Thyroid Part I Lecture Notes PDF

THYROID PART I Brad Case, ND, DC Endocrine System NM7356-CA Bastyr University—San Diego  2 HYPOTHYROIDISM 3  4 Hypothyroidism Affects ~10% of the adult population and >20% of seniors (based on blood tests...

THYROID PART I Brad Case, ND, DC Endocrine System NM7356-CA Bastyr University—San Diego  2 HYPOTHYROIDISM 3  4 Hypothyroidism Affects ~10% of the adult population and >20% of seniors (based on blood tests) Some estimates are ~25% of the population is affected Others have suggested as many as 40% (based on basal body temperature and symptoms) Females are affected much more Can range from mild symptoms with undetectable changes on blood tests to severe life-threatening myxedema coma Depression, weakness, and fatigue are usually the first symptoms Causes a decreased metabolic rate—utilization of fats, carbs, and protein declines—leads to weight gain  5 Hypothyroidism—Causes Primary (95%) Hashimoto’s thyroiditis; radioactive iodine ablation therapy; thyroidectomy; genetic/congenital; subacute thyroiditis caused by viral infections (usually transient); postpartum thyroiditis; iodine deficiency (rare in North America) or excess; drugs like lithium, amiodarone, or interferon-alpha Secondary Hypopituitarism from pituitary adenoma causing TSH deficiency (uncommon; usually associated with other S/S of pituitary insufficiency); Sheehan syndrome—pituitary ischemia during childbirth (d/t blood loss or hypotension) Tertiary Dysfunction of the HPA axis due to granulomatous conditions such as amyloidosis or sarcoidosis (rare) Peripheral Resistance to thyroid hormones in target tissues; lack of T4 to T3 conversion; or conversion from T4 to rT3 Subclinical Mild increase in TSH with normal levels of T 3 and T4  6 Hypothyroidism—Causes Hashimoto’s Thyroiditis (aka Autoimmune Thyroiditis or Chronic Lymphocytic Thyroiditis) The most common cause of hypothyroidism (by far) in the US Affects women 8x more than men Antibodies (especially to thyroid peroxidase (TPO) and thyroglobulin (TG)) form and bind to the thyroid and/or TSH receptors This destroys thyrocytes and prevents the synthesis of sufficient levels of thyroid hormones Causes diffuse enlargement/inflammation of the gland—goiter Causes diffuse iodine uptake on RAIU test Cellular infiltration of immune cells, esp. lymphocytes, is seen on biopsy May present as hyperthyroidism in the early phases, followed by a period of euthyroidism, and finally hypothyroidism  7 Hypothyroidism—Causes Certain toxins are known to be taken up by the sodium-iodide symporter and concentrated in the thyroid follicles. These generate free radicals, which activate immune responses, and possibly sensitize immune cells to thyroid proteins. They also damage antioxidant enzyme systems that protect cell membranes from lipid peroxidation. Heavy metals and chemicals that have been documented to correlate with Hashimoto’s include: Fluorine Perchlorate (chlorine) Bromine Iodine (in excess) Lithium Mercury Cadmium Lead Bisphenol A Organophosphate pesticides especially Hexachlorobenzene (HCB)  8 Hypothyroidism—Causes Genetics—correlated with HLA-B8 and HLA-DR 3—5 Iatrogenic: Lithium carbonate (bipolar), oral hypoglycemic agents, mercaptopurine (acute lymphoblastic leukemia), Para-aminosalicylic acid (TB), amiodarone (arrhythmias), tricyclic antidepressants, and interferon (hepatitis, et al.) block thyroid hormone synthesis Dexamethasone (corticosteroid), propylthiouracil (Grave’s), lopanic acid (radiographic contrast agent), amiodarone, and propranolol (β-blocker) alter peripheral conversion of T4 to T3 9  10 Hypothyroidism—Causes Pathologies—sarcoidosis, amyloidosis, scleroderma—replace thyroid parenchymal tissue with connective tissue Postpartum Thyroiditis—inflammation of the gland may occur months after childbirth; results in hyperthyroidism followed by hypothyroidism Estrogen connection?