HYPERTHYROIDISM

Dharma Lindarto
Div. Endokrin-Metabolisme dan Diabetes. Dep Ilmu
Penyakit Dalam FK USU / RSUP HAM Medan

Anatomy of the Thyroid Gland

Tiroid Disease

Aspect
function
eutiroid,
hypotiroid

morphology

hypertiroid,
normal, atrophic, nodule,
diffus

HypothalamusPituitary- Thyroid Axis

Typical Thyroid Hormone Levels

in Thyroid Disease

Hypothyroidism
Hyperthyroidism
Subclinical Hypothyroidsm
Subclinical Hyperthyroidsm

TSH

T4

T3

High
Low
High
Low

Low
High
normal
normal

Low
High
normal
normal

Thyrotoxicosis and Hyperthyroidism

Definitions
Thyrotoxicosis
The clinical syndrome of hypermetabolism that
results when the serum concentrations of free
T4, T3, or both are increased

Hyperthyroidism
Sustained increases in thyroid hormone
biosynthesis and secretion by the thyroid gland

The 2 terms are not synonymous

Braverman LE, et al. Werner & Ingbars The Thyroid. A
Fundamental and Clinical Text. 8th ed. 2000.

 Thyroid Storm Rare complication of

hyperthyroidism where manifestations of
thyrotoxicosis become life threatening. Also may be
termed Thyrotoxic Crisis.
Apathetic Thyrotoxicosis Rare form usually
occurring in the elderly. Often presents as single
organ failure (CHF). Patient may develop thyroid
storm without the typical manifestations.

Prevalence of Thyrotoxicosis
In a cross-sectional study of urban and
rural adults, the prevalence of
thyrotoxicosis ranged from
1.9% to 2.7% in women
0.16% to 0.23% in men

Tunbridge WMG, et al. Clin Endocrinol. 1977;7:481-493.

Hyperthyroidism Etiology

Graves disease
Multinodular goiter
Autonomous nodule
Exogenous thyroid hormone
Transientsubacute thyroiditis,
postpartum thyroiditis
Drugsamiodarone

Causes of Thyrotoxicosis
Divided by Degree of Radioiodine Uptake
High I123 Uptake
Graves disease
I
Toxic nodular goiter
TSH-mediated thyrotoxicosis
Pituitary tumor
Pituitary resistance to
thyroid hormone
HCG-mediated thyrotoxicosis
Hydatidiform mole
Choriocarcinoma
Other HCG-secreting tumors
Thyroid carcinoma (very rare)
123

Low I123 Uptake

Subacute thyroiditis
Hashitoxicosis
Drug-induced
Iodide
Thyroid hormone
Struma ovarii
Factitious

I123

Common Signs and Symptoms

of Thyrotoxicosis
Symptoms

Signs

Nervousness
Fatigue
Weakness
Increased perspiration
Heat intolerance
Tremor
Hyperactivity
Palpitations
Appetite/weight changes
Menstrual disturbances

Hyperactivity
Tachycardia
Systolic hypertension
Warm, moist, or smooth skin
Stare and eyelid retraction
Tremor
Hyperreflexia
Muscle weakness

Braverman LE, et al. Werner & Ingbars The Thyroid. A

Fundamental and Clinical Text. 8th ed. 2000.

SYSTEMIC EFFECTS
RESPIRATORY
Dyspnea, panting, hyperventalation
respiratory muscle weakness
increased tissue carbon dioxide levels
+/- congestive heart failure

SYSTEMIC EFFECTS
CARDIOVASCULAR
Thyrotoxic cardiomyopathy
Hypermetabolic state
Systemic hypertension
Direct T3 and T4 action on heart
muscle
LV hypertrophy, IVS hypertrophy, RA
and aortic dilation, enhanced
contractility

1. Graves Disease (Toxic Diffuse Goiter)

The most common cause of hyperthyroidism

Accounts for 60% to 90% of cases
Incidence in the United States estimated at 0.02% to
0.4% of the population
Affects more females than males, especially in the
reproductive age range

Graves disease is an autoimmune disorder

possibly related to a defect in immune tolerance

Graves Disease
Autoimmune disorder
Production of TSH receptor autoantibodies
Stimulate thyroid hormone overproduction

Characterized by the presence of B- and Tlymphocytes in thyroid tissue

TSH receptor activation
Thyroglobulin and thyroid peroxidase antibodies
Sodium/iodide cotransporter (NIS) activity enhanced
(increased RAI)
Autoantigens
Abbott Laboratories Diagnostics Division Web site. Available at: et al. Werner & Ingbars The
Thyroid.
A Fundamental and Clinical Text. 8th ed. 2000.

