TREATMENT AND MANAGEMENT

OF GRAVE’S DISEASE
a discussion paper

Dr. Hidvard Caminero, PGI

Department of Internal Medicine

Bicol Regional Training and Teaching Hospital
Legazpi city, Albay

July 29, 2022

1
TABLE OF CONTENTS

TABLE OF CONTENTS 2

OBJECTIVES 3

I INTRODUCTION 4

II BRIEF REVIEW OF THYROID ANATOMY AND 5-11

PHYSIOLOGY

III EPIDEMIOLOGY OF GRAVE’S DISEASE AND 12

RISK FACTORS

IV PATHOPHYSIOLOGY OF GRAVE’S DISEASE 13

V DIAGNOSIS OF GRAVE’S DISEASE 14-15

VI CLINICAL MANIFESTATION OF GRAVE’S 16-17

DISEASE

VII TREATMENT AND MANAGEMENT OF 18-25

GRAVE’S DISEASE

VIII COMPLICATIONS 26

IX PROGNOSIS & FOLLOW-UP 27

X CITED LITERATURES 28

2
OBJECTIVES

A. To write an overview or brief discussion on thyroid anatomy and physiology,

epidemiology and pathophysiology of grave’s disease as well as its diagnosis and
clinical manifestations.

B. To discuss the treatment and management of grave’s disease. Specifically, via 1)

using antithyroid drug to reduce thyroid hormone synthesis, and 2) by reducing the
amount of thyroid tissue using radioiodine and thyroidectomy.

C. To discuss the use of drugs directed to treat other signs and symptoms such as
palpitations, disturbance in mentation, grave’s ophthalmopathy, etc.

D. To incorporate relevant information about the drug dosage as well as the treatment
and management in those cases with comorbid conditions.

3
INTRODUCTION

Grave’s disease is also known as toxic diffuse goiter and it is caused by the existence of
autoantibodies which mimics the action of TSH that can stimulate the thyroid stimulating
hormone receptor leading to abnormality in the production of thyroid hormone.
The relative increase in circulating T4 and T3 produces symptoms related to abnormal
metabolic rate, hypermobility, and problems of mentation.
Grave’s disease is the most common cause of hyperthyroidism with 20-30 cases per
100,000 individuals each year.

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BRIEF REVIEW ON THYROID ANATOMY AND PHYSIOLOGY

A. Organ description

Embryonic origin: ENDODERM The knowledge on

Fourth week- thickening of the floor of primitive pharynxduct its embryonic origin
formationcaudal migrationduct atrophyformation of bilobe and emergence in
and differentiation to follicular cells (9th week)secretion of early gestation is
colloid (14th week) important in
understanding why
7th week: migration of cells from fourth pharyngeal pouch to fuse in grave’s disease
with the cells of the thyroid, giving “C cells” the fetus is affected,
and the rationale
Morphology: roughly butterfly-shaped, with two lobes wrapping behind the change
around the trachea and connected in the middle by an isthmus in treatment in the
case of grave’s
Location: ductless alveolar gland found in the anterior neck, just disease in
below the laryngeal prominence (Adam's apple) pregnancy.

Information from Histology book by Ross’ 7th edition Surgeons often find
it very important to
Variation: know the variations
1. Pyramidal lobe (PL) or lobe of Lalouette in the anatomy of
2. Origin of levator glandulae thyroidae thyroid gland.
3. Absence of isthmus
4. Agenesis
5. Ectopic thyroid
6. Accessory thyroid tissue
7. Thyroglossal duct cysts

5
B. Blood supply Arteries:
1. Superior thyroid
(from external
carotid)
2. Inferior thyroid
(from thyrocervical
trunk)
3. Sometimes the
thyroidea ima.
(from
brachiocephalic
artery or arch of
aorta)

Veins:
1. Superior thyroid
2. Middle thyroid
3. Inferior thyroid
(1&2 drain to IJV
while 3 drain to left
BCV)

Lymph:
Mainly: Deep
cervical LN
Few: Paratracheal
nodes

C. Nerve supply ANS has nothing to

do with the
Superior, middle, and inferior cervical sympathetic regulation of
Ganglia thyroid hormone

D. 1. Histology

6
Figure 1 is the
histologic image of
a normal thyroid
gland, no signs of
increase in
follicular size, no
abnormal glandular
formations, and no
hyperplasia is
noted.

