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        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
       Clinical Symptoms

   Clinical manifestations of hyperthyroidism
    are largely independent of its cause.
   However, causing disorder may have other
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.
       -Delirium                     -Dehydration
       -Severe tachycardia           -Vomiting
Clinical symptoms

   Skin
           -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
    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
     Clinical symptoms

   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
   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
  -Celiac Disease (in Grave’s Disease)
  -Hyperphagia (weight gain in younger patient)
  -Anorexia- weight loss in elderly
  -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
 Increased SHBG

 High serum estradiol

 Low free estradiol

 High LH

 Reduce mid-cycle LH surge

 Oligomenorrhea and amenorrhea

 Anovulatory infertility
Clinical symptoms

GU System
 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
   Osteoporosis, Fractures
Clinical symptoms

Skeletal System
Grave’s disease is associated with thyroid acropathy
  -Clubbing of nails
  -Periosteal bone formation in metacarpal bone or
Clinical symptoms

Neuromuscular System

   Tremors-outstretched hand and tongue
   Hyperactive tendon reflexes
Clinical symptoms

 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 Grave’s disease.
Clinical symptoms

 Increased sensitivity of pancreatic beta cells to

 Increased insulin secretion

 Antagonism to peripheral action of insulin

 Latter effects usually predominate leading to

1 Grave’s disease
   Autoimmune disease caused by antibodies to TSH
   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

3 Toxic adenoma
 More common in young patients

 Autonomically functioning nodule

4 Thyroiditis
 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
 Transient hypothyroidism occurs before resolution

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

Amiodarone Induced Thyroiditis
  Up to 12% of patients, especially in iodine deficient
  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

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

                                     High TSH (rare)

                                          Measure T4



                               Image pituitary gland
                                      Low TSH
                               Measure Free T4 Level

         Normal                                              High

  Measure Free T3 Level                               Primary hyperthyroidism
                                                      Thyroid uptake
Normal              High
-Subclinical       T3 Toxicosis
hyperthyroidism                    Low                              High
-Resolving                Measure thyroglobulin
                                                  DIffuse              Nodular
-Medication       decreased          Increased Graves Multiple       One “hot” area
-Pregnancy        Exogenous                     disease areas
                   hormone          Thyroiditis                           Toxic
-New thyroid illness                Iodide exposure Toxic multinodular
                                                      goiter              adenoma
   Hyperthyroidism with high RIU
     - Grave’s disease
     - Toxic adenoma
     - Toxic multinodular goiter
     - TSH- producing pituitary adenoma
     - Hyperemesis gravidarum
     - Trophoblastic disease

   Hyperthyroidism with low RIU
     - Subacute thyroiditis
     - Exogenous harmone intake
     - Ectopic ovarii
     - Metastatic follicular thyroid CA
     - Radiation thyroiditis
     - palpation thyroiditis
     - Amiodarone induced

   Treatment depends upon
     -Cause and severity of disease
     -Patients age
     -Goiter size
     -Comorbid condition
     -Treatment desired

The goal of therapy is to correct hyper-metabaolic state
with fewest side effects and lowest incidence of
   Anti-thyroid drugs
   Radioactive iodine
   Surgery
   Beta-blocker and iodides are adjuncts to above
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

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 Grave’s

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 iodine—suppress
  thyroid hormone levels

Two agents:
     -Tapazole (methimazole)
     -PTU (propylthiauracil)
    Anti-thyroid Drugs

   Remission rate: 60% when therapy continued for two
   Relapse in 50% of cases.
   Relapse more common in
       -elevated TS antibodies at end of therapy
Anti-thyroid Drugs


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
  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

 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
 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

 Prefered for pregnant patients

 Methimazole is associated with rare genetic
  Dose 100 mg t.i.d
  Maintenance 100-200 mg/day
  Goal: Keep Free T4 at upper level of normal
Anti-thyroid Drugs

 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 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

   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
 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
   Iodine containing meds need to be stopped several
    weeks before therapy
Radioactive Iodine

 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

   Radioactive iodine has replaced surgery for Tx of
   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