Thyroid Flashcards
What are the three hormones secreted by the thyroid gland?
Triiodothyronine (T3),t1/2 1-2 dys (9%)
Thyroxine (T4), t1/2 6-7 dys (90%)
Calcitonin
Which is more potent T3 or T4?
T3 is 4x more potent than T4
Where is the majority of T3 produced?
Majority of T3 produced from peripheral conversion of T4 to T3
What medications inhibit the peripheral conversion of T4 to T3?
Inhibited by beta-blockers, corticosteroids, amiodarone
What is the biosynthesis of thyroid hormones?
Hypothalamus produces thyrotropin-releasing hormone (TRH)
Stimulates pituitary gland to synthesize and release thyroid stimulating hormone (TSH)
Circulating TSH stimulates thyroid gland
Concentrate iodine
Synthesize thyroid hormone
release thyroid hormone
Peroxidase enzymes catalyze iodination of tyrosine on thyroglobulin forming MIT and DIT
Coupling of 1 DIT and 1 MIT or 2 DIT, to form T3 and T4
What do cardiac glycosides do to iodine concentration?
Cardiac Glycosides-by inhibiting potassium accumulation can block iodide uptake
What do bromine, fluorine, and lithium do to iodine concentration?
Bromine, Fluorine, Lithium- block transport of iodide into thyroid
What is the ratio release of T3:T4?
Release ratio (T4:T3) = 4:1 (releasing more T4 than T3
Is T3 or T4 absorbed at a higher rate and which is more active?
T3 absorbed at higher rate, more active
How is T3 transported into the plasma?
Thyroid Binding Globulin (TBG)
Albumin
Thyroid Binding PreAlbumin (TBPA)
What percentage of thyroid hormone is protein bound?
99%
What is the only portion of hormone that is available to elicit biological effect and regulate TSH?
Free hormone
What are the effects of thyroid hormone?
- Determination of basal metabolic rate
- Influence of growth through stimulation of growth hormone synthesis and action
- Body temp
- Fetal development
- Cardiac rate and contractility
- Peripheral vasodilatation
- Red cell mass and circulatory volume
- Respiratory drive
- Peripheral nerves (reflexes)
- Hepatic metabolic enzymes
- Bone turnover
- Skin and soft tissue effects
What is a clinical and biochemical syndrome resulting from decreased thyroid hormone?
Hypothyroidism
What is a clinical and biochemical syndrome resulting from increased thyroid hormone?
Hyperthyroidism
What labs should be assessed for thyroid dysfunction?
Total T4- free and bound
Free T4 (FT4)- more reliable than total T4 and T3 levels
Sensitive TSH- evaluates the negative feedback system
What is TSH increased in?
Increased in primary hypothyroidism (something is wrong with the thyroid its not releasing enough thyroid hormone and its feedback to the pituitary saying to release TSH)
What is sensitive TSH decreased in?
Decreased in primary hyperthyroidism (thyroid is producing thyroid hormone and sending feedback to pituitary saying not to release TSH)
What are the thyroid function test results with hyperthyroid?
Total T4- Elevated
Free T4- Elevated
Total T3- Elevated
TSH- LOW
What are the thyroid function test results with hypothyroid?
Total T4- low
Free T4- low
Total T3- low
TSH- ELEVATED
What are the increased thyroid binding globulin thyroid function test results?
Total T4- Elevated
Free T4- Normal
Total T3- Elevated
TSH- Normal
What is a serum TSH concentration above statistically defined upper limit of reference range?
Sub-clinical hypothyroidism
What are the CV effects of sub-clinical hypothyroidism?
Increased risk of coronary heart disease
What are the fertility and pregnancy effects of sub-clinical hypothyroidism?
Placental abruption risk 3x higher
Preterm delivery risk 2x higher
Women with thyroid autoantibodies have increased risk for abortion
What are the signs and sx of HYPOthyroidism?
Tiredness Lethargy, Muscle pains Weight gain Intolerance to cold Dry skin, Coarse skin Bradycardia Mental impairment Dry thinning hair
What are the effects of hypothyroidism on the cardiovascular system?
