L9: Thyrotoxicosis Flashcards
Anatomy of Thyroid Gland
Histology of Thyroid Gland
Synthesis of thyroid Hormones
Forms of thyroid hormone
Thyroid hormones circulate in 2 forms:
- Protein bound, mainly thyroxin binding globulin ( TBG ): > 99%
- Free part ( active part ) : less than 1 %
Hypothalamic-Pituitary-Thyroid Axis
Actions of Thyroid Hormones
Def of Thyrotoxicosis
A clinical state that results from any condition leading to high thyroid hormone action in tissues. Irrespective of the source.
Def of Hyperthyroidism
Form of thyrotoxicosis caused by high synthesis and
secretion of thyroid hormone by the thyroid gland.
Characters of Subclinical
hyperthyroidism/thyrotoxicosis
- Biochemically as the presence of low thyroid-
stimulating hormone (TSH) and normal free thyroxine
(FT4) and free triiodothyronine (FT3) concentrations. - Patients can be asymptomatic or symptoms of thyrotoxicosis may be present.
Characters of Overt primary
thyrotoxicosis
- Refers to suppressed TSH with high levels of FT4, FT3, or both.
- Patients can be asymptomatic or more commonly present with symptoms of hyperthyroidism.
Def of Thyrotoxic crisis
(thyroid storm)
- a life-threatening, acute, and rapid collapse of homeostasis, developing as a result of undiagnosed or inadequately treated thyrotoxicosis and involving altered mental status that may progress to coma, cardiac and multiorgan failure, shock, and death.
Etiology of Thyrotoxicosis
Def of Grave’s Disease
The most common causes of Thyrotoxicosis
raves’ disease, followed by toxic multinodular goiter and toxic adenoma.
Incidence of Grave’s Disease
- it is the most common cause of hyperthyroidism & occurs at all ages but especially in women of reproductive age
- Peak incidence 20-40 years.
- Female to male incidence 5-8 :1
Pathogenesis of Grave’s Disease
Abs in Grave’s Disease
Immune Mechanisms in Grave’s Disease
Include:
- molecular mimicry and thyroid-cell expression of human leukocyte antigen (HLA) class II molecules (notably HLA-DR).
Who is suseptible to Grave’s Disease?
Female sex and genetic susceptibility
(cluster in families)
What are possible ppt factors for Grave’s Disease?
Infection
Stress- Smoking
Pregnancy
Iodine and iodine-containing drugs.
Mechanism of autoimmunity in Grave’s Disease
The pathophysiology of GO & pretibial myxedema involves
involves the synergism of insulin-like growth factor 1 receptor (IGF1R) with TSHR autoantibodies, causing retro orbital tissue expansion and inflammation.
CP of Subclinical Thyrotoxicosis/Hyperthyroidism
CP of Long-Standing Subclinical Thyrotoxicosis/Hyperthyroidism
Aspects of CP of Overt thyrotoxicosis
Refer to summary
General Symptoms
- CP of TTx
Refer to notes …
Neuropsychiatryic Symptoms
- CP of TTx
MSK Symptoms
- CP of TTx
CVS Symptoms
- CP of TTx
Resp Symptoms
- CP of TTx
GIT Symptoms
- CP of TTx
Reproductive Symptoms
- CP of TTx
Renal Symptoms
- CP of TTx
Dermatologic Symptoms
- CP of TTx
Eye Symptoms
- CP of TTx
Metabolic Symptoms
- CP of TTx
Bone Symptoms
- CP of TTx
Neck Abnormalities
- CP of TTx
Autommune Diseases associated with GD
Lab Dx of Graves Disease
- Thyroid Function Tests
- Thyroid-stimulating antibody (TSab)
- Other lab tests
Thyroid Function Tests in Graves Disease
T3 Toxicosis
T3 level only may be ↑ in some cases (T3 toxicosis)
Subclinical hyperthyroidism
low serum TSH concentrations (<0.4 mU/L) but normal serum free T4, and T3
TSAB in Graves Disease
- Also known as thyroid-stimulating immunoglobulin (TSI), or TSH-receptor antibody (TRAb)
- Positive test is diagnostic and specific for Graves’ disease.
Significance of TGB
Serum thyroglobulin TG levels are useful only for excluding thyrotoxicosis caused by exogenous thyroid hormone excess, in which case serum TG is low
Other Lab tests of Graves Disease
Rad investigations for Graves Disease
- RAIU
- Thyroid scan (scintigraphy)
- Ultrasonography
- Orbital CT or magnetic resonance imaging (MRI)
- Neck CT
RAIU in Graves Disease
Measures the percentage of function of the thyroid gland.
- A high (typical of GD or toxic nodule or nodules)
- A low uptake suggests inflammation or destruction of the thyroid gland (such as in thyroiditis)
Thyroid Scan in Graves Disease
US in Graves Disease
- of the thyroid gland with assessment of thyroid blood flow also useful to characterize palpable nodules
- Normoechogenic and diffuse large glands, may be enlarged LNs.
