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Hypothyroidism, Hyperthyroidism, Pregnancy - Coggle Diagram
Hypothyroidism
Monitoring
For idiopathic and Hashimotos hypothyroidism: HRT should bring TSH and T4 serum concentrations within normal range
thyroid cancer: TSH should be suppressed to low levels
Montior levels no more often than 4 weeks based on T4 half-life (7 days)
s/sx of hypothyroidism should improve or be absent, but can take several months for the full benefit of therapy to manifest
Risk Factors
Gender (female 8x as likely to develop than males)
age
postpartum women, FX of autoimmune thyroid disorders, Surgical Hx of head adn neck or thyroid irradiation, other autoimmune diseases (T1DM, adrenal insufficiency, ovarian failure)
Diagnosis
Primary Hypothyroidism
A rise in the TSH
Secondary hypothyroidism
In patients with pituitary disease, serum TSH concentrations are generally low or normal
Many patients will have a free T4 level within the normal range (compensated or subclinical hypothyroidism), with few, if any, symptoms of hypothyroidism.
As the disease progresses, the free T4 concentration will drop below the normal level.
With increased TSH stimulation thyroidal production will shift toward greater amounts of T3, and thus T3 concentrations will often be maintained in the normal range in spite of a low T4.
Eventually, free and/or total T4 and T3 serum concentrations should be low.
Pharmacologic Therapy
Levothyroxine
T4
1st-line for hypothyroidism
PK/PD: chemically stable, long t1/2 (7 days)
BBW: do not use as monotherapy for weight loss; large doses cause toxicity
Dose: for primary hypothyroidism 1.6 mcg/kg/day PO
Dose adjustment needed for coronary heart disease
ADRs: related to hyperthyroidism due to overdose
Liothyronin
T3
BBW: do not use as monotherapy for weight loss; large doses cause toxicity
Dose: 25 mcg PO once daily, may increase by up to 25 mcg.day every 1-2 weeks to max 75 mcg once daily if needed
ADRs: cardiac arrhythmia; tachycardia; hypotension; MI
Dose adjustment needed for coronary heart disease
PK/PD: short-acting, requires multiple doses per day to achieve stable hormone concentration
Liotrix
T4 and T3 in a 4:1 ratio
Not available in U.S.
Clinical Presentation
dry itchy skin
cold intolerance
weight gain
constipation
muscle weakness
lack of energy - muscle cramps
myalgia + stiffness
Objective weakness
Slow relaxation of deep tendon reflexes
Coarse skin and hair, cold or dry skin, periorbital puffiness,
and bradycardia
Slow speech
Reversible neurologic syndromes such as carpal tunnel syndrome,
polyneuropathy, and cerebellar dysfunction may also occur
Galactorrhea may be found in women
Pathophysiology
TSH above the normal range
free thyroxine and/or triiodothyronine levels below reference range
Non-Pharmacologic Therapy
Surgery for thyroid >80 g
Goals of Therapy
Restore normal thyroid hormone concentrations in tissue, provide symptomatic relief, prevent neurologic deficits in
newborns and children, and reverse the biochemical abnormalities of hypothyroidism
Hyperthyroidism
Pathophysiology
Thyroid glad is over producing T4, T3, or both.
