Hypothyroidism Lecture Notes PDF

Hypothyroidism CMS200 learning outcomes Understanding the essentials of hypothyroidism diagnosis, including differential diagnosis and clinical findings. Recognizing the common causes of hypothyroidism, such as autoimmune thyroiditis and iodine deficiency, and their impact on body functions....

Hypothyroidism CMS200 learning outcomes Understanding the essentials of hypothyroidism diagnosis, including differential diagnosis and clinical findings. Recognizing the common causes of hypothyroidism, such as autoimmune thyroiditis and iodine deficiency, and their impact on body functions. Identifying potential complications of hypothyroidism, such as cognitive impairment and increased susceptibility to infections, and understanding the importance of adherence to treatment. Knowing when to refer patients with hypothyroidism to a specialist for further evaluation and management. Understanding the signs and symptoms of myxedema and its relationship to severe hypothyroidism. Recognizing the potential impact of hypothyroidism on pregnancy and the importance of appropriate management. learning outcomes (continued) Understanding the potential causes of a low or suppressed serum TSH level in patients receiving levothyroxine therapy and how to manage concurrent conditions such as celiac disease or Addison disease. Understanding the epidemiology and etiology of hypothyroidism, including primary and central hypothyroidism, and how to diagnose each condition. Understanding the role of TSH measurement in screening for primary hypothyroidism and the importance of interpreting laboratory measurements within the context of laboratory-specific normative ranges. Recognizing the difference between overt hypothyroidism and subclinical hypothyroidism and how to diagnose each condition. Understanding the diagnostic criteria for subclinical hypothyroidism and the role of TSH in diagnosing this condition. learning outcomes (continued) Develop skills in patient-centered care and shared decision-making for patients with subclinical hypothyroidism Understanding the consequences of untreated hypothyroidism, including increased morbidity and mortality. Learning about the different drugs that can cause hypothyroidism and understanding the causes of secondary and tertiary hypothyroidism. Know the importance of evaluating for autoimmune thyroid diseases and ruling out or treating adrenal insufficiency in patients with severe hypothyroidism. hypothyroidism - hypometabolic state that occurs when there is inadequate thyroid hormone production (T4, T3) by the thyroid gland or insufficient stimulation by the hypothalamus (TRH) or pituitary gland (TSH) (osmosis.org) types of hypothyroidism primary - thyroid gland dysfunction (inability to produce adequate thyroid hormones, T3 and T4) - 95% of hypothyroid cases secondary (aka. central) - inadequate production of thyroid stimulating hormone (TSH, aka. thyrotropin) tertiary - inadequate thyrotropin releasing hormone (TRH) iatrogenic - thyroid dysfunction caused by medical examination or treatment image from: osmosis.org resistance to thyroid hormone (rare) etiology of primary hypothyroidism - iodine deficiency: common cause in iodine-deficient geographic regions - relative iodine excess hypothyroidism may occur in vulnerable persons - autoimmunity: most common cause in North America - chronic autoimmune thyroiditis (Hashimoto thyroiditis) - most common - subacute granulomatous thyroiditis (de Quervain disease) - rare - transient: postpartum thyroiditis, pregnancy, silent thyroiditis, subacute thyroiditis, thyroiditis associated with TSH receptor-blocking antibodies - congenital abnormalities: aplasia/agenesis of thyroid, dyshormonogenesis - infiltrative thyroid diseases (rare): amyloid goiter, black thyroid, cystinosis, diffuse lipomatosis, hereditary hemochromatosis, langerhans cell histiocytosis, reidel’s thyroiditis, sarcoidosis, scleroderma (Nature, 2022) etiology of central (secondary + tertiary) hypothyroidism - pituitary tumors - pituitary adenomas are most common - Sheehan syndrome - a rare condition involving injury to your pituitary gland following extreme blood loss during childbirth - lymphocytic hypophysitis - a rare, autoimmune condition of the pituitary gland - brain tumors compressing hypothalamus - thyroid releasing hormone (TRH) resistance - TRH deficiency - radiation therapy to the brain iatrogenic hypothyroidism medications - dopamine - amiodarone - opioids - antibiotics: rifampin, ethionamide - prednisone - anti-convuslants: phenytoin, carbamazepine - anti-neoplastics: tyrosine kinase inhibitors procedures (sunitinib, imatinib), bexarotene, interleukin-2, - radiotherapy to head or anti-CTLA-4 and anti-PD-L1/PD-1 neck area - interferon-α - thyroid radioactive - lithium iodine therapy - perchlorate - thyroid surgery - phenobarbital - stavudine - thalidomide hypothyroidism symptom presentation thyroid hormones affect many functions in the body images from: osmosis.org  impact of low thyroid hormones on body functions - skin: reduced sweating, skin discoloration, coarse hair (or loss), brittle nails, non- pitting edema, periorbital edema - hematologic: hypocoagulability (bleeding risk), pernicious anemia - cardiovascular: bradycardia, pericardial effusion, diastolic hypertension - respiratory: shortness of breath on exertion, rhinitis, decreased exercise capacity - gastrointestinal: constipation, decreased taste, nonalcoholic fatty liver disease - reproductive: menstrual irregularities, decreased libido, infertility, miscarriage, erectile dysfunction, delayed ejaculation, reduced sperm morphology - neurologic: hashimoto encephalopathy, myxedema coma - muscular: weakness, cramps, myalgias (high serum creatine kinase) - mental: depression, anxiety, poor concentration, decreased short-term memory - metabolic: hyponatremia, hyperlipidemia, hypercholesterolemia, hyper- homocysteinemia, hyperuricemia, reduced drug clearance (e.g. hypnotic, opioid) - weight gain symptoms associated with hypothyroidism can mostly be attributed to: generalized slow metabolism or accumulation of polysaccharides in interstitial spaces (Nature, 2022) common symptoms of hypothyroidism - weight gain - fatigue, lethargy, depression - weakness, dyspnea on exertion, arthralgias or myalgias, muscle cramps - menorrhagia - constipation - dry skin, hair changes (dryness, thinning, loss) - headache, paresthesias, carpal tunnel syndrome, raynaud syndrome - cold intolerance - voice changes image from: osmosis.org common clinical findings in hypothyroidism - bradycardia - diastolic hypertension - thin, brittle nails - thinning hair or alopecia (including lateral ⅓ of eyebrow thinning) - peripheral edema - puffy face and eyelids - skin pallor or yellowing (carotenemia) - delayed relaxation of deep tendon reflexes - goiter (chronic autoimmune hypothyroidism: firm, then shrinks with fibrosis) goiter - enlargement of the thyroid gland, can be diffuse, nodular or multinodular physiologic goiter: adolescence, pregnancy endemic goiter: iodine deficiency a symptom of inflammatory disorders (thyroiditis): autoimmune, postpartum, silent, radiation, subacute, suppurative a symptom of hyperthyroidism: Grave disease, toxic nodular/multinodular goiter thyroid cancer or infiltrative disease (e.g. sarcoidosis) female (4x) can be euthyroid, hypothyroid or hyperthyroid - most goiters are euthyroid management: referral for ultrasound, fine-needle aspiration biopsy (if nodule), treatment varies with serum findings prognosis: generally good prognosis, if enlarges can cause difficulty breathing, swallowing, or hoarseness and may require surgery  lateral view of goiter frontal view of goiter (BMC Research Notes, 2014) (Stanford Medicine 25) symptom experience in autoimmune hypothyroidism Symptom Sensitivity LR + LR - anterior neck pain 16% 3.50 0.88 difficulty swallowing / globus sensation 29% / 35% 2.59 / 2.09 0.80 / 0.78 shortness of breath / wheezing 51% / 27% 1.74 / 2.20 0.69 / 0.83 constipation 38% 2.29 0.74 dry, sensitive skin 62% 2.16 0.53 hair loss 31% 3.50 0.76 mood lability / bad mood every day 46% / 5% 2.23 / 2.16 0.68 / 0.97 tiredness 81% 1.96 0.33 (Eur J Endocrinol, 2014) symptom presentation (hypothyroid compared to euthyroid) (JAMA, 2000) symptom progression in autoimmune hypothyroidism changed symptom Sensitivity LR + LR - hoarser voice 5.5% 1.10 0.99 drier skin 28.3% 1.12 0.96 feeling colder * LR+ >2 in overt cases 14.6% 1.24 0.97 more tired 18.3% 1.14 0.97 weaker muscles 22.2% 1.20 0.95 more constipation 6.1% 1.22 0.99 slower thinking 22.3% 1.21 0.95 poorer memory 24.5% 1.17 0.95 (JAMA, 2000) number of symptoms reported (hypothyroid compared