- Color flow Doppler shows high blood flow
Orbital CT or magnetic resonance imaging (MRI)
- Graves Disease
- In patients with Graves’ orbitopathy —> an increased volume of extraocular muscles and/or retro bulbar connective tissue
Neck CT in Graves Disease
only for selected suspicious cases.
Cytology in Graves Disease
Used to classify thyroid nodules as malignant (thyroid cancer), suspicious, or nonmalignant in order to determine indications for surgery.
DDx of Graves Disease
TTT of Graves Disease
A. Medical ( Antithyroid drugs and others )
B. Thyroidectomy
C. Radiotherapy
D. Management of thyrotoxicosis in pregnancy
E. Treatment of complications
Members of Anti-thyroid Drugs
Methimazole, carbimazole and propylthiouracil (PTU)
MOA of Anti-thyroid Drugs
These drugs inhibit the formation of thyroid hormones.
Propylthiouracil also inhibits conversion of T4 to T3
Drug of Choice in GD
Methimazole
Dose of Methimazole in GD
⇒ The dose depends on the severity of thyrotoxicosis and varies between 2.5 and 40 mg/day orally.
⇒ Thyroid function tests should be monitored closely and Methimazole tapered to a maintenance dose aiming to achieve euthyroidism.
⇒ In severe hyperthyroidism use up to 60 mg/d orally in 2 to 3 divided doses, and in impending Thyrotoxic crisis, up to 120 mg/d orally or IV (in hospitalized patients).
Monitoring of Methimazole
Thyroid function tests should be monitored closely and Methimazole tapered to a maintenance dose aiming to achieve euthyroidism.
DOC in GD in pregnancy
propylthiouracil (PTU) is used (in the first trimester)
Check up in GD
Indications of Anti-Thyroid Drugs
1) Mild disease and small goiter because they have high chance of remission
2) Elderly or other comorbidities increasing surgical risk.
3) Limited life expectancy
4) Previous operation or irradiation to the neck
CI of Anti-Thyroid Drugs
- Huge and retro-sternal goiter.
- Suspicion of malignancy.
SE of Anti-Thyroid Drugs
what are adjuvant medical therapy in GD?
B-Blockers
Indicatins of adjuvant medical therapy in GD
- All thyroid patients with resting heart rate >90/min.
- Elderly patients with symptomatic thyrotoxicosis.
Classes of adjuvant medical therapy in GD
- Non selective (propranolol in divided doses) Controls both cardiac and psychomotor manifestations.
- Selective B blockers: atenolol 25 to 50 mg daily, once : Control cardiac arrhythmias resulting from hyperthyroidism
what are Other adjuvant medical therapy in GD?
- iodine, glucocorticoid, cholestyramine, lithium, and Rituximab.
uses of other adjuvant medical therapy in GD
May benefit in patients with severe hyperthyroidism or who are allergic to thionamides.
Surgery of Choice in GD
Near-total or total thyroidectomy is the procedure of choice
Indications of Surgery in GD
Failure of response to anti-thyroid drugs.
Severe adverse reactions to anti-thyroid drugs.
Patient refuses radioactive iodine treatment.
Huge goiter which cause pressure symptoms.
Suspected malignancy in thyroid gland.
POC for Surgery in GD
Anti-thyroid drugs to reduce hyperfunction.
β-blockers to control pulse rate below 80/min.
Potassium iodide may be given for 2 weeks before surgery. It reduce intraoperative blood loss.
Complications of Surgery in GD
- Early bleeding, hematoma.
- Laryngeal nerve palsy occurs in 1%.
- Transient hypocalcaemia occurs in up to 10% but with Permanent hypoparathyroidism in less than 1%.
- Recurrent hyperthyroidism
- Hypothyroidism occurs in about 10% of patients within 1 year, and this percentage increases with time.
- Complications of general anesthesia.
Characters of RAI in GD
⇒ Suitable for most patients with Graves’ disease.
⇒ It is effective, safe, and does not require hospitalization.
⇒ Given orally in a single dose in a capsule or liquid form.
⇒ Very few side effects as no other tissue absorb RAI.
Precautions before RAI in GD
Patients with severe hyperthyroidism, elderly patients or patients with underlying heart disease should be pretreated with anti-thyroid drugs and β- blockers to achieve a euthyroid state prior to radio-active iodine.
Indications of RAI in GD
- ↑ Surgical risk due to associated comorbidities.
- Previous operation or irradiation to the neck.
- Contraindication for use of anti-thyroid drugs.
- Recurrence after surgery.
Disadvantages of RAI in GD
- Permanent hypothyroidism
- Rarely radiation thyroiditis
- Worsening or development of Graves opthalmopathy
- Patient must take radiation precautions for several days after treatment, avoiding contact with young children and pregnant women.
