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Dr.danil Hammoudi











Follicular cells synthesize : thyroglobulin and secrete into the cavity.

contain tyrosine==> thyroid hormone when iodide ions are added by peroxidase enzyme.





Thyroglobulin is synthesized in the thyroid follicular cells and secreted into the lumen of the thyroid follicles.


Iodinating: Iodinating thyroxines---> MIT and DIT -----> T3 and T4
In the outside of the membrane , in the lumen , peroxidase catalyses the oxidation of iodide and its attachment to Thyroglogulin.
==> MIT [mono-iodothyronine] - DIT [di-iodothyronine].
MIT+DIT===>T3 and T4.


TSH promotes the endocytosis and breakdown of the colloid.
primary mode of stimulating thyroid secretion.



Tyroxine [T4] : The most common form of thyroid released
                         Less potent than T3.
                         More prevalent than     T3.
                         Binds to TBG more readily than T3.

TRIODOTHYRONINE [T3]: T4 is converted to T3 in the bloodstream.
                                                  More potent.
                                                  lower binding affinity to TGB.


Thyroid hormone increases the metabolic rate , especially catabolic  and also Anabolic.

  1. catabolism functions:
  2. Anabolism functions.

- stimulates mitochondrial oxidative phosphorylation.

-stimulates thermogenesis by uncoupling oxidative phosphorylation from ATP production.

-Raises blood sugar by enhancing gluconeogenesis and glycogenolysis.

-promote lipolysis in adipose tissue.

-Promotes glucose utilization and fatty acid synthesis in the liver.






Thyroid hormones readily cross cell membrane.

Bind intracellular receptors in nucleus to regulate gene expression [ enz involved in glycolysis and ATP production].

Released in response to TSH when T3/T4 levels are low or when body temperature drops.

Also bind receptors on surface of mitochondria to increase rate of mitochondrial ATP production.

Thyroid hormones increase metabolic activity [ calorigenic effect] and along with this the rate of O2 consumption.

Thyroid hormones increase the level of Na/K ATPase synthesis, so cells use more ATP and make more heat.

Thyroid hormone important in children for normal skeletal, neural and musculature development.

  • Hypothyroidism:

cretinism - retard neural and muscle development.

In adult this leads to decreased metabolism and inability to adjust to cold = myxedema.

  • hyperthyroidism:


grave's disease

restless , mood shift, drive but no energy.


c cells:

synthesize calcitonin.

decreases calcium ion concentration in the body fluids

  • stimultes osteoblasts : make more bones
  • inhibiting osteoclasts : less release of calcium from bone.
  • stimulating calcium excretion in kidneys : less calcium resorption.
  • inhibiting parathyroid hormone secretion.

calcitonin release is stimulated directly by increased calcium in blood [most important in childhood and pregnancy.

















Thyroid Hormones

Thyroid Hormones


Thyroid Hormones

Thyroid Hormones

Health Guides on Thyroid Disease #1

The Thyroid Gland: A General Introduction

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The thyroid gland is located in the front of the neck attached to the lower part of the voicebox (or larynx) and to the upper part of the windpipe (or trachea). It has two sides or lobes. These lobes are connected by a narrow neck (or isthmus). Each lobe is about 4 cm long and 1 to 2 cm wide. The name "thyroid" comes from the Greek word which means "shield".

Thyroid Hormones

The thyroid gland produces thyroid hormones. These are peptides containing iodine. The two most important hormones are tetraiodothyronine (thyroxine or T4) and triiodothyronine (T3). These hormones are essential for life and have many effects on body metabolism, growth, and development.


Iodine plays an important role in the function of the thyroid gland. It is the chief component of thyroid hormones, and is essential for their production. Iodine is obtained from the water we drink and the food we eat. The taking of excess amounts of iodine, such as kelp, will aggravate autoimmune thyroid disease and make the antibodies higher. In areas of the world where there is an iodine deficiency, iodine must be added to the salt or bread. The Great Lakes area of Canada and the U.S., the Swiss Alps and Tasmania are such areas.


Enlargement of the thyroid gland is called goitre. Goitre does not always indicate a disease, since thyroid enlargement can also be caused by physiological conditions such as puberty and pregnancy.

Hypothalamic - Pituitary - Thyroid Axis

The thyroid gland is influenced by hormones produced by two other organs:

  1. The pituitary gland, located at the base of the skull produces thyroid stimulating hormone (TSH)
  2. The hypothalamus, a small part of the brain above the pituitary, produces thyrotropin releasing hormone (TRH).

Low levels of thyroid hormones in the blood are detected by the hypothalamus. TRH is released, stimulating the pituitary to release TSH. Increased levels of TSH, in turn, stimulate the thyroid to produce more thyroid hormone, thereby returning the level of thyroid hormone in the blood back to normal.

The three glands and the hormones they produce make up the "Hypothalamic - Pituitary - Thyroid axis."

The ways a goitre forms in those geographic areas of the world which have a deficiency of iodine is a good example of how the axis functions. Normally, TSH increases the uptake of iodine by the thyroid gland and increases production of thyroid hormone. If there is little iodine available in our diet, hypothalamic TRH causes TSH to be released from the pituitary in large amounts. This enables the thyroid to capture most of the iodine presented to it from food and water. But, TSH has a second action - it causes growth of thyroid cells.

The gland grows and becomes very large under the influence of this high level of TSH secretion. Therefore, most people who live in iodine deficient areas have goitre, thus allowing them to produce enough thyroid hormone for normal body function. Once thyroid hormone levels are restored, TSH secretion stabilizes at a high level.

