thyroid disorders Flashcards
inadequate hormones, manifested as tired
Hypothyroidism
too much secretion of thyroid hormones → fast metabolism + uses energy → tiring
(pagod pa rin)
Hyperthyroidism
One of the largest endocrine glands
A small organ located in front of the neck, wrapped around the windpipe or trachea
Thyroid gland
Butterfly-shaped, smaller in the middle with two wings or lobes that extend around the side of the throat
Two cone-like lobes or wings
Thyroid gland
_____________ (right lobe) and _____________ (left lobe) connected via the ___________ (the bridge between the lobes of the thyroid)
lobus dexter; lobus sinister; isthmus
Hypothalamus releases ______________ which stimulates the anterior pituitary gland
thyrotropin releasing hormone (TRH)
Pituitary gland releases __________________ which stimulates the thyroid gland
In the presence of TRH
thyroid stimulating hormone (TSH)
Thyroid gland releases ___ and ___, which perform the thyroid functions
T3 and T4
Regulate the rate of metabolism and physiological functions (heart rate, sweating
and energy consumed)
Affect the growth and rate of function of many other systems in the body
T3 and T4
If thyroid hormone levels are adequate, T3 and T4 signals the hypothalamus and anterior pituitary gland to stop stimulating = no thyroid hormone production (t or f)
T
Thyroid hormones (T3 and T4) is regulated by
TSH
Low levels: Hypothalamus releases _________ that triggers TSH release from the pituitary gland
TRH
High levels: Hypothalamus _______ TRH release and anterior pituitary gland ________TSH release
stops
system that regulates the levels of TRH, TSH, T3 and T4
Negative feedback system
85% - 90% (majority)
T4
Majority is converted into T3 (removal of ___________)
1 iodine – deiodination
10% - 15% (more active)
T3
T3 bulk is derived by deiodination of T4 in ____________
peripheral tissues (liver, kidneys)
Deiodination of T4 yields __________ T3
■ a molecule with no known metabolic
activity
Reverse
Two principal thyroid hormones:
Thyroxine (T4)
Triiodothyronine (T3)
L-3,5,3’,5’-tetraiodothyronine
Thyroxine (T4)
T3 and T4 are derivatives of _________ bound covalently to iodine
Tyrosine
L-3,5,3’-triiodothyronine
Triiodothyronine (T3)
“pro-hormone of T3”
is better for transport through the body
T4
more stable and durable molecule (due to many iodine attachments); must travel through the circulatory system to get to the tissues
T4
Once in the tissues, T4 needs to convert to T3, the less biologically active, through deiodination (removal of iodine) (t or f)
F; more
sourced from diet
Iodine
The lobes of the thyroid contain hollow, spherical structure called __________, which are the functional units of the thyroid gland
follicles
Interspersed between the follicles are ____________, secreting calcitonin
parafollicular C-cells
Another hormone released by thyroid gland responsible for modulating blood calcium levels
in conjunction with PTH (Parathyroid hormone)
calcitonin
Each follicle is filled with a thick sticky substance called __________
colloid
The major constituent of colloid is a large glycoprotein called ____________, produced by follicle cells
thyroglobulin
site of thyroid hormone synthesis
colloid
Thyroid hormone synthesis and secretion is regulated by two main mechanisms:
- “autoregulation” mechanism which reflects the available levels of iodine
- regulation by the hypothalamus and anterior pituitary regulation of thyroid hormone levels
TH are highly _________
lipophilic
Less than ____% of T3 and T4 are in unbound form, unattached to TBG protein
1%
unbound form of TH = __________
biologically active
An indispensable component of the thyroid hormones - ____% of T4 and ______% of T3 weights
iodine; 65%, 58%
The thyroid hormones are one of few iodine-containing hormone
F; the ONLY iodine containing hormone
Minimum requirement of iodine per day
75 micrograms
iodine deficiency =
goiter
Lack of thyroid hormone during development results in short stature and mental deficits __________
cretinism
Cardiovascular:
______ heart rate
______ cardiac contractility
______ cardiac output
______ vasodilation
all increase; promotes
CNS:
both increased and decreased thyroid hormone concentrations leading to alteration in mental state
too low: __________
too high: _________
feel mentally sluggish; anxiety and nervousness
Reproductive:
normal reproductive behavior and physiology is dependent on essentially normal levels of thyroid
hormones
hypothyroidism is commonly associated with __________
infertility
signals hypothalamus to stop TRH secretion → decreased TSH
High T3, T4
signals hypothalamus to produce TRH →
high TSH
Low T3, T4
secondary and tertiary
central hypothyroidism
Primary hypothyroidism
Thyroid gland problem
Secondary hypothyroidism
problem with the pituitary gland
Tertiary hypothyroidism
problem with the hypothalamus
To differentiate between secondary and tertiary check:_____-
T3 levels
Thyroid function tests
- TSH test
- T4 test
- T3 test
- Thyroid antibody test
> thyroid peroxidase
> thyroglobulin - Radioactive iodine uptake
- Most appropriate test
- Very sensitive and specific parameter to assess thyroid function
- Differentiates primary (thyroid gland problem) from secondary (pituitary gland problem) and tertiary (hypothalamus problem) hypothyroidism
● In most healthy individuals, a normal ______value means that the thyroid is functioning properly.
