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THYROID DISORDER

THYROID
• The thyroid is a endocrine gland usually located in the lower
front of the neck below the larynx (the voice box).

• The thyroid's job is to make thyroid hormones, which are


secreted into the blood and then carried to every tissue in the
body.

• Thyroid hormone helps the body use energy, stay warm and
keep the brain, heart, muscles, and other organs working as
they should.

• The main hormone made by the thyroid is thyroxine, also


called T4 because it contains four iodine molecules. T3 in the
blood is made from T4 (Tri-idothyronine) in other body tissues.
THYROID
• Imbalance in thyroid hormones can lead to two types of
condition-

 Hypothyroidism

 Hyperthyroidism

• Hyperthyroidism and hypothyroidism are the clinical and


biochemical syndromes resulting from increased and
decreased thyroid hormone production, respectively.

• Thyroiditis and Goiter


Difference Between Hyperthyroidism & Hypothyroidism
Hypothyroidism
 The thyroid does not make enough thyroid hormone to keep
the body running normally. Common causes of
hypothyroidism are autoimmune disease (Hashimoto’s
disesae), iodine deficiency, surgical removal of the thyroid,
and radiation treatment.
• Myxedema coma
 It is a loss of brain function as a result of severe,
longstanding low level of thyroid hormone in the blood.
 It is considerd a life threatening complication of
hypothyroidism and represent a far more serious side of the
spectrum of thyroid disease.
Pathophysiology
• The thyroid gland predominantly secretes thyroxine (T4),
which is converted into tri-iodothyronine (T3) in other organs
by the selenium-dependent enzyme iodothyronine deiodinase.
• Tri-iodothyronine binds to the thyroid hormone receptor in
the nucleus of cells, where it stimulates the turning on of
particular genes and the production of specific protiens.
• The thyroid gland is the only source of thyroid hormone in the
body the process requires iodine and the amino acid tyrosine.
• Iodine in the bloodstream is taken up by the gland and
incorporated into thyroglobulin molecules.

• The process is controlled by the thyroid-stimulating


hormone (TSH, thyrotropin), which is secreted by the pituitary.

• Not enough iodine, or not enough TSH, can result in decreased


production of thyroid hormones.
CAUSES
There are many reasons why the cells in the thyroid cannot
make enough thyroid hormone. Here are the major causes:

• Autoimmune disease

In autoimmune hypothyroidism, the immune system


accidentally attacks cells in the thyroid. This causes the cells to
become inflamed and damaged, interfering with their ability to
make thyroid hormone. When enough thyroid cells have been
destroyed, too few are left to meet the body's need for thyroid

hormone.
• Surgical removal of part or all of the thyroid
Some people with thyroid nodules, thyroid cancer, need to have
part or the entire thyroid removed. Hypothyroidism results when
the entire thyroid is removed or when the remaining thyroid
tissue no longer works properly.
• Radiation treatment
Some people with Hashimoto’s disease, nodular goiter, or
thyroid cancer are treated with radioactive iodine (131I).
Radioactive iodine destroys the thyroid, which can result in
hypothyroidism. Hodgkin's disease, lymphoma, or cancers of
the head or neck are treated with radiation which can destroy the
thyroid and result in hypothyroidism.
• Congenital Hypothyroidism

About 1 in 4,000 babies each year are born without a thyroid or


with a partly formed thyroid. A few babies have part or their
entire thyroid in the wrong place (ectopic thyroid). In some
babies, the thyroid cells or their enzymes do not function
correctly or are affected by medications taken by the mother. In
others, the thyroid may make enough hormone for a while but
later stop stops functioning as the child gets older or becomes an
adult.
• Thyroiditis

Thyroiditis is an inflammation of the thyroid. It is usually


caused by an autoimmune attack or by a viral infection.
Thyroiditis can make the thyroid release its whole supply of
stored thyroid hormone into the blood at once, causing the
thyroid to become overactive for a brief period of time. Once
the entire stored hormone has been released, the thyroid
becomes underactive.
DIAGNOSIS
• The most sensitive test is TSH. A rise in the TSH level is the first
evidence of primary hypothyroidism.

