Hyperthyroidism Flashcards
State of thyroid hormone excess of ANY etiology
Thyrotoxicosis
State of thyroid hormone excess due specifically to excessive thyroid gland function
Hyperthyroidism
Primary thyroid disorder is a disorder that originates from the
thyroid gland
Secondary thyroid disorder is a disorder due to the stimulation of thyroid gland by excess
TSH
HCG
The most common cause of hyperthyroidism
Grave’s disease
Life-threatening exacerbation of hyperthyroidism
Thyroid storm
Throid crisis
Grave’s disease prevalence
Lifetime risk
Associated with increased intake of
Sex
Age
1%
Iodine intake
F>M 7-10:1
Rare before adolescence
Typical range: 20-50
May occur in elderly as “apathetic hyperthyroidism”
Most common etiology of thyrotoxicosis
Grave’s (60-80%)
Genetic risk factors for Grave’s
HLA DR
Cytotoxic T lymphocyte-associated antigen 4 variants
Protein tyrosine phosphatase-22 (PTPN22)
A cell regulatory gene
PTPN22
Monozygotic concordance of Grave’s
Dizygotic twin concordance of Grave’s
20-30%
<5%
Smoking in
Grave’s
Ophthalmopathy
Minor risk factor for Grave’s
Major risk factor for ophthalmopathy
Sudden increase in dietary iodine intake
Radiocontrast materials containing high iodine content
Medications (amiodarone)
Iodine intake
Grave’s
3 fold increase in Grave’s
Postpartum
Grave’s disease is caused by thyroid-stimulating
immunoglobulin against the thyrotropin TSH receptor
Antibodies against the thyrotropin TSH receptor in Grave’s cause
Autonomous growth of thyroid
Autonomous production of thyroid hormones
Intrathyroidal inflammatory cells in Grave’s produce cytokines:
IL-1
TNF a
IFN a
cytokines help sustain intrathyroidal autoimmune process
IL-1
TNFa
IFNa
induce expression of
adhesion
regulatory
HLA II
which in turn activate local inflammatory cells
Edema
Inflammation of EOM
Increase in orbital connective tissue and fat
Thyroid-associated ophthalmopathy
Edema in Grave’s ophthalmopathy is due to hydrophilic action of
secreted by
Glycosaminoglycans
Fibroblast
Inflammation in Grave’s ophthalmopathy is due to infiltration of EOMs and orbital connective tissue by
lymphocytes
macrophages
Thyroid associated opthalmopathy may result from immunoglobulins directed to specific antigens ie
thyrotropin TSH receptors on preadipocyte subpopulation of orbital FIBROBLASTS
Lymphocytic infiltration of dermis
Accumulation of glycosaminoglycans
Non-pitting edema
Dermopathy
Pretibial myxedema
Unusual disorder associated with
hyperthroidism
sporadic episodes of acute muscle weakness
hypokalemia
Asian men
Prodrome: muscle ache, stiffness, LE proximal muscle weakness progressing to flaccid quadriplegia
Serum K not always below normal
Subtle hyperthyroidism symptom
Thyrotoxic period paralysis
Tx: K supplement
Classic hyperthyroidism symptoms
Unintentional weight loss with ravenous apetite Heat intolerance and sweating Palpitations Hyperactivity/anxiety Tremulousness Fatigue and weakness Insomnia Irritability Impaired concentration Increased stool frequency with diarrhea and steatorrhea Pruritus Oligomenorrhea or amenorrhea Erectile dysfunction
Unusual hyperthyroidism symptoms
Weight gain: 5% due to disproportionate increase in caloric intake
Gynecomastia
Urticaria
Diffusely enlarged goiter
Pantay ang laki ng lahat
Grave’s disease
Nodular
Toxic adenoma
Toxic multinodular goiter
Cardiovascular signs of Grave’s
Sinus tachycardia
Bounding pulse/widened pulse pressure
Aortic systolic murmur (Mitral regurg)
Atrial fibrillation >50 years of age
Neurologic Grave’s signs
Hyperreflexia
Muscle wasting
Proximal myopathy without fasciculation
Rare: chorea, hypokalemic periodic paralysis
Dermatologic Grave’s signs
Warm, moist skin
Palmar erythema
Onycholysis
Finer hair texture - diffuse alopecia up to 40% of patients
Opthalmologic Grave’s signs
Lid retraction or lag
Stare
Rarified blinking
