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Thyroid Disorders, Pregnancy & Lactation - Coggle Diagram
Thyroid Disorders
liotrix
Warnings: adrenal insufficiency (treat with glucocorticoids before TRT), CVD (reduce dose because overtreatment could increase risk of CV events), diabetes, myxedema (dose reduction at first)
Regimen: levothyroxine 25 mcg/liothyronine 6.25 mcg once daily initially, increase in increments of levothyroxine 12.5 mcg/liothyronine 3.1 mcg every 2-3 weeks, maintenance dose levothyroxine 50-100 mcg/liothyronine 12.5-25 mcg once daily
lower initial dose for patients with long history of myxedema (severely advanced hypothyroidism)
decrease dose if CV impairment
take on an empty stomach
Monitoring: TSH 4-6 weeks after initiation or dose changes and 4-6 months after adequate dose replacement and every 12 months after, T4, HR, BP, CV symptoms, signs of hyper/hypothyroidism
Special Populations
Pediatrics: age-based dosing
Geriatric: levothyroxine 12.5-25 mcg/liothyronine 3.1-6.25 mcg once daily, can increase by levothyroxine 12.5 mcg/liothyronine every 2-3 weeks
TRT indicative in infertile females with hypothyroidism who want to become pregnant
Pregnancy: TRT reduces risk of adverse pregnancy outcomes in females with hypothyroidism
Contraindications: hypersensitivity, uncorrected adrenal insufficiency, untreated thyrotoxicosis
PK
A: T4 40-80%, T3 95%
D: T4 highly protein bound
M: hepatic, T4 deiodinated in kidney and periphery, enterohepatic recirculation
E: half life of T4 depends on condition of thyroid
MOA: T3 converted from T4 that circulates throughout body to influence growth and maturation of tissues
formulation is a uniform mixture of synthetic T4 and T3 in 4:1 ratio
ADR: levothyroxine and liothyronine side effects
Patient Education
take 30 minutes before eating
NOT AVAILABLE IN US
monotherapy with levothyroxine is preferred
BBW: thyroid hormone drugs have been used for obesity. In euthyroid patients, doses that reflect daily hormonal requirements are ineffective for weight loss. Higher doses may result in life-threatening toxicity, especially when used with sympathomimetic amines
hypothyroidism
DDI: I-131
Levothyroxine
BBW:
Weight reduction (should not be used for obesity)
MOA:
synthetic form of thyroxine which then binds to thyroid receptors and exhibit metabolic effects
PK/PD
A: oral ( may decrease with age); 79-81% bioavailability in fasting state
99% protein binding
M: Hepatic metabolism (T3 active); T4 deiodinated in kidney
T1/2: 7 days
E: Major route - urine (decrease with age)
Monitoring:
Pediatric:
monitor for over/undertreatment; perform routine clinical evaluation (mental; physical growth; development)
Undertreatment - decrease intellectual development and linear growth and lead to poor school performance due to impaired concentration and slowed mentation
Overtreatment: may adversely affect brain maturation and accelerate bone age (leading to premature closure of the epiphyses and reduced adult height); craniosynostosis has been reported in infants
Monitor TSH + free T4 at 2 and 4 weeks after starting tx; every 1 to 2 months during the first year of life, every 2 to 3 months between ages 1 to 3 years, and every 3 to 12 months thereafter until growth is completed; repeat if dosage if changed
Adult:
Heart rate, BP, new/worsened cardiac symptoms (eg, chest pain, palpitations, edema), clinical signs of hypo- and hyperthyroidism; bone mineral density (particularly with long term use in postmenopausal women).
Primary hypothyroidism: monitor TSH response at 6 weeks if pt shows improvement and titrate as needed; measure free T4 and TSH at 3 weeks if pt still shows symptoms. Continue to measure TSH every 3-6 weeks and titrate dose until TSH concentration is in goal range
Hypothyroidism in pregnancy: TSH evaluation every 4 weeks until midgestation and at least once every near 30 week gestation; if levothyroxine initiated during pregnancy then TSH should be measured 6 weeks after dosage adjustment or d/c
Postpartum thyroiditis: Evaluate TSH every 2 months following resolution of the thyrotoxic phase of PPT until 1 year following delivery.
