Thyroid gland Disorders
Thyroid Disorders: involve thyroid hormone production or secretion and
result in alterations of metabolic stability.
THYROID HORMONE PHYSIOLOGY:The thyroid gland consists of two lobes
and is situated in the lower neck. The gland synthesizes, stores and releases two
active hormones: Tetra-iodothyronine (Thyroxine, T4) and tri-iodothyronine (T3).
• The thyroid hormones thyroxine (T4) and triiodothyronine (T3) are
formed within thyroglobulin, a large glycoprotein synthesized in the
thyroid cell. Inorganic iodide enters the thyroid follicular cell and is
oxidized by thyroid peroxidase and covalently bound (organified) to
tyrosine residues of thyroglobulin.
• Iodinated tyrosine residues monoiodotyrosine (MIT) and diiodotyrosine
(DIT) combine (couple) to form iodothyronines in reactions catalyzed by
thyroid peroxidase. Thus, two molecules of DIT combine to form T4,
and MIT and DIT join to form T3.
• Proteolysis within thyroid cells releases thyroid hormone into the bloodstream.
The T4 and T3 are transported by thyroid-binding globulin (TBG),
transthyretin, and albumin. Only the unbound (free) thyroid hormone
can diffuse into cells, elicit biologic effects, and regulate thyroid
stimulating hormone (TSH) secretion from the pituitary.
• T4 is secreted solely from the thyroid, but <20% of T3 is produced there;
Most T3 is formed from breakdown of T4 in peripheral tissues. The T3
is five times more active than T4. Also, T4 may be cleaved to form reverse
T3, which has no significant biologic activity.
• Thyroid hormone production is regulated by TSH secreted by the
anterior pituitary, which in turn is under negative feedback control by
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the circulating level of free thyroid hormone and the positive influence of
hypothalamic thyrotropin-releasing hormone (TRH). Thyroid hormone
production is also regulated by extrathyroidal deiodination of T4 to T3,
which can be affected by nutrition, nonthyroidal hormones, drugs, and
illness.
A- Thyrotoxicosis (Hyperthyroidism)
• Thyrotoxicosis results when tissues are exposed to excessive levels of T4, T3 ,
or both. Hyperthyroidism, which is one cause of thyrotoxicosis, refers to
overproduction of thyroid hormone by the thyroid gland.
• TSH-secreting pituitary tumors occur sporadically and 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.
Resistance to thyroid hormone occurs rarely and can be due to various
molecular defects, including mutations in the TRβ gene. Pituitary resistance to
thyroid hormone (PRTH) refers to selective resistance of the pituitary thyrotrophs
to thyroid hormone.
Causes:
• Graves’ disease is the most common cause of hyperthyroidism, which
results from the action of thyroid-stimulating antibodies (TSAb)
directed against the thyrotropin receptor on the surface of thyroid cells.
These immunoglobulins bind to the receptor and activate the enzyme
adenylate cyclase in the same manner as TSH.
• An autonomous thyroid nodule (toxic adenoma) is a benign thyroid mass
that produces thyroid hormone independent of pituitary and TSH
control. Hyperthyroidism usually occurs with larger nodules (>3 cm in
diameter).
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• In multinodular goiter, follicles with autonomous function coexist with
normal or even nonfunctioning follicles. Thyrotoxicosis occurs when
autonomous follicles generate more thyroid hormone than is required.
• Painful subacute (granulomatous or de Quervain) thyroiditis often
develops after a viral syndrome, but rarely has a specific virus been
identified in thyroid parenchyma.
• Painless (silent, lymphocytic, or postpartum) thyroiditis is a common cause of
thyrotoxicosis. Its etiology may be attributed to autoimmunity in most cases. •
Thyrotoxicosis factitia is hyperthyroidism due to ingestion of exogenous
thyroid hormone. This may occur when thyroid hormone is used for
inappropriate indications, excessive doses are used for accepted medical
indications, or when there is accidental ingestion or it is used surreptitiously. •
Amiodarone may induce thyrotoxicosis (2%–3% of patients), overt
hypothyroidism (5% of patients), subclinical hypothyroidism (25% of
patients), or euthyroid hyperthyroxinemia. Because of amiodarone’s high
iodine content, increased thyroid hormone synthesis commonly exacerbates
thyroid dysfunction in patients with preexisting thyroid disease.