A presentation of Grave’s in elderly the elderly
Paucity of classic symptoms
Fatigue
Weight loss
Atrial fibrillation
May be mistake for Depression
Apathetic hyperthyroidism
Life-threatening exacerbation of hyperthyroidism usually precipitated by surgery or acute illness
Fever Delirium Seizures Coma Vomiting Diarrhea Jaundice
Thyrotoxic crisis
Thyroid storm
Occurs in the absence of thyroid dysfunction in 10% of patients
Early symptom:
Grittiness
Eye discomfort
Excessive tearing
Late symptom:
Diplopia (5-10% due to eye muscle swelling and fibrosis)
Proptosis (1/3 often asymmetrical)
Periorbital edema
Conjunctival injection
Chemosis
Papilledema due to optic nerve compression
Peripheral field defects due to optic nerve compression
Unilateral in up to 10%
Grave’s ophthalmopathy
Thyroid-associated ophthalmopathy
Thyromegaly in Graves
Bilateral, symmetric enlargement
Firm
Accompanied by thrill or bruit due to increased vascularity of the gland and hyperdynamic circulation
Noninflamed, indurated plaque
Deep pink or purple color
Orange skin appearance
Anterior and lateral aspects of lower leg (pretibial myxedema) or in other sites after trauma
Nodular involvement, rarely can extend over the whole lower leg and foot mimicking elephantiasis
Accompanied with moderate to severe ophthalmopathy
Thyroid dermopathy (<5%)
Form of clubbing
Strongly associated with thyroid dermopathy
Thyroid acropachy (<1%)
Diagnostic test to reliably distinguish euthyroidism from mild hyperthyroidism
serum TSH with 3rd or 4th-generation immunoassay
When thyrotoxicosis is suspected on clinical grounds, order
serum TSH and free thyroxine T4
When serum TSH level is low, and free T4 level is within the normal range, order
free triiodothyronine T3
Accurate diagnosis of hyperthyroidism during pregnancy can be difficult because total thyroid hormone levels increase reflecting an increased
thyroid-binding globulin level
actions of HCG
Essential after biochemical diagnosis of thyrotoxicosis
Determine underlying cause
Supportive information that may be useful in identifying an underlying cause of thyrotoxicosis
Previous thyroid function test results
History of recent upper respiratory illness
Amiodarone
Pregnancy
Antibody that will support diagnosis of Grave’s
+ TPO Thyroid peroxidase antibodies
Features sufficient to confirm a diagnosis of Grave’s in a patient with biochemical hyperthyroidism WITHOUT NEED FOR FURTHER TESTING:
meaning Grave’s talaga
Diffuse goiter
Signs of ophthalmopathy or dermopathy
Features supporting Grave’s
Diffuse goiter
ophthalmopathy
Positive TPO antibodies
Personal/family history of autoimmune
Studies indicated to distinguish other causes of thyrotoxicosis in patients with biochemical thyrotoxicosis if lacking features of Diffuse goiter or opthalmopathy:
Meaning, mukang di grave’s
Radionuclide (99mtechnetium, 123iodine or 131iodine) uptake
Scan of thyroid
In select cases of Grave’s measurement of this antibody may be useful to establish diagnosis
serum TSH receptor antibodies
A diagnosis of secondary hyperthyroidism should be followed by further investigation
Elevated TSH
Elevated HCG
endocrinologic referral
Norma TSH
Normal free T4
exclude thyrotoxicosis
no further testing necessary
Primary thyrotoxicosis is indicated in the following 3 patterns:
Low TSH, high free T4
Low TSH, high free T4, high free T3
Low TSH, normal free T4, high free T3 (T3 toxicosis)
Subclinical thyrotoxicosis will show
Low TSH level
Normal free T4 and normal T3
Subclinical hyperthyroidism
TSH-secreting pituitary adenoma
Thyroid hormone resistance
will show
Normal or Increased TSH level
High free T4
Secondary hyperthyroidism
Gestational thyrotoxicosis
Germ-line tumor
will show
Low TSH level
High Free T4
Secondary hyperthyroidism
Other laboratory abnormalities associated with thyrotoxicosis
