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Thyroid Disease:Diagnosis and Management
Internal Medicine Resident Lecture Series
Michael Pascolini D.O.
8/18/2004
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Goal
The residents will understand how to diagnose and manage thyroid disease
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Objectives
The residents will: – understand the basic hormonal actions of
the thyroid gland– evaluate and diagnose a patient with
thyroid disease using clinical skills and lab work
– understand the four different types of Malignant thyroid tumors
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Question #1
In X-linked TBG deficiency, the TSH level is:– A. increased– B. decreased– C. normal
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Thyroid Axis
Hypothalamus
Pituitary
Thyroid
DopamineGlucocorticoidsSomatostatin
TRH
TSH
T3 and T4
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Thyroid Axis
Thyroid hormones (T3 and T4) are the dominant regulator of TSH & TRH production
TSH production– pulsatile; diurnal (highest levels at night)– long plasma 1/2 life (50 min)
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Iodine
Iodine transport is a critical first step in thyroid hormone synthesis
Normal thyroid extracts 10-25% radioactive iodine trace over 24 hrs.– Thyroid of Graves disease can extract 70-90%
Areas of iodine deficiency have increased incidence of Goiter
Oversupply of iodine is associated with increased incidence of autoimmune thyroid disease
Decreased iodine increases thyroid bloodflow Excess iodine inhibits thyroid iodide organification (Wolff-
Chaikoff effect)
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Thyroid hormones
T4 is secreted 20x in excess of T3 from thyroid gland– both are bound to plasma proteins thyroxine-
binding thyroglobulin(TBG), transthyretin (TTR) and Albumin (99.98% T4 and 99.7% T3)
– Free T3 > Free T4 (only free hormone is available to tissues)
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Thyroid hormones
Homeostatic mechanisms maintain normal concentration of free hormones
– X-linked TBG deficiency - There are low levels of total T3 & T4, however free hormone levels are normal.
• patients are euthyroid, TSH levels are normal
– TBG are increased by estrogen (pregnancy, estrogen birth control pills) TBG, total T3 & T4 are increased. Free T3 and T4 are normal.
– Do not try to normalize the total hormone levels
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Question #1
In X-linked TBG deficiency, the TSH level is:– A. increased– B. decreased– C. normal
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Question #1
In X-linked TBG deficiency, the TSH level is:– A. increased– B. decreased– C. normal
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Question #2
Which of the following can cause a decreased TSH level?– A. severe non thyroid illness– B. medications (increased levels of
dopamine and glucocorticoids) – C. TSH secreting pituitary tumor– D. Thyroid hormone resistance (increased
free T4 & T3 with normal TSH)
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Physical Exam
Extrathyroid features: Opthalmopathy and Dermopathy
Inspect pt from front and side Palpate thyroid from behind pt
– note tenderness, fixation, nodularity, masses Bruit over gland suggests increased vascularity
(hyperthyroidism)
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Physical Exam
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Physical Exam
If low boarders are not clearly felt, pt may have retrosternal goiter– Venous distention, difficulty breathing, especially when arms
are raised (Pemberton’s sign)
Central Masses - have pt stick out tongue, thyroglossal cysts will move upward
Asses lymphadenopathy in supraclavicular and cervical regions
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Lab Eval
First determine TSH level– normal TSH level excludes primary abnormalities
of thyroid function, with rare exceptions– Abnormal TSH, next get a free T4 and T3 resin
uptake tests• Resin uptake test - compares amount of T3
bound to Resin as opposed to unoccupied thyroid hormone binding proteins
– uptake increased when proteins are low or Thyroid hormone levels are increased
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Lab Eval
TSH as screening test may be misleading (especially without Free T4)– Increased TSH level
• severe non thyroid illness• TSH secreting pituitary tumor• Thyroid hormone resistance (increased free T4 & T3 with normal TSH)• Artifact
– Decreased TSH level• 1st trimester of pregnancy (2o hCG secretion)• Treatment of hyperthyroidism (suppression lasts several weeks)• medications (increased levels of dopamine and glucocorticoids)
TSH should not be used to assess a patient with known pituitary disease.
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Hypothyroidism - signs and symptoms (decreasing order of frequency)
Signs– Dry coarse skin
– Puffy face, hands and feet
– Diffuse alopecia
– Bradycardia
– Peripheral edema
– Delayed tendon reflex relaxation
– Carpal tunnel syndrome
– Serous cavity effusion
Symptoms– Tiredness, weakness– Feeling cold– Difficulty concentrating and
poor memory– Constipation– Weight gain with poor
apatite– Dyspnea– Hoarse voice– Menorrhagia– Parasthesias– Impaired hearing
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Hypothyroidism
increased TSH and a decreased free T4 Congenital Autoimmune Iatrogenic
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Hypothyroidism Congenital
– 1 in 3000-4000 newborns– <10% are diagnosed with clinical features
• prolonged jaundice, feeding problems, hypotonia, enlarged tongue, delayed bone maturation.
