Lecture 37-38 Thyroid conditions Flashcards
(28 cards)
What are the thyroid hormones, their t1/2, etc
T4 (thyroxine): main hormone secreted, biologically inactive ⇒ converted to T3, 99.96% protein bound, t1/2 = 7 days
T3 (triiodothyronine): 80% converted in periphery from T4, biologically active, 3x as potent as T4 inhibiting TSH, 99.5% protein bound, t1/2 = 1-2 days
What is the TSH lab test (ref range, what it indicates)
primary screening test for thyroid dysfunction and for monitoring response to thyroid hormone replacement
Ref Range: 0.2-6.5 mIU/L
varies diurnally by up to 50% of mean values - values tend to be lowest in late afternoon and highest around midnight
not reliable in cases of suspected pituitary disease (free T4 preferred)
ref range differs in pregnancy and old age
this elevated - hypothyroidism, recovery from severe illness
this low - hyperthyroidism
What is the free T4 lab test (ref range, what its used for)
Ref Range: 10-25 pmol/L,, measures unbound this in serum
most accurate reflection on thyrometabolic status - primary hormone released from thyroid
measured to confirm diagnosis of hypo/hyperthyroidism
What is the free T3 lab test (ref range, what its used for)
Ref Range: in adults 3.5-6.5 pmol/L
generally not used to assess hypothyroidism
these levels are often low in absence of thyroid disease - severe illness also shows reduced peripheral conversion of T4 to T3
mainly used to differentiate different etiologies of hyperthyroidism - ordered when TSH low but fT4 normal
Who should be screened for thyroid disorders and what tests should be ordered?
recommends against screening for dysfunction in asymptomatic non-pregnant adults
recommends toward screening when: sx present, pt at increased risk (ex. women > 45, postpartum, pt taking lithium or amiodarone, pt with other autoimmune diseases such as T1D, strong family hx)
Tests: TSH, fT4 or fT3 should not be used to screen for hypothyroidism or to monitor and adjust levothyroxine dose in pt with known primary hypothyroidism
How is hypothyroidism grouped based on test values?
may either be subclinical or overt
Subclinical: serum TSH above upper limit of ref range with normal fT4, measurement of Thyroid Peroxidase Abs may help predict risk of progression to overt disease
Overt: elevated TSH (typically above 10 mIU/l) in combo with low fT4
S&S of Hypothyroidism
tiredness, forgetfulness/slower thinking, moodiness, depression, inability to concentrate, thinning hair or hair loss, loss of body hair, dry patchy skin, weight gain, cold intolerance, elevated cholesterol, puffy eyes, swelling (goiter), hoarseness/deepening of voice, persistent dry or sore throat, difficulty swallowing, infertility, slower heartbeat, menstrual irregularities/heavy period, constipation, muscle weakness or cramps
Test algorithm tree for hypothyroidism testing, what does the lab value mean for the patient
TSH ⇒ if 0.2-6.5 mIU/L = euthyroid
if > 10 mIU/L = hypothyroid and should have tx,, if 6.5-10 mIU/L ⇒ now should test fT4 ⇒ if fT4 is low = tx for hypothyroidism, if fT4 is normal = tx decision based on clinical status, thyroid Ab status, goiter, pregnancy ⇒ if tx not started repeat TSH in 6-12 months
How is hypothyroidism classified (prevalence, at risk pops, etc)
Prevalence - approx 1-4%
Increased Risk - women (including postpartum) at least 3x risk, prior hx of Graves’ disease, increasing age (especially after 60), family hx of autoimmune thyroid disorders, other autoimmune endocrine conditions (ex. T1D) and non-endocrine (ex. celiac, pernicious anemia)
Primary (>99%): Hashimoto’s disease - elevated thyroid peroxidase (TPO) antibodies, iatrogenic this (RAI, thyroidectomy), drugs - iodine excess or deficiency, amiodarone, lithium, antithyroid
congenital
Secondary/Tertiary (<1%): pituitary disease, hypothalamic disease
What is the main tx of hypothyroidism?
levothyroxine (T4) - synthetic, long t1/2 with once daily dosing
dose dependent on: age, sex, lean body weight, pregnancy status, severity of hypothyroidism (ex. subclinical requires lower doses, pt with radioactive iodine or surgical removal require higher doses), general clinical context (ex. presence of CVD)
better absorbed when taken 60 min before meal - ex. for adherence counsel to take with water 30-60 min before breakfast
What is the dosing for levothyroxine for hypothyroidism?
Healthy Adult: replacement doses average around 1.6 mcg/kg (around 100-150 mcg/day), can start at dose close to target dose (more rapid normalization of TSH) especially if TSH markedly elevated
Elderly: 1 mcg/kg, avg maintenance dose = 100 mcg, consider starting lower (ex. 12.5-25 mcg) and titrate slowly, dose often needs to be decreased as pt ages (20%)
Cardiac Patient or those at risk: start at low dose (ex. 12.5-25 mcg) and titrate slowly, avoid cardiac compromise (increase HR and BP) and ischemia
for all pt titration can be 12.5-25 mcg increments
How should levothyroxine dosing be monitored in patients to find an optimal dose?
monitor TSH level if the patient has primary hypothyroidism or fT4 if they have secondary hypothyroidism every 6-8 weeks until euthyroid
adjust the dosage until lab tests are normal,, the goal TSH is 0.5-4 mIU/L or normal fT4 10-25 pmol/L ⇒ once euthyroid monitor TSH at least yearly (or sooner if new sx suggest dose adjustment required)
What are risks associated with over and under treatment of levothyroxine?