In healthy individuals and in those with goitre, the hypothalamic - pituitary - thyroid axis maintains thyroid hormone production at a finely controlled level and enables the thyroid to respond to situations requiring more or less thyroid hormone production.

Thyroid Disorders

The main causes of thyroid disease are:

  1. too much thyroid hormone production or hyperthyroidism.
  2. too little thyroid hormone production or hypothyroidism.

The state of normal thyroid function is called euthyroidism.

Abnormalities of the thyroid gland are common and affect one in twenty (1 in 20) of the Canadian population. All thyroid disorders are much more common in women than in men. Because of the widespread use of iodized salt and bread, lack of iodine is no longer a cause of thyroid disease in Canada as it was some 50 years ago.

"Autoimmune disorders" of the thyroid gland are common. These autoimmune disorders are caused by abnormal proteins, (called antibodies), and the white blood cells which act together to stimulate or damage the thyroid gland. Graves' disease (hyperthyroidism) and Hashimoto's thyroiditis, are diseases of this type. Each affects about 1 in 100 of the population.

Other less common causes of thyroid disease include nodule, thyroid cancer, subacute thyroiditis and primary hypothyroidism.

Graves' Disease

Graves' disease (thyrotoxicosis) is due to a unique antibody called "thyroid stimulating antibody" which stimulates the thyroid cells to grow larger and to produce excessive amounts of thyroid hormones. In this disease, the goitre is due not to TSH but to this unique antibody.

Hashimoto's Thyroiditis

In Hashimoto's thyroiditis, the goitre is caused by an accumulation of white blood cells and fluid (inflammation) in the thyroid gland. This leads to destruction of the thyroid cells and, eventually, thyroid failure (hypothyroidism). As the gland is destroyed, thyroid hormone production decreases; as a result, TSH increases, making the goitre even larger.

Thyroid Nodules

Sometimes, thyroid enlargement is restricted to one part of the gland; the rest of the gland being normal. The most common cause of this is a cyst or nodule, which may be benign or malignant. Occasionally there are many nodules. This so called "multinodular goitre" is probably caused by an abnormality of iodine metabolism.

A printed version of this Health Guide is available to health care professionals and the public. For more information call the National Office or contact your local chapter.

Production of the printed version of this Health Guide was made possible through partial funding assistance from Health Canada. The views expressed herein are solely those of the authors and do not necessarily represent the official policy of Health Canada.Original published 1983. Revised February 1995.
Copyright © 1996 Thyroid Foundation of Canada/La Fondation canadienne de la Thyroïde.

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Richland College

Student Projects for Biol. 2402 - Anatomy & Physiology
Project Members:

The thyroid gland is a butterfly shaped gland located at the base of the throat. It secretes two major hormones, thyroxine (T4) and triiodothyronine (T3). These hormones are collectively referred to as thyroid hormone. Thyroid hormone affects almost every cell in the body with the exception of the brain, spleen, testes, and uterus.

The following is a description of the effects of thyroid hormones on metabolism and the major Organ Systems of the human body.


T3 and T4 stimulate enzymes concerned with glucose oxidation,(the addition of oxygen to blood sugar to produce energy). This increases metabolic rate ( the body's rate of energy expenditure), oxygen consumption, and body heat production. The increase in body heat production is known as the calorigenic effect.

Thyroid hormone also enhances the rate of uptake of glucose,( the breakdown product of carbohydrates) by adipose tissues and muscle.


Thyroid hormone increases the production of enzymes which promote protein synthesis. Protein synthesis is responsible for the growth of an individual. Variations in the overall growth rate are probably the most general reflection of the effects of thyroid hormone. In immature people growth is retarded by too little hormone and is inhibited by excessive doses of the hormone.


Thyroid hormone effects synthesis, mobilization and degradation of lipids. The breaking down of lipids is affected to a greater extent. The breaking down of free fatty acids by oxidation is increased. This also elevates body heat production and accounts for some of the calorigenic effect described earlier.

Thyroid hormone lowers blood cholesterol by increasing the rate at which cholesterol is excreted and degraded.


Thyroid hormones promote normal GI motility. They increase secretion of digestive juices. The ability of the intestines to absorb glucose and galactose is enhanced by thyroid hormone.


Thyroid hormone facilitates cardiac contraction and cardiac output. Increased secretion may result in:

T3 and T4 also mediate changes in sensitivity to catecholamines such as epinephrine.


T3 and T4 affect the mammary glands. Increased T4 has been credited with increasing the development of lobule-aveolar in the breast. Thyroid hormone deficency may cause delayed puberty (lack of sexual maturation before the age of 15). In immature humans, thyroid deficiency is usually associated with stunting of ductal system.


Thyroid hormone influences adrenal cortex and medulla. Increased levels of thyroxine produces enlargement of adrenal cortex, low levels cause a decrease in sizeof the adrenal cortex. Excess thyroid hormone diminishes the amount of adrenal corticoids formed. Thyroid hormone increases sensitivity to the actions of adrenal medullary secretions of epinephrine and norepinephrine.


In a developing fetus thyriod hormone, supplied by the mother promote normal develompent of the nervous system. This exchange of hormones at normal levels protect the unborn child from cretinism a form of mental retardation, which is irreversible. After birth the newborn produces his own thyroid hormone, which continue to maintain normal nervous system function throughout life.


Thyroid hormone effects on the skeletal system is to encourage bone growth until adulthood is reached. Thyroxine (T4) is the mainly responsible for bone growth. T4 activates cells called osteoclast that break down bone material releasing this material into the blood stream. Normal levels of Thyroxine help control osteoclast form breaking down of bone. By T4 controlling osteoclast this will control the building of bone.


