1 Thyroid Disease: Overview Kenneth B. Ain, M.D. Professor of Medicine The Carmen L. Buck Chair of Oncology Research Director, Thyroid Oncology Program Div. of Endocrinology & Molecular Medicine Dept. of Internal Medicine University of Kentucky Medical Center &Veterans Affairs Medical Center, Lexington, KY Thyroid Gland: In Situ Copyright retained by Dr. Kenneth B. Ain Copyright retained by Dr. Kenneth B. Ain O O O OH I I I I N deiodinase 5-d T4 (Pro-Hormone) levothyroxine Copyright retained by Dr. Kenneth B. Ain O O O OH I I I N O O O OH I I I N 5 ' -d -deiodinase T3 (Active Hormone) triiodothyronine reverse T3 (Inactive Metabolite) Free T4 l T4 T4 Bound to Serum Proteins Free T4 0 . 03% of Total T4 Metabolically available to tissues. Feedback regulation. Copyright retained by Dr. Kenneth B. Ain Tota (TBG, TBPA, Albumin, etc.) 99 . 97% of Total T4 Copyright retained by Dr. Kenneth B. Ain Regulates Gene Transcription
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36 Thyroid Ain.ppt - UK HealthCare CECentral · • Thyroid acropachy (similar to clubbing: rare) • Discriminate from: – Exogenous L-T4 – Toxic adenoma or multinodular goiter
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Thyroid Disease:Overview
Kenneth B. Ain, M.D.
Professor of Medicine
The Carmen L. Buck Chair of Oncology ResearchDirector, Thyroid Oncology Program
Div. of Endocrinology & Molecular MedicineDept. of Internal Medicine
University of Kentucky Medical Center&Veterans Affairs Medical Center, Lexington, KY
Thyroid Gland: In Situ
Copyright retained by Dr. Kenneth B. Ain
Copyright retained by Dr. Kenneth B. Ain
O
O
O
OH
I
I
I
I
N
deio
dina
se
5-d
T4 (Pro-Hormone) levothyroxine
Copyright retained by Dr. Kenneth B. Ain
O
O
O
OH
II
I
N
O
O
O
OH I
I
I
N
5'-d
-deiodinase
T3 (Active Hormone) triiodothyronine
reverse T3 (Inactive Metabolite)
Free T4
al T
4 T4 Bound to Serum Proteins
(TBG TBPA
Free T4
0 .03% of Total T4
Metabolically available to tissues.
Feedback regulation.
Copyright retained by Dr. Kenneth B. Ain
Tot
a (TBG, TBPA, Albumin, etc.)
99 . 97% of
Total T4
Copyright retained by Dr. Kenneth B. Ain
Regulates Gene Transcription
2
Copyright retained by Dr. Kenneth B. Ain
10
100
1000
Relationship Between TSH Levels and Free T4
Copyright retained by Dr. Kenneth B. Ain
Hyperthyroid
Free T4
0.01
0.1
1.0
Hypothyroid Euthyroid
Undetectable
Spencer CA, et al. J Clin Endocrinol Metab. 1990;70:453-460.
Normal
Causes of Hypothyroidism
• Primary– Destructive
• Hashimoto’s thyroiditis
• Post-131I therapy
• Post-thyroidectomy
R ibl
• Secondary• Pituitary tumor
• Pituitary granuloma
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– Reversible• Endemic goiter:
– Iodine deficiency
– &/or natural goitrogens
• Iodine Excess
• Drugs: thioureas, lithium, etc.