Figure 1. Normal thyroid gland

In contrast to figure
1, in figure 2, the
image is a thyroid
gland in grave’s
disease, there is
hyperplasia of the
epithelial cells that
results to crowding,
so the epithelial
cells project into
the follicles, and
because that these
epithelial cells
actively resorb the
colloid in the center
of the follicles,
scalloped
appearance is
Figure 2. Thyroid gland in grave's disease. Photo adapted from seen.
robbin’s pathology book 10th edition.

2. Gross anatomy

Normal thyroid
gland in gross

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appearance, there is
right lobe and left
lobe connected via
isthmus. Averagely
this is 10 to 30
grams by weight.

Figure 3. Normal thyroid gland. Photo adapted from

https://www.slideserve.com/breena/thyroid-normal-in-situ-gross

The gland is
diffusely swollen
and hyperemic
described as juicy
or beefy appearance
in gross section.

Figure 4. Gross appearance of thyroid gland in grave's disease.

Photo adapted from Histology book by Ross 7th edition

E. Endocrinology

HypothalamicPituitaryThyroid axis and feedback loops

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F. Thyroid hormone synthesis

This can start upon binding of the TSH to TSHR, which triggers a
molecular cascade via G-protein mechanism and adenylyl cyclase.

The following are the result of stimulation of TSHR:

1. Iodide uptake
via upregulation of sodium/iodide symporter
2 sodium/1 iodine ratio. Driven by sodium concentration
gradient
Via enzyme upregulation
2. Iodination
3. Conjugation
4. Endocytosis
5. Proteolysis
6. Secretion
7. Hyperplasia via growth promoting effects of TSH
G. Difference between T4 and T3

T4 is produced in the thyroid up to 90% compared to T3 (10%).

T4 is more bound to plasma proteins
they both enter target cells via facilitated diffusion

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most of cytoplasmic T4 is converted to T3 by 5’/3’
monoiodenase, so they nearly have equal cytoplasmic levels
T3 is more potent at binding to nuclear receptors than T4, so that
90% of the bound hormones are T3
those nuclear receptors in the nucleus are already in heterodimer
form with RXR as its preference and are already bound to DNA
response elements

Information taken from Boron’s physiology book 3rd edition

H. Effects of T4 and T3 to target cells

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they leave plasma and exert both metabolic and developmental effects
they bind to nuclear receptors
2 thyroid receptor genes: alpha and beta (2 isoforms)
expression of nuclear receptors is tissue specific and varies with time of development
these receptors form dimer with RXR and both bind to DNA response elements, and
they take effect either by suppressing or activating the transcription of related proteins.
some enzymes and receptors being regulated by T4 or T3 are N/K pump,
gluconeogenic enzymes, respiratory enzymes, myosin heavy chain, beta adrenergic
receptors and many others

Information taken from Boron’s physiology book 3rd edition

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EPIDEMIOLOGY OF GRAVE’S DISEASE AND RISK FACTORS

 Clinical features generally worsen without treatment; mortality was 10–30% before the
introduction of satisfactory therapy

 accounts for 60–80% of thyrotoxicosis.

 Graves’ disease occurs in up to 2% of women but is one-tenth as frequent in men

 Rarely begins before adolescence and typically occurs between 20 and 50 years of age

 Also occurs in the elderly

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PATHOPHYSIOLOGY OF GRAVE’S DISEASE

-an autoimmune disorder characterized by the production of autoantibodies against

multiple thyroid proteins, most importantly the TSH receptor.
Pathogenesis:
Emergence of autoantibodies to TSHRAbnormal stimulation of
TSHRThyrotoxicosisRelated signs and symptoms

Two cited factors that increase the of developing autoantibodies:

1. Environmental susceptibility: via neuroendocrine effects of stress
2. Genetic susceptibility (Polymorphisms)
a. TSH receptor gene
b. Immunoregulatory genes: CTLA-4, CD25, PTPN22,
FCRL3, and CD226
c. HLA-DR

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DIAGNOSIS OF GRAVE’S DISEASE

A. Straight-forward diagnosis in a patient with biochemically confirmed thyrotoxicosis, diffuse

goiter on palpation, ophthalmopathy, and often a personal or family history of autoimmune
disorders.

