Thyroid Gland

Hayder Hussien Alawi

 ANATOMY OF THYROID GLAND

A butterfly-shaped organ, the thyroid gland is located anterior to the trachea,

just inferior to the larynx . The medial region, called the isthmus, is flanked by

wing-shaped left and right lobes. Each of the thyroid lobes are embedded with

parathyroid glands, primarily on their posterior surfaces. The tissue of the

thyroid gland is composed mostly of thyroid follicles. The follicles are made up

of a central cavity filled with a sticky fluid called colloid. Surrounded by a wall

of epithelial follicle cells, the colloid is the center of thyroid hormone

production, and that production is dependent on the hormones’ essential and

unique component: iodine.

Synthesis and Release of Thyroid

Hormones
Hormones are produced in the colloid when atoms of the mineral
iodine attach to a glycoprotein, called thyroglobulin, that is
secreted into the colloid by the follicle cells. The following steps
outline the hormones’ assembly:Binding of TSH to its receptors in
the follicle cells of the thyroid gland causes the cells to actively
transport iodide ions (I ) across their cell membrane, from the
–

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bloodstream into the cytosol. As a result, the concentration of
iodide ions “trapped” in the follicular cells is many times higher
than the concentration in the bloodstream.

1. Iodide ions then move to the lumen of the follicle cells that
border the colloid. There, the ions undergo oxidation (their
negatively charged electrons are removed). The oxidation of two
iodide ions (2 I ) results in iodine (I ), which passes through the
–
2

follicle cell membrane into the colloid.

2. In the colloid, peroxidase enzymes link the iodine to the
tyrosine amino acids in thyroglobulin to produce two
intermediaries: a tyrosine attached to one iodine and a tyrosine
attached to two iodines. When one of each of these
intermediaries is linked by covalent bonds, the resulting
compound is triiodothyronine (T ), a thyroid hormone with
3

three iodines. Much more commonly, two copies of the second

intermediary bond, forming tetraiodothyronine, also known
as thyroxine (T ), a thyroid hormone with four iodines.
4

These hormones remain in the colloid center of the thyroid follicles

until TSH stimulates endocytosis of colloid back into the follicle
cells. There, lysosomal enzymes break apart the thyroglobulin
colloid, releasing free T  and T , which diffuse across the follicle cell
3 4

membrane and enter the bloodstream.

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In the bloodstream, less than one percent of the circulating T  and 3

T  remains unbound. This free T  and T  can cross the lipid bilayer
4 3 4

of cell membranes and be taken up by cells. The remaining 99

percent of circulating T  and T  is bound to specialized transport
3 4

proteins called thyroxine-binding globulins (TBGs), to albumin, or

to other plasma proteins. This “packaging” prevents their free
diffusion into body cells. When blood levels of T  and T begin to
3 4 

decline, bound T  and T  are released from these plasma proteins

3 4

and readily cross the membrane of target cells. T  is more potent
3

than T , and many cells convert T  to T  through the removal of an

4 4 3

iodine atom.

Regulation of TH Synthesis
The release of T  and T  from the thyroid gland is regulated by
3 4

thyroid-stimulating hormone (TSH). low blood levels of T  and 3

T  stimulate the release of thyrotropin-releasing hormone (TRH)

4

from the hypothalamus, which triggers secretion of TSH from the

anterior pituitary. In turn, TSH stimulates the thyroid gland to
secrete T  and T . The levels of TRH, TSH, T , and T  are regulated by
3 4 3 4

a negative feedback system in which increasing levels of T  and 3

T  decrease the production and secretion of TSH.

4

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Functions of Thyroid Hormones

The thyroid hormones, T3 and T4, are often referred to as metabolic

hormones because their levels influence the body’s basal metabolic
rate, the amount of energy used by the body at rest. When T3 and
T4 bind to intracellular receptors located on the mitochondria, they
cause an increase in nutrient breakdown and the use of oxygen to
produce ATP. In addition, T3 and T4initiate the transcription of
genes involved in glucose oxidation. Although these mechanisms
prompt cells to produce more ATP, the process is inefficient, and an
abnormally increased level of heat is released as a byproduct of
these reactions. This so-called calorigenic effect (calor- = “heat”)
raises body temperature.

