Management of Thyroid Disease: Too much, too little, masses Margaret A. Fitzgerald, DNP, FNP-BC, NP-C, FAANP, CSP, FAAN, DCC President, Fitzgerald Health Education Associates, Inc., North Andover, MA Family Nurse Practitioner, Greater Lawrence (MA) Family Health Center Editorial Board Member The Nurse Practitioner Journal, The Prescribers Letter, American Nurse Today Member, Pharmacy and Therapeutics Committee Neighborhood Health Plan, Boston, MA 1 Objectives Upon completion of this program, the participant will be able to: Discuss the pathophysiology of common thyroid disorders. Identify expected laboratory findings in common thyroid disorders including TSH, free T4, total T4, T3, and antithyroid antibodies. 2 Objectives Upon completion of this program, the participant will be able to: (cont.) Discuss treatment options for the person with select thyroid disorders including thyroid masses. 3
Thyroid Disorders 4 References American Association of Clinical Endocrinologist Medical Guidelines for Clinical Practice: Hyperthyroidism and Hypothyroidism, available at https://www.aace.com/publications/guidelines American Thyroid Association: Topics Related to Hypothyroidism, available at http://www.thyroid.org/thyroidguidelines/hypothyroidism/topics/ 5 Key Concepts in Thyroid Disease The thyroid produces two hormones, thyroxine (T4) and triiodothyronine (T3). These hormones act as cellular energy release catalysts and influence the function and health of every cell in the body. 6
In Hypothyroidism Less Cellular Energy Release Area affected Skin Reflexes Mentation Weight change Change noted Thick, dry Hung up patellar reflex, slow arc out, slower arc back, overall hyporeflexia esp Achilles tendon Can t make sense, thoughts too slow. Small gain 7 In Hypothyroidism Less Cellular Energy Release Area affected Stool pattern Menstrual issue Heat/cold perception Change noted Constipation Menorrhagia Easily chilled 8 Hypothyroidism: Common Etiology Condition Hashimoto thyroiditis Post radioactive iodine (RAI) treatment Select medication use Comment Autoimmune in nature S/P Graves disease, thyroid cancer treatment Lithium, amiodarone, interferon, others 9
In Hyperthyroidism Excessive Cellular Energy Release Area affected Skin Reflexes Mentation Change noted Smooth, silky Hyperreflexia Can t make sense, mind racing 10 In Hyperthyroidism Excessive Cellular Energy Release Area affected Weight Stool pattern Menstrual issue Heat/cold tolerance Change noted Loss Frequent, low volume, loose Oligomenorrhea Heat intolerance 11 Hyperthyroiditis: Common Etiology Condition Graves disease Toxic adenoma Thyroiditis Common etiology Multisystem presentation Metabolically active lesion Viral, autoimmune, post partum, often transient 12
Exophthalmus in Graves' Disease 13 Thyroid Test Test Evaluates Comment Thyroid stimulating hormone (TSH) NL=0.4-4.0 miu/l True population distribution= 0.5-1.5 miu/l range with M=1.18 miu/l Hypothalamicpituitarythyroid axis function, reflects anterior pituitary lobe s ability to detect amount of circulating free thyroxine Per American Thyroid Association, single most reliable test to diagnose all common forms of hypo- and hyperthyroidism, particularly in the ambulatory setting 14 Thyroid Test Test Evaluates Comment Free T4 (FT4, free thyroxine) NL=0.5-1.3 ng/dl (6-16.7 pmol/l ) Total T4 (total thyroxine) NL=4.5-12.0 mcg/dl (57.9-154.4 nmol/l) Unbound, metabolically active portion of thyroxine Reflects the total of the protein-bound and free thyroxine About 0.025% of all T4 Often altered in the absence of thyroid disease but with the use of select medications (exogenous estrogen {HT, OC}, methadone) and presence of clinical conditions such as pregnancy, chronic hepatitis 15