Systolic Dysfunction Reduced stress tolerance during exercise Cardiac autonomic dysfunction Reduced oxygen uptake during exercise Diastolic hypertension Increased arterial stiffness Pro-atherosclerotic profile Increased total cholesterol Increased LDL Insulin resistance Pro-coagulative pattern Decreased fibrinolytic capacity Decreased activity Von Willebrand factor Factor VIII
What are the effects of hypothroidism on digitalis (digoxin)?
Decreased volume of distribution (push them into digoxin toxicity)
What are the effects of hypothyroidism on insulin?
Impaired degradation
What are the effects of hypothyroidism on warfarin?
Delayed catabolism of clotting factors
What are the causes of primary hypothyroidism?
Hashimotos Disease
Iatrogenic hypothryoidism
Iodine deficiency
What are the causes of secondary hypothyroidism?
Pituitary disease (Most common reason) Hypothalamic disease
What are the increased risk factors for hypothyroidism?
Postpartum women
Family history of autoimmune thyroid disorders
Patients with previous head and neck of thyroid irradiation or surgery
Other autoimmune endocrine (DM type 1, adrenal insufficiency)
Non endocrine conditions (celiac disease, vitiligo, MS, pernicious anemia, Down’s syndrome)
What are the signs and sx of hypothyroidism in the elderly?
Hypothyroidism often with few specific signs or symptoms, often subtle Hoarseness Deafness Confusion Dementia Ataxia Depression Dry skin Hair loss
What is an autoimmune disease resulting in fibrosis of the thyroid gland, antibodies to TSH receptor?
Hashimotos thyroiditis
What is the most common cause of hypothyroidism?
Hashimotos Thyroiditis
How does hashimotos thyroiditis work?
Selective destruction of thyroid gland ↓ thyroid hormone and ↑ TSH levels
What does congenital (infantile) hypothyroidism result in?
Dwarfism and mental retardation (cretinism)
What is myxedema?
Patients appear to have edema beneath the skin (Thickening of facial features, puffy & pallid skin, somnolence, slow mentation, muscle weakness, hypothermia, hoarseness, dryness/loss of hair) (End stage hypothyroidism)
Due to removal or loss of functioning thyroid gland
What is the most severe form of hypothyroidism that sometimes causes a coma?
Myxedema
What are the clinical features of myxedema?
Hypothermia
Advanced hypothyroid symptoms
Altered sensorium (from delirium to coma)
What are the drug treatments for HYPOthyroidism?
Thryoid USP Armour Thyroglobulin Proloid Levothyroxine, synthroid, levothroid, levoxyl, unithroid Liothyronine, thyro-tabs, cytomel Liotrix
What is the content of Levothyroxine, synthroid, levothroid, levoxyl, unithroid?
Synthetic T4
What is the content of Liothyronine, thyro-tabs, cytomel?
Synthetic T3
Which two hypothyroidism managements are rarely used today due to allergic reactions?
Thyroid USP; (Thyrar, Thyroid Strong, S-P-T)
Thyroglobulin (Tg; Proloid)
Levothyroxine (Synthroid, Levothroid, Levoxyl, Unithroid)- MOA
Isomer of T4 (L-thyroxine) is converted to T3
What is the DOC for hypothyroidism?
Levothyroxine (Synthroid, Levothroid, Levoxyl, Unithroid)
Due to being chemically stable, inexpensive, free antigenicity, uniform potency
Should Levothyroxine (Synthroid, Levothroid, Levoxyl, Unithroid) be taken with food or on an empty stomach?
TAKE ON AN EMPTY STOMACH
What is different about the script for levothyroxine?
MUST check the DO NOT substitute line
Levothyroxine- ADRs
Arrhythmias Tachycardia Anginal pain Cramps HA Restlessness Sweating Weight loss Osteoporosis
Levothyroxine- contraindications
Thyrotoxicosis
Levothyroxine- Monitoring
Every 6-8 weeks until TSH normalized, then every 6-12 months
If doses changed, recheck TSH in 2-3 months
Clinical evaluation of symptoms indicative of treatment response
Levothyroxine- drug interactions
Altered absorption -Cholestyramine, Ferrous sulfate, Sucralfate, Aluminum hydroxide
Increased metabolism- Rifampin, Phenytoin, Carbamazepine
Oral (if pt is on these drugs then levo is no longer DOC) Contraceptives/Estrogens
Increase thyroid binding globulin, resulting in lower free thyroid hormone
Lithium
Inhibits synthesis and release of thyroid hormone
Amiodarone
Blocks conversion to T4 to T3
Warfarin
Increases metabolism of clotting factors
Liothyronine Sodium (Cytomel, Triostat)- Indications
Initial therapy of myxedema (skin disorder) and myxedema coma
Short-term suppression of TSH in patients undergoing surgery for thyroid cancer.
