Clin Med - Thyroid Disorders.pdf

Thyroid Disorders ASHLEY NORDAN, MHPE, MSCR, MPAP, PA-C CAMPBELL PA PROGRAM SPRING 2024 The Basics: Anatomy Also note location of parathyroid glands The Basics: Physiology need to know these hormones need to know the negative feedback loop TRH = thyrotropin releasing hormone TSH = thyroid stimulatin...

Thyroid Disorders ASHLEY NORDAN, MHPE, MSCR, MPAP, PA-C CAMPBELL PA PROGRAM SPRING 2024 The Basics: Anatomy Also note location of parathyroid glands The Basics: Physiology need to know these hormones need to know the negative feedback loop TRH = thyrotropin releasing hormone TSH = thyroid stimulating hormone T4 = thyroxine T3 = triiodothyronine The Basics: Physiology Two different cell types:  Follicular cells: synthesize and secret T4 and T3  Parafollicular cells: secrete calcitonin T4 and T3 synthesis: 1) Iodide enters follicular cell and is oxidized by thyroid peroxidase (TPO). 2) TPO then mediates iodination of tyrosine molecules carried by thyroglobulin. 3) Mono and diiodotyrosine couple up to make T4 and T3, bind to thyroglobulin, and stay stored in the follicular cells. 4) TSH stimulates proteolytic digestion of thyroglobulin and thus secretion of free T4 and free T3 from cells. 5) T4 and T3 then tightly bind to thyroxine-binding globulin (TBG), thyroxinebinding prealbumin, and albumin in serum. 6) T4 converts to T3 by deiodination in peripheral tissues. The Basics: Physiology Key Points about Thyroid Physiology  Iodine is essential to production of thyroid hormones.  T4/T3 are mostly bound to protein (TBG) in circulation. Smaller percentage thyroid binding globulin in blood circulation is free.  T4 predominates but T3 is the bioactive hormone.  T4 converts to T3 in the peripheral tissues.  There are T3 receptors on a vast amount of organ systems. T3 is actually used T4 is like a pro-hormone Diagnostic Tools for Thyroid Evaluation  Physical Exam  Labs:   Thyroid Stimulating Hormone (TSH)  Thyroxine (T4) and Triiodothyronine (T3)  Antibody testing Imaging:  Ultrasound (1st line)  Radioactive Iodine Scan and Uptake if you have a patient you suspect have a thyroid disorders you would start with a PE then you can order labs, including antibodies (which are specific to certain disorders) first line imaging is ultrasound the Thyroid Scan (the radioactive iodine scan and uptake) is both diagnostic and therapeutic and can be used to better understand the FUNCTION of the thyroid Thyroid Exam thyroid exam is completed from behind using both hands ask patient to swallow Abnormal PE Findings Goiter goiter means enlarged thyroid can be symmetric = whole thing is enlarged asymmetric = only one side is enlarged nodule or multi-nodule  Enlargement of the thyroid gland  Does not tell you anything about thyroid function   Pts can be hyperthyroid, euthyroid or hypothyroid with a goiter Thyroid carcinoma causes focal thyroid enlargement Abnormal PE Findings Thyroid Nodules  VERY common, often incidental  Most are follicular adenomas, colloid nodules, benign cysts or nodular thyroiditis  Malignancy still needs to be on DDx! can cause a goiter very common if found on PE, must be evaluated! most are benign but still cannot be ignored Thyroid Labs: Thyroid Function TSH is the gold standard - used for screening and monitoring disease  TSH – 1st line screening test for thyroid abnormalities    TSH has long half life T3/T4 (total or free) T3/T4 total and/or free  Free = available for uptake into cells; Total = circulating storage pool  Most T3/T4 is bound to thyroxine-binding globulin (TBG) – T4 (99.96%), T3 (99.4%)  Levels fluctuate throughout the day (short half life) T3-uptake – available binding sites on TBG  Indirectly measures TBG  Designed to distinguish TBG excess and deficiency from hyper- and hypothyroidism T3 has a shorter half life, but it is provider dependant on which is most important to check Thyroid Labs: Antibodies  Thyroid Peroxidase (TPO) Ab.  Thyroglobulin (Tg) Ab.  Thyrotropin Receptor Ab. (TRAb) – stimulating, blocking, or neutral  thyroglobulin ab SHOULD be ZERO (it lives in the thyroid) Thyroid Stimulating Immunoglobulins (TSI) = Graves Dz. Imaging  Ultrasound: useful for evaluating volume, location, parenchyma, identifies nodules, and lymphadenopathy  Parenchyma: heterogenous (autoimmune) vs homogenous  Describes nodule characteristics (solid vs cystic)  Used for guidance during FNA biopsy Imaging  Radioactive Iodine Scan and Uptake  Nuclear medicine exam using radioactive iodine (I-123)  Contraindicated in pregnancy  Thyroid Scan: uses gamma camera to assess the size, shape, and location of functional activity in the gland  Uptake: used to quantify the thyroid uptake.  Increased uptake = “warm or hot” = functioning (hyperthyroidism, toxic aka functional nodule)  Decreased uptake = “cold” = non-functioning (thyroiditis, malignancy) cold nodules are BAD hot nodules are functioning Graves Disease Toxic Multinodular Goiter Thyroiditis Autonomous Nodule Hypothyroidism Hypothyroidism all thyroid conditions are more common in women   presentation is always slowed down s/s Epidemiology:  0.1-2% of US population  5-8x more common in women Presentation: (Dry, Slow and Cold)  cold intolerance (versus feeling cold) - cannot respond quick enough to deal with temperatures COMMON: fatigue, dry skin, hair loss, constipation, cold intolerance, weight gain, depression, and only thing that does menorrhagia not follow slow rule is menstrual cycles - which speed syndrome, sleep up  LESS COMMON: Carpal tunnel apnea, hoarseness, dysphagia, decreased taste and smell  PE Findings: Myxedema* (Preorbital or peripheral edema), delayed reflexes, bradycardia, +/- goiter looks puffy in the face these pics show before and after treatment Hypothyroidism  if the problem is above the thyroid in the pituitary or hypothalamus Lab Findings: it understimulated the thyroid Primary Hypothyroidism Thyroid is the problem Secondary Hypothyroidism Pituitary or Hypothalamus is the problem TSH High Low/Normal Free T4/T3 Low Low Hypothyroidism  Etiology:   Primary Hypothyroidism  Hashimoto’s thyroiditis  Euthyroid Sick Syndrome  Subclinical Hypothyroidism  Iatrogenic - Thyroidectomy, radioactive iodine ablation  Iodine deficiency  Congenital  Drugs: Lithium, Amiodarone, antithyroid drugs need to know the ones in blue Secondary Hypothyroidism  Pituitary dysfunction—radiation, neoplasms, surgery, hypopituitarism Hashimoto’s Thyroiditis  Auto-immune destruction of the thyroid more common in women most common cause of hypothyroidism in adults starts as a hyperthyroidism  Most common cause of hypothyroidism in adults  Initially causes hyperthyroidism from spillage of T4/T3, the progresses to hypothyroidism  TSH – low in early dz.; high in late dz.  T4 – high in early dz.; low in late dz.  Positive TPO +/- Thyroglobulin antibodies high in late disease bc trying to signal thyroid (that was attacked) to make more (but cannot) directly attacking the thyroid thyroglobulin (the storage unit of T3 and T4) is being directly attacked the T3 and T4 spills into blood stream causing symptoms of HYPERthyroidism due to the spilling, but the patient will eventually become hypothyroid because there is no storage unit Euthyroid Sick Syndrome  A condition occurring in acutely ill patients  Total T4 low (and maybe free T4 too)  TSH normal  Thyroid labs return to normal following resolution of illness  require treatment it will eventually go back to normal it is due to a transcient increase of a sick patient do not check thyroid levels of a sick patient Do NOT Subclinical Hypothyroidism pituitary gland is working by sending TSH to fix T3/T4 levels  Normal T4 and T3; mildly elevated TSH  Pt’s are asymptomatic  Some may progress to overt hypothyroidism (think early autoimmune dz.)  