Thyroid Potpourri for the Primary Care Physician Ramya Vedula DO, MPH, ECNU Endocrinology, Diabetes and Metabolism Princeton Medical Group Assistant Professor of Clinical Medicine Rutgers Robert Wood Johnson School of Medicine Chief of Endocrinology Penn Medicine Princeton Health April 26, 2018 Disclosures None Learning Objectives To better understand thyroid, thyroid functions and when to go beyond a screening TSH To better understand common medications that can affect the thyroid functions To better understand the role of primary care in screening and referring for thyroid nodules 1
TSH level is typically opposite the clinical problem *there are exceptions T3 is 20% secreted by thyroid and liver and 80% converted from T4 Thyroid Function Tests: Thyroid Stimulating Hormone (TSH) Primary screening test for: thyroid dysfunction for thyroid hormone replacement in patients with primary hypothyroidism for assessment of suppressive therapy in patients with differentiated thyroid cancer Diurnal variation Highest in AM and PM Lowest in afternoon Therefore, variations of serum TSH values within the normal range of up to 40%-50% do not necessarily reflect a change in thyroid status 2
Thyroid Function Tests: Thyroid Stimulating Hormone (TSH) Varies with age and ethnicity TSH values above 3.0 miu/l occur with increasing frequency with age For every 10-year age increase after 30-39 years, serum TSH increases by 0.3 miu/l Some population studies suggested having a TSH cut off of 3 (especially for younger individuals) Exquisitely sensitive to both minor increases and decreases in serum free T4 Acute illness and hospitalizations Thyroid Function Tests: Total T4 ~ 99.97% of T4 is protein-bound (mainly thyroglobulin - Tg) Total T4 = T4 bound to Tg + T4 not bound to Tg (Free T4) Affected by factors that alter binding independent of thyroid disease Thyroid Function Tests: Free T4 metabolically available moiety now largely replaced measurement of serum total T4 as a measure of thyroid status 3
Thyroid Function Tests: Total T3 and Free T3 ~ 99.7% of T3 is protein-bound (mainly thyroglobulin - Tg) Total T3 = T3 bound to Tg + T3 not bound to Tg (Free T4) Affected by factors that alter binding independent of thyroid disease Measured similarly to the Free T4 assays to minimize interference Most of conversion and action happens intracellular Thyroid Function Tests: Total T3 and Free T3 Can be influenced by polymorphisms in deiodinases (enzymes that convert T4 to T3 intracellular) What about Antibody Tests?... Hypothyroid anti-thyroglobulin antibodies (TgAb), anti- microsomal/anti-thyroid peroxidase antibodies (TPOAb), and TSH receptor antibodies (TSHRAb) pathologically by infiltration of the thyroid with sensitized T lymphocytes and serologically by circulating thyroid autoantibodies 5-10 times more common in women than in men Inherited and linked with the presence of other autoimmune diseases Once present, don t go away No need to keep following them ~11% of general population without thyroid disease have elevated levels Check in: subclinical hypothyroid (4.3% per yr), overt hypothyroidism, goiter, other autoimmune disease, medications that affect the thyroid, pregnancy 4
What about Antibody Tests?... Hyperthyroid TSHRAb may act as a TSH agonist or antagonist. Thyroid stimulating immunoglobulin (TSI), thyrotropin binding inhibitory immunoglobulin (TBII) level The risk for thyrotoxicosis correlates with the magnitude of elevation of TSI Once present, can disappear with treatment of hyperthyroidism Value in following levels intermittently in treatment of Grave s disease Check in: suppressed or low TSH, symptomatic, pregnant with h/o Graves Should I screen everyone with a TSH?.. Disagreement among expert panels Should I screen everyone with a TSH?.. 5
1 st degree relative with thyroid disease Z83.4 Z92.3 Should I screen everyone with a TSH?.. Neck radiation to the thyroid gland or external beam radiation for head and neck malignancies History of thyroid surgery or dysfunction E89.0; E07.9 Abnormal thyroid exam R94.6 Psychiatric disorders Amiodarone or Lithium F99 Unspecified anemia D53.9 Other autoimmune diseases (i.e. adrenal insufficiency, vitiligo, alopecia, celiac) E06.4; E05.80; T56.891A D89.89 Dysmenorrhea N94.4; Z87.42 Hypercholesterolemia E78.00 Unspecified myopathy M33.92 Congestive Heart Failure I50.9 Cardiac dysrhythmia I49.9 Hypertension Dementia F03.90 Malaise and Fatigue R53.83 I10 Should I check T4 and T3? Checking T4 can be a good thing In evaluating common thyroid disorders Can lead to finding zebras: Thyroid hormone resistance, secondary hypothyroid from pituitary dysfunction, TSHoma Should be measured before taking thyroid hormone as levels of T4 can be transiently increased by 20% 2 to 3 hrs after ingestion Checking T3 Minimal utility in hypothyroid Best used to evaluate hyperthyroid assessment and treatment (along with T4), thyroiditis What about other thyroid tests?... Free thyroxine index T3 uptake rt3 Minimal utility especially since development and standardization of reliable T4 and T3 assays 6
Symptoms: It must be my thyroid. Article compiled by Dr Ajith Joy K, email: joyajith@gmail.com Various Names Primary Hypothyroidism /N Underactive Thyroid Chronic Lymphocytic Thyroiditis Hashimoto s Thyroiditis Subclinical Hypothyroid Relative prevalence 4.3% in US General consensus of overt hypothyroidism is TSH >10 What about the range in between 4.5 and 10? ATA states no evidence to treat in this range AACE states there maybe CV benefit (i.e. lipid profile, carotid intimal thickness and endothelial function) but no overall recommendation Use your judgement based on clinical symptoms and lack of other etiologies Exception is pregnancy 7