TSH test
equal or normal TSH value
euthyroid
thyroid gland is not making enough thyroid hormone (primary hypothyroidism) → low T3, T4
Increased TSH
thyroid gland is producing too much thyroid hormone (hyperthyroidism); → high T3, T4
Decreased TSH
- Often useful to diagnose hyperthyroidism, determine the severity of the hyperthyroidism, assess abnormal protein binding disorders, monitor thyroid replacement and suppressive therapies
- Rarely helpful in hypothyroidism
○ It is the last test to become abnormal
○ Patients can be severely hypothyroid with a high TSH and low Free T4 or Free T4 Index (FTI),
but have a normal _____
T3 test
A more sensitive indicator of hyperthyroidism than Total T4
T3 test
Hypothyroidism: T3 is often normal even when the T4 is low (t or f)
T
Increased T3: in almost all cases of hyperthyroidism (T3 usually goes up before T4) (t or f)
T
Decreased T3: during acute illness and starvation, affected by several medications: ___________________
beta blockers, steroids, and amiodarone
● The main form of thyroid hormone circulating in the blood
● Important element in routine clinical diagnosis and in suspected thyroid function disorders (with TSH)
T4 test
measures the bound and free hormone and can change when binding proteins differ
Total T4
measures what is not bound and able to enter and affect the body tissues
Free T4
hyperthyroidism, subacute thyroiditis in its first stage and with thyrotoxicosis due to Hashimoto’s
disease
inc T4
hypothyroidism and in the third stage of subacute thyroiditis
dec T4
Tests measuring free T4:
either a free T4 (FT4) or free T4 index (FTI) - more accurately reflect how the thyroid
gland is functioning when checked with a TSH
TSH: High
FT4: Low
(Thyroid Panel Test)
Primary Hypothyroidism
TSH: Low
FT4: Low
(Thyroid Panel Test)
Secondary Hypothyroidism
TSH: Low
FT4: High
(Thyroid Panel Test)
Hyperthyroidism
“Total” =
Protein bound + free thyroid hormones
- Provide a reliable index of thyroid gland activity if levels of thyroid binding proteins are normal
● Changes in serum concentration of thyroid-binding proteins (TBP) or the presence of drugs that affect the binding of T3 and T4 to TBP will modify total hormone levels, but not the biologically active free T3 and T4 levels
Total T3 and T4
-A protein produced by normal thyroid and thyroid cancer cells
● Not a measure of thyroid function, do not diagnose thyroid cancer when the thyroid gland is still present
>Precursor only
● Most often used in patients who have had surgery for thyroid cancer to monitor them after treatment
● Tg is not a primary measure of thyroid hormone function
Thyroglobulin (Tg)
- Thyroid peroxidase (TPO) (or antimicrosomal (TMAb) and antithyroglobulin (TgAb) antibodies
> Produced in patients with hypothyroidism or hyperthyroidism when lymphocytes react against thyroid and make antibodies against the thyroid cell proteins
> Measured to confirm, diagnose or rule out autoimmune thyroid disease, not specific for the type of a disease
● High titers of these antibodies are present in 97% of patients with Grave’s disease or Hashimoto’s thyroiditis
Thyroid Autoantibodies
Thyroid Scan or Thyroid Imaging
● Oral administration of Iodine-123 by swallowing the isotope
● Measure radioactivity over the thyroid area after 4 or 6 hours and after 24 hours
● The normal uptake at 6 hours is 5-15% and at 24 hours 8-30%
Radioactive Iodine Uptake (RAIU)
