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![Page 1: Thyroid Disorders - Boston College Home Page · PDF fileThyroid Disorders Giuseppe Barbesino, MD. DISCLOSURES • Advisory Board Member for Akrimax. • There has been no commercial](https://reader034.vdocument.in/reader034/viewer/2022042800/5a7084e27f8b9aa7538c1896/html5/thumbnails/1.jpg)
22nd Annual Northeast Regional Nurse Practitioner Conference – May 6-8, 2015
Thyroid DisordersGiuseppe Barbesino, MD
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D I S C L O S U R E S
• Advisory Board Member for Akrimax.• There has been no commercial support
or sponsorship for this program.• The program co-sponsors do not endorse
any products in conjunction with any educational activity.
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A C C R E D I TAT I O N
Boston College Connell School of Nursing Continuing Education Program is accredited as a provider of continuing nursing education by the American Nurses Association Massachusetts, an accredited approver by the American Nurses Credentialing Center’s Commission on Accreditation.
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22nd Annual Northeast Regional Nurse Practitioner Conference – May 6-8, 2015
S E S S I O N O B J E C T I V E S
• Describe the key aspects of thyroid physiology.
• Interpret thyroid function tests.• Summarize the workup of hyperthyroidism
and hypothyroidism as well as treatment.• Explain the diagnostic work-up of thyroid
nodules.
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THYROID DISEASE
PRIMER Giuseppe Barbesino, MD
Massachusetts General Hospital
Harvard Medical School
Thyroid Unit
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Objectives
• Review key aspects of thyroid physiology
• Ordering and interpreting thyroid function tests
• Diagnostic workup of hyperthyroidism
• Diagnostic workup of hypothyroidism, and treatment, with
special reference to pregnancy
• Diagnostic work-up of thyroid nodules
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HYPERTHYROIDISM
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Case 1:
• 25M with no PMHx presents with a 10lb weight loss, feeling on edge, trouble concentrating.
• Additional history
• Appetite normal to increased
• Increased frequency of bowel movements
• + palpitations
• + trouble sleeping
• + irritability
• + exercise intolerance
• Symptoms for ~3 months
• Family history:
• Sister takes thyroid hormone
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Case 1:
• Exam:
• T = 97.6 P112, regular, BP 136/66
• Gen: thin man in NAD, somewhat on edge
• HEENT: notable stare, no conjunctival injection, periorbital edema
or proptosis
• Neck: symmetric goiter, nontender, 30gm, no audible thyroid bruit,
+ palpable pyramidal lobe
• CV: regular tachycardia
• Pulm: CTA-B
• Abdomen: no organomegaly, NTND
• Ext: thin, 2+ peripheral pulses, no LEE
• MSK: mild (4+) proximal muscle weakness
• Neuro: fine resting tremor, brisk DTRs
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Thyroid Physiology
From DPC Online
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The thyroid is simple…
Thyroxine (T4)
Triiodothyronine (T3)
TSHR
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Thyroid hormones
• T3 = active hormone, shorter half life
• T4 = predominant circulating hormone, longer half life
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Thyroid follicles
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Thyroid hormone metabolism
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Circulating thyroid hormone forms
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
Free
Albumin
TTR
TBG
TT4
FT4
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Thyroid Hormone Action
• Mediated by nuclear hormone receptors
Williams Endocrinology, Ch10, Fig 10-7, pg 311
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Thyroid hormones
• T4 – thyroxine
• higher affinity for TBG –
• ~10% cleared per day
• T ½ = ~7 days
• T3 –triiodothyronine
• lower affinity for TBG
• 60% turnover per day
• T ½ = 0.75 days
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End organ effects -1
• Brain/Nervous System:
• Neurogenesis (Cretinism)
• Catecholamine sensitivity
• Vascular:
• Increased heart contractility via α-MHC, β-adrenergic receptors
• Increased cardiac O2 consumption
• Vasodilation of vascular smooth muscle (NO2)
• Metabolic:
• Increase lipolysis
• Increased thermogenesis
• Insulin resistance (and turnover)
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End organ effects -2
• Skeletal Muscle
• Increased adrenergic tone
• Adrenal:
• Cortisol metabolism
• Bone
• Increased bone turnover (hypercalcemia, osteopenia)
• Blood
• Turnover of vitamin-K dependent clotting factors
• Reproductive
• Conversion of testosterone (gynecomastia)
• Altered LH/FSH pulses (GnRH signaling)
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Thyroid Physiology
From DPC Online
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Control and regulation of thyroid function
pituitary/hypothalamus (TRH)
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Evaluation of thyroid function
• Laboratory:
• TSH – best test (mU/mL)
• Free T4 – “free” fraction of circulating T4 (ng/mL)
• Total T3 (ng/dL)
• Total T4 (μg/dL)
• T3 Resin Uptake – free T4 index
• Imaging:
• Radioactive Iodine uptake and scan (123I)
• Thyroid ultrasound
• Role beyond thyroid nodule evaluation only in special circumstances
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Thyrotoxicosis
• Overt thyrotoxicosis: • Low/undetectable TSH
• High free T4, T4, or T3
• Subclinical hyperthyroidism: • Low/undetectable TSH
• Normal free T4, T3 WNL
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Case 1: thyrotoxicosis
• Labs:
• TSH <0.01 (0.4-5)
• FT4 4.2 (0.8-1.8)
• Total T3 570 (60-181)
• Diagnosis
• Thyrotoxicosis
• Etiology?