Thyroid hormones stimulate production of proteins needed for muscle contraction and relaxation. These activated proteins are controlled by the thyroid hormone. The protiens provide the building blocks for musle tissue.


The thyroid affects on the integumentary system are very simple. Through the control of sweat glands and oil glands, thyroid hormone ensures that the skin is not too dry or cracked . When the thyroid levels are low, a condition known as Myxedema results. This lack of hormone thickens and drys the skin. The thyroid also has some control over color of the skin.


In addition to T3 & T4 the thyroid produces another hormone called calcitonin. Its primary function is to lower blood calcium levels, and to promote calcium storage in the bones. Excessive blood calcuim levels stimulate the thyroid gland to release more calcitonin.

Basal Metabolic Rate CarbohydrateLipid/ProteinMetabolism Nervous System Muscular System Cardiovascular System
Controls the rate of energy that is used by the body Controls the breakdown of food into energy for cell use. And helps control Cholesterol  Helps in the development of the Nervous system in childhood and maintains the system in adulthood  Controls proteins used to contract muscles Helps in the control of Basal Metabolic rate which effects heart beat


Skeletal System Digestive System Reproductive System
Controls the break down of the bone to allow growth  Helps in the movement of food through GI tract and the release of digestive juices  Effects on Females only Helps in ability to have children and form breast milk 


Thyroid|Nuclear Medicine - Page THY01 [ Previous | Next ]


Thyroid Physiology

Thyroid Physiology




     The horseshoe-shaped THYROID gland consists of 2 lateral lobes which are connected by a narrow isthmus section running anterior to the trachea.  It can be palpated when enlarged.

anterior to the trachea, just below the larynx
deep to the sternocleidomastoid muscles of the neck
at the level of C5-T1 vertebrae
     The thyroid produces triiodothyronine (T3), thyroxine (T4), and calcitonin.  The production of T3 and T4, both involved with growth and metabolism, is stimulated by TSH, thyroid-stimulating hormone, from the pituitary gland.  Calcitonin is involved with calcium uptake and calcium blood levels.


     Thyroid disorders are among the most common endocrinological diseases.  Hypothyroidism can reduce the metabolic rate to as low as 1/2 the normal rate, whereas hyperthyroidism can possibly double it.
Thyroid diseases fall into 3 main categories:




Hashimoto's thyroiditis (myxedema) 
nontoxic goiter (iodine deficiencies) 
neonatal goiter or cretinism 
Riedel's thyroiditis


toxic goiters or thyrotoxicosis (Graves' disease) 
toxic nodular goiter 
neonatal hyperthyroidism 
iatrogenic hyperthyroidism


thyroid carcinoma


Our anatomy and physiology class projects cover most of these problems, along with basic information on functions of the hormones, diagnoses and prognoses, and treatments.  We hope that this website will help you to better understand the thyroid and problems related to it.


Demographics of thyroid disorders

 The hormones and their functions



 Diagnoses and Assessments


For feedback:
Jackie Reynolds (Professor of Biology, Richland College)



Thyroid|Nuclear Medicine - Page THY02 [ Previous | Next ]



Physical Characteristics

I-123 decays by electron capture, has a physical half-life of 13.6 hours, and a gamma energy of 159 keV. It is produced in a cyclotron by either one of two methods:


I-127(p,5n) Xe 123 -> I 123

This method requires more energy, but produces I-123 of higher purity with no I-124 contamination and very little I-125 (I-125 has a half-life 60 days and emits 25 to 35 keV x-rays which contribute significantly to the radiation exposure to the patient). Because I-123 decays much faster than these contaminants, doses which are more than 24 hours old should not be used.

Te-124 (p,2n) I-123

This method results in impurities such as I-124 (5%), I-125, I-126, and Na-24. The I-124 has higher energy gamma emissions and a 4.2 day half-life which contribute to image degradation and patient dose, respectively.


200-400 uCi


I-123 is the agent of choice when evaluating substernal goiters because there is usually substantial mediastinal blood pool activity associated with Tc-pertechnetate. The maximal count rate in the thyroid occurs approximately 6 hours following the oral administration of the agent. Images are typically acquired 4 hours following administration of the tracer, and uptake values are determined at 4 and 24 hours.


Physical Characteristics

I-131 has a physical half-life of 8.05 days and emits a high energy gamma (364 keV) and particulate emissions. Beta particles with average energy = 192 keV, max energy = 607 keV are emitted and deposit the majority of their energy within 2.2 mm of their site of origin.


I-131 is reactor produced.


Diagnostic: 2-5 mCi po for whole body iodine scans for following a patient with thyroid carcinoma.

Therapeutic: 80-150 uCi per gram of thyroid tissue for Graves' disease (refer to radiotherapy in non-neoplastic thyroid disease).

100-200 mCi for thyroid carcinoma (refer to section on I-131 ablation in thyroid neoplasm

Thyroid hormone should be discontinued for several (2-6) weeks in advance of study or treatment. A serum TSH level is very helpful to gauge the adequacy of thyroid hormonal withdrawal. Unless the TSH level is increased, the validity of an I-131 body scan, especially if it is normal, should be questioned.


The long half-life, high energy gamma, and beta emissions described above limit the usefulness of I-131 for imaging purposes. Its administration results in a very high radiation dose to the thyroid, 90% of which is the result of beta decay (see below). I-131 is not the tracer of choice for imaging applications, except in the case of delayed imaging for thyroid carcinoma metastases or mediastinal masses, where the higher energy gamma and improved target-to-background ratio following washout are useful. Because of the beta emission, however, the agent is useful for therapeutic purposes.