Patients w/5’-deiodinase deficiency who cannot convert T4 to T3.
Is Liothyronine used for maintenance?
Liothyronine generally not used for maintenance replacement therapy because of its short half-life and duration of action.
Liotrix (Euthroid, Thyrolar)- indications
Used for thyroid hormone replacement
The idea is that the combo mimics the normal ratio secreted by the thyroid gland but is not any more effective than levothyroxine.
How do you treat myxedema coma?
IV bolus levothyroxine 300-500mcg
Maintenance 75-100 mcg IV until able to switch to PO
IV hydrocortisone 100mg q 8h until coexisting adrenal suppression is ruled out
Supportive therapy- ventillation, euglycemia, blood pressure, body temp maintained
How do you treat with congenital hypothyroidism?
Initial therapy within 45 days of birth at 10-15mcg/kg/d, associated with improved IQ’s in treated infants
Dose progressively decreased to typical adult dose beginning 11-20 years
AGGRESSIVE THERAPY IMPORTANT FOR NORMAL DEVELOPMENT
What is hypothyroidism in pregnancy associated with?
Associated with increased risk of still-births
IQ of children born to women with untreated hypothyroid have lower IQ
Thyroid necessary for fetal growth; provided by mom during first 12 weeks of gestation
Congenital deficiency associated with decreased physical/ mental activity, CV, GI, neuromuscular function
Where does the fetus get thyroid hormone?
hormone comes form mom during first 12 wks of pregnancy and not until after 12 wks so they produce their own.
What is the treatment for hypothyroidism in pregnant patients?
Treatment: levothyroxine
20% requires dose increase during pregnancy/ decrease after (if they have hypothyroidism before pregnancy)
Typically require 36 mcg/day increase in dosage
Mostly important during the first 12 wks of pregancy
What does hyperthyroidism result from?
Overproduction of endogenous hormone
Exposure to excess endogenous hormone
Elevated free and total T3, T4 or both serum
What is the TSH level with hyperthyroidism?
Low serum concentrations TSH Suppressed TSH Peaks among 20-39 yo Declines among 40-79 yo Increases among 80+ Female>men Subclinical TSH 13.2 mcg/dL
What are the signs and sx of HYPERthyroidism?
Nervousness Anxiety Palpitations Increased basal metabolic rate (BMR) Weight loss Increased appetite Increased body temp (heat intolerance) Sweating Fine Tremor Tachycardia Classical ophthalmic signs
What is the most common cause of hyperthyroidism?
Graves Disease
What is an autoimmune syndrome that includes hyperthyroidism, diffuse thyroid enlargement, myxedema and thyroid acropachy?
Graves disease
What is happening with graves disease?
Antibodies against thyroid cell
IgG type antibodies against the TSH receptors that bind to and activate the receptor.
Genetic predisposition
8x more likely in women than men
What is the TSH level with Graves disease?
TSH undetectable from negative feedback from elevated thyroid hormone (thryoid levels get so high that the TSH levels drop to nearly undetectable)
What is hyperthyroidism in pregnancy almost always caused by?
Graves Disease
Inappropriate production of human chorionic gonadotropin (hCG) can cause subclinical or overt hyperthyroidism
Gestational trophoblastic disease
In untreated women with hyperthyroidism caused by graves disease what are the complications that are more common?
Spontaneous abortion Premature delivery Low birth weight Eclampsia Pregnancy itself can improve Graves with decreased doses of drug or even discontinuation of treatment by 3rd trimester
What is the treatment of choice for graves disease and pregnancy?
PTU is drug of choice at lowest effective dose
Methimazole has some data suggesting possible teratogenicity
RAI contraindicated in pregnancy
Surgery not recommended
What should patient treated for hyperthyroidism during pregnancy be reevaluated for?