High RAIU
hyperthyroidism (overactive thyroid gland)
= overperforming
Low RAIU
hypothyroidism (underactive thyroid gland)
= not enough iodine from the blood
Thyroid Imaging
○ Radionuclide Imaging
○ Radioisotope Scanning
○ Fluorescent Scanning
○ Thyroid Ultrasonography
○ Magnetic Resonance Imaging
Gland Destruction
Hypothyroidism
Under-production of thyroid hormones, Myxedema (Gull Disease), Cretinism, Thyroiditis
Hypothyroidism
Thyrotoxicosis
Hyperthyroidism
Over-production of thyroid hormone, Grave’s Disease
Hyperthyroidism
Diffuse and multi-nodular
Goiter
- Weight Gain
- Decreased Appetite
- Cold Intolerance Increased Sensitivity to Cold
- Bradycardia
- Constipation
- Fatigue, Depression, Impaired Memory, Impaired Concentration, “Mental Fog”
- Hair Loss and Thin Nails Dry Skin
HYPOTHYROIDISM
- Weight Loss
- Increased Appetite
- Heat Intolerance Increased Sensitivity to Heat
- Tachycardia, Palpitations, Arrhythmias
- Diarrhea
- Anxiety, Nervousness, Irritability, insomnia, Tremors
- Increased Hair and Nail Growth Increased Sweating
HYPERTHYROIDISM
- A condition in which the thyroid gland is underactive resulting in low levels of thyroid hormone in the blood
- May be congenital, primary or central (secondary or tertiary)
Hypothyroidism
In areas of iodine sufficiency, autoimmune disease _______________ and iatrogenic causes
(treatment of hyperthyroidism) are most common
Hashimoto’s thyroiditis
Congenital: in children, hypothyroidism leads to delay in
growth _____________, and intellectual development _______________
dwarfism, cretinism
measurement of TSH or T4 levels at birth through heel-prick blood specimens
Neonatal screening programs
preferred form of thyroid hormone replacement in all patients with hypothyroidism
Levothyroxine
can be crushed and mixed into a baby’s milk, formula or water
Thyroid hormone pills
Classification of Hypothyroidism
- Primary
- Secondary
- Tertiary
Most common type due to thyroid gland diseases, high TSH levels
Causes:
- Autoimmune thyroiditis (Hashimoto’s thyroiditis)
■ Congenital hypothyroidism (thyroid aplasia or hypoplasia, thyroid hormone synthesis defect, genetic abnormalities)
■ Iatrogenic (radioiodine therapy, total thyroidectomy)
■ Iodine deficiency (most common cause worldwide)
■ Thyroid ablation or surgery (removal of part or whole)
■ Taking excess goiterogenic food (broccoli, cauliflower, cabbage, cassava, soybeans, kale, brussels
sprouts) → inhibits iodine uptake
■ Drugs (lithium, amiodarone, iodine, antithyroid agents)
Primary
Hypothyroidism due to insufficient stimulation by the TSH of an otherwise normal thyroid gland
○ Low TSH to differentiate it from primary (high TSH)
■ Secondary – disease in the pituitary gland
■ Tertiary – disease in the hypothalamus
Central (secondary and tertiary)
Absence of associated deficiencies
(Pituitary Hormone Deficiencies)
Primary
Associated with multiple pituitary hormone deficiencies (amenorrhea, infertility, hypoglycemia,
hyponatremia, anorexia, weight loss, and diabetes)
(Pituitary Hormone Deficiencies)
Central
Usually present
(Goiter)
Primary
Absence
(Goiter)
Central
Invariably present
(Antithyroid Antibodies)
Primary
Normal, low, sometimes high
(TSH)
Central
Usually above
(TSH)
Primary
Invariable absent
(Antithyroid Antibodies)
Central
Normal
(TRH Stimulation Test)
Primary
Abnormal
(TRH Stimulation Test)
Central
- is usually irregular and firm in consistency.
