thyroid disorders pt 1 Flashcards
What organ releases TRH
hypothalamus
what organ releases TSH
anterior pituitary
T3 and T4 comes from what organ?
thyroid
explain the HPT axis
Hypothalamus releases TRH, causing anterior pituitary to release TSH, which causes thyroid to release T3 and T4
T3 and T4 tells hypothalamus and anterior pituitary to stop making TRH and TSH
large glycoprotein synthesized by follicular cells of the thyroid; released into the colloid
Thyroglobulin (Tg)
element actively absorbed by the thyroid for hormone synthesis
iodine
an enzyme; helps process iodine for use by thyroid
Thyroid Peroxidase (TPO)
how much iodine is in the thyroid compared to in serum?
30x concentration in thyroid vs serum
what deficiency is common in developing countries and is associated with goiter, hypothyroidism, and mental retardation
iodine
if there is no thyroglobulin, what happens to T3 and T4 lvls? TSH and TRH lvls?
decreases
increases
if a pt has an iodine deficiency, what happens to their T3 and T4 lvls? TSH and TRH?
decreases
increases
describe the process of when thyroid hormone is needed
- Organified Tg (with attached T3/T4 molecules) is absorbed via pinocytic vesicles into the thyroid cells
- Proteases release T3 and T4 molecules in free form
- T3 and T4 then diffuse through the cell
- T3 and T4 are released into circulation
once T3 and T4 enter the blood, what happens next?
99% of T3 and T4 bind immediately with plasma proteins synthesized by the liver
what is the primary binding protein (80% of T3/T4) of thyroid hormones? others?
Thyroxine-binding globulin (TBG)
transthyretin (TTR), albumin
which thyroid hormone is mostly bounded to protein, T4 or T3?
about 99.8% of T4 and 70-99% of T3 are protein-bound
pts taking oral thyroid hormone replacement therapy should avoid doing what?
taking it with meals
- T3 and T4 have high affinity to bind to proteins = decreasing effects
onset of when T4 and T3 are released into tissues
T4 - ½ of serum T4 is released to the cells every 6 days
T3 - ½ of serum T3 is released to the cells every day (due to lower affinity)
Most T4, once absorbed by tissues, is converted to? By?
T3 by deiodinases
rT3 may be elevated in:
Starvation/Anorexia
Trauma
Shock
Severe infections
Postoperative state
Burn patients
Certain medications
- increases functional activity in tissues
- Promote nuclear transcription of numerous genes
- ↑ enzymes, structural and transport elements, metabolic activities
thyroid hormones
which thyroid hormone binds to thyroid hormone receptors (TRs), which then bind to retinoid x receptors (RXRs)
T3
____ complex alters gene expression
Typically cause the target gene to be expressed
TR-RXR complex
how does thyroid affect growth?
Promotes growth of skeletal tissue and skeletal maturation
Promotes growth/development of brain in fetal phase, first few years of life
how does thyroid affect carbohydrate metabolism
Promotes all aspects of carbohydrate metabolism
Glucose absorption and uptake, gluconeogenesis, glycolysis, insulin secretion
how does thyroid affect fat metabolism
- Promotes all aspects of fat metabolism
- Increased free fatty acids and decreased body fat stores
- Decreased concentrations of cholesterol, phospholipids, triglycerides
- Increased secretion of cholesterol in bile acids - Helps reduce likelihood of fatty deposits in the liver
how does thyroid affect vitamin metabolism
Thyroid hormone increases numbers of many enzymes
Many vitamins are used in enzymes/coenzymes
Thyroid hormone increases our baseline need for vitamins
how does thyroid affect BMR
- Promotes healthy basal metabolic rate through keeping metabolic activity of the body at a standard level
- Increased thyroid hormone → 60-100% increase in BMR
- Decreased thyroid hormone → up to 50% reduction in BMR
how does thyroid affect body weight?
Thyroid hormone generally helps decrease/maintain healthy body weight
Thyroid hormone can also increase appetite
how does the thyroid affect the CV system
- Increased blood flow to tissues
- Increased metabolism → increased O2 utilization
- Increased metabolic heat generation → vasodilation
- Increased cardiac output - Increased heart rate
- From increased cardiac output and excitatory effect on the heart - Increased heart strength
- Only if there is a slight increase in thyroid hormone
- Major increase (pathologic) → weakened heart due to long-term and excessive protein catabolism
how does thyroid affect the CNS
- Excitatory effects on nerve stimulation
- High (pathologic) levels → nervousness, anxiety, paranoia, tremor, insomnia (with associated fatigue)
- Low (pathologic) levels → depression, fatigue, cognitive difficulties, hypersomnia
how does thyroid affect the muscles?
