History of Present Illness 5 years PTC Noted presence of 2x2 cm
anterior neck mass No accompanying symptoms 4 years PTC Progressive
increase in size and felt a lump in the throat which prompted
consult Prescribed L thyroxine 100 ug/tab 1 tab TID which she took
for one month until she noted easy fatigability, palpitations, and
weight loss. She consulted again and the physician requested for
serum T3,T4, and TSH after which she was advised to discontinue
taking the medication. Consult Due to persistence of the mass, she
sought consult at your clinic.
Slide 4
Physical Examination Neck: 8 X 6 cm firm anterior neck mass
with well defined borders and moves with deglutition No palpable
cervical adenopathies BP=120/80 PR=85/min RR=28/min
Heart/Chest/Abdomen unremarkable Pink palpebral conjunctive,
anicteric sclerae
Slide 5
Salient Features 65 y/o Female 2 X 2 cm anterior neck mass
Progressive increase in size lump in throat Prescribed L thyroxine
100 ug/tab 1 tab TID took for one month until she noted easy
fatigability, palpitations, and weight loss Discontinued medication
as advised by physician Physical Examination VS: BP=120/80
PR=85/min RR=28/min Pink palpebral conjunctive, anicteric sclerae
Neck: 8 X 6 cm firm anterior neck mass with well defined borders
and moves with deglutition; no palpable cervical adenopathies
Heart/Chest/Abdomen unremarkable
Slide 6
1. If you were the physician who initially saw the patient one
year ago, what would you have done?
Slide 7
2. What do you think were the serum T3,T4, and TSH levels in
the previous consult? What do you call this condition?
Slide 8
Low circulating levels of T 4 and T 3 Primary Thyroid Failure
Raised TSH levels Secondary Hypothyroidism Low TSH levels that do
not increase following TRH stimulation
Slide 9
HYPOTHYROIDISM Deficiency in the circulating levels of thyroid
hormone leads to hypothyroidism, and, in neonates, to cretinism,
which is characterized by neurologic impairment and mental
retardation. Hypothyroidism may also be associated with deafness
(Pendred's syndrome)4 and Turner's syndrome.
Slide 10
Slide 11
In adults, symptoms in general are nonspecific: Tiredness,
weight gain, cold intolerance, constipation, and menorrhagia
Patients with severe hypothyroidism or myxedema Facial and
periorbital puffiness Characteristic facial features as a
consequence of the deposition of glycosaminoglycans in the
subcutaneous tissues The skin becomes rough and dry and often
develops a yellowish hue from reduced conversion of carotene to
vitamin A. Hair becomes dry and brittle, and severe hair loss may
occur Loss of the outer two-thirds of the eyebrows.
Slide 12
An enlarged tongue may impair speech, which is already slowed,
in keeping with the impairment of mental processes. Myxedema
madness Untreated dementia Nonspecific abdominal pain accompanied
by distention and constipation. Libido and fertility are impaired
in both sexes. Cardiovascular changes in hypothyroidism include:
Bradycardia, cardiomegaly, pericardial effusion, reduced cardiac
output, and pulmonary effusions Cardiac failure is uncommon When
hypothyroidism occurs as a result of pituitary failure, features of
hypopituitarism such as pale, waxy skin, loss of body hair, and
atrophic genitalia may be present
Slide 13
LABORATORY FINDINGS Hypothyroidism is characterized by low
circulating levels of T 4 and T 3. Raised TSH levels are found in
primary thyroid failure, whereas secondary hypothyroidism is
characterized by low TSH levels that do not increase following TRH
stimulation. Thyroid autoantibodies are present and are highest in
patients with autoimmune disease (Hashimoto's thyroiditis, Graves'
disease), although they are also elevated in patients with nodular
goiter and thyroid neoplasms. Other findings include anemia,
hypercholesterolemia, and decreased voltage with flattening or
inversion of T waves on electrocardiogram. Comatose patients with
myxedema also have hyponatremia and CO 2 retention.