- puffy face, edematous eyelids, non-pitting pretibial edema
goiter
A physical exam usually reveals a small (_____________) or an enlarged (____________) thyroid gland
(signs and tests)
central; primary
Vital signs
(signs and tests)
a slow heart rate, low blood pressure, and low temperature
A chest x-ray may reveal ________________
(signs and tests)
cardiomegaly
Laboratory tests to determine thyroid function include
- Free T4 test
○ Total T3
○ Serum TSH
- An autoimmune disorder involving chronic thyroid inflammation characterized by the destruction of thyroid cells by various cell and antibody-mediated immune processes
- Over time, the ability of the thyroid gland to produce thyroid hormones often becomes impaired and leads to a gradual decline in function and eventually an underactive thyroid
Hashimoto’s Thyroiditis
No adverse effects if taken in the appropriate dose
■ Underdose: elevated serum TSH
(____thyroidism)
■ Overdose: suppressed serum TSH
(____thyroidism)
hypo; hyper
- Also known chronic lymphocytic thyroiditis
● The most common cause of hypothyroidism in iodine-sufficient regions (most common cause
worldwide: iodine deficiency)
○ In places with sufficient iodine, the most common cause is autoimmune or sometimes
iatrogenic
Hashimoto’s Thyroiditis
- A term generally used to denote severe hypothyroidism
● Also used to describe the dermatologic changes that occur in hypothyroidism
Myxedema
- Treatment of choice for Hashimoto’s Thyroiditis
○ Thyroid hormone replacement usually for life
Levothyroxine sodium
- Myxedema Crisis
● A rare, life-threatening clinical condition that represents
severe hypothyroidism with physiologic decompensation
● Occurs in long-standing, undiagnosed hypothyroidism
● Most often precipitated by infection, cerebrovascular
disease, heart failure, trauma or drug use
Myxedema Coma
Management for Myxedema Coma
- Supportive therapy for airway and rewarming
○ Hydrocortisone
○ Levothyroxine sodium (T4)
>With or without T3 supplementation, no clinical and pharmacologic significance
- A synthetic version of one of the body’s natural thyroid hormones: thyroxine (T4)
- Recommended as the preparation of choice for the treatment of hypothyroidism due to its efficacy in resolving the symptoms of hypothyroidism, long-term experience of its benefits, favorable side effect profile, ease of administration, good intestinal absorption, long serum half-life, and low cost
Levothyroxine
- Major hormone secreted from the thyroid gland
■ Chemically identical to the naturally secreted T4
■ Increases metabolic rate, decreases thyroid-stimulating hormone (TSH) production from the anterior lobe of the pituitary gland, and, in peripheral tissues, is converted to T3
Levothyroxine: Thyroxine (T4)
- Treatment of primary, secondary, and tertiary hypothyroidism
■ Adjunct to surgery and radioiodine therapy in the management of thyrotropin-dependent well-differentiated thyroid cancer
Levothyroxine: Oral Form
Treatment of myxedema coma or severe hypothyroidism
Levothyroxine: Injectable
Do not administer levothyroxine in conjunction with __________ or ___________
antacids or proton pump inhibitors
Oral levothyroxine: Administer on an full (acidity increases
absorption), at least 30 to 60 minutes before breakfast or 3 to 4 hours after
dinner. (t or f)
F; empty stomach
Do not administer levothyroxine within 4 hours of administration of products that may contain _________ or _________
iron or calcium
○ An autoimmune disorder that causes hyperthyroidism or overactive thyroid
○ Immune system attacks the thyroid and causes it to make more thyroid hormones than the body needs
Grave’s disease (Toxic Goiter)
Hyperthyroidism caused by Graves’ disease, accounts for _______% of thyrotoxicosis
60- 80%
- A synthetic form of the natural thyroid hormone (T3) converted from T4.
○ It is not intended for use as sole maintenance therapy, but in rare cases it can be used together with LT4 in small doses (5-15 µg/day).