Treat if…  1. TSH > 5mU/L x2 and TPO Ab positive  2. TSH > 10mU/L and TPO Ab negative Hypothyroidism Treatment   First line replacement is synthetic T4 only---levothyroxine  (Synthroid, Unithroid, Tirosint, Levoxyl)  Long half-life (8 days) replace what the patient is deficient in - see pharm lecture Why is T4 first line treatment when T3 is the bioactive thyroid hormone? Alternatives are :  Desiccated porcine derived combination T4/T3 replacement   safer to give T4 than T3 the body does a better job to move from T4 to T3 than the other way Synthetic T3 only replacement---liothyronine   (Armour, NP thyroid, Nature-Throid, Westhroid) (Cytomel) Synthetic compounded combination T4/T3 replacement **Ask about biotin use. Large doses (>5000mcg daily) can cause falsely elevated TFTs. Hypothyroidism   Follow-up:  Recheck TSH q6 weeks until steady state reached then at least yearly  Dose adjustments based on TSH and clinical symptoms Goal TSH  0.45-4.5 mU/L is normal in most labs  TSH goal higher for elderly, cardiac dz, osteoporosis  TSH goal lower in pregnancy and thyroid cancer Myxedema Coma Extreme hypothyroidism  life threatening state of hypothyroidism - this patient needs to go to the ER Life threatening complication of hypothyroidism  High mortality  Precipitated by cold exposure, illness/infection or psychoactive drugs  Presentation: hypothermia, extreme weakness, stupor, hypoventillation, hypotension, hypoglycemia, hyponatremia  Treatment: ICU admission, blood pressure support (fluids, pressors), passive rewarming   300-400mcg levothyroxine IV loading dose then 50mcg daily  Hydrocortisone 100mg IV TID Those that improve do so quickly high high doses Questions? Hyperthyroidism AKA “THYROTOXICOSIS” Hyperthyroidism overactive thyroid any patient with new onset afib must have their thyroid checked   Epidemiology:  More common in Women (5:1)  More common in smokers Presentation: (Think Fast & Hot)  COMMON: nervousness, heat intolerance, fatigue/ weakness, palpitations, increased appetite, weight loss, oligomenorrhea NO period  PE: HTN, tachycardia, afib, wide pulse pressure, brisk reflexes, tremor, exopthalmos exopthalmos - especially in graves disease Hyperthyroidism  Labs: like pituitary or hypothalamus cause Primary Hyperthyroidism Secondary Hyperthyroidism TSH Low or undetectable High/Normal Free T4/T3 High High specific antibody is TRab  Thyroid Receptor antibody (TRab)/Thyroid Stimulating Immunoglobulin (TSI): positive in Graves  TRab/TSI: negative in toxic nodule  Thyroid peroxidase antibody (TPO): positive in Hashimoto  Other abnormalities: hypercalcemia, elevated alkaline phosphatase Hyperthyroidism  Etiology:   COMMON causes:  Graves dz.  Toxic multinodular goiter  Hashimoto thyroiditis* (early dz.)  Toxic adenoma (solitary)  Overcorrection of hypothyroidism (Thyrotoxicosis factitia) Others: Subacute (De Quervain) thyroiditis, postpartum, thyroid cancer, hydatiform mole, TSH secreting pituitary tumor, ectopic thyroid hormone production (struma ovarii = rare) Hyperthyroidism  Imaging:  Ultrasound – heterogenous tissue, enlarged thyroid, possible nodules  Thyroid Scan and Uptake:  Diffuse increased uptake – Graves Dz.  Focal increased uptake – toxic adenoma or toxic multinodular goiter  Diffuse low uptake – thyroiditis (subacute), Hashimoto’s Grave’s Disease  Auto-immune overproduction of thyroid stimulating immunoglobulin (TSI)  More common in younger women *  Presentation: in this case the antibodies do not DESTROY but STIMULATE the thyroid and cause enlargement of the thyroid  Symmetric goiter  Exophthalmos  Elevated T3/T4  Positive Thyroid Receptor Antibody (TRAb) anything antibody that stimulate thyroid = graves disease Toxic Nodular Goiter hyperfunctioning nodules - so HOT nodules on scan, but HYPERfunctioning  Hyperthyroidism caused by autonomous hyperfunctioning nodule(s)  More common in older women  Presentation:  similar presentation to graves dz, but OLDER women  PE  Asymmetric goiter and/or palpable nodules  Thyroid Scan  Single (toxic adenoma) or multiple (toxic multinodular goiter) “hot” nodules can be present 5% associated with concomitant thyroid cancer Hyperthyroidism Treatment there are definitive treatments, see next slide  Heart rate and symptom control: beta blockers  Antithyroid drugs: methimazole and PTU (propylthiouracil) anti-thyroid medications PTU used in the beginning of