Graves disease

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.

•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.

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

• 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)

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

Propylthiouracil

• 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)

Ans. All of the above

Ans. Retraction of the upper lid

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.

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

Ans. A: Proptosis

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).

Ans. A: More common in males

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.

Ans. C: Anti-TPO antibodies

Ans. is ‘d’ i.e., Inferior oblique

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