Elevated bilirubin and liver aminotransferase
Elevated ferritin level
Microcytic anemia
Thrombocytopenia
Test for Grave’s
Antibody against thyrotropin TSH receptor
Second-generation assay
Test With High sensitivity and specificity for Grave’s
Predict likelihood of remission in patients who have been treated with thionamides
Second generation
Antibody thyrotropin TSH
Used in pregnancy or after iodine load where nuclear imaging cannot be performed
Thyrotropin TSH antibody with second generation assay
Measurement of thyrotropin TSH antibody is recommended in pregnant women at
third trimester
to assess the likelihood of neonatal hyperthyroidism
Test that helps distinguish hyperthyroidism from other causes of thyrotoxicosis
Radionucleotide UPTAKE
Diseases that present with high radionucleotide uptake
Grave’s
Toxic adenoma
Toxic multinodular goiter
Trophoblastic disease and germ-cell tumors that produce HCG
Diseases that present with Low radionucleotide uptake
Any form of thyroiditis (<1%)
Ectopic thyroid tissue (strums ovarii)
Functioning metastasic follicular thyroid carcinoma (rare)
Factitious thyrotoxicosis
If radionucleotide uptake of the thyroid is HIGH, this will help distinguish among causes of high radionucleotide uptake:
Radionucleotide SCAN
Enlarged gland
Homogenously increased uptake
Grave’s
Focal area of increased uptake with supressed uptake in remainder of gland
Toxic adenoma
Enlarged gland with multiple areas of increased and decreased uptake
Toxic multinodular goiter
Orbital imaging for Grave’s opthalmopathy
Ultrasonography or CT of orbits
More sensitive for detecting opthalmopathy than is clinical examination
Ultrasonography or CT of the orbits detect
Enlarged EOM muscles
Indicated for the further evaluation of secondary hyperthyroidism to search for a TSH-secreting pituitary adenoma
Pituitary MRI
Regardless of etiology, as sson as biochemical confirmation of thyrotoxicosis is made, patient must be started on
B adrenergic blockers
Atenolol 25-50 mg/d
Propranolol 20-40 mg; 4x daily
The Grave’s goals of treatment are to
alleviate symptoms
reduce thyroid hormone synthesis
through
3 forms
Radioiodine (131iodine) treatment
Administration of thionamide (antithyroid)
Subtotal thyroidectomy
Factors important to consider in choice of treatment for Grave’s
Pregnancy, breastfeeding, planning pregnancy
Presence of ophthalmopathy
Patient age
Used as initial treatment or
for relapses after failed surgical or medical therapy
Radioiodine therapy
Radioiodine is transported to thyroid cells and cause
progressive destruction
Dose range of radioiodine therapy
5-15 mCi dependending on size and radioiodine uptake
Small risk immediatelt after radioiodine therapy
minimized by
Thyrotoxic crisis
Pretreatment with thionamide 1 MONTH BEFORE treatment
Pretreatment with thionamide is highly recommended for
elderly patients
cardiovascular disease
High doses of radioiodine therapy are associated with high rate of cure but may cause
hypothyroidism
Full effect of radioactive therapy requires
2-3 months
If hyperthyroidism persists, patient can be treated with
second dose of radioiodine
6 months after first dose
Side effect of Radioactive therapy
Mild pain occuring 1-2 weeks after
Radiation thyroiditis
Carbimazole or Methimazole must be stopped at least how many days before radioiodine administration to achieve iodine uptake
3 days before
PTU had prolonged radiolrotective effect and must be stopped how many days before radioiodine
Weeks before
Or larger dose of radioiodine necessary
Antithyroid and beta blockers may be resumed after administration until full effects of radioiodine are achieved
Precaution after radioiodine therapy
Avoid close prolonged contact with children and pregnant during the first few days after treatment due to transmission of isotope and radiation from the gland