Pts treated for hyperthyroidism during pregnancy need to be reevaluated postpartum- disease can worsen
What is a life threatening medical emergency characterized by sever thyrotoxicosis, high fever (often >103F), tachycardia, tachypnea, dehyration, delirium-coma, N/V, and diarrhea associated with hyperthyroidism?
Thyroid storm
What are the precipitating factors for thyroid storm?
Infection, trauma, surgery radioactive iodine treatment, withdrawl from antithyroid drugs
What is the tx for thyroid storm?
Aggressive treatment lowers mortality to 20%
Suppression of thyroid hormone formation and secretion
Anti-adrenergic therapy
Administration corticosteroids
Treatment of complications
What are the thioamides for tx of hyperthyroidism?
Propylthiouracil (PTU) (DOC in pregnancy)
Methimazole (Tapazole)
Propylthiouracil (PTU), Methimazole (Tapazole) (thioamides)- MOA
Thioamide
MOA: Block thyroid hormone Synthesis
Propylthiouracil (PTU), Methimazole (Tapazole) (thioamides)- indications
Management of hyperthyroidism
Thyrotoxic crisis- to get patient undercontrol before you undergo surgery or radiation
In the preparation of patients for surgical subtotal thyroidectomy
Does MMI or PTU have less side effects?
MMI
Which is more potent MMI or PTU?
MMI generally has fewer side effects
MMI 10x more potent than PTU
Requires lower dosages
Propylthiouracil (PTU), Methimazole (Tapazole) (thioamides)- ADRS
If given in excessive amounts over a long period, thioamides may cause hypothyroidism and enlargement of the thyroid gland.
Most serious ADRs—these usually occur in ~ 0.5% of pts w/in first 3 months of therapy
Arganulocytosis-must obtain baseline white blood cell count (stop if develop fever or sore throat)
Hepatotoxicity-baseline white blood cell count (stop if pt. develops fever or sore throat)
Vasculitis-drug induced lupus or anti-neutrophil
Most frequent ADRs Rash Arthralgia Myalgia Cholestatic jaundice Lymphadenopathy Drug fever Psychosis Alopecia
Iodines and Iodine-Containing Agents (Potassium Iodine (KI)(Thyro-block,Lugol’s)- MOA
Iodine causes inhibition of thyroid hormone secretion
Iodines and Iodine-Containing Agents (Potassium Iodine (KI)(Thyro-block,Lugol’s)-indications
Indications- trying to get the thyroid gland down in size before surgery
Preoperatively for thyroidectomy (7-14 days)
Used after RAI (3-7 days), to allow RAI to concentrate in thyroid
Iodines and Iodine-Containing Agents (Potassium Iodine (KI)(Thyro-block,Lugol’s)-contraindications
Should not be given to breastfeeding women, can cause a goiter in infants.
When should iodine and iodide not be given?
Iodine and iodide are given 10-14 days prior to partial thyroidectomy w/PTU or methimazole. They should not be given long-term because they loose their effectiveness.
Iodines and Iodine-Containing Agents (Potassium Iodine (KI)(Thyro-block,Lugol’s)- ADRS
Hypersensitivity rxn HA Lacrimation Conjunctivitis Laryngitis Thyrotoxicosis in patients w/nontoxic goiter Drug fever Acneform rash Metallic taste in mouth
What is the DOC for hyperthyroidism?
Radioiodine
Radioiodine- Indications
Agent of choice for Graves, toxic autonomous nodules, toxic multinodulor goiters
Radioiodine MOA
Goal is to destroy overactive thyroid cells:
Radioiodine- major disadvantage
Hypothyroidism in most patients
Can not be used in pregnancy
Hypothyroid often occurs months-years after RAI
Women more likely to become hypothyroid
African Americans are most likely to be resistant to RAI (require multiple doses)
Lithium Carbonate- MOA
Lithium inhibits thyroidal incorporation of I- into thyroid gland
Inhibits the secretion of thyroid hormones from follicular cells
Lithium carbonate- Indications
Offers no advantage over thioamide but maybe used for temporary control of thyrotoxicosis in patients allergic to thioamides and iodine.