Amiodarone also causes a destructive thyroiditis with leakage of
thyroglobulin and thyroid hormones.
Clinical presentation
• Symptoms of hyperthyroidism/thyrotoxicosis include nervousness,
anxiety, palpitations, easy fatigability, heat intolerance, weight loss
associated with increased appetite, increased frequency of bowel
movements, proximal muscle weakness (noted on climbing stairs or arising
from a sitting position), and in women there is scanty or irregular menses.
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• Physical signs include warm, smooth, moist skin, and unusually fine hair;
separation of the ends of the fingernails from the nail beds
(onycholysis), retraction of the eyelids, tachycardia at rest, occasional
gynecomastia in men and fine tremor of the protruded tongue and
hands. Thyromegaly is usually present.
• Graves’ disease is manifested by hyperthyroidism with diffuse thyroid
enlargement, and extrathyroidal findings of exophthalmos and pretibial
myxedema. In severe disease, a thrill may be felt and a systolic bruit may be
heard over the gland.
• In subacute thyroiditis, patients have severe pain in the thyroid region,
which often extends to the ear. Systemic symptoms include fever,
myalgia, and signs and symptoms of thyrotoxicosis. The thyroid gland is
firm and exquisitely tender on physical examination.
• Painless thyroiditis has a triphasic course that mimics painful subacute
thyroiditis. Most patients present with mild thyrotoxic symptoms; lid
retraction and lid lag are present, but exophthalmos is absent. The
thyroid gland may be diffusely enlarged without tenderness (pain on
touching).
• Thyroid storm is a life-threatening medical emergency characterized by
decompensated thyrotoxicosis, high fever (often >39.4°C), tachycardia,
tachypnea, dehydration, nausea, vomiting, diarrhea delirium, or even
coma. Precipitating factors for thyroid storm include infection, trauma,
surgery, radioactive iodine (RAI) treatment, and withdrawal from
antithyroid drugs.
• Note: Hyperthyroidism is characterized by increased thyroid hormone
synthesis and secretion from the thyroid gland, whereas thyrotoxicosis
refers
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to the clinical syndrome of excess circulating thyroid hormones, irrespective
of the source.
Complications
• Heart problems. Some of the most serious complications of
hyperthyroidism involve the heart.
• Brittle bones. Untreated hyperthyroidism can also lead to weak, brittle
bones (osteoporosis).
• Eye problems.
• Red, swollen skin.
• Thyrotoxic crisis.
Diagnosis
• Thyroid function test involves T3, T4 and TSH which are important in
diagnosis in addition to patient history and signs/symptoms. In patients
with symptomatic disease, measurement of serum total & free T4, total
T3, and TSH will confirm the diagnosis of thyrotoxicosis.
T3 T4 TSH
Thyrotoxic increase increase very low
Graves’ disease
Toxic adenomas = normal normal
TSH-induced elevated free thyroid hormone levels, and elevated
hyperthyroidis serum TSH concentrations.
m (secondary
etiology)
Thyrotoxicos thyrotoxic patient without evidence of increased
is factitia hormone production, thyroidal inflammation, or
ectopic thyroid tissue & RAIU is low
Painless 24-hour RAIU is suppressed & Antithyroglobulin
thyroiditis and antithyroid peroxidase antibody levels are
elevated.
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• Elevated 24-hour radioactive iodine uptake (RAIU) indicates true
hyperthyroidism: A low RAIU indicates that the excess thyroid hormone
is likely caused by thyroiditis, struma ovarii, or exogenous thyroid
hormone ingestion. If the patient is not pregnant or lactating, an increased
24-hour RAIU indicates that the thyroid gland is inappropriately using
iodine to produce more thyroid hormone when the patient is thyrotoxic.
• In subacute thyroiditis, thyroid function tests typically run a triphasic
course in this self-limited disease. Initially, serum T4 levels are elevated
due to release of preformed thyroid hormone and TSH suppression by the
elevated T4 level. As the disease progresses, intrathyroidal hormone
stores are depleted, and the patient may become mildly hypothyroid
with appropriately elevated TSH level. During the recovery phase,
thyroid hormone stores are replenished, and serum TSH elevation
gradually returns to normal.