Radioiodine should be used cautiously in
Children and adolescents
Iodine allergy
Concurrent severe ophthalmopathy in smokers
Prevents exacerbation of opthalmopathy
Prednisone 40 mg/d at time of radioiodine treatment tapered over 3 months
Absolute contraindication for radioiodine therapy
Pregnant - patient can conceive safely after 6 months of treatment
Breastfeeding
Used as initial therapy to attain euthyroidism
Before radioiodine therapy or surgery
As prolonged course with goal of tapering
Thionamides
Reduces oxidation and organification of iodine
Inhibiting the TPO enzyme and thyroid hormone synthesis
Possible immunomodulatory role to attenuate the autoimmune process
Thionamides
As thyrotoxicosis improves, starting doses may be gradually reduced after
3-4 weeks
Thionamides
PTU 100-200mg every 6-8h
Methimazole 10-20mg every 8-12h
Carbimazole 10-20mg every 8-12h
OD if euthyroid
High doses of thionamide combined with
Levothyroxine
Avoid possibility of hypothyroidism
Does not provide index of treatment response
Exposes patients to higher doses
Alternative regimen
Block-replace regimen
Euthyroidism with the use of thionamides canbe achieved in
4-6 weeks
Treatment with thionamides is continued for
6 - 12 months
Long term remission after cessation of thionamides is possible in
20%
PTU is given to pregnants only until
1st trimester
Rare but serious side effect that require discontinuation of thionamide
Agranulocytosis (<1%)
Sore throat, fever, mouth ulcers
CBC
Hepatitis
SLE
Common side effects that resolve spontaneously after thionamide drug
Rash Urticaria Fever Mild leukopenia Arthralgia (1-5% of patients)
Should be given in higher doses when given concurrently with thionamides due to accelerated plasma clearance
Warfarin
Needs increased dose during thyrotoxic state because of increased clearance
Digoxin
In pregnancy this regimen should be employed to avoid feta hypothyroidism
Titration
Preferred thionamide for pregnant because of greater safety profile
First line in pregnancy
PTU
Spontaneous remission of hyperthyroidism occurs in this trimester permitting discontinuation of thionamides
third
Breastfeeding is safe with low doses of
PTU <450 mg/day
Use of carbimazole and methimazole in pregnancy is discouraged because of weak association with:
May be used if allergic
aplasia cutis
choanal atresia
Subtotal thyroidectomy indications
Pregnant whose thyrotoxicosis is not controlled by thionamide
Relapse after thionamide drugs and decline treatment with radioiodine
Very large goiters with probability of effective treatment with radioiodine or thionamide is judged to be low
Risk for cancer
Surgery prep to avoid thyrotoxic crisis
Control of thyrotoxicosis with antithyroid drugs Potassium iodide (3 drops of saturated solution PO TID)
Possible surgical complications
Bleeding
Laryngeal edema
Hypoparathyroidism
Damage to recurrent laryngeal nerves
Thyroid storm treatment
Large dose of PTU (600 mg loading dose and 200-300 mg every 6 hours)
PO, NGT, rectum
1 hour after first dose give stable iodine to block thyroid hormone synthesis
Saturated solution of potassium iodide, 5 drops every 6 hours
Ipodate or iopanoic acid (0.5 mg q12 PO)
Sodium iodide (0.25 g IV q6)
Propranolol 40-60mg q4 for tachycardia and other adrenergic manifestations
Dexamethasone 2mg q 6 to inhibit peripheral T4-T3 conversion and reduce thyroid hormone by supressing TSH secretion
Supportive measures during thyroid storm
Antibiotics (if infection is present)
Cooling
Oxygen
Intravenous fluids
Intensive monitoring/supportive care
Identification and treatment of precipitating cause
Urgent reduction of thyroid hormone synthesis
Mild/moderate ophthalmopatht treatment:
Meticulous Control of thyroid hormone levels
smoking cessation
Explanation on Natural history of ophthalmopathy