—hypothyroidism is much more common in women between the ages of 20 and 50, i.e., childbearing years  11 Hypothyroidism—Causes Stress—changes to serum cortisol, even in the normal range, such as occurs after critical illness, trauma, or grief can significantly alter thyroid hormone levels; low thyroid function may be a coping mechanism for stress Sleep deprivation and excess alcohol appear to impair thyroid function  12 Hypothyroidism—Causes Nutrition: Deficiency of: Vitamins—riboflavin, niacin, vitamin E Minerals—selenium, iodine, iron, zinc, potassium Amino acids—tyrosine, cysteine Iodine deficiency is still common in the developing world and is the most common cause of hypothyroidism world wide, though it is rarely seen in the US due to the iodination of salt Keep in mind, however, that thyroid glands with autoimmune inflammation are very susceptible to excessive iodine intake  13 Iodine Levels Worldwide  14 Hypothyroidism—Causes Nutrition: Goitrogens: excess consumption of cruciferous veggies can induce hypothyroidism Brassicas—cabbage, kale, arugula, Brussels sprouts, broccoli, bok choy, collard, rutabaga, turnips, radishes, watercress, wasabi, shepherd’s purse (Capsella), mustard, cauliflower… Also: peanuts, peaches, pears, spinach, and soy Clinical Pearl—soy makes TPO inactive— can’t organify iodide, so can’t make thyroid hormone  15 Hypothyroidism—History Iodine Toxicity: Exposure to ionizing radiation (especially as a child): Nuclear bomb/testing—Hiroshima & Nagasaki (Japan, 1945); Marshall Islands (testing1946—’58) Nuclear reactor leaks—Chernobyl (Ukraine, 1986) or Fukushima (Japan, 2011) Iatrogenic causes: Amiodarone (iodine-containing anti- arrhythmic drug) Iodine-containing contrast media Cancer treatments using radioactive iodine  16 Hypothyroidism—History Family Hx: Goiter, hyperthyroid, hypothyroid, or thyroid cancer Autoimmune diseases: T1DM, pernicious anemia, alopecia, vitiligo, myasthenia gravis MEN types 2A and 2B Toxins, Infections, & Hormone Imbalances 17 18  19 Hypothyroidism—Clinical Features General/Metabolic Signs: Cold intolerance, weight gain, shortness of breath, constipation, decreased sweating (decreased sympathetic activity), slow reflexes Enlargement of tongue, coarsening of facial features, deepening of voice/hoarseness CNS/Psychological Signs: Slowing of physical and mental activity, fatigue, decreased exercise capacity, slow speech, mental sluggishness, forgetfulness, apathy, listlessness, lethargy, inability to concentrate May be severely depressed, or extremely agitated (myxedema madness) Hearing impairment or tinnitus  20 Hypothyroidism—Clinical Features Skin, Hair, Nails: Skin dry and rough with superficial scales; later, it may become pale, yellow, cool, and edematous Dry, course, brittle hair; diffuse hair loss (may be severe); premature graying of hair; loss of lateral 1/3 of eyebrows Nails become thin (or thick) and brittle, often with vertical ridges Intestinal Peristalsis: Markedly slowed; results in chronic constipation Occasionally severe fecal impaction or ileus  21 Hypothyroidism—Clinical Features Cardiovascular Signs: Pts have impaired ventricular contraction, bradycardia, and increased peripheral resistance → decreased cardiac output CHF or pulmonary edema are rare, however ECG may show low voltage P, QRS, and T waves Total cholesterol, LDL, CRP, lipoprotein A, and homocysteine may be increased → coronary artery disease/atherosclerosis is common Cardiac enlargement may occur due to interstitial edema Pericardial effusion may also occur Capillaries become more permeable and lymphatic drainage is slowed → edema  22 Hypothyroidism—Clinical Features Pulmonary Function: Pts have shallow, slow respirations and impaired ventilatory responses to hypoxia and hypercapnia Respiratory failure occurs in pts with myxedema coma Renal Function: Impaired, with decreased GFR and impaired ability to excrete water → pts are predisposed to hyponatremia/water intoxication from drinking excess water Hypothyroidism leads to decreased cardiac output, which leads to increased ADH secretion Albuminuria may occur  23 Hypothyroidism—Clinical Features Anemia: Occurs through four different mechanisms: 1.) Impaired hemoglobin synthesis—d/t T4 deficiency 2.) Iron deficiency d/t iron loss in pts w/menorrhagia (low MCV) 3.) Folate deficiency from impaired intestinal absorption Results in macrocytic/megaloblastic anemia (high MCV) 4.) Pernicious anemia d/t cluster of autoimmune diseases sometimes referred to as polyendocrine failure