Goals of treatment
1. Eliminate excess thyroid hormone.
2. Minimize symptoms and long-term consequences; and reduce or
eliminate the potential for side effects.
3. Provide individualized therapy based on the type and severity of disease,
patient age and gender, and existence of nonthyroidal conditions, and
response to previous therapy.
Non-pharmacological therapy:
• Surgical removal of the thyroid gland should be considered in patients with
a large gland (>80 g), severe ophthalmopathy, or lack of remission on
antithyroid drug treatment.
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• If thyroidectomy is planned, methimazole is given until the patient is
biochemically euthyroid (usually 6–8 weeks), followed by addition of
iodides (500 mg/day) for 10–14 days before surgery to decrease vascularity
of the gland.
• Propranolol has been used for several weeks preoperatively and 7–10
days after surgery to maintain pulse rate <90 beats/min. Combined
pretreatment with propranolol and 10–14 days of potassium iodide also
has been advocated.
Pharmacologic therapy
1. Thionamides (Thioamides)
Methimazole (carbimazole) and propylthiouracil (PTU) block thyroid
hormone synthesis by inhibiting the peroxidase enzyme & and by inhibiting
coupling of MIT and DIT to form T4 and T3. PTU (but not methimazole) also
inhibits peripheral conversion of T4 to T3.
Usual initial doses include methimazole 30–60 mg daily given in two or three
divided doses or PTU 300–600 mg daily (usually in three or four divided doses).
Evidence exists that both drugs can be given as a single daily dose
Improvement in symptoms and laboratory abnormalities should occur within
4–8 weeks, at which time a tapering regimen to maintenance doses can be started.
Doses can be changed monthly because the endogenously produced T4 will reach a
new steady-state concentration in this interval. Typical daily maintenance doses are
methimazole 5–30 mg and PTU 50–300 mg.
Continue therapy for 12–24 months to induce long-term remission. Monitor
patients every 6–12 months after remission. If a relapse occurs, alternate therapy
with radioactive iodine (RAI) is preferred over a second course of antithyroid drugs
because subsequent courses are less likely to induce remission.
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Minor adverse reactions include pruritic rashes, arthralgias, fever, and benign
transient leukopenia (WBC count <4000/mm3 or 4 × 109/L). The alternate
thioamide may be tried in these situations, but cross-sensitivity occurs in about
50% of patients.
Major adverse effects include agranulocytosis (with fever, gingivitis,
oropharyngeal infection, and granulocyte count <250/mm3 or 0.25 × 109/L),
aplastic anemia, polymyositis, GI intolerance, hepatotoxicity, and
hypoprothrombinemia. If agranulocytosis occurs, it usually develops in the first
3 months of therapy; routine WBC count monitoring is not recommended
because of its sudden onset.
Because of the risk of serious hepatotoxicity, PTU should not be considered first
line therapy in either adults or children. Exceptions to this recommendation include
(1) the first trimester of pregnancy (when the risk of methimazole-induced
embryopathy may exceed that of PTU induced hepatotoxicity), (2) intolerance
to methimazole, and (3) thyroid storm.
2. Radioactive iodine (RAI):
Sodium iodide–131 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
interstitial tissue. RAI is the agent of choice for Graves’ disease, toxic
autonomous nodules, and toxic multinodular goiters.
Pregnancy is an absolute contraindication to use of RAI because radiation would be
delivered to the fetal tissue.
β-Blockers are the primary adjunctive therapy to RAI because they may be
given anytime without compromising RAI therapy. If iodides are
administered,
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they should be given 3–7 days after RAI to prevent interference with uptake of
RAI in the thyroid gland.
Patients with cardiac disease and elderly patients are often treated with
thioamides prior to RAI ablation because thyroid hormone levels transiently
increase after RAI treatment due to release of preformed thyroid hormone.
Administering antithyroid drug therapy immediately after RAI may result in
a higher rate of posttreatment recurrence or persistent hyperthyroidism. Use
of lithium as adjunctive therapy to RAI has benefits of increased cure rate,
shortened time to cure, and prevention of posttherapy increases in thyroid hormone
levels.
The goal of therapy is to destroy overactive thyroid cells, and a single dose of
4000–8000 rad results in a euthyroid state in 60% of patients at 6 months or
sooner. A second dose of RAI should be given 6 months after the first RAI
treatment if the patient remains hyperthyroid.