Slide 14
TREATMENT THYROXINE Treatment of choice 50 to 200 mcg per day,
depending upon patient's size and condition. Starting doses of 100
mcg of thyroxine daily are well tolerated Elderly patients and
those with coexisting heart disease and profound hypothyroidism
should be started on a considerably lower dose such as 25 to 50 mcg
daily because of associated hypercholesterolemia and
atherosclerosis. The dose can be slowly increased over weeks to
months to attain a euthyroid state.
Slide 15
A baseline ECG should always be obtained in patients with
severe hypothyroidism prior to treatment. Patients are instructed
to take tablets in the morning, usually without other medications,
or at mealtime to assure good absorption. Thyroxine dosage is
titrated against clinical response and TSH levels, which should
return to normal. Patients who present with myxedema coma, in
contrast to the patients with mild to moderate hypothyroidism,
require an initial emergency treatment with large doses of
intravenous thyroxine (300 to 400 g), and careful monitoring in an
ICU setting.
Slide 16
3. What is your diagnosis? Other considerations? Explain.
Slide 17
Diagnosis Hyperthyroidism secondary to over dosage to L
thyroxine
Nodular Non-toxic Goiter FAMILIAL GOITER ENDEMIC GOITER
SPORADIC GOITER Inherited enzyme defect Impaired iodine metabolism
Usually associated with hypothyroidism Due to iodine- deficient
diet Mountainous regions intake of substances (goitrogens) that
inhibit production of thyroid hormone common goitrogens include
foods such as cabbage, turnips, brussel sprouts, seaweed, and
millet Tx: iodized salt No definite cause can be established
Slide 21
Enlargement of the thyroid gland No toxicity; no cancer The
following factors increase your chance of developing nontoxic
goiter: Sex: female (nontoxic goiter is more common in women than
men) Age: over 40 years Reference:
http://www.mbmc.org/healthgate/GetHGContent.aspx
Slide 22
SYMPTOMS Nontoxic goiters usually do not have noticeable
symptoms. Swelling on the neck Breathing difficulties, coughing, or
wheezing with large goiter Difficulty swallowing with large goiter
Feeling of pressure on the neck Hoarseness
Slide 23
MANAGEMENT A goiter only needs to be treated if it is causing
symptoms. Treatments for an enlarged thyroid include: Radioactive
iodine to shrink the gland, particularly if the thyroid is
producing too much thyroid hormone Surgery (thyroidectomy) to
remove all or part of the glandthyroidectomy Small doses of Lugol's
iodine or potassium iodine solution if the goiter is due to iodine
deficiency Treatment with thyroid hormone supplements if the goiter
is due to underactive thyroid Reference:
http://www.nlm.nih.gov/medlineplus/ency/article/001178.htm
Slide 24
INDICATIONS FOR SURGERY Huge goiter which is cosmetically
unacceptable Compression symptoms Suspicion of malignancy
Slide 25
GRAVES DISEASE A type of hyperthyroidism, is caused by a
generalized overactivity of the entire thyroid gland. An autoimmune
disease; thyroid-stimulating antibodies directed at TSH receptors
on follicular cells. It is named for Robert Graves, an Irish
physician, who was the first to describe this form of
hyperthyroidism about 150 years ago.
Slide 26
ETIOLOGY The trigger for auto-antibody production is not known.
Genetic predisposition HLA DR3 Since Graves' disease is an
autoimmune disease which appears suddenly, often quite late in
life, it is thought that a viral or infection may trigger
antibodies which cross- react with the human TSH receptor (a
phenomenon known as antigenic mimicry, also seen in some cases of
Type I diabetes). Yersinia enterocolitica Reference:
http://en.wikipedia.org/wiki/Graves%27_disease
Slide 27
CLINICAL FEATURES Triad: Goiter including the pyramidal lobe
Thyrotoxicosis Exophthalmos Symptoms: Heat intolerance Thirst
Sweating Weight loss despite adequate caloric intake Amenorrhea
Tachycardia or atrial fibrillation Congestive heart failure
Slide 28
PE: Weight loss Flushing Warm and moist skin Inappropriate
sweating Tachycardia Widening of pulse pressure Fine tremor Muscle
wasting Hyperactive tendon reflexes Pretibial myexedema
Gynecomastia Audible bruit over the gland Laboratory Findings:
Decreased TSH Increased circulating T3/T4 levels Increased
circulating thyroid autoantibodies Thyroid stimulating
immunoglobulins (TSI) Tyhroid stimulating antibodies (TSAb)
Radioactive iodine scan shows diffuse uptake through the gland of
45-90 percent.
