Thyroid gland path Flashcards
a rare form of congenital hypothyroidism includes inborn errors of thyroid metabolism . . called what
dyshormonogenetic goiter
Genetic susceptibility to Graves is linked to polymorphisms in what genes
- CTLS4
- PTPN22
- HLA-DR3
Normally, T3 and T4 cross the placenta and are critical for what?
fetal brain development
Laboratