The Thyroid Hormone- Metabolism and Control Flashcards
THE THYROID
The thyroid gland is responsible for the production of two hormones: _______ and _______
thyroid hormone and calcitonin.
Calcitonin is secreted by _____________ cells and is involved in calcium homeostasis.
parafollicular C
Thyroid Anatomy
The thyroid gland is positioned in the (upper or lower?) (anterior or posterior?) part of the neck and is shaped like a _____.
It is made up of ____ lobes that rest on each side of the _______, with a band of thyroid tissue—called the ________—running anterior to the trachea and bridging the lobes.
Low anterior
butterfly; two; trachea
isthmus
(Anterior or Posterior?) to the thyroid gland are the parathyroid glands that regulate serum calcium levels and the __________ nerves that innervate the vocal cords.
Posterior
recurrent laryngeal
Thyroid Hormone Synthesis
Thyroid hormone is made primarily of the trace element ____, making _______ metabolism a key determinant in thyroid function.
iodine; iodine
The recommended minimum daily intake of iodine is ____ g, If iodine intake drops below ___ g daily, the thyroid gland is unable to manufacture adequate amounts of thyroid hormone and thyroid hormone deficiency—hypothyroidism—results.
150; 50
Thyroid Hormone Synthesis
Thyroid cells are organized into ________.
These are spheres of thyroid cells surrounding a core of a ____ substance termed ________, whose major component is _________, a glycoprotein manufactured exclusively by thyroid ______ cells.
follicles; viscous; colloid
thyroglobulin
follicular
Thyroglobulin is rich in the amino acid _________. Some of these ______ residues can be ________, producing the building blocks of thyroid hormone.
On the outer side of the follicle, _____ is (passively or actively?) transported into the thyroid cell by the —————— located on the basement membrane.
tyrosine; tyrosyl
iodinated
iodine; actively
Na/I symporter
Thyroid Hormone Synthesis
Inside the follicle, catalyzed by a membrane-bound enzyme called __________, concentrated _____ is oxidized and bound with _______ on thyroglobulin.
This results in production of ________ and ————-
This same enzyme also aids in the coupling of _______ to form_________________ or __________
These are the two active forms of thyroid hormone.
thyroid peroxidase (TPO)
iodide; tyrosyl residues
monoiodothyronine (MIT) and diiodothyronine (DIT).
two tyrosyl residues
triiodothyronine (T3)
thyroxin (T4)
Protein Binding of Thyroid Hormone
When released into the circulation, only _____% of T4 and _____% of T3 are unbound by proteins and available for hormonal activity.
0.04; 0.4
The three major binding proteins, in order of significance, are
____________
—————-
_______________.
thyroxine-binding globulin (TBG)
thyroxine-binding prealbumin (TBPA)
albumin
The quantity of T4 and T3 in the circulation can be significantly affected by the amount of binding protein available for carrying these hormones.
T/F
T
high estrogen levels during pregnancy lead to ___eased thyroxine-binding protein production by the liver.
incr
Protein Binding of Thyroid Hormone
High TBG levels result in higher levels of bound thyroid hormones, leading to (low or high?) levels of total T3 and total T4.
In _________ individuals, levels of the active free thyroid hormone remain in the normal range. In some instances, however, measurement of free T4 and free T3 may be necessary to eliminate any confusion caused by abnormal binding protein levels.
High
euthyroid
Control of Thyroid Function
Understanding of the hypothalamic-pituitary-thyroidal axis is essential for correctly interpreting thyroid function testing.
TRH is synthesized by neurons in the _______ and ———— nuclei of the _______ and stored in the _________ of the hypothalamus.
When secreted, this hormone stimulates cells in the ________ gland to manufacture and release ________(_____), which , in turn, circulates to the thyroid gland and leads to increased production and release of thyroid hormone.
supraoptic and supraventricular
hypothalamus; median eminence
anterior pituitary ; thyrotropin (TSH).
TESTS FOR THYROID EVALUATION
______
___________
_______
________
RADIO IODINE (NUCLEAR MEDICINE TECHNIQUES) THYROID ULTRASOUND
FNAC
TSH
T3
T4
THYROID AUTOANTIBODIES
The most useful test for assessing thyroid function is the _______
TSH
TESTS FOR THYROID EVALUATION- Blood Tests
TSH
Over the years, three generations of assays have been developed.
All the assays are capable of diagnosing primary ____thyroidism with _______ levels of TSH.
Second-generation TSH immunometric assays, with detection limits of 0.1 mU/L, can effectively screen for ____________.