Slide 29
GRAVES OPHTHALMOPATHY Thyroid-associated ophthalmopathy is one
of the most typical symptoms of Graves' disease. Thyroid eye
disease is an inflammatory condition, which affects the orbital
contents including the extraocular muscles and orbital fat.
Iextraocular muscles t is almost always associated with Graves'
disease but may rarely be seen in Hashimoto's thyroiditis, primary
hypothyroidism, or thyroid cancer. Hashimoto's
thyroiditishypothyroidismthyroid cancer The ocular manifestations
that are relatively specific to Grave's disease include soft tissue
inflammation, proptosis (protrusion of one or both globes of the
eyes), corneal exposure, and optic nerve compression.cornealoptic
nerve There are more general symptoms include lid retraction, lid
lag, and a delay in the downward excursion of the upper eyelid,
during downward gaze. It is believed that fibroblasts in the
orbital tissues may express the Thyroid Stimulating Hormone
receptor (TSHr). This may explain why one autoantibody to the TSHr
can cause disease in both the thyroid and the eyes. Reference:
http://en.wikipedia.org/wiki/Graves%27_disease
Slide 30
Classification of Graves Eye Disease Mnemonic: "NO SPECS Class
0: No signs or symptoms Class 1: Only signs (limited to upper lid
retraction and stare, with or without lid lag) Class 2: Soft tissue
involvement (oedema of conjunctivae and lids, conjunctival
injection, etc) Class 3: Proptosis Class 4: Extraocular muscle
involvement (usually with diplopia) Class 5: Corneal involvement
(primarily due to lagophthalmos) Class 6: Sight loss (due to optic
nerve involvement) Reference:
http://en.wikipedia.org/wiki/Graves%27_disease
Relapse rate in 12-18 months Risk for fetal goiter,
hypothyroidism No morbidity related after surgery Treatment of
choice for small goiters and pregnant patients (PTU) Euthyroid
state is achieved in 4-6 weeks
Slide 33
Radioactive Iodine Ease of treatment Highly effective
especially in diffuse goiters No morbidity related to surgery
Treatment of choice for failed surgical management The effect is
seen in 1.5-4 months Standard dose = 10 mCl = 8500 cGy
Slide 34
Surgery Complete and permanent control of toxicity Rapid
control of symptoms Removal of mass Treatment of choice for huge
goiters Needs pre-operative preparation Overall morbidity of
1-2%
Slide 35
Toxic Multinodular Goiter Usually occur in individuals older
than 50 years of age who often have a prior history of a nontoxic
multinodular goiter Over several years, enough thyroid nodules
become autonomous to cause hyperthyroidism. Similar to Graves
disease, but symptoms and signs of hyperthyroidism are less severe
and extrathyroidal manifestations are absent. May present with
atrial fibrillation or palpitations, tachycardia, nervousness,
tremor or weight loss. Low TSH, normal or minimally increased T4,
elevated T3, T3>T4.
Slide 36
Toxic Multinodular Goiter Thyroid scan heterogenous uptake with
multiple regions of increased and decreased uptake. 24hr uptake of
radioiodine may not be increased. Management Antithyroid drugs +
beta blockers normalize thyroid function and address the clinical
features of thyrotoxicosis, but often stimulates the growth of the
goiter; spontaneous remission does not occur. Radioiodine treat
areas of autonomy, decrease the mass of the goiter A trial of
radioiodine should be considered before subjecting patients to
surgery.
Slide 37
Toxic Multinodular Goiter Surgery Definitive treatment of
underlying thyrotoxicosis and goiter. Subtotal thyroidectomy is the
standard procedure. Patients should be rendered euthyroid using
antithyroid drugs before operation.