pregnancy then changed to methimazole  Inhibit TPO  PTU also decreases conversion of T4 to T3 in peripheral tissue  Check baseline WBC and LFTs and monitor for fever, rash, pruritus, jaundice  40-50% can achieve remission after 1-2 years of therapy (Grave’s only) methimazole is the better drug Hyperthyroidism Treatment definitive treatment is radioactive iodine or thyroidectomy  Radioactive Iodine  131-I therapy to ablate and shrink tissue   Make patient euthyroid with antithyroid hormone if severe presentation or cardiac disease as preformed hormone can be released  Likely will require thyroid hormone replacement in future  Contraindicated in pregnancy (within 6 months) Thyroidectomy  followed by thyroid hormone replacement (levothyroxine)  Complications are hypoparathyroidism and laryngeal nerve palsy Thyroid Storm Extreme hyperthyroidism  Life threatening complication of hyperthyroidism life-threatening conditions with high mortality these patients need to be in ICU, call 911 WAY too much thyroid hormone  High mortality (30-40%)  Precipitated by surgery, radioactive iodine therapy or physiologic stress (ie, uncontrolled DM, MI, acute infection)  Presentation: fever, flushing, sweating, significant tachycardia, afib, cardiac failure, significant agitation, restlessness, delirium, N/V, diarrhea and coma   Hyperpyrexia = when out of proportion to exam is hallmark of thyroid storm* Treatment: ICU admission, beta blockade, antithyroid medication, hydrocortisone, iodine (Lugol’s solution or sodium iodide) treatment with iodine T4 versus T3 Who should be screened for thyroid dz when asymptomatic?  Consider screening TSH and T4 on the following:  Those with other autoimmune disorders--T1DM, Adrenal insufficiency, Celiac, Vitiligo, etc  Family History  Infertility  Pregnancy*  Those taking medications that affect thyroid gland esp if they have Hashimotos or Graves Dz (not hereditary - but still check) thyroid could cause difficulty with fertility  Amiodarone  Lithium screening meaning the patient is asymptomatic (diagnostic would mean they have symptoms) Thyroiditis things that can inflammation of the thyroid acute, subacute, and chronic  Signs and Symptoms  Acute suppurative (bacterial)—painful, red neck, fever---sick  Subacute hospital  Viral (de Quervain’s thyroiditis)—painful, fever—hyper to hypo then euthyroid  Postpartum (silent)— transient hyper and/or hypo then euthyroid or chronic hypo. most of these patients will go back to normal (due to all the hormone shifting with pregnancy)   Hereditary predisposition  Develops within 1 year of delivery. Chronic—post subacute process (ie. postpartum) or Hashimoto’s thyroiditis hashimotos could be on this list Thyroiditis continued due to inflammation and its a inflammatory marker (ESR) thyroid level derangement = will look like a primary thyroid issue with hormone levels  Labs: ESR elevated, thyroid level derangement  Imaging   Ultrasound: maybe enlarged tissue, maybe normal, maybe incidental nodule  Scan and Uptake: decreased uptake diffuse, decreased uptake Management as long as it isn’t bacterial (needs abx at hospital) most self resolve  Monitor  Treat symptoms ie beta blocker  May require levothyroxine if chronic hypothyroidism ensues. Questions? Putting it all together Hypothyroid Hyperthyroid Iatrogenic Iodine deficiency Pituitary dysfunction (2º) Congenital Drugs: Amiodarone, Lithium, etc. Subclinical Hypothyroidism Euthyroid Sick Syndrome Hashimoto’s Thyroiditis Grave’s Disease Post-partum Thyroiditis Toxic Adenoma Infectious Thyroiditis Toxic Multinodular Goiter Back To Thyroid Nodules Say you incidentally discover a thyroid nodule…  Evaluation includes :  Labs – thyroid function (hypo- vs. hyper- vs. euthyroid)  Imaging –   Ultrasound is best initial  features?  