Adequate levels of thyroid hormones are also required for protein

synthesis and for fetal and childhood tissue development and
growth. They are especially critical for normal development of the
nervous system both in utero and in early childhood, and they
continue to support neurological function in adults. As noted
earlier, these thyroid hormones have a complex interrelationship
with reproductive hormones, and deficiencies can influence libido,
fertility, and other aspects of reproductive function. Finally, thyroid
hormones increase the body’s sensitivity to catecholamines
(epinephrine and norepinephrine) from the adrenal medulla by

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upregulation of receptors in the blood vessels. When levels of T3 and
T4 hormones are excessive, this effect accelerates the heart rate,
strengthens the heartbeat, and increases blood pressure. Because
thyroid hormones regulate metabolism, heat production, protein
synthesis, and many other body functions, thyroid disorders can
have severe and widespread consequences.

THYROID DISORDERS
1- Thyroid Hormone Excess

The manifestations of hyperthyroidism are protean.70 The

hyperthyroid patient is hot when others are cool, is hungry and
eating all the time but losing weight, has thinning hair, is anxious
and jittery, and has a fine tremor and tachycardia. The most
common causes of excess production of thyroid hormone are TSH-
stimulating autoantibodies (Graves’ disease) and thyroid hormone–
secreting nodules (toxic nodules). The classic feature of Graves’
disease or hyperthyroidism is a “stare” with proptosis caused by
deposition of glycosaminoglycans in the orbital musculature (Figure
12). In these patients, there is often periorbital edema, and the
thyroid gland is diffusely enlarged and smooth. A rare complication

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of Graves’ disease is Graves’ dermopathy or pretibial myxedema,
characterized by asymmetric or symmetric nonpitting edema of the
anterior and lateral aspects of the lower leg . An increase in size of
the midline pyramidal lobe of the gland is diagnostic of Graves’
disease. Enlarged asymmetric thyroid nodules are also associated
with MEN2B syndrome.

Diagnosis
Since the vast majority of cases of hyperthyroidism are caused by
primary thyroid gland dysfunction with overproduction of T4
and/or T3, and resultant suppression of pituitary TSH, a suppressed
TSH is the most sensitive diagnostic test for hyperthyroidism (see
Table 12). Therefore, a low TSH is the single best test for the
diagnosis of hyperthyroidism. After primary hyperthyroidism is
diagnosed, the clinician must identify the exact cause, which could
be stimulating antibodies, autonomous nodule(s), or gland
destruction with hormone release. This is done by assessing the
uptake and pattern of diagnostic radioactive iodine by the thyroid
gland; it is diffuse in Graves’ disease, patchy in autonomous
nodules, and little or none in gland destruction.

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Treatment
The treatment of hyperthyroidism depends on the severity of the
disease and the underlying cause. The initial step is to ameliorate
the symptoms. This usually involves b-blockers (for tachycardia)
and antithyroidal medications (thionamides), which block hormone
synthesis by the gland. Definitive treatment is variable; radioactive
iodine (131I) is the treatment of choice in the United States, whereas
surgery is recommended more commonly elsewhere. Thionamides
are sometimes used chronically. If the cause is a TSH-secreting
adenoma, transsphenoidal surgery is recommended.

2- Hypothyroidism

The hypothyroid patient is the mirror image of the hyperthyroid

patient.72 Patients are chronically fatigued, cold when others are
comfortable, gaining weight without eating more, constipated, and
bradycardic, with slowed reflexes. A slowed relaxation phase on the
Achilles tendon reflex is an accurate physical sign of
hypothyroidism. As the disease progresses, mental slowing,
depression, and hypothermia can develop. The most common cause
of hypothyroidism is autoimmune destruction of the gland
(Hashimoto’s thyroiditis). It is more common in women and may

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often be found in the context of a family or personal history of other
autoimmune diseases. Hypothyroidism may also result from the
loss of the TSH producing cells of the pituitary gland (secondary
hypothyroidism). Although less common, it can be caused indirectly
by a large, nonfunctioning pituitary adenoma.

Diagnosis
As with hyperthyroidism, since the vast majority of the cases of
hypothyroidism are primary (thyroid gland) in nature, and since the
pituitary response is to increase TSH secretion, an elevated TSH is
the single best test for the diagnosis of hypothyroidism. This is
accompanied by a low T4 or free T4. However, in the rare cases of
secondary (pituitary) disease, the low thyroid hormone levels are
accompanied by a low TSH. As in secondary hyperthyroidism, this is
usually caused by a nonfunctioning pituitary tumor.

Treatment
Treatment of hypothyroidism involves replacement of the missing
hormone. T4 has a long half-life, can be administered once per day,
and is inexpensive. T4 acts as a prohormone that is converted at the
tissue level to the active T3.

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Oral Manifestations of Thyroid Gland Disorders
As part of a routine head and neck examination, the oral health
practitioner should palpate the thyroid gland. During a screening,
the thyroid gland is examined with the patient’s head extended to
one side. The examiner uses the fingers of both hands to palpate the
thyroid gland. Next, the patient is instructed to swallow while the
examiner evaluates the anatomic extent of the lobules using the last
three fingers of one hand. In healthy patients, the right lobule is
usually larger than the left, and the outline of the relaxed gland
cannot be easily observed. The presence of an asymmetric thyroid
gland enlargement on routine examination should be referred for
follow-up by an internist or endocrinologist. This is particularly true
for the patient with a history of hyperthyroidism or hypothyroidism.

Hyperthyroidism

Hyperthyroidism can exacerbate the patient’s response to dental

pain and anxiety. Routine examination of the head and neck may
disclose signs of thyroid disease, including changes in oculomotor
function, protrusion of the eyes, excess sweating, enlargement of the
thyroid or the tongue, lingual thyroid tissue, and difficulty in
swallowing. Patients may have increased susceptibility to dental
caries and periodontal diseases.

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Hypothyroidism
In hypothyroidism, orofacial findings include facial myxedema, an
enlarged tongue (macroglossia), compromised periodontal health,
delayed tooth eruption, delayed wound healing, and a hoarse voice.
Salivary gland enlargement, changes in taste, and burning mouth
symptoms have also been reported. Hashimoto’s thyroiditis has
been associated with xerostomia and impaired salivary output.

Dental Management of Thyroid

Gland Disorders
The first concern in treating the patient with thyroid disease is the
level of metabolic control and the second concern is concomitant
medications. Well-controlled hyperthyroidism and hypothyroidism
should not present major risks to the patient undergoing dental
care. A complete history and physical examination are necessary to
define the particular thyroid disease and assess its level of control. If
the thyroid disorder is undiagnosed, untreated, or unstable, the
patient’s physician should be consulted to determine possible risks
associated with use of local anesthetics, infection, bleeding, wound
healing, and ability to withstand stress. Inquiry about

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cardiovascular status, coagulation factors, level of disease control,
and a history of other disease complications are important aspects
of medical consultations. Drug interactions may result from the
increased metabolic rate associated with hyperthyroidism or the
decreased metabolic rate associated with hypothyroidism. Before
prescribing any medications for a poorly controlled patient with
hyperthyroidism or hypothyroidism, the clinician should consult
with the patient’s physician to determine the appropriate
medication, dosage, and delivery schedule. Patients with a history of
thyroid cancer have probably undergone surgery or radiation
therapy to the neck that would have affected regional hard and soft
tissues. Salivary gland dysfunction is one of the most common side
effects of high-dose 131I therapy for thyroid cancer. 131 I targets the
salivary glands where it is concentrated and secreted into saliva.
Dose-related damage to the salivary parenchyma results from the
131I irradiation and causes parotid swelling, pain, and
hypofunction. As with the complications of other head and neck
cancer therapies, postsurgical or postradiation complications may
require special oral health care measures, depending on the
patient’s presentation. Tooth loss, diminished mandibular bone
density, decreased salivary flow, dysgeusia, dysphagia, and skin and
mucosal ulcerations are potential complications of radiation
therapy. Patients with autoimmune thyroid diseases (Hashimoto’s

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thyroiditis) may also be susceptible to other autoimmune connective
tissue disorders, including Sjögren’s syndrome. Antinuclear
antibodies (ANAs) are found in one-third of patients with
autoimmune thyroid disorders, and Sjögren’s syndrome is found in
nearly one-tenth of ANA-positive patients with autoimmune thyroid
disorders. The most common additional autoimmune disease
identified in patients with primary Sjögren’s syndrome has been
identified as hypothyroidism84; also, there is a 7 to 17% prevalence
of detectable thyroid antibodies in patients with primary and
secondary Sjögren’s syndrome and rheumatoid arthritis. Therefore,
the thyroid patient who presents with signs and symptoms of
xerostomia and xerophthalmia should be evaluated further for
evidence of Sjögren’s syndrome. Similarly, a patient with Sjögren’s
syndrome should be monitored for the risk of developing thyroid
disease. Oral health complications resulting from salivary
hypofunction should be prevented in all patients who have received
head and neck radiotherapy or 131I treatment or those with
autoimmune thyroid diseases. They must be counseled on their
increased risk of developing dental caries, gingival and periodontal
problems, oral candidiasis, dysgeusia, difficulty wearing dentures,
and dysphagia.

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Hyperthyroidism
The most important concern in treating the patient with
hyperthyroidism is the risk of development of thyrotoxicosis or a
“thyroid storm,” which includes symptoms of extreme irritability
and delirium, hypotension, vomiting, and diarrhea. It can be
triggered by surgery, sepsis, and trauma. Emergency medical
treatment is required for this condition. Epinephrine is
contraindicated, and elective dental care should be deferred for
patients who have hyperthyroidism and exhibit signs or symptoms
of thyrotoxicosis. In general, stress management and short
appointments are recommended in these patients, and treatment
should be discontinued if signs or symptoms of a thyrotoxic crisis
develop. Patients who have hyperthyroidism are susceptible to
cardiovascular diseases, including atrial dysrhythmias, tachycardia,
and hypertension. Patients with high arteriolar pressures may
require increased attention and a longer duration of local pressure
to stop bleeding. Consultation with the patient’s physician is
required to document these and other organ system problems and
to ascertain the level of control of hyperthyroidism. Due to chronic
medication use for hyperthyroidism and the risk of developing
polypharmacy problems, the oral health practitioner should be
familiar with the patient’s current medications. Increased

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susceptibility to infection may develop as a drug side effect since
one commonly used drug (propylthiouracil) can cause
agranulocytosis or leukopenia. Propylthiouracil can also cause
sialolith formation and can increase the anticoagulant effects of
warfarin. Certain analgesics must be used with caution in these
patients. Aspirin and NSAIDs may cause increased levels of
circulating T4, leading to thyrotoxicosis. NSAIDs can also decrease
the effect of b-blockers. However, pain can complicate cardiac
function in patients who have hyperthyroidism and should be
treated by a multidisciplinary team with an emphasis on accurate
diagnosis and reduction of risks associated with polypharmacy. The
use of epinephrine and other sympathomimetics requires special
consideration when treating hyperthyroid patients and those taking
nonselective b-blockers. Epinephrine acts on a-adrenergic
receptors, causing vasoconstriction, and on b2 receptors, causing
vasodilation. Nonselective b-blockers eliminate the vasodilatory
effect, potentiating an a-adrenergic increase in blood pressure. This
pathophysiology is applicable to any patient taking nonselective b-
blockers and those with hyperthyroidism due to concurrent
cardiovascular complications.

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Hypothyroidism
Lethargy is a common finding in the patient with uncontrolled
hypothyroidism, and the oral health practitioner should be aware of
lethargy, which could indicate a poorly controlled condition.
Lethargy could become a concern due to a diminished respiratory
rate and increased risk of aspiration of dental materials. These
patients are susceptible to cardiovascular diseases; therefore,
consultations with medical providers are required to ascertain a
patient’s cardiovascular status. Patients who have atrial fibrillation
may be taking anticoagulants and may also require antibiotic
prophylaxis before invasive procedures, depending on the severity
of the arrhythmia. Coagulation tests (prothrombin time, partial
thromboplastin time, international normalized ratio) are required
when the patient is taking an oral anticoagulant and thyroid
hormone replacement therapy. The presence of cardiac valve
pathology may also require antibiotic prophylaxis. Intraoral use of
epinephrine is not contraindicated if hypothyroidism is well
controlled, but in patients who have cardiovascular disease
(congestive heart failure, atrial fibrillation) or who have uncertain
control of their thyroid disease, local anesthetic and retraction cord
with epinephrine should be used cautiously. Hypothyroidism
patients are sensitive to central nervous system depressants and

PAGE 15
barbiturates, so these medications should be used carefully, with
input from the patient’s physician. For postoperative pain control,
narcotic use should be limited since there is greater susceptibility to
these agents in patients with hypothyroidism. Patients with long-
standing hypothyroidism may experience increased bleeding after
trauma or surgery. Subcutaneous mucopolysaccharide deposition is
increased in these patients due to its decreased degradation. The
presence of excess subcutaneous mucopolysaccharides may
decrease the ability of small vessels to constrict when cut and may
result in increased bleeding from the infiltrated tissues, including
mucosa and skin. Extended application of local pressure should
control the small vessel bleeding in most cases. Patients with
hypothyroidism may have delayed wound healing due to decreased
metabolic activity in fibroblasts. Delayed wound healing may
increase the risk of infection because of the longer exposure of the
unhealed tissue to pathogenic organisms. However, this may also
relate to the level of disease control because a study of well-
controlled primary hypothyroid patients treated with dental
implants demonstrated no differences in the risk of implant failures
when compared with matched controls. Therefore, hypothyroid
patients are not considered to be immunocompromised, but the
health care practitioner must assess the level of disease control
when planning oral surgical procedures.

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