Hypothyroidism commonly occurs months to years after RAI. The acute, short
term side effects include mild thyroidal tenderness and dysphagia. Long-term
follow-up has not revealed an increased risk for development of mutations or
congenital defects.
3. Iodides
Iodide acutely blocks thyroid hormone release, inhibits thyroid hormone
biosynthesis, and decreases size and vascularity of the gland. Symptom
improvement occurs within 2–7 days of initiating therapy, and serum T4 and
T3 concentrations may be reduced for a few weeks.
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, or to inhibit thyroid hormone release after RAI therapy.
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Potassium iodide is available as a saturated solution (SSKI, 38 mg iodide per
drop) or as Lugol solution which contains 6.3 mg of iodide per drop. Typical
starting dose of SSKI is 3–10 drops daily (120–400 mg) in water or juice. When
used to prepare a patient for surgery, it should be administered 7–14 days
preoperatively.
As an adjunct to RAI, SSKI should not be used before but rather 3–7 days
after RAI treatment so that the RAI can concentrate in the thyroid. Adverse
effects of iodide therapy include hypersensitivity reactions (skin rashes, fever,
and rhinitis, conjunctivitis), salivary gland swelling, “iodism” (metallic taste,
burning mouth, sore teeth and gums, and sometimes stomach upset and
diarrhea), and gynecomastia.
Iodide is contraindicated in toxic multinodular goiter because the autonomous
tissue utilizes the iodine for subsequent thyroid hormone synthesis. 4. Adrenergic
blockers
β-Blockers are used to ameliorate symptoms such as palpitations, anxiety,
tremor, and heat intolerance. They have no effect on peripheral and do not reduce
TSAb or prevent thyroid storm. Propranolol and nadolol partially block conversion
of T4 to T3, but this contribution to overall effect is small.
β-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. The only conditions for which β-blockers are
primary therapy for thyrotoxicosis are those associated with thyroiditis.
Propranolol doses required to relieve adrenergic symptoms vary, but an initial
dose of 20–40 mg orally four times daily is effective for most patients (heart
rate <90 beats/min). Younger or more severely toxic patients may require
240–480 mg/day, perhaps because of increased clearance.
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β-Blockers are contraindicated in decompensated heart failure unless it is caused
solely by tachycardia (high output). Other contraindications are sinus bradycardia,
concomitant therapy with MAO inhibitors or tricyclic antidepressants, and patients
with spontaneous hypoglycemia.
Side effects include nausea, vomiting, insomnia, lightheadedness, and bradycardia.
Centrally acting sympatholytics (e.g., clonidine) and calcium channel
antagonists (e.g., diltiazem) may be useful for symptom control when
contraindications to β-blockade exist.
Treatment of thyroid storm
Initiate the following therapeutic measures promptly: (1) suppression of thyroid
hormone formation and secretion, (2) antiadrenergic therapy, (3)
administration of corticosteroids, and (4) treatment of associated
complications or coexisting factors that may have precipitated the storm.
A-PTU in large doses may be preferred because it blocks peripheral
conversion of T4 to T3 in addition to interfering with thyroid hormone
production. However, β-blockers and corticosteroids serve the same purpose.
Methimazole has a longer duration of action, which offers a theoretical
advantage. B-Iodides, which rapidly block the release of preformed thyroid
hormone, should be administered after a thioamide is initiated to inhibit
iodide utilization by the overactive gland.
C-Antiadrenergic therapy with the short-acting agent esmolol is preferred
because it can be used in patients with pulmonary disease or at risk for cardiac
failure and because its effects can be rapidly reversed.
D-Corticosteroids are generally recommended; their benefits may be attributed to
their antipyretic action and stabilization of blood pressure (BP). E-General
supportive measures, including acetaminophen as an antipyretic (avoid aspirin
or other nonsteroidal anti-inflammatory drugs, which may displace
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bound thyroid hormone), fluid and electrolyte replacement, sedatives, digoxin,
antiarrhythmics, insulin, and antibiotics should be given as indicated.
Evaluation of therapeutic outcomes
• After therapy (surgery, thionamides, or RAI) for hyperthyroidism has been
initiated, evaluate patients monthly until they reach a euthyroid condition. •
Assess for clinical signs of continuing thyrotoxicosis or development of
hypothyroidism.