B. In those without the above features radionuclide (99mTc, 123I, or 131I) scan and uptake of
the thyroid is used, which will distinguish the diffuse, high uptake of Graves’ disease from
destructive thyroiditis. In the picture below there is diffuse uptake of iodine in grave’s disease
secondary to the balanced distribution of abnormally stimulated TSHR by autoantibodies
which can penetrate diffusely in the thyroid.

Figure 5. Differences in the distribution of radionuclide uptake in thyroid

parenchyma. Photo adapted from medscap.org

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C. TRAb measurement can be used to diagnose Graves’ disease and color-flow Doppler
ultrasonography may distinguish between hyperthyroidism (with increased blood flow) and
destructive thyroiditis. In TSH-secreting pituitary tumor, the difference is that there is the
presence of a nonsuppressed TSH level and the finding of a pituitary tumor on CT or
magnetic resonance imaging (MRI).

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CLINICAL MANIFESTAION OF GRAVE’S DISEASE

Signs and symptoms include features that are common to any cause of thyrotoxicosis as listed on
the table:

Apathetic thyrotoxicosis presents mainly with fatigue and weight loss and is common in elderly
Thyrotoxicosis:
 Weight loss despite good appetite because of increase metabolic rate
 Weight gain in 5% of patients because of increase food intake
 Fine tremor – best elicited upon stretching the patients fingers against the examiners palm
Neurologic manifestations:
 Hyperreflexia
 Muscle wasting
 Proximal myopathy without fasciculation
Cardiac manifestations:
 Sinus tachycardia most common cardiac manifestation
 Atrial fibrillation is more common in patients >50 years of age
Thyroid gland:
Thyroid is usually diffusely enlarged to two to three times its normal size. The consistency is
firm, but not nodular. There may be a thrill or bruit, best detected at the inferolateral marginsof
the thyroid lobes, due to the increased vascularity of the gland.
Skin:
 Warm and moist, and the patient may complain of sweating and heat intolerance
 Palmar erythema, onycholysis, and, less commonly, pruritus, urticaria, and diffuse
hyperpigmentation

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Eyes:
 Lid retraction, causing a staring appearance, can occur in any form of thyrotoxicosis and
is the result of sympathetic overactivity
GIT: Increased stool frequency
Genito-urinary:
 Oligomenorrhea or amenorrhea in women
 In men, there maybe impaired sexual function and, rarely, gynecomastia

The clinical presentation of grave’s disease depends on the following:

 Severity of thyrotoxicosis
 Duration of disease
 Individual susceptibility to excess thyroid hormone
 Patient’s age

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TREATMENT AND MANAGEMENT OF GRAVE’S DISEASE

Treatment of hyperthyroidism: Reduce thyroid hormone production

1. Reducing thyroid hormone synthesis Antithyroid drugs

Mechanism of action: Inhibit the function of

TPO, reducing oxidation and organification of
iodide. Peripherally acts by inhibiting the
conversion T4 to T3.

1. Propylthiouracil
Half-life: 90 minutes
Hepatotoxic (need monitoring and liver
function test)
Limited indications (US-FDA):
a. first trimester pregnancy
b. thyroid storm
c. minor adverse reactions to methimazole

2. Carbimazole or methimazole
Half-life: 6 hours

Discussion on the use of Propylthiouracil versus methimazole

The propylthiouracil has an advantage versus carbimazole or methimazole because it

can inhibit the peripheral conversion of T4 to T3 as well as it has an early onset of action, so
its better used in emergency cases such as in “Thyroid storm”.
In pregnant cases also, the propylthiouracil is selected over methimazole, because
various researches shows that methimazole causes embryopathy.
However, propylthiouracil has hepatotoxic side effects and lower half-life in plasma,
so the majority of the cases, methimazole is selected over propylthiouracil.

