THYROTOXICOSIS 1

1.     What is hyperthyroidism and thyrotoxicosis?
·        Hyperthyroidism specifically refers to the synthesis and secretion of excess thyroid hormone from the thyroid gland;
·        In contrast, thyrotoxicosis refers to any state of excess circulating thyroid hormone (and its clinical manifestations) regardless of its source.
·        Often the 2 words are used interchangeably.
 
2.     What is the most common cause of hyperthyroidism in children?
·        Graves disease.
 
3.     What is common age group?
·        Graves disease is more common in adults and in children 11-15 years is the common age group.
·        It is common in female.
 
4.     What are the other causes?

                Source: Nelson Textbook of Pediatrics 21e

5.     What is Graves Disease?
Graves disease is an autoimmune disorder that results in the production of thyrotropin (TSH) receptor–stimulating antibodies (TRSAbs) that bind and activate the G protein–coupled TSH receptor (TSHR ) to cause increased thyroid hormonogenesis and diffuse glandular growth.
 
6.     How hyperthyroidism difference in children and adults?
 

Source: Springer Pediatric Endocrine rounds

7.     What are the monosymptomatic presentations of childhood hyperthyroidism?
The monosymptomatic presentations of childhood hyperthyroidism include
·        Accelerated growth velocity,
·        Poor scholastic performance and
·        Attention deficit hyperkinetic disorder, and diffuse goiter.
 
In addition, children with thyrotoxicosis can rarely present with headache due to benign intracranial hypertension and polydypsia.
 
 

Source: Nelson Textbook of Pediatrics 21e

8.     What is the Pathophysiology of Graves disease?
Abnormal functioning of Treg cells and excessive activation of helper T cells lead to activation of B cells and T cells leading to autoimmune activation.
 
9.     Which HLA have higher risk?
HLA-B8 & HLA-DR3
 
10.     What are other conditions associated with Graves Disease?
·        Type 1 DM
·        Addison disease
·        Vitiligo
·        Psoriasis
·        Trisomy 21
·        Turner
·        Myasthenia gravis
·        Celiac disease
·        Rheumatoid arthritis
 
11.     What is apathetic thyrotoxicosis?
In the elderly, features of thyrotoxicosis may be subtle or masked, and patients may present mainly with fatigue and weight loss, a condition known as apathetic thyrotoxicosis.
 
12.     Increased appetite but weight loss is present.
 
 
13.     What is the time of tremor?
·        Fine tremor is present.
 
14.     What are the other common neurological manifestations in adults?
·        Hyperreflexia
·        Proximal myopathy without fasciculation but normal CPK enzyme.
·        Muscle wasting.
 
15.     Thyrotoxicosis is sometimes associated with a form of hypokalemic periodic
·        Paralysis.
 

16. What is the nature of heart rate in thyrotoxicosis?
·        Sinus tachycardia rarely SVT
·        High cardiac output leads to bounding pulse, widened pulse pressure, and an aortic systolic murmur.
 
17.  What is Means–Lerman scratch?
It is an uncommon type of heart murmur heard in patients  with hyperthyroidism.
It is a mid-systolic scratching sound best heard over the upper part of the sternum or second left intercostal space at the end of expiration.
It is due to rubbing of pericardium with pleura due to hyperdynamic circulation.
However it is not specific for hyperthyroidism and can be found in other hyperdynamic conditions like anemia,pregnancy etc.
 
18. Thyrotoxicosis is often associated with Atrial fibrillation in elderly which gets reverted when thyrotoxicosis is treated.
 
19.The skin is usually warm and moist, and the patient may complain
of sweating and heat intolerance, particularly during warm weather.
 
 

 
20.  What is the hair change in thyrotoxicosis ?
Hair texture may become fine, and a diffuse alopecia occurs in up to 40% of patients,persisting for months after restoration of euthyroidism.
 
 
21. Women frequently experience oligomenorrhea or amenorrhea; in men, there may be impaired sexual function and, rarely, gynecomastia.
 
22. How is the thyroid gland in Graves thyrotoxicosis?
·        Gland is increased 2-3 times the normal.
·        A bruit can be heard in the inferolateral margin due to the increased vascularity.
 
 
23.What is Grave’s Opthalmopathy ot thyroid associated Ophthalmopathy?
Specific signs in eye which is present in graves disease.
 
24.  In 75% of cases it occurs within 1 year before or after development of Graves disease but may occur several years as well.
 
25.Unilateral opthalmopathy can be found in 10% of cases.
 
26.What are the earliest features of Graves Opthalmopathy?
Gritting sensation, discomfort excessive watering from eyes.
 
27.  What is the Pathophysiology of Graves Opthalmopathy?
It is an autoimmune condition where the main culprit is TSH-R.
 
The TSH-R present in thyroid gland can also be found on fibroblasts and adipocytes.
 
As we know in Graves disease TSH-R ab is increased which acts on TSH-R in fibroblasts and adipocytes of eyes(orbit) as well leading to fibroblast proliferation, inflammation of surrounding muscles and connective tissue leading to swelling of retroocular area.
 
Deposition of glycosaminoglycans produced by fibroblasts draws water leading to futher increase in volume of muscles and retoorbital space causing various manifestations.
 

28. What is the cause of lid retraction and lid lag?
Sympathetic overactivity.      
 
29.What are the components of Graves’ congestive ophthalmopathy?
·        Edema of Lid and periorbital area &
·        Conjunctival edema and injection) &
·        Ophthalmoplegia
·        Optic nerve compression, resulting in optic nerve edema (papilledema), atrophy, and visual loss.
 
