Pathology of the Thyroid Gland Flashcards
Describe how goiters develop, generally.
The function of the thyroid gland can be inhibited by a variety of chemical agents, collectively referred to as goitrogens (no, seriously). Because they suppress T3/T4 synthesis, the level of TSH increases, and subsequent hyperplastic enlargement of the gland (goiter) follows.
What is the effect of Iodide when given to individuals with HYPERfunction of the thyroid.
Inhibits the proteolysis of thyroglobulin, thus preventing the release of T3/T4. Thyroid hormone is produced and incorporated into colloid, but never released into the blood.
Calcitonin is secreted by what cells in the thyroid gland?
What does it do?
Parafollicular cells. Decreases plasma levels of Ca2+ by promoting absorption of Ca2+ by the skeletal system and inhibiting resorption of bone by osteoclasts.
List the 3 most common causes of thyrotoxicosis (hypermetabolic state caused by elevated circulating levels of T3/T4)
1) Diffuse hyperplasia of the thyroid gland associated with Graves Disease (~85% of cases)
2) Hyperfunctional multinodular goiter
3) Hyperfunctional thyroid adenoma
Quickly describe the multi system changes that are clinically relevant in hyperthyroidism.
Skin is soft, warm, and flushed b/c of incr. blood flow & peripheral vasodilation.
Head intolerance.
Sweating.
Weight loss.
Elevated cardiac contractility and CO.
Tachycardia, palpitations, and cardiomegaly.
Arrhythmias.
Tremor, hyperactivity, emotional lability, anxiety, inability to concentrate, insomnia.
Proximal muscle weakness, decreased muscle mass.
GI hypermotility, diarrhea, malabsorption.
Wide, staring gaze and lid lag due to symp. overstim. of the sup. tarsal muscle.
Protruding eyes in Graves due to excess loose conn. tissue in posterior orbit.
Loss of bone mass (osteoporosis).
Generalized lymphoid hyperplasia & lymphadenopathy in pts with Graves.
Thyroid storm (medical emergency) in pts with Graves due to abrupt cessation of antithyroid meds, infxn, surgery, stress.
Describe the diagnosis of hyperthyroidism.
A Dx of hyperthyroidism is made using both clinical and lab findings. The measurement of serum [TSH] is the most useful single screening test because its levels are decreased even at the earliest stages. Free T4 will be predictably increased and is used to confirm. Once the Dx of thyrotoxicosis has been confirmed by the aforementioned methods, measurement of radioactive iodine uptake by the thyroid gland can help determine the etiology. For example, there may be diffusely incr. uptake by the whole gland (Graves), incr. uptake in a solitary nodule (toxic adenoma), or decr. uptake (thyroiditis).
What is the most common cause of congenital hypothyroidism?
Endemic iodine deficiency in the diet.
What is the most common cause of hypothyroidism in iodine-sufficient areas of the world?
Autoimmune hypothyroidism. The vast majority due to Hashimoto thyroiditis- circulating auto-Abs including anti-microsomal, antithyroid peroxidase, and antithyroglobulin. Thyroid is typically enlarged.
Describe the origins of the word Cretinism.
Describe its clinical features.
The term cretin was derived from a French word meaning “Christian” or “Christ-like,” and was applied to these unfortunates because they were considered to be so mentally retarded as to be incapable of sinning. (You will never forget that)
Clinical features:
Impaired development of the skeletal system and CNS, manifested by severe mental retardation, short stature, coarse facial features, protruding tongue, umbilical hernia.
Describe myxedema.
Myxedema is applied to hypothyroidism developing in the older child or adult. 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. It is marked by a slowing of physical and mental activity.
Pts are frequently cold intolerant, listless, and overweight.
Measurement of serum TSH level is the most sensitive screening test for this disorder. TSH levels will be increased.
List the 3 most common and clinically significant subtypes of thyroiditis.
1) Hashimoto thyroiditis
2) Granulomatous (de Quervain) thyroiditis
3) subacute lymphocytic thyroiditis
What is Hasimoto thyroiditis?
An autoimmune disease that results in destruction of the thyroid gland and gradual and progressive thyroid failure.
Most common cause of HYPOthyroidism in iodine-sufficient parts of the world.
Initially you will see HYPERthyroidism, then function drops as disease progresses
THIS IS THE ONLY HYPOTHYROID THYROIDITIS
Caused by a breakdown in self-tolerance to thyroid autoantigens. Presence of circulating autoantibodies against thyroglobulin and thyroid peroxidase.
Inciting events have not been elucidated, but possibilities include abnormalities of regulatory T cells (Tregs), or exposure of normally sequestered thyroid antigens.
Genetics: polymorphisms of CTLA4 and PTPN22, both coding for regulators of T-cell responses. Also associated with HLA-DR3 & HLA-DR5
Describe the histologic manifestations of Hashimoto thyroiditis.
Induction of thyroid autoimmunity is accompanied by a progressive depletion of thyroid epithelial cells by apoptosis and replacement of the thyroid epithelial cells by mononuclear cell infiltrates and fibrosis. You will see well developed germinal centers. The thyroid follicles are atrophic and are lined in many areas by epithelial cells distinguished by the presence of abundant eosinophilic, granular cytoplasm, termed Hurthle cells.
What mediates Hashimoto thyroiditis on a cellular level?
:: CD8+ mediated cell death.
:: Cytokine-mediated cell death- activation of CD4+ T cells leads to the production of inflammatory cytokines such as IFN-gamma in the thyroid gland, with resultant recruitment and activation of MPGs and damage to follicles.
:: A less likely mechanism involves binding of antithyroid abs followed by ab-dependent cell mediated cytotoxicity.
What is subacute Lymphocytic (painless) Thyroiditis?
Describe its histological features.
Comes to clinical attention because of mild HYPERthyroidism, goitrous enlargement of the gland, or both. As many as a third of those affected eventually progress to overt HYPOthyroidism over a 10-yr period.
Abs against thyroid peroxidase.
MOST ARE HYPERTHYROID
With the exception of possible mild symmetric enlargement, the thyroid appears grossly normal. Microscopic examination reveals lymphocytic infiltration with large germinal centers within the thyroid parenchyma and patchy disruption and collapse of thyroid follicles. Unlike Hashimoto thyroiditis, fibrosis & Hurthle cell metaplasia are not prominent.
What is granulomatous thyroiditis (De Quervain thyroiditis)?
Describe its histological features.
Most common cause of thyroid PAIN. Believed to be triggered by a viral infection. Majority of pts have a Hx of URTI just before the onset of thyroiditis. One model suggests that it results from a viral infxn that leads to exposure to a viral or thyroid antigen secondary to virus-induced host cell damage. This antigen stimulates CD8+ cells, which then damage thyroid follicular cells. Since it is NOT autoimmune, the process is limited.
The gland may be unilaterally or bilaterally enlarged and firm. Histologically, early in the early inflammatory phase, scattered follicles may be disrupted and replaced by neutrophils forming microabscesses. Later, more characteristic features appear in the form of aggregates of lymphocytes, activated macrophages, and plasma cells associated with collapsed and damaged thyroid follicles. Multinucleate giant cells enclose naked pools or fragments of colloid, hence the designation granulomatous thyroiditis. In later stages of the disease a chronic inflammatory infltrate and fibrosis may replace the foci of injury.
Pts have high serum T3/T4 and low serum TSH.
Radioactive iodine uptake is DIMINISHED.
Pt usually recovers fully in 6-8 wks.