Two types of regimens:

1.) Titration regimen: Drug dosage is reduced through time depending on the result of the level
of thyroid hormone monitored starting 4-6 weeks from starting the treatment.

 Carbimazole or methimazole: 2.5-10 mg daily maintenance dose

 Propylthiouracil: 50-100 mg

2.) Block-replace regimen: a replacement dose of levothyroxine is added, and the antithyroid
drug is continued in an unchanged dose.

Minor side effects (1.5% of patients)

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1. Rash
2. Urticaria
3. Fever
4. Arthralgia
 Rashes can respond well to antihistamine. These signs and symptoms resolve
spontaneously or after use of other alternative drugs.

Rare but Major side effects:

1. Hepatitis (Propylthiouracil)
2. Cholestasis (Methimazole or carbimazole)
3. Vasculitis
4. Agranulocytosis (<1%)
 When any of this rare side effects are noted, it is important to stop the drug and not to
be restarted.

2. Reducing the amount of thyroid tissue

a. Radioiodine treatment, I131

Discussion:

The rationale for the use of radioactive iodine (I131) in the case of hyperthyroidism in
Grave’s disease is via reduction in the amount of thyroid tissue in the thyroid gland which in
effect reduce or normalize the levels of hormones produced from the thyroid gland, the reason
for the reduction in thyroid tissue is due to the effect of ionizing radiation emitted by the
radioactive iodine which creates damage to DNA fragments and triggers apoptosis. According
to Russo, et. Al (2013) this apoptotic process was confirmed by the generation of caspase-3
and PARP cleavage products which results demonstrate that I131 induces apoptosis in human
thyrocytes.

Since the thyrocytes after radioiodine treatment undergo apoptosis, there may be a
release of thyroid contents into the blood stream, and that includes the T3 and T4 leading to an
abrupt rise in its level in the blood stream, this makes the patient predispose to a small risk of
thyrotoxic crisis which is also mentioned in Harrison’s (Internal medicine, 20 th ed.). That is
why it is suggested that antithyroid drugs be used a month before radioiodine therapy.
Moreover, when using radioiodine treatment, antithyroid drugs must be stopped 2-3 days
before the procedure this is secondary to the effect on the uptake concentration of Iodine in
thyrocytes. The antithyroid drugs will be continued 3-7 days after radioiodine to counter the
relative rise of thyroid hormones released from apoptotic cells. For propylthiouracil, it should
be longer secondary to its radioprotective effects.

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From those apoptotic cells, not only the hormones are released but also some other
autoantibodies, which theoretically has an effect in retrobulbar tissues, the rise in the level of
the said autoantibodies may impact or aggravate the already existing Grave’s ophthalmopathy,
so precaution is needed especially those that are smokers.

It is suggested in Harrison’s to take Prednisone, 30mg/day at the time of radioiodine

treatment, and be tapered 6-8 weeks to prevent exacerbation of ophthalmopathy. However,
those with moderate to severe eye diseases should avoid radioiodine therapy.

Use of beta-blockers:

Because the effect of radioiodine therapy is gradual, there will be hyperthyroid symptoms
before it can take its full effect, and in that case beta-adrenergic symptoms, which can be
treated with beta adrenergic blockers. If the hyperthyroid state is persistent, a second dose of
radioiodine can be done 6 months after the first dose. Also in the elderly, whom has cardiac
problems, may also be given beta blockers.

Thyroiditis

Pain from thyroiditis secondary to inflammatory response from damaged thyroid tissues can be
treated with NSAID’s (Shah et. al, 2015)

Dosage of Radioiodine: Ranges between 370 MBq (10 mCi) and 555 MBq (15 mCi)

Accordingly, it is difficult to calculate because of the differences in biologic effects of

radiation from individual to individual. And that it was strategized to base it on the severity of
thyrotoxicosis, size of goiter, and the level of radioiodine uptake.