Graves' Disease
Goiter
Hyperthyroidism
Exophthalmos
Localized myxedema
Thyroid acropachy
Thyroid stimulating immunoglobulins

Clinical Characteristics of Goiter

in Graves Disease
Diffuse increase in thyroid gland size
Soft to slightly firm
Non-nodular
Bruit and/or thrill
Mobile
Non-tender
Without prominent adenopathy

Graves Disease - Localized Myxedema

Margins sharply
demarcated
Nodularity

Thickened skin
Margins sharply
demarcated

Graves Ophthalmopathy

Class one: spasm of upper

lids with thyrotoxicosis
Class two: periorbital edema
and chemosis
Class three: proptosis
Class four: extraocular
muscle involvement
Class five: corneal
involvement
Class six: loss of vision due
to optic nerve involvement

DIAGNOSTICS
Endocrine Testing
Total T4: 5-10% will be normal
Total T3: 30% will be normal
Free T4: false negative with NTI and
shipping
fT4d better
T3 supression
TRH stimulation and TSH response

DIAGNOSTICS
RADIONUCLIDE IMAGING
Pertechnetate imaging

extent of involvement
detect metastasis to other gland
no palpable enlargement (within thorax)
Carcinoma metastasis

2. Toxic Multinodular Goiter

More common in places with lower iodine
intake
Accounts for less than 5% of thyrotoxicosis cases in
iodine-sufficient areas

Evolution from sporadic diffuse goiter to toxic

multinodular goiter is gradual
Thyrotropin receptor mutations and TSH
mutations have been found in some patients
with toxic multinodular goiters
Surgery or 131I is recommended treatment
Braverman LE, et al. Werner & Ingbars The Thyroid. A
Fundamental and Clinical Text. 8th ed. 2000.

Toxic Multinodular Goiter

MNG is an enlarged thyroid gland containing multiple
nodules
The thyroid gland becomes more nodular with increasing
age
In MNG, nodules typically vary in size
Most MNGs are asymptomatic

MNG may be toxic or nontoxic

Toxic MNG occurs when multiple sites of autonomous
nodule hyperfunction develop, resulting in thyrotoxicosis
Toxic MNG is more common in the elderly

3. Toxic Adenoma
Autonomously functioning thyroid
nodule hypersecreting T3 and T4
resulting in thyrotoxicosis (Plummers
disease)
Almost never malignant
Manage with antithyroid drugs followed
by either I-131 or surgery

Laboratory Testing in Thyroid

Disease
TSH:
Pituitary hormone which stimulates thyroid
May rise transiently in recovery from other illness

Free T4:
direct measure of thyroxine activity
May be transiently suppressed in severe acute illness
Free T3: suspect hyperthyroid but normal FT4

Thyroid peroxidase/thyroperoxidase antibody:

Anti-TPO
High levels in Hashimotos (95%) & Graves
TSH receptor stimulating Ab measures activity in Gravesuse in pregnancy

Scans/Ultrasound

Radioiodine uptake (RAIU)

Thyroid Scan
Ultrasound
Fine needle Aspiration

Treatment of Hyperthyroidism
1. Antithyroid drugs
2. Surgical resection
3. Radioactive iodine therapy

Braverman LE, et al. Werner & Ingbars The Thyroid. A

Fundamental and Clinical Text. 8th ed. 2000.