- Increased reactivity and vigor
- High (pathologic) levels → weakness (excess protein catabolism)
- Low (pathologic levels → sluggish; slow post-contraction relaxation
how does thyroid affect the rsp system?
↑ metabolism → higher O2 need → increased breathing rate/depth
how does thyroid affect the endocrine system?
- Pancreas - increased insulin secretion
- Parathyroid - increased PTH secretion
- Adrenal - increased glucocorticoid secretion
- Reproductive - promotes normal sexual function
- High (pathologic) level → impotence in males, oligomenorrhea in females
- Low (pathologic) level → decreased libido, menstrual irregularities (heavy or light/absent)
what does the typical thyroid panel include?
TSH
T3
T4
Free T4 or FT4
purpose of TSH lab and any interfering factors
- Uses: General assessment of thyroid function
- Sometimes ordered alone to screen - Interfering Factors
- Elevation: antithyroid medications, lithium, iodine, severe illness
- Depression: heparin, NSAIDs (including ASA), dopamine, steroids, severe illness
- Diurnal variation: Peak TSH at ~10 pm and trough TSH at ~10 am
if a pts lab showed high TSH, what does that mean? what could be the causes?
-
Not enough T3/T4
- Primary hypothyroidism
- Thyroiditis
- Large doses of iodine (including radioactive iodine)
- Inadequate thyroid hormone dose - Overfunctioning pituitary gland
- Pituitary TSH-secreting tumor
if a pt shows low TSH labs, what does that mean?
-
Too much T3/T4
- Primary hyperthyroidism
- Excess or suppressive doses of thyroid hormone - Underfunctioning pituitary gland (secondary hypothyroidism)
- Underfunctioning hypothalamus (tertiary hypothyroidism)
uses for T3 and T4 labs and interfering factors
- Uses: Assessment of thyroid function
- Part of thyroid panel or follow-up to other abnormal thyroid studies - Interfering Factors
- Elevation: increased TBG (estrogenic meds, pregnancy, methadone)
- Depression: decreased TBG, protein-bound drugs (NSAIDs, phenytoin), androgens, lithium
- Note: T3 is less stable than T4 due to lower protein binding
uses for Free T3 and Free T4 labs and interfering factors
- Assessment of thyroid function
- Usually ordered as part of thyroid panel or as combo (e.g., TSH+FT4)
- May be a follow-up to other abnormal thyroid function studies
- Helps reduce confounding factor of serum protein levels - Interfering Factors
- Note: Neonates have higher levels of FT4; typically screened using total T4
if a pt shows high levels of T3, T4, free T3, and free T4, what does that mean?
- Excess amounts of thyroid hormone
- Hyperthyroid states (over-functioning thyroid gland)
- Acute thyroiditis
- Ectopic thyroid tissue
- Excess dosing of thyroid meds - Increased serum proteins, including TBG
if a pt shows low T3, T4, Free T3, and Free T4, what does that mean?
- Insufficient amounts of thyroid hormone
- Hypothyroid states (under-functioning thyroid gland)
- Iodine insufficiency
- Inadequate dosing of thyroid medication - Protein-depleted state
- Malnutrition, nephrotic syndrome - T3 and Free T3 - Decreased conversion of T3 (liver disease, severe illness)
- T4 and Free T4 - T3-only medications
uses and interfering factors of TBG labs
- Uses: Evaluation of abnormal total T3 or total T4 levels
- Can help determine if patient is truly hypo/hyperthyroid versus just having abnormal levels of bound/unbound T3/T4 - Interfering Factors
- Conditions affecting protein production: Liver disease, Malnutrition, meds
high TBG lvl means?
- Elevated estrogen
- Pregnancy, oral contraceptives, MHT - Infectious hepatitis
low TBG lvls mean? (causes)
- Hypoproteinemia
- Nephrotic syndrome
- Liver disease
- Malabsorption/malnutrition - Ovarian failure
- Elevated testosterone levels
- Major stress
what is the TRH stimulation test? (uses, interfering factors)
- Released from: Hypothalamus (TRH)
- Uses: Assessment of pituitary response to TRH
- help differentiate etiology of hypothyroidism
- help evaluate degree of pituitary suppression in hyperthyroid pts
— Not commonly used since highly sensitive TSH assays developed - Interfering Factors
- Normal response may be exaggerated in women and pregnancy
- Normal response may be diminished in the elderly and in pts with MDD
if the TRH stimulation test comes back normal what does that mean?
2x increase in baseline TSH within 30 minutes of TRH IV bolus
May also be seen in hypothyroidism due to severe illness
if there is no increase in TSH during the TRH stimulation test what is the interpretation?
