Thyroid pathology

Question 1

42-year-old female presents with increased sweating, pounding heart, and weight loss

Physical exam reveals slightly enlarged, nontender thyroid, with no nodules

Answer 1

hyperthyroidism

Question 2

Thyroid function testing

Answer 2

Serum TSH & T4

Ultrasound & radionucleotide uptake studies

Serum antibodies

Question 3

thyroid function testing- levels of TSH, T4, T3

Answer 3

euthyroid- all normal
hyperthyroid- TSH down, T4 up
hypothyroid- TSH up, T4 down

Question 4

hyperthyroidism and its 3 main causes

Answer 4

Thyrotoxicosis is a hypermetabolic state caused by elevated circulating levels of free T3 and T4

The three most common causes of thyrotoxicosis are associated with hyperfunction of the gland:

Diffuse hyperplasia of the thyroid associated with Graves disease (approximately 85% of cases)
Hyperfunctional multinodular goiter
Hyperfunctional thyroid adenoma

Question 5

The clinical manifestations of hyperthyroidism

Answer 5

are protean and include changes referable to the hypermetabolic state induced by excess thyroid hormone and to overactivity of the sympathetic nervous system (i.e., an increase in the β-adrenergic “tone”).

Excessive levels of thyroid hormone result in an increase in the basal metabolic rate.

skin- soft, warm, and flushed because of increased blood flow and peripheral vasodilation, adaptations that serve to increase heat loss.

Heat intolerance is common. Sweating is increased because of higher levels of calorigenesis. Heightened catabolic metabolism results in weight loss despite increased appetite.

**Cardiac manifestations -among the earliest and most consistent features. can have elevated cardiac contractility and cardiac output, in response to increased peripheral oxygen requirements.

Tachycardia, palpitations, and cardiomegaly are common.(–> arrhythmias, CHF)

Some - left ventricular dysfunction and “low-output” heart failure, so-called thyrotoxic or hyperthyroid cardiomyopathy.

Overactivity of the sympathetic nervous system

GI- hypermotility, diarrhea, malabsorption

Question 6

lid lag in thyrotoxicosis

Answer 6

Ocular changes often call attention to hyperthyroidism. A wide, staring gaze and lid lag are present because of sympathetic overstimulation of the superior tarsal muscle (also known as Müller’s muscle), which functions alongside the levator palpebrae superioris muscle to raise the upper eyelid. However, true thyroid ophthalmopathy associated with proptosis occurs only in Graves disease

Question 7

Thyroid storm

Answer 7

brupt onset of severe hyperthyroidism. This condition occurs most commonly in patients with underlying Graves disease and probably results from an acute elevation in catecholamine levels, as might be encountered during infection, surgery, cessation of antithyroid medication, or any form of stress.

Patients are often **febrile and present with tachycardia out of proportion to the fever. Thyroid storm is a medical emergency. A significant number of untreated patients die of cardiac arrhythmias.

Question 8

hyperthyroidism and the skeletal system

Answer 8

Thyroid hormone stimulates bone resorption, increasing porosity of cortical bone and reducing the volume of trabecular bone.
The net effect is osteoporosis and an increased risk of fractures in patients with chronic hyperthyroidism.

Question 9

hyperthyroid Treatment

Answer 9

can include β-blocker to control symptoms induced by increased adrenergic tone, a thionamide to block new hormone synthesis, an iodine solution to block the release of thyroid hormone, and agents that inhibit peripheral conversion of T4 to T3.

Radioiodine, which is incorporated into thyroid tissues, resulting in ablation of thyroid

Question 10

42-year-old female presents to clinic with weight gain, constipation, and feeling cold

On examination the thyroid gland is symmetric and diffusely enlarged

TSH up, T4 down

Answer 10

hypothyroidism

Question 11

causes of hypothyroidism

Answer 11

1- hashimoto thyroiditis (autoimmune)

genetic defects
thyroid hormone resistance syndrome
postablative
iodine deficiency
drugs (lithium, iodides, p-aminosalicylic acid)
congenital biosynthetic defect

Secondary (pituitary or hypothalamic failure)

Question 12

congenital hypothyroidism is most often the result of

Answer 12

endemic iodine deficiency in the diet

high altitude bigger risk (due to rain washing down iodine into the water…?…)

Question 13

Cretinism

Answer 13

refers to hypothyroidism that develops in infancy or early childhood

severe mental retardation, short stature, coarse facial features, a protruding tongue, and umbilical hernia.

depends on when the mom was low in thyroid; if before fetal thyroid dev’t, severe

Question 14

myxedema

Answer 14

hypothyroidism developing in the older child or adult.

manifestations vary with the age of onset of the deficiency. Older children show signs and symptoms intermediate between those of the cretin and those of the adult with hypothyroidism. In the adult the condition appears insidiously and may take years before arousing clinical suspicion.