Secondary hypothyroidism: Monitor response to treatment with measurement of FT4 concentrations; goal of treatment is to maintain FT4 concentrations in upper half of the reference range
Myxedema coma: Monitor thyroid function tests (FT4 or T4, T3) every 1 to 2 days. Monitor clinical response (eg, mental status, temperature, respiratory function, cardiovascular status, electrolytes [eg, serum sodium]) to ensure adequate parenteral thyroid hormone replacement; monitor safety with parenteral therapy (eg, tachycardia, arrhythmia, myocardial infarction)
Patient education
Take on an empty stomach at least 30 minutes before food and avoid soybean flour (infant formula), soy, grapefruit juice, espresso coffee, cottonseed meal, walnuts, calcium, iron, and dietary fiber which may interfere with absorption
Warning/Precautions/ Special Populations:
Adrenal insufficiency - use with caution; symptoms may be exaggerated or aggravated
Not recommended in pt with benign thyroid nodules
CV- use reduced initial dosage and conservative dose titration; over treatment may increase CV adverse risk
Diabetes: use with caution ( may worsen glycemic control in diabetes mellitus; may increase glomerular filtration rates and down regulate aquaporin channels in renal tubule in diabetes insipidus)
Osteoporosis: may decrease bone mineral density ( appears dose-related)
Elderly: use with caution; suppressed TSH may increase risk of a-fib and mortality secondary to CV disease. Increase dose slowly and monitor for angina
Contraindication
Injection: Uncorrected adrenal insufficiency
Oral: Uncorrected adrenal insufficiency; hypersensitivity to glycerol (Tirosint oral solution)
AE:
CV events (angina, arrhythmia, cardiac failure, flushing, increase bp, increased pulse, MI); CNS ( anxiety, fatigue, headache, hyperactivity, insomnia, irritability)
Clinical pearls
always express in mcg (not mg) to avoid errors
Significant dosing difference exists between IV and oral; use caution if converting
Narrow therapeutic drug so use with caution with titrating and determining initial dosing
Dosing:
Hypothyroidism: Adjust initial dose by 12 to 25 mcg/day every 3 to 6 weeks based on clinical response and serum TSH and/or free T4 concentrations until TSH is normalized at a stable dose for ≥6 weeks.
Patients ≤60 years of age without evidence of coronary heart disease: Oral: Initial: 1.6 mcg/kg/day
Patients >60 years of age without evidence of coronary heart disease: Oral: Initial: 25 to 50 mcg once daily
Patients with coronary heart disease: Oral: Initial: 12.5 to 50 mcg once daily
Preexisting hypothyroidism in women receiving levothyroxine prenatally: Patients with suspected or confirmed pregnancy: Oral: Immediately increase the current dose by ~20% to 30% (eg, administer 2 additional tablets weekly of the current dose) and adjust dose as needed every 4 weeks
Newly diagnosed overt hypothyroidism: Oral: Initial: 1.6 mcg/kg/day; adjust dose by ~25 mcg/day as needed every 4 to 6 weeks to restore patient to euthyroidism as soon as possible
Postpartum thyroiditis: Initial: 25 to 75 mcg once dailly; adjust dose as needed once every 4 to 6 weeks until TSH is normalized. Tapering of the dose with a goal of d/c, if possible, may begin after 6 to 12 months of treatment
Secondary hypothyroidism: Initial: 1.6 mcg/kg/day; some experts initiate treatment at a lower dose in older patients or patients with underlying coronary heart disease. Adjust dose based on clinical response and serum free T4 concentrations. TSH
cannot be
used to monitor therapy
Myxedema coma: IV: Initial loading dose of 200 to 400 mcg as a slow bolus; followed by a daily replacement dose of 50 to 100 mcg until the patient improves clinically and can transition to oral therapy;
liothyronine
BBW
: Weight Reduction -- should not be used for the treatment of obesity or for weight loss
Dose
Hypothyroidism
Initial: 25 mcg once daily; may increase by 25 mcg/day every 1-2 weeks
Maintenance: 25-75 mcg once daily
CV disease: Initial: 5 mcg once daily; may increase by 5 mcg/day every 2 weeks.
