Download Hypothyroidism Pathophysiology

Kharkov National Medical University
Department : pathophysiology
Medicine: N2 KNMU
Teacher :Natalya
** Abstract by**
Abu baker maklef
Group :17
Course:3
Faculty:M
**Subject**
( Thyroid disorders )
(hypothyroidism and hyperthyroidism)
Kharkov
2013
Contents
1-Introduction
2-Difference Between Hypothyroidism and Hyperthyroidism
3-Diagnosis Hypothyroidism and Hyperthyroidism
4-Hypothyroidism
4-1Definition
4-21Etiology
4-3Clinical manifestations
4-4Hypothyroidism Pathophysiology
4-5Symptoms
4-6Treatment
4-7Emergency Situation
5-Hyperthyroidism
5-1Definition
5-2Etiology
5-3Clinical manifestations
5-4Hypothyroidism Pathophysiology
5-4Symptoms
5-5Treatment
5-6Emergency Situations
6-Conclusion
7- References
Introduction
The thyroid is a small butterfly shaped gland that lies just under the skin
below the Adam’s apple in the neck. It measures about 2 inches across. The
thyroid gland secretes hormones that help regulate the body’s metabolism
(how the body uses energy.) There are two main thyroid hormones: T3
(triiodothyronine) and T4 (thyroxine.) T3 is the more active form of
hormone, and T4 is converted into T3 by the body as needed. Most of T3
and T4 are bound to proteins in the blood steam. They are inactive until they
are separated from the protein. To make these hormones the thyroid gland
uses proteins and iodine supplied by the diet. Normally the amount of
thyroid hormones that is made and produced is controlled by the pituitary
gland. This tiny gland is located at the base of the brain and controls several
glands in the body in addition to the thyroid. The pituitary gland is itself
controlled by hormones released by the hypothalamus (part of the base of
the brain very near the pituitary gland.) The whole system is like a
thermostat. For example, when the body senses there is not enough thyroid
hormone the hypothalamus releases a hormone TRH (thyrotropin releasing
hormone) that causes the pituitary to secrete TSH (thyroid stimulating
hormone) that causes the thyroid gland to make and release thyroid
hormone. When there is too much thyroid hormone the releasing hormones
are turned off and the thyroid stops producing thyroid hormone.
When the thyroid gland is overactive and produces too much thyroid
hormone an individual develops hyperthyroidism. When the thyroid gland is
under active and produces too little thyroid hormone an individual develops
hypothyroidism. A section on each of these topics follows our general
review of the thyroid gland.
Individuals with developmental disabilities are more likely to develop
thyroid gland disorders than people in the general population. Individuals
with Down, Congenital Rubella, Klinefelter and Turner Syndromes are at
particular risk. Annual screening of thyroid function should be a routine part
of the health maintenance program for all individuals with developmental
disabilities.
Difference Between Hypothyroidism and
Hyperthyroidism
Hypothyroidism is a condition when there is a deficiency of thyroid
hormone in the body. Hyperthyroidism is characterized by excessive
amounts of thyroid hormone in the body. Both hypothyroidism and
hyperthyroidism are extremely different cases.
The signs and symptoms of hyperthyroidism include increased heart rate ‘“
tachycardia, increased activity of bowel movements, difficulty in sleeping,
intolerance to heat, nervousness and palpitation, increased respiratory rate,
increased moisture of the skin, increased metabolic rate, soft and fine hair,
wandering mind, sweating, scanty menstrual periods, infertility, muscle
weakness, nervousness and soft nails.
In hypothyroidism, there are symptoms such as bradycardia- decreased heart
rate, constipation, intolerance to cold, memory problems, coarse dry hair,
slow speech movements, slow walking movements, dry skin, brittle nails,
weight gain, fatigue, irritability, infertility, puffy face, loss of eyebrow hair,
and heavy menstrual periods.
The causes of hypothyroidism include medications like lithium carbonate,
genetic, decreased level of iodine in the body, disturbances in the pituitary
gland and hypothalamus, and infections mainly viral and bacterial.
Hashimoto’s thyroiditis is an immune disorder in which the thyroid gland is
attacked and damaged.
Hyperthyroidism is caused by any growth present in the thyroid gland.