CI of RAI in GD
Pregnancy and lactation.
Children
Associated severe opthalmopathy
Radioactive TTT of TTx during Preganncy
Absolutely contraindicated (teratogenic)
TTT of HF
Complications of GD
bed rest, salt restriction, digitalis & diuretics.
Medical TTT of TTx during Preganncy
Surgery in TTx during Preganncy
- Indicated in women who cannot tolerate side effects of anti-thyroid drugs.
- Surgery can be performed (preferably in the second trimester).
TTT of Dermopathy
Complications of GD
- Milder cases do not require ttt, for other cases therapy with topical steroids applied under an occlusive plastic dressing film for 3-10 weeks
has been helpful.
TTT of Bone Disease due to hyperthyroidism
Complications of GD
- Treat hyperthyroidism, give adequate amounts of calcium and vitamin D in diets, typically 1000 to 1200 mg of calcium (total of diet and supplement) and 600 to 800 international units of vitamin D., Only those with highest risk for fracture could benefit from
bisphosphonate therapy
what is thyrotoxic Crisis?
- Thyrotoxic crisis is an acute life-threatening exacerbation of thyrotoxicosis in patients who have undiagnosed or inadequately treated thyrotoxicosis and superimposed precipitant factors
- A rare, life-threatening, hypermetabolic condition of severe clinical manifestations of thyrotoxicosis.
Physiology of thyrotoxic Crisis
Caused by excessive release of thyroid hormones
what percipitates thyrotoxic Crisis?
CP of thyrotoxic Crisis
TTT of thyrotoxic Crisis
Start treatment immediately, without waiting for confirmation by laboratory tests.
Continue treatment at an intensive care unit.
- Drugs
- Symptomatic
- TTT of Cause
Drugs in TTT of thyrotoxic Crisis
Symptomatic TTT of thyrotoxic Crisis
Antipyretics : ice bags and acetaminophen
IV fluids for dehydration
Digoxin and diuretics for AF& HF
Nasogastric tube for bulbar palsy, nausea and vomiting
TTT of Cause of thyrotoxic Crisis
antibiotics for infection
what are other names of Thyroid eye disease (TED)?
Graves’s opthalmopathy or Graves’s
orbitopathy
Incidence of Thyroid eye disease (TED)
- It is the most common cause of unilateral and bilateral proptosis in adults.
- About 25 to 50% of Grave disease (GD) cases present with thyroid eye disease.
Pathology of Thyroid eye disease (TED)
- A chronic immunemediated inflammation of the orbit.
- There is an orbital inflammation or infiltration involving the soft tissues, proptosis, and ophthalmoplegia.
Etiology of Thyroid eye disease (TED)
Pathophysiology of Thyroid eye disease (TED)
CP of Thyroid eye disease (TED)
Symptoms of Thyroid eye disease (TED)
- The patient complains of gritty sensations, photophobia, lacrimation, dry eye, discomfort, and forward protrusion of the eye.
- In more advanced cases, patient may complain eye socket (orbital) pain, double vision, or blurred vision
Eye Signs of Thyroid eye disease (TED)
Dx of Thyroid eye disease (TED)
- Exophthalmometer
- Imaging
Exophthalmometer
Dx of Thyroid eye disease (TED)
Assess the degree of proptosis by
- Measurement of the distance between the lateral angle of the bony orbit and an imaginary line tangent to the most anterior part of the cornea.
- The upper limit of normal is 21 mm in males and 19 mm in females.
Imaging
Dx of Thyroid eye disease (TED)
Managment of Thyroid eye disease (TED)
Etiology of Toxic MNG
- It occurs more commonly in elderly individuals, especially those with a long-standing goiter.
- Caused by hyperplasia of thyroid follicular cells due to activating somatic mutations of the TSH receptor genes.
CP of Toxic MNG
Nodular thyroid enlargement.
Manifestations of thyrotoxicosis.
No opthalmopathy or dermopathy.
Thyroid Scan in Toxic MNG
Multiple areas of hyperactivity (hot areas)
Interspersed with hypoactive regions.
TTT of Toxic MNG
- Surgery or radioiodine can be used.
- If surgery is chosen, near-total or total thyroidectomy should be performed.
Etiology of Toxic adenoma
- Caused by a single hyper functioning follicular thyroid adenoma due to mutation in TSH receptor gene.
CP of Toxic adenoma
Solitary thyroid nodule.
Manifestations of thyrotoxicosis.
No opthalmopathy or dermopathy
Thyroid scan of Toxic adenoma
- Hyperactive (hot) area,
- the rest of the gland may be hypoactive.
TTT of Toxic adenoma
- Surgery or radioiodine can be used.
- If surgery is chosen, an ipsilateral thyroid lobectomy or isthmusectomy should be performed
Done
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