I-125 is not used for imaging. The agent decays by electron capture with a physical half-life of 60.2 days. It emits a gamma photon of 35 keV. The agent is primarily used for radioimmunoassays and other in vitro procedures.

Technetium-99m Pertechnetate

Chemistry and Pharmacology

Pertechnetate (TcO4-) is a monovalent anion trapped by the thyroid gland in the same manner as iodine (an active transport mechanism). After trapping pertechnetate slowly "washes" from the gland- it does NOT undergo organification. Peak thyroid activity occurs between 20 and 40 minutes after injection. Only 2-4% of the administered dose is trapped in the thyroid. Pertechnetate is secreted in human milk (discontinue breast feeding for 48 hours after dosing) and also crosses the placenta to accumulate in the fetus.

Iodine and pertechnetate share the same active transport uptake pathway. The uptakes of radioiodine and pertecnetate by the follicular trapping system are both decreased by perchlorate, thiocyanate ions, and expansion of the circulating iodide pool (iodinated contrast, dietary, or the antiarrhythmic agent amiodarone) [Annual 94, p.256].


The typical dose used for thyroid imaging is 3 mCi intravenously.


Dr. Fink-Bennet feels that a rough estimate of thyroid uptake can be obtained from the Tc-pertechnetate exam by obtaining a 1 minute anterior planar image over the thyroid and salivary glands 5 minutes after injection of the tracer. A hypofunctioning gland will appear less intense than the salivary glands, a normal gland equal to the salivary glands, and a hyperfunctioning thyroid hotter than the salivary glands.

In comparison to I-123 studies, more background activity is usually present on pertechnetate images. Linear esophageal activity, due to tracer secreted by the salivary glands which is swallowed, may be seen. This can be cleared from the esophagus by drinking water. (Note: See Pyramidal Lobe below). A pinhole collimator is used for enhanced resolution and also facilitates oblique views.

The size of nodules that can be detected by pertechnetate imaging depends upon the nodules function and size. Hot nodules may be seen even if they are very small, but a hypofunctioning nodule less than 0.8 to 1.0 cm in size lying within the gland may not be discernible. In general, Tc-pertechnetate 5-mm pinhole imaging has a sensitivity of 80 to 95% for cold nodules between 8 to 18 mm, but nearly 0% for nodules less than 5 mm. There are reported cases of thyroid carcinomas that are capable of trapping but not organifying iodine. Therefore, it is possible to have a warm or hot nodule on a Tc-99m scan that would be cold on I-123. Therefore, any patient with a non cold nodule on a Tc-99m scan should be repeated with I-123 to avoid this disparity. Cold nodules with Tc-99m scan will inevitably be cold with an I-123 scan.


Pertechnetate is the preferred imaging agent when:

Radiation dose to the thyroid, by agent

Assuming normal sized adult gland (20 gm) with normal RAIU (15%):

* 131I: 800-1000 rad/mCi; 16,000 rad/mCi in the neonate [Miller, p.46]

* 123I: 7.5 rad/mCi (adult); 160 rad/mCi (neonate)

* 125I: 450 rad/mCi

* 99mTc-O4: 0.13 rad/mCi (adult); 3.4 rad/mCi (neonate)

Pregnancy is an absolute contraindication to thyroid scanning, especially after the 12th week of gestation when the fetal thyroid begins to trap iodine. Prior to this time tests should be avoided if possible despite the fact that the fetal dose will be very low (1 mrad/mCi of I-131). Iodine, Thionamides, Thyroid Stimulating Antibodies, and TRH all cross the placenta easily. T3 and T4 cross only minimally. TSH does not cross the placenta.

Nuclear Imaging Tests

Radioactive Iodine Uptake Test (RAIU)


RAIU can be determined using either I-131 (7 uCi) or I-123 (200-300 uCi). Normal 24 hour RAIU is between 8 to 35%. Normal 4 hour RAIU is generally between 5 to 15%.

% Uptake= [(net neck counts - net thigh counts)x 100] /(net standard counts)

The RAIU test provides a useful assessment of thyroid function: in general, the higher the iodine uptake, the more active the gland. Note, however, that in patients with hypothyroidism such as Hashimoto's disease, the % uptake may be low, normal or high depending on the steps affected in thyroid hormone synthesis. This is therefore of no value in establishing the diagnosis of hypothyroidism.


RAIU test may be helpful in the following clinical conditions:

To confirm hyperthyroidism

To calculate therapeutic dose of I-131

To determine autonomous thyroid tissue (i.e. toxic nodules, - combined with thyroid scan)

To determine the cause of thyrotoxicosis*

* The most useful role of RAIU test is in determining the etiology of thyrotoxicosis. Thyrotoxicosis simply refers to excess thyroid hormone in the body and may be due to overactivity of the thyroid gland (hyperthyroidism), or other causes such as inflammation of the gland (thyroiditis) or ingestion of excess thyroid hormone. In "true hperthyroidism" - RAIU uptake will be high while thyrotoxic patients with thyroiditis or who abuse thyroid hormones will have a low RAIU. Other factors that affect RAIU uptake are listed below.

Factors affecting uptake

Patient's iodine pool:

- Dietary variations: RAIU can be falsely elevated in patients who are iodine deficient.

- Renal function: Poor renal function results in decreased excretion of iodine, the larger iodine pool will compete with the radiopharmaceutical for uptake thus falsely lowering RAIU.