Grave’s disease is an immunological disorder affecting the thyroid gland.
The classical feature of it is exophthalmos ‘“ a protruding eye ball, which is
absent in hypothyroidism. Hyperthyroidism can also lead to thyrotoxicosis.
The treatment for hypothyroidism includes thyroid hormones. It is given life
long to the patient. Thyroxine is the supplement given to the patient.
Thyroxine is T4 hormone of the thyroid gland. The patient is advised to take
this medication early in the morning. The treatment for hyperthyroidism is
anti-thyroid drugs which include propylthiouracil. It will decrease the
production of thyroid hormones.
Before taking any medications for hypo or hyperthyroidism, the drug
interactions should be considered. If there are high levels of thyroid
stimulating antibodies in the blood of an infant, then the recommended
treatment is exchange blood transfusion. This will decrease the antibody
levels in the blood.
The diagnosis for hypothyroidism and hyperthyroidism includes the
estimation of levels T3 and T4, the thyroid hormones and TSH level. In
hypothyroidism, there is decrease in the thyroid hormones level ‘“ T3 and
T4 and increase in the levels of TSH. In hyperthyroidism, there are increased
levels of thyroid hormones T3 and T4 and decrease in the levels of TSH.
TSH is thyroid stimulating hormone.
Diagnosis
When screening for abnormalities of thyroid gland function most doctors
will order blood tests that measure the level of TSH (thyroid stimulating
hormone) and freeT4. Depending upon the results of these tests and upon the
specific thyroid disorder, a number of other tests may be ordered. Some
other tests include levels of T3, thyroxine-binding protein, antithyroid
antibodies, and serum thyroglobulin. Occasionally tests that evaluate
functional responses to stimulation of the thyroid or pituitary glands may be
performed. The anatomy of the thyroid gland can be evaluated by a thyroid
ultrasound or by a thyroid scan. The scan in done by injecting a minute
amount of radioactive iodine into the individual, waiting 30 minutes and
then measuring the radioactivity over the thyroid gland (which has the
unique capacity of trapping iodine.) The scan produces a picture of the
active part of the thyroid gland. A needle biopsy (taking a sample of tissue)
or needle aspiration (taking a sample of fluid) from nodules in the thyroid
gland can also be done by a physician.
Hypothyroidism
Definition Hypothyroidism
Hypothyroidism is a condition in which the thyroid gland is under active and
produces too little thyroid hormone. When the condition is very severe it is
sometimes called myxedema because a substance collects in subcutaneous
tissues (under the skin) that causes nonpitting edema. About 95% of the time
hypothyroidism is the result of malfunction of the thyroid gland itself
(primary hypothyroidism.) Causes of primary hypothyroidism can be either,
congenital (something an individual is born with) or acquired (something an
individual gets.) The most common
causes of primary hypothyroidism are acquired and are the result of
destruction of the gland by an autoimmune disease (such as Hashimoto’s
thyroiditis) or by radioactive iodine therapy or surgery for hyperthyroidism.
Other causes of primary hypothyroidism include goiter due to iodine
deficiency and too much iodine in individuals with thyroid disease. Some
drugs can also cause hypothyroidism including lithium carbonate, paraaminosalicylic acid, thiourea drugs, sulfonamides, phenylbutazone and
others. Decades ago congenital hypothyroidism was a common cause of
mental retardation and severe disability in affected children. Now thanks to
newborn screening, most babies with this condition are diagnosed early,
treated and the most devastating consequences of the disease are avoided.
About 5% of the time hypothyroidism is the result of a problem outside of
the thyroid gland itself (secondary hypothyroidism.) Tumors or other
abnormalities of the hypothalamus or pituitary gland are examples of
conditions that can cause secondary hypothyroidism. Rarely an individual’s
tissues are resistant to thyroid hormone.
Etiology
Hypothyroidism is classified as primary when it is caused by failure of the
stimulated thyroid gland to release adequate amounts of thyroxine and
triiodothyronine, secondary when it is caused by inadequate pituitary
secretion of thyrotropin (thyroid-stimulating hormone), and tertiary when it
is due to insufficient production of thyrotropin-releasing hormone by the
hypothalamus. Primary hypothyroidism is much more common than the
other 2 forms. In the United States, primary hypothyroidism is most often
the result of chronic autoimmune thyroiditis or of surgical or radioiodine
ablation of an overactive thyroid gland (Kaplan 1999; Tews et al 2005;
Devdhar et al 2007). Other causes include iodine deficiency, iodine excess,
congenital conditions, and drugs or environmental chemicals that impair
hormone biosynthesis, such as lithium, amiodarone, sulfonamides,
sulfonylureas, carbamazepine, oxcarbazepine, phenytoin, valproate,
interleukins, sunitinib and other tyrosine kinase inhibitors, propylthiouracil,
methimazole , polychlorinated biphenyls, bisphenol-A, and polybrominated
diphenyl
Clinical manifestations
The systemic manifestations of hypothyroidism include fatigue, lethargy,
constipation, cold intolerance, menorrhagia, reduced appetite, weight gain,
dry skin, dryness and thinning of the hair, and deepening of the voice.
Patients with severe hypothyroidism have pale, cool skin that feels doughy,
sparse hair, a large tongue, and periorbital puffiness. The heart is usually
enlarged, and adynamic ileus can occur. Congenital hypothyroidism is
associated with an increased risk of systemic malformations, especially
cardiac and urogenital anomalies
Altered mental status. Congenital hypothyroidism is associated with
persistent, subtle, neurocognitive deficits, even though mental retardation is
now rare because of newborn screening and early treatment
Seizures. Seizures are most common in myxedema coma but can occur with
less severe disease. In a series of 56 patients with adult myxedema, 10
patients (18%) presented with seizures or syncope (Jellinek 1962). The
seizures are typically generalized, but complex partial seizures have also
been reported.
Strokes. No clear association is seen between hypothyroidism and strokes,
but hypothyroidism is associated with diastolic hypertension and increased
total and LDL cholesterol levels. It is also associated with elevated plasma
homocysteine levels, and it may affect endothelial function and coagulation
profiles. Thus, hypothyroidism affects stroke risk factors in ways that could
lead to an increased risk of stroke, but the relationship requires further study
(Squizzato et al 2005). Preexisting hypothyroidism or subclinical
hypothyroidism may be associated with milder clinical presentation and
improved outcome (Alevizaki et al 2006; Baek et al 2010; Akhoundi et al
2011).
Headaches. Many patients with hypothyroidism report headaches. In 1
series, 14% of patients had this complaint (Sanders 1962b). The headaches
do not have any distinguishing characteristics; they are usually chronic,
recurrent, and diffuse.
Ataxia. Ataxia is present in 25% to 33% of patients with hypothyroidism
(Cremer et al 1969). These patients all have an unsteady gait, and many of
them also have limb incoordination. Dysarthria also occurs but is less
common. There is 1 report of Hashimoto encephalopathy presenting with
progressive ataxia (Nakagawa et al 2007).
Movement disorders. Some features of hypothyroidism, such as
bradykinesia and voice abnormalities, mimic parkinsonism, but no
association has been documented between hypothyroidism and Parkinson
disease (Munhoz et al 2004). One case has been reported of a 12-year-old
girl in whom titubation and paroxysmal dyskinesia were the presenting
symptoms of hypothyroidism due to lymphocytic thyroiditis (Hopkins et al
2007).
Cranial nerve abnormalities. Hypothyroid patients frequently report
hearing loss, but it is thought to be due to fluid accumulation in the inner ear
rather than neurologic dysfunction. It improves after hormone replacement.
Tinnitus and vertigo are less common complaints. Ptosis occurs in 50% to
75% of hypothyroid patients, apparently due to decreased sympathetic tone.
Patients with autoimmune thyroid disease can develop thyroid
ophthalmopathy, a condition in which infiltration of the extraocular muscles
with glycosaminoglycans and inflammatory edema cause diplopia,
exophthalmos, pain behind the eyes, and blurred vision (Hattori et al 2006).
In primary hypothyroidism, secondary pituitary enlargement can cause
chiasmal compression leading to visual field defects. Distortions of taste and
smell are common in patients with hypothyroidism, and they are largely
reversed with hormone replacement (McConnell et al 1975). Hoarseness and
articulation defects are also common, but they are probably a result of
mucopolysaccharide deposition in the larynx, vocal cords, and tongue, rather
than cranial nerve dysfunction (Stollberger et al 2001; Kovacs et al 2010).