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Hyperthyroidism: differential diagnosis
• TSH independent autonomous hormone production
• Graves’ disease
• Hyperfunctioning thyroid nodules
• Single/multiple
• hCG-mediated – gestational trophoblastic disease
• Struma ovarii (extremely rare)
• Metastatic thyroid cancer (extremely rare)
• Release of stored hormone
• Thyroiditis
• Painless/painful
• Amiodarone
• Exogenous administration of hormone • Factitious hyperthyroidism
• TSH-dependent thyrotoxicosis – Pituitary tumors
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Graves’ disease
TSH receptor
TSH Receptor Antibody
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Toxic Nodules
Mutated TSHR
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Thyroiditis
TSHR
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Destructive thyroiditis
• Painful subacute thyroiditis
• Painless subacute thyroiditis
• Sporadic
• Postpartum
• Palpation thyroiditis (surgery)
• Radiation thyroiditis
• Amyloidosis
• Pneumocystis thyroiditis
• Malignant pseudothyroiditis (mets)
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Destructive thyroiditis – natural history
Pearce EN et al. N Engl J Med 2003;348:2646-2655.
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Functional test
• Radioiodine uptake and scan
• Need simultaneous TSH measurement for accurate
interpretation
Adapted from Ross DS. N Engl J Med 2011;364:542-550.
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Thyrotoxicosis: clinical clues
• Pathognomonic for Graves’ • Ophthalmopathy – conjunctival injection, periorbital edema, proptosis
• Dermopathy (rare)
• Thyroid bruit
• Clinical pearl: it’s not thyroiditis if symptoms and/or
thyrotoxicosis lasts more than 3-4 months
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Thyrotoxicosis: diagnostic testing
• Antibody testing: ruling Graves’ diseases in or out
•
• Thyroid stimulating immunoglobulins (TSI)
• Thyrotropin binding inhibitory immunoglobulins (TBII)
• Specificity and sensitivity >95%
• TPO (thyroid peroxidase) antibody can be positive in any
autoimmune thyroid disease, therefore is not useful in
thyrotoxicosis-> do not order
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TSH receptor antibody in GD
Ota et al., Clin.Endocrinol, 2007
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Thionamides
Cooper DS. N Engl J Med 2005;352:905-917.
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Effect of thionamides
TSHR
TSH RECEPTOR AUTOANTIBODY
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Graves’ disease – medical therapy
• Goals
• Control of thyroid hyperfucntion
• Inhibit thyroid hormone synthesis: thionamides
• Inhibit thyroid hormone effects on target organs: beta-blockers
• Propranolol 20-80 MG TID
• Atenolol (daily dosing) – 25-50mg, goal HR <90
• Cure
• Natural history of TSI
• Treatment for ~1 year then withdrawal
• 40-50% in remission
• 50% of these will relapse – long term remission in ~25%
• Surgery
• Radioactive iodine
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Methimazole vs PTU
Reaction PTU MMI
Minor Reactions (fever, rash) 1-5% 1-5%
Agranulocytosis 0.2-.5% 0.2-.5%
Hepatotoxicity hepatitis cholestasis
Vasculitis ANCA + very rare
Teratogenicity Moderate Severe
Nakamura et al, JCEM 2007, 92:2157
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Special Scenarios
• Pregnancy:
• PTU may be preferred due to MMI embryopathy (choanal atresia
and aplasia cutis) during first trimester.