syndrome Causes B12 deficiency with megaloblastic anemia (high MCV) Polyendocrine failure syndrome includes Hashimoto’s, pernicious anemia, diabetes mellitus, and adrenal insufficiency (Addison’s)  24 Hypothyroidism—Clinical Features Neuromuscular Signs: Muscle cramps, pain, and weakness; peripheral and/or poly- neuropathy, e.g., carpal tunnel syndrome (decreased conduction velocities); cerebellar ataxia, tremor, dysmetria, chronic/recurrent headache, myopathy, hypotonia, cranial nerve deficits, slowing of voluntary movements Paresthesia, arthralgia, fibromyalgia/chronic fatigue syndrome Infants & Children: Hypothyroidism in infants and children results in major slowing of growth and development Permanent consequences such as mental retardation occur in infants (Cretinism) Later in childhood, it can result in short stature  25 Hypothyroidism—Clinical Features Reproductive Signs: Impaired conversion of estrogen precursors to estrogens Lack of negative feedback → ↑TRH → ↑PRL → ↓ FSH and LH secretion → anovulatory cycles and infertility Men have decreased libido and erectile dysfunction Increased risk of miscarriage, premature delivery, and stillbirth Menorrhagia—prolonged & heavy with shorter cycle; perhaps d/t altered platelet function Other Endocrine Signs: Adrenal dysfunction is common with both primary and secondary hypothyroidism; treat/fix the adrenals first as the increased metabolism from proper thyroid function will add extra burden on the adrenals Pts with thyroid antibodies often have adrenal cortex antibodies as well Cortisol secretion may increase to compensate for low T3 levels  26 Hypothyroid—Physical Exam Vitals: HR, temperature, and BP may be lower than normal in hypothyroidism (systolic BP may be low with high diastolic BP, i.e., narrow pulse pressure) Pt may be overweight Palpation of the Thyroid: The normal thyroid is barely palpable—if you feel it at all, it feels smooth/homogeneous, soft, and slightly rubbery, without any nodularity Each lobe measures about 2 cm vertically x 1 cm wide In Hashimoto’s, there may be a diffuse (goiter) or, it may have a bosselated (cobblestone) or finely nodular surface In older pts, it may have atrophied and be non-palpable  27 Thyroid Palpation  28 Hypothyroid—Physical Exam Reflexes: Patients with hypothyroidism will have delayed deep tendon reflexes, or slow recovery, especially of the ankle reflex Observation/Palpation: Hoarse, husky voice Skin is cool, rough, and dry; may be yellowish The pt may have non-pitting edema and/or myxedema; most evident in the skin, heart muscle, and striated muscle Most notably: Puffy face and hands This is due to decreased metabolism of glycosaminoglycans (mostly hyaluronic acid), which accumulate in the interstitial tissues; these are hydrophilic substances; also capillaries become more permeable to albumin and lymphatic drainage is slowed  29 Myxedema  30 Hypothyroid—Physical Exam In Infants & Children (Cretinism): Intellectual disability (declining school performance), short stature, puffy appearance of the face and hands, deaf mutism, neurologic signs of pyramidal and extrapyramidal tract abnormalities; precocious puberty may occur Signs of respiratory difficulty, cyanosis, jaundice, poor feeding, hoarse cry, umbilical hernia, retardation of bone maturation In the developed world, newborns are typically screened for this by checking TSH or T4 Heel stick performed 24–48 hrs after birth T4 < 6 µg/dL or TSH > 25 mU/L suggests hypothyroidism Early treatment of cretinism can prevent permanent intellectual disability  31 Cretinism  32 Hypothyroid—DDX Condition Clinical Features Chronic Fatigue Defined by CDC as medically unexplained, persistent, or relapsing Syndrome fatigue of 6 months’ duration; worse with physical activity; depression may occur; arthralgia and myalgia; unrefreshed sleep; persistent flu-like symptoms Post-Partum Depression Depression occurring within the first year of giving birth Major Depressive · Depressed mood · Lack of energy Disorder · Anhedonia · Poor concentration · Sleep disturbance · Feelings of worthlessness or Five of listed to right: · Change in appetite or weight guilt · Psychomotor problems · Suicidal ideation Sleep Apnea