Myxedema Coma (IV)
Adjunctive therapy in combination with levothyroxine: Initial: 5 to 20 mcg loading dose; maintenance: 2.5 to 10 mcg every 8 hours; continue therapy as clinically indicated.
Dosage Forms:
IV solution, oral tab
CI
: uncorrected adrenal Insufficiency
Warnings
: use with caution In adrenal Insufficiency & DM, risk of CV events (angina, arrhythmia), long-term therapy can decrease BMD
Reproductive Considerations:
Overt hypothyroidism increases risk of irregular menses and infertility; thyroid replacement is recommended to normalize thyroid function in infertile females with overt hypothyroidism who desire pregnancy
Monitoring
: TSH 4-6 weeks after initiation or dose changes, 4-6 months after adequate replacement dose determined, followed by every 12 months thereafter
HR, BP, new/worsened cardiac symptoms (eg, chest pain, palpitations, edema); clinical signs of hypo- and hyperthyroidism; bone mineral density
T4 (thyroxine) serum concentrations: Adults: ~4-12 mcg/dL
T4 free (free thyroxine; free T4) serum concentrations: Adults: 0.7-1.8 ng/dL
T3 total (triiodothyronine; total T3) serum concentrations: Adults: 80 to 230 ng/dL
PK
Onset of action: few hours, peak onset 2-3 days
A: 95% orally within 4 hours
t1/2 = 0.75 days
E: urine (primary)
synthetic form of a natural thyroid hormone
thyroid USP
MOA: T3 (converted to T4) impacting growth and maturation of tissues through control of DNA transcription and protein synthesis
PK/PD/PGx
A: T3 95%, T4 40-80%
Hepatic Metabolism
Urine Excretion
T1/2: T4, 2-3 days (hyperthyroid) 9-10 days (hypothyroid)
99% Protein Bound T4
Initial Dosage 30 to 32.5 mg/day
Use 15 or 16.25 of CVD or long-standing myxdema
Titrate 15 to 16.25 mg every 2 to 3 weeks
Maintenance dosages between 60 to 130 mg/day
Contraindications
Hypersenstivity
Untreated thyrotoxicosis
Uncorrected adrenal insufficiency
Warnings/Precautions
CVD
DM
Myxedema
Monitoring
TSH 4 to 6 weeks after initiation, 4 to 6 months after a stable dose, yearly thereafter
T4
BP, HR, Cardiac symptoms
S/Sx of hypo/hyperthyroid
DDI
Rifampin
SSRIs
Warfarin
Growth hormone analogues
Phenytoin
Special Pops
Not recommended in geriatrics
Education/Counseling
Take on an empty stomach
Stick with the same product
methimazole
MOA
: inhibits the oxidation of iodine in the thyroid to prevent the synthesis of thyroid hormones; blocks synthesis of thyroxine and T3; does not inactivate circulating T4 and T3
Regimen
:
Adult Initial: individualize dose based on clinical status and gland size; free T4 levels may be used to guide therapy
free T4 levels 1-1.5 x ULN: 5 to 10 mg PO daily
free T4 levels >1.5-2 x ULN: 10 to 20 mg PO daily
free T4 levels >2 x ULN: 20 to 40 mg/day. (May give in 2 to 3 divided doses)
Dose adjustments
: usual maintenance dose: 5-10 mg PO daily. assess free T4 and total T3 at 4-6 week intervals; when normal, reduce dose 30-50% and repeat thyroid fxn tests in 4-6 weeks; continue to adjust to achieve euthyriodism
Pediatric Dosing
: initial 0.4 mg/kd/day in 3 divided doses (~Q8H); maintenance 0.2 mg/kg/day in 3 divided doses (50% of initial)
PK/PD
: 12 to 18 hours onset of action; distribution concentrated in thyroid gland; no protein binding, plasma; hepatic metabolism; urine excretion
Monitoring
: s/sx of illness (fever, sore throat, general malaise); CBC w/ differential at baseline & if febrile illness or pharyngitis; prothrombin time (esp before surgery); LFTs (bilirubin, alkaline phosphatase; ALT, AST) at baseline and if sx of liver injury occur
Special pops
: no dose adjustments for renal or hepatic impairment or for geriatrics provided.
