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SUBCLINICAL THYROID DYSFUNCTION: A CONUNDRUM. T. Cook FRCPC Nov 2006. STRUCTURAL Enlargement (goitre) Diffuse Nodular (multiple vs solitary) Nodule Benign Malignant. FUNCTIONAL Hyper Hypo GRAVE’S EXTRA-GLANDULAR Ophthalmopathy Dermopathy Osteopathy.
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SUBCLINICAL THYROID DYSFUNCTION:A CONUNDRUM T. Cook FRCPC Nov 2006
STRUCTURAL Enlargement (goitre) Diffuse Nodular (multiple vs solitary) Nodule Benign Malignant FUNCTIONAL Hyper Hypo GRAVE’S EXTRA-GLANDULAR Ophthalmopathy Dermopathy Osteopathy COMMON THYROID PROBLEMS in AMBULATORY IMED
CASES • 67 yo woman presents with palpitations, is found to be in atrial fibrillation. On exam noted to have a goiter, which is long-standing. Echo is normal. The sTSH is <.05 mU/L and T3 & T4 are normal. 1. What is this called & how common is it?
SUBCLINICAL HYPERTHYROIDISM • UK study, 1210 consecutive pts >60, single general practice, NOT on T4 • 16 (.13) had suppressed TSH • Followed for 1 y only 1 developed thyrotoxicosis • However, higher progression if MNG (5%) or if on amiodarone • Most studies show prevalence 0.1 – 1% 2) What are the common causes of it?
Same as for thyrotoxicosis • MNG (older age, iodine exposure incl amio) • Subacute Thyroiditis • Grave’s Disease • “Hashitoxicosis” • Exogenous T4 (this may be commonest!) • Hyperfunctioning “toxic”Adenoma
3) How do you distinguish these? • Clinically • History • PE • Labs • Imaging
Hx Meds (Li, amio) Goitrogens (cruciferous veg, dulce) Autoimmune disease (Type I DM, vitiligo, PA, myasthenia, Addison’s) PE Diffuse goitre Ophthalmopathy Pretibial myxedema LABS Free T3 (MNG) Thyrotropin receptor Ab (absent 5-20% Grave’s) IMAGING Structure (U/S, Scan) Function (RAI Uptake) – best to distinguish Grave’s vs thyroiditis DIAGNOSIS
Nuclear Scans Cold Nodule Hot Nodule Ultrasound of a “Complex” Nodule 4) What is the natural history of this problem?
Risk of progression to frank hyperthyroidism - Esp in MNG Risk of chronic TSH suppression (<0.1) • What’s the evidence for: • Atrial Fibrillation • Other cardiac effects (Tachycardia, LVH, Diastolic dysfunction, reduced exercise capacity) • Osteoporosis • Alzheimer’s Dementia
A.FIB • Framingham study • Cohort 2007 >60 followed for 10 yrs • AF development compared with initial TSH • Of 61 < 0.1, AF in 13 RR = 3.1 • NNT over 10 y = 4.2 • TSH of 0.1 – 0.4 not a risk for AF • AF (non-valvular) with thyrotoxicosis increases risk of embolism
“Subclinical Thyroid Dysfunction as a Risk Factor for Cardiovasc. Disease” • Busselton Health Study, Australia • Large longitudinal study 1981 – 2001! • No increased risk in subclinical hyperT
OSTEOPOROSIS • 2 cross-sectional studies of MNG and subclinical hyperT showed signif lower BMD than age-matched controls, esp femoral neck • Does TSH itself mediate bone remodeling (receptors found on osteoblasts / clasts), Arch Med Research, May 2006 • Post-menopausal women with subclinical hyperT have 2% loss of BMD / y
OTHER • Cardiac changes statistically demonstrated but clinically significant?? • Increased AD (one study of >55 yo with anti-thyroid peroxidase and suppressed TSH but recent study in Annals -> no incr risk) 5) Should subclinical hyperthyroidism be treated? And if so how?
