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Terms in this set (76)
the two biologically active thyroid hormones produced by the thyroid gland in response to hormones released by the pituitary and hypothalamus
Triiodothyronine (T3) and thyroxine (T4)
The hypothalamic thyrotropin-releasing hormone (TRH) stimulates release of thyrotropin (e.g. thyroid-stimulating hormone [TSH]) from the pituitary in response to
low circulating levels of thyroid hormone
TSH in turn promotes...
hormone synthesis and release by increasing thyroid activity
When sufficient synthesis has occurred, high circulating thyroid hormone levels...
block further production by inhibiting TSH release (Negative feedback); The intra-pituitary deiodination of T4 to T3 also plays a critical role in the inhibition of TSH secretion
As the serum concentrations of thyroid hormone decrease...
the hypothalamic-pituitary centers again become responsive by releasing TRH and TSH
four times more potent than T4, but its serum concentration is lower
the major circulating hormone secreted by the thyroid
about 80% of the total daily T3 production results from the peripheral conversion of
T4 to T3 through deiodination of T4
this has intrinsic biological activity and does NOT function solely as a pro-hormone
Approximately 35% to 40% of secreted T4 is...
converted peripherally to T3; another 45% of secreted T4 undergoes peripheral conversion to inactive reverse T3 (rT3)
a clinical syndrome that results from a deficiency of thyroid hormone
Autoimmune disorder and the most common cause of primary hypothyroidism and appears to have a strong genetic predisposition
The pathogenesis of Hashimoto's thyroiditis results from...
from impaired immune surveillance, causing dysfunction of normal suppressor T lymphocytes and excessive production of thyroid antibodies by plasma cells
Hashimoto's thyroiditis, The destruction of thyroid cells by circulating thyroid antibodies produces an underlying defect or block in the intrathyroidal, organobinding of iodide
As a result...
inactive prehormones or insufficient amounts of active hormones are synthesized, and this eventually produces hypothyroidism
Drug induced hypothyroidism
Iodides, amiodarone, lithium, tyrosine kinase inhibitors, interferon-alpha, etc
The goal of therapy of hypothyroidism is ...
to reverse the signs and symptoms of hypothyroidism and normalize the TSH and FT4 levels
Some improvement of hypothyroid symptoms is often evident within...
2 to 3 weeks of starting T4 therapy
Overreplacement of L-thyroxine (manifested by below-normal or suppressed serum concentrations of TSH) is associated with...
osteoporosis and cardiac changes (e.g. atrial fibrillation, heart failure, and tachycardia)
**The optimal T4 replacement dosage must be administered for approximately...
approximately 6 to 8 weeks before steady-state levels are reached bc Evaluation of thyroid function tests before this time is misleading
Once a euthyroid state is attained...
laboratory tests can be monitored every 3 to 6 months for the first year and then yearly thereafter
Medications that interfere with T4 absorption
iron, aluminum-containing products, some calcium preparations [carbonate], cholesterol resin and phosphate binders, raloxifene)--> should be separated by at least 4 hours from concomitant T4 administration
Desiccated thyroid is...
derived from pork thyroid glands, although beef and sheep are also used--> •Many problems with use and have fallen out of favor
•Potency may vary with changes in proportion of T3 and T4
•Allergic reactions to the animal protein are another concern
In addition, desiccated thyroid suffers from two problems inherent to all T3-containing preparations
•Because T3 is absorbed more rapidly than T4, supraphysiological elevations in plasma T3 levels occur after oral ingestion, which can produce mild thyrotoxic symptoms in some patients
•FT4 levels are low during T3 administration and, if misinterpreted, can result in the erroneous administration of more hormone
•These problems with T3 are easily missed unless T3 levels are routinely monitored
•**Because significant amounts of T4 are converted to T3 peripherally, oral administration of T3 offers no advantage and is NOT usually needed
Because the only apparent advantage of desiccated thyroid is low cost, it should...