- Recent iodine contrast study: The excess iodine will falsely lower the RAIU. It may require weeks prior to scanning in order to obtain an accurate value. The Wolff-Chaikoff effect refers to a transient decrease in iodide organification and hormone synthesis in normal or Graves patients following an iodide load.


- Antithyroid drugs: Propythiouracil and methimazole result in a poor 24 hour scan because they block iodide oxidation and organification. Because the agents do not inhibit iodine trapping, a pertechnetate scan, may be technically adequate.

- Thyroid hormone

- Amiodarone

Etiologies resulting in an Increased RAIU

* Hyperthyroidism (Grave's disease or TSH-secreting pituitary adenoma)

* Rebound following abrupt withdrawal of antithyroid meds

* Long term antithyroid therapy: Prolonged therapy may result in decreased circulating levels of T4- hence TSH levels will increase. This will accentuate radioiodine uptake.

* Enzyme defects

* Iodine starvation

* Lithium Therapy

* Early Hashimoto's Thyroiditis (Patients rarely present at this stage, RAIU is typically normal [early] or decreased [late] in these patients)

* Rebound during recovery from subacute thyroiditis

Etiologies resulting in a Decreased RAIU

* Blocked Trapping:

- Iodine load (most common). An iodine load can "falsely" lower the RAIU through two

mechanisms: 1) producing the Wolf-Chaikoff effect 2) causing a dilutional effect, i.e.,

diluting the I-123 atoms with nonradioactive I-127 atoms.

- Exogenous thyroid hormone replacement depressing TSH levels

- Ectopic thyroid: Struma Ovarii

* Blocked Organification:

- Antithyroid medication (PTU): Note- Tc-99m uptake should not be affected

* Parenchymal Destruction:

- Acute, Subacute and Chronic Lymphocytic Thyroiditis

* Hypothyroidism:

- Primary or Secondary (insufficient pituitary TSH secretion)

- Surgical/Radioiodine Ablation of Thyroid

Thyroid Suppression Test


The thyroid suppression test is based on the premise that normal thyroid activity is suppressed by exogenously administered thyroid hormone. The test is used to determine the autonomy of a hot nodule or diffusely enlarged gland. A baseline scan and uptake are performed. The patient is then placed on T3 (Cytomel 25 ug TID [50-75 ug daily] for 7 days) to suppress TSH production. Iodine uptake should normally fall to 50% of presuppression value in a non-autonomously functioning nodule.


In most cases of hyperthyroidism, the diagnosis will be apparent on baseline scan and uptake. In Graves' disease, the uptake will be elevated with a homogenous distribution. In autonomous nodules, uptake may be high normal or elevated with the remainder of the normal gland suppressed. This together with the availability of sensitive TSH assays has virtually eliminated the need to do thyroid suppression test. Some conditions where this test may provide additional information include:

*Early Graves' disease with borderline hyperthyroidism or in euthyroid Graves' disease (patients presenting with opthalmopathy but normal function tests).

*Nodules which are indeterminate (warm or nondelinated) where a distinction between hot and cold is unclear. A repeat scan on cytommel (T3) or levothyroxine therapy with suppression of TSH may reveal whether the thyroid nodule is autonomous (hot on non autonomous (cold). A non autonomous nodule should be treated as a cold nodule and require further evaluation. [Ridgway Clinical Review 30: Clinician's Evaluation of a Solitary Thyroid Nodule, J of Clin Endoc Metab 74:231-235, 1992]

*Evaluation of Toxic Multinodular Goiter (Plummer's Disease)

*Hypothyroid patients recently treated with I-131 for Graves' disease and started on hormone replacement may present with elevated thyroid hormone levels, suppressed TSH and show evidence of recurrent thyrotoxicosis. A high normal or elevated RAIU would confirm recurrent hyperthyroidism. However, a simpler alternative would be to discontinue hormone replacement and observe the patient.

TSH Stimulation Test

The TSH stimulation test is used to identify thyroid tissue which is being suppressed by an autonomously functioning thyroid nodule (high levels of circulating thyroid hormone may suppress TSH release and thus, normal glandular function) or functioning thyroid metastasis.

Exogenous bovine TSH is administered once daily for 1 to 3 days. Suppressed normal thyroid tissue should be visualized following TSH stimulation. Patients with thyroid atrophy or diseased or damaged thyroid tissue will not have significant change in the appearance of their scans. Although this test was used frequently in the past to distinguish primary from secondary hypothyroidism, it no longer is necessary now that serum TSH levels are now available. In addition, the use of bovine protein may be associated with the risk of a major allergic reaction.

More recently, the administration of recombinant human TSH (rhTSH) has been proposed as an effective agent for detecting residual or metastatic thyroid tissue in patient with thyroid carcinoma. [MEIER CA et al. Diagnostic Use of Recombinant Human Thyrotropin in Patients with Thyroid Carcinoma, J Clin Endoc Metab 78:188-196, 1994] The traditional procedure for performing a follow-up whole body radioiodine scan requires the withdrawal of thyroid medications to allow endogenous TSH levels to increase above 40 mU/L so as to stimulate residual thyroid tissue. However, most patients become clinical hypothyroid during this period and are exposed to the potential risk of increased tumor growth associated with elevated serum TSH levels. Meier et al. reported in phase I/II study that the use of rhTSH was just as safe and effective in stimulating I-131 uptake by residual thyroid tissue without the disadvantages of having to withdraw thyroid hormones and causing hypothyroidism. Studies are still ongoing and currently, rhTSH is still not available for general clinical use.