Repeated airway obstructions during sleep causing daytime somnolence, forgetfulness, and depression; snoring and witnessed episodes of gasping during sleep  33 Hypothyroid—Labs TSH—High if primary; low/normal if secondary or tertiary Labcorp reference range = 0.45—4.5 uIU/mL Functional reference range 1—3 uIU/mL Total T4 and fT4—Low Total T3 and fT3—May be low or normal (used more for hyperthyroid) Antibody tests for Hashimoto’s Autoimmune Thyroiditis: anti-TPO (most sensitive/earliest indicator)—elevated anti-Tg (least sensitive)—often/usually elevated rT3—may be high in “Wilson’s syndrome” or adrenal cortex hyperfunction (ref range 8—25 ng/dl) High TSH with normal T4 is considered subclinical hypothyroidism 34  35 Hypothyroid—Labs  36 Hypothyroid—Labs  37 Hypothyroid—Labs T3 Uptake: Measures the percentage of binding sites on carrier proteins (primarily TBG) that are currently occupied by T3 Allows you to compare TBG level with free hormone levels Will be low in hypothyroid (because of low T3); acute hepatitis, pregnancy, and pt’s on estrogen (because of higher TBG synthesis) Will be high in pts with hyperthyroid (because of high T3); kidney failure/nephrotic syndrome, or protein malnutrition (because of low TBG synthesis) Important when Total T4 is (falsely) low due to protein deficiency  38 Hypothyroid—Labs Free Thyroxine Index (FTI); aka Thyroid Index (T7): FTI = (T4 x TU)/TU median of Reference interval TU = T3 Uptake In most clinical situations, direct measurement of free thyroxine (fT4) has replaced the FTI test, however, it can still be useful for diagnosing central hypothyroidism in some cases The FTI increases in hyperthyroidism and decreases in hypothyroidism Hypothyroid—Labs 39  40 Hypothyroid—Labs Total cholesterol and triglycerides may be increased Cortisol—in pts with adrenal cortex hyperfunction, it will be normal in a.m. and increase throughout the day Radioactive iodine uptake (RAIU)—low uptake in Hashimoto’s thyroiditis Hair analysis—increased Ca:K ratio  41 Hypothyroid—Labs Iodine Labs: Serum or Plasma Iodine—takes longer to read than urine tests; rarely done Urinary Iodine (random)—a single urine sample—this is the test performed by most MDs Urine Iodine-to-Creatinine ratio  42 Hypothyroid—Labs Iodine Labs (cont): 24-hour Urine Iodine—Patient voids at 8 AM and discards the specimen, then collects all urine including the final specimen voided at the end of the 24-hour collection period (i.e., 8 AM the next morning) Second best test Iodine Loading Test—pt collects a baseline urine sample, then takes 50 mg of iodine, then collects their urine for 24 hours. A person with sufficient iodine will excrete 90% of the iodine in that time period. The lower the excretion rate, the greater the deficiency. Most accurate test, but more inconvenient  43 Iodine Patch Test How to Do the Test: Buy the brownish-red iodine from a drug store Paint a patch on your abdomen, inner forearm, etc. (somewhere you can easily observe) about the size of a silver dollar (~1.5–2 inches in diameter) Pay attention to how quickly the stain disappears  44 Iodine Patch Test How to Interpret the Test: If it disappears (or lightens considerably) in less than 24 hours, you may be deficient in iodine; if it disappears in less than 18 hours, the deficiency may be moderate to severe Disclaimer: I would take this test with a big “grain of salt” as there are many factors that can lead to the early disappearance of the stain; and there is little to no evidence of its accuracy  45 Barnes Basal Body Temperature How to Do the Test: Get a mercury thermometer (glass is best) and shake it down before going to bed First thing in the morning, while still in bed, place it under your arm (armpit) and leave it there for 10 minutes Do this for several days in a row (3—10) and record your temperature Women who are still having menstrual cycles should do the test during their period (2nd and 3rd days are most accurate) Menopausal women and men can take their temperature on any day  46 Barnes Basal Body Temperature How to Interpret the Test: An average below 97.8ºF (36.6ºC) suggests hypothyroidism A basal pulse of 65 bpm or below may also be an indication of hypothyroidism