Trigeminal neuralgia and facial palsy have been reported in patients with
hypothyroidism but so rarely that the association may have been due to
chance. Genis and colleagues reported 1 case of a patient with hemifacial
spasm that resolved with thyroid replacement, reappeared when treatment
was stopped, and disappeared again when treatment was resumed (Genis et
al 1993). According to one group of investigators, Hashimoto thyroiditis is
common among patients with benign paroxysmal positional vertigo, but the
association is independent of thyroid status (Papi et al 2010).
Sleep disorders. Obstructive sleep apnea was documented in 45% of
successive hypothyroid patients in 1 prospective study (Hira and Sibal
1999). It can occur either on the basis of associated obesity or because of
mucopolysaccharide deposition in the tongue and upper airway (Kaminski
and Ruff 1989). Central sleep apnea has also been reported. The symptoms
of idiopathic hypersomnia have also been reported to improve after initiating
treatment with thyroxine in patients with subclinical hypothyroidism
(Shinno et al 2009).
Spastic paraparesis. Paraplegia and extensor plantar responses have been
reported in hypothyroid patients but so infrequently that the association may
have been fortuitous. A single case has been reported of a patient with
hypothyroidism of hypothalamic origin who had spastic paraplegia that
resolved with physiologic doses of thyroid replacement (Jackson et al 1978).
However, the patient also received a small physiologic dose of prednisone.
Peripheral nerve involvement. Hypothyroid patients commonly report
limb paresthesias, but electrodiagnostic studies demonstrate a peripheral
polyneuropathy in only a minority of patients (Rao et al 1980; Duyff et al
2000; El-Salem and Ammari 2006; Orstavik et al 2006; Nebuchennykh et al
2010). Elevated thermal thresholds have been described in patients with
hypothyroidism and unexplained pain in the extremities, suggesting the
possibility of small-fiber neuropathy (Orstavik et al 2006). Severe
neuropathy is rare. The most common peripheral nerve manifestation of
hypothyroidism is carpal tunnel syndrome, probably resulting from either
obesity or mucopolysaccharide deposition within the nerve itself and in the
surrounding tissue. Some hypothyroid patients have recurrent laryngeal
nerve lesions as a result of prior thyroid surgery or because of compression
by an enlarged thyroid gland. Thyroid enlargement can also compress the
sympathetic chain in the neck to produce unilateral or bilateral Horner
syndrome.
Neuromuscular junction dysfunction. A few hypothyroid patients with
myasthenic syndromes that responded to thyroid replacement have been
reported (Norris 1966; Takamori et al 1972). The neuromuscular
transmission abnormality was different from that seen in myasthenia gravis.
Autoimmune thyroiditis may be associated with a myasthenic syndrome, but
this is presumably due to the autoimmune disorder rather than a direct
manifestation of hypothyroidism (Turker et al 2008).
Muscle abnormalities. Proximal muscle weakness develops in about 25%
of patients with hypothyroidism (Rao et al 1980). The weakness is usually
mild, and most of the patients complain of associated pain, slowness, or
stiffness. The weakness is slowly progressive over months to years. Serum
creatine kinase measurement cannot be used as an indication of myopathy in
hypothyroidism because creatine kinase levels are increased in about 90% of
hypothyroid patients, most of whom do not have overt myopathy (Graig and
Smith 1965; Finsterer et al 1999; Biondi and Cooper 2008). Conversely,
markedly elevated creatine kinase levels do not exclude the diagnosis of
hypothyroid myopathy (Scott et al 2002).
Several abnormalities of muscle contraction are characteristic of
hypothyroidism. Prolongation of both contraction and relaxation phases
results in slow or "hung up" reflexes that normalize with thyroid hormone
replacement. Measurement of reflex time was even used to assess adequacy
of therapy before radioimmunoassays became readily available.
Hypothyroidism can also lead to muscle enlargement, especially in children.