Pregnancy
: crosses placenta; birth defects in neonates exposed to maternal methimazole during 1st trimester; hypothyroidism may occur in newborn; uncontrolled maternal hyperthyroidism may result in adverse neonatal & maternal outcomes. Antithyroid drugs tx of choice, but recommendations vary by guideline.
AEs
: (common) rash, arthritis, N/V, loss of taste, abnormal alopecia, HA, drowsiness; (serious) vasculitis, erythroderma, pancreatitis, agranulocytosis, aplastic anemia, hepatotoxicity, insulin autoimmune syndrome
Hyperthyroidism
associated with Graves disease, toxic multi nodular goiter, and toxic adenoma (or iodine-induced thyrotoxicosis--off-lable)
DDI
: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Check for DDIs
propylthiuracil
BBW
: hepatotoxicity (severe liver injury and acute liver failure have been reported); pregnancy (may be treatment of choice when antithyroid drug is indicated during/prior to the first trimester)
Dosing
: 100 mg Q8H (inital); 400 mg daily in severe hyperthyroidism and/or large goiters; 100-150mg/day (3 divided doses)(maintenance)
Pearls
: Dose adjustments can be made to achieve/maintain serum T3/T4/TSH levels; an elevated T3 can be only indicator of inadequate treatment; high-alert medication
Special Populations
: No renal/hepatic dose adjustments; not recommended in children
Target Population
: patient's w GD or toxic multinodular goiter who are intolerant of methimazole and surgery/radioactive iodine therapy is not appropriate
ADRs
not well defined; may cause hepatotoxicity; bleeding, bone marrow suppression, dermatologic toxicity; fever
Monitoring
: S/s of illness or vasculitis; CBC w/ differential (baseline and if clinically indicated); prothrombin time (especially before surgeries); LFTs (at baseline and if clinically indicated); thyroid function tests (Serum free T4 and total T3 2 to 6 weeks after initiation, repeat in 4 to 6 weeks if dose is adjusted and then every 2 to 3 months once euthyroid levels are achieved - may extend to 4-6 months if long term therapy)
MOA
: inhibits synthesis of thyroid hormones by interfering with thyroid peroxidase; blocks conversion of T4 to T3 in peripheral tissues
PK/PD
: 24-36h onset of action; highly protein bound; hepatic metabolism; excreted in urine
Goals
Monitoring
Hormones + s/x evaluated monthly (half life of thyroid hormones)
Restore normal thyroid function/thyroid hormone levels
Prevent long-term complications
Reverse biochemical abnormalities
Non-Pharm
Surgery considered for pt with large thyroid (more than 80g), severe ophthalmopathy, and a lack of remission on antithyroid drug treatment.