Slide 38
Toxic Adenoma A solitary, autonomously functioning thyroid
nodule Typically occurs in younger patients (+) thyroid nodule with
symptoms of hyperthyroidism Size is at least 3cm before
hyperthyroidism occurs. Absent clinical features suggestive of
Graves disease or other causes of thyrotoxicosis
Slide 39
Toxic Adenoma Thyroid scan definitive diagnostic test Focal
uptake in the hyperfunctioning nodules Diminished uptake in the
remained of the gland Suppression of the activity of the normal
thyroid
Slide 40
Toxic Adenoma Radioiodine ablation treatment of choice 131I is
concentrated in the hyperfunctioning nodule with minimal uptake and
damage to normal thyroid tissue. Relatively large doses correct
thyrotoxicosis in about 75% of patients within 3 months.
Hypothyroidism occurs in
Toxic Adenoma Medical therapy using antithyroid drugs and beta
blockers normalize thyroid function but is not an optimal long term
treatment Ethanol injection under ultrasound guidance Repeated
injections often >5 sessions Reduce nodule size
Slide 43
Solitary Thyroid Nodule Present in approximately 4 percent of
the population Pain is unusual. When present, it should raise
suspicion for intrathyroidal hemorrhage in a benign nodule,
thyroiditis, or malignancy. History of hoarseness - may be
secondary to malignant involvement of the recurrent laryngeal
nerves Risk factors for malignancy exposure to ionizing radiation
and family history of thyroid and other malignancies associated
with thyroid cancer.
Slide 44
Solitary Thyroid Nodule Mass moves with swallowing. Hard,
gritty of fixed nodules are more likely to be malignant. Most are
euthyroid. If a patient with a nodule is found to be hyperthyroid,
the risk of malignancy is approximately 1 percent. FNAB most
important diagnostic test Benign 65% (includes cysts and colloid
nodules) Suspicious 20% Malignant 5% Nondiagnostic 10%
Slide 45
Solitary Thyroid Nodule Ultrasound For detecting nonpalpable
thyroid nodules For differentiating solid from cystic nodules For
diagnosing suspicious nodules with microcalcifications For
identifying adjacent lymphadenopathy CT and MRI unnecessary in
except for large, fixed, or substernal lesions. 123I or 99mTc
rarely necessary, unless evaluating patients for hot or autonomous
thyroid nodules
Slide 46
Solitary Thyroid Nodule Malignant tumors generally treated by
total or near- total thyroidectomy Simple thyroid cysts - resolve
with aspiration in approximately 75 percent of cases Unilateral
thyroid lobectomy - if the cyst persists after three attempts at
aspiration Lobectomy For cysts >4 cm in diameter For complex
cysts with solid and cystic components
Slide 47
Solitary Thyroid Nodule Colloid nodule should be observed with
serial ultrasound and Tg measurements Repeat FNAB if nodule
enlarges L-thyroxine in doses sufficient to maintain a serum TSH
level between 0.1 and 1.0 U/mL. 50% decrease in size Thyroidectomy
if a nodule enlarges on TSH suppression, causes compressive
symptoms, or for cosmetic reasons Exceptions: Patient who has had
previous irradiation of the thyroid gland or who has a family
history of thyroid cancer. In these patients total or near-total
thyroidectomy is recommended. High incidence of thyroid cancer (
40%) Decreased reliability of FNA biopsy
Slide 48
4. How would you manage this patient now?
Slide 49
Goal: restoration of clinical and biochemical euthyroid state
by omitting or reducing the dosage of medications and other
measures as needed depending on clinical status. ECG Blood test:
TSH, T3, T4 levels, monitored regularly SYMPTOMATIC TREATMENT: To
control tachycardia, hypertension and atrial fibrillation: 20 - 40
mg doses of propranolo Q 6hours; d If beta blockers are
contraindicated: Diazepam and/or chlorpromazine
Slide 50
RADIOACTIVE IODINE ingestion of a radioactive iodine tablet
(6-12 wks) which is then taken up by thyroid cells. These
overactive cells are destroyed so that the thyroid can shrink in
size and produce hormone at normal levels. In patients with
underlying heart disease and in elderly patients, it is desirable
to treat with antithyroid drugs (methimazole) until the patient is
euthyroid. The medication is then stopped for 5-7days before the
appropriate dosage of 131 I. Although it is a safe treatment, most
people become hypothyroid after radioactive iodine therapy and
therefore require lifelong thyroid hormone replacement
therapy.
