Thyroid: Hyperthyroidism Flashcards
Most common cause of thyrotoxicosis
Graves’ disease (60-80%)
Concordance for Graves’ disease in twins
20-30% in monozygotic twins
<5% in dizygotic twins
Is smoking a risk factor for Graves’ disease?
Smoking is a minor risk factor for Graves’ disease and a major risk factor for the development of ophthalmopathy.
What is the pathogenesis of Graves’ disease?
The hyperthyroidism of Graves’ disease is caused by thyroid-stimulating immunoglobulin (TSI) that are synthesized in the thyroid gland, as well as in bone marrow and lymph nodes.
What is the term that refers to thyrotoxicosis which occurs primarily in the elderly and which presents mainly as fatigue and weight loss.
Apathetic thyrotoxicosis
What are the most frequent symptoms of thyrotoxicosis?
Hyperactivity, irritability, dysphoria
What are the most frequent signs of thyrotoxicosis?
Tachycardia; atrial fibrillation in the elderly
Characteristic muscle weakness in thyrotoxicosis
Proximal myopathy
Most common cardiovascular manifestation of thyrotoxicosis
Sinus tachycardia
In thyrotoxicosis, where is the thrill or bruit best detected?
Inferolateral margins of the thyroid lobes
How is proptosis best detected?
By visualization of the sclera between the lower border of the iris and the lower eyelid, with the eyes in the primary position
Most serious manifestation of Graves’ ophthalmopathy
Compression of the optic nerve at the apex of the orbit, leading to papilledema; peripheral field defects; and if left untreated, permanent loss of vision
“NO SPECS” scoring system for ophthalmopathy
0 = No signs or symptoms 1 = Only signs (lid retraction or lag), no symptoms 2 = Soft tissue involvement (periorbital edema) 3 = Proptosis (>22 mm) 4 = Extraocular muscle involvement (diplopia) 5 = Corneal involvement 6 = Sight loss
Scoring system more preferable than NO SPECS for monitoring and treating Graves’ orbitopathy
European Group On Graves’ Orbitopathy (EUGOGO)
Most frequent site of thyroid dermopathy
Anterior and lateral aspects of the lower leg (“pretibial myxedema”)
Typical lesion of thyroid dermopathy
Noninflamed, indurated plaque with a deep pink or purple color and an “orange skin” appearance
Term used to denote a form of clubbing found in <1% of patients with Graves’ disease
Thyroid acropachy
TRUE OR FALSE: Thyroid acropachy is strongly associated with thyroid dermopathy, which is almost always develops with moderate or severe ophthalmopathy.
TRUE. An alternative cause of clubbing should be sought in a Graves’ patient without coincident skin and orbital involvement.
TRUE OR FALSE: A normal TSH doesn’t exclude Graves’ disease as a cause of diffuse goiter.
FALSE. A normal TSH excludes Graves’ disease as a cause of diffuse goiter.
What is the typical clinical course of Graves’ ophthalmopathy?
Ophthalmopathy typically worsens over the initial 3-6 months, followed by a plateau phase over the next 12-18 months, and then some spontaneous improvement, particularly in the soft tissue changes.
Mechanism of action of antithyroid drugs
1) Inhibit the function of TPO, reducing oxidation and organification of iodide
2) Also reduce thyroid antibody levels by mechanisms that remain unclear
Additional mechanism of action of propylthiouracil aside from TPO inhibition
Inhibits deiodination of T4 to T3
Half-life of antithyroid drugs
Propylthiouracil - 90 mins
Methimazole - 6 hours
3 indications for use of propylthiouracil (limited due to hepatotoxicity)
1) first trimester of pregnancy
2) thyroid storm
3) minor adverse reactions to methimazole
When to check TFTs after starting treatment for hyperthyroidism
4-6 weeks after starting treatment (most do not achieve euthyroidism until 6-8 weeks after treatment is initiated)
Dose titration of antithyroid drugs is based on ________ levels
Unbound T4 levels (TSH levels often remain suppressed for several months)
Duration until maximum remission rates are achieved in hyperthyroidism
12-18 months
Risk factors for relapse after treatment for hyperthyroidism is stopped
Younger patients
Males
Smokers
Patients with a history of allergy, severe hyperthyroidism, or large goiters
Major side effects of antithyroid drugs
Hepatitis (especially with propylthiouracil)
Cholestasis (especially with methimazole and carbimazole)
Vasculitis
Agranulocytosis (<1%)
Symptoms of possible agranulocytosis
Sore throat, fever, mouth ulcers (stop treatment pending an urgent CBC)
Dose requirement for 1) warfarin and 2) digoxin is ______ (increased/decreased) in the thyrotoxic state.
Warfarin - decreased doses are required
Digoxin - increased doses are required
How many days before RAI must carbimazole or methimazole be stopped, and when can they be restarted?
Carbimazole or methimazole must be stopped 2-3 days before radioiodine administration to achieve optimum iodine uptake, and can be restarted 3-7 days after radioiodine in those at risk of complications from worsening thyrotoxicosis.
After RAI, the patient must avoid close, prolonged contact with children and pregnant women for ___ days.
5-7 days
Hyperthyroidism can persistent for ___ months before radioiodine takes full effect.
2-3 months
Pregnancy and breastfeeding are absolute contraindications to radioiodine treatment, but patients can conceive safely ___ months after treatment.
6 months
TRUE OR FALSE: Radioiodine should generally be avoided in those with active moderate to severe eye disease.