• Decline in autoimmunity may enable reduction or discontinuation of
medication (likely relapse in post-partum period).
• Goal of treatment – prevent fetal hyper- and hypo-thyroidism
(maintain mother in slightly thyrotoxic range). Involve high-risk OB-
GYN and endocrinology.
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Graves’ – definitive therapy
• Radioactive Iodine – 131I • Successful in ~85% of patient with a single dose
• Contraindications:
• Pregnancy
• Lactation
• Inability to comply with radiation safety guidelines
• Moderate to severe ophthalmopathy
• Surgery (total thyroidectomy) • Adverse effects:
• 1-3% chance of recurrent laryngeal nerve injury, hypoparathyroidism
• Surgical expertise (volume) important
• Very large goiter, MNGs
• Pregnant with allergy to ATDs
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HYPOTHYROIDISM
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Hypothyroidism
• Overt hypothyroidism: • Elevated TSH
• Low free T4, T4, or T3
• Subclinical hypothyroidism: • Elevated TSH
• Free T4, T3 WNL
• TSH level correlates with degree of hypothyroidism
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Hypothyroidism - Manifestations
• Goiter
• Cold intolerance
• Constipation
• Fatigue, lethargy
• Weight gain
• Coarse hair
• Brittle nails
• Dry skin
• Bradycardia
• Hypos of hypothyroidism: hyponatremia, hypotension,
hypoventilation, hypothermia, hypometabolism
• Hypertension
• Menstrual irregularities
(polymenorrhea)
• Infertility
• Elevated cholesterol
• Psychiatric abnormalities
• Pericardial effusion
• Ventricular arrhythmias
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Hypothyroidism - etiology
• Hashimoto’s thyroiditis - Most common
• Hashimoto’s thyroiditis - Second most common
• Hashimoto’s thyroiditis – Third most common
• Prior thyroid surgery
• Radioactive iodine treatment
• External radiation
• Drugs (amiodarone, lithium, TKIs)
• Congenital hypothyroidism • Thyroid dysgenesis
• Enzymatic defects
• Mutant TSH receptor
• TSH receptor antibodies (inhibitory)
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Hashimoto’s thyroiditis
• Chronic autoimmunity to thyroid
• Common in iodine sufficient areas
• Thyroid peroxidase antibody positive (TPO) in >90% of
cases
• Can be associated with other autoimmune diseases
• Goitrous, or atrophic
• Typical exam, a rubbery moderately enlarged thyroid
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Hashimoto’s thyroiditis- variable clinical
course
Course Intervention
Euthyroid No treatment, except in
pregnancy
Subclinical hypothyroidism Levothyroxine if <60 y/o
Consider monitoring in >60y/o
Overt hypothyroidism Levothyroxine
Transient thyrotoxicosis, followed
by transient or permanent
hypothyroidism
Treat thyrotoxic symptoms,
Treat hypothyroidism if
permanent
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TPO antibodies in thyroid disease
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T3 in hypothyroidism
TSH
T4
T3 T4
+ −
TSH
− Exogenous T4
+
T3
X
Peripheral tissues
Peripheral tissues
Normal
Hypo
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Hypothyroidism – treatment
• Levothyroxine (LT4) • Standard of care
• ~1.4mcg/kg/d
• Single daily dose, but adjust based on T ½ - weekly dosage
• Empty stomach
• Generics are fine in my experience, but opinions vary
• Liothyronine (LT3) • No proven benefit, additional risks
• Not routinely used -> can be tested in additio to T4 in select individuals
• Used in psychiatry
• Dessicated animal thyroid (Armour) • Contains both LT4 and LT3, with supraphysiologic T3
• Difficult titration
• It is a form of thyroid replacement
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Changes in TSH after changes in T4
dose
Carr et al. Clin Endocrinol (Oxf). 1988
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Causes of thyroxine ineffectiveness
Reduced absorption
• Calcium • Moderate
• Iron • Major
• Multivitamins • Variable
• Cholestyramine • Major
• PPI • Minor
• GI disease • Celiac disease
• RYGBP
Increased metabolism
• Rifampin
• Dilantin
• Phenobarbital
• TKIs
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THYROID PHYSIOLOGY AND
THYROID DISEASE IN
PREGNANCY
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Reciprocal changes in TSH and HCG
during pregnancy
Glinoer et al. JCE&M, 1990
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Changes in TBG levels during pregnancy
Glinoer et al. JCE&M, 1990
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Effects of pregnancy on total and free
T4
0
20
40
60
80
100
120
140
160
180
Normal Pregnancy
Free
Albumin
TTR
TBGTT4
FT4
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Effects of normal pregnancy on thyroid
function tests
•Lower TSH
•Higher TT4, TT3
•Normal FT4
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Hypothyroidism and
Pregnancy:
Need for Increased doses
of T4
Alexander et al. NEJM, 2004
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Hypothyroidism in Pregnancy: Long Term
Effects on the Offspring
Haddow et al., NEJM 1999
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Hypothyroidism in Pregnancy: Long Term Effects on
the Offspring
94
96
98
100
102
104
106
108
110
112
IQ
Hypothyroid
Hypothyroid + T4
Controls
Haddow et al., NEJM 1999
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Hypothyroidism and Pregnancy: key
points • Pre-conception TSH should be >0.3-<2.5 mU/L
• Euthyroid women with Hashimoto’s thyroiditis may benefit
from treatment even when euthyroid.