NOT be considered the drug of choice for replacement therapy
Patients maintained on desiccated thyroid should...
be encouraged to change to L-thyroxine (T4)
thyroid replacement of choice
Levothyroxine or L-Thyroxine
•Its advantages include stability, uniform potency, relatively low cost, and lack of allergenic foreign protein content
Levothyroxine or L-Thyroxine
•The long half-life of 7 days permits once-a-day dosing and, if necessary, the creation of special convenience schedules, such as the omission of medications on weekends
Levothyroxine or L-Thyroxine
•Absorption is optimal on an empty stomach, at least 60 minutes before or 2 hours after meals or at bedtime
Levothyroxine or L-Thyroxine
preferred thyroid replacement preparation
The signs and symptoms of hypothyroidism can be easily corrected in most patients by administration of...
L-thyroxine on an empty stomach at an oral replacement dose of 1.6 to 1.7 mcg/kg/day
•Elderly--> may require less than younger patients. Sensitive to small dose changes
•Patients with severe and long-standing hypothyroidism --> sensitive to CV effects of T4. Steady state may be delayed because of decreased clearance of T4
•Patients with cardiac disease--> these patients are very sensitive to the CV effects of T4; replace thyroid deficit slowly and cautiously
who should not get levothyroxine
NOT recommended for routine thyroid hormone replacement because of the problems identified earlier with T3 administration
Triiodothyronine/ T3 (Cytomel)
Although T3 is well absorbed, it has a relatively short...
half-life (1.5 days), necessitating multiple daily dosing to ensure a uniform response
disadvantages include higher expense and a greater potential for cardiotoxicity
•Its primary use is for patients who require short-term hormone replacement therapy and rarely in those in whom T4 conversion to T3 might be impaired
•Proponents favoring thyroid treatment of the euthyroid sick syndrome identify this as the hormone replacement of choice
T3 therapy should be monitored using...
the TSH and TT3 or FT3 levels
What would you recommend as appropriate starting and maintenance dosages of T3
the maintenance dose can be estimated from weight--> average replacement doses of 1.6-1.7 are sufficient in most patients to normalize the TSH--> •The appropriate replacement dose will produce a TSH of 1 to 2 microunits/mL, normalize FT4 or FT4 I levels, and reverse clinical symptoms of hypothyroidism
should be avoided to prevent osteoporosis and cardiac toxicity
L-thyroxine dosages that suppress TSH levels to below normal or undetectable levels
Excessive L-thyroxine can cause...
•tachycardia, atrial arrhythmias, impaired ventricular relaxation, reduced exercise performance, and increased risk of cardiac mortality
Generally, dosing adjustments should not exceed monthly increments of...
12.5 to 25 mcg/day
the hypermetabolic syndrome that occurs when the production thyroid hormone is excessive
Hyperthyroidism or thyrotoxicosis
the most common cause of hyperthyroidism
is an autoimmune disorder characterized by one or more of the following features: hyperthyroidism, diffuse goiter, exophthalmos, pretibial myxedema, and acropachy
•The production of excessive quantities of thyroid hormone is attributed to a circulating immunoglobulin G or thyroid receptor antibody (TRAb), which has TSH-like ability to stimulate hormone synthesis
Untreated hyperthyroidism can progress to... **
thyroid storm, a life-threatening form of hyperthyroidism characterized by exaggerated symptoms of thyrotoxicosis and the acute onset of high fever
The primary treatment options for hyperthyroidism are...
antithyroid drugs (thioamides), radioiodine, and surgery--> All three modalities are effective, and the treatment of choice is influenced by the etiology of the hyperthyroidism, the size of the goiter, the presence of ophthalmopathy, coexisting conditions (e.g. angina, pregnancy), patient age, and patient preference
Older patients and those with existing cardiac disease, ophthalmopathy, and hyperthyroidism 2/2 to a toxic multinodular goiter are treated best with...
radioactive iodine (RAI)
if obstructive symptoms are present or concomitant malignancy is suspected with hyperthyroidism...