Thyroid Test Test Evaluates Comment Free T3 NL=0.2-0.5 ng/dl (3.5-7.7 pmol/l) Unbound, metabolically active portion of triiodothyronine (T3) When compared to T4 (prodrug for T3), T3 is about 4 X more metabolically active. About 20% of circulating (T3) is from the thyroid, rest as a result of conversion of T4 to T3 16 Thyroid Test Test Evaluates Comment Total T3 NL=95-190 ng/dl (1.5-2.9 pmol/l) Reflects the total of the protein bound and free triiodothyronine See comments on total T4 17 Thyroid Test Test Evaluates Comment Antiperoxidase (antimicrosomal) antibody NL=Depends on lab method, from negative to <1:1000 An antibody against peroxidase, an enzyme held within the thyroid Also known as thyroid peroxidase (TPO) antibody (TPO Ab) test, thyroid peroxidase autoantibody test, antimicrosomal antibody test and antithyroid antibody 18
American Thyroid Association: Thyroid Function Tests Available at www.thyroid.org/blood-test-for-thyroid/ 19 Measuring TSH and FT4? When thyroid status is stable and hypothalamic-pituitary function is intact, serum TSH measurement is more sensitive than free T4 (FT4) for detecting mild (subclinical) thyroid hormone excess or deficiency. 20 Measuring TSH and FT4? The superior diagnostic sensitivity of serum TSH reflects the log/linear relationship between TSH and FT4 and the exquisite sensitivity of the pituitary to sense free T4 abnormalities relative to the individual s genetic free T4 set-point. Source: www.aacc.org/sitecollectiondocuments/nacb/lmpg/thyroid/thyroidfullversion.pdf 21
Measuring TSH and FT4? Serum FT4 measurement is a more reliable indicator of thyroid status than TSH when thyroid status is unstable, such as during the first 2-3 months of treatment for hypo- or hyperthyroidism. Source: www.aacc.org/sitecollectiondocuments/nacb/lmpg/thyroid/thyroidfullversion.pdf 22 True or false? TSH levels peak in the evening and are lowest in the afternoon. TSH varies with physiologic conditions such as illness, psychiatric disorders and low energy intake. 23 Thyroid Test Results Low Thyroxine (FT4)=High TSH Example TSH=84 miu/l (0.4-4.0 miu/l) Free T4=3 pmol/l (10-27 pmol/l) Etiology Untreated hypothyroidism Inadequate thyroxine dose 24
From Levothyroxine PI Synthetic T 4 is identical to that produced in the human thyroid gland. Levothyroxine (T 4 ) sodium has an empirical formula of C 15 H 10 I 4 N NaO 4 H 2 O, molecular weight of 798.86 g/mol (anhydrous) Source-www.rxabbvie.com/pdf/synthroid.pdf 25 From Levothyroxine PI T ½ In hypothyroid state=9-10 d In euthyroid state=7 d In hyperthyroid state=3-4 d How many T ½ to reach steady state? Eliminate drug from the body? 26 Intervention in Hypothyroidism Calculating anticipated levothyroxine dose 1.6 mcg/kg/day in adults 1.0 mcg/kg/day in elderly 4.0 mcg/kg/day in children =>50% increase during pregnancy Increase levothyroxine dose by =>33% as soon as pregnancy is confirmed. 27
True or false? When calculating the levothyroxine dose for a patient, ideal body weight (IBW) should be used for the person who is obese. For the person who is underweight, actual body weight should be used. 28 Therapy is usually initiated in patients under the age of 50 years with full replacement. For those patients who are older than 50 years, or in younger patients with a history of cardiac disease, a lower initial dosage is indicated, starting with 0.025 to 0.05 mg of levothyroxine daily, with clinical and biochemical reevaluations at 6- to 8-week intervals until the serum TSH concentration is normalized. 29 What about desiccated porcine thyroid preparations? Source: American Thyroid Association Treatment Guidelines for Patients with Hypothyroidism, available at http://thyroidguidelines.net 30
T4/T3 Combinations Desiccated thyroid preparations (T4/T3 combination, porcine origin such as Armour Thyroid, Nature- Throid, Bio-Throid, Westhroid ) 1 grain=60-65 mg thyroid USP=100 mcg levothyroxine Thyroid USP 60-120 mg per day for typical adult daily dose 31 Per American Thyroid Association (ATA) Biological and synthetic thyroid hormone preparations containing both T 4 and T 3 are also not currently recommended for therapy since they produce fluctuating and often elevated T 3 concentrations, although their use is not necessarily contraindicated. 32 Monitoring Thyroxine Therapy TSH No sooner than 6-8 (AACE) or 8-12 (ATA) weeks Long T ½ TSH too high Dose too low Adherence Drug interaction TSH too low Excessive use Dose too high 33
