Transcript Definition, clinical symptoms, serum lipids, respiratory system, GI

This lecture was conducted during the Nephrology Unit
Grand Ground by Medical Student rotated under
Nephrology Division under the supervision and
administration of Prof. Jamal Al Wakeel, Head of
Nephrology Unit, Department of Medicine and Dr.
Abdulkareem Al Suwaida, Chairman of Department of
Medicine. Nephrology Division is not responsible for the
content of the presentation for it is intended for learning
and /or education purpose only.
HYPERTHYROIDISM
Presented by:
Muteb Al-Rowaili
Medical Student
August 2008
What is Hyperthyroidism?
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“Hyperthyroidism” refers to overactivity of the thyroid gland
leading to excessive synthesis of thyroid hormones and
accelerated metabolism in the peripheral tissues. The secretion
of thyroid hormone is no longer under the regulatory control of
the hypothalamic-pituitary center.
Prevalence
Women
2%
Men
0.2%
15% of cases occur in
patients
than 60 years of age
older
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
GI System
-Weight loss due to increased calorigenesis
-Malabsorption
-Steatorrhea
-Celiac Disease (in Grave’s Disease)
-Hyperphagia (weight gain in younger patient)
-Anorexia- weight loss in elderly
-Dysphagia
-Abnormal LFT especially phosphate
Hematological System
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Normochromic normocytic anemia
Serum ferritin may be high
Grave’s disese
 ITP
 Pernicious anemia
 Anti-neutrophiliac antibody
GU System
Urinary frequency and nocturia
 Enuresis is common in children
Women
 High serum estradiol
 Low free estradiol
 High LH
 Oligomenorrhea and amenorrhea
 Anovulatory infertility
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GU System…cont
Men
 High total testosterone
 Low free testosterone
 High serum LH
 High serum estradiol
 Gynecomastia
 Decreased libido
 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
Skeletal System
Grave’s disease is associated with :
-Clubbing of nails
-Periosteal bone formation in metacarpal bone or
phalanges
Neuromuscular System
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Tremors-outstretched hand and tongue
Hyperactive tendon reflexes
Psychiatric
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Hyperactivity
Emotional lability
Anxiety
Decreased concentration
Insomnia
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
Myesthenia Gravis, especially in Grave’s disease.
Endocrine
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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
Most common cause of iodine excess in US.
Amiodarone contains
37% iodine.
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 ( > 0.1mu/ml )
Measure Free T4 Level
High
Normal
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
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Grave’s disease
Toxic adenoma
Toxic multinodular goiter
TSH- producing pituitary adenoma
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:
such as palpitation , tremor , and anxiety
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Propranolol widely used
Increase progressively until symptoms are controlled
Most cases 80-320 mg qd is sufficient
Ca-CB can be used if beta blocker not tolerated or
contraindicated.
Verapamil cab be used to control tachycardia in pt
with CI to β-adrenergic antagonists.
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 (SSKI)
Dose 1 gram/ 12 weeks
Anti-thyroid Drugs
They interfere with organification of iodine—suppress
thyroid hormone levels
Thionamides :
two agents:
- (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:
Starting dose: 10-40 mg PO daily
Monthly evaluation of
* clinical finding.
* plasma T4 .
until euthyroid.
then the dose adjusted to maintain plasma T4 within
the normal range.
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
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Agranulocytosis up to 0.5%
minor S/E: rash , urticaria , arthralgias , transient
leukopenia.
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 immediately if they develop
(sudden fever , chills 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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Follow up:
Usually , several months are needed to restore euthyroidism .
Patients are evaluated at 4-6 week interval , with assessment
of clinical finding and plasma free T4
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If thyroid function stabilizes within the normal range, the
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If symptomatic HYPOthyroidism develops, thyroxine Rx is
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If symptomatic HYPERthyroidism persists after 6 months,
interval between follow up visits is gradually increased to
annual intervals
started.
RAI treatment is repeated.
Radioactive Iodine
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Higher dose is favored in older patient
A pregnancy test is done immediately before therapy
in potentially fertile women.
A 24-hour RAIU is usually measured and used to
calculate the dose.
Thionamides interfere with RAI therapy and should
be stopped 3 days before Rx.
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.
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
The pts should be prepared for surgry by:
* a Thionamide which given until the pt is nearly euthyroid.
* supersaturated KI (SSKI) 40-80mg PO BID
both drugs are stopped postoperatively.
* atenolol (50-100 mg daily) is started 1-2 weeks before surgry.
if needed, increase the dose to reduce the resting H.R. below
90 bpm & continued 5-7 days postop
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