Graves disease

Graves disease

Q. 1 A 30-year-old woman is found to have a low serum thyroxine level after being evaluated for fatigue. Five years ago she was treated for Graves’ disease with radioactive iodine. The diagnostic test of choice is

 A Serum TSH          


Serum T3


TRH stimulation test 


Radioactive iodine uptake

Q. 1

A 30-year-old woman is found to have a low serum thyroxine level after being evaluated for fatigue. Five years ago she was treated for Graves’ disease with radioactive iodine. The diagnostic test of choice is


Serum TSH          


Serum T3


TRH stimulation test 


Radioactive iodine uptake

Ans. A


TSH levels are always increased in patients with untreated hypothyroidism (from primary thyroid disease) and would be the test of choice in this patient. Serum T3 is not sensitive for hypothyroidism. The TRH stimulation test is used to assess pituitary reserve of thyroid-stimulating hormone. A decreased RAIU is of limited value because of the low value for the lower limit of normal. In goitrous hypothyroidism, the RAIU may even be increased.

Q. 2

Which of the following conditions is the most common complication of radioiodine treatment of Grave’s disease-


 Thyroid storm               


Sub acute thyroiditis


Thyroid cancer



Ans. D


•Radioactive iodine treatment destroys thyroid cells and reduces the mass of cell functioning tissue.

•Radioactive iodine is  generally used for adults over 40 years of age and contraindicated in pregnant and nursing mothers.

Disadvantages are-

1.Chances of developing thyroid insufficiency and permanent myxoedema.

2.Requires some time to control the disease.

3.Nodules may develop into thyroid during this therapy

4.Not very satisfactory in cases of nodular toxic goiter.

5.Very high incidence of hypothyroidism as the years passes by.

Advantages are-

1.Do not require a prolonged drug therapy or surgery.

2.Cheap in comparison to other available treatment modalities.

Q. 3

True statement about dysthyroid eye disease (grave’s opthalmopathy) is


Decreased power of divergence


Most common cause of U/L proptosis in


Extreme exopthalmos is usually seen in hypothyroidism


On looking upwards lower lid does not follow eye movements

Ans. C


C. i.e. Extreme exopthalmos is usually seen in hypothyroidism

A mild exopthalmos is associated with thyrotoxicosis and an extreme exopthalmos may be associated with any state of thyroid activity, but usually in hypothyroidism often after thyroidectomy.Q

Dysthyroid / Graves-Opthalmopathy or Endocrine / Malignant-Exopthalmos

•  Etiology

Clinical Features


Autoimmune in

General (Thyrotoxicosis)


•   GuanethidineQ may

which there is

•   SymptomsQ

•  Dalrympe’s Sign-

decrease lid


– Tiredness

Retraction of upper eye lid producing Staring

retraction caused by

mediated attack

–   Emotional lability

& Frightened appearanceQ

over.action of

on orbital

–    Heat intolerance

Mn-“D for Dar”

muller’s muscleQ


– Weight loss

•  Von Graefe’s Sign-

•   Systemic Steroids &



–    Excessive appetite

–   Palpitation

Lid lag i.e on looking downwardsQ (towards

Ground) upperlid follows tardily or not at all

Radiotherapy (if

steroids not

muscles being

•   SignsQ

Mn-“Graefe-Lid lag on looking Ground”

effective) 1000 rad


– Tachycardia (persist during

•   Stellwag’s Sign-

from each lateral



Infrequent blinking with deficient closure of

port for reducing

•  Pathology

– Hot, moist palms


orbital edema

Mononuclear cell

–   Agitation

Mn-“S for Still”

•   Artificial tears &


– Thyroid goiter & bruit

•  IVRibius Sign-


with presence of

– Myopathy of proximal

Decreased power of convergenceQ

tarsorrhaphy to



Mn- “M for On looking Medially”

prevent exposure


•   Stages of development of

•  Enroth’s Sign-



cardiac arrhythmias

Fullness of eylids d/1 puffy Edematous

•  Prismatic glasses for

hyluronic acid

– Tachycardia which persist



together with

during sleep

Mn- “E for Edematous lid”

•  Orbital

Interstial edema


•  Gifford’s Sign-


& inflamatory

–   Multiple extra systole

Difficulty in eversion of upper lid

When steroid & RT


–   Paroxysmal atrial

•  Exopthalmos (Proptosis)