Radioactive Iodine - used for tx of toxic nodules and toxic multi nodular goiter
Pregnancy & Lactation
Physiology/Characteristics
Early symptoms
fatigue, increased frequency of urination
Signs
cessation of menses, change in cervical mucus consistency, bluish discoloration of the vagina mucosa, increased skin pigmentation, anatomic breast changes
Physiology
fertilizations occur within the fallopian tube, travels down tube over 2 days, reaches the uterus at day 3; most pregnancy losses occur 2 weeks after fertilization; hcG can be detected in maternal urine 8-9 days after ovulation; most body structures are formed during the embryonic period (2-8 weeks postfertilization), called a fetus after 8 weeks postfertilization; pregnancy lasts 280 days
Pregnancy History Sequence
(1)term deliveries, (2)premature deliveries, (3)aborted pregnancies, (4)number of living children
Definitions
gravidity - number of times a woman has been pregnant; parity - number of pregnancies exceeding 20 weeks of gestation
PK Changes
Begin during the first trimester; peak during the second trimester
Increased
: plasma volume, cardiac output, GFR, hepatic perfusion, CYP3A4, CYP2C9, CYP2D6, gastrin production
can lower the concentration of renally cleared drugs; hepatic extraction of drugs increased by changes in perfusion ; absorption of drugs can be altered by changes in gastrin
Decreased
: plasma albumin, CYP1A2, delayed gastric emptying
Increased Vd of highly protein bound drugs; unbound drugs more rapidly cleared by the liver/kidney
Common Meds to Avoid
<1% of all birth defects caused by medication exposure
Exposure during organogenesis (18-60 days postconception) = structural anomalies
methotrexate, lithium, retinoids, thalidomide, AEDs, coumarin derivatives
Later exposure = growth retardation, CNS defects, death
NSAIDs and tetracycline derivatives In 2nd and 3rd trimesters
All NSAIDs and aspirin CI In 3rd trimester for risk of closure of ductus arteriosus; maternal and fetal bleeding
Medication selection affected by trimester of pregnancy, route of administration, and dose
MW < 500 Da readily cross placenta
MW > 1000 Da do not cross In significant amounts (insulin, heparin)
Pregnancy-Influenced Complications
GI Tract Issues
Constipation
Treat with nonpharm/exercise first
Osmotic laxatives preferred
AVOID mineral oil and castor oil
GERD
Treat w/lifestyle and diet modification
Antacids or sucralfate
Avoid sodium bicarb, magnesium triscilicate, large doses of aluminum
H2RAs (cimetidine)
PPI (omeprazole)
Gestational Diabetes
Screen at prenatal visit and 24 to 28 weeks
Diet modification, exercise, BG monitoring
Human insulin drug of choice (does not cross placenta)
Hypertensive Disorders
Exercise first line
Preeclampsia
HTN, proteinuria, elevated AST/ALT, low platelets
81 mg aspirin
Can become eclampsia (presents as tonic-clonic seizures) a medical emergency
Magnesium sulfate can prevent and also treat eclamptic seizures
labetalol, nifedipine, methyldopa
Thyroid Abnormalities
Stimulation may occur bc of structural similarities b/t TSH and hCG
Treatment not usually needed
Can treat associated N/V
Postpartum thyroiditis (PPT)
BB can provide symptomatic relief
Levothyroxine replacement can be done for 6 to 12 months
Overt Hyper/hypothyroidism treated with a thiomide and hormone replacement respectively
VTE
increased risk while pregnant and 6 weeks postpartum
LMWH preferred, continued through pregnancy and for 6 weeks after delivery
mechanical heart valve: low dose warfarin (<5mg) during pregnancy despite teratogenic risk
Pospartum Issues
Postpartum Depression
"Postpatrum blues" are common in first 10 days postpartum; usually does not require treatment;
S/S
: anger, anxiety, sadness, fatigue, insomnia
S/S
can develop during pregnancy or up to 6 months after delivery; various types of therapy/CBT show benefit, if pharmacologic therapy is needed selection of treatment with low-placenta/milk transfer desired
Mastitis
Can be infectious or noninfectious (most commomly Staph Aureus); most common cause is milk stasis
S/S
breast tenderness, warmth, redness, flu-like symptoms, fever;
Risk Factors
: breast engorgement, plugged milk ducts, oversupply of milk, cracked nipples
Treatment
10-14 day antibiotics, commonly penicillinase-resistant penicillins or cephalosporins; ibuprofen may provide relief; heat/massage may be helpful
Supplements/Vaccines
Folic acid 0.4-0.9 mg throughout reproductive years to reduce risk for neural tube defects
annual dose of IIV or RIV -
LAIV not recommended
1 dose Tdap each pregnancy
PPSV23, HepA, HepB, MenACWY recommended with certain risk factors/indications
Contraindicated vaccines in pregnancy: LAIV, MMR, VAR