Third-generation TSH chemiluminometric assays, with detection limits of 0.01 mU/L, can more accurately _____________________________
hypo; elevated
hyperthyroidism
distinguish between euthyroidism and hyperthyroidism
TSH assays
The sensitivity of the ______-generation TSH assays has led to the ability to detect what is termed _______ disease—or a (mild or severe?) degree of thyroid dysfunction—due to the large reciprocal change in ____ levels seen for even small changes in ______
third; subclinical
TSH
free T4
TSH assays
In subclinical hypothyroidism, the TSH is __________ while the free T4 _______________
Likewise, in subclinical hyperthyroidism, the TSH is ________ while the free T4 is ______.
minimally increased
stays within the normal range.
suppressed; normal
Serum T4 and T3
Serum total T4 and T3 levels are usually measured by ________,__________, or similar immunometric technique.
Because more than _____% of thyroid hormone is protein bound, alteration in _____________, unrelated to thyroid disease, frequently lead to total T4 and T3 levels outside of the normal range.
Because of this, assays have been developed to measure ———- and ———, the biologically active forms of thyroid hormone, and free T4 kits have replaced total T4 determinations.
radioimmunoassay (RIA), chemiluminometric assay
99.9; thyroid hormone–binding proteins
free T4 and T3
Thyroglobulin
This prohormone in the circulation is proof of ___________________. This fact makes thyroglobulin an ideal tumor marker for thyroid cancer patients.
the presence of thyroid tissue, either benign or malignant.
Patients with well-differentiated thyroid cancer who have been treated successfully with surgery and radioactive iodine ablation should have undetectable thyroglobulin levels.
T/F
T
Thyroglobulin
Thyroglobulin is currently measured by double-antibody RIA, enzyme- linked mmunoassay (ELISA), immune radiometric assay (IRMA), and immune chemiluminescent assay (ICMA) methods.
T/F
T
Thyroglobulin
The accuracy of the thyroglobulin assay is primarily dependent on the ________________ used and the absence of _____________________
Even with modern assays, ______________________ interfere with measurements and lead to unreliable thyroglobulin results.
specificity of the antibody
antithyroglobulin autoantibodies
anti thyroglobulin auto antibodes
Thyroglobulin
For this reason, it is critically important to screen for ___________ whenever thyroglobulin is being measured. If antibodies are present, the value of the thyroglobulin assay is marginal.
Approximately ___% of patients with well-differentiated thyroid cancer will have ____________________________.
This is approximately twice as high as in the general population.
autoantibodies
25
anti thyroglobulin autoantibodies
Thyroglobulin
If a patient with well-differentiated thyroid cancer and anti thyroglobulin autoantibodies has been successfully treated with ________ and ___________________, autoantibodies should disappear over time.
surgery and radioactive iodine ablation
Thyroid Antibodies
In autoimmune thyroid disease,antibodies are directed at thyroid tissue with variable responses.
The most common cause of hyperthyroidism is an autoimmune disorder called ___________. The antibody in this condition is directed at the _____ receptor and stimulates the receptor, leading to growth of the thyroid gland and production of excessive amounts of thyroid hormone.
This condition can be diagnosed with tests that detect antibodies to the TSH receptor.
Graves’ disease
TSH
Thyroid Antibodies
____________________________ (TSAb, TSI) use a bioassay to determine presence of autoimmune hyperthyroidism.
Tests for TSH receptor antibodies (TSHR-Ab) can detect antibodies directed against the _______ whether they act to _________ or _____________
Thyroid stimulating antibodies
TSH receptor ; stimulate or block the TSH receptor.
Both stimulating and blocking antibody assays will be positive in 70%–100% of patients with Graves’ disease.
T/F
T
__________________—commonly known as Hashimoto’s thyroiditis—is at the other end of the autoimmune continuum.
Chronic lymphocytic thyroiditis
Hashimoto’s thyroiditis
In this condition, antibodies lead to decreased thyroid hormone production by the thyroid gland.
The best test for this condition is the ___________, which is present in 10%–15% of the general population and 80%–99% of patients with autoimmune hypothyroidism
thyroid peroxidase (TPO) antibody
Nuclear Medicine Evaluation
_____________ is useful in assessing the metabolic activity of thyroid tissue and assisting in the evaluation and treatment of thyroid cancer.
Radioactive iodine
the most common cause of hypothyroidism in the developed world is???
Hashimoto thyroiditis
When radioactive iodine is given ______, a percentage of the dose is taken up by the thyroid gland.
This percentage is called the _____________.
High uptake suggests that the gland is _____________ and ________________________.