TRUE
Target T4 levels in pregnant patients with Graves’ disease
Just above the pregnancy reference range
Congenital defects caused by methimazole/carbimazole
Aplasia cutis, choanal atresia, tracheoesophageal fistulae
Conversion of PTU to methimazole
Ratio of 15-20mg PTU to 1mg methimazole
What is the Wolff-Chaikoff effect
It is an autoregulatory phenomenon that occurs upon initial exposure to iodine, which inhibits iodine organification and release of thyroid hormones into the bloodstream
SSKI is given 1 hour after PTU because the delay allows the antithyroid drug to prevent the excess iodine from being incorporated into the new hormone
Initial treatment for severe ophthalmopathy, with optic nerve involvement or chemosis resulting in corneal damage
Pulse therapy with IV methylprednisolone
Most common cause of suppurative infection of the thyroid that leads to acute thyroiditis in children and young adults
Presence of a piriform sinus, a remnant of the 4th branchial pouch that connects the oropharynx with the thyroid
3 distinct phase of subacute thyroiditis
1) thyrotoxic phase
2) hypothyroid phase
3) recovery phase
Over about 6 months
TRUE OR FALSE: In subacute thyroiditis, there is a high uptake of radioactive iodine.
FALSE
Treatment of subacute thyroiditis
Large doses of aspirin and NSAIDs
If inadequate or if with marked local or systemic symptoms, glucocorticoids should be given
Factors that differentiate silent thyroiditis from subacute thyroiditis
In silent thyroiditis:
1) Goiter is painless
2) ESR is normal
3) TPO antibodies are present
4) Glucocorticoid treatment is not indicated
Characteristics of Riedel’s thyroiditis
Rare
Typically occurs in middle-aged women
Insidious, painless goiter with local symptoms due to compression of the esophagus, trachea, neck veins, or recurrent laryngeal nerves
Dense fibrosis disrupts normal gland architecture
Thyroid dysfunction is uncommon
Goiter is hard, non-tender, often asymmetric, and fixed, leading to suspicion of malignancy
Diagnosis requires OPEN biopsy
Treatment: Surgery
Tamoxifen may be beneficial
Most common hormone pattern in sick euthyroid syndrome / nonthyroidal illness
Low T3
Normal T4 and TSH
Pathophysiology of sick euthyroid syndrome
T4 conversion to T3 via peripheral 5’ (outer ring) deiodination is impaired, leading to increased reverse T3 (rT3)
- probably an adaptive response to limit catabolism in starved or ill patients
Pattern of thyroid hormone abnormalities in acute liver disease
Initial rise in total (but not unbound) T3 and T4 due to TBG release –> become subnormal with progression to liver failure
Pattern of thyroid hormone abnormalities in acutely ill psychiatric patients
Transient increase in total and unbound T4 levels, usually with a normal T3 level
Pattern of thyroid hormone abnormalities in HIV infection
Early stage: Elevated T3 and T4
Progression to AIDS: T3 levels fall, but TSH remains normal
Pattern of thyroid hormone abnormalities in renal disease
Low T3 Normal rT3 (due to an unknown factor that increases uptake of rT3 into the liver)
Treatment of sick euthyroid syndrome
Monitor TFTs without administering thyroid hormone, unless there is historic or clinical evidence suggestive of hypothyroidism
Amiodarone is structurally related to thyroid hormone and contains __% iodine by weight.
39%
Amiodarone is stored in adipose tissue, hence high iodine levels persist for >__ months after discontinuation of the drug.
> 6 months
What are the 3 effects of amiodarone on thyroid function?
1) Acute, transient suppression of thyroid function
2) Hypothyroidism in patients susceptible to the inhibitory effects of a high iodine load
3) Thyrotoxicosis that may be caused by either a Jod-Basedow effect from the iodine load, in the setting of MNG or incipient Graves’ disease, or a thyroiditis-like condition
Expected TFTs after initiation of amiodarone treatment
Transient decrease of T4 levels (reflecting the inhibitory effect of iodine on T4 release)
Increased T4, decreased T3, increased rT3, and transient TSH increase (escape from iodide-dependent suppression of the thyroid (Wolff-Chaikoff effect), and the inhibitory effects on deiodinase activity and thyroid hormone receptor action become predominant)
TSH levels normalize or are slightly suppressed within 1-3 months
Treatment of amiodarone-induced hypothyroidism
Levothyroxine can be used to normalize thyroid function
TSH levels should be monitored (because T4 levels are often increased)
Usually unnecessary to discontinue amiodarone
Types of amiodarone-induced thyrotoxicosis (AIT)
Type 1 AIT
- Associated with underlying thyroid abnormality (preclinical Graves’ disease or nodular goiter)
- Thyroid hormone synthesis becomes excessive as a result of increased iodine exposure (Jod-Basedow phenomenon)
- Increased thyroid gland vascularity
Type 2 AIT
- No intrinsic thyroid abnormalities
- The result of drug-induced lysosomal activation leading to destructive thyroiditis with histiocyte accumulation in the thyroid
- Decreased thyroid gland vascularity
Treatment of amiodarone-induced thyrotoxicosis (AIT)
Amiodarone should be stopped if possible
Type 1 AIT
- Potassium perchlorate (associated with agranulocytosis)
- High doses of antithyroid drugs are often ineffective
Type 2 AIT
- Glucocorticoids and lithium (block thyroid hormone release) have modest benefit
- Near-total thyroidectomy (may be the most effect long-term solution)
Most common clinically apparent cause of chronic thyroiditis
Hashimoto’s thyroiditis
How can you distinguish silent thyroiditis from subacute thyroiditis (since they have the same clinical course)?
Normal ESR and the presence of TPO antibodies (silent thyroiditis usually occurs in patients with underlying autoimmune thyroid disorder)