Secondary Hypothyroidism
if there is a Delayed increase in baseline TSH (60-120 minutes) from TRH stimulation test, what is the interpretation
Tertiary Hypothyroidism
during a TRH stimulation test is shows a Blunted TSH response due to maximal pituitary suppression by T3/T4
what interpretation?
hyperthyroidism
hypothyroidism Due to failure of thyroid to release T3 and T4
is what type?
primary
hypothyroidism Due to failure of pituitary to release TSH
is what type?
secondary
hypothyroidism Due to failure of hypothalamus to release TRH
is what type?
tertiary
hypothyroidism is MC in who?
women - 5-8x more common
Maternal hypothyroidism can lead to what result?
significant decrease in fetal IQ
causes of hypothyroidism
- Worldwide - Iodine deficiency
-
Developed Countries - Hashimoto
- Chronic lymphocytic thyroiditis, Chronic autoimmune thyroiditis - Also seen with:
- Iatrogenic - thyroidectomy, radioiodine therapy, radiation
- Cancer - Cancer and/or chemotherapy
- Meds - Amiodarone, Lithium
- Hepatitis C
clinical presentation of hypothyroidism
General - fatigue, weakness, weight gain
Integumentary - dry skin, hair loss
GI - dysphagia, constipation, poor appetite
Neuro - cognitive impairment, paresthesias
Psych - depression
EENT - hoarseness
MSK - arthralgias, myalgias
Respiratory - dyspnea
Reproductive - lower libido, ED, irregular menses
—-
General - weight gain
Integumentary - dry skin, sparse and coarse hair, thin and brittle nails
Cardiovascular - bradycardia, edema
Myxedema - puffiness of face, hands, feet
Neuro - Delayed DTR relaxation, carpal
tunnel syndrome (CTS)
EENT - Thinning of the outer eyebrows
Other -
Serous effusions (joints, peritoneal, pleural)
Cool extremities
what labs would you get for primary hypothyroidism, what would you see? other lab abnormalities?
- Screen with serum TSH (+/- FT4)
- TSH - high
- FT4 - low - other labs
- Anemia
- Lipid abnormalities - increased LDL, triglycerides, lipoprotein(a)
- Hyponatremia
- Hypoglycemia
- Elevated prolactin
if your thyroid labs show (+) anti-thyroid peroxidase antibody (anti-TPO) and (+) anti-thyroglobulin antibody (anti-Tg), what does that indicate?
Hashimoto’s Thyroiditis
90-95% chance of (+) anti-thyroid peroxidase antibody (anti-TPO)
70% chance of (+) anti-thyroglobulin antibody (anti-Tg)
what is usually not needed to make a diagnosis of hypothyroidism (Acute)
Imaging Studies
- Often not indicated in simple cases
- Consider if thyromegaly or thyroid nodule noted on exam
if you need to do imaging for hypothyroidism, what can you get? what else could you find?
-
Thyroid Ultrasonography - noninvasive, relatively inexpensive
- Dependent on skill of sonographer
- May be limited in patients with obesity - Other Imaging - CT, MRI can be used to visualize thyroid gland
-
Other Imaging Findings
- Enlarged thymus - possible if autoimmune thyroiditis is present
- Enlarged pituitary - possible if hyperplasia of TSH-secreting cells occurs
(imaging not indicated in simple cases)
complications with hypothyroidism
- Cardiovascular Disease - Exacerbations of CAD and HF possible when starting LT4 therapy
- Adrenal Disease - Starting LT4 may cause adrenal crisis
- Reproductive - Untreated, may cause infertility
- If untreated during pregnancy, may lead to miscarriage - Pulmonary - May have higher bacterial pneumonia risk
- GI - May have increased risk of megacolon
-
Myxedema Crisis - Severe, life-threatening hypothyroidism
- triggered by infection, illness, cold exposure, or drug use
- MC - elderly women who have a stroke or stop taking thyroid meds
an elderly woman with a hx of hypothyroidism comes into the ER with hypothermia, hypotension, hypoventilation, hyponatremia, hypoglycemia, cognitive impairment. what could she be experiencing?