Thyroid Test Results High Thyroxine (FT4)=Low TSH Example TSH<0.15 miu/l (0.4-4.0 miu/l) Free T4=79 pmol/l (10-27 pmol/l) Etiology Hyperthyroidism Excessive thyroxine dose 34 Intervention in Hyperthyroidism at the Time of Diagnosis Beta adrenergic antagonist B1, B2 blockade if possible Propranolol, nadolol Antithyroid medication PTU, methimazole Radioactive iodine (RAI) Thyroid ablation 35 From PTU PI PTU inhibits synthesis of thyroid hormone by interfering with the incorporation of iodine into thyroglobulin; it also inhibits the formation of iodothyronine. Besides blocking hormone synthesis, it also inhibits the peripheral deiodination of thyroxine to triiodothyronine (liothyronine). 36
FDA Advisory on PTU FDA is notifying healthcare professionals of the risk of serious liver injury, including liver failure and death, with the use of propylthiouracil in adult and pediatric patients. Source: http://www.fda.gov/drugs/drugsafety/postmarketdrugsafety InformationforPatientsandProviders/DrugSafetyInformationfor HeathcareProfessionals/ucm162701.htm 37 From Methimazole PI Methimazole inhibits synthesis of thyroid hormone by interfering with the incorporation of iodide into tyrosyl. Methimazole also inhibits the formation of iodothyronine. 38 From Methimazole PI There have been rare reports of fulminant hepatitis, hepatic necrosis, encephalopathy, and death. Symptoms suggestive of hepatic dysfunction (anorexia, pruritus, right upper quadrant pain, etc.) should prompt evaluation of liver function. 39
Subclinical Hypothyroidism Elevated TSH, NL Free T4 Example TSH=8.9 miu/l (0.4-4.0 miu/l) Free T4=15 pmol/l (10-27 pmol/l) Antithyroid antibodies=1:1,800 (<1:1,000) 40 Per AACE Guidelines Subclinical Hypothyroidism AACE guidelines recommend treatment of patients with TSH>5 miu/l if the patient has a goiter or if thyroid antibodies are present. The presence of symptoms compatible with hypothyroidism, infertility, pregnancy or imminent pregnancy would also favor treatment. Source: https://www.aace.com/publications/position-statements 41 Samantha, 47 YO Woman Last year s results TSH=1.2 miu/l 0.35-4.0 miu/l FT4=14 pmol/l 10-27 pmol/l This year s results TSH=6.4 miu/l FT4=6 pmol/l Long-standing hypothyroidism States continues to take her levothyroxine every day, just like clockwork 42
Samantha Interim History Since last visit with you, saw gyn for heavy menstrual bleeding Underwent endometrial ablation procedure and is quite pleased with the results 43 Iron Ingestion and Levothyroxine Therapy Ferrous sulfate effect on TSH levels in patients with hypothyroidism TSH Level, µiu/ml 6 5 4 3 2 1 0 P<.001 Before Ingestion Campbell NR, et al. Ann Intern Med. 1992;117:1010-1013. After Ingestion 44 LT4 Interactions Iron Calcium Aluminum antacids Sucralfate Soy milk Formation of inactive drug compound Separate=>2h Empty stomach 45
Medications Increasing Metabolism of Thyroid Hormone Phenytoin Phenobarbital Carbamazepine Rifampin 46 NTI with Many Drug-drug, Drug-nutrient Interactions Take your levothyroxine Always at the same time of day Empty stomach, =>½ h before or =>2 h after meal Separate from other meds including OTC, minerals, vitamins by =>2 h 47 Generic or brand? Per AACE Statement "Patients should be maintained on the same brand name levothyroxine product. If the brand of levothyroxine medication is changed, either from one brand to another brand, from a brand to a generic product, or from a generic product to another generic product, patients should be retested by measuring serum TSH in six (6) weeks, and the drug reiterated as needed. 48
Generic or brand? Per AACE Statement Since small changes in levothyroxine administration can cause significant changes in TSH serum concentrations, precise and accurate TSH control is necessary to avoid potential adverse iatrogenic effects. Source: http://dig.pharm.uic.edu/faq/levothyroxine.aspx 49 Continued Fatigue With NL TSH and free T4 Consider checking T3 T4 ~40% converted in peripheral tissue to T3 50 Should we also give T3? Triiodothyronine (T3) About 4 X as active as T4 Can be important to brain function 51