Slide 51
THYROIDECTOMY Now uncommonly performed; the surgeon removes
most or all of the gland Candidates for surgery: include pregnant
hyperthyroid patients intolerant of anti-thyroid drugs, patients
desiring definitive therapy without the use of radioactive iodine,
children, and patients with very large or multinodular goiters.
Patients are treated with antithyroid drugs until euthyroid (about
6wks). In addition, 10-14 days prior to surgery, they receive
saturated solution of potassium iodide 5 drops BID, to diminish
vascularity of the gland and simplify surgery However, in cases of
total removal of the thyroid gland, patient must take thyroid
replacement pills for the rest of his or her life
Slide 52
NON-PHARMACOLOGICAL High calorie diet in order to replace all
the energy burned by the body in hyperthyroid state Drink plenty of
water and juices to replace all the fluid losses. Avoid or limit
caffeinated drinks for such could produce anxiety.
Slide 53
Journals on Diagnosis and Treatment of Drug Induced
Hyperthyroidism
Slide 54
Diagnosis Newly diagnosed thyrotoxicosis in hospitalized
patients: clinical characteristics Rotman-Pikielny P et. Al
Slide 55
Background: Thyrotoxicosis is often diagnosed in an outpatient
setting. Most common symptoms include irritablility, heat
intolerance,palpitations and weakness The prevalent symptoms in
hospitalized patients with newly diagnosed thyrotoxicosis have not
been fully characterized
Slide 56
Objective To determine the clinical characteristics of patients
with thyrotoxicosis newly diagnosed during hospitalization.
Slide 57
Design Retrospective computer-based search was undertaken to
detect patients that were hospitalized in our medical centre during
1999-2006, and discharged with thyrotoxicosis or thyroiditis
primary diagnosis.
Slide 58
Results Fifty-eight patients (36F/22M; mean age 52.1 +/- 17.5
years) were identified. Weakness, weight loss and palpitations were
the most common manifestations (50, 40 and 35%, respectively) and
were predominantly present in patients with hyperthyroidism. Sore
throat was present in 41% of patients with thyroiditis.
Slide 59
Sinus tachycardia and atrial fibrillation occurred in 65.5 and
15.5% of the patients, more common in those with hyperthyroidism.
The diagnoses on discharge were Graves' disease, subacute
thyroiditis and multinodular goiter in 39.7, 34.5 and 8.9%,
respectively.
Slide 60
Conclusion Weakness, weight loss and palpitations were the main
symptoms in patients diagnosed with thyrotoxicosis during
hospitalization. Thyrotoxicosis should be included in the
differential diagnosis when patients are admitted to the hospital
with those symptoms.
Slide 61
Treatment Drug induced thyrotoxicosis: the surgical option
Lorberboym M., Schacter P. Background: Drug induced thyrotoxicosis
is not uncommon, It may worsen life threatening arrythmias and
become refractory to medical treatment
Slide 62
Summary The Article talks about a near total thyroidectomy as
valid alternative to medical therapy The article pursues to promote
near total thyroidectomy as an early management of the disease
Slide 63
Methods The study included 12 patients 7 men and 5 women aged
63-82 years of age with drug induced fulminant thyrotoxicosis Drugs
such as Iodine containing Amiodarone or IFN a treatment Patients
has adjunct medical therapy of an anti thyroid Propylthiouracil
1200 mg and a Beta receptor antagonist
Slide 64
Thyroid scan was performed in all patients using Tc-99m
pertechnate
Slide 65
Results 4 patients did not respond to 3 months of medical
therapy required surgical thyroidectomy due to unremitting
thyrotoxicosis. Near total thyroidectomy resulted into rapid
correction of thyrotoxicosis enabling continuation of
anti-arrythmic drugs All patients recovered rapidly and remained
well and euthyroid on thyroxine replacement therapy