Thyroid and the Elderly Presentation may not be straight forward be vigilant Remember in an otherwise healthy person with no symptoms no need to treat a higher TSH as it can increase with age No need to start at the lowest dose and work up unless active cardiac disease Hypothyroid: When to Treat?... Overt hypothyroid with TSH >10 Clinical presentation with TSH 4.5 to 10 Medications that may cause thyroid disease Thyroid surgery Hyperthyroid treatment Pituitary disease Pregnancy not at TSH goal Hypothyroid: What to Treat with?.. Lots of options Brand vs. generic No good way to assess interchangeability and bio-equivalence among preparations Generic made at various places across the world Consistent L-thyroxine preparation for individual patients to minimize variability from refill to refill Can ask pharmacist to use the same manufacturer for generic Specific situations for brand absorption issues and gluten sensitivity 30 to 60 min before breakfast; 4 hr. after dinner; supplements at lunch or dinner time 8
Hypothyroid: What to Treat with?.. Starting dose replacement therapy requires approximately 1.6 μg/kg of L- thyroxine daily based on ideal body weight No need to start at lowest dose and work up especially for healthy individuals Caution for elderly, frail individuals or those with active cardiac issues Hypothyroid: What about T4/T3(liothyronine) combination? Type 2 deiodinase polymorphisms RCT 552 hypothyroid patients with 16% polymorphisms for type 2 deiodinase those with polymorphisms reported better subjective scores on T4/T3 T4/T3 combination showed better subjective scores but not sure if this translates to better clinical outcomes in the future 1:4 ratio Panicker V, J Clin Endo Metab 2009; 94:1623-9 Escobar-Morreale, J Clin Endocrinol Metab. 2005;90:4946-4954 Hypothyroid: What about Natural thyroid hormone? Porcine or bovine T4/T3 in each pill but variable ratios per pill Supra - physiologic to a human thyroid No studies to show its superiority over T4 Follow only TSH Not approved in pregnancy 9
What about supplements/diet to help my thyroid?... What about supplements/diet to help my thyroid?... Selenium Essential dietary mineral Antioxidant and co-factor in deiodinases Meta-analysis: decreased anti-tpo titers and improved wellbeing or mood, but there were no significant changes in thyroid gland ultra sonographic morphology or L-thyroxine dosing Some role in improving Graves eye disease No recommendation for supplementation at this time in selenium sufficient areas Toulis, KA. Thyroid. 2010;20:1163-1173 What about supplements/diet to help my thyroid?... Iodine Most common cause of hypothyroid around the world Iodine, kelp not recommended for use in Iodine sufficient areas Ashwaghanda/Turmeric Anti-inflammatory / antioxidant properties Gluten free diet No recommendation unless patient has celiac disease Weight loss? Better absorption/metabolism? 10
Hypothyroid: When to Refer to Endocrinology? Difficult to render and maintain a thyroid state Pregnancy Women planning conception Cardiac disease Presence of goiter, nodule, or structural change in the thyroid Presence of other endocrine disease such as adrenal and pituitary disorders Unusual constellation of thyroid function tests Unusual causes of hypothyroidism Children and Infants Primary Hyperthyroidism N/ Hyperthyroid: Low or suppressed TSH 11
Subclinical Hyperthyroid To treat or Not to Treat? Subnormal TSH with normal TT4 and FT3 1% of population Increased fracture risk, osteoporosis and atrial fibrillation Hyperthyroid: Suggested Approach If TSH is low or suppressed Check FT4 and TT3 and may be TSI If suspect Graves disease, consider starting methimazole 10mg and beta-blocker Refer to Endocrinology Suppressed TSH with TT4 and FT3 2 to 3x upper limit Elevated TSI If picture still not clear, consider uptake and scan refer to Endocrinology Hyperthyroid: When to refer? Above situations Pregnancy or contemplation of pregnancy with suppressed TSH, subnormal TSH, history of Graves disease Any time there is a low or suppressed TSH 12
Medications Medications Medications 13
Medications Medications Thyroid Nodules: Epidemiology Very common 2x more in women Most thyroid nodules are not clinically detected Only 6.4% of women and 1.5% of men had clinically apparent nodules Autopsy surveys, 37 to 57% of patients had thyroid nodules Unselected subjects using ultrasound, 20 to 76% of women had at least 1 nodule Patients with single palpable nodule, 20 to 48% had more nodules on ultrasound Prevalence increases with age likelihood corresponds ~ to decade of age 14
Thyroid Nodules: Incidence of Thyroid cancer Most thyroid nodules are benign In 5 to 15% of nodules Overall 3.4% of all cancers Incidence depends on Family history Male gender Neck radiation Nodule characteristics Thyroid Nodules: Incidence of Thyroid cancer 15
Thyroid Nodules: When to Ultrasound?... Palpable neck abnormality Nodules on other imaging Rapidly expanding neck mass Family history of thyroid cancer Patient concern Thyroid Nodules: When to Refer?... Can refer directly to your ECNU certified Endocrinologist or Endocrinologist in general Get ultrasound and refer to your Endocrinologist Thank you! 16