– permanent neurological damage could occur if treatment is delayed
– Treatment is levothyroxine at 10-15 mcg/kg/day, monitoring effects by TSH levels
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Hypothyroidism
Autoimmune– may be associated with goiter
(Hashimoto’s) or minimal residual thyroid tissue (atrophic thyroiditis), later in the disease.
– patients present with typical signs and symptoms
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Hypothyroidism
Iatrogenic– may be caused by radioiodide treatment (in
the 1st 3-4 months after treatment)
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Hypothyroidism
Treatment– Start daily replacement dose of
levothyroxine at 1.5 mcg/kg of body weight– adjust the dose based on TSH levels– once replacement is achieved, annual TSH
are recommended to follow
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Thyrotoxicosis - signs and symptoms (decreasing order of frequency)
Signs– Tachycardia; A-fib in the
elderly
– Tremor
– Goiter
– Warm, moist skin
– Muscle weakness, proximal myopathy
– Lid retraction or lag
– Gynecomastia
Symptoms– Hyperactivity, irritability,
dysphoria
– Heat intolerance and sweating
– Palpitations
– Fatigue and weakness
– Weight loss with increased apatite
– Diarrhea
– Polyuria
– Oligomenorrhea
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Thyrotoxicosis
Thyrotoxicosis - the state of thyroid hormone excess Hyperthyroidism - result of excessive thyroid function Labs: Decreased TSH and increased free T3 & T4 Etiologies
– Graves’ disease– Thyroiditis– Toxic Adenoma
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Thyrotoxicosis
Graves’ disease– 60-80% of thyrotoxicosis, depending on iodine
intake (increased intake= increased prevalence)– Diagnosis can be excluded if TSH is normal– clinical features worsen without treatment;
mortality 10-30%
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Thyrotoxicosis
Graves’ disease– Treatment goal is to reduce thyroid hormone
synthesis using antithyroid drugs• Thionamides
– Propylthiouracil 100-200mg q 6-8 hours– Carbimazole 10-20 mg BID or TID– Methimazole 10-20 mg BID or TID
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Thyrotoxicosis Thyroiditis
– Acute• pt presents in thyroid pain• infection of thyroid, rare, usually secondary to presence
of piriform sinus• Treatment guided by Gram stain and culture of FNA
biopsy
– Subacute (deQuervain’s thyroiditis)• many viruses implicated as cause; peak incidence 30-50
yrs F>M• Treat with relatively large doses of Aspirin or other
NSAIDs.(600mg q4-6 hrs)
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Thyrotoxicosis
Thyroiditis– Silent (painless thyroiditis)
• usually pts have underlying autoimmune thyroid disease
• clinical course same as subacute thyroiditis without the pain
• glucocorticoids are not indicated• Propranolol may be used to treat sever
thyrotoxicosis
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Thyrotoxicosis
Toxic adenoma• autonomously functioning thyroid nodule
– hypersecretion of T4 and T3; leads to thyrotoxicosis
• etiology related to iodine deficiency• Always greater than 3cm in diameter• Labs: decreased TSH and marked elevation of T3 levels,
borderline elevation of T4• Almost never malignant• May treat with antithyroid drugs but if size continues to
increase, then surgery or I-131 therapy
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Sick Euthyroid Syndrome
Any acute, severe illness can cause abnormalities in TSH of thyroid hormone levels in the absence of underlying disease. These measurements can be misleading
Common pattern: Decreased Total and Free T3 with normal levels of T4 and TSH
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Amiodarone effects on Thyroid
Amiodarone is structurally related to thyroid hormone and contains 39% iodine by weight
increased iodine levels for >6 months after discontinuation of drug
Multiple effects on thyroid function:– acute, transient changes in thyroid function– hypothyroidism in susceptible patients with
increased iodine– thyrotoxicosis, possibly by induction of
autoimmune Graves’ disease
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Question #2
Which of the following can cause a decreased TSH level?– A. severe non thyroid illness– B. medications (increased levels of
dopamine and glucocorticoids) – C. TSH secreting pituitary tumor– D. Thyroid hormone resistance (increased
free T4 & T3 with normal TSH)
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Question #2
Which of the following can cause a decreased TSH level?– A. severe non thyroid illness– B. medications (increased levels of
dopamine and glucocorticoids) – C. TSH secreting pituitary tumor– D. Thyroid hormone resistance (increased
free T4 & T3 with normal TSH)
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Question #3
Which of the following malignant tumors has the poorest prognosis?– A. Anaplastic carcinoma– B. Follicular (well-differentiated thyroid
carcinomas)– C. Papillary – D. Medullary thyroid carcinoma
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Benign lesions
Can be categorized into:– nontoxic - diffuse and multinodular goiter– toxic - toxic multinodular goiter, solitary toxic
adenoma, and diffuse toxic goiter (Graves’ disease)– inflammatory - Thyroiditis: acute, subacute and
chronic Benign thyroid diseases are significant to the surgeon
because: – mechanical constraint on the upper aerodigestive structures– it’s not possible to rule out carcinoma within a nodular lesion
of the thyroid gland
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Malignant tumors
Primary epithelial tumors, they account for 1.5% of all cancer in the US– Papillary– Follicular (well-differentiated thyroid carcinomas)– Medullary thyroid carcinoma– Anaplastic carcinoma