Thyroid Scan  Order TSH and Free and total T3/T4 single vs. multiple; suspicious hot vs. cold function scan +/- Biopsy (Fine needle aspiration) can use labs and U/S to determine if thyroid scan is needed then use scan to determine if biopsy is needed Bethesda Criteria Bethesda Class do not memorize this just need to know there are a category of results with imaging that links with cancer risk (just like a mammogram) Diagnostic Category Cancer Risk I Nondiagnostic (unsatisfactory) 5-10% II Benign 0-3% III Atypia of undetermined significance (AUS) or follicular lesion of undetermined significance (FLUS) 10-30% IV Follicular neoplasm (or suspicious for follicular neoplasm) 25-40% V Suspicious for malignancy 50-75% VI Malignant 97-99% maybe know the name! Monitoring of Benign Thyroid Nodules Per ATA Guidelines After FNA  FNA normal but suspicious characteristics repeat FNA and U/S in 12 months (strong recommendation)  FNA normal and low suspicion repeat U/S q 1-2 years? No FNA performed (ie does not meet size criteria)  If suspicious characteristics, repeat U/S in 6-12 months (weak recommendation)  If intermediate suspicion, repeat 12- 24 months (weak recommendation)  If low suspicion, repeat > 24 months (weak recommendation) Thyroid Cancer Thyroid Cancer  Risk Factors:   Family hx - medullary and 5% of papillary thyroid cancers hereditary Head or neck radiation as a child or adolescent  Exposure to nuclear radiation – Chernobyl  Total body radiation – bone marrow transplant  Nodule characteristics associated with malignancy  Rapidly growing thyroid nodule  Young age at time of diagnosis  Hard, fixated  Concomitant lymphadenopathy  Vocal cord paralysis  Elevated calcitonin  “Cold” nodule  Solid lesion with macrocalcifications non-mobile (cancer likes to stick to things) need to know the star info Thyroid Cancer most common type of thyroid cancer is papillary scaner medullary thyroid cancer presents at a earlier age onset (20-50 years) thyroid cancer treatment = thyroidectomy + RIA except lymphoma radioactive iodine ablation = RIA Characteristics of Thyroid Cancers Type of Cancer Percent Age of Onset Treatment Prognosis Papillary 80% 40-80 Thyroidectomy + RIA Good Follicular 15% 45-80 Thyroidectomy + RIA Fair to good Medullary 3% 20-50 Thyroidectomy and central compartment lymph node dissection Fair Anaplastic 1% 50-80 Isthmusectomy followed by palliative XRT Poor Lymphoma 1% 25-70 XRT and/or chemotherapy Fair Hints to help remember the differences 1. Papillary---Usually peaceful. Usually local. Most common. 2. Follicular---A fairly friendly foe that must be watched. Can spread more aggressively than papillary. 3. Medullary---Calcitonin to diagnose and monitor. Spreads local and distal. Sporadic versus inherited syndrome---MEN (familial multiple endocrine neoplasia) 4.  MEN2A: medullary thyroid cancer, pheochromocytoma and primary hyperparathyroidism  MEN2B: medullary thyroid cancer, pheochromocytoma and neuromas. Anaplastic---Angry, Angry, Angry. Poor prognosis. Least common. Thyroid Cancer Monitoring  Thyroglobulin levels: should be < 0.2 ng/mL after thyroidectomy  Keep TSH suppressed 0.1-2.0  Lifelong levothyroxine therapy  Periodic ultrasound and exam to assess for recurrent tissue.  Thyrogen whole body scan if higher risk features.  Calcitonin levels to monitor medullary thyroid carcinoma. Why? Summary  Refer the following to an endocrinologist:  Hyperthyroidism  Secondary or central hypothyroidism  Thyroid nodules that require FNA or you prefer they be monitored by a specialist  Anything you are not comfortable managing  If you suspect myxedema coma or thyroid storm, Call 911 and get them the heck out of your clinic! Questions? References  Andreoli, Thomas E. Cecil Essentials of Medicine. 8th ed. Philadelphia, PA. Elsevier Inc., 2010.  Ross, D.S. (2019). Diagnostic approach to and treatment of thyroid nodules. In D.S. Cooper & J.E. Mulder (Eds.), UpToDate. Available from: https://www.uptodate.com/ contents/diagnostic-approach-to-and-treatment-of-thyroid-nodules  Haugen, Alexander. “2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer: The American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer.” American Thyroid Association, Jan. 2016, www.thyroid.org/professionals/ata-professional-guidelines/.  Diaz, Dawn. “Thyroid disorders”. 2018.  Google Images