Thyroid disease -...

Presented by: Ontario’s Geriatric Steering Committee

Thyroid disease Maria Wolfs MD MHSc FRCPC

Presented by: Ontario’s Geriatric Steering Committee 2

Thyroid nodules

Subclinical hypothyroidism

Subclinical hyperthyroidism

Outline

Presented by: Ontario’s Geriatric Steering Committee 3 Presented by: Ontario’s Geriatric Steering Committee

Thyroid Nodules

Thyroid nodule - prevalence

Prevalence on palpation: – in iodine sufficient parts of the world

– 5% in women – 1% in men

Prevalence on ultrasound: – 19-67% of randomly selected patients

Risk of cancer in thyroid nodule: – 5-10 %

Cooper DS et al. Thyroid 2009;19(11)

Investigating a thyroid nodule

LOW TSH N/HIGH TSH

Investigating a nodule

LOW TSH

Hyperfunctioning

nodules = very low

risk for malignancy

N/HIGH TSH

Thyroid Ultrasound

Suspicious ultrasound features

Microcalcifications

Hypoechoic

Increased nodular vascularity

Infiltrative margins

Taller than wide on transverse view

? Fine needle aspiration biopsy

N/HIGH TSH

Thyroid Ultrasound

Who needs a biopsy? > 0.7 cm nodule

High-risk history + nodule WITH suspicious sonographic features

Abnormal cervical lymph nodes

≥ 1 cm nodule

Solid nodule AND hypoechoic

Microcalcifications present in nodule

≥1-1.5 cm nodule

Solid nodule AND iso- or hyperechoic

≥1.5-2.0cm nodule

Mixed cystic–solid nodule WITH any suspicious ultrasound features

> 2.0cm nodule

Mixed cystic–solid nodule WITHOUT suspicious ultrasound features

Spongiform nodule

Who needs a biopsy?

> 0.7 cm nodule

High-risk history + nodule WITH suspicious sonographic features

Abnormal cervical lymph nodes

≥ 1 cm nodule

Solid nodule AND hypoechoic

Microcalcifications present in nodule

≥1-1.5 cm nodule

Solid nodule AND iso- or hyperechoic

≥1.5-2.0cm nodule

Mixed cystic–solid nodule WITH any suspicious ultrasound features

> 2.0cm nodule

Mixed cystic–solid nodule WITHOUT suspicious ultrasound features

Spongiform nodule

•≥ 1 cm Solid

•≥ 2 cm Mixed solid-cystic

Fine-needle biopsy

Benign

Non-diagnostic

Malignant

Suspicious (indeterminate) for neoplasm

Follicular lesion

Fine-needle biopsy

Benign

–5% false-negative rate of FNA

–Higher in larger nodules (> 4cm)

Non-diagnostic

Malignant

Follicular lesion

Follow-up benign nodules

Yearly physical exam

Follow up ultrasound – in 6-18 months after initial FNA

If stable – next follow up 3-5 years later

If evidence of growth – 20% increase in two nodule dimensions with minimal increase of 2

mm in two dimensions on ultrasound – Repeat FNA – Refer to endocrine

LT4 suppression therapy is not recommended

Follow up ultrasound – in 6-18 months after initial FNA

If stable – next follow up 3-5 years later

If evidence of growth – 20% increase in two nodule dimensions with minimal

increase of 2 mm in two dimensions on ultrasound

– Repeat FNA

– Refer to endocrine

Follow up ultrasound

– in 6-18 months after initial FNA

If stable

– next follow up 3-5 years later

If evidence of growth

– 20% increase in two nodule dimensions with minimal increase of 2 mm in two dimensions on ultrasound

– Repeat FNA

– Refer to endocrine

Fine-needle biopsy

Benign

Non-diagnostic

–Repeat FNA

Malignant

Follicular lesion

Fine-needle biopsy

Benign

Non-diagnostic

Malignant – 95% risk of malignancy

Suspicious (indeterminate) for neoplasm – 50-75% risk of malignancy

Follicular lesion – 5-15% risk of malignancy

Refer to endocrine or ENT

Indications for thyroid surgery

Malignant or suspicious pathology

Family history of familial medullary thyroid cancer Recurrent cystic nodule with benign FNA

Compressive symptoms

Increasing in size

Size > 4 cm

Patient preference

Thyroid Nodules

Take home message

Thyroid nodule - summary

N/HIGH TSH

Thyroid Ultrasound

LOW TSH

Thyroid Uptake and Scan

Fine needle aspiration biopsy if:

• ≥ 1 cm Solid

• ≥ 2 cm Mixed solid-cystic

N/HIGH TSH

Thyroid Ultrasound

Fine needle aspiration biopsy if:

• ≥ 1 cm Solid

• ≥ 2 cm Mixed solid-cystic

N/HIGH TSH

Thyroid Ultrasound

Ultrasound in 6-18 months after initial FNA

If stable Next follow up 3-5 years

Biopsy: – Malignant

– Suspicious (indeterminate) for neoplasm

– Follicular lesion

Follow-up US shows significant growth

Indications for surgery: – Family/personal history of familial thyroid cancer (MEN2,

– Recurrent cystic nodule with benign FNA (cosmetic concerns)

– Compressive symptoms

– > 4 cm

Refer to endocrine or ENT

Thyroid nodules

Outline

Subclinical

Hypothyroidism

log/linear inverse relationship

between serum TSH and FT4

Presented by: Ontario’s Geriatric Steering Committee 29 Surks M I , Hollowell J G JCEM 2007;92:4575-4582

TSH distribution by age groups

% TSH >4.5 mIU/L

prevalence 4 to 15% – USA NHANES III 4.3 %

– Europe • 4.2 % iodine-deficient areas

• 23.9 % abundant iodine intake

↑ with age

females > males whites > blacks

75% have TSH <10

Endocrine Reviews 29: 76–131, 2008

Causes of SHypo

Inadequate replacement therapy for overt hypothyroidism – inadequate dosage

– non-adherence

– drug interactions • iron, calcium carbonate, cholestyramine, dietary soy, fiber,

– increased T4 clearance • phenytoin, carbamazepine, phenobarbital, etc.

– malabsorption

CMAJ 2012;184:205

Causes of SHypo

Chronic autoimmune thyroiditis

Recovery from thyroiditis

Central hypothyroidism

TSH receptor gene mutations

CMAJ 2012;184:205

Causes of SHypo

Drugs impairing thyroid function: – iodine and iodine-containing medications

• amiodarone, radiographic contrast agents

– lithium carbonate

– cytokines (especially interferon α)

– aminoglutetimide

– ethionamide

– sulfonamides

– sulfonylureas

CMAJ 2012;184:205

Progression to overt hypothyroidism

% /year TSH

TPO + 4.3% 2.0%

- 2.6% 0.5%

Vascular effects of SHypo

↑ systemic vascular resistance

↑ arterial stiffness

Altered endothelial function

↑ atherosclerosis

Altered coagulability

Rodondi N. et al. JAMA. 2010;304(12):1365-1374

Presented by: Ontario’s Geriatric Steering Committee Biondi B , Cooper D S Endocrine Reviews 2008;29:76-131

Increased CHD events and mortality

Rodondi N. et al. JAMA. 2010;304(12):1365-1374

Lipid effects of hypothyroidism

Pearce E N JCEM 2012;97:326-333

Effect of LT4 on dyslipidemia

Biondi B , Cooper D S Endocrine Reviews 2008;29:76-131 Cochrane Database Syst Rev 2007 Jul 18;(3):CD003419

Overall - no effect on cholesterol levels, HDL-C, LDL-C, triglycerides, ApoA, ApoB, or Lp(a)

Hypothyroid symptoms score

Cochrane Database Syst Rev 2007 Jul 18;(3):CD003419

Emotional Function tests

Jul 18;(3):CD003419

Health Related Quality of Life Cochrane Database Syst Rev 2007 Jul 18;(3):CD003419

Cognitive function

Cochrane Database Syst Rev 2007 Jul 18;(3):CD003419

Consider LT4 treatment

High background CV risk

– Diastolic dysfunction

– Diastolic hypertension

– Atherosclerotic risk factors

– Dyslipidemia

– Diabetes

Consider LT4 treatment

Ongoing trials of SHypo in the elderly

IEMO 80-plus Thyroid Trial Collaboration

– www.iemo.nl

Thyroid Hormone Replacement for

Subclinical Hypo-Thyroidism Trial (TRUST)

– www.trustthyroidtrial.com

Subclinical

Hypothyroidism Take home message

Repeat TSH, FT4, Thyroid antibodies in 3-6

months

No evidence of benefit for Rx with LT4

Consider treatment if:

– TSH > 10 mU/L

– Cardiac disease

– Symptoms

Thyroid nodules

Outline

Subclinical

Hyperthyroidism

Prevalence (NHANES III)

– TSH < 0.4 mU/L: 2%

– TSH < 0.1 mU/L: 0.7%

Latrogenic

– 14 - 21% of those on LT4 therapy

Most patients are asymptomatic

– Elderly can present with hypothyroid symptoms

Biondi B , Cooper D S Endocrine Reviews 2008;29:76-131

Causes of SHyper

Endogenous causes

– Graves’ disease

– Autonomously functioning thyroid adenoma

– Multinodular goiter

Exogenous causes

– Excessive thyroid hormone replacement

– Intentional thyroid hormone suppression

Non-thyroid causes of SHyper

1st trimester pregnancy

Non-thyroidal illness

Psychiatric illness

Administration of drugs – dopamine, glucocorticoids

Pituitary or hypothalamic insufficiency

Decreased age-related thyroid hormone clearance or pituitary set point

SHyper Mood and cognition

Conflicting data – reduced feeling of well-being

– feelings of fear, anxiety, hostility

– inability to concentrate

– ↑ risk of dementia and Alzheimer’s Disease

Confounding factors – autoimmunity

– depression itself

Screening bias

SHyper Cardiovascular effects

Impaired quality of life

– increased heart rate

– reduced exercise capacity

Atrial fibrillation - elderly

↑ Left ventricular mass

– negative prognostic cardiovascular factor in the

general population

SHyper Skeletal effects

Accelerated bone turnover

– In postmenopausal patients

Increased fracture risk

– TSH ≤ 0.1 mU/L vs. N TSH

– 3-fold increased risk of hip fracture

– 4-fold increased risk of vertebral fracture

Fracture risk and LT4 dose

BMJ 2011;342:d2238

SHyper management algorithm

Physical exam

↓TSH and N FT4 + N FT3

Large goitre

Surgical intervention

if significant airway

compression

Physical exam

Large goitre

Surgical intervention

if significant airway

compression

No goitre

Depends on

degree of TSH

suppression

Repeat TSH FT4 FT3 in 3-6 months

TSH 0.1 - 0.4 mU/L

Age >65 years

Post-menopausal women

Cardiac risk factors

Cardiac disease

Osteoporosis

Repeat TSH FT4 FT3 in 3-6 months

TSH 0.1 - 0.4 mU/L

Repeat TSH FT4 FT3 in 6 weeks

(sooner if CVS problems)

TSH < 0.1 mU/L

Work-up for overt

hyperthyroidism

TSH < 0.1 mU/L

Work-up for overt

hyperthyroidism

Referral to endocrinology

Low TSH + high FT4

Increased uptake:

Graves disease

Toxic nodule

Toxic multi-nodular goitre

Thyroid gland stimulation by HCG

Decreased uptake: Thyroiditis

Extra-thyroidal sources Exogenous

Endogenous

Thyroid scan

Thyroid uptake

Increased uptake:

Graves disease

Toxic nodule

Thyroid gland stimulation

by HCG

Low TSH + high FT4

Thyroid uptake

Presented by: Ontario’s Geriatric Steering Committee Thyroid scan

Increased uptake:

Graves disease

Toxic nodule

by HCG

Low TSH + high FT4

Thyroid uptake

Decreased uptake:

Thyroiditis

Extra-thyroidal sources Exogenous

Endogenous

Thyroid scan

Increased uptake:

Graves disease

Toxic nodule

by HCG

Low TSH + high FT4

Thyroid uptake

LOW TSH

Thyroid scan – toxic nodule(s)

Normal scan Abnormal scan

uptake on R side with

suppression on L side

Toxic nodule

Management

– Radioactive I131

– Surgery

– Consider pre-treatment with anti-thyroid drugs

if symptomatic or poor surgical candidate

Thyroid scan – Grave’s disease

Normal uptake (<15%) Increased uptake in Graves disease (30-50%)

Thyroid Receptor Ab - TRAb (Thyroid Stimulating

Immunoglobulin - TSI) in 85-

90% of Grave’s disease

Thyroid Receptor Ab -

TRAb (Thyroid

Stimulating

Immunoglobulin - TSI) in

85-90% of Grave’s

disease

NB TRAb (TSI)

NOT covered

by MOH labs

Graves’ disease

Management

– Consider beta-blocker

– Anti-thyroid drugs

• Propylthiouracil (ODB coverage)

• Methimazole

– Consider bone health

Subclinical

Hyperthyroidism Take home message

SHyper

Clinical effects in the elderly

– Mood and cognition

– Atrial fibrillation

– Increased fracture risk

Take home message - SHyper

Repeat TSH FT4 FT3

in 3-6 months

TSH 0.1 - 0.4 mU/L

TSH < 0.1 mU/L

Take home message - SHyper

Thyroid uptake and scan

Repeat TSH FT4 FT3

in 3-6 months

TSH 0.1 - 0.4 mU/L

TSH < 0.1 mU/L

Thyroid nodules

Outline

Thank you!

Thyroid disease -...

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