• TSH , free T4  (But in some cases T4 level with in normal range)

• Ultrasound of thyroid – little value

• Anti thyroid antibodies – anti-TPO

• S-CK , s-Chol , s-Trigliseride 

• ECG: Bradycardia with small QRS complexes


Management of hypothyroidism

• Levothyroxine(LT4) – first drug of choice


– If no residual thyroid function 1.5 μg/kg/day
– Patients under age 60, without cardiac disease can be
started on 50 – 100 μg/day. Dose adjusted according to
TSH levels
– In elderly especially those with CAD the starting dose
should be much less (12.5 – 25 μg/day).
– Choice of drug in pregnant women and objective of t/t is to
decrease TSH to 1mIu/L and maintain free T4
concentrations in the normal range.
Treatment of myxedema coma

• Immediate therapy with intravenous (IV) bolus thyroxine,


300 to 500 mcg, is needed to prevent mortality.
• Glucocorticoid therapy with IV hydrocortisone 100 mg
every 8 hours should be given until coexisting adrenal
suppression is ruled out.
• Maintenance thyroxine doses are typically 75 to 100 mcg
IV until the patient stabilizes and oral therapy is begun.
Cholestyramine, calcium carbonate, sucralfate,
aluminum hydroxide, ferrous sulfate, soyabean
formula and dietary fiber supplements may impair
absorption of levothyroxine from GIT.

Drugs that increase non-deiodonative T4 clearance


include rifampin, carbamazepine and phynytoin.

Amiodarone may block the conversion of T4 to


T3.
Hyperthyroidism (Thyrotoxicosis)

The term hyperthyroidism refers to any condition in which


there is too much thyroid hormone produced in the body. In
other words, the thyroid gland is overactive. It is also called
thyrotoxicosis.
Symptoms

• nervousness, irritability
• increased perspiration, heart racing, hand tremors
• anxiety, difficulty sleeping, thinning of your skin
• weakness in your muscles—especially in the upper arms and
thighs
• More frequent bowel movements.
• may lose weight despite a good appetite
• for women, menstrual flow may lighten and menstrual periods
may occur less
• In Graves’ disease the eyes may look enlarged because the
upper lids are elevated.
Hyperthyroidism Signs
• Tachycardia (AF)
• Tremor
• Goiter
• Warm moist skin
• Proximal muscle
weakness
• Lid retraction or lag
• Gynecomastia
Causes of Hyperthyroidism
Most common causes Rarer causes
– Graves disease – Thyroiditis or other causes of
destruction
– Toxic multinodular
– Thyrotoxicosis factitia
goiter
– Iodine excess (Jod-Basedow
– Autonomously phenomenon)
functioning nodule – Secondary causes (TSH or
ßHCG)
Graves Disease
• Autoimmune disorder
• Abs directed against TSH
receptor with intrinsic activity.
Thyroid and fibroblasts
• Responsible for 60-80% of
Thyrotoxicosis
• More common in women
Diagnosis of Graves Disease
• TSH , free T4 
• Thyroid auto antibodies
• Nuclear thyroid
scintigraphy (I123, Te99)
Treatment of Graves Disease
• Reduce thyroid hormone production or reduce the
amount of thyroid tissue.
– Antithyroid drugs: Propyl-thiouracil, Carbimazole
– Radioiodine
– Subtotal thyroidectomy – relapse after antithyroid therapy,
pregnancy, young people?

• Smptomatic treatment
– Propranolol
Hyperthyroidism Pathophysiology
• Thyrotoxicosis results when tissues are exposed to
excessive levels of T4, T3, or both.

• TSH-secreting pituitary tumors release biologically


active hormone that is unresponsive to normal
feedback control. The tumors may co-secrete prolactin
or growth hormone therefore, patients may present
with amenorrhea, galactorrhea, or signs of acromegaly.
Pathophysiology
 In Graves' disease, hyperthyroidism results from the action of
thyroid-stimulating antibodies (TSAb) directed against the
thyrotropin receptor on the surface of the thyroid cell. These
immunoglobulin G (IgG) antibodies bind to the receptor and
activate the enzyme adenylate cyclase in the same manner as TSH.

An autonomous thyroid nodule (toxic adenoma) is a discrete


thyroid mass whose function is independent of pituitary control.
Hyperthyroidism usually occurs with larger nodules.
Pathophysiology

• In multinodular goiters (Plummer's disease), follicles with


a high degree of autonomous function coexist with
normal or even nonfunctioning follicles. Thyrotoxicosis
occurs when the autonomous follicles generate more
thyroid hormone than is required.