• Once a stable dose of T4 is identified, monitor the patient every 6–12 months.
B- Hypothyroidism
Hypothyroidism is the clinical status resulting from decreased production of
thyroid hormones or very rarely from tissue resistance. Subclinical hypothyroidism
is defined by an elevated TSH with normal thyroid hormone levels. The vast
majority of patients have primary hypothyroidism (thyroid gland failure)
which is due to failure of thyroid gland itself to produce sufficient hormones due
to: 1-Most commonly chronic autoimmune thyroiditis (Hashimoto ׳s disease).
Defects in suppressor T lymphocyte function lead to interaction stimulates B
lymphocytes to produce thyroid antibodies.
2-Iatrogenic hypothyroidism due to: a-exposure to destructive amounts of
thyroid radiation, b-after total thyroidectomy, c- or with excessive thionamide
doses used to treat hyperthyroidism; all these are primary form of
hypothyroidism.
3-Other causes of primary hypothyroidism include iodine deficiency, enzymatic
defects within the thyroid, and thyroid hypoplasia.
Secondary hypothyroidism (reduced TSH levels) (due to pituitary failure) is
uncommon. Pituitary insufficiency may be caused by destruction of
thyrotrophs by pituitary (tumors or surgery), external pituitary radiation,
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postpartum pituitary necrosis (Sheehan syndrome), and pituitary (metastatic
tumors or tuberculosis). while tertiary disease due to failure of the
hypothalamus to secrete the necessary TRH.
Peripheral hypothyroidism is due to tissue in sensitivity or resistance to the action
of often higher levels of thyroid hormones.
Clinical presentation
Symptoms Physical signs
dry skin, cold coarse skin and hair, Reversible neurologic
intolerance, weight cold or dry skin, syndromes such as
gain, constipation, periorbital puffiness, polyneuropathy, and
weakness, lethargy, bradycardia, and cerebellar dysfunction
exercise intolerance, slowed or hoarse may also occur.
muscle cramps, speech. Objective
myalgia, and stiffness. weakness (with
Menorrhagia and proximal muscles
infertility are affected more than
common in women. distal muscles) and
In children, thyroid slow relaxation of
hormone deficiency deep tendon reflexes
may manifest as are common.
growth or intellectual
retardation.
Most patients with secondary hypothyroidism due to inadequate TSH
production have clinical signs of generalized pituitary insufficiency, such as
decreased libido, or evidence of a pituitary adenoma, such as visual field defects,
galactorrhea, or acromegaloid features.
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Myxedema coma is a rare consequence of decompensated hypothyroidism
manifested by hypothermia, advanced stages of hypothyroid symptoms, and altered
sensorium ranging from delirium to coma. Mortality rates of myxedema coma is
60%–70% and necessitate immediate and aggressive therapy.
Complications
Untreated hypothyroidism can cause:
• Goiter. Constant stimulation of your thyroid to release more hormones may
cause the gland to become larger — a condition known as a goiter. • Heart
problems.
• Mental health issues.
• Peripheral neuropathy.
• Myxedema.
• Infertility.
• Birth defects.
Pathophysiology
Hypothyroidism can be caused by permanent loss or atrophy of functional
thyroid tissue (primary hypothyroidism); insufficient stimulation of a normal
thyroid gland as a result of hypothalamic or pituitary disease (secondary
hypothyroidism, often accompanied by compensatory thyroid gland
enlargement); or a defect in the TSH molecule (control hypothyroidism).
Primary hypothyroidism accounts for approximately 90-95% of hypothyroidism,
with a predominantly autoimmune-mediated etiology.
Diagnosis
Rise in TSH level is the first evidence of primary hypothyroidism. Many
patients have a free T4 level within the normal range (compensated or subclinical
hypothyroidism) and few symptoms of hypothyroidism. As the disease progresses,
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the free T4 drops below normal. The T3 concentration is often maintained in
the normal range despite low T4. Eventually, free and/or total T4 and T3
serum concentrations should be low.
In secondary hypothyroidism in patients with pituitary disease, serum TSH
concentrations are generally low or normal accompanied with low T4 levels.