The Kocher-Debre-Semelaigne syndrome refers to an "infant Hercules"
appearance in some children with cretinism who manifest a striking increase
in muscle bulk without an accompanying increase in muscle function
(Salaria and Parmar 2004). Some hypothyroid adults have enlarged, firm
muscles that become increasingly stiff and painful with exercise, forcing
them to rest briefly before resuming activity, a condition known as Hoffman
syndrome (Deepak et al 2004). Although this muscle activity bears a
superficial resemblance to myotonia, it is not accompanied by electrical
activity. Electrically silent contraction also occurs in myoedema, a local
mound of contracting muscle induced by percussion or some other
mechanical irritation of the muscle. Myoedema is present in about one third
of hypothyroid patients.
Hypothyroidism Pathophysiology
Thyroid hormone deficiency affects different organs and body systems.
Clinical data of hypothyroidism patophysiology usually depend on the
degree of biochemical changes, however may occur that a person with a
severe deficiency of hormones present mild symptoms while a person with a
minor deficiency may show strong signs of hypothyroidism.
Due to increase of medical information in all media, is possible to find welldocumented notes about hypothyroidism but in some cases it is also possible
to find information only with a commercial purpose. This causes confusion
among patients who consult their doctor wanting to know if they have a real
hypothyroid problem even when their thyroid function is normal or if they
have just some symptoms without laboratory values that support any thyroid
disease and for which the physician may only catalog the problem as a
probable thyroid dysfunction or thyroid imbalance.
Symptoms
fatigue, exhaustion
feeling run down and sluggish
depression
difficulty concentrating, brain fog
unexplained or excessive weight gain
dry, coarse and/or itchy skin
dry, coarse and/or thinning hair
feeling cold, especially in the extremities
constipation
muscle cramps
increased menstrual flow
more frequent periods
infertility/miscarriage
Treatment
Hypothyroidism is an easily treated disease. Several preparations for thyroid
replacement are on the market. The most frequently prescribed is Synthroid
(levothyroxine.) Other preparations include Liotrix, Desiccated Thyroid, and
Levotriiodothyronine. Regulating the dose of thyroid replacement hormone
may take a few weeks and several blood tests to determine if the correct
amount of medication is being given. After thyroid function is back to
normal the doctor will want to monitor therapy by checking serum free T4,
TSH and T3 levels annually.
Emergency Situations – What can go wrong?
Symptoms of hypothyroidism develop slowly and acute emergency
situations are very rare. Since we know now that individuals with
developmental disabilities are more prone to thyroid disorders than other
people, we hope that physicians are checking thyroid function every year as
part of health maintenance of every individual with a developmental
disability. Early diagnosis and treatment is the solution to avoiding the only
potentially life threatening complication of untreated hypothyroidism that is
myxedema coma. In myxedema coma the breathing slows, the person has
seizures and blood supply to the brain is decreased. It can be triggered by
cold exposure, infection, trauma or medications like sedatives or
tranquilizers.
What to do?
1. Suspect hypothyroidism long before any of these symptoms occur so it
can be diagnosed and treated early.
2. If an individual presents to you with the symptoms of myxedema coma
call 911 for immediate transport to a hospital emergency room.
Hyperthyroidism
Definition Hyperthyroidism
is hyperthyroidism the thyroid gland is overactive and produces too much
thyroid hormone. Over 2 ½ million Americans have hyperthyroidism. It is
much more common in women than in men.
There are several causes of hyperthyroidism. The most common include
immunologic conditions (like Graves’ disease and thyroiditis,) toxic thyroid
nodules (adenomas), and toxic multinodular (many nodules or adenomas)
goiter (enlargement of the thyroid gland.) Graves disease is a syndrome of
hypermetabolism, enlarged thyroid gland and exopthalmous (bulging of the
eyeballs due to the collection of abnormal substances in the tissues of the
orbit.) Autoimmune thyroiditis is an inflammation of the thyroid gland that
may cause damage to the gland and eventually result in hypothyroidism.
Thyroid nodules (one or many) are areas of abnormal thyroid tissue within
the thyroid gland. They can be benign or malignant (cancer) but most are
benign (not cancer.)
Etiology
Hyperthyroidism may result from increased synthesis and secretion of
thyroid hormones (thyroxine [T4] and triiodothyronine [T3]) from the
thyroid, caused by thyroid stimulators in the blood or by autonomous thyroid
hyperfunction. It can also result from excessive release of thyroid hormone
from the thyroid without increased synthesis. Such release is commonly
caused by the destructive changes of various types of thyroiditis. Various
clinical syndromes also cause hyperthyroidism.