Contraindications:

Pregnancy and breastfeeding are the contraindications, this is secondary to the relative effects
of exposure of the developing conceptus and breastfeeding neonate to radiation and absorption
of radioactive iodine to other tissues like the breast milk (Hartman, 2016).

Precautions:

The patient should avoid close and prolonged contact with children and pregnant women for
5–7 days because of possible transmission of residual isotope and exposure to radiation
emanating from the gland

Follow-up:

The patient should be informed of the risk of hypothyroidism before the procedure is done
because it has a risk of 10-20% in the first year after treatment and 5% per year thereafter
according to Harrison’s. The patient should have a close follow-up during the first year.

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Risk of cancer:

In adults, the risk is statistically not increased. But for children, it is avoided because of the
theoretical risk of neoplastic transformation of the radiation-exposed cells.

b. Thyroidectomy or near total thyroidectomy

This treatment option is indicated for those relapses after treatment using antithyroid
drugs or those who prefer this treatment to radioiodine or to those young individuals with large
goiter.

Potassium iodide (SSKI)

There is a need to give the patient with 1-2 drops of potassium iodide orally 3 times a day for
10 days prior to surgery to avoid thyrotoxic crisis and to decrease the vascularity of thyroid
tissue minimizing the risk of bleeding and hematogenous leak of thyroid contents to the blood
stream

Complications of surgery:
1. Bleeding
2. laryngeal edema
3. hypoparathyroidism
4. damage to recurrent laryngeal nerves

Recurrence rates in the best series are <2%, but the rate of
hypothyroidism is similar to that following radioiodine treatment.

Management of Grave’s disease in pregnancy

The transplacental passage of the drugs used in pregnancy may produce fetal

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hypothyroidism and goiter if the maternal dose is excessive, maternal antithyroid dose titration
should target serum free or total T4 levels at or just above the pregnancy reference range.

As was said propylthiouracil is used until 14–16 weeks gestation because of the
association of rare cases of methimazole/carbimazole embryopathy, including aplasia cutis
and other defects, such as choanal atresia and tracheoesophageal fistulae. Aplasia cutis is a
condition characterized by the absence of certain layer of skin, on the scalp, on the trunk, or
on arms and legs

Because of its rare association with hepatotoxicity, propylthiouracil should be limited

to the first trimester and then maternal therapy should be converted to methimazole (or
carbimazole) at a ratio of 15–20 mg of propylthiouracil to 1 mg of methimazole.

Treatment maybe stopped in the last trimester because TSIs tend to decline in pregnancy. But,

When the thyrotoxicosis is 3x higher than normal in pregnant, it will result to thyrotoxicosis of
the fetus, manifested by the following:
 Poor intrauterine growth
 Fetal heart rate of >160 beats/min,
 Advanced bone age
 Fetal goiter
 High levels of maternal TSI after 26 weeks gestation

If this is the case, antithyroid drugs given to the mother may also be used to treat the
fetus and may be needed even for 1–3 months after delivery, until the maternal
antibodies disappear from the baby’s circulation.

The postpartum period is a time of major risk for relapse of Graves’ disease.

 Breast-feeding is safe with low doses of antithyroid drugs

 Graves’ disease in children is usually managed initially with methimazole or
carbimazole .
 Surgery or radioiodine is indicated for severe or relapsing disease

Thyrotoxic crisis, or thyroid storm

Thyrotoxic crisis, or thyroid storm, is rare and presents as a life-threatening

exacerbation of hyperthyroidism, accompanied by fever, delirium, seizures, coma, vomiting,
diarrhea, and jaundice.