Low uptake suggests that the gland is __________________
orally
radioactive iodine uptake (RAIU)
metabolically active and producing significant amounts of thyroid hormone
metabolically inactive.
Because ______ stimulates iodine uptake by the thyroid gland, it is important to interpret the scan with _________ in conjunction with an assessment of ____ levels.
TSH
radioactive iodine
TSH
An undetectably low TSH should _______ the thyroid gland’s uptake of iodine.
If the uptake is high despite an undetectable TSH, the thyroid must be either ______________ in regards to the usual hypothalamus- pituitary-thyroid feedback system or through a ________
turn off
acting autonomously
TSH surrogate.
Radioactive iodine can also be useful in the evaluation of thyroid ______ in the presence of a low or undetectable TSH.
nodules
Thyroid nodules that take up significant amounts of radioactive iodine on thyroid scans—termed “ ______ ” nodules—are (likely or unlikely?) to be thyroid cancer.
The converse, however, __________ as nodules that show little or no radioiodine uptake—indeterminate or “____” nodules, respectively—may ________, but the majority of such nodules are _______.
hot; unlikely
does not hold true
cold
be cancerous; benign
OTHER TOOLS FOR THYROID EVALUATION
Thyroid ______
________ Aspiration
Ultrasound
Fine-Needle
DISORDERS OF THE THYROID-
HYPOTHYROIDISM
-__________
-_________ aka ___________
HYPERTHYROIDISM
• -___________
-___________ disease
-_______________ and ______________
Iodine deficiency
-Chronic lymphocytic thyroiditis aka Hashimoto’s thyroiditis
Thyrotoxicosis
-Grave’s disease
-Toxic Adenoma and Multinodular Goiter
DISORDERS OF THE THYROID-
•______-INDUCED THYROID DYSFUNCTION
SUBACUTE THYROIDITIS (________,________,________)
NON THYROIDAL ILLNESS
DRUG
postpartum thyroiditis, painless thyroiditis, and painful thyroiditis
When thyroid hormone is significantly decreased, symptoms of :
______ intolerance, fatigue, _____ skin
(constipation or diarrhea?) , hoarseness
____ on exertion, _____ dysfunction
____ loss, and weight _____ have been reported.
cold; dry
constipation
dyspnea ;cognitive
hair loss; weight gain
On physical examination, those with severe hypothyroidism may have :
(low or high?) body temperature
_______ movements
_______cardia
delay in the __________ reflex testing.
low
slowed
bradycardia
relaxation deep tendon reflex
Hypothyroidism can be divided into _____,________,_______ disease, dependent on the location of the defect.
This disorder is an autoimmune disease targeting the thyroid gland, often associated with an ______ gland, or ______.
primary, secondary, or tertiary
enlarged; goiter
Types of hypothyroidism
Primary : _______ dysfunction
Secondary : _______ dysfunction
Tertiary : _________ dysfunction
Thyroid gland
Pituitary
Hypothalamus
Occasionally, individuals will experience transient hypothyroidism associated with inflammation of the thyroid gland.
T/F
T
Examples of transient hypothyroidism include recovery from _______ illness and the ________ phase of any of the forms of ____________
nonthyroidal
Hypothyroid
subacute thyroiditis (painful thyroiditis, postpartum thyroiditis, and painless thyroiditis).
Treatment for Hypothyroidism
Hypothyroidism is treated with thyroid hormone replacement therapy.
_________(____) is the treatment of choice.
Levothyroxine (T4)
Treatment for Hypothyroidism
In primary hypothyroidism, the goal of therapy is to achieve a normal ______ level.
TSH
If hypothyroidism is of secondary or tertiary in origin, TSH levels will
be useful in managing the condition
T/F
F
If hypothyroidism is of secondary or tertiary in origin, TSH levels will not be useful
A mid-normal free T4 level becomes the target of therapy.
Levothyroxine has a half-life of approximately ______
When doses of thyroid hormone are changed, it is important to wait at least ________ before rechecking thyroid function tests in order to achieve a new steady state.
7 days.
five half-lives
Thyrotoxicosis : Thyrotoxicosis is a constellation of findings that result when
_____________________________
peripheral tissues are presented with, and respond to, an excess of thyroid hormone.
Thyrotoxicosis
The manifestations of thyrotoxicosis vary, depending on the ________________ and the ______ of the affected individual.
degree of thyroid hormone elevation
status
Thyrotoxicosis
Symptoms typically include
anxiety, _______ lability
weakness, tremor, palpitations
_____ intolerance, ____eased perspiration
weight ____ despite a normal or increased appetite.
emotional
heat; incr
loss
___________ is the most common cause of hyperthyroidism with associated thyrotoxicosis.
Graves’ disease
Graves’ Disease
Features of Graves’ disease include
___________,________
_______ opathy and dermopathy (skin changes in the _______ that have ___________ texture).
thyrotoxicosis, goiter
ophthalm; lower extremities
an orange peel
Graves’ Disease
There is a (weak or strong?) familial disposition to Graves’ disease
(Men or Women?) are five times more likely than (men or women?) to develop this condition.