30.Which is the most commonly involved muscle in Graves ophthalmoplegia?
Medial and inferior recti.
 
31.What are the different signs of thyoid eye disease?
 
Dalrymple’s* (lid retraction [i.e., ‘‘thyroid stare’’])
Abnormal widening of the palpebral fissure. Normally, the margin of the upper lid covers 1 mm of the iris, but in lid retraction the upper eyelid is pulled backward, thus displaying a bit of sclera and giving the patient a typical scared/staring look. May result in corneal exposure with ulceration.
 

source:Nelson textbook of Pediatrics 21e

 Von Graefe’s* (lid lag)
 On downward gaze, the globe moves briskly while the upper lid lags behind, thus disclosing the sclera between the corneal limbus and lid).
 
 Rosenbach’s*.
 Fine tremor of the gently closed eyelids. Especially the upper.
 
Mobius’ 
Failure of ocular convergence following close accommodation at 5’’.
 
 Stellwag’s.
 Infrequent (and incomplete) blinking, plus proptosis.
 
Kocher’s
On upward gaze, the upper lid retracts briskly while the globe lags behind (counterpart to Von Graefe’s).
 
Joffroy’s.
 Absent wrinkling of the forehead when the eyeballs are rolled upward.
 
 Sainton’s
On upward gaze, the frontalis muscle contracts after the upper lid has completely retracted.
 
Jellinek’s E.
Brownish pigmentation of eyelids, especially the upper.
 
Topolansky’s.
Pericorneal congestion in patients with Graves’, with conjunctival edema (chemosis) and hyperemia.
 
32.What is the most serious manifestation?
Optic nerve compression causing peripheral visual field defect and permanent vision loss.
 
33.How can we evaluate a case of Graves opthalmopathy?
Various scoring systems are present.
1.     NO SPECS where
·        N= no sign amd symptoms.
·        O= only signs(lid lag,lid retraction) no symptoms
·        S = Soft tissue involvement (periorbital edema)
·        P = Proptosis (>22 mm)
·        E = Extraocular muscle involvement (diplopia)
·        C = Corneal involvement
·        S= Sight loss.
2.     EUGOGO developed by European group.
3.     Clinical activity scoring
In clinical activity score score more than 3 is s/o active ophthalmopathy.
 
34. How do you detect and assess the degree of proptosis?
The ‘‘poor man’s’’ test is to have the patient bend the head forward while you look down on the orbits and estimate the distance to the corneal surface.
 
Hertel exophthalmometer is used for accurate measurement.
 

35.What are the thyroid dermatopathy?
·        Warm,shiny skin with excess sweating
·        Pretibial myxedema.
 
36.What is pretibial myxedema?
·        It is a local infiltrative process, present in 4% of cases and usually involving the shins (pretibial myxedema). It manifests as dermal thickening, with presence of lymphocytes, various inflammatory cells, and lots of mucopolysaccharides.
 
·        It has an orange peel appearance.
 
·        The myxedema in hypothyroid is generalized but in Graves it is localized to pretibial region.
 
·        It is almost always present in moderate to severe Graves Ophthalmopathy.
 

Adapted from Physical Diagnosis secrets

37.Pretibial is not due to hyperthyroidism rather it is an infiltrative process with an autoimmune cause like ophthalmopthy. It occur in euthyroid patients as well.
 
38.  Hyaluronic acid is the m/c GAGs depositied in myxedema and opthalmopathy.
 
39. What is thyroid acropachy?
o   It is the clubbing along new periosteal bone formation that can occur in 5% of Graves’ patients.
 
o   Unlike the bony enlargement of pulmonary hypertrophic osteoarthropathy, thyroid periostitis occurs in the hands and feet, but not the long bones.
 
o   It also is typically asymptomatic and painless. The cause is long-acting thyroid-stimulating hormone (LATS). Hence, it is absent in other causes of thyrotoxicosis.
 

40.What are Plummer Nails?
When onycholysis is associated with Graves disease it is called   Plummers nail.
It is due to sympathetic overactivity.

Adapted from Oxfordmedicine online

 
41. A 10 years old male child was brought to your clinic with h/o of restlessness, hyperactivity and bulging of eyes. On examination you find the child have features of hyperthyroidism. In addition to that he has cafe-au-lait macules, bony swellings, signs of sexual precocity, acro-gigantism). What may be the probable diagnosis?
 
McCune Albright Syndrome.
 
42.How to approach a case of Graves disease?

Source: Harrison Textbook of Internal Medicine 20e

·        Measurement of TSH-R antibodies (discussed in http://www.a2zmedicalnote.in/2020/05/thyroid-series-part-3-tfts.html )
 
43.When is radionuclide study done?
·        When the diagnosis cannot be established by history, physical examination,and laboratory evaluation, RAI uptake can be measured.
 
·        ¹²³ I is the radionucleotide of choice for thyroid uptake and scintigraphy.
 
·        The RAI uptake (typically assessed at 4 and 24 hr after isotope administration) is elevated in Graves disease, whereas it is low in other causes of thyrotoxicosis like thyroiditis or exogenous thyroid hormone ingestion.
 
·        If scintigraphy is also performed, the increased RAI uptake in Graves disease is present diffusely throughout the gland, whereas focally increased uptake is observed inhyperfunctioning thyroid nodules.
 
 
44. What is thyrotoxicosis factitia?
When thyrotoxicosis is caused by exogenous thyroid hormone (thyrotoxicosisfactitia), levels of free T4 and TSH are the same as those seen in Graves disease but, in contrast to Graves disease, thyroid size is small, serum thyroglobulin is very low, and 123 I radioiodine uptake is suppressed.