• Painful subacute (DeQuervain's) thyroiditis is believed to


be caused by viral invasion of thyroid parenchyma.
Pathophysiology
 Painless (silent, lymphocytic, postpartum) thyroiditis is a
common cause of thyrotoxicosis; its etiology is not fully
understood and may be heterogeneous.
 Thyrotoxicosis factitia is hyperthyroidism produced by the
ingestion of exogenous thyroid hormone. This may occur
when thyroid hormone is used for inappropriate indications,
when excessive doses are used for accepted medical
indications, or when it is used surreptitiously by patients.
Pathophysiology

• Amiodarone may induce thyrotoxicosis (2% to 3% of


patients) or hypothyroidism. It interferes with type I 5′
-deiodinase, leading to reduced conversion of T4 to T3,
and iodide release from the drug may contribute to iodine
excess. Amiodarone also causes a destructive thyroiditis
with loss of thyroglobulin and thyroid hormones.
Management
• Thioureas (Thionamides)

 Propylthiouracil (PTU) and Methimazole (MMI)

 MOA: block thyroid hormone synthesis by inhibiting the peroxidase


enzyme system of the thyroid gland, thus preventing oxidation of trapped
iodide and subsequent incorporation into iodotyrosines and ultimately
iodothyronine and by inhibiting coupling of monoiodotyrosine and
diiodotyrosine to form T4 and T3. PTU (but not MMI) also inhibits the
peripheral conversion of T4 to T3.

 Initial doses include PTU 300 to 600 mg daily (usually in three or four
divided doses) or MMI 30 to 60 mg daily given in three divided doses.
 Improvement in symptoms and laboratory abormalities should occur
within 4 to 8 weeks.
 Antithyroid drug therapy should continue for 12-24 months to induce a
long-term remission.
 Patients should be monitored every 6 to 12 months after remission.
 If a relapse occurs, alternate therapy with radioactive iodine is preferred
to a second course of antithyroid drugs.
 Major adverse effects include agranulocytosis (with fever, malaise,
gingivitis, oropharyngeal infection and a granulocyte count ˂250/mm3),
aplastic anemia, GIT tolerance and hepatotoxicity.
Note: Agranulocytosis, if it occurs, almost always develops in the first 3
months of therapy.
• IODIDES
 Iodide acutely blocks thyroid hormone release, inhibits
thyroid hormone biosynthesis by interfering with intrathyroidal
iodide utilization, and decreases the size and vascularity of the
gland.
 Iodides are often used as adjunctive therapy to prepare a
patient with Graves' disease for surgery, to acutely inhibit
thyroid hormone release and quickly attain the euthyroid state
in severely thyrotoxic patients with cardiac decompensation.
• Potassium iodide is available as a saturated solution
(SSKI, 38-mg iodide per drop) or as Lugol's solution,
containing 6.3 mg of iodide per drop.
• The typical starting dose of SSKI is 3 to 10 drops daily
in water or juice. When used to prepare a patient for
surgery, it should be administered 7 to 14 days
preoperatively.
• Adnergic blockers
 Adnergic Blockers have been used widely to ameliorate
thyrotoxic symptoms such as palpitations, anxiety, tremor, and
heat intolerance. They have no effect on peripheral
thyrotoxicosis and protein metabolism and do not reduce TSAb
or prevent thyroid storm. Propranolol and nadolol partially
block the conversion of T4 to T3.
 Adnergic Blockers are usually used as adjunctive therapy
with antithyroid drugs, RAI, or iodides when treating Graves'
disease or toxic nodules; in preparation for surgery; or in thyroid
storm. β Blockers are primary therapy only for thyroiditis and
iodine-induced hyperthyroidism.
 Initial dose- 20-40 mg four times a day
• Radioactive iodine
• Sodium iodide 131 (131 I) is an oral liquid that
concentrates in the thyroid and initially disrupts hormone
synthesis by incorporating into thyroid hormones and
thyroglobulin. Over a period of weeks, follicles that have
taken up RAI and surrounding follicles develop evidence
of cellular necrosis and fibrosis of the interstitial tissue.

• RAI is the agent of choice for Graves' disease, toxic


autonomous nodules, and toxic multinodular goiters.
THYROID HORMONES
• Iodine & tyrosine form both T3 & T4
under TSH stimulation. However, 10% of
T4 production is autonomous and is
present in patients with central
hypothyroidism.
• When released into circulation T4 binds
to:
Globulin TBG 75%
Prealbumin TBPA 20%
Albumin TBA 5%