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Papillary Adenocarcinomas
80% of all thyroid carcinomas incidence in the 3rd and 4th decade both lobes involved in 80% of the cases; often
multicentric tumor spreads by regional lymphatics to paratracheal
or lateral cervical lymph nodes locoregional metastasis is high from 37-65% 5-year survival rates range from 70-95% with
mortality of 10-20% over 10-20 year period– significant mortality occurs from intrathyroidal lesions > 5cm
in diameter or extracapsular spread
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Follicular Carcinomas
10% of all thyroid cancers more prevalent in areas of endemic goiter occurs exclusively in patients older than 40 years Multicentricity is uncommon as is lymph node
metastasis tumor spreads by angioinvasion; distant mets to
lungs or bone in 65%of patients 5-year survival rate is about 70%, decreasing to 40%
at 10 years.– if distant mets present, 5-year survival is 20%
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Medullary Thyroid Carcinoma
5-7% of thyroid carcinomas originate from parafollicular cells (neural crest cells) calcified areas in the thyroid is a radiological feature
of this tumor 60-80% are sporadic cases;10-40% are familial. sporadic case is unilateral; familial cases are bilateral Familial cases occur in the MEN syndrome type II
– better prognosis than the sporadic cases 5- and 10-year survival rates range from 88% and
78%, respectively– cervical lymph node mets affects 10 year rate down to 46%
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Anaplastic Carcinoma
one of the most lethal carcinomas; 1-5% of thyroid malignancies
mainly affects patients older than 65 years. only small-cell type responds to radiation therapy Approximately 10% of patients will survive 1 year.
– Average duration of survival after diagnosis is 3-6 months
Effective treatment is rarely feasible.
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Thyroid Ultrasound
Can differentiate cystic from solid thyroid nodules in >80% cases
used increasingly in the diagnosis of thyroid disease 10MHz instruments with detection of nodules >3mm Can also be used to monitor nodular sizes, guide
FNA biopsies and aspiration of cystic lesions
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Thyroid scanning
Radioisotopes of iodine can be used to trace the fractional uptake into the gland– Graves’ disease - shows and enlarged thyroid with
homogenous tracer uptake– Toxic Adenoma - shows areas of increased uptake
with suppressed tracer uptake in remainder of gland
– Toxic Multinodular goiter - Enlarged gland with multiple areas of increased and decreased uptake
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Thyroid scanning
– Subacute thyroiditis - very low uptake due to cell damage
– Thyrotoxicosis factitia (self-administration of thyroid hormone) - low uptake
Cold nodules are usually benign, but have 5-10% chance of being malignant
Hot nodules are almost never malignant Scans are also used to follow up on thyroid cancer.
Uptake in the thyroid bed after surgery may show metastatic thyroid cancer deposits.
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Thyroid scanning
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Fine Needle Aspiration
most accurate preop diagnostic modality for evaluation of thyroid nodules
Has decreased the need for thyroid surgeries by 50% and increased yield of thyroid malignancies by 50%
reports classified as benign, indeterminate or malignant– fewer than 5% false-positives on malignancies
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Indications for Operation
Scan
Needle Bx
Solid Cystic
Pos. or ? Neg Rapid recurrence disappearance
growth or failure to suppress
Suppression cont.
Surgery Surgery
Surgery
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Treatment
Thyroidectomy– hemithyroidectomy - half of the thyroid is removed,
parathyroids preserved– total thyroidectomy - entire thyroid is removed, parathyroids
preserved
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Complications of Surgery
complication rate is low reported complications with surgery
– transient hypocalcemia (7.1%)– permanent hypocalcemia (0.4%)– Vocal cord paralysis (1.2%)
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Further management
131I thyroid ablation and treatment should be coordinated with the surgical approach– ablation is much more effective when there is less
normal thyroid tissue in the thyroid bed.– Patient is kept on thyroid treatment for a few
weeks post op, then withdrawn.– TSH rise correlates to the amount of normal tissue
left.– The residual tissue is then ablated with 131I
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Further management
An initial whole-body scan should be performed about 6 months after surgery and thyroid ablation for more residual tissue. – if positive another larger ablative dose is given– if negative and thyroglobulin (Tg) levels are low, a repeat
scan should be done 1 year later– if negative again, then patient can be managed with
suppressive therapy and Tg levels every 6 to 12 months
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Question #3
Which of the following malignant tumors has the poorest prognosis?– A. Anaplastic carcinoma– B. Follicular (well-differentiated thyroid
carcinomas)– C. Papillary – D. Medullary thyroid carcinoma
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Question #3
Which of the following malignant tumors has the poorest prognosis?– A. Anaplastic carcinoma– B. Follicular (well-differentiated thyroid
carcinomas)– C. Papillary – D. Medullary thyroid carcinoma