DEPENDS! • DEFINITELY • MNG, toxic adenoma or Grave’s Esp if assoc with AF / osteoporosis etc • PROBABLY • AF / osteoporosis and other cause
TREAT WITH? • RAI – MNG / Grave’s • PTU or methimazole – Grave’s • Treatment of thyroiditis controversial • Wait and see! • RAI • OR
SUBCLINICAL HYPOTHYROIDISM B) Case 59 yo woman has sTSH = 7 on routine screening. Only symptoms are mild fatigue, present for > 10 yrs, and difficulty losing weight. Exam normal except for a small firm thyroid with a slightly irregular surface. Total T4 is normal but TC = 5.69 mmol/L and LDL = 3.62. Anti thyroid peroxidase is pos. 1) How common is this scenario?
DEPENDS! WHAT’S YOUR DEF’N OF UPPER NORMAL TSH ? “The Evidence for a Narrower Thyrotropin Reference Range is Compelling”, J.Clin. Endo & Metab, 2005 Sept • Prev reference pop’n “contaminated” by individuals with thyroid dysfunction (esp Hashimotos) • Nat’l Academy Clin. Biochem: >95% normals have TSH < 2.5 (African-Americans’ v. low rates of Hashimoto’s have mean TSH 1.18 = true pop’n mean?)
PREVALENCE (if using < 5) • 1-10% worldwide • Up to 20% in women > 60 • 16% in one study of men > 74 • 75% have TSH in 5-10 range • 50-80% positive anti thyroperoxidase • RR of goitre = 2
INCREASED RISK • Treated hyperthyroidism • Neck irradiation • Postpartum thyroiditis • Autoimmune diathesis (esp Type 1 DM) • Meds: Amiodarone, lithium, interferon alfa 2) What is the natural history / consequences?
POTENTIAL RISKS • Progression to overt hypothyroidism • “Whickham survey” – 2800 randomly selected adults 1972-1992 • If baseline TSH high AND Ab + 4.3% /y RR=38! • If either TSH up OR Ab + 2.6%/y • NNT range 4.3 – 14.3
DYSLIPIDEMIA • Meta-analysis of effect of Rx for subclinical HypoT on lipids • Mean TC reduction 0.2 mmol/L • Mean LDL reduction 0.26 “ • Risk of CAD and vascular death • Data conflicting, probably increased • Busselton Health Study – Australia OR 1.8 (1.0 – 3.1)
SYMPTOMS, MOOD, COGNITION, BMD • Several studies show more symptom prevalence in this population • 3 prospective RPCT of Rx for subclinical hypoT • 2 reported signif improvements in QOL (in up to 28% of those treated) NNT ~ 4 • If ovulatory dysfunction and infertility present Rx shown to be helpful • BMD signif reduced in women with subclinical hypoT (Archives of Med Research, 2006 May) 3) Should subclinical hypoT be treated?
PROBABLY… BUT STILL CONTROVERSIAL! • “Society” Consensus guidelines: Amer. Assoc. Clin. Endo, The Endo Society, Amer. Thyroid Assoc. actually CONFLICT with USPSTF (US Preventive Services Task Force) • Routine screening gen pop’n? YES NO • Routine screening preg women? YES YES • Routine Rx pts with TSH 4.5-10? YES NO • Generally No Rx recommended IF • Thyroid Ab Negative AND • TSH < 10 AND • No symptoms, goiter, dyslipidemia, pregnancy or ovulatory dysfunction / infertility • BUT annual TSH recommended
REFERENCES • NEJM REVIEW ARTICLES • Vol 345, No 4 July 26, 2001 • Vol 345, No 7 Aug 16, 2001 • “Effects of Subclinical Thyroid Dysfunction on the Heart” Ann Intern Med 2002;137; 904-914 • “Subclinical thyroid disease: scientific review and guidelines for diagnosis and management”, JAMA. 291(2):228-38, 2004 Jan 14 • “Screening for subclinical thyroid dysfunction in nonpregnant adults: a summary of the evidence for the U.S. Preventive Services Task Force”,] Annals of Internal Medicine. 140(2):128-41, 2004 Jan 20.
REFERENCES CONT’D • “Subclinical thyroid dysfunction as a risk factor for cardiovascular disease”, Arch Intern Med, 2005 Nov = Busselton health Study • “Relationship between subclinical thyroid dysfunction and femoral neck BMD in women”, Arch Med Research, 2006 May