Liothyronine (LT3)
- A condition in which the thyroid gland is overactive resulting in high levels of thyroid hormone in the blood
● Thyrotoxicosis is a state of thyroid hormone excess and is not synonymous with hyperthyroidism, which is the result of excess thyroid function
Hyperthyroidism
Causes of Hyperthyroidism
- Grave’s disease (Toxic Goiter)
- Toxic multinodular goiter (Plummer’s disease)
- Toxic adenoma
○ Thyroid gland nodules produce too much thyroid hormones
○ Seldom causes bulging of the eyes or exophthalmos
Toxic multinodular goiter (Plummer’s disease)
A single nodule making the extra amount of thyroid hormone
Toxic adenoma
Antithyroid medication
- Methimazole
- Propylthiouracil
- Belong to the class of thionamides
○ Initial treatment for hyperthyroidism
Antithyroid medication
■ Drug of choice in the first trimester of pregnancy
■ Inhibits thyroid hormone synthesis and T4 to T3 conversion
> Won’t illicit effects of T3
■ Higher risk of causing severe liver injury
Propylthiouracil
■ Preferred antithyroid medication
> Drug of Choice
■ Except in the first trimester of pregnancy, since it may cause birth defects, and in patients with an adverse reactions
■ Inhibit thyroid hormone synthesis
Methimazole
○ Taking radioactive oral iodine one time
○ Iodine is taken up by the thyroid gland
○ Radioactive iodine destroys most or all tissues in thyroid gland, but does not harm any other body parts
Radioactive iodine ablation of the thyroid gland
contraindicated in severe Grave’s orbitopathy and in patients who are pregnant or nursing
Radioactive iodine
Do not approach or stay near the vicinity of a patient receiving radioactive therapy (t or f)
T
Removal of all or part of the hyperfunctioning thyroid tissues
Surgical thyroidectomy
Beta-blockers used
Propranolol and Atenolol
■ inhibits 5’-monodeiodase
■ blocking peripheral conversion of T4 to T3
Propranolol
■ safer than propranolol in patients with asthma and COPD
■ allows once daily dosing for better compliance
Atenolol
- First-line treatment for children, adult and pregnancy
■ Initial treatment in severe cases or preoperative preparation
(Hyperthyroidism caused by Grave’s Disease)
Methimazole
- Best treatment for toxic nodules and toxic multinodular goiter
Radioactive iodine (I-131)
■ Rapid, effective treatment, especially in large goiters
■ Potential choice in 2nd trimester pregnancy
Surgery
Ancillary Agents
- Cholestyramine
- NSAIDs
- Supersaturated potassium iodide
Treats pain in subacute thyroiditis
NSAIDs
■ Acute inhibition of thyroid hormone
synthesis and release, reduced
vascularity and T4 to T3 conversion
■ Given at least one hour after
methimazole or propylthiouracil
■ Do not give before radioactive iodine
treatment
Supersaturated potassium iodide
Binds with the thyroid hormones in the
intestine, increasing fecal excretion
Cholestyramine
Glucocorticoids
Prednisone, Dexamethasone
■ No exposure to radiation or to surgical
risks
■ No permanent hypothyroidism
■ PTU is safe for the fetus in the first
trimester of pregnancy
Antithyroid Medications (Methimazole and PTU)
benefits
Used in severe cases or thyroid storm
to reduce T4 to T3 conversion, and in
severe subacute thyroiditis
Prednisone, Dexamethasone
■ Agranulocytosis, hepatotoxicity (with
PTU), rash
■ Methimazole can cause aplasia cutis
and other birth defects in the first
trimester of pregnancy
Antithyroid Medications (Methimazole and PTU)
Risks
Benefits
■ No exposure to potential adverse
effects of an antithyroid medication or
to surgical risks
■ Treatment of choice in the US
Radioactive iodine ablation
Risks
■ Aggravation of Grave’s orbitopathy,
especially in smokers, permanent
hypothyroidism, radiation exposure,
failure to cure hyperthyroidism if iodine
is insufficient, risk of Grave’s disease
recurrence, contraindicated in
pregnancy
Radioactive iodine ablation
Benefits
■ No exposure to adverse effects of an
antithyroid medication or to radiation
■ Little chance of Grave’s disease
recurrence
Thyroidectomy
Risks
■ Risks of general anesthesia, damaging
recurrent laryngeal nerve leading to
hoarse voice (unilateral) or respiratory distress (bilateral), and inadvertent
damage or removal of parathyroid
glands leading to permanent
hypoparathyroidism
Thyroidectomy