• Test TSH FT4 immediately (4-6 wks)
• Expect increased need of T4 (50%) early
• Monitor every 4-6 weeks
• Return to pre-pregnancy T4 dose after delivery
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THYROID NODULES
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Welch & Davies, JAMA Otolaryngol Head Neck Surg., 2014
Current Thyroid Cancer Trends in the
United States
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Tan, G. H. et al., 1997
Prevalence of Thyroid Incidentalomas Detected on Ultrasonography
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Incidence of Malignancy in Solitary and
Multiple Thyroid Nodules-US
Frates et al., 2006
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Incidence of Malignancy in Thyroid
Nodules According to Nodule Size
Frates et al., 2006
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Malignancy Rates in Subcentimetric
Nodules
Papini et al., 2002
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Impact of Tumor Size on Papillary Thyroid
Cancer Mortality
Perc
en
t S
urv
ivin
g
Hay et al., 1993
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A typical US report
• Left lobe:
– 0.9 x 0.7 x 1.2 cm hypoechoic nodule in the lower pole.
– 1.4 x 1.3 x 1.6cm isoechoic nodule with central flow in the midpole
– 0.3 x 0.6 x 0.9 cm nodule with microcalcifications in the upper pole
• Right lobe:
– 3.3 cm partially cystic nodule in the lower pole
– 2.1 x 2.1 x 1.8 cm solid isoechoic nodule in the upper lobe
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Evaluation of thyroid nodules: role of fine
needle aspiration biopsy • Office procedure, local anesthesia, virtually with no risk
• False negative results: 2-4%
• False positive results: almost nil
• Non-diagnostic: 5-15%
• Indeterminate: 15-25%
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First Rule: Only Cold Nodules Should Be
Considered for FNA
Corollarium: always order a TSH!
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Risk Assessment In Thyroid Nodules
Mortality from Thyroid Malignancy
Risk of Malignancy in Thyroid Nodule
X
=
Mortality from Thyroid Nodules
Ultrasound
features
Size
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Value of some U/S features in predicting
malignancy in thyroid nodules.
Macrocalcific.Absent Halo Microcalcific. Hypoechoic Very Hypoechoic Central Flow Taller Than Wide
Specificity
Sensitivity
Irreg. Margins
Pe
rce
nt
25
50
75
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Nodule Features Associated With
Benignity
Feature Malignant/Total Malignancy
Rate
Spongiform 0/210 0%
Cyst with Colloid Clot 0/53 0%
Giraffe 0/23 0%
White knight 0/17 0%
Red Light 15/52 28.8%
Hypoechoic 14/45 31.1%
Isoechoic without
Halo
2/37 5.4%
Isoechoic with Halo 4/42 9.5%
Ring of Fire 4/10 40%
Other 1/12 8.3% Bonavita et al., 2008
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ATA recommendations for FNA of thyroid
nodules
Almost never If highly suspicious
on U/S
If moderately
suspicious on U/S If not purely cystic
<1 1-1.5 1.6-2.0 >2
-Microcalcifications
-Deeply hypoechoic
-Familial syndromes
-H/O neck XRT
-Solid
-Hypoechoic
-Spongiform
Size(cm)
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THANK YOU!