Question 15

dx of hypothyroidism

Answer 15

increased TSH

serum TSH level is the most sensitive screening test for this disorder

Question 16

symptoms of myxedema

Answer 16

generalized fatigue, apathy, and mental sluggishness, which may mimic depression

listless, cold intolerant, and frequently overweight. Decreased sympathetic activity results in constipation and decreased sweating. The skin is cool and pale (reduced blood flow)

shortness of breath

Question 17

hypothyroidism and LDL levels

Answer 17

hypothyroidism promotes an atherogenic profile—an increase in total cholesterol and low-density lipoprotein (LDL) levels—that probably contributes to the increased cardiovascular mortality in this disease.

Question 18

histology of hypothyroidism

Answer 18

accumulation of matrix substances, such as glycosaminoglycans and hyaluronic acid, in skin, subcutaneous tissue, and a number of visceral sites. This –> nonpitting edema, a broadening and coarsening of facial features, enlargement of the tongue, and deepening of the voice.

Question 19

Thyroiditis

3 clinical subtypes

Answer 19

The three most common and clinically significant subtypes:

(1) Hashimoto thyroiditis
(2) Granulomatous (de Quervain) thyroiditis
(3) Subacute lymphocytic thyroiditis

Question 20

thyroiditis possible conditions

Answer 20

• conditions that result in acute illness with severe thyroid pain (e.g., infectious thyroiditis, subacute granulomatous thyroiditis)
  -disorders with relatively little inflammation and the illness is manifested primarily by thyroid dysfunction—
  A. subacute lymphocytic thyroiditis
  B. fibrous (Reidel) thyroiditis

Question 21

Hashimoto Thyroiditis

Answer 21

Hashimoto thyroiditis is an autoimmune disease that results in destruction of the thyroid gland and gradual and progressive thyroid failure

Hashimoto thyroiditis is caused by a breakdown in self-tolerance to thyroid autoantigens

Question 22

Clinical Course of Hashimoto’s thyroiditis

Answer 22

painless enlargement of the thyroid,
usually associated with some hypothyroidism
(middle-aged woman.)
enlargement: symmetric and diffuse, but in some cases it may be sufficiently localized to raise the suspicion of a neoplasm.

usually gradual onset, but sometimes preceded by transient thyrotoxicosis

increased risk of other autoimmune diseases and extranodal marginal zone B-cell lymphomas in the thyroid

Question 23

hashitoxicosis

Answer 23

transient thyrotoxicosis caused by disruption of thyroid follicles, leading to release of thyroid hormones. During this phase, free T4 and T3 levels are elevated, TSH is diminished, and radioactive iodine uptake is decreased. As hypothyroidism supervenes, T4 and T3 levels fall, accompanied by a compensatory increase in TSH.

Question 24

Subacute lymphocytic thyroiditis

Answer 24

which is also referred to as painless thyroiditis, usually comes to clinical attention because of mild hyperthyroidism, goitrous enlargement of the gland, or both.

most often seen in middle-aged adults and is more common in women.

Question 25

postpartum thyroiditi

Answer 25

A disease process resembling painless thyroiditis can occur during the postpartum period in up to 5% of women (postpartum thyroiditis). Painless and postpartum thyroiditides are variants of autoimmune thyroiditis.

Question 26

antithyroid peroxidase antibodies

Answer 26

Most of the patients with subacute lymphocytic thyroiditis have circulating antithyroid peroxidase antibodies or a family history of other autoimmune disorders. As many as a third of cases can evolve into overt hypothyroidism over time, and the thyroid histology may resemble Hashimoto thyroiditis.

anti-TPO also in Hashimoto’s!

Question 27

Hurthle cells

Answer 27

metaplasia in the thyroid

giant eosinophilic cells

Question 28

Clinical Course subacute lymphocytic thyroiditis

Answer 28

may present with a painless goiter, transient overt hyperthyroidism, or both. Some patients transition from hyperthyroidism to hypothyroidism before recovery.
* a third of affected individuals eventually progress to overt hypothyroidism over a 10-year period

Question 29

Granulomatous Thyroiditis

Answer 29

ages 40-50

more women

believed to be triggered by a viral infection. The majority of patients have a history of an upper respiratory infection just before the onset of thyroiditis. The disease has a seasonal incidence, with occurrences peaking in the summer, and clusters of cases have been reported in association with coxsackievirus, mumps, measles, adenovirus, and other viral infections.