Hyperthyroidism is a cause of thrytoxicosis
Graves Disease: autoimmune condition where thyroid-stimulating antibodies (TSAbs) attack and stimulate thyrotropin receptor in the thyroid, acting similarly to TSH; Results in enlarged thyroid
Increased RAIU: TSAb(Graves disease, multi-nodular goiter, toxic adenoma, hCG (trophoblastic diseases), TSH-induced hyperthyroidism, TSH-secreting tumors, Selective pituitary resistance to T4, thyroid stimulators other than TSH
Decreased RAIU: exogenous sources of thyroid hormone, medications containing thyroid hormone or iodine, painless thyroiditis, subacute thyroiditis, inflammatory thyroid disease, food sources containing thyroid gland, ectopic thyroid tissue, struma ovarii, metastatic follicular carcinoma
Toxic adenoma: benign tumor that produces mass-related thyroid hormone
Monitoring
Clinical signs of continuing thyrotoxicosis (tachycardia, weight loss, and heat intolerance, among others
Development of hypothyroidism (bradycardia, weight gain, and lethargy, among others) should
Pt's adherence
Labs (eg, TSH, FT4, TT3, anti-TG antibodies, TPO antibodies; serum electrolytes, Scr, ALT)
Monthly until euthyroid
Diagnosis
Low TSH serum concentration
Elevated free and and total T4 and T3 serum concentrations
Elevated radioactive iodine uptake (RAIU)
Can also assess levels of thyroid-stimulating antibodies (TSAbs), TG, and thyrotropin receptor antibodies
Pharmacologic Therapy
Thionamide drugs
MMI: 90-120 mg/day PO in 4-6 divided doses
MOA: divert iodine away from iodination sites, inhibit formation of T3 and T4;
PTU: 900-1200 mg/day PO in 4-6 divided doses
Iodide
MOA: block thyroid hormone release, inhibit thyroid hormone biosynthesis, decrease size and vascularity of gland
Adrenergic blockers
Adjunctive therapy to help with sx; can be used with antithyroid drugs, RAI, or iodides
Can be used for surgery preparation of during thyroid storm
Drugs included: propranolol, nadolol
Radioactive iodine
Non-Pharmacologic Therapy
Surgery - usually reserved for pts with thyroid gland >80g, severe ophthalmopathy, and lack of remission on antithyroid medication regimen
Radioiodine therapy
Percutaneous ethanol injection therapy
Clinical Presentation
Nervousness, anxiety, palpitations, emotional lability, easily fatigued, menstrual disturbance, heat intolerance, weight loss and increased appetite
Warm, moist skin, unusually fine hair, separation of nails from fingertips, tachycardia at rest, systolic ejection murmur, gynecomastia, lid retraction, fine tremor of tongue and hands, thyromegaly
Special Populations
Pregnancy
Hyperthyroidism during pregnancy commonly due to Graves' disease
2 sx suggestive of hyperthyroidism during pregnancy: failure to gain weight and persistent tachycardia
Potential for postpartum thyroid storm, fetal loss, low-birth-weight infants and eclampsia
RAI is contraindicated in pregnancy so antithyroid drugs must be used
Propylthiouracil recommended in first trimester, MMI recommended during second and third
Neonatal
Some babies of hyperthyroid mothers may be hyperthyroid due to placental transfer of TSAbs
Disease is expressed 7 to 10 days postpartum
Can be managed with PTU (5-10 mg/kg/day) or MMI (0.5-1mg/kg/day) for as long as 8 to 12 weeks or until antibody is cleared
Risk Factors
Genetics, female sex, advanced age (adenoma)
Goals of Therapy
Eliminate the excess thyroid hormone and minimize the symptoms and long-term consequences of
hyperthyroidism
Pregnancy
Pharmacokinetic Changes
Maternal plasma volume, cardiac output, and glomerular filtration increase by 30% to 50% or higher -> potentially lowering the concentration of renally cleared drugs
Volume of distribution of drugs may be
affected
Plasma albumin concentration decreases -> increases the volume of distribution of drugs that are highly protein bound
Unbound drugs are more rapidly cleared by the liver and kidney
Hepatic perfusion is increased -> increase the hepatic extraction of drugs; activity of metabolic enzymes and drug transporters
Activity of cytochrome P450 3A4, 2C9, and 2D6 is increased while that of 1A2 is decreased
