Download HYPERTHYROIDISM

HYPERTHYROIDISM
Prevalence
Women
2%
Men
0.2%
15% of cases occur in patients
older than 60 years of age
Clinical Symptoms
Depends on
 Age of patient
 Magnitude of hormonal excess
 Presence of co-morbid condition
Mechanism of Clinical Symptoms
1. Catabolism
2. Enhancement of sensitivity to
catecholamines
Clinical Symptoms
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Clinical manifestations of hyperthyroidism
are largely independent of its cause.
However, causing disorder may have other
effects.
Clinical Symptoms
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Older patient presents with lack of clinical signs and
symptoms, which makes diagnosis more difficult
Thyroid storm is a rare presentation, occurs after
stressful illness in under treated or untreated patient.
Characteristics
-Delirium
-Dehydration
-Severe tachycardia
-Vomiting
-Fever
-Diarrhea
Clinical symptoms
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Skin
-Warm
-May be erythematous (due to
increased blood flow)
-Smooth- due to decrease in keratin
-Sweaty and heat intolerance
-Onycholysis –softening of nails and loosening
of nail beds
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Clinical symptoms
Hyperpigmentation
-Due the patient increase ACTH secretion
Pruritis
-mainly in graves disease
Thinning of hair
Vitilago and alopecia areata
-mainly due to autoimmune disease
Infilterative dermopathy
-Graves disease, most common on shins
Clinical symptoms
Eyes
Stare
Lid lag
*Due to sympathetic over activity
*Only Grave’s disease has ophthalmopathy
-Inflammation of extraocular muscles, orbital fat and
connective tissue.
-This results in exopthalmos
-More common in smokers
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Clinical symptoms
Eyes
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Impaired eye muscle function (Diplopia)
Periorbital and conjunctival edema
Gritty feeling or pain in the eyes
Corneal ulceration due to lid lag and proptosis
Optic neuritis and even blindness
Clinical symptoms
Cardiovascular System
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Increased cardiac output (due to increased oxygen
demand and increased cardiac contractibility.
Tachycardia
Widened pulse pressure
High output – heart failure
Clinical symptoms
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Cardiovascular System
Atrial fibrillation, 10-20% of patients. More common
in elderly
Atrial ectopy
60% of A-fib will convert to normal sinus rhythm with
treatment (4-months of becoming euthyroid)
Mitral valve problems
LVH and cardiomyopathy
Serum Lipids
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Low total cholesterol
Low HDL
Low total cholesterol/HDL ratio
Respiratory System
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Dyspnea on rest and with exertion
Oxygen consumpation and CO2 production increases.
Hypoxemia and hypercapnea, which stimulates
ventilation
Respiratory muscle weakness
Decreased exercise capacity
Tracheal obstruction
May exacerbate asthma
Increased pulmonary arterial pressure
Clinical symptoms
GI System
-Weight loss due to increased calorigenesis
-Hyperdefecation
-Malabsorption
-Steatorrhea
-Celiac Disease (in Grave’s Disease)
-Hyperphagia (weight gain in younger patient)
-Anorexia- weight loss in elderly
-Dysphagia
-Abnormal LFT especially phosphate
Clinical symptoms
Hematological System
 Normochromic normocytic anemia
 Serum ferritin may be high
 Grave’s disese
 ITP
 Pernicious anemia
 Anti-neutrophiliac antibody
Clinical symptoms
GU System
 Urinary frequency and nocturia
 Enuresis is common in children
Clinical symptoms
GU System
Women
 Increased SHBG
 High serum estradiol
 Low free estradiol
 High LH
 Reduce mid-cycle LH surge
 Oligomenorrhea and amenorrhea
 Anovulatory infertility
Clinical symptoms
GU System
Men
 High SHBG
 High total testosterone
 Low free testosterone
 High serum LH
 High serum estradiol
 Gynecomastia
 Decreased libido
 Erectile dysfunction
 Decreased or abnormal sperm
Clinical symptoms
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Skeletal System
Bone resorption
Increased porosity of cortical bone
Reduced volume of trabecular bone
Serum alkaline phosphate is increased
Increased osteoblasts
Inhibit PTH secretions
Decreased calcium absorption and increased
excretion
Osteoporosis, Fractures
Clinical symptoms
Skeletal System
Grave’s disease is associated with thyroid acropathy
-Clubbing of nails
-Periosteal bone formation in metacarpal bone or
phalanges
Clinical symptoms
Neuromuscular System
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Tremors-outstretched hand and tongue
Hyperactive tendon reflexes
Clinical symptoms
Psychiatric
 Hyperactivity
 Emotional lability
 Anxiety
 Decreased concentration
 Insomnia
Clinical symptoms
Muscle Weakness
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Proximal muscle weakness in 50% pts.