to euthyroid) * (JAMA, 2000) hypothyroidism diagnosis: elevated serum TSH differential diagnosis thyroidal diseases - chronic autoimmune thyroiditis - subclinical thyroiditis - iodine deficiency - goiter - myxedema coma - euthyroid sick syndrome - often seen in hospitalized settings (patients with severe critical illness, deprivation of calories, and following major surgeries) - riedel thyroiditis - a rare inflammatory disease of the thyroid, causing compression and fibrosis of the thyroid and adjacent tissues - subacute thyroiditis - an immune reaction of the thyroid gland that often follows an upper respiratory infection - thyroid lymphoma - a rare thyroid malignancy where lymphoid cancer cells cause the thyroid gland to rapidly enlarge differential diagnosis (if TSH is normal but symptoms persist; may co-exist) anemia (vitamin B12 or iron deficiency) autoimmune (rare) - adrenal insufficiency (aka. Addison’s disease) - atrophic gastritis with pernicious anemia - celiac disease or gluten sensitivity - diabetes mellitus type 1 - rheumatoid arthritis chronic kidney disease liver disease menopause mental health disorder (i.e. depression, anxiety or somatoform disorder) obstructive sleep apnea viral infection (e.g. mononucleosis, lyme disease, HIV) factors that may cause aberrations in lab tests: high TSH Acute psychiatric illness (transient,14%) Following prolonged primary hypo- Anti-mouse antibodies thyroidism Antithyrotropin antibodies Heterophile antibodies Anti-TSH receptor antibodies Laboratory error Autoimmune disease (assay Macro-thyrotropin interference) Nonadherence to thyroid replacement Drugs therapy Amiodarone Older adults (especially women) Amphetamines Pituitary TSH hypersecretion Atypical antipsychotics Recovery from acute nonthyroidal Dopamine agonists illness (transient) Heroin Strenuous exercise (acute) Phenothiazines Sleep deprivation (acute) Exercise before testing TSH resistance (Current Medical Diagnosis & Treatment, 2023) factors that may cause aberrations in lab tests: low T4 + T3 Acute psychiatric illness Diclofenac (T3), naproxen (T3) Cirrhosis Didanosine Familial thyroid-binding globulin Fenclofenac deficiency 5-Fluorouracil Laboratory error Halofenate Nephrotic syndrome Imatinib Severe illness Mitotane Drugs Nicotinic acid Androgens Oxcarbazepine Antiseizure drugs (Carbamazepine, Phenobarbital Phenobarbital, Phenytoin) Phenytoin Asparaginase Salicylates, large doses (T3 + T4) Carbamazepine (T4) Sertraline Chloral hydrate Stavudine Corticosteroids T3 therapy (T4) (Current, 2023) natural health products to be aware of biotin - does not impair thyroid function but can interfere with laboratory testing falsely high fT4 and fT3 falsely low TSH - appears as hyperthyroidism or thyroid replacement dosing is too high - avoid interference by having patients discontinue biotin at least 48hr prior to testing st johns wort - retrospective case-control study (2001) suggests association between St. John's wort and transiently elevated TSH levels (no effect on fT4), but not statistically significant findings  Signs or symptoms of hypothyroidism (AAFP, 2021) Measure TSH low high TSH < 0.4 mIU/L TSH within range TSH > 4.0 mIU/L Consider hyperthyroid state Patient is euthyroid Measure fT4 low high fT4 below normal range fT4 within normal range fT4 above normal range Primary Subclinical not primary hypothyroidism hypothyroidism hypothyroidism central hypothyroidism - hypothyroidism due to insufficient stimulation by thyroid stimulating hormone (TSH) of an otherwise normal thyroid gland; can be secondary (pituitary) or tertiary (hypothalamus) in origin 1 in 80,000-120,000; < 1% of hypothyroid cases children: craniopharyngiomas, hx of cranial irradiation (brain or hematological cancer) adults: pituitary macroadenomas, pituitary surgeries or post-irradiation transient: sick euthyroid syndrome, over-replacement of T4 (primary hypothyroidism) hypothyroid symptoms (often milder) diagnosis: serum TSH + fT4 - low serum fT4, relatively low serum TSH management: referral - TRH Stimulation Test (Health Canada Special Access) prognosis: similar to primary hypothyroidism subclinical hypothyroidism - an endocrine disorder presenting with elevated TSH but normal thyroxine (fT4) 5-8% of females, 3% of males in US; 3-15% general population increased risk in females, age > 65 yrs, autoimmune