have proved



•  Weakness of extraocular muscles particularly

ineffective two wall


– Paroxysmal atrial

elevators (inferior oblique)Q causing diplopia

(orbital floor &



•  Conjunctival injection over insertion of recti

medial wall


–   Persistent atrial fibrillation

• Increased intra ocular pressure



not responding to digoxin

• Superior limbic keratopathy

decompression is done

  • 28) Grade 4 Extraocular muscle involvement Q (limitation of movement & diplopia) Grade 5 Corneal involvement (exposure keratitis) Grade 6 Loss of Sight (d/t optic nerve involvement with disc pallor or papilloedema & visual field defect) ” v:shapes=”_x0000_s1026″>Graves opthalmopathy is most common cause of U/L or B/L proptosis in adults between age of 25-50 yearsQ
  • Werner Classification reflect severity of opthalmopathy and is well known  by acronym of NO SPECS.
  1. Grade 0 –      No signs or symptoms
  2. Grade 1 –      Only signs (lid retraction with or without lid lag Q & mild proptosis)
  3. Grade 2 –     Soft tissue involvement (chemosis, grit, lacrimation, photophobia, lid or conjuctival swelling)
  4. Grade 3        Proptosis Q (minimal28)
  5. Grade 4        Extraocular muscle involvement Q (limitation of movement & diplopia)
  6. Grade 5        Corneal involvement (exposure keratitis)
  7. Grade 6 Loss of Sight (d/t optic nerve involvement with disc pallor or papilloedema & visual field defect)

Q. 4 A pregnancy woman is diagnosed to suffering from Graves’ disease. The most appropriate therapy for her would be:

 A Radioiodine therapy


Total thyroidectomy


Carbimazole parenteral


Propylthiouracil oral

Ans. D


Answer is D (Propylthiouracil):

Propylthiouracil (PTU) is not associated with an increased risk of congenital malformations and is considered the drug of choice for treating hyperthyroidism is Pregnancy.

Hyperthyroidism in Pregnancy

  • Maternal Hyperthyroidism in Pregnancy is usually due to Grave’s Disease. TRAb crosses the placenta and if mother is thyrotoxic it must be assumed that the foetus is similarly affected
  • The treatment of choice for thyrotoxicosis in Pregnancy is therapy with safe Antithyroid Drugs
  • Thionamides (Carbimazole/Propylthiouracil) are equally effective in controlling Grave’s Hyperthyroidism in Pregnancy and are considered the drugs of choice.
  • Amongst Carbimazole (Methimazole) and Propylthiouracil, Propylthiouracil is typically the preferred agent (Traditional drug of choice)

Radioactive Iodine Therapy is contraindicated in pregnancy as it may destroy the fetal thyroid Thyroidectomy (Surgery) is rarely required during Pregnancy. When indicated preoperative treatment with antithyroid drugs and iodine is undertaken and surgery is performed during the second trimester


  • Effective in controlling Grave’s Hyperthyroidism in Pregnancy
  • Not associated with increased risk of congenital malformation

(Aplasia Cutis Congenita has not reported with the use of Propylthiouracil))

  • Considered the drug of choice for treatment of Hyperthyroidism in pregnancy
  • Considered the drug of choice for mothers during Breast feeding (Transferred to the milk one tenth as much as Carbimazole)
  • Effective in controlling Grave’s Hyperthyroidism in Pregnancy
  • Aplasia Cutis Congenita is a rare disorder reported in neonates of mothers who received Methimazole (Carbimazole) during pregnancy.

(Consensus: Insufficient data to establish a direct causal relationship)

  • Considered as an effective alternative where Propylthiouracil is not available or cannot be used for any reason
  • May be used in mothers during breast feeding at a low dose (Transferred to milk more than Propylthiouracil but usually does not adversely affect the infant’s thyroid function)

Q. 5 Ocular Graves disease is associated with:

 A Hyperthyroidism




Euthyroid state


All of the above

Ans. D


Ans. All of the above

Q. 6

Dalrymple’s sign of ocular Graves’ disease refers to:


Retraction of the upper lid


Lid lag




All of the above combinedly

Ans. A


Ans. Retraction of the upper lid

Q. 7

The most common ocular motility defect noted in ocular Graves’ disease is due to involvement of:


Inferior rectus


Medial rectus


Lateral rectus


Inferior oblique

Ans. A


Ans. Inferior rectus

The inflammation and edema of the extraocular muscles lead to gaze abnormalities. The inferior rectus muscle is the most commonly affected muscle and patient may experience vertical diplopia on upgaze and limitation of elevation of the eyes due to fibrosis of the muscle.

Q. 8

The most common lid sign associated with Grave’s ophthalmopathy is


Von Graefe’s sign


Dalrymple’s sign


Stellwag’s sign


Rosenbach’s sign

Ans. B


Ans. Dalrymple’s sign

  • A patient shows bilateral lid retraction (Dalrymple sign) with staring and frightened appearance of the eyes (Kocher sign) along with chemosis and proptosis typically seen in thyroid eye disease.

 The clinical signs of thyroid-related orbitopathy can be generally grouped into two independent manifestations.

  • Type 1 orbitopathy comprises of symmetric proptosis with symmetric eyelid retraction, minimal orbital inflammation, and minimal EOM inflammation or restrictive myopathy.
  • Type 2 orbitopathy comprises EOM myositis, restrictive myopathy, orbital inflammation and chemosis as in the figure shown. Compressive optic neuropathy is more commonly seen in type 2 orbitopathy.

