completing anterior inspection of the thyroid, observe the neck from the side - Estimate the smooth, straight contour from the cricoid cartilage to the suprasternal notch - Measure any prominence beyond this imagined contour, using a ruler placed in the area of prominence

Inspection Inspection: anterior approach - The patient should be seated or standing in a comfortable position with the neck in a neutral or slightly extended position - Cross-lighting increases shadows, improving the detection of masses - To enhance visualization of the thyroid, you can: Extending the neck, which stretches overlying tissues, and have the patient swallow a sip of water, watching for the upward movement of the thyroid gland

Palpation: Anterior Approach 1. The patient is examined in the seated or standing position 2. Attempt to locate the thyroid isthmus by palpating between the cricoid cartilage and the suprasternal notch 3. Use one hand to slightly retract the sternocleidomastoid muscle while using the other to palpate the thyroid 4. Have the patient swallow a sip of water as you palpate, feeling for the upward movement of the thyroid gland

Palpation: Posterior Approach 1. The patient is examined in the seated or standing position 2. Standing behind the, attempt to locate the thyroid isthmus by palpating between the cricoid cartilage and the suprasternal notch 3. Move your hands laterally to try to feel under the sternocleidomstoids for the fullness of the thyroid 4. Have the patient swallow a sip of water as you palpate, feeling for the upward movement of the thyroid gland

Treatment approach of thyroid disease

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