T4 and Liothyronine Sodium (Cytomel )? Add to T4? Liothyronine sodium, LT3 (Cytomel ) usual dose=12.5 mcg Short T ½ Usual daily dose 25-75 mcg per day Reduce T4 dose by 50 mcg Inconclusive study in effectiveness but anecdotal, patient-by-patient reports 52 T3 Replacement Per ATA After taking a tablet of Cytomel there are very high levels of T3 for a short time, and then the levels fall off very rapidly. This means that T3 has to be taken several times each day, and even doing this does not smooth out the T3 levels properly. Source: http://www.thyroid.org/patients/patient_brochures/hormonetreatment.html 53 Sonia 35-year-old Woman Afebrile Pharynx and TM benign Hyperreflexia Tender, slightly enlarged thyroid 54
Sonia describes where her throat and ears hurt. 55 Sonia 35-year-old Woman TSH<0.15 miu/l (0.15 4.0) Free T 4 =33 pmol/l (10 27) ESR=66 mm/hr (<15 mm/hr) 56 Thyroiditis: Subacute (Granulomatous) Thyroiditis In hyperthyroid phase Neck pain, a tender diffuse goiter, and elevated T 4 and/or T 3 Caused by damage to thyroid follicular cells and breakdown of stored thyroglobulin, leading to unregulated release of thyroxine (T 4 ) and triiodothyronine (T 3 ) 57
Thyroiditis: Subacute (Granulomatous) Thyroiditis Duration of hyperthyroid phase Lasts 2 6 weeks until T 4 and T 3 stores are depleted Low TSH minimizes thyroid follicular stimulation Hypothyroidism often follows, usually transient 58 Thyroiditis: Subacute (Granulomatous) Thyroiditis Etiology Likely viral infection trigger Common report of recent URI symptoms Multiple case reports post Coxsackievirus outbreaks Also strong association with HLA-B35?Viral trigger with genetic basis 59 Additional More Common Thyroiditis Forms Subacute lymphocytic thyroiditis Most common form of postpartum thyroiditis Often presents with nervousness, poor sleep, painless thyroid, in first year postpartum, most often around month 3 after birth Lasts 1 2 months with self-resolution 60
61 Thyroiditis Testing Additional evaluation Check anti-tpo antibodies More commonly positive in postpartum thyroiditis, rarely positive in granulomatous thyroiditis Consider thyroid scanning Generally increased uptake in Graves disease, low uptake in thyroiditis 62 Thyroid Scanning 63
American Thyroid Association: Thyroid Nodules Guideline Available at www.thyroid.org/thyroidguidelines/revised/nodules/ 64 Evaluation of a Thyroid Nodule The evaluation of a palpable thyroid nodule presents a challenge. In the absence of hyperthyroidism symptoms, the presentations of benign and malignant thyroid lesions are typically the same; the risk that any thyroid nodule is malignant is about 5%. 65 Evaluation of a Thyroid Nodule A history of head or neck irradiation, localized pain, dysphonia, hemoptysis, regional lymphadenopathy, or a hard fixed mass should raise suspicion. 66
Evaluation of a Thyroid Nodule Initial testing for a person with a thyroid nodule should include obtaining a TSH measurement. A metabolically active or hot nodule has a low risk of malignancy and can cause a reduction in TSH production from the pituitary. A thyroid scan can identify areas of increased uptake. 67 Hot Nodule 68 Cold Nodule 69
Thyroid Ultrasound without and with Doppler 70 Evaluation of a Thyroid Nodule Fine needle aspiration biopsy is advised, regardless of TSH results, and is more helpful and cost-effective in arriving at a definitive diagnosis than ultrasound or thyroid scan. A properly performed fine needle aspiration biopsy has a falsenegative rate of less than 5% and a false-positive rate of about 1%. 71 Additional Reference Fitzgerald, M. A. Endocrine In Nurse Practitioner Certification Examination and Practice Preparation, Philadelphia, PA: F.A. Davis Company. Available at fhea.com/store 72
End of Presentation Thank you for your time and attention. Margaret A. Fitzgerald, DNP, FNP-BC, NP-C, FAANP, CSP, FAAN, DCC www.fhea.com, e-mail: cs@fhea.com 73 All websites listed active at the time of publication. 74