Myxedema Crisis
- Cognition ranges from mild confusion to myxedema coma
- May rarely see rhabdomyolysis and acute kidney injury
tx for myxedema crisis
IV levothyroxine (LT4) therapy
- myxedema coma - supplement with IV T3 (liothyronine)
- Supportive - warming blankets, intubation, tx of underlying cause
what is Subclinical Hypothyroidism
- Normal serum FT4 with TSH above reference range
- MC in elderly (>65 y/o) pts - up to 13% - Manifestations - asx or mild hypothyroid s/s
-
Tx - observation if no s/s
- May do trial of LT4 if symptomatic - Resolves spontaneously in ⅓ of cases within 2 years
management/tx for hypothyroidism
-
First-line - levothyroxine
- Combination T3/T4 therapies - dessicated thyroid; liotrix
- Synthetic T3 - liothyronine - Starting levothyroxine
- Healthy, young/middle-aged pts - 25-75 mcg PO QD = stronger
- Elderly or CAD pts - 25-50 mcg PO QD = weaker
- Note - evaluate clinically for adrenal insufficiency/angina before start
dosage considerations for levothyroxine
Take on an empty stomach, with water, at a regular time daily
Peak response usually seen in ~4 weeks
Different preparations = different bioavailability!
what factors would have increased thyroid hormone requirements
- Medications - many anticonvulsants, sertraline, bile acid-binding resins, PPIs
- Increased estrogen - pregnancy, estrogen-containing medications
- GI Disorders - celiac disease, IBD, lactose intolerance, gastritis
- Weight gain - over 10% body weight
what factors would have Decreased thyroid hormone requirements
- Decreased estrogen - cessation of estrogenic meds, postpartum, post-oophorectomy
- Increased androgen - starting testosterone therapy
- Weight loss - over 10% body weight
BBW for thyroid hormone replacement therapies
the use of thyroid hormone replacement as a treatment for obesity
pt on thyroid replacement hormone shows elevated TSH, how do you manage?
inadequate thyroid hormone replacement therapy
Verify how patient is taking medication!
pt on thyroid replacement hormone shows normal TSH, how do you manage?
adequate thyroid hormone replacement therapy
1. May need high-normal TSH if pt has history of CAD or atrial fibrillation
2. If still symptomatic…
- May consider free T3/T4 levels to evaluate adequacy of therapy
- May consider T3 supplement or changing to combination T3/T4 (controversial)
pt on thyroid replacement hormone shows low/suppressed TSH, how do you manage?
excess thyroid hormone replacement therapy
- Consider severe systemic illness or hypopituitarism
- Meds - NSAIDs, opioids, CCBs, steroids
- Suppressed TSH (0.03 mIU/L or less) - risk of atrial fibrillation, osteoporosis
indications for levothyroxine (LT4)
Hypothyroidism, TSH suppression (cancer/goiter)
dosing for Levothyroxine (LT4)
- 25-75 mcg daily OR 1.6 mcg/kg; titrate every 4-6 weeks to euthyroid status
- Elderly or CAD - 25-50 mcg daily; titrate by 12.5-25 mcg every 4-6 weeks
- Timing - take with water 30-60 min before food or other meds
SE of Levothyroxine (LT4)
Similar to effects of hyperthyroidism!
CV - angina, palpitations, tachycardia, arrhythmia, CHF, flushing
CNS - anxiety, fatigue, insomnia, irritability, pseudotumor cerebri (peds)
Endocrine - menstrual irregularities, weight loss
GI - abdominal cramps, V/D, increased appetite
CI of LT4
hypersensitivity to rx; acute MI; thyrotoxicosis; uncorrected adrenal insufficiency
monitoring needed for LT4
TSH Q 4-6 wks after start/dose changes, then Q 6-12 mo
indications for Liothyronine (LT3)
Hypothyroidism, myxedema, goiter suppression
SE of LT3
Similar to effects of hyperthyroidism!
CV - arrhythmia, tachycardia, hypotension or HTN, MI, CHF
CNS - twitching, irritability, nervousness
Endocrine - menstrual irregularities, weight loss
GI - abdominal cramps, diarrhea, vomiting
CI of LT3
hypersensitivity to rx; acute MI; thyrotoxicosis; uncorrected adrenal insufficiency
monitoring for LT3
TSH Q 4-6 wks after start/dose changes, then Q 6-12 mo
indications for desiccated thyroid
Hypothyroidism
AACE does not recommend use for tx of hypothyroidism
dosing for desiccated thyroid
15-30 mg (¼-½ grain) daily initially; titrate every 6 weeks to euthyroid status
- Elderly - Not recommended
- Dose equivalency - 65 mg (1 grain) = ~88-100 mcg of levothyroxine
- Timing - ideally, take with a sip of water 30-60 min before food or other meds
SE of desiccated thyroid
Similar to effects of hyperthyroidism!
- CV - angina, palpitations, tachycardia, arrhythmia, CHF
- CNS - anxiety, fatigue, insomnia, irritability
- Endocrine - menstrual irregularities, weight loss
- GI - abdominal cramps, diarrhea, vomiting, increased appetite
CI of desiccated thyroid
hypersensitivity to rx, beef, or pork; acute MI; thyrotoxicosis; uncorrected adrenal insufficiency
monitoring for desiccated thyroid
TSH Q 4-6 wks after start/dose changes, then Q 6-12 mo