1. Antithyroid Drug Therapy

Acute hyperthyroid symptoms
Goal of therapy:
Inhibit peripheral conversion of T4 to T3
Inhibit synthesis and release of T4 and T3
from thyroid gland

Propylthiouracil (PTU)
Methimazole [generic] or Tapazole

Antithyroid Drug Therapy

A. PTU:
Inhibits peripheral conversion of T4 to T3
Inhibits thyroid hormone synthesis and
release from thyroid gland

B. Methimazole [generic]:
Inhibits thyroid hormone synthesis and
release from thyroid gland

 C. Beta-blocker therapy:
Ameliorates tachycardia, sweating, tremor,
nervousness
Propanolol: starting dose 20-40 mg PO
q6h
Caution in patients with CHF or
bronchospasm

2. Subtotal Thyroidectomy
Surgical complications:
Vocal cord paralysis (1%)
Hypothyroidism (up to 43% after 10 years)
Hypoparathyroidism
Recurrence of hyperthyroidism (10-15%)

3. Radioactive Iodine 131[I]

Ablation
Treatment of choice in patients > 21
years old with Graves Disease
Treatment of choice in patients < 21
years old without remission after
antithyroid drug therapy
Treatment of choice in patients with toxic
multinodular goiter or toxic thyroid
adenoma

Radioactive Iodine Ablation (cont)

Single dose of 131[I] orally
80% euthyroid after single dose
> 50% of patients will develop
hypothyroidism
Assay TSH every 3 months after therapy

Radioactive Iodine Ablation (Cont)

Levothyroxine therapy when patient
becomes hypothyroid
Life-long Levothyroxine therapy
RIA contraindicated in pregnancy,
lactation, iodine allergy
Screen pre-menopausal women for
pregnancy prior to treatment

Thyroid Storm
A life-threatening crisis .
Estimated mortality : 20-30% .
the result of thyroid surgery .
Caused more often by antecedent
Graves disease .

Precipitants of Thyroid Storm

Surgery .
Radioiodine therapy .
Iodinated contrast dyes .
Thyroid hormone ingestion .
Diabetic Ketoacidosis .
Cerebrovascular accident .
Pulmonary embolism and CHF .

Pathophysiology of Thyroid
Storm
1) An acute decrease in thyroxinebinding globulin => high levels of free
hormone .
2) Thyroid hormone increases the
density of beta-adrenergic receptors &
alters responsiveness to
catecholamines at a postreceptor level .

Laboratory Diagnosis of
Thyroid Storm
A combination of low TSH and elevated
free T4 => makes the diagnosis .
If TSH is lower than normal and free T4
is normal => free T3 testing is
recommended .
ED measurement of thyroglobulin or
thyroid antibodies : No indication .

Treatment of Thyroid Storm

Block hormone synthesis with either :
a) Propylthiouracil 100-600 mg loading
PO or NG , 200-250 mg q4h for total
daily dose of 1200-1500 mg ; or
b) methimazole 20 mg PO ( 10-40 mg
range ) q 4h .

Treatment of Thyroid Storm

( continued )
Inhibit hormone release :
Iodides Potassium iodide ( SSKI ) 5 drops PO
Q6-8H , or
Lugols solution 7-8 drops ( 1 mL PO Q6H ) or
Ipodate 1-3 g daily ( as 1 g Q8H for 24 hours ,
then 500 mg Q12H ) .
If severe iodide allergy , lithium carbonate 300
mg Q6H .

Treatment of Thyroid Storm

( continued )
Glucocorticoids : Hydrocortisone ( 300
mg IV , then 100 mg IV q8h ) ;
dexamethasone ( 2 mg Q6H ) .
Adrenergic blockade : Propranolol ( 0.53 mg IV over 15 minutes slow IV , then
60-80 mg PO Q4H ) ; Esmolol ( 0.25-0.5
mcg/kg loading , infusion of 0.05-0.1
mcg/kg/min ) .

Adjunctive Therapy for

Thyroid Storm
Treat fever aggressively with
acetaminophen .
IV fluid containing 10% dextrose are
recommended .
Administer vitamin supplements ,
including thiamine .
Treat CHF with conventional methods .

Adjunctive Therapy for

Thyroid Storm ( continued )
Identify the precipitating event ,
including infection .
Consider plasmapheresis ,
hemodialysis or peritoneal dialysis for
removal of metabolically active
hormone .

Thyrotoxic Periodic Paralysis

Most common cause of hypokalemic
periodic paralysis
Flaccid paralysis
Lower extremities affected most often
Ocular and bulbar muscles uninvolved,
respiratory muscles rarely involved
Most often starts during sleep
Precipitated following exercise, high
salt intake or high carbohydrate diet
Hypokalemia during the paralysis

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