Over: a-fib and stroke, cardiac pt (increased risk of angina and MI), bone loss and fractures, anxiety, sleep disturbances, irritability
Under: increased lipids, decreased HR and ventricular contractility, increased peripheral vascular resistance and diastolic pressure, memory loss, mood impairment
What are other tx for hypothyroidism apart for levothyroxine?
desiccated thyroid: animal derivative (ex. pigs) - not recommended as not systemically studied
content of thyroid hormone and ratio of T4:T3 sig lower than that secreted by human thyroid gland (supraphysiological levels of T3)
liothyronine (T3): short t1/2 so BID dosing required, increase cardiac ADR secondary to increase potency, not physiologic
Is a combo of levothyroxine and T3 a viable option for hypothyroidism?
meta-analyses suggest no benefit in combo in terms of mood, health related QoL or cog fxn
may be small subset of pt that will do better on combo - may be due to genetic subtypes of Type 2 deiodinases which are important for conversion of T4 to T3
ATA guidelines suggest insufficient or no strong evidence in using combo - small proportion of pt who remain symptomatic on levothyroxine may be considered for addition of T3 if careful supervision by experienced clinician
What are some factors that may reduce the effectiveness of levothyroxine?
malabsorption syndromes - short bowel, celiac disease
reduced absorption - sucralfate, food, ferrous salts, Ca2+ supplements, Al(OH)3, cholestyramine
drugs that increase clearance - rifampin, carbamazepine, phenytoin
factors that decrease T4 to T3 conversion - amiodarone
How should hypothyroidism be managed during pregnancy?
overt hypothyroidism may increase incidence of maternal HTN, preeclampsia, postpartum hemorrhage, spontaneous abortion, fetal death or stillbirth
mild asymptomatic untreated maternal hypothyroidism during pregnancy may have AE of cog fxn of child
people with hypothyroidism who become pregnant ⇒ thyroid fxn can change and dose of thyroid hormone usually needs to be increased
if TSH above pregnancy specific ref range (or > 4.0 mIU/L) consider tx (especially if TPOAb-+)
Target: TSH 0.2-2.5 mIU/L in the 1st trimester, 0.2-3.5 mIU/L after 20 weeks
What are factors that can influence TSH levels?
time of this measurement (these levels peak in very early morning, lowest in late afternoon)
levothyroxine admin with or without food
change to non-equivalent levothyroxine products - products differing by 12.5% or more may be designated as equivalent
change in levothyroxine dose
drug intx
variance in absorption
non-adherence
Hyperthyroidism (epidemiology, prevalence, causes/etiology)
Prevalence: around 1-2%,, more common in females
subclinical this (TSH suppressed but thyroid hormone levels normal) is common and can be risk factor for a-fib
Causes: Graves’ disease, toxic nodules, tumours, subacute thyroiditis, hashitoxicosis, excessive dosage with T3 or T4
S&S of hyperthyroidism
nervousness, irritability, difficulty sleeping, bulging eyes/unblinking stare, swelling (goiter), menstrual irregularities or light period, frequent bowel movements, warm moist palms, excessive vomiting in pregnancy, hoarseness or deepening of voice, persistent sore or dry throat, difficulty swallowing, infertility, rapid or irregular heartbeat, weight loss, heat intolerance, increased sweating, first-trimester miscarriage, family hx of thyroid disease or diabetes
What are autoimmune disorders that are associated with Graves’ disease?
Endocrine: Addison’s disease, T1D, primary gonadal failure, Hashimoto’s thyroiditis
Nonendocrine: celiac, myasthenia gravis, pernicious anemia, immune thrombocytopenic purpura, RA
What does tx for hyperthyroidism involve?
drugs, radioactive iodine, surgery
individualize tx based on type, severity, age/gender, existence of nonthyroidal conditions, previous response to tx
How are beta blockers involved in hyperthyroidism?
increased beta-adrenergic activity responsible for palpitations, tachycardia, tremors, anxiety, and heat tolerance
all blockers are equally effective and some impair T4⇒T3 conversion but unlikely of clinical significance (ex. propranolol)
use of SR propranolol or QD/BID dosing of B1-selective antagonists (ex. atenolol or metoprolol) is recommended
blockers are not recommended as sole therapy and are used to control sx ⇒ consider for pt with symptomatic thyrotoxicosis (especially elderly or with HR > 90 bpm or coexistent CVD), can be initiated at presentation before completion of diagnostic tx
What are antithyroid drugs (ATDs) used in hyperthyroidism?
remission rate 40-50%,, higher likelihood of response in older pt (> 40), small goiters, short duration of disease (< 6 months), and negative or low-titer TSAb
long term tx with methimazole is more commonly considered as acceptable option
methimazole preferred first line (except in 1st trimester pregnancy ⇒ prefer propylthiouracil (PTU))
