Underactive Thyroid. Diagnosis, Treatment & Controversies

Size: px

Start display at page:

Download "Underactive Thyroid. Diagnosis, Treatment & Controversies"

Meghan Horn
5 years ago
Views:

1 Underactive Thyroid Diagnosis, Treatment & Controversies Dr. Asif Malik Humayun Consultant Endocrinologist Milton Keynes University Hospital NHS Foundation Trust

3 Thyroid Hormone Control of metabolism - energy generation and use Regulation of growth in children Exists in two form T4 and T3 T3 is more biologically active than T4 T3 is the major feedback regulator of TSH

4 Thyroid Disorders Most common endocrine disease Affects ~ 1 in 20 people Autoimmune thyroid disorders may be associated with other autoimmune diseases (e.g. T1 DM, autoimmune adrenal insufficiency) Thyroid diseases are more common in women than men (1:10)

5 Hypothyroidism Most common cause of abnormal thyroid function, 2-3% of general population Primary hypothyroidism: most common, elevated TSH. Central hypothyroidism: Uncommon, pituitary cause, low TSH Subclinical hypothyroidism is defined biochemically as a normal free T4 concentration in the presence of an elevated TSH concentration.

Populations at Risk for Hypothyroidism Caraccio N, et al. J Clin Endocrinol Metab. 2002;87:1533-1538. Carmel R, et al. Arch Intern Med. 1982;142:1465-1469. Perros P, et al. Diabetes Med.

6 Populations at Risk for Hypothyroidism Caraccio N, et al. J Clin Endocrinol Metab. 2002;87: Carmel R, et al. Arch Intern Med. 1982;142: Perros P, et al. Diabetes Med. 1995;12: Women Prior history of Graves disease or postpartum thyroid dysfunction Elderly Other autoimmune disease Family history of Thyroid disease Pernicious anemia Type 1 Diabetes mellitus

7 Cretinism lack of thyroxine from birth or before birth could be from lack of thyroid gland or lack of iodine in mother severe and irreparable mental defects stunted growth reduced growth and function of many organs

8 Kim J. N Engl J Med 2015;372: Myxedema

9 Causes of Hypothyroidism Hashimoto's thyroiditis Thyroiditis inflammation due to viruses etc. Congenital Hypothyroidism present at birth Drug induced e.g. amiodrone Post radiation Radiotherapy to neck for cancer Thyroid surgery For a benign or malignant conditions

Clinical Features of Hypothyroidism Tiredness Forgetfulness/Slower Thinking Moodiness/ Irritability Depression Inability to Concentrate Thinning Hair/Hair Loss Loss of Body Hair Dry, Patchy Skin

10 Clinical Features of Hypothyroidism Tiredness Forgetfulness/Slower Thinking Moodiness/ Irritability Depression Inability to Concentrate Thinning Hair/Hair Loss Loss of Body Hair Dry, Patchy Skin Weight Gain Cold Intolerance Elevated Cholesterol Family History of Thyroid Disease or Diabetes Puffy Eyes Enlarged Thyroid (Goiter) Hoarseness/ Deepening of Voice Persistent Dry or Sore Throat Difficulty Swallowing Slower Heartbeat Menstrual Irregularities/ Heavy Period Infertility Constipation Muscle Weakness/ Cramps

11 Percentage of Euthyroid, Subclinical and Hypothyroid Patients Reporting Symptoms 60% euthyroid have 1 symptom 15% 4 symptoms R5. Clinical scoring systems should not be used to diagnose hypothyroidism. Grade A, BEL 1 Canaris et al.