Nausea and vomiting, as well as delayed gastric
emptying, may alter the absorption of drugs
HCl secretion in the stomach is variable
Gastrin production is increased -> increases gastric acidity and may affect absorption of drugs
Pregnancy-Induced Conditions
Constipation
Non-pharmacologic treatment
High-fiber diet, adequate fluid intake, sitz baths, moderate physical activity
Pharmacologic treatment
Bulk-forming agents: psyllium; methylcellulose; polycarbophil
Osmotic laxatives: PEG; lactulose; sorbitol
Stimulant laxatives (short-term use is ok): senna; bisacodyl
Do not use: Mg2+ and Na+ salts; castor oil; mineral oil
GERD
Non-pharmacologic treatment: lifestyle and dietary modifications
Pharmacologic treatment
H2RAs: ranitidine or cimetidine
PPIs not preferred
Do not use: sodium bicarb; magnesium trisilicate; large doses of aluminum
Hyperemesis
Pyridoxine alone or with doxylamine: 1st-line
Metoclopramide: 2nd line b/c risk of EPS effects
Other options: ondansetron; ginger; corticosteroids (not in 1st trimester)
Gestational diabetes
Non-pharmacologic treatment: dietary modifications and exercise
Pharmacologic treatment
Human insulin (does not cross placenta)
Metformin: alternative option (but supplemental insulin will still be required
Risk factors: BMI >25; previous gestational diabetes; HTN; or CVD; strong hx of DM
Preeclampsia
Low-dose aspirin 1x daily at 12-28 weeks
Defined as elevated BP + proteinuria (>300 mg/24 hours) OR new onset HTN + thrombocytonpenia (<100,000), SCr >1.1 or 2x baseline or liver transaminases 2x normal limit
Definition: sBP >140 or dBP >90 based on 2+ measurements >4 hours apart
Thyroid abnormalities
Hypothyroidism
Levothyroxine
Hyperthyroidism
PTU
Thromboemolism
LMWH: continue throughout pregnancy and 6 weeks post-delivery
Do not use: warfarin (only use if have mechanical heart valve); fondaparinux and injectable thrombin inhibitors
Not recommended: DOACs
Chronic Condition Drugs to Avoid/Replace
Allergic Rhinitis
Oral Corticosteroid duration should be limited because they cross the placenta and may cause hypoadrenalism
Preferred treatment is oral/intranasal antihistamines, intranasal cromolyn, and intranasal corticosteroids (budesonide and beclomethasone)
Asthma
Albuterol as rescue SABA and budesonide is preferred ICS
Epilepsy
Avoid phenytoin, VPA, phenobarbitol, and topiramate because they may cause cleft palate or cardiac malformations (phenobarbital)
Monotherapy is safer than polytherapy
Carbamazepine, lamotrigine, and leveteracetam are safest
HTN
Stop ACE/ARB, renin inhibitor
Use labetalol, nifedipine, and/or methyldopa
Mental Health Conditions
SSRIs are not considered major teratogens, but perhaps greater risk with paroxetine...pulmonary HTN of the newborn and neonatal adaptation syndrome
Avoid diazepam for anxiety; Oral clefts
Benzodiazepines in 2nd and 3rd trimester cause infant sedation, and withdrawal
Avoid or closely monitor lithium in bipolar because cardiac malformation of the fetus
Typical antipsychotics are safe: chlorpromazine, haloperidol, and perphenazine
Atypical antipsychotics may cause low birth weight and CV defects, especially risperidone
Physiology of Pregnancy
Pregnancy starts when sperm binds to the protein layer of the egg: zona pellucida
This stops other sperm from attaching to the egg
Sperm releases enzymes allowing it to penetrate the egg (
zygote
)
Day 3
--> egg reaches uterus
Day 6,--
> egg is considered a
blastocyte
implantation begins wehn blastocyte exits the zonna pellucida to rest on endometrium
Day 10
--> blastocyte implants under endometrial surface + receives nutrients from maternal blood
- Day 15
- considered an
embryo
- 1st day of 3rd week
After 8 weeks: called
fetus
Recommended Supplements/ Vaccines
Folic acid
0.4 and 0.8 mg daily is recommended
throughout a woman’s reproductive years
Influenza vaccine
TDap during weeks 27-36 of pregnancy to protect baby from pertussus
Get live vaccines 1 month or more before pregnancy if possible: HPV, MMR, varicella, travel vaccines like yellow fever and typhoid
Resources for Determining Drug Safety
LactMed, motherrisk.org, reprotox.org