Strong
Women; men
Graves’ Disease
Laboratory testing will usually document a _____ free T4 and/or T3 level with ____________ TSH.
_____________ (TSIs) and TSH receptor antibodies are usually positive in this condition.
RAIU will be elevated, and the thyroid scan will show diffuse uptake
high
an undetectable
Thyroid-stimulating immunoglobulins
Graves’ Disease
Thyroid disease associated with Graves’ disease is treated with ———,________,_______
medication, radioactive iodine, or surgery.
Graves’ Disease Cont’d
Initially, many thyrotoxic patients require _______ to control symptoms of adrenergic excess, such as tremor and tachycardia.
———— or _________ can be added to inhibit thyroid hormone biosynthesis and secretion.
These anti-thyroidal medications carry a significant risk profile that includes rash, hepatoxicity, agranulocytosis, and aplastic anemia.
alpha-blockers
Propylthiouracil (PTU) or methimazole (MMI)
Grave’s disease
(Men or Women?) are more likely to achieve remission than (men or women?).
Likewise, patients with (small or large?) goiters and (mild or severe?) hyperthyroidism are more likely to achieve remissions.
Women; Men
Small; Mild
Grave’s disease
____ dietary iodine increases the chance of staying in long-term remission.
Patients experiencing such a remission do not require therapy with thyroid hormone replacement.
When radioactive iodine or surgery is used, the goal is to ___________________ so that the patient becomes ________.
Subsequent __________________ is usually required.
Low
destroy or remove enough thyroid tissue
hypothyroid
lifelong treatment with thyroid hormone replacement therapy
Radioactive iodine therapy has been used for treatment of Graves’ disease for more than 50 years and is both safe and effective
T/F
T
Graves’ Disease
Surgery is associated with risk of _______ nerve injury, leading to permanent ______ , and injury to the _______ glands, causing _______ leading to _______.
recurrent laryngeal
hoarseness; parathyroid
hypoparathyroidism; hypocalcemia
Graves’ Disease
Because of their comparative risks for adverse events, ____________ is generally the preferred treatment modality in the United States.
radioactive iodine
Graves’ Disease
__________ medications are typically used either because of patient preference or during pregnancy and breastfeeding.
Antithyroidal
Toxic Adenoma and Multinodular Goiter
Toxic adenomas and multinodular goiter are two relatively common causes of hyperthyroidism.
These conditions are caused by ________________
In these instances, neither ———— now ________________ is required to stimulate thyroid hormone.
autonomously functioning thyroid tissue.
TSH nor TSH receptor–stimulating immunoglobulin
Toxic Adenoma and Multinodular Goiter
Thyroid hormone receptor mutations have been identified. These mutations have the same effect as __________________________ on thyroid hormone production.
chronic stimulation of the TSH receptor
Clinically, toxic adenomas present in patients with ________ and a __________________
hyperthyroidism
palpable thyroid nodules.
Toxic Adenoma and Multinodular Goiter
Treatment for these two conditions involves surgery, radioactive iodine, or medication (PTU or MMI).
Although the medications can __________________, they are not expected to _____________ in these two conditions.
block thyroid hormone production
lead to remission
Toxic Adenoma and Multinodular Goiter
Often, the toxic nodules produce so much thyroid hormone that the rest of the thyroid gland is ________ and _______
When radioactive iodine is given, it tends to destroy only the _____________________, leaving normal (suppressed) thyroid tissue undamaged.
Because the normal thyroid tissue is hypofunctioning and takes up little of the radioactive iodine, when treatment is given the patient may be left with ______________ without the need for thyroid hormone replacement therapy.
suppressed and metabolically inactive.
hyperactive (autonomous) portions of the thyroid gland
normal thyroid function
DRUG-INDUCED THYROID
DYSFUNCTION. Amiodarone-Induced
Thyroid Disease
Several drugs other than PTU and methimazole can affect thyroid function.