– Congenital• Thyroid agenesis
• Ectopic thyroid
• Dyshormonogenesis
y g
• Pituitary apoplexy
• Tertiary• Hypothalamic disease
– Tumor
– Craniopharyngioma
Tiredness
Forgetfulness/Slower Thinking
Moodiness/ Irritability
DepressionPersistent Dry or Sore Throat
Hoarseness/Deepening of Voice
Enlarged Thyroid (Goiter)
Puffy Eyes
Clinical Features of Hypothyroidism
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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
Muscle Weakness/Cramps
Constipation
Infertility
Menstrual Irregularities/Heavy Period
Slower Heartbeat
Difficulty Swallowing
Persistent Dry or Sore Throat
Hypothyroidism and DepressionHave Many Common Features
– Abnormalities of thyroid hormone binding or resistance
Graves’ Ophthalmopathy
• Risks:– Cosmetic problem– Restriction of eye movement– Diplopia– Corneal ulceration– Optic nerve damage and blindness
Copyright retained by Dr. Kenneth B. Ain
• Evaluate:– Lids: retraction– Cornea: ulcer, keratitis– Proptosis: may need decompression surgery– Muscles: diplopia, may need surgery– Nerve: papilledema, field defect, loss of color vision & acuity
• Treatment:– Keratitis or chemosis: lubrication & protection– Rapidly worsening proptosis: systemic steroids, XRT– Severe proptosis &/or diplopia: orbital decompression surgery
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Treatment of Thyrotoxic Graves’ Disease
• Surgery (bilateral subtotal thyroidectomy)• Risk of surgery, anesthesia, recurrent laryngeal nerve damage,
Uses:• acute reduction in thyroid hormone; preparation for surgery or I-131• Primary therapy (remission <20%); Use in pregnancy
– Side Effects:• Minor: rash, urticaria, transient leukopenia• Major (rare): agranulocytosis, aplastic anemia, hepatitis, SLE-like
• Radioactive Iodine (131I):– Safe, administered orally, relatively inexpensive– No evidence for long-term adverse effects (aside from hypothyroidism)– Frequently 1st line therapy; can be used at any age
Other Causes of Thyrotoxicosis
• Toxic autonomous nodule (TSH receptor mutation)
– Tx: I-131 vs Surgery
• Toxic Multinodular Goiter– Tx: I-131 vs Surgery
Transient thyroiditis
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• Transient thyroiditis– Tx: Beta-blockade & supportive care
• Exogenous Levothyroxine– Psychiatric counseling
• Pituitary Tumor (extremely rare)
– Inappropriate TSH, Evaluate with MRI, Often aggressive
– Tx: Surgery (if resectable), Gamma-knife, anti-thyroid Rx, octreotide
Post-Partum Thyroiditis
• Prevalence: approx 10% of pregnancies; <25% clinically obvious
• Presentation:– Onset of thyrotoxicosis: 1 - 6 months PP
– Onset of hypothyroidism: 4 - 12 months PP
– Some with thyrotoxicosis or hypothyroidism only
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Some with thyrotoxicosis or hypothyroidism only
• Associations:– Type I Diabetes Mellitus: 25% PPT
– Possible associations with miscarriage
– Post-partum Depression: hypothyroid phase
– TPO-Abs: + Abs have 33% PPT
• Screening:– All patients with Type I Diabetes Mellitus
– Patients with positive antibodies
Thyroid Cancer:Overview of Diagnosis & Clinical
Management
Thyroid Cancer Statistics: 2007
• Incidence around 34,000 U.S. cases– 75% Female/25% Male– 1.6% of cancers of all ages
3 8% of cancers in children (0 19 yrs)
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– 3.8% of cancers in children (0-19 yrs)
• Mortality: 1,530 in U.S.– 58% Female/42% Male
• Prevalence: > 450,000 cases in U.S.
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Presentations of Thyroid Cancer
• Thyroid noduleSolitary nodule
Dominant nodule of multinodular gland
• Cervical Node or Mass
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• Distant metastases– Lung
– Bone
– Brain
• Incidental to Resection of Benign Thyroid Mass
Clinical vs. Occult Disease
• 5-60% (depending on method) of thyroid glands contain a microscopic (<1.0 cm) focus of papillary cancer
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• Macroscopic (>1.0 cm) Nodules– Single: 10% malignant– Single Dominant in multinodular gland: 10% malignant– Palpable Nodule in irradiated gland: 30% malignant
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Evaluation of Thyroid Nodules
• Exam & History– Size, Location, Nodes– Is patient thyrotoxic?
• Yes: Get thyroid scan• NO: Do NOT do scan!!!
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• Fine Needle Aspiration Biopsy– Requires some expertise– Specially trained Cytologist– Results (If Adequate Sample):
Ipsilateral Total Lobectomy with IsthmusectomyMinimal Initial Surgery
C l t T t l Th id t
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Complete Total ThyroidectomyHistological or gross evidence of cancer during 1st surgeryPalpably abnormal contralateral lobe or XRT HxAt 2nd surgery (within 2 weeks) if cancer later confirmed
NEVER do nodulectomy or partial lobectomy
Primary Thyroid Cancer Surgery
Known Thyroid carcinoma (positive cytology or known metastases)
Total Thyroidectomy = minimum surgery(exception: primary unifocal non-metastatic papillary microcarcinoma)
Node Resection: Ipsilateral and Central Modified Neck Dissection vs
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Node Resection: Ipsilateral and Central Modified Neck Dissection vsModified Central Neck Dissection vs Node Picking
Special cases:Medullary Thyroid carcinoma: Requires TOTAL thyroidectomy and
complete nodal resection
Anaplastic Thyroid cancer: Try for total thyroidectomy; the more resected the greater the chance of longer-term survival.
• Magnitude of Dose: limited only by toxicity– Dosimetry (200 REM red marrow limited)
External Beam Radiotherapy
• Purpose– Local control of tumor: critical sites– “Clean-up” after surgery– Debulk tumor prior to surgical resection– Palliation (bone mets painful sites)
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Palliation (bone mets, painful sites)
• Method– High dose, hyperfractionation– Chemoradiosensitization: unproven, higher morbidity