Disclaimer: I do not know how accurate this test really is. It is given to you here because you will likely hear about it. I suggest using it as additional information in your diagnostic workup. Do not base a medical diagnosis solely on this test.  47 Barnes Basal Body Temperature Why the Test May Be Important: This test may be helpful in a person who is making plenty of T4, but who can’t convert it to T3 (for e.g., due to a selenium deficiency); someone who converts T4 to rT3 (such as in high cortisol); or someone who’s cells are T3 resistant Each of these pts would show normal TSH, normal T4 and fT4 levels, and still have all the symptoms of hypothyroidism; thus, they would be missed by screens that only tested these hormones This has been dubbed “Wilson’s (temperature) syndrome” This is not an acceptable medical diagnosis, however  48 Naturopathic Treatment The Gut Connection—autoimmune diseases such as celiac disease and Hashimoto’s are correlated with leaky gut and food allergies ~14% of pts with celiac disease have positive anti-TPO antibodies Studies show, putting these pts on a gluten-free diet gradually eliminated their TPO antibodies over the course of 2 years Work on healing the gut: Test for celiac and/or have pt perform a 3-month trial of gluten-free diet Glutamine (2,000—3,000 mg), probiotics, colostrum, demulcents, etc. Test for and avoid food allergies Pts who are lactose intolerant and have Hashimoto’s see their TSH levels decrease when they avoid lactose Correcting for candidiasis can also help decrease antibody levels  49 Naturopathic Treatment Diet/Nutrition: Eat an anti-inflammatory diet Tyrosine is the amino acid used to make thyroglobulin Vegans have lower levels of tyrosine than people who eat meat and/or fish Zinc, vitamin E, and vitamin A function together in the manufacture of thyroid hormones Vegans are often deficient in zinc, as well Vitamin B6 (pyridoxine), riboflavin, niacin, and vitamin C are also necessary for thyroid hormone production  50 Naturopathic Treatment Diet/Nutrition: Iodine: Only give if pt is truly deficient; too much iodine inhibits thyroid hormone synthesis; not usually recommended with Hashimoto’s RDA is 150 mg/d; most US adults get > 600 mg/d, however, goitrogens can combine with dietary iodine and create a deficiency Vegans are often deficient in iodine, too  51 Naturopathic Treatment Diet/Nutrition: Zinc (20—30 mg/d), copper (1—2.5 mg/d), and selenium (200—400 µg/d) are required to synthesize the iodothyronine deiodinase enzymes, needed to deiodinate T4 to T3 Selenium supplementation has also been shown to decrease thyroid antibody levels; it is deficient in ~50% of the population Fish oils may help reduce inflammation Glutathione can help reduce free radicals from toxins PABA seems to decrease TPO levels to some extent  52 Naturopathic Treatment Iodine sources—ocean fish, sea vegetables (kelp, dulse, etc.) Zinc sources—seafood (esp. oysters), beef, oatmeal, chicken, liver, spinach, nuts, seeds Copper sources—liver and other organ meats, eggs, yeast, beans, nuts, seeds Selenium sources—Brazil nuts (best), tuna, eggs, rice  53 Naturopathic Treatment Goitrogens: Brassicas—turnips, cabbage, rutabagas, mustard greens, collard greens, radishes, horseradishes, kale, cauliflower, broccoli, bok choy Cassava root, soybeans, almonds, peanuts, pine nuts, millet, sweet potatoes These foods should all be cooked to break down the goitrogenic constituents and/or probably not eaten in large quantities in pts with hypothyroidism  54 Naturopathic Treatment Goitrogens (continued): Environmental goitrogens include: the halogens: chlorine (perchlorate), fluorine, and bromine (same group/column of periodic chart as iodine), and iodine in excess Medications that can induce goiters and affect thyroid function include: amiodarone, carbamazepine, lithium, potassium iodine, phenobarbitone, phenytoin, and rifampin  55 Naturopathic Treatment Toxins: Many autoimmune diseases have toxicity as a root cause Consider testing for heavy metals and chemicals and/or detoxing your patient of these toxins MosaicDX—Metals (urine, hair, RBC, whole blood, or stool), Organic Acid Test (OAT), Glyphosate Filter water (chlorine/perchlorate, fluorine)—both