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

Clinical manifestations of hyperthyroidism
are largely independent of its cause.
However, causing disorder may have other
effects.

Clinical Symptoms
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
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

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 Graves disease has ophthalmopathy
-Inflammation of extraocular muscles, orbital fat and
connective tissue.
-This results in exopthalmos
-More common in smokers

Clinical symptoms


Eyes
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

Increased cardiac output (due to increased oxygen
demand and increased cardiac contractibility.
Tachycardia
Widened pulse pressure
High output heart failure
Clinical symptoms

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
Low total cholesterol
Low HDL
Low total cholesterol/HDL ratio
Respiratory System
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 Graves 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
Graves 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

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
Graves disease is associated with thyroid acropathy
-Clubbing of nails
-Periosteal bone formation in metacarpal bone or
phalanges


Clinical symptoms

Neuromuscular System

Tremors-outstretched hand and tongue
Hyperactive tendon reflexes


Clinical symptoms

Psychiatric
Hyperactivity
Emotional lability
Anxiety
Decreased concentration
Insomnia


Clinical symptoms

Muscle Weakness

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 Graves 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 Graves disease
Autoimmune disease caused by antibodies to TSH
receptors
Can be familial and associated with other
autoimmune diseases
2 Toxic multi-nodular goiter
5% of all cases
10 times more common in iodine deficient area
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
Up to 12% of patients, especially in iodine deficient
cases
Most common cause of iodine excess in US.
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
Measure Free T3 Level
Normal
High
-Subclinical
hyperthyroidism
-Resolving
Hyperthyroidism
-Medication
-Pregnancy
-New thyroid illness
T3 Toxicosis
Primary hyperthyroidism
Thyroid uptake
Low High
Measure thyroglobulin
decreased
Increased
Exogenous
Thyroiditis
Iodide exposure
Exrtraglandular
production
DIffuse Nodular
hormone
Graves
disease
Multiple
areas
One hot area
Toxic multinodular
goiter
Toxic
adenoma
Etiology
Hyperthyroidism with high RIU
- Graves disease
- Toxic adenoma
- Toxic multinodular goiter
- TSH- producing pituitary adenoma
- Hyperemesis gravidarum
- Trophoblastic disease
Etiology
Hyperthyroidism with low RIU
- Subacute thyroiditis
- Exogenous harmone intake
- Ectopic ovarii
- Metastatic follicular thyroid CA
- Radiation thyroiditis
- palpation thyroiditis
- Amiodarone induced
Treatment
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
Anti-thyroid drugs
Radioactive iodine
Surgery
Beta-blocker and iodides are adjuncts to above
treatment
Beta Blockers
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
Before emergency non-thyroid surgery
Beta blockers cannot curtail symptoms
Decrease vascularity before surgery for Graves
disease
Iodides
Iodides are not used for routine treatment because of
paradoxical increase of hormone release with
prolonged use
Commonly used:
Radiograph contrast agents
-Iopanoic acid
-Ipodate sodium
Potassium iodide
Dose 1 gram/ 12 weeks
Anti-thyroid Drugs
They interfere with organification of iodinesuppress
thyroid hormone levels

Two agents:
-Tapazole (methimazole)
-PTU (propylthiauracil)


Anti-thyroid Drugs

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


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 anti-
thyroid 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
Treatment of choice for Graves 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
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 Graves 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
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
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
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