Decreased muscle mass and strength
May take up to six months after euthyroid state to
gain strength
Hypokelemic periodic paralysis especially in Asian
men (cause is not known)
Myesthenia Gravis, especially in Grave’s disease.
Clinical symptoms
Endocrine
 Increased sensitivity of pancreatic beta cells to
glucose
 Increased insulin secretion
 Antagonism to peripheral action of insulin
 Latter effects usually predominate leading to
intolerance.
Etiology
1 Grave’s disease
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Autoimmune disease caused by antibodies to TSH
receptors
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Can be familial and associated with other
autoimmune diseases
2 Toxic multi-nodular goiter
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5% of all cases
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10 times more common in iodine deficient area
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Typically occurs in older than 40 with long standing
goiter
Etiology
3 Toxic adenoma
 More common in young patients
 Autonomically functioning nodule
Etiology
4 Thyroiditis
Subacute
 Abrupt onset due to leakage of hormones
 Follows viral infection
 Resolves within eight months
 Can re-occur
Lymphatic and postpartum
 Transient inflammation
 Postpartum can occur in 5-10% cases in the first 3-6
months
 Transient hypothyroidism occurs before resolution
Etiology
5 Treatment Induced Hyperthyroidism
Iodine Induced
 Excess iodine indirect
 Exposure to radiographic contrast media
 Medication
Excess iodine increases synthesis and release of thyroid
hormone in iodine deficient and older patients with
pre-existing goiters
Etiology
Amiodarone Induced Thyroiditis
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Up to 12% of patients, especially in iodine deficient
cases
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Most common cause of iodine excess in US.
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Two types:
*Type I - due to excess iodine Amiodarone
contains
37% iodine.
*Type II –– occurs in normal thyroid
Etiology
Thyroid Hormone Induced
 Factitious hyperthyroidism in accidental or intentional
ingestion to lose weight
 Tumors
-Metastatic thyroid cancer
-Ovarian tumor that produces thyriod hormone
(struma ovarii)
-Trophoblastic tumor
-TSH secreting tumor
Signs and symptoms of hyperthyroid
TSH level
Low TSH
High TSH (rare)
Measure T4
High
Secondary
hyperthyroidism
Image pituitary gland
Low TSH
Measure Free T4 Level
Normal
High
Primary hyperthyroidism
Measure Free T3 Level
Normal
-Subclinical
hyperthyroidism
-Resolving
Hyperthyroidism
-Medication
High
T3 Toxicosis
Low
Measure thyroglobulin
decreased
Exogenous
hormone
-New thyroid illness
-Pregnancy
Thyroid uptake
High
DIffuse
Nodular
Increased Graves Multiple
One “hot” area
disease areas
Thyroiditis
Toxic
Iodide exposure Toxic multinodular
adenoma
goiter
Exrtraglandular
production
Etiology
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Hyperthyroidism with high RIU
- Grave’s disease
- Toxic adenoma
- Toxic multinodular goiter
- TSH- producing pituitary adenoma
- Hyperemesis gravidarum
- Trophoblastic disease
Etiology
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Hyperthyroidism with low RIU
- Subacute thyroiditis
- Exogenous harmone intake
- Ectopic ovarii
- Metastatic follicular thyroid CA
- Radiation thyroiditis
- palpation thyroiditis
- Amiodarone induced
Treatment
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Treatment depends upon
-Cause and severity of disease
-Patients age
-Goiter size
-Comorbid condition
-Treatment desired
Treatment
The goal of therapy is to correct hyper-metabaolic state
with fewest side effects and lowest incidence of
hypothyroidism.