Perchlorate Washout Test

This test is used to identify congenital or acquired organification defects which most commonly involves the enzyme iodide peroxidase. In normal subjects, radioiodine when taken up by the thyroid is immediately organified and bound to thyroglobulin. However, in patients with defects in peroxidase activity (usually hypothyoid), trapped radioiodine is rapidly discharged when sodium perchlorate (an inhibitor of thyroid iodide trapping) is administered.

Thyroid uptake is then determined between 2 and 4 hours after administration of the dose. Potassium perchlorate 109 mg/kg is then administered orally and a repeat measurement of RAIU performed in 30 to 60 minutes. A decrease in RAIU greater than 10-15% following perchlorate administration is indicative of any organification defect. The test is rarely performed since the treatment for primary hypothyroidism is thyroid hormone replacement regardless of the cause or site of defective thyroid hormone synthesis. 

Thyroid|Nuclear Medicine - Page THY02 [ Previous | Next ]

(C) 1995-96 Ralph Blumhart, M.D. and Scott Williams, M.D.



Thyroid Releasing Hormone (TRH) is a peptide hormone synthesized in the hypothalamus and passed through the hypophyseal portal venous system. In the anterior pituitary, TRH stimulates synthesis and release of Thyrotropin (TSH). TSH in turn acts on the thyroid glad to stimulate thyroid gland growth and thyroid hormone synthesis. A simple negative feedback relationship exists between the pituitary and the thyroid. The release of TSH is inhibited at the pituitary by elevated circulating levels of thyroxine (T4) that is ccnverted by intrapituitary type II deiodinase to triidothyronine (T3).

Thyroid Hormone Synthesis

There are 4 basic steps involved in thyroid hormone synthesis which include:

Approximately 90% of the released thyroid hormone is in the form of T4, and 10% in the form of T3. The great majority of T3 (80-90%) is produced by the peripheral conversion of T4. The metabolic activity of thyroid hormone is determined by the amount of free T3 and free T4. Thyroxine (T4) is very highly protein bound in plasma (99.95% bound, about 0.05% free). Therefore, a rough estimate of the total T4 can be approximated by the amount of bound thyroxine.

Tri-iodothyronine (T3) is produced by the peripheral deiodination of T4. T3 is much more potent than T4. About 99.5% of circulating T3 is bound (0.5% free). Reverse T3 is also produced by the deiodination of T4, but only when there is excess circulating thyroid hormone (hyperthyroid states). Reverse T3 is not physiologically active, so its production helps to prevent excess catabolism. Levels of reverse T3 are also elevated during periods of severe illness. Elevated levels of reverse T3 are also present during periods of severe nonthyroidal illness such as sepsis, congestive heart failure or burns. Since reverse T3 is not physiologically active, the conversion of T4 to T3 instead of the more active T3 is a metabolic compensation to prevent excess catabolism.

Thyroid Hormone Transport/TBG

More than 99% of thyroid hormone is carried in circulation firmly bound to three major binding proteins: thyroid binding globulin (TBG), transthyretin (TTR, formerly called thyroxine binding pre-albumin - TBPA) and albumin. TBG is the primary serum binding protein because of its higher affinity for T4. Under normal conditions, 75% of T4 is bound to TBG, 10-15% to TTR, and 5-15% to albumin. When bound, T4 is not physiologically active but provides a storage pool of thyroid hormone which can last 2-3 months (mean half-life of T4=6.7 days in adults).

TBG is synthesized by the liver under the influence of estrogen. An increase in TBG concentration in response to higher estrogen levels may result in higher measured total T4 concentration. However, the amount of free T4 concentration remains constant and the patient remains clinically euthyroid.

Conditions associated with increased levels of TBG:

In contrast, factors that cause a decrease in TBG concentration or lower affinity for T4 binding to TBG may result in low measured total T4 concentration without affecting free T4 levels.

Conditions associated with decreased binding of T4 by TBG:

Thyroid Function Tests

Total serum thyroxine (T4)

This includes both bound and free T4 concentration. Under most conditions with normal TBG concentrations, the total T4 level reflects the functional state of the thyroid. However, changes in binding proteins as described above, may alter total T4 concentration without affecting the unbound free T4 level. In these circumstances, calculating the free thyroxine index (FT4I) or obtaining a direct free T4 or free T3 level would provide a more accurate estimate of the patients true thyroid status.

T3 resin uptake (T3RU)

This test has been renamed thyroid hormone binding index (THBI) or thyroid hormone binding ratio (THBR), although most clinicians are still more familiar with the use of the term T3RU. It is important not to confuse T3RU with the serum total T3 by radioimmunoassay (total T3-RIA) that measures the total serum triidothyronine (T3) concentration. The T3 Resin uptake test measures the amount of unsaturated binding sites on the thyroid hormone transport proteins. A proportion of the labeled T3 will bind to available sites on the serum TBG; any excess will bind to the resin. Resin uptake is inversely proportional to the number of vacant binding sites, and therefore inversely proportional to the total TBG.

In thyrotoxicosis, there are fewer vacant binding sites available on thyroxine binding globulin due to the high circulating levels of thyroid hormone. This means less radioactive T3 will be able to bind to TBG and more will bind to the resin. Hence, resin uptake is higher in hyperthyroid patients than it is in normals. The converse is true in hypothyroid states. In high TBG states, such as pregnancy or estrogen therapy, the T3RU will be low. However the physiologically active free thyroxine level will still be normal.