drinking water and shower/bath water Avoid mercury sources—“silver” fillings (amalgams), large fish (tuna, shark, etc.), vaccinations (e.g., flu shot) Use non-fluoridated toothpaste and don’t cook with teflon Oral chelation agents (e.g., chlorella) and binders (e.g., bentonite clay or activated charcoal), along with mineral supplementation should be done long before any IV chelation is attempted  56 Naturopathic Treatment I recommend: Water filters for drinking water and shower/bath Biological/Holistic dentist for mercury amalgam removal Fluoride-free toothpastes  57 Naturopathic Treatment Estrogen Dominance: Pts with high estrogen, such as in pregnancy, or those taking HRT or OCPs, (or Tamoxifen) or those with liver disease may have high TBG levels. This leads to lower levels of free thyroid hormone. Transdermal estrogens (vs. oral) may lessen this effect by not going to the liver on their first pass through circulation  58 Naturopathic Treatment Other Hormones: Be sure to rule out secondary or tertiary hypothyroidism, i.e., pituitary or hypothalamus as the true cause These patients would have low TSH and low thyroid hormones  59 Naturopathic Treatment Other Hormones: Also, you may want to test your patient’s adrenal function: Many hypothyroid patients also have adrenal cortex hyperfunction, which can be primary or secondary to the thyroid Cortisol and DHEA testing—blood, urine, or salivary Ragland’s (orthostatic BP) test is a functional adrenal test Pupillary Hippus test is another functional adrenal/parasympathetic test Adrenal testing and support will be discussed in the Adrenal lectures  60 Adrenal vs. Thyroid T4 converts to rT3 rT3 Blocks T3 Adrenal Stress receptors Decreased Metabolism Weight Gain, Fatigue, and reduced Thyroid altered sugar control Function  61 Naturopathic Treatment Botanicals: Withania somnifera Fucus vesiculosus (Bladderwrack)—6 mL/d—has iodine, so be careful using with Hashimoto’s Eleutherococus senticosus—5 mL/d Coleus forskohlii—10 mL/d—helps with wt. loss Curcuma longa Rehmannia—for autoimmune Rhodiola rosea Glycyrrhiza glabra Centella asiatica—depression, dry skin, cold extremities, poor digestion, weight gain, poor endurance Echinacea—Hashimoto’s Galium aparine—anti-inflammatory; lymph tonic Gentiana—promotes metabolism; Wilson’s Temp Syndrome Juglans Nigra Phytolacca americana—immuno-stimulant; lymphatic; goiter—2 drops/d for 10 days Taraxacum officinalis—promotes metabolism; Wilson’s Temp Syndrome Urtica dioica—diuretic  62 Naturopathic Treatment Other Important Determinants of Health: Invigorating activity/exercise—e.g., water sports Stimulates thyroid gland secretion; increases tissue sensitivity to thyroid hormones; speeds up metabolism; also helps with, stress (so less conversion to rT3), depression, and weight loss Full spectrum light stimulates T3, T4, and TSH production Avoid becoming overheated Get plenty of restful sleep Cold plunges; contrast showers; constitutional hydro  63 Naturopathic Treatment Protomorphogens: These are powerful products similar to glandulars, but they don’t contain any hormone SP—Thytrophin PMG, Symplex F/M, Paraplex They are the chromatin or genetic materials, i.e., the building blocks for that organ or gland They help repair and rebuild the damaged gland; or, they can act as decoys where antibodies attack them rather than the gland, thus, allowing the gland to heal Protomorphogens are available for most of the organs and glands of the body including the thyroid, adrenals, pituitary, hypothalamus, gonads, liver, heart… Dose is 1—6 tabs/d (most commonly 2—3/d)  64 Naturopathic Treatment Warning! Naturopathic Treatment of Hypothyroidism Works! Therefore: If the pt is also taking thyroid medications, have the patient watch for symptoms of hyperthyroidism: Palpitations, loose stool, racing feeling, sleeplessness, etc. As they improve under your care, they will need less and less of the exogenous hormone You or the prescribing doctor will need to ween the pt off of their meds or lower their dose  65 Conventional Treatment Thyroid Hormone Replacement: Levothyroxine (Synthroid/Levoxyl)—bioidentical T4—taken once daily in a.m. a half hour before food or beverages (other than water) Start at 50 µg/d and titrate up (or down) until TSH and T4 are in the normal (functional) range and symptoms have abated Typical adult dosages = 50—200 µg/d (mean 125 µg/d) Pts with concurrent heart disease should start at 25 µg/d Adjustments are made based on labs and symptoms; re-check every 4—6 weeks until optimal Soy products, PPIs, aluminum hydroxide antacids, bile acid-binding resins (e.g., cholestyramine), calcium supplements, sucralfate, or iron compounds decrease T4 absorption, so these should be taken ≥ 4 hours away from thyroid meds Pregnancy, estrogen replacement, and anti-seizure medications (e.g., carbamazepine) may also increase T4 requirements Half life = 7 days, so missing a few days is usually not detrimental to pts  66 Average Levothyroxine Dose by Age Because of more rapid metabolism, children require a surprisingly large dose compared to adults Dose in pregnancy is typically increased by 30–50% Note: doses are in micrograms, not milligrams  67 Conventional Treatment Thyroid Hormone Replacement: Liothyronine (Cytomel)—bioidentical T3 —good for those who cannot deiodinate T4 (used in addition to levothyroxine) 5—10 µg/d; titrated until labs are in reference range and basal body temperature and symptoms have normalized Well absorbed Half-life ~ 2.5 days Most patients do not benefit from this addition to levothyroxine, but some clearly do  68 Conventional Treatment Thyroid Hormone Replacement: Armour thyroid—desiccated (porcine) thyroid extract—only available by prescription; contains all thyroid hormones: T4, T3, and T2; as well as relevant amino acids and micronutrients; may be harder to regulate dosage due to small inconsistencies in amount of hormones; contains ~38 µg of T4 and 9 µg of T3 per grain (65 mg); 4:1 ratio Start dose somewhere between half a grain and 2 grains (depending on the pt’s size and thyroid hormone levels), and titrate from there May act as decoys for anti-thyroid antibodies too, thus protecting the gland  69 Conventional Treatment Thyroid Hormone Replacement: NP Thyroid—another brand of desiccated (porcine) thyroid extract (DTE) What’s the “issue” with desiccated thyroid extracts? Healthy human thyroid glands secrete T4 and T3 in a ~14:1 ratio whereas the ratio of T4 to T3 in DTE preparations is ~4:1. Using these products could lead to: Symptoms of hyperthyroidism and greater risk of thyrotoxicosis  70 Other Thyroid Hormone Medications Thyrolar—T3 & T4 (was a combination of levothyroxine and liothyronine); it has been discontinued WP Thyroid and Nature-Throid (desiccated thyroid extracts) are unavailable currently (since August 2020) due to a nation-wide voluntary recall because, apparently, the products contained < 90% of the active ingredient 71  72 Conventional Treatment Adverse Effects of Thyroid Medications: Typical are symptoms of thyroid hormone overdose, leading to hyperthyroidism, i.e., palpitations, arrhythmias (paroxysmal atrial tachycardia, atrial fibrillation) Insomnia, tremor, restlessness, and excessive warmth Increased bone resorption may occur if allowed to continue long-term Simply omitting the daily dose for 3 days and then lowering the dose (titrating downward) will usually correct the problem  73 Trial Withdrawal of Medications Patients who’ve undergone treatment to affect the cause of their condition, or who now have normal antibody levels for any other reason, may be withdrawn from their medication for 6 weeks on a trial basis It takes 1 week for the thyroid hormone to wash out of the system and another 5 weeks for the pituitary to begin secreting TSH again after being suppressed If at the end of 6 weeks, the pt’s fT4, TSH, and antibodies are in the normal range, they can continue without meds If their labs are not normal, they should go back on the medication  74 Hypothyroidsim—Complications Myxedema Coma: The (rare) end stage result of untreated hypothyroidism Progressive weakness, stupor, hypothermia, hypoventilation, hypoglycemia, and hyponatremia May result in shock and death More common in winter, in female pts with underlying pulmonary and vascular disease Exam reveals bradycardia, hypothermia (75—95.9℉) Pt usually obese and elderly with yellowish