Grave’s Disease
(differentials)
By – Dr. Anshul
Moderator : Dr. Ashwani Sood

CLASSICAL SYMPTOMS OF

CAUSES
Excessive TSH
receptor stimulation
Autonomous thyroid
hormone secretion
Destruction of thyroid
follicles
Extra thyroidal source
of thyroid hormone
Graves’ disease Multi-nodular goiter Autoimmune
thyroiditis
Factitious thyroiditis
Chorionic
Gonadotropin
secreting tumors
Toxic adenoma Sub acute thyroiditis Struma ovarii
TSH secreting pituitary
adenoma
Acute thyroiditis
Drug induced
thyroiditis

Causes Frequency
Graves’ disease ~70%
Thyroiditis ~20%
Toxic multinodular goiter ~5%
Toxic adenoma ~5%
Others < 1%

Grave’s disease
•A/k/a Von Basedow’s disease
•Accounts for 60-80% of thyrotoxicosis.
•Incidence: 2% women, 1/10th in men
•Peak incidence between 20 and 40 years of age.
•Prevalence: depends on genetics and iodine consumption.
•Have diffuse goiter and thyrotoxicosis.

Etiopathogenesis of Graves’ Disease
• Genetic & Environmental factors play a role in triggering the
autoimmune response
•It is characterised by the presence of the serum
antibodies against
• TSH receptor (TSH-R)
• Thyroid peroxidase (TPO)
• Thyroglobulin (Tg)

GRAVES OPHTHALMOPATHY
GRAVES DERMOPATHY
GRAVES
ACROPATHY
Inflammatory disease caused
by infiltration of orbital
muscles leading to
accumulation of
glycosaminoglycans
Accumulation of
glycosaminoglycans in skin
leading to dermopathy in <5%
of GD patients
Clubbing that occurs in <1% of
GD patients
Diamond triad

stellwag's sign-infrequent blinking
Joffroy sign - absent crease in forehead on superior gaze

Numerous signs associated with Graves’ ophthalmopathy
von Graefe's sign lid lag in down gaze
Joffroy sign absent creases in the forehead on superior
gaze
Stellwag sign incomplete and infrequent blinking
Möbius sign poor convergence
Dalrymple's sign Upper lid retraction
Kocher's sign eye globe lag in up gaze
Vigouroux sign eyelid fullness
Ballet sign restriction of extra ocular muscles
Griffith sign Lower lid lag on down gaze
Jellink's sign Increased pigmentation on the lids

 Graves’ dermopathy (occurs in approximately 10% of
patients with Graves’ disease)
Myxedema (red, edematous skin) predominantly of
hands and lower extremities
Thyroid acropachy (soft tissue enlargement of fingers
with clubbing)
Alopecia or premature hair graying
Vitiligo

Thyroid dermopathy
Thyroid acropachy

Thyroiditis

Clinical presentation of thyroiditis
 In thyrotoxic phase of thyroiditis patient can present with
symptoms of hyperthyroidism.
 Additional symptoms found in sub acute thyroiditis
Neck pain radiating to ears
Sore throat
Malaise
Myalgia

Subacute Thyroiditis
Painful
Firm to hard on palpation
ESR >50 mm
Painless Thyroiditis
Look for h/o Post partum period
Look for h/o Autoimmune disease
Low to mod Anti TPO Ab
FACTITIOUS THYROTOXICOSIS
V/s
Via proper history
Serum Tg levels
RAIU
Fecal T4 ( i.c.o countering antibodies)

Toxic multinodular goiter (Plummer disease)
 Hyper functioning thyroid nodules that produce
thyroid hormones in excess.
 Most commonly seen in the elderly.
 Patients present with tachyarrhythmias, weight loss,
anxiety, and insomnia, atrial fibrillation or
tachycardia .
 Weakness and wasting of muscles are common, the
so-called apathetic or masked thyrotoxicosis.

Toxic adenoma
 Autonomously hyperfunctioning nodule that produces thyroid
hormones in excess.
 Pathogenesis
 Toxic adenomas are true follicular adenomas
 Somatic point mutations in the TSHR gene, commonly in the third
transmembrane loop.
 On ultrasound it appears as a single hypoechogenic nodule.
 Absence of infiltrative orbitopathy and myopathy, although
cardiovascular manifestations may occur.

Iodine-Induced Thyrotoxicosis
 JOD-BASEDOW phenomenon
It used to occur previously because of introduction
of iodinated salt in iodine deficient areas.
Now a days its mostly because of iodine contrast in
CT.

AIT 1 AIT 2
Underlying thyroid
disease
Yes No
Onset after starting
Amiodarone
~ 3 months ~ 30 months
Thyroid antibodies Present in Graves’ Usually absent
Vascularity High Low
RAIU Low/normal/high Suppressed
Treatment Antithyroid drugs Oral prednisone
Amiodarone
continuation
No Possible

Hamburger Thyrotoxicosis
• It is an unusual exogenous thyrotoxicosis occurred in mid
west US in 1985.
• The source was the inclusion of large quantities of bovine
thyroid in ground beef preparations.
• When slaughtering practices changed, this condition
disappeared.
• Such possibility although remote, should be considered in
case of epidemic exogenous thyrotoxicosis.

Miscellaneous
 Thyrotoxicosis Factitia - Occurs on thyroid medication but mostly
occurs when patients take thyroid hormone superstitiously .
 HCG secreting tumor - tumors like choriocarcinoma, trophoblastic
tumor and hydatidiform mole produce HCG which is weak TSH
agonist. S.TSH – suppressed and RAIU% - Elevated.
 Metastatic thyroid carcinoma rarely cause hyperthyroidism mostly
follicular carcinoma
 Struma ovarii - benign rare ovarian teratoma with functioning
thyroid tissue.

Hashitomotos Disease
 Usually presents as hypothyroidism
 But 5 % develop thyrotoxicosis K/A HASHITOXICOSIS
Considered as overlap of Grave’s and Hashimoto’s disease
RAIU is RAISED during this phase.
Scan shows diffuse increased uptake.
Treatment = Radioiodine.

Investigations - TFT
TSH level
Most sensitive test for hyperthyroidism.
Suppressed TSH level and elevated peripheral
hormone level confirms suspected
Thyrotoxicosis.
Free T₄ level
Total T₃ or free T₃ levels

Investigations

Other laboratory tests
 TSH receptor antibodies test
 High titers of TSH receptor antibodies support a diagnosis of
Graves’ disease.
 Third-generation TSH receptor antibody tests are 98% sensitive
and 99% specific for Graves’ disease.
 Thyroid peroxidase antibodies test
 High titers support thyroiditis as a cause of thyrotoxicosis.
 Thyroglobulin test
 Circulating thyroglobulin level is elevated in all forms of
thyroiditis and suppressed in factitious thyrotoxicosis.

USG neck
To measure the increased blood flow and
vascularity of the thyroid gland.
To look for increased size.
To look for nodules in the thyroid gland.

99mTc Thyroid Scan

RAIU
 For differential diagnosis of Thyrotoxicosis
Normal Range of % RAIU
TIME
1-6% 2 hours
6-18% 24 hours

Thank YOU

Hallmarks of the disease were palpitation, goiter, and exophthalmos, called the
Merseburg triad after the hometown of von Basedow (Merseburg,Germany).