The most common causes overall include




Graves' disease
Thyroiditis
Multinodular goiter
Single, autonomous, hyperfunctioning "hot" nodule
Graves' disease (toxic diffuse goiter), the most common cause of
hyperthyroidism, is characterized by hyperthyroidism and one or more of the
following:



Goiter
Exophthalmos
Infiltrative dermopathy
Graves' disease is caused by an autoantibody against the thyroid receptor for
thyroid-stimulating hormone (TSH); unlike most autoantibodies, which are
inhibitory, this autoantibody is stimulatory, thus causing continuous
synthesis and secretion of excess T4 and T3. Graves' disease (like
Hashimoto's thyroiditis) sometimes occurs with other autoimmune disorders,
including type 1 diabetes mellitus, vitiligo, premature graying of hair,
pernicious anemia, connective tissue disorders, and polyglandular deficiency
syndrome. The pathogenesis of infiltrative ophthalmopathy (responsible for
the exophthalmos in Graves' disease) is poorly understood but may result
from immunoglobulins directed to the TSH receptors in the orbital
fibroblasts and fat that result in release of proinflammatory cytokines,
inflammation, and accumulation of glycosaminoglycans. Ophthalmopathy
may also occur before the onset of hyperthyroidism or as late as 20 yr
afterward and frequently worsens or abates independently of the clinical
course of hyperthyroidism. Typical ophthalmopathy in the presence of
normal thyroid function is called euthyroid Graves' disease.
Inappropriate TSH secretion is a rare cause. Patients with hyperthyroidism
have essentially undetectable TSH except for those with a TSH-secreting
anterior pituitary adenoma or pituitary resistance to thyroid hormone. TSH
levels are high, and the TSH produced in both disorders is biologically more
active than normal TSH. An increase in the α-subunit of TSH in the blood
(helpful in differential diagnosis) occurs in patients with a TSH-secreting
pituitary adenoma.
Molar pregnancy, choriocarcinoma, and hyperemesis gravidarum
produce high levels of serum human chorionic gonadotropin (hCG), a weak
thyroid stimulator. Levels of hCG are highest during the 1st trimester of
pregnancy and result in the decrease in serum TSH and mild increase in
serum free T4 sometimes observed at that time. The increased thyroid
stimulation may be caused by increased levels of partially desialated hCG,
an hCG variant that appears to be a more potent thyroid stimulator than more
sialated hCG. Hyperthyroidism in molar pregnancy, choriocarcinoma, and
hyperemesis gravidarum is transient; normal thyroid function resumes when
the molar pregnancy is evacuated, the choriocarcinoma is appropriately
treated, or the hyperemesis gravidarum abates.
Nonautoimmune autosomal dominant hyperthyroidism manifests during
infancy. It results from mutations in the TSH receptor gene that produce
continuous thyroid stimulation.
Toxic solitary or multinodular goiter (Plummer's disease) sometimes
results from TSH receptor gene mutations causing continuous thyroid
activation. Patients with toxic nodular goiter have none of the autoimmune
manifestations or circulating antibodies observed in patients with Graves'
disease. Also, in contrast to Graves' disease, toxic solitary and multinodular
goiters usually do not remit.
Inflammatory thyroid disease (thyroiditis) includes subacute
granulomatous thyroiditis, Hashimoto's thyroiditis, and silent lymphocytic
thyroiditis, a variant of Hashimoto's thyroiditis (see Thyroid Disorders:
Silent Lymphocytic Thyroiditis). Hyperthyroidism results from destructive
changes in the gland and release of stored hormone, not from increased
synthesis. Hypothyroidism may follow.
Drug-induced hyperthyroidism can result from amiodarone
and interferon alfa, which may induce thyroiditis with hyperthyroidism and
other thyroid disorders. Although more commonly causing hypothyroidism,
lithium
can rarely cause hyperthyroidism. Patients receiving these drugs should be
closely monitored.
Thyrotoxicosis factitia is hyperthyroidism resulting from conscious or
accidental overingestion of thyroid hormone.