Occular discomfort: artifical tears (1% methycellulose) and dark glasses with frames
Periorbital edema may respond to more upright sleeping position or diuretic
Corneal exposure during sleep can be avoided by using patches or taping eyelids shut
Minor degrees of diplopia improve with prisms fitted to spectacles
Optic nerve involvement
Chemosis with corneal damage
Prednisone 40-80mg/d in 2/3 of patients Taper by 5 mg every 1-2 weeks over 3 months Pulse therapy with IV methylprednisone Orbital decompression surgery External beam radiotherapy
Thyroid dermopathy treatment
Topical high potency glucocorticoid
Ocreotide
Primary hyperthyroidism
Monitoring
on antithyroid drug:
Follow free T4 until TSH normalizes
Then use both TSH and FT4
Anithyroid medication should be titrates on the basis of
FT4 until TSH normalizes
Patients should be followed up closely for relapse until after discontinuation of antithyroid drug therapy
Then
First year after discontinuing antithyroid drug therapy
annually thereafter for life
Patients treated with radioiodine especially higher doses are at particularly high risk for
hypothyroidism
Patients who underwent radioiodine ablation should have close follow-up
for the first year after ablation followed by at least annual thyroid function test
Should be monitored for the first several months following ablation rather than TSH levels
FT4
Useful in third trimester to assess the risk of neonatal hyperthyroidism
TSH receptor antibodies
Monitor thyroid levels throughout pregnancy
Monitor thyroid function closely in postpartum
Fetal hyperthyroidism may develop even if the mother has previously been rendered euthyroid because TSH receptor antibodies can persist
Develops in up to 15% of patients with Grave’s
Spontaneous immune HYPOTHYROIDISM
Develops in 80% of patients treated with radioiodine
HYPOTHYROIDISM
Thyrotoxic crisis may be precipitated by
Acute illness (stroke, infection, trauma, diabetic ketoacidosis)
Surgery (especially on thyroid)
Radioiodine treatment for partially treated or untreated hyperthyroidism
Pregnancy complicated by uncontrolled hyperthyroidism is associated with increased risks of
Spontaneous abortion
Premature labor
Preeclampsia
Stillbirth
Postpartum period has risk for relapse of Grave’s
Grave’s disease may fluctuate between hypo and hyperthyroidism due to changes in the
functional activity of TSH receptor antibodies
Incomplete treatment with radioiodine ablation or early relapse is more common in
Men <40 years
Predictors of persistent hyperthyroidism
Younger age
Larger thyroid gland
Higher serum T4 concentrations at diagnosis
Higher 24-hour 123 iodine thyroid uptake value
Hyperthyroidism prognosis
Pretreatment with a thionamide before radioiodine is associated with a lower rate of successful treatment
Risk of hypothyroidism after RAI depends on dosage of at least 10-20% in first year, 5% per year after
Most patients progress to hypothyroidism over 5-10 years
Predictors of remission
Disappearance of TSH receptor antibodies Smaller goiters Mild hyperthyroidism Age >40 years Female sex
15% who achieve remission after use of antithyroid drugs develop hypothyroidism 10-15 years later
Recurrent rates for subtotal thyroidectomy
<2%
Ophthalmopathy prognosis
Clinical course does not parallel that of thyroid disease
Typically worsens over the initial 3-6 months, plateaus over the next 12-18 months, then gradually improves, particularly in the soft-tissue changes
Course is fulminant in 5% of patients, requiring intervention in the acute phase (for optic nerve compression or corneal ulceration)
Radioiodine treatment may WORSEN eye disease in smokers
Appears 1-2 years after development of Graves
May improve spontaneously
Thyroid dermopathy
In thyrotoxic crisis or thyroid storm, there is 30% risk of death even with treatment due to
Cardiac failure
Arrhythmia
Hyperthermia