12 Physical Findings * Comatose or semi comatose Dry coarse skin Hoarse voice Thin dry hair Delayed reflex relaxation time Very low body temperature Fluid around heart, lungs and tummy *In very advanced disease

13 Lab Tests to Diagnose and Monitor Hypothyroidism Free Hormone Hypothesis Only free hormone metabolically active and determines thyroid status (not total which is largely bound to binding proteins) Gold standard: Equilibrium Dialysis

14 Severity of Primary Hypothyroidism by Thyroid Levels TSH rises first and abruptly Decline of T4 and T3 slower and later

15 Hypothyroidism Subclinical Normal Free T4 Overt Low Free T4 Estimate TSH usually below 10 TSH usually above 10 5% or more ~1%

16 TSH Population Reference Range 95% Limits ~ TSH miu/l

Disease-Free Thyroid Function Levels: May Narrow in Young But widens in Elderly Age 20-29

17 Disease-Free Thyroid Function Levels: May Narrow in Young But widens in Elderly Age Age Age 80+ Surks MI, Hollowell JG. J Clin Endocrinol Metab. 2007;92: FROM LADENSON

18 Total T3 - Principal use is diagnosing and following Thyrotoxic patients, NOT Hypothyroid patients Free T3 Total and Free T3 should not be used in hypothyroid diagnosis or management - Not as reliable as Total T3 - Can estimate with Total T3 X T3 UPTAKE T3 and FT3 not useful for the Hypothyroid patient

19 TSH an excellent test except some pitfalls Central disease Abnormal isoforms, TSH receptor polymorphisms Drugs (glucorticoids, dopaminergic drugs [metoclopramide]) Heterophilic antibodies--particularly low titer Requires steady state: pitfalls in an inpatient population and early phases of pregnancy

20 TSH is Lower Particularly in 1st trimester Free T4 in pregnancy unreliable weeks gestation E2 hcg TBG +50 TT4 % Change vs. Non-pregnant 0 TSH FT4-50 1st. Trimester 2nd. Trimester 3rd. Trimester

21 Anti-Thyroid Antibodies Markers of Chronic Thyroiditis Anti- Thyroglobulin Antibodies Does not Correlate with hypothyroidism Anti-Thyroid Peroxidase Antibodies (formerly known as Anti-microsomal Antibodies) Correlate with the development of hypothyroidism

22 Treatment Treatment of TSH levels > 10 is recommended Patients whose serum TSH levels exceed 10 miu/l are at increased risk for heart failure and cardiovascular mortality, and should be considered for treatment with L-thyroxine Surks et al JAMA 291: (EL4). Rodondi N et al JAMA 304: (EL2). Razvi S et al JCEM 95: (EL3). Gencer B et a.2012 Circulation Epub before print (EL1).

23 Treatment of TSH between 5 and 10? Depends Treatment should be considered particularly if they have symptoms suggestive of hypothyroidism, positive TPO antibodies or evidence of atherosclerotic cardiovascular disease, heart failure or have associated risk factors for these diseases. Vanderpump MP et al Clin Endo 43:55-68 (EL2). Vanderpump MP & Tunbridge WM 2002 Thyroid 12: (EL4). Hollowell JG et al JCEM 87: (EL1). Huber G et al JCEM 87: (EL2). McQuade C et al Thyroid 21: (EL3). Ochs N et al Ann IM 148: (EL1).

24 Value of Treating Patients with TSH Values Between 3 and 5 No prospective study has shown TSH levels lower than 5 are associated with more cardiovascular disease Pregnancy outcomes notable exception Many who do are mild, at low risk for progression, and may even remit The risk of overtreatment is not trivial (approximately 20%) Surks MI, et al. J Clin Endocrinol Metab. 2005;90: Walsh JP, et al. J Clin Endocrinol Metab. 2006;91:

25 Normal Total daily Thyroid hormone secretion Thyroid T4 = 101ug/day T3 = 6ug/day (20%) Peripheral tissue Conversion from T4 to T3 20ug/day (80%) Total tissue T3 26ug/day

26 L-T4 is the Preferred Treatment Patients with hypothyroidism should be treated with L-thyroxine monotherapy Grade A, BEL1. Evidence does not support using L-T4 and L-T3 combinations to treat hypothyroidism. T4 is converted tot3 in the peripheral tissue Very few patient subgroups may benefit from L-T4 and L-T3 combination. Escobar-Morreale HF et al JCEM 90: (EL4). Grozinsky-Glasberg S et al JCEM 91: (EL1). Panicker V et al JCEM 94: (EL3). Applehof BC et al JCEM 90: (EL3). Clarke N et al Treat Endo 3: (EL4).