Excess iodine ingestion causes hyperthyroidism with a low thyroid
radioactive iodine uptake. It most often occurs in patients with underlying
nontoxic nodular goiter (especially elderly patients) who are given drugs that
contain iodine (eg, amiodarone
, iodine-containing expectorants) or who undergo radiologic studies using
iodine-rich contrast agents. The etiology may be that the excess iodine
provides substrate for functionally autonomous (ie, not under TSH
regulation) areas of the thyroid to produce hormone. Hyperthyroidism
usually persists as long as excess iodine remains in the circulation.
Metastatic thyroid cancer is a possible cause. Overproduction of thyroid
hormone occurs rarely from functioning metastatic follicular carcinoma,
especially in pulmonary metastases.
Struma ovarii develops when ovarian teratomas contain enough thyroid
tissue to cause true hyperthyroidism. Radioactive iodine uptake occurs in the
pelvis, and uptake by the thyroid is usually suppressed.
Clinical Manifestations
The clinical consequences of thyroid endocrine excess are exaggerated
expressions with the physiologic activity of T3 and T4. An extra of thyroid
hormone brings about enough extra heat production to outcome inside a
slight rise in body temperature and to activate heat-dissipating mechanisms,
such as cutaneous vasodilation and a decrease in peripheral vascular
resistance and elevated sweating. The increased basal metabolic fee leads to
fat loss, especially in older sufferers with poor appetite. In younger patients,
food intake usually increases, and some patients have seemingly insatiable
appetites.
The apparent increased catecholamine effect of hyperthyroidism is probably
multifactorial in origin. Thyroid hormones improve -adrenergic receptors in
many tissues, including center muscle, skeletal muscle, adipose tissue, and
lymphocytes. They also decrease -adrenergic receptors in center muscle
tissue and may amplify catecholamine action at a postreceptor site.
Therefore, thyrotoxicosis is characterized by an elevated metabolic and
hemodynamic sensitivity with the tissues to catecholamines. However,
circulating catecholamine levels are normal. Drugs that block -adrenergic
receptors reduce or eliminate the tachycardia, arrhythmias, sweating, and
tremor of hyperthyroidism. When beta-blockers are used within the
treatment of hyperthyroidism, it appears that "nonselective" -blockers (such
as propranolol), which block each 1 and 2 receptors, have an advantage
more than "selective" 1-blockers (for example metoprolol).
Hyperthyroidism Pathophysiology
The thyroid is a hormone that controls the metabolism of the body.
The hypothalamus and the pituitary gland control the secretion of
TSH which stimulates the secretion of the thyroid hormones,
triiodothyronine, or T3 and thyroxine, or T4. When the body secretes
an over abundance of these hormones it is referred to as
hyperthyroidism. ("Hyperthyroidism", 2010)
The most common form of hyperthyroidism is Graves Disease which
occurs in 75% of all cases of hyperthyroidism. It is an autoimmune
disorder in which the patient an enlarged thyroid which excretes
excess amounts of thyroid hormone. “In this disease the patient
develops antibodies to the TSH receptor. These antibodies attach to
the receptors and stimulate the thyroid gland to release T3, T4, or
both.” Another cause is toxic nodular goiters. These nodules will
release thyroid hormones regardless of the TSH production of the
body. (Lewis, et al., 2011)Other causes include, thyroiditis, tumors of
the testes or ovaries, receiving too much iodine, or taking too much
thyroid hormone.
Symptoms
Too much thyroid hormone speeds up metabolism and the symptoms can be
dramatic. The heart pounds rapidly and may develop an irregular beat
(arrhythmia.) Blood pressure goes up. The individual looses weight despite
an increased appetite. There is usually heat intolerance and excess sweating,
diarrhea, sleep disturbance, and muscle weakness. Many individuals feel
nervous, tremulous (shaky) and emotionally labile. The skin feels smooth,
warm and moist. With Graves’ disease there may be mild or marked bulging
of the eyes that leads to irritation, drying, inflammation, and increased
sensitivity to light.
nervousness
irritability
increased perspiration
thinning of your skin
fine brittle hair
muscular weakness especially involving the upper arms and thighs
shaky hands
panic disorder
Treatment
Treatment of hyperthyroidism depends upon the cause of the condition.