Free thyroxine Index (FT4I)

FT4I is a reflection of the amount of free hormone (free T4) in most situations. It is a calculated value and corrects for changes in TBG concentrations by using the following formula:

FTI = (Total T4) X (T3 Resin Uptake / T 3RU control).

mean normal T3RU for the particular assay (i.e. normal range 25-35% m

mean normal is 30%)

With extreme changes in TBG concentrations, acute medical illness, heparin therapy or low protein states secondary to nephrotic syndrome, the FT4I may not accurately reflect the amount of free T4 concentrations.

Free T4 and T3

More direct methods are now available for measuring free T4 and T3 levels. These tests have replaced the FT4I and FT3I in many centers. In reality, most methods of measuring "free T4" provide only indirect estimates of true levels of circulating free hormone and its accuracy may be affected by severe TBG changes or alterations in binding protein affinity. The gold standard for obtaining a true free T4 concentration is by direct equilibrium dialysis but is limited by cost and availability.


The devlopment of new sensitive immunoradiometric (IRMA) assays to measure serum thyroid hormone (TSH, thyrotropin) has been a valuable tool in the diagnosis and management of thyroid diseases. The expected normal range for TSH is 0.5-5.0 mU/L. Older insensitive TSH-RIA assays could only measure concentrations as low as 0.5 mU/L. With the new sensitive TSH assays, TSH concentrations as low as 0.001 mU/L. With the new sensitive TSH assays, TSH concentrations as low as 0.001 mU/L can be detected.

Measuring the serum TSH has become the screen test of choice for thyroid disease. Primary hypothyroidism produces elevated TSH levels whereas patients with primary hyperthyroidism (i.e. Graves) should have undetectable TSH values. This relationship is true only in individuals with an intact hypothalamic-pituitary-thyroid axis. Patients who present with a normal or detectable TSH level and elevated thyroid hormone concentrations require further evaluation to exclude central causes of hyperthyroidism.

TRH test

The administration of thyrotropin releasing hormone (TRH) causes a rise in TSH concentration in normal subjects (TSH = 2-30 MU/L.) An exaggerated response occurs in primary hypothyroid subjects (TSH often > 30 mU/L, depending on the baseline TSH elevation.) Hyperthyroid patients have a mild or absent TSH response (TSH < 2 m U/L) since the suppressed TSH cannot be stimulated by exogenous TRH. The introduction of sensitive TSH assays that can detect low suppressed TSH levels, identifying patients with primary hyperthyroidism, has virtually made the TRH stimulation test obsolete.


Plasma iodine in the form of iodide is concentrated (trapped) in the thyroid cells by an energy requiring active transport mechanism where it is incorporated into T3 (triiodothyronine) and T4 (thyroxine) via organification (Therefore, iodine measures both trapping and organification by the thyroid gland). These active hormones are stored in follicles as thyroglobulin.

The normal distribution of iodine, and therefore its radiotracer isotopes, is in the thyroid, salivary glands, gastric mucosa, small and large bowel, urinary bladder, liver, and breast (esp. during lactation; see below). Iodine undergoes both renal (up to 75% in 24 hours) and GI excretion.

The normal daily dietary intake of iodine is about 500 ug. The amount of iodine in a typical uptake dose (10 uCi) is about 8 nanograms. This is significantly less than the amount of iodine in I.V. contrast- which, assuming a 40% content of iodine, contains about 40 grams of iodine in 100 ml.

Fetal and Neonatal Thyroid Function

Iodine and Technetium both cross the placenta and will be concentrated in the fetal thyroid. The fetal thyroid does not concentrate iodine during the first 12 weeks of gestation; beyond this point, iodine uptake increases progressively until term. There is probably only minimal transfer of maternal TSH, T4 and T3 across the placenta. However, Iodine, Thionamides, and TRH can cross the placenta without difficulty.

Following delivery there is an abrupt increase in serum TSH and thyroid uptake of iodine is elevated from 10 hours to 2 days post-delivery. TSH levels and uptake return to normal levels within a few days. Both Iodine and Technetium are secreted in the breast milk of lactating women, so nursing should be delayed for 48-72 hours following Tc99m, and for 2-3 weeks following I-131 imaging- essentially this translates to discontinuance of breast feeding. We recommend that women who are breast feeding permanently discontinue breast feeding if they are to undergo I-131 therapy. 

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(C) 1995-96 Ralph Blumhart, M.D. and Scott Williams, M.D.

Health Guides on Thyroid Disease #2

To Confirm the Clinical Diagnosis

Laboratory Investigation Of Thyroid Disease

For many patients with thyroid disease, the gland produces excessive amounts of thyroid hormone (hyperthyroidism) or insufficient amounts of thyroid hormone (hypothyroidism). Such patients will usually have an associated goitre (swelling of the thyroid gland). However, many patients with a goitre will have normal thyroid function. Most patients who develop a lump or nodule in the thyroid will have a normal thyroid function as well. A minority of patients, with thyroid nodules, will have a hyperfunctioning nodule that will make the patient hyperthyroid.

The most important uses of laboratory tests are:

  1. to confirm the clinical diagnosis of thyroid disease;
  2. to monitor patients with thyroid disease who have been treated;
  3. to select, for removal by the surgeon, those single nodules which may be malignant.

Measurement Of TSH (Thyrotropin)

The pituitary hormone TSH stimulates the thyroid gland to make and release the thyroid hormone. When thyroid hormone levels decrease, the TSH rises and vice versa. Measurement of TSH using a sensitive assay is presently the recommended initial screening test when thyroid disease is suspected. The TSH assay is able to separate hypothyroid and hyperthyroid patients from normal individuals. Basically, a normal TSH excludes primary thyroid disease. When the TSH is elevated, this suggests hypothyroidism and when suppressed suggests hyperthyroidism. Rarely the TSH level may be suppressed by drugs (such as corticosteroids) or by severe psychiatric or non-thyroidal illness. However, such circumstances are extremely rare in the out-patient setting.