Options
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Anti-thyroid drugs
Radioactive iodine
Surgery
Beta-blocker and iodides are adjuncts to above
treatment
Beta Blockers
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Prompt relief of adrenergic symptoms
Propranolol widely used
Any beta blocker can be used, but non-selectives
have more direct effect on hyper-metabolism
Start with 10-20 mg q6h
Increase progressively until symptoms are controlled
Most cases 80-320 mg qd is sufficient
CCB can be used if beta blocker not tolerated or
contraindicated
Iodides
Iodide blocks peripheral conversion of T4 to T3 and
inhibits hormone release. These are used as
adjunct therapy
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Before emergency non-thyroid surgery
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Beta blockers cannot curtail symptoms
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Decrease vascularity before surgery for Grave’s
disease
Iodides
Iodides are not used for routine treatment because of
paradoxical increase of hormone release with
prolonged use
Commonly used:
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Radiograph contrast agents
-Iopanoic acid
-Ipodate sodium
 Potassium iodide
Dose 1 gram/ 12 weeks
Anti-thyroid Drugs
They interfere with organification of iodine—suppress
thyroid hormone levels
Two agents:
-Tapazole (methimazole)
-PTU (propylthiauracil)
Anti-thyroid Drugs
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Remission rate: 60% when therapy continued for two
years
Relapse in 50% of cases.
Relapse more common in
-smokers
-elevated TS antibodies at end of therapy
Anti-thyroid Drugs
Methimazole
Drug of choice for non-pregnant patients because of :
 Low cost
 Long half life
 Lower incidence of side effects
 Can be given in conjunction with beta-blocker
 Beta-blockers can be tapered off after 4-8 weeks of
therapy
Dose 15-30 mg/day
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Anti-thyroid Drugs
Methimazole
Monthly Free T4 or T3 until euthyroid
Maintenance dose 5-10 mg/day
TSH levels may remain undetectable for months after
euthyroid and not to be used to monitor the therapy
Anti-thyroid Drugs
Methimazole
 At one year if patient is clinically and biochemically
euthyroid and TS antibodies are not detectable,
therapy can be discontinued
 Monitor every three months for first year then
annually
 Relapses are more common in the first year but can
occur years later
 If relapse occurs, iodide or surgery although antithyroid drugs can be restarted
Anti-thyroid Drugs
PTU
 Prefered for pregnant patients
 Methimazole is associated with rare genetic
abnormalities
Dose 100 mg t.i.d
Maintenance 100-200 mg/day
Goal: Keep Free T4 at upper level of normal
Anti-thyroid Drugs
Complications
 Agranulocytosis up to 0.5%
 High with PTU
 Can occur suddenly
 Mostly reversible with supportive Tx
 Routine WBC monitoring controversial
 Some people monitor WBC every two weeks for first
month then monthly
 Advised to stop drug if they develop sudden fever or
sore throat
Radioactive Iodine
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Treatment of choice for Grave’s disease and toxic
nodular goiter
Inexpensive
Highly effective
Easy to administer
Safe
Dose depends on estimated weight of gland
Higher dose increases success rate but higher chance
of hypothyroidism
Some studies have shown increase of hypothyroidism
irrespective of dose
Radioactive Iodine
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Higher dose is favored in older patient
Cardiac disease
Other group needs prompt control
Toxic nodular goiter or toxic adenoma
Radioactive Iodine
Side effects
 50% of Grave’s ophthalmology can develop or
worsen by use of radioactive iodine
 Use 40-50 mg Prednisone for at least three months
can prevent or improve severe eye disease in 2/3 of
patients
 Use lower dose in ophthalmology because post Tx
hypothyroidism may be associated with exacerbation
of eye disease
 Smoking makes ophthalmopathy worse.
Radioactive Iodine
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Use of anti-thyroid drugs with iodine is not
recommended in most cases
May improve safety for severe or complicated cases
Withdraw three days before iodine Tx
Beta blockers used to control symptoms before
radioactive iodine and can be combined throughout
Tx
Iodine containing meds need to be stopped several
weeks before therapy
Radioactive Iodine
Safety
 Most radioactive iodine is eliminated in the urine,
saliva and feces in 4-8 weeks.
 Have double flushing of toilet and frequent hand
washing for several weeks
 No close contact with children and pregnant patients
for 48-72 hours
 Additional Tx may be needed after three months if
indicated
Surgery
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Radioactive iodine has replaced surgery for Tx of
hyperthyroidism
Subtotal thyroidectomy is most common
This limits incidence of hypothyroidism to 25%
Total thyroidectomy in large goiter or severe disease
New Treatment
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Endoscopic subtotal thyroidectomy
Embolization of thyroid arteries
Plasmaphoresis
Percutaneous ethanol injection into toxic nodule
L-Carnitine supplementation may improve symptoms
and may prevent bone loss