Thyroid Disease:Diagnosis and Management

Internal Medicine Resident Lecture Series

Michael Pascolini D.O.

8/18/2004

Goal

The residents will understand how to diagnose and manage thyroid disease

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

Question #1

In X-linked TBG deficiency, the TSH level is:– A. increased– B. decreased– C. normal

Thyroid Axis

Hypothalamus

Pituitary

Thyroid

DopamineGlucocorticoidsSomatostatin

TRH

TSH

T3 and T4

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)

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)

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)

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

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

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

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

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

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

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.

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

Hypothyroidism

increased TSH and a decreased free T4 Congenital Autoimmune Iatrogenic

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

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

Hypothyroidism

Iatrogenic– may be caused by radioiodide treatment (in

the 1st 3-4 months after treatment)

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

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

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

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%

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

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)

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

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

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

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

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 #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

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

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

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

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

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%

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%

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.

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

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

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.

Thyroid scanning

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

Indications for Operation

Scan

Needle Bx

Solid Cystic

Pos. or ? Neg Rapid recurrence disappearance

growth or failure to suppress

Suppression cont.

Surgery Surgery

Surgery

Treatment

Thyroidectomy– hemithyroidectomy - half of the thyroid is removed,

parathyroids preserved– total thyroidectomy - entire thyroid is removed, parathyroids

preserved

Complications of Surgery

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

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

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

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