Surgery is preferable
Pregnant patients with hyperthyroidism can be managed with...
thioamides or surgery in the second trimester; RAI is absolutely contraindicated
The three major treatment modalities for Graves-related hyperthyroidism are the...
thioamides, RAI, and surgery
Patients who are older and those with cardiac disease, concomitant ophthalmopathy, and hyperthyroidism caused by a toxic multinodular goiter are treated best with...
the preferred therapy for pregnant women who are drug intolerant, when obstructive symptoms are present, or if malignancy is suspected
used as primary therapy for hyperthyroidism and as adjunctive short-term therapy to produce euthyroidism before surgery or RAI
primarily prevent hormone synthesis but do not affect existing stores of thyroid hormone
The thioamides (e.g. methimazole, propylthiouracil)
after beginning thioamide therapy,...
hyperthyroid symptoms will continue for 4 to 6 weeks and initial treatment with B-blockers or iodides is often required for symptomatic relief
preferred treatment for children, pregnant women, and young adults with uncomplicated Graves disease
the only treatment that leaves the thyroid gland intact and does NOT carry the added risk of permanent hypothyroidism often associated with RAI or surgery
•Because the thyrotoxicosis of Graves disease might be self-limiting, these are used to control the symptoms until spontaneous remission occurs
•should also be given before treatment with RAI or surgery to deplete the gland of stored thyroid hormone, which prevents subsequent thyroid storm
Although hyperthyroidism from toxic nodules will also respond to thioamides...
•more definitive therapy (surgery or RAI) is needed because these conditions do not undergo spontaneous remission
numerous tablets required, patient adherence, possible drug toxicity, the long duration of treatment, and the low remission rates after discontinuation of therapy
Disadvantages of thioamide therapy
considered the thioamide of choice because propylthiouracil (PTU) has been associated with severe hepatitis that has resulted in fatalities
should be reserved for use during the first trimester of pregnancy, in thyroid storm, and in those experiencing adverse reactions to methimazole (other than agranulocytosis or hepatitis)
The onset of action of PTU is...
more rapid than methimazole in thyroid storm because PTU can also inhibit the peripheral conversion of T4 to T3
preferred during the first trimester of pregnancy because congenital defects have been reported with methimazole
•Although both drugs are secreted in breast milk, no adverse effects have been reported in the exposed infants
Methimazole and PTU
can enhance adherence because it can be administered once daily, whereas PTU must be given two or three times daily
-maculopapular pruritic rash common in early treatment
-hepatitis / hepatotoxicity
-agranulocytosis is the most severe adverse hematologic reaction --> rash, fever, sore throat, flu-like sx
Thioamides Adverse effects
Tx of myxedema coma
•Emergency treatment, usually in the ICU, of myxedema coma is directed toward thyroid replacement, maintenance of vital functions, and elimination of precipitating factors; •L-thyroxine should be given IV immediately
•Because myxedema can impair oral absorption, the IV route is preferred to ensure adequate drug concentrations
•Supportive measures included assisted ventilations, glucose for hypoglycemia, restriction of fluids for hypernatremia, and the use of blood or plasma expanders to prevent circulatory collapse and to maintain blood pressure
extreme hypothyroidism(abrupt med cessation), rare with a high mortality rate = decreased cardiac output leads to decreased tissue perfusion which leads to brain and organ depletion leading to multi-organ failure
tx of thyroid storm to decrease in synthesis and release of hormones
-decrease in synthesis and release of hormones; •High dose thioamides, preferably PTU, should be given orally
•PTU is the thioamide of choice because it acts more rapidly than methimazole by blocking the peripheral conversion of T4 to T3, a dominant source of the hormone
•Iodides, which rapidly block further release of intraglandular stores of T4, should be given at least 1 hour after thioamide administration
•Given in this way, the substrate for hormone synthesis is not increased, and the therapeutic effect of thioamdie is not blocked
•The addition of iodides (e.g. Lugol iodine solution) to the thioamides often ameliorates symptoms within 1 day
•Cholestyramine may assist in lowering hormone levels rapidly but should be administered apart from other agents to prevent inhibiting their absorption
increased temp, pulse and HTN
tx for Reversal of the peripheral effects of hormones and catecholamines in thyroid storm
•Beta-adrenergic blocking drugs are preferred agents to decrease the tachycardia, agitation, tremulousness, and other symptoms of excessive adrenergic stimulation seen in thyroid storm
•Propanolol is the beta-blocker of choice because its clinical efficacy in storm is well documented and because it inhibits the peripheral conversion of T4 to T3
•Supportive treatment of vital functions in thyroid storm
•Because hypoadrenalism is often suspected, hydrocortisone should empirically be given IV
•Because pharmacologic doses of steroids acutely depress serum T3 levels, a beneficial effect in storm, their routine use is recommended
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