Painful- most common cause of thyroid pain.

cytology: big blobs with lots of nuclei

Question 30

Clinical Course of granulomatous thyroiditis

Answer 30

painful
short-lived

Inflammation of the thyroid and hyperthyroidism are transient, usually diminishing in 2 to 6 weeks, even if the patient is not treated. Nearly all patients have high serum T4 and T3 levels and low serum TSH levels during this phase.

However, unlike in hyperthyroid states such as Graves disease, radioactive iodine uptake is diminished. After recovery, generally in 6 to 8 weeks, normal thyroid function returns.

Question 31

Graves Disease

Answer 31

most common cause of endogenous hyperthyroidism

Hyperthyroidism associated with diffuse enlargement of the gland

Infiltrative ophthalmopathy with resultant exophthalmos

Localized, infiltrative dermopathy, sometimes called pretibial myxedema, which is present in a minority of patients

women 10:1

autoantiodies against multiple thyroid proteins, most importantly the TSH receptor

Question 32

thyroid-stimulating immunoglobulin (TSI)

Answer 32

most common antibody subtype in graves (90%)

Question 33

Clinical Course of Graves’ disease

Answer 33

Diffuse enlargement of the thyroid is present in all cases.

The thyroid enlargement may be accompanied by increased flow of blood through the hyperactive gland, often producing an audible “bruit.”

Sympathetic overactivity produces a characteristic wide, staring gaze and lid lag.

The ophthalmopathy of Graves disease results in abnormal protrusion of the eyeball (exophthalmos). The extraocular muscles are often weak. The exophthalmos may persist or progress despite successful treatment of the thyrotoxicosis, sometimes resulting in corneal injury.

Question 34

pretibial myxedema

Answer 34

in Graves disease

The infiltrative dermopathy, or pretibial myxedema, is most common in the skin overlying the shins, where it presents as scaly thickening and induration. The basis of such localization is not clear, and it is present only in a minority of patients.

Question 35

Diagnosis of graves disease

Answer 35

Laboratory findings in Graves disease include elevated free T4 and T3 levels and depressed TSH levels.

Because of ongoing stimulation of the thyroid follicles by thyroid-stimulating immunoglobulins, radioiodine scans show a diffusely increased uptake of iodine.

Question 36

prognosis/ treatment of graves

Answer 36

is treated with β-blockers, which address symptoms related to the increased β-adrenergic tone (e.g., tachycardia, palpitations, tremulousness, and anxiety), and by measures aimed at decreasing thyroid hormone synthesis, such as the administration of thionamides (e.g., propylthiouracil), radioiodine ablation, and thyroidectomy.

Radioiodine, which is incorporated into thyroid tissues, resulting in ablation of thyroid function over a period of 6 to 18 weeks.

Surgery is used mostly in patients who have large goiters that are compressing surrounding structures.

Question 37

Graves key concepts

Answer 37

most common cause of endogenous hyperthyroidism.
Triad: thyrotoxicosis, opthalmopathy, dermopathy

autoimmune- activation of thyroid epithelial cells by autoantibodies to the TSH receptor that mimic TSH action

diffuse hypertrophy and hyperplasia of follicles and lymphoid infiltrates; glycosaminoglycan deposition and lympohid infiltrates are responsible for opthalmopathy and dermopathy

lab features: elevations in free T3 adn T4 and decreased serum TSH

Question 38

autoimmune thyroid diseases

Answer 38

Graves- TSHR autoantibodies = TSI

Hashiimoto- TPO autoantibodies, TPO-specific T cells, cytokines

Question 39

Riedel thyroiditis

Answer 39

rare disorder
extensive fibrosis involving the thyroid and contiguous neck structures.
a hard and fixed thyroid mass clinically simulates a thyroid carcinoma.

may be associated with fibrosis in other sites in the body- (retroperitoneum, e.g.)
appears to be another manifestation of a systemic autoimmune IgG4-related disease, which is associated with fibrosis and tissue infiltration by plasma cells producing IgG4

Question 40

key concepts: thyroiditis

Answer 40

hashimoto- most common cause of hypothyroidism where iodine is sufficient. autoimmune- destruction of thyroid parenchyma, hurthle cell change, mononuclear infiltrates with germinal centers and with or without fibrosis

subacute lymphocytic thyroiditis- often after pregnancy, painless, lymphocytic inflammation. also autoimmune

granulomatous (de quervain) thyroiditis- self-limited, secondary to viral infection, pain and granulomatous inflammation