Amiodarone, a drug used to treat cardiac arrhythmias, is a ____-soluble drug with a long half-life (————-) in the body that interferes with normal thyroid function.
fat
50 days
DRUG-INDUCED THYROID
DYSFUNCTION. Amiodarone-Induced
Thyroid Disease
Iodine, when given in large doses, acutely leads to ___________________________. This is called the __________ effect.
inhibition of thyroid hormone production
Wolff-Chaikoff
The fact that ____% of the molecular weight of amiodarone is ______ accounts for a significant part of the thyroid dysfunction seen
37
iodine
DRUG-INDUCED THYROID DYSFUNCTION. Amiodarone-Induced Thyroid Disease
Amiodarone also blocks _____________.
The combination of these two actions leads to _____thyroidism in 8%–20% of patients on chronic amiodarone therapy.
T4-to-T3 conversion.
hypo
Amiodarone can also lead to hyperthyroidism
T/F
T
in 3% of patients treated chronically with this medication.
DRUG-INDUCED THYROID DYSFUNCTION. Amiodarone-Induced Thyroid Disease
Certain patients develop hyperthyroidism as they escape the ____________ and use the ________ for thyroid hormone production.
Others develop hyperthyroidism if the medication leads to _______________ and subsequent _______________________
Wolff-Chaikoff effect
excess iodine
inflammation of the thyroid gland (subacute thyroiditis)
leakage of stored thyroid hormone into the circulation.
Subacute Thyroiditis
Several conditions occur that lead to transient changes in thyroid hormone levels.
These conditions are associated with _______________, ________ of _______ thyroid hormone, and then _______ of the gland.
inflammation of the thyroid gland
leakage of stored ; repair
Subacute Thyroiditis
Although nomenclature varies between authors, grouping together _________ thyroiditis, _________ thyroiditis, and _________ thyroiditis as forms of subacute thyroiditis is one of the simplest classification schemes.
postpartum thyroiditis
painless thyroiditis
painful thyroiditis
Subacute Thyroiditis
These conditions are often associated with a
•———— phase when thyroid hormone is ____________
• a ________ phase when the thyroid gland is ___________, and a
•_________ phase when the gland is ________.
These phases can last from ______ to ______
thyrotoxic; leaking into the circulation
hypothyroid; repairing itself,
euthyroid; repaired
weeks to months.
____________ thyroiditis is the most common form of subacute thyroiditis.
Postpartum
Subacute Thyroiditis
It is strongly associated with the presence of ___________ and ————
Patients may experience a period of ________ followed by _________ or simply __________ or ____________.
TPO antibodies and chronic lymphocytic thyroiditis.
thyrotoxicosis; hypothyroidism
hypothyroidism or hyperthyroidism
Subacute Thyroiditis
Thyroid hormone levels usually return to normal after several months; however, by _______’ postpartum, 25%–50% of patients have —————,————— or both.
4 years
persistent hypothyroidism, goiter,
Subacute Thyroiditis
During the thyrotoxic phase, ________ can be used if treatment is necessary.
During the hypothyroid phase, _________________________________ can be given if symptoms require, usually for ___________, unless permanent ________ evolves.
alpha blockers
thyroid hormone replacement therapy
3–6 months; hypothyroidism
Subacute Thyroiditis
Painless thyroiditis or subacute lymphocytic thyroiditis shares many characteristics of postpartum thyroiditis, except there is no associated ________.
pregnancy
The thyrotoxic phase of post partum thyroiditis , as well as other forms of subacute thyroiditis, can be distinguished from Graves’ disease by a _______ and _____________
low RAIU
an absence of TSI or TSH receptor antibodies.
Subacute Thyroiditis
Painful thyroiditis, also called _______,___________, or _________, is characterized by _______, ____-grade fever, myalgia, a tender diffuse goiter, and swings in thyroid function tests (as discussed earlier).
subacute granulomatous, subacute non suppurative thyroiditis, or de Quervain’s thyroiditis
neck pain; low
Subacute Thyroiditis
Painful thyroiditis
__________ are felt to trigger this condition. TPO antibodies are usually ________; erythrocyte sedimentation rate and thyroglobulin levels are often _______.
Viral infections
absent; elevated
NONTHYROIDAL ILLNESS
Hospitalized patients, especially critically ill patients, often have abnormalities in their thyroid function tests.
Because illness decreases _____________ activity, therefore less _____________________.
This leads to decreased levels of____ and higher levels of ______
5-monodeiodinase
T4 is converted to active T3
T3; reverse T3.
NONTHYROIDAL ILLNESS
There also seems to be an element of ____________ and thyroid hormone–binding changes associated with severe illness.
It is believed that many of these changes are an appropriate adaptation to illness.
central hypothyroidism
In non-thyroidal illness, Thyroid hormone replacement therapy is indicated.
T/F
F
Thyroid hormone replacement therapy is not indicated.