Goals of treatment
1- Restore thyroid hormone concentrations in tissue,
2- Provide symptomatic relief,
3- Prevent neurologic deficits in newborns and children, and 4-
Reverse the biochemical abnormalities of hypothyroidism.
TREATMENT OF HYPOTHYROIDISM
Levothyroxine (L-thyroxine, T4) is the drug of choice for thyroid hormone
replacement because it is chemically stable, relatively inexpensive, active when
given orally, free of antigenicity, and has uniform [Link] a particular product
is selected, therapeutic interchange is discouraged. Because T3 (and not T4) is the
biologically active form, levothyroxine administration results in a pool of
thyroid hormone that is readily and consistently converted to T3.
Levothyroxine Dose
longstanding disease and older 50 mcg daily and increase
individuals without known cardiac after 1 month.
disease
Initial dose for older patients with known cardiac disease.
25 mcg/day, increments of 25 mcg at monthly intervals to prevent stress on the
cardiovascular system.
Average maintenance dose for most adults is ∼125 mcg/day, but there is a wide
range of replacement doses, necessitating individualized therapy and appropriate
TSH monitoring to determine an appropriate dose.
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Treatment of subclinical hypothyroidism is controversial, patients with
elevations in TSH (>10 mIU/L) and high titers of thyroid peroxidase antibody
or prior treatment with sodium iodide–131 may be most likely to benefit from
treatment.
1-Levothyroxine is the drug of choice for pregnant women, and the goal is to
decrease TSH to the normal reference range for pregnancy. Cholestyramine,
calcium carbonate, aluminum hydroxide, ferrous sulfate, dietary fiber supplements,
and espresso coffee may impair the GI absorption of levothyroxine. Acid
suppression with histamine blockers and proton pump inhibitors may also
reduce levothyroxine absorption. Drugs that increase T4 clearance include
rifampin and carbamazepine and possibly phenytoin. Selenium deficiency and
amiodarone may block conversion of T4 to T3. 2-Liothyronine (synthetic
T3): has uniform potency but has a higher incidence of cardiac adverse
effects, higher cost, and difficulty in monitoring with conventional laboratory
tests. It must be administered three times a day and may require a prolonged
adjustment period to achieve stable euthyroidism. 3-Liotrix (synthetic T4:T3
in a 4:1 ratio): is chemically stable, pure, and has a predictable potency but is
expensive. It also lacks therapeutic rationale because most T3 is converted
peripherally from T4.
Excessive doses of thyroid hormone may lead to heart failure, angina pectoris,
and myocardial infarction (MI). Hyperthyroidism leads to reduced bone density
and increased risk of fracture.
4-Thyroid USP (or desiccated thyroid) is usually derived from pig thyroid
gland. It may be antigenic in allergic or sensitive patients. Inexpensive generic
brands may not be bioequivalent.
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Treatment of Myxedema coma
• Immediate and aggressive therapy with IV bolus levothyroxine 300–500
mcg, has traditionally been used. Initial treatment with IV liothyronine
or a combination of both hormones has also been advocated because of
impaired conversion of T4 to T3.
• Give glucocorticoid therapy with IV hydrocortisone 100 mg every 8 hours
until coexisting adrenal suppression is ruled out.
• Consciousness, lowered TSH concentrations, and improvement in vital signs
are expected within 24 hours.
• Maintenance levothyroxine doses are typically 75–100 mcg IV until the
patient stabilizes and oral therapy is begun.
• Provide supportive therapy to maintain adequate ventilation, euglycemia, BP,
and body temperature. Diagnose and treat underlying disorders such as
sepsis and MI.
Evaluation of therapeutic outcomes
• Serum TSH concentration is the most sensitive and specific monitoring
parameter for adjustment of levothyroxine dose. Concentrations begin
to fall within hours and are usually normalized within 2–6 weeks.
• Check both TSH and T4 concentrations every 6 weeks until a euthyroid state
is achieved. An elevated TSH level indicates insufficient replacement. Serum
T4 concentrations can be useful in detecting noncompliance, malabsorption,
or changes in levothyroxine product bioequivalence. TSH may also be used
to help identify noncompliance.
• In patients with hypothyroidism caused by hypothalamic or pituitary failure,
alleviation of the clinical syndrome and restoration of serum T4 to the
normal
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range are the only criteria available for estimating the appropriate
replacement dose of levothyroxine.
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