27 Treatment and Monitoring of Hypothyroidism L-thyroxine should be taken with water consistently 30 to 60 minutes before breakfast or at bedtime 4 hours after the last meal. It should be stored properly per product insert and not taken with substances or medications that interfere with its absorption. When initiating therapy in young healthy adults with overt hypothyroidism, beginning treatment with full replacement doses should be considered. When initiating therapy in patients older than years old with overt hypothyroidism, without evidence of coronary heart disease, an L-thyroxine dose of 50 mcg daily should be considered.

28 Generic Vs brand name There has been considerable controversy about the bioequivalence of the various T4 formulations A study of two brand-name and two generic formulations of T4, using FDA recommended methodology for determining bioequivalence, reported that all four preparations were equivalent Either formulation of T4 is acceptable If there is concern regarding equivalent efficacy of the preparations, measure a serum TSH six weeks after to document that TSH is still within the therapeutic target

29 Monitoring Stabilisation of TFT may take up to 4 months Measure serum TSH 6-8 weeks after initiation/dose change Annual TFT once stable a dose Aim of treatment is to restore a normal clinical and biochemical thyroid state and avoid overtreatment

30 Initiating treatment in subclinical hypothyroidism In patients with subclinical hypothyroidism initial L- thyroxine dosing is generally lower than what is required in the treatment of overt hypothyroidism. Dose of 25 to 75 mcg should be considered, depending on degree of TSH elevation. Further adjustments should be guided by clinical response and follow up laboratory determinations including TSH values.

31 Factors that increase LT4 requirement Malabsorption or increased excretion of T4 Gastrointestinal disorders (eg, celiac disease) Impaired acid secretion Drugs that interfere with T4 absorption Ferrous sulfate Iron supplement Pregnancy Estrogen therapy Weight gain of 10% body weight Drugs which increase catabolism of T4 Epilepsy tablets, some antibiotics Cholestyramine or colestipol For some liver problems Sucralfate For stomach Aluminum hydroxide gels - Antacids Calcium carbonate - Supplement Sertraline - Antidepressant Omeprazole For stomach acid Nephrotic syndrome (leaky kidneys)

32 Hazards of Overtreatment Heart, Bone, Psychiatric High risk subclinical hyperthyroid in patients on thyroid medication Colorado Prevalence Study, % (316) of patients on thyroid medication had subclinical hyperthyroidism 0.9% (13) Overt hyperthyroidism More adverse effects with poor monitoring Only 56% received standard monitoring Atrial fibrillation, unstable angina with poor monitoring Canaris GJ, et al. Arch Intern Med. 2000;160: Stelfox HT, et al. J Eval Clin Pract. 2004;10:

33 T4/T3 combination Meta-analysis of 11 RCT has shown no clinical benefit Current T3 formulation does not result in normal physiological profile Not recommended by national and international guidelines Risk of overtreatment and complications

34 Increased risk of developing atrial fibrillation in patients with subclinical hyperthyroidism Mcdermott and Ridgeway

35 Factors That May Reduce Levothyroxine Effectiveness Absorption issues Postjejunoileal bypass surgery Short bowel syndrome Celiac disease Medications, Food Colestipol hydrochloride Sucralfate Ferrous sulfate Food (eg, soybean formula) Aluminum hydroxide Cholestyramine Sodium polystyrene sulfonate Drugs That Increase Clearance Rifampin Carbamazepine Phenytoin Factors That Reduced T 4 to T 3 Clearance Amiodarone Selenium deficiency Braverman LE, Utiger RD, eds. The Thyroid: A Fundamental and Clinical Text. 8 th ed Synthroid [package insert]. Abbott Laboratories; 2003.

36 Thank you

Hypothyroidism and Hyperthyroidism. Paul V. Tomasic, MD, MS, FACP, FACE Nevada AACE EFNE & Annual Meeting October 6, 2018

Hypothyroidism and Hyperthyroidism Paul V. Tomasic, MD, MS, FACP, FACE Nevada AACE EFNE & Annual Meeting October 6, 2018 Disclosures: None related to this program or presentation Objectives: Hypothyroidism