Non-neoplastic Thyroid Diseases Flashcards
Where are the most common sites for ectopic thyroid tissue?
Base of the tongue
Pharynx/larynx
What secondary messenger system does thyroid hormone use?
Gs protein and AC/cAMP
Why is T4 found more in the blood, but is converted almost entirely to T3 inside cells?
T4 has a much longer half life and is more stable/harder to degrade
T3 however has a much higher activity when bound to THR’s and binds with 10x more affinity
Thyrotoxicosis
Also known as hyperthyroidism
- this is because the #1 cause is hyper function fo thyroid gland
Is a hyper metabolic state caused by increased circulating levels of free T3 and T4
- *3 most common causes of thyrotoxicosis**
1) Graves’ disease (85%)
2) hyperfunctioning multi nodular goiter
3) hyperfunctioning adenoma of thyroid gland
Common constitutional symptoms of hyperthyroidism
Soft warm and flushed skin w/ associated heat intolerance and excessive sweating
- caused by increased blood flow and peripheral vasodilation as well as increase BMR
Weight loss and increased appetite
- caused by increased sympathetic activity
Steatorrhea and DEAK deficency
- caused by hypermotility of GI tissues
Heart palpitations and tachycardia
- increased B1 adrenergic receptor activation in cardiac tissue as well as increased peripheral oxygen requirements
Proximal muscle weakness, tremors, anxiety
- caused by increased sympathetic
Ocular changes in hyperthyroidism
Causes a wide staring gaze and lid lag
- this is due to excessive sympathetic stimulation to the superior tarsal muscle (mullers muscle)
- this muscle works with levator palpabrae superioris to elevate eyelid
Thyroid storm
Caused by abrupt onset of severe hyperthyroidism
Most often seen in Graves’ disease and occurs due to acute elevation in catecholamines levels
Medical emergency since untreated = cardiac arrhythmias
Symptoms = all hyperthyroid symptoms except to the extreme
Apathetic hyperthyroidism
Thyrotoxicosis that occurs in older adults usually incidentally since the thyroid hormone effects are blunted
Usually only found with work up of unexplained weight loss or worsening CV disease
Lab values for hyperthyroidism
Low TSH is the most clinically relevant value
- NOT T3/T4 since these values can be deceiving
- however T4 is almost always increased when TSH is low (negative feedback)
Rare cases of 2nd or tertiary cause of hyperthyroidism = TSH may be normal or increased
After lab values, get a radioactive iodine uptake test
- increased uptake diffusely = Graves’ disease most likely
- increased up take localized = toxic adenoma
- decreased uptake = thyroiditis
Causes of primary hypothyroidism
Congenital
- most common congenital = thyroid dysgenesis or dyshormorgentic goiter (non functional goiter)
Iatrogenic
- caused by surgical or radiation damage or bad ADRs from meds
Autoimmune (most common)
Improper iodine dietary (most common underdeveloped only)
What are the two most common clinical manifestations of severe hypothyroidism?
Cretinism (at birth)
- more common in iodine Deficencies
- shows: intellectual disability, short stature, coarse facial features, protruding tongues, umbilical hernias and CNS abnormalities
- NOTE: mental disability is directly tied to time of onset of hypothyroidism (if mother has hypothyroidism before thyroid development = severe mental disability)
Myxedema (in adult hood)
- generalized fatigue, mental sluggishness and apathy (mimics depression)
- also shows decreased sweating, cold intolerance and constipation as well as decreased exercise capacity
- shows increases in total cholesterol and low density lipoprotein levels (LDL)
- in chronic stages = non pitting edema, enlargement of tongue, deepening of voice and coarse facial features (caused by accumulation of matrix substances in skin) n
Diagnosis of hypothyroidism
TSH levels will be elevated
- no feed back from T4 which is low
In secondary or tertiary however, TSH levels will be normal but T4 will still be low
3 most common causes of thyroiditis
1) hasimotos
2) granulomatous (De’Quervian)
3) subacute lymphocytic
Chronic lymphocytic hashimoto thyroiditis
Is the most common cause of hypothyroidism in areas where iodine is sufficient
Most prominent in women between ages 45-65
- can occur at any age and sex though
Pathogenesis: “antibody-dependent, cell mediated cytotoxicity
- autoimmune response with circulating autoantibodies that bring CD8Tcells to induce chronic fibrosis and infiltrates into thyroid parenchyma via
Genetics and hasimoto thyroidits
Heavily linked to genetics with 40% in monozygotic twins
Also 50% of siblings of infected kids also have anti-thyroid antibodies
Increased susceptibility = CTLA4 gene mutations
- normal gene codes for negative regulators of T-cell responses
Clinical features of hashimoto thyroiditis
Usually initially presents as mild transient and gradual hypothyroidism with a painless enlargement of thyroid gland
- enlargement is usually symmetric
Other diseases that hashimoto is related to
Almost always presents with other autoimmune conditions
Increased risk for B-cell non-Hodgkin lymphomas