Beta-Adrenergic Antagonists
Used to ameliorate thyrotoxic symptoms: palpitations, anxiety, tremor, heat intolerance
Symptoms of thyrotoxicosis mimic symptoms associated with sympathetic stimulation, thyroid hormone ↑ β1 receptors in the heart by 50-100%
Adjunct therapy- no effect on peripheral thyrotoxicosis and therapeutic effect
What are the corticosteroids?
Dexamethasone
Prednisone
Methylprednisolone
Hydrocortisone
Corticosteroids (Dexamethasone, Prednisone, Methylprednisolone, hydrocortisone)- Effects and indications
Effects:
Decreases thyroid action
Decreases immune response in Grave’s disease
USEFUL IN THYROIDITIS AND THYROID STORM
What are the indications for a thyroidectomy?
Large glands
Severe ophthalmopathy
Lack of remission on treatment
On who should thyroidectomy not be done one?
Should not be done on patients with low RAI uptake
What should be given up until the thryoidectomy?
Propylthiouracil (PTU) or methimazole (MMI) until pt is euthyroid (6-8 weeks) followed by iodide 500 mg/day x 10-14 days Beta blocker (propranolol/ nadolol) pre- and post-surgery to maintain HR <90 bpm
What are the complications of thyroidectomy?
Complications depend on how much of the thyroid is removed. Hyperthyroidism Hypothyroidism Hypoparathyroidism Vocal cord abnormalities
What are the drug interactions that need to be considered when adding a thyroid agent or an antithyroid agent?
WARFARIN
LITHIUM
Diabetes medication requirements may change
Potassium iodide used as expectorants
CARDIAC GLYCOSIDES SUCH AS DIGOXIN MAY REQUIRE DOSE ADJUSTMENTS
AMIODARONE
CNS depressants
What drugs can cause decreased TSH?
Dopamine Levodopa Bromocriptine Octreotide Amphetamin Glucocorticoids (dexamethasone, hydrocortisone)
What drugs can cause increased TSH?
Metoclopramide
Amiodarone
Iodinated contrast media
What drugs can cause increased free T4?
IV fureosemide IV heparin Amiodarone Iodinated contrast media NSAIDS Salicylates Salsalate Diclofinac Naproxen
What drugs can cause decreased free T4?
Phenytoin
Carbamazepine
Where does most T3 result from?
Peripheral conversion of T4
What drugs inhibit the conversion of T4 to T3?
Beta blockers and corticosteroids interfere minimally (Propranolol, atenolol, metoprolol)
Corticosteroids reduce T3 (useful in thyroid storm or severe hyperthyroidism)
Amiodarone and iodinated contrast media can inhibit conversion in the peripheral and pituitary gland
What can cause drug induced thyroid disease?
Iodides Iodine induced hyperthryoidism Iodine induced hypothyroidism Lithium Interferon alpha (IFNalpha)
What iodides cause thyroid disease?
In multiple prescription products Amiodarone Radiocontrast dye Povidone iodine- soaps used prior to surgery Iodinated glycerol In non-prescription products Cough and cold Kelp Herbals Dietary supplements/ weight loss products
When does iodine induced hyperthryoidism (Jod-Basedow diease) develop and how is it treated?
Develops within 3-8 weeks after exposure in up to 5% pts
Treatment with thioamides and beta blockers
What is the treatment of iodine induced thyroid disease?
Up to 10% of amiodarone treated patients will develop
Treat with levothyroxine replacement
What is the treatment of lithium induced thyroid disease?
Up to 50% of pts can develop hypothyroidism
Important to monitor TSH first
Goiter may develop in pts without developing hypothyroidism
More likely in patients on lithium treatment for >2 years
More likely in patients with pre-existing autoantibodies
Treatment with levothyroxine can reverse hypothyroidism
Can spontaneously resolve without treatment
Stopping lithium does not always resolve symptoms or goiter
May require surgical intervention
What thyroid disease results from interferon alpha?
used For hepatitis C treatment or chemotherapy
Not likely with interferon beta
Prevalence 2.5% to 20% induced thyroid disease
Can occur within 6-8 weeks of starting therapy or occur 6-23 months after start
Hypothyroidism most likely, hyperthyroid may occur
Typically dysfunction is transient and does not necessitate treatment in all cases
Can “unmask” pre-existing thyroid disorder
Hypothyroidism resolves spontaneously within 2-3 months after stopping therapy in most patients- may take longer
