Transcript Thyroid and Parathyroid Disease: Diagnosis and Management

Thyroid Disease:
Diagnosis and Management
Internal Medicine Resident Lecture
Series
Michael Pascolini D.O.
8/18/2004
Goal
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The residents will understand how to
diagnose and manage thyroid disease
Objectives
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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
Question #1
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In X-linked TBG deficiency, the TSH
level is:
– A. increased
– B. decreased
– C. normal
Thyroid Axis
Hypothalamus
TRH
Pituitary
TSH
Thyroid
T3 and T4
Dopamine
Glucocorticoids
Somatostatin
Thyroid Axis
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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)
Iodine
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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)
Thyroid hormones
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T4 is secreted 20x in excess of T3 from thyroid gland
– both are bound to plasma proteins thyroxinebinding thyroglobulin(TBG), transthyretin (TTR)
and Albumin (99.98% T4 and 99.7% T3)
– Free T3 > Free T4 (only free hormone is available
to tissues)
Thyroid hormones
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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
Question #1

In X-linked TBG deficiency, the TSH
level is:
– A. increased
– B. decreased
– C. normal
Question #1

In X-linked TBG deficiency, the TSH
level is:
– A. increased
– B. decreased
– C. normal
Question #2
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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)
Physical Exam
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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)
Physical Exam
Physical Exam
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If low boarders are not clearly felt, pt may have
retrosternal goiter
– Venous distention, difficulty breathing, especially when arms
are raised (Pemberton’s sign)
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Central Masses - have pt stick out tongue,
thyroglossal cysts will move upward
Asses lymphadenopathy in supraclavicular and
cervical regions
Lab Eval
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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
Lab Eval
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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)
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TSH should not be used to assess a patient with known
pituitary disease.
Hypothyroidism - signs and
symptoms (decreasing order of frequency)
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Signs
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Dry coarse skin
Puffy face, hands and feet
Diffuse alopecia
Bradycardia
Peripheral edema
Delayed tendon reflex
relaxation
– Carpal tunnel syndrome
– Serous cavity effusion
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Symptoms
– Tiredness, weakness
– Feeling cold
– Difficulty concentrating and
poor memory
– Constipation
– Weight gain with poor
apatite
– Dyspnea
– Hoarse voice
– Menorrhagia
– Parasthesias
– Impaired hearing
Hypothyroidism
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increased TSH and a decreased free T4
Congenital
Autoimmune
Iatrogenic
Hypothyroidism
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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
Hypothyroidism
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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
Hypothyroidism
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Iatrogenic
– may be caused by radioiodide treatment (in
the 1st 3-4 months after treatment)
Hypothyroidism
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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
Thyrotoxicosis - signs and
symptoms (decreasing order of frequency)
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Signs
– Tachycardia; A-fib in the
elderly
– Tremor
– Goiter
– Warm, moist skin
– Muscle weakness, proximal
myopathy
– Lid retraction or lag
– Gynecomastia
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Symptoms
– Hyperactivity, irritability,
dysphoria
– Heat intolerance and
sweating
– Palpitations
– Fatigue and weakness
– Weight loss with increased
apatite
– Diarrhea
– Polyuria
– Oligomenorrhea
Thyrotoxicosis
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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
Thyrotoxicosis
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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%
Thyrotoxicosis
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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
Thyrotoxicosis
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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)
Thyrotoxicosis
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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
Thyrotoxicosis
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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
Sick Euthyroid Syndrome
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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
Amiodarone effects on Thyroid
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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
Question #2
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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)
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)
Question #3
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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
Benign lesions
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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
Malignant tumors
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Primary epithelial tumors, they account for 1.5% of all
cancer in the US
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Papillary
Follicular (well-differentiated thyroid carcinomas)
Medullary thyroid carcinoma
Anaplastic carcinoma
Papillary Adenocarcinomas
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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
Follicular Carcinomas
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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%
Medullary Thyroid Carcinoma
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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
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5- and 10-year survival rates range from 88% and
78%, respectively
– cervical lymph node mets affects 10 year rate down to 46%
Anaplastic Carcinoma
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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
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Effective treatment is rarely feasible.
Thyroid Ultrasound
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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
Thyroid scanning
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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
Thyroid scanning
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– 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.
Thyroid scanning
Fine Needle Aspiration
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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
Indications for Operation
Scan
Needle Bx
Cystic
Solid
Neg
Pos. or ?
Rapid recurrence
Surgery
Surgery
growth or
failure to
suppress
Surgery
Suppression cont.
disappearance
Treatment
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Thyroidectomy
– hemithyroidectomy - half of the thyroid is removed,
parathyroids preserved
– total thyroidectomy - entire thyroid is removed, parathyroids
preserved
Complications of Surgery
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complication rate is low
reported complications with surgery
– transient hypocalcemia (7.1%)
– permanent hypocalcemia (0.4%)
– Vocal cord paralysis (1.2%)
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
Further management
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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
Question #3
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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
Question #3
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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