Measurement Of Blood T3 And T4

When the TSH is abnormal, measurement of thyroxine (T4) or triiodothyronine (T3) are performed to determine the extent of the thyroid abnormality. An elevated T4 or T3, in association with a low or suppressed TSH, establishes hyperthyroidism. An elevated TSH in conjunction with a low T4, establishes hypothyroidism. Since using the TSH assay as a primary test, doctors have identified patients who have an isolated low or high TSH in association with normal T4 and T3 levels. Although some of these patients will eventually develop overt thyroid disease, it is presently difficult to predict who they will be. The assessment and management of such patients needs to be individualized.

Thyroid Hormone Binding Proteins

Thyroid hormones circulate in association with proteins which bind thyroid hormones. It is only the free or unbound portion which we believe to be active at the tissue level. However, free levels represent less than 1% of the total thyroid hormone levels. In certain circumstances, such as pregnancy or the birth control pill, the elevated estrogen or female sex hormone, associated with these conditions, raises the level of thyroid hormone binding protein. The body will compensate by increasing the production of T4 and T3 so that the free level remains normal. However, such individuals will have a higher total T4 and T3. Because the free level remains normal, their TSH does not change. In many circumstances, measurement of the free T4 and free T3 is available. Alternatively, the T3 resin uptake test can be performed and provides an indirect measurement of the level of thyroid binding protein. The FT4 index is the total T4 multiplied by the T3 resin uptake and should be proportional to the true free T4 level. In pregnancy, the total T4 is elevated, the T3 resin decreased and the free T4 index is normal. The availability of the TSH screening has largely eliminated any confusion caused by changes in thyroid binding proteins as the TSH will remain normal in these circumstances.

Radioactive Iodine Uptake And Thyroid Scan

The thyroid gland takes up iodine and uses this to make thyroid hormone. Radioactive iodine is taken up and metabolized by the thyroid in exactly the same way. Approximately 20% of a dose of radioactive iodine, given orally, is taken up by the thyroid gland within 24 hours after the dose is given. This is measured by counting the radioactivity over the thyroid gland. The test is safe since the radiation dose is very small, although it is usually not carried out in children or pregnant women. In a patient with hyperthyroidism the radioactive iodine uptake test will separate those permanent causes of hyperthyroidism such as Graves' disease in which it will be elevated from those temporary causes of hyperthyroidism such as thyroiditis in which it will be suppressed. Alternatively, the gland can be photographed or "imaged" and the distribution within the gland of a radio labelled tracer, (usually technetium) recorded. This is called a thyroid scan. The scan can be used as an alternative to the radioactive iodine uptake as described. In addition, the scan gives an idea of the shape and size of the thyroid gland and can be used for patients with thyroid nodules to determine whether the nodule is functioning.

Thyroid Antibodies

Patients with Hashimoto's thyroiditis have an autoimmune disease. Thyroid antibodies are blood proteins which react against certain of the patient's own proteins (called antigens) within the thyroid gland. In patients with Hashimoto's thyroiditis high levels of antibodies are usually found and, therefore, are markers of the autoimmune process. Low levels of antibodies are sometimes found in older, normal women and do not indicate disease. Patients with Graves' hyperthyroidism have circulating thyroid stimulating antibodies which act like TSH and cause the thyroid cells to over-function.

Thyroid Biopsy

Thyroid biopsy is presently in common use and is considered to be the first line of investigation for patients with solitary thyroid nodules (by many physicians). In this procedure, a small needle on the end of a syringe is inserted into the abnormal part of the thyroid gland. The plunger of the syringe is drawn out and a small number of thyroid cells is drawn up into the base of the needle. These cells are then smeared onto glass slides. The pathologist can then examine the smears for evidence of thyroid disease. This procedure is simple, quick, and painless and is equivalent to having blood taken. In patients with a thyroid nodule due to thyroid cyst, the fluid can be evacuated using the biopsy technique. The patients may experience mild pain at the site and, rarely, swelling and bruising. It is almost unheard of that the needle would damage structures outside the thyroid gland. There have been no reports of spread of thyroid cancer. Local anaesthetic is usually not necessary even with children.

Thyroid biopsy is not carried out if there is no thyroid swelling or nodule to feel. However, for patients with thyroid nodules, multinodular goitre, or possible thyroiditis, the procedure can be extremely useful. Although only surgery can absolutely guarantee the nature of the thyroid nodule, the thyroid biopsy is 85-90% effective in diagnosing the nature of the nodule and distinguishing between benign tumours and thyroid cancer.

However, the main factor determining the success of the thyroid biopsy is the experience of the individual performing the biopsy and the pathologist reading the smears.

A printed version of this Health Guide is available to health care professionals and the public. For more information call the National Office or contact your local chapter.

Production of the printed version of this Health Guide was made possible through partial funding assistance from Health Canada. The views expressed herein are solely those of the authors and do not necessarily represent the official policy of Health Canada.Original published 1983. Revised October 1994.
Copyright © 1996 Thyroid Foundation of Canada/La Fondation canadienne de la Thyroïde.

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"Endocrinology and Birth Defects." April 8, 1998 <>

"Metabolism and Metabolic Rate." December 24, 1997 <>

"Thyroid Disease and the Skin." April 29, 1998 <>

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