Several options are available including medications, radioactive iodine
therapy and surgery. Antithyroid medications used to treat hyperthyroidism
include propylthiouracil (PTU) and methimazole (Tapazole.) They have
several unpleasant side effects including rash, damage to white blood cell
production (agranulocytosis,) liver damage and inflammation of blood
vessels (vasculitis.) The doctor will monitor the white blood cell count
(WBC) and liver function tests (LFTs) on a regular basis as long as the
patient is taking one of these drugs. Very often treatment will be done in two
stages. In the short-term, antithyroid drugs will be prescribed to decrease the
production and release of thyroid hormone. Plenty of rest, good nutrition and
stress management are also important pieces of the initial management of
hyperthyroidism. Sometimes B-adrenergic blocking agents (like Propanolol)
are prescribed to reduce the symptoms of hyperthyroidism during this phase
of treatment. These medications slow down the heart rate, reduce the
shakiness and control anxiety. Some patients (10-20%) may go into
remission with this therapy. Most will need to be reassessed between 12-18
months and a decision made about long-term management Options for longterm management include continuation of antithyroid medication, surgery or
radioactive iodine therapy. It is up to the individual and the physician to
decide the best method of treatment in each case. Individuals with eye
involvement will need to be followed by an ophthalmologist.
Emergency Situations – What can go wrong?
The most serious, life-threatening complication of hyperthyroidism is
thyroid storm. This condition can be precipitated by infection or extra stress
in an individual who has hyperthyroidism. Many of the symptoms of
hyperthyroidism are exaggerated.
1. Racing heart
2. Palpitations
3. Excessive sweating
4. High fever
5. High blood pressure
6. Abdominal pain
What to do?
1. When a marked increase in the symptoms noted above occurs in an
individual with hyperthyroidism, suspect thyroid storm.
2. Notify the individual’s PCP or endocrinologist.
3. Call 911 for transport to the hospital. Thyroid storm requires intensive
in-patient hospital treatment.
Conclusion
Abnormalities of thyroid gland function are more common among
individuals with developmental disabilities than in the general population.
Most will have either hypothyroidism (underactive thyroid function) or
hyperthyroidism (over active thyroid function.) Both conditions are
treatable. Onset of hypothyroidism can occur over a fairly long time and the
symptoms can be subtle. In contrast, onset of hyperthyroidism is usually
more rapid and the symptoms are often dramatic. If we can keep the
possibility of abnormal thyroid function in mind we will not be likely to
miss the diagnosis. Screening tests of thyroid function should be a part of
routine health maintenance for all individuals with a developmental
disability.
In summary, a susceptible person develops Graves' disease because of one or
more factors that trigger off thyroid overactivity. As thyroid function
increases, more thyroid hormones are released into the blood stream,
producing the symptoms of hyperthyroidism.
Congenital hypothyroidism can result in profound cognitive and developmental delays in
infants and children unless diagnosed within days of birth and treatment initiated. The
incidence of congenital hypothyroidism may have doubled during the past decade, but
variability of screening techniques and criteria for a positive newborn screening result
vary across the United States. Pediatric primary care providers and pediatric nurses must
monitor newborn screening results and make sure infants with a positive screen are seen
by a pediatric endocrinologist for diagnosis and initiation of treatment. They must
educate parents on the condition and importance of frequent serum monitoring of thyroid
levels to assure optimal growth and development of the
References
Pathophysiology book ( N.K.SIMEONOVA)
Huether, S., & McCance, K. (2007). Understanding Pathophysiology
(4th ed.). St. Louis:
Mosby.
Guyton, A.C., & Hall, J.E. (2000). Medical Physiology. (10th ed.).
Philadelphia: W.B. Saunders.
drbrodabarnes.com
Cecil Textbook of Medicine,19th Edition, W.B.Saunders Company,
1992 pp.1248-1271
Sharon Witemeyer MD (Pediatrician)
Continuum of Care 2350 Alamo Avenue SE, Suite 155
Albuquerque, NM 87106 505.925.2350 Fax 505.925.2389
hsc.unm.edu/som/coc
Douglas J Gelb MD PhD, author. Dr. Gelb of the University of
Michigan has no relevant financial relationships to disclose.
Zachary N London MD, editor. Dr. London of the University of
Michigan has no relevant financial relationships to disclose.