Is believed to be tied in some way to increased risks of papillary carcinomas of the thyroid
Subacute granulomatous thyroiditis
De’Quervian
Much less common than hashimoto
More common in 30-50 aged women
- can be anyone though
- is believed to be initiated via a viral infection or inflammatory processes (NOT AUTOIMMUNE)*
- many patient’s have a PMH of URI’s shortly before onset
this process spontaneously resolves on its own
Histologically:
- shows disruption of thyroid follicles which initially have neutrophils built are replaced with macrophages and plasma cells over time
- also presents with granulomatosis giant cells via colloid reactions and mononuclear infiltrates
- gross anatomy shows firm enlarged thyroid
Clinical features of De’Quervian thyroiditis
Is often acute and initially characterized by neck pain (especially with swallowing) fever, malaise and enlargement of thyroid
Also shows transient hyperthyroidism initially and then with progression shows transient hypotension
Also leukocyte and ESR are elevated
Is self-limiting most of the time within 6-8 weeks
Subacute lymphocytic thyroidits
Painless/silent thyroiditis
Most often precedes pregnancy
- hence why also nicknamed “postpartum thyroiditis”
Is autoimmune etiology and most commonly affects middle-aged women
Always presents with PAINLESS neck masses and hyperthyroidism symptoms
- the thyroid for the most part is NOT enlarged
Is also self-limiting and takes a few months to return to normal
Riedel thyroiditis
Rare disorder that is a IgG4-related thyroiditis that causes extensive fibrosis of the thyroid and surrounding neck structures
Will simulate a thyroid neoplasm on palpation and often presents with hyperthyroidism first
Graves’ disease
MOST common cause of endogenous hyperthyroidism
- effects 3% of women in the entire US
Characterized by a triad of
1) thyrotoxicosis
2) infiltrative opthalmopathy with orbital edema and exophthalmos in 40% of patients
3) localized myxedema usually pretibial
Peaks around 20-40 years of age and much more common in women
Very genetic concordance rates in monxygotic twins = 60%
- HLA-DR3 antigens and CTLA-4 (inhibitory T-cell receptor) /PTPN22 (tyrosine phosphatase) genetic mutations all lead to increased
Gross Histology shows symmetrically enlarged thyroid gland with diffuse hypertrophy and hyperplasia of follicular cells
- capsule is still intact though
Microscopic histology shows small papillae in the follicular lumen and tall columnar follicular epithelial cells with a pale staining follicular lumen
- lymphoid infiltrates of primarily T cells is also present through the interstitum
Pathogenesis of Graves’ disease
Presence of thyroid stimulating immunoglobulin antibody (TSI)
- seen in 90% of patients
This antibody not only destroys circulating TSH, built also binds to TSH receptors and chronically activates them
- this produces hyperthyroidism without elevated T3/T4
Opthalmopathy and orbital edema seen in Graves’ disease is caused by the following:
1) marked infiltration of the retroribtal space by mononuclear cells (predominantly T-cells)
2) inflammatory edema and swelling of extraocular muscles
3) accumulation of extracellular matrix components (especially hyaluronic acid and chondroitin sulfate)
4) increased number of adipocytes
What autoimmune diseases are seen in high frequency with graves and hasimotos?
SLE
Pernicious anemia
Type 1 diabetes
Addison disease
Pathogenesis of dermopathy in Graves’ disease
Glycosaminoglycans and T-cell lymphocyte infiltration
Manifests as thickening and scaling fo the skin
- skin also may be slightly pigmented with orange papules
Lab values of Graves’ disease
Elevated serum T3/T4 With lowered TSH
If using radioactive iodine however, its uptake will be increased compared to normal, even with elevated T3/T4
Goiter
Enlargement of the thyroid
- mostly common form of all thyroid abnormalities
Diffuse and multi nodular goiters are most common subtypes and are a result of impaired synthesis of thyroid hormones
- most common underlying cause = iodide deficiency
Enlargement of the thyroid is caused by excess TSH being bound to thyroid which induces Hypertrophy of the thyroid
- if mild = goiter is enough to restore euthyroid
- if severe = goitrous hypothyroidism
Sporadic goiters
Less frequent than endemic (iodide induced) goiters
Are more common in females than males and is seen more in puberty/young adulthood
Caused by several conditions including:
- excessive ingestion of cabbage and cauliflower
- anything that blocks thyroid hormone synthesis
- enzyme defects
in most cases = not apparent
Multi Nodular goiters
Are caused by recurrent episodes or hyperplasia and involution of goiters
Results in long-standing goiters that are massive and ASYMMETRIC
Most commonly are known for causing mass effects
- airway obstruction
- dysphagia
- “superior vena cava syndrome”
If the goiter causes thryotoxicosis = Plummer syndrome
- DOENST show infiltration opthalmopathy
Need to surgically removes these usually
What are red flag signs for thyroid malignancies associated with goiters
Sudden abrupt enlargement or mass effect symptoms
- especially hoarseness