thyroiditis asymptomatic (most often) or hypothyroid symptoms diagnosis: serum TSH and fT4 +/- symptoms +/- TPO antibodies - elevated TSH > 4.0 mIU/L; fT4 within range management: treatment recommended if TSH >10 mIU/L, TPO antibodies present, patient is symptomatic or has cardiovascular risk factors (e.g. ↑ cholesterol) if TSH is 4.0 - 10.0 mIU/L, monitor TSH q6-12mo prognosis: 60% resolve without intervention within 5yrs, 2-6% develop overt thyroid dysfunction (if anti-TPO present, risk is up to 50% over 20 yrs) - increased risk of fracture, ischemic heart disease and heart failure if TSH > 10 mIU/L (overt) primary hypothyroidism - an endocrine disorder presenting with elevated serum TSH and low thyroxine (fT4) 0.3% US adults, female (7-10x), > 65 yrs of age autoimmune disease (e.g. T1DM, celiac disease), Down or Turner syndrome hypothyroid symptoms (as listed previously) diagnosis: serum TSH, fT4 - high thyrotropin (TSH) > 4.0 mIU/L, low thyroxine (fT4) < 12 pmol/L - thyroid peroxidase antibody (anti-TPO) testing does not help diagnosis, but indicates autoimmune etiology management: thyroid hormone replacement therapy (T4) prognosis: with treatment, good prognosis without treatment: high risk of morbidity and mortality (i.e. heart failure) CTFPHC screening recommendations (CMAJ, 2019) - The Canadian Task Force on Preventive Health Care (CTFPHC) strongly recommends against screening for thyroid dysfunction in asymptomatic, nonpregnant adults - not likely to confer clinical benefit, but could lead to unnecessary treatment for some patients and consume resources - treating asymptomatic adults for screen-detected hypothyroidism may result in little to no difference in clinical outcomes - Clinicians should remain alert to signs and symptoms suggestive of thyroid dysfunction and investigate accordingly The US Preventive Services Task Force (USPSTF) states that current evidence is insufficient to assess the balance of benefits and harms of screening for thyroid dysfunction in nonpregnant, asymptomatic adults (2015). managing hypothyroidism in special populations  management of hypothyroidism Primary Subclinical Secondary hypothyroidism hypothyroidism hypothyroidism Levothyroxine TSH > 10 mIU/L + Brain MRI (T4 replacement therapy) positive thyroid antibodies, cardiovascular risk, or treatment-resistant depression Consider levothyroxine (T4 replacement therapy) thyroid function in pregnancy 20% to 40% increase in thyroid hormone requirement as early as 4 weeks - estrogen-mediated increase in thyroid-binding globulin, increased volume of distribution of thyroid hormone, as well as the placental metabolism and transport of maternal thyroxine - notable increase in thyroid gland size in about 15% of pregnant females trimester-specific reference ranges Test Nonpregnant 1st Trimester 2nd Trimester 3rd Trimester TSH (mIU/L) 0.4 - 4.3 0.1 - 3.0 0.1 - 4.0 0.5 - 5.0 fT4 (pmol/L) 11 - 23 10 - 25 10 - 19 9 - 17 fT3 (pmol/L) 3.4 - 5.9 3.5 - 6.0 3.5 - 6.0 3.0 - 5.2  thyroid antibodies and TSH during pregnancy (Lancet, 2018) TSH = thyroid-stimulating hormone, TAb = thyroid antibodies (e.g. anti-thyroperoxidase, anti-thyroglobulin) hypothyroidism in pregnancy - 0.3–0.5% of pregnancies (overt hypothyroidism); 2–3% subclinical - predominantly chronic autoimmune hypothyroidism effects associated with hypothyroidism and pregnancy - miscarriage - postpartum hemorrhage - gestational hypertension - abruptio placentae - pre-eclampsia - preterm birth + low birth weight - anemia - fetal neurocognitive deficits note about thyroid hormone replacement therapy (levothyroxine, LT4): - little to no effect on hypertensive disorders and placental abruption - reduces miscarriage, preterm birth - improves fetal intellectual development hypothyroid-related complications in pregnancy Odds Ratio (%) miscarriage risk - with antibodies elevated 1.8 - 3.9 recurrent loss - euthyroid with antibodies elevated 2.3 pre-term delivery - with antibodies (medicated) 2.07 (1.13) risk of placental abruption - first trimester, second 1.78, 2.14 risk of pre-eclampsia - primary hypothyroidism (medicated) 1.47 (1.32) postpartum thyroiditis risk 34.1 lower offspring IQ 7.5  known hypothyroidism prior to (UCalgary) increase thyroxine by 30% once pregnancy Yes No no screening pregnancy is confirmed unless recommended preconception TSH