skin, a horse voice, a large tongue, thin hair, puffy eyes, ileus, and slow reflexes These pts should be hospitalized in the ICU; may require ventilation and close monitoring of fluids and electrolytes in addition to thyroid medications  75 Hypothyroidsim—Complications Myxedema Coma: Labs: Markedly elevated TSH; low fT4 Thyroid autoantibodies highly elevated (if Hashimoto’s) High serum carotene Hyponatremia High BUN and Creatinine High cholesterol and lactescent (whitish) serum (indicates extremely elevated triglycerides) High protein level in CSF Pleural, pericardial, or peritoneal effusion ECG—sinus bradycardia with low voltage  76 Hypothyroidsim—Complications Hypothyroidism & Heart Disease: Levothyroxine can sometimes exacerbate angina, heart failure, or MI in pts with severe hypothyroidism and heart disease β-adrenergic-blocking agents, coronary stenting, and coronary artery bypass surgery should be employed first in these pts, then, levothyroxine will be better tolerated  77 Hypothyroidsim—Complications Hypothyroidism and Neuropsychiatric Disease: Hypothyroidism is often associated with severe depression Rarely, the pt may be confused, paranoid, or even manic (myxedema madness) Screening these pts with serum fT4 and TSH will help identify pts who will respond to T4 therapy with or without psychopharmacological agents  78 Hypothyroidism—Prognosis When managed properly, hypothyroidism has an excellent prognosis Once medications are titrated to the correct dose, pts should be monitored every 6—12 months with at least TSH and fT4 labs Some patients, after an extended period of taking exogenous hormone (especially desiccated) can be removed from therapy and are cured  79 Hypothyroidism—Case A 43-year-old woman presents to your office with complaints of fatigue, weight gain, and constipation. She states that her weight has gradually increased over the last year despite no change in her activity level or eating habits. She eats a Standard American Diet and tries to drink about 8 cups (64 oz) of water/d. She works 8 hours a day as a nutrition assistant. She sits for most of the day, but states that she barely has the energy to get through the day, and climbing the two flights of stairs to get up to her third floor apartment when she gets home is becoming a challenge. She usually takes a two-hour nap as soon as she gets home in the afternoon before finally making herself some dinner. She goes to bed shortly after that. Her sleep quality is good and she averages 9—11 hours/night (including naps), but she does not feel refreshed on waking. She lacks motivation to exercise or do anything during the weekend, and notes that she does not feel like her old self. Her medical history includes the removal of three silver amalgams and replacement with safer materials by a traditional dentist about eighteen months ago. No special precautions were taken. Upon questioning, the patient  80 Hypothyroidism—Case Vital Signs: HR: 72 bpm BP: 108/70 mmHg Temp: 97.8 ℉ Wt: 165 lbs Ht: 5’4” RR: 12 cpm Physical examination confirms dry skin, brittle nails, coarse and dry hair, and abdominal distention. Her thyroid palpates as normal sized with no nodules noted. Heart exam is normal. Reflexes are +2 except for achilles which is +1 bilaterally. Muscle strength is 5/5 for all.  81 Hypothyroidism—Case What labs and imaging would you run, and what would be the expected results (high, low, etc.)? What specific determinants of health issues would you be sure to ask about and/or correct? What other treatments would you recommend? Be comprehensive with your Tx plan; include doses and how to titrate. Conventional (medications) Natural (botanicals, supplements, lifestyle…) 82 To Learn More: 83 References Greenspan's Basic & Clinical Endocrinology Textbook of Natural Medicine, 4th edition, by Pizzorno and Murray Fundamentals of Naturopathic Endocrinology by Michael Friedman, ND The 5-Minute Clinical Consult 2017, 25th Edition, by Frank Domino Nutritional Medicine, by Alan Gaby, MD Lippincott’s Pharmacology, 5th Edition, by Richard Harvey Endocrine Handbook, by Henry Harrower, MD Practice guidelines and classifications GARD - NIH Databases UpToDate DynaMed Plus BMJ Best Practice