The mortality rate due to cardiac failure, arrhythmia, or hyperthermia is as high as

30%, even with treatment. Thyrotoxic crisis is usually precipitated by acute illness (such as
stroke, infection, trauma, diabetic ketoacidosis), surgery (especially on the thyroid), or
radioiodine treatment of a patient with partially treated or untreated hyperthyroidism.
Management:

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1.) Intensive monitoring and
2.) Supportive care
3.) Identification and treatment of the precipitating cause, and measures that reduce thyroid
hormone synthesis

 Large doses of propylthiouracil: 500–1000 mg loading dose and 250 mg

every 4 h) given orally or by nasogastric tube or per rectum
This is the drug of choice because of its effective inhibition of the
conversion of T4 to T3

If the drug of choice is not available,

 Methimazole can be used in doses of 20 mg every 6 hours

One hour after the first dose of propylthiouracil
 Stable iodide (5 drops SSKI every 6 h) is given to block thyroid hormone
synthesis via the Wolff-Chaikoff effect

To the tachycardia and related adrenergic manifestations,

 Propranolol should be given: 60–80 mg PO every 4 h

or 2 mg IV every 4 h
 Other β-adrenergic blockers can be used
 Short-acting IV esmolol can be used to decrease heart rate while monitoring for signs
of heart failure

Other additional therapeutic measures,

 Glucocorticoids: hydrocortisone 300 mg IV bolus
then 100 mg every 8 h
 Antibiotics if infection is present
 Cholestyramine to sequester thyroid hormones
 Cooling
 Oxygen
 IV fluids.

Grave’s ophthalmopathy

The clinical manifestations of Grave’s ophthalmopathy includes proptosis, chemosis,

periorbital edema, and altered ocular motility. These are all produced because of the
glycosaminoglycan deposition in the orbit, active inflammatory process, fibrosis of the extra-
ocular muscles and fat accumulation within the orbit (Hadas et.al, 2010).
When it is mild to moderate, no active treatment is needed according to Harrison’s
because there is a usual spontaneous improvement. The general measures include 1) Control of
thyroid hormone and 2) Cessation of smoking, as smoking statistically is a major risk factor
for grave’s ophthalmopathy.

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Problems of discomfort:

1) Dry eye mucosa

Can be managed with artificial tears examples are hypromellose 0.3% or carbomer
0.2% ophthalmic gel, paraffin-based eye ointment, and the use of dark glasses with side
frames.

2.) Periorbital edema

Maybe managed by positioning the patient to a more upright sleeping position or a use
of diuretic. Corneal exposure during sleep can be avoided by using patches or taping the
eyelids shut. Minor degrees of diplopia improve with prisms fitted to spectacles. Some
authorities also advocate selenium 100 μg twice a day.

3.) Severe ophthalmopathy (chemosis)

Severe swelling can impinge adjacent structures such as the nerve which can undergo
ischemia and cell death. Nerve involvement or chemosis resulting in corneal damage, is an
emergency which requires joint management with an ophthalmologist.

Pulse therapy with IV methylprednisolone: 500 mg of methylprednisolone once weekly for 6

weeks, then 250 mg once weekly for 6 weeks.

Orbital decompression

Orbital decompression can be achieved by removing bone from any wall of the orbit, this is
done when glucocorticoid is ineffective. Decompression will allow displacement of fat and
swollen extraocular muscles.

4.) Proptosis

Recedes an average of 5 mm, but there may be residual or even worsened diplopia. Once the
eye disease has stabilized, surgery may be indicated for relief of diplopia and correction of the
appearance.

Thyroid dermopathy

According to Tapan & Chahar (2015) the occurrence of thyroid dermopathy takes
place late in the course of disease and it was theorized that the cause is the binding of thyroid
stimulating hormone receptor antibodies to fibroblast components of the skin leading to
deposition of large amounts of glycosaminoglycans in the tissue.

This is only a cosmetic problem wherein surgical removal is not indicated. However, if
there is a necessity to treat, Harrison’s suggested the use of topical, high potency
glucocorticoid ointment under an occlusive dressing. Intralesional triamcinolone 40 mg/ml in
every 3 weeks can be used in cases of cutaneous myxedema (Tapan & Chahar, 2015).

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COMPLICATIONS

Complications of Graves' disease if left untreated can include:

1.) Pregnancy issues. Possible complications of Graves' disease during pregnancy include
miscarriage, preterm birth, fetal thyroid dysfunction, poor fetal growth, maternal heart failure

25
and preeclampsia. Preeclampsia is a maternal condition that results in high blood pressure and
other serious signs and symptoms.
2.) Heart disorders. If left untreated, Graves' disease can lead to heart rhythm disorders, changes
in the structure and function of the heart muscles, and the inability of the heart to pump enough
blood to the body (heart failure).
3.) Thyroid storm. A rare but life-threatening complication of Graves' disease is thyroid storm,
also known as accelerated hyperthyroidism or thyrotoxic crisis. It's more likely when severe
hyperthyroidism is untreated or treated inadequately.The sudden and drastic increase in thyroid
hormones can produce many effects, including fever, sweating, vomiting, diarrhea, delirium,
severe weakness, seizures, irregular heartbeat, yellow skin and eyes (jaundice), severe low blood
pressure, and coma. Thyroid storm requires immediate emergency care.
4.) Brittle bones. Untreated hyperthyroidism also can lead to weak, brittle bones (osteoporosis).
The strength of your bones depends, in part, on the amount of calcium and other minerals they
contain. Too much thyroid hormone interferes with your body's ability to incorporate calcium
into your bones.
Reference: Information adapted from Mayoclinic.org website accessed on July 28, 2022 at
https://www.mayoclinic.org/diseases-conditions/graves-disease/symptoms-causes/syc-20356240#:~:text=If%20left
%20untreated%2C%20Graves'%20disease,Thyroid%20storm

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PROGNOSIS AND FOLLOW-UP

 Long-term remission of 56.5% (This is relatively higher in iodine-sufficient are, and

where ATD is offered to most patients, this reflects the importance of antithyroid drugs in
the treatment of Grave’s disease).
 Relapse is common during the first year after treatment
 Excellent prognosis after 4 years without relapse
 Smoking is a risk factor in developing grave’s ophthalmopathy, but smoking shows a
protective effect in this research which may warrant further research.

This is coming from follow-up that includes 829 patient years with a median follow-up of
2.8 years and maximal follow-up of 10 years.

Reference: Mohlin, et al. (2014) Long-term prognosis after medical treatment of Graves' disease in a
northern Swedish population 2000–2010. European Journal of Endocrinology. Accessed on: July 27, 2022
athttps://eje.bioscientifica.com/view/journals/eje/170/3/419.xml#:~:text=In%20total%2C%20follow
%2Dup%20includes,2A%20and%20Table%202).

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REFERENCES

 Main reference: Harrison’s internal medicine textbook 20th edition

 Robbin’s pathology textbook 10th edition
 Ross’ histology textbook 7th edition
 Boron’s physiology textbook 3rd edition
 Snell’s anatomy textbook 9th edition

Internet references:

 Mohlin, et al. (2014) Long-term prognosis after medical treatment of Graves' disease in a northern Swedish
population 2000–2010. European Journal of Endocrinology. Accessed on: July 27, 2022
athttps://eje.bioscientifica.com/view/journals/eje/170/3/419.xml#:~:text=In%20total%2C%20follow%2Dup
%20includes,2A%20and%20Table%202).
 Information adapted from Mayoclinic.org website accessed on July 28, 2022 at
https://www.mayoclinic.org/diseases-conditions/graves-disease/symptoms-causes/syc-20356240#:~:text=If
%20left%20untreated%2C%20Graves'%20disease,Thyroid%20storm
 Russo et.al (2013). Radioiodide induces apoptosis in human thyroid tissue in culture. National library of
medicine. Accessed on July 25, 2022 at https://pubmed.ncbi.nlm.nih.gov/23543460/
 Hadas et. al (2010). Pathophysiology of Graves' ophthalmopathy. National library of medicine. Accessed
on July 25, 2022 at https://pubmed.ncbi.nlm.nih.gov/20467359/#:~:text=Pathohistological
%20characteristics%20of%20Graves'%20ophthalmopathy,fat%20accumulation%20within%20the
%20orbit.
 Shah et.al (2015). Painful acute radiation thyroiditis induced by 131I treatment of Graves’ disease. National
library of medicine. Accessed on July 26, 2022 at
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4289741/
 Tapan & chahar (2015). Thyroid dermopathy—a diagnostic clue of hidden hyperthyroidism. National
library of medicine. Accessed on July 20, 2022 at
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4580047/

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