 Clinical signs in TED:

  • Facial signs
  • Joffroy’s sign-absent creases in the forehead on superior gaze.           
  •  Eyelid signs
  •  Kocher’s sign-staring appearance
  • Vigouroux sign-eyelid fullness
  • Rosenbach’s sign-tremors of eyelids
  • Riesman’s sign-Bruit over the eyelids
  •  Upper eyelid signs
  • Von Graefe’s sign-lid lag on downgaze
  • Dalrymple’s sign-lid retraction
  • Stellwag’s sign-incomplete & infrequent blinking
  • Grove sign-resistance to pulling the retracted upper lid
  • Boston sign-jerky movements of the lid on downgaze
  • Gellineck’s sign-abnormal pigmentation of the upper lid
  • Gifford’s sign-difficulty in everting the upper lid
  •  Lower eyelid signs
  •  Enroth’s sign-edema of the lower lid
  •  Griffith’s sign-lid lag on upgaze
  •  Conjunctival signs
  • Goldzeiher’s sign-conjunctival injection
  •  Extraocular movement signs
  •  Moebius sign-unable to converge eyes
  • Ballet’s sign-restriction of one or more EOM
  • Jendrassik’s sign-paralysis of all EOM


Q. 9

Grave’s ophthalmopathy mostly presents as

September 2010






Reduced intraocular tension


Increased power of convergence

Ans. A


Ans. A: Proptosis

Graves’ ophthalmopathy (also known as thyroid eye disease (TED), dysthyroid/thyroid-associated orbitopathy (TAO), Graves’ orbitopathy) is an autoimmune inflammatory disorder affecting the orbit around the eye, characterized by upper eyelid retraction, swelling (edema), redness (erythema), conjunctivitis, reduce dpower convergence and bulging eyes (proptosis).

Q. 10 All are true for Grave’s disease except:   

March 2012


Commoner in males


Eye signs are frequent


Family history of autoimmune endocrine disorders may be present


Presence of thyroid stimulating antibodies

Ans. A


Ans: A i.e. Commoner in males

Grave’s disease

  • Graves’ disease usually occurs in younger women & is frequently associated with eye signs
  • 50% of the patients have a family history of autoimmune endocrine disease
  • Hyperplasia & hypertrophy of thyroid tissue is due to abnormal thyroid stimulating antibodies (TSH-RAbs).

Q. 11 All of the following are features of Grave’s disease except:           

September 2005

 A More common in males




Pretibial myxedema


Intolerance to heat

Ans. A


Ans. A: More common in males

Graves disease, a syndrome of primary thyrotoxicosis, is caused by circulating thyroid receptor autoantibodies (TRab/ TSH-RAbs).

The antibodies not only displace thyrotropin from the thyroid receptors but also mimic thyrotropin by activating the receptor to stimulate the synthesis and release T3 and T4.

Because autoantibody production is not linked to the normal pituitary negative feedback loop, thyroid gland function becomes autonomous, and serum T4 and T3 levels become abnormally high and lead to clinical thyrotoxicosis. Because hormone synthesis is accelerated and thyroid gland radioiodine uptake is elevated, radionuclide scans demonstrate a diffuse increase in iodine uptake by the gland.

Graves disease is closely associated with Hashimoto’s disease (chronic lymphocytic thyroiditis) in which thyrotoxic/ cytotoxic antithyroid antibodies attack the gland.

Thyrotoxicosis is eight times more common in females.

Major clinical signs include weight loss (often accompanied by a increased appetite), anxiety, intolerance to heat, fatigue, hair loss, weakness, hyperactivity, irritability, apathy, depression, polyuria, polydipsia, and sweating.

Additionally, patients may present with a variety of symptoms such as palpitations and arrhythmias (notably atrial fibrillation), shortness of breath (dyspnea), loss of libido, nausea, vomiting, and diarrhea.

Long term untreated hyperthyroidism can lead to osteoporosis

Neurological manifestations can include tremor, chorea, myopathy, and in some susceptible individuals (particularly of asian descent) periodic paralysis.

The goiter in primary thyrotoxicosis is diffuse and vascular; it may be large or small, firm or soft, and a thrill and a bruit may be present.

The onset is abrupt but remissions and exacerbations are not infrequent.

Hyperthyroidism is usually more severe than in secondary thyrotoxicosis but cardiac failure is rare.

Manifestations of thyrotoxicosis not due to hyperthyroidism per se, for example orbital proptosis, ophthalmoplegia and pretibial myxoedema, may occur in primary thyrotoxicosis.

Thyroid dermopathy/ pretibial myxoedema is characterized by thickening of the skin, usually in areas of trauma, by deposition of hyaluronic acid in the dermis and subcutis.

Q. 12 All of the following are true regarding Grave’s disease except:       

March 2008

 A Orbital proptosis


Presents as primary thyrotoxicosis


Anti-TPO antibodies


Pretibial myxoedema

Ans. C


Ans. C: Anti-TPO antibodies

Q. 13

Last ocular muscle to be involved in Grave’s disease‑


Inferior rectus


Lateral rectus


Superior rectus


Inferior oblique

Ans. D


Ans. is ‘d’ i.e., Inferior oblique

Order of involvement (Mnemonic : IM SLO(W)) :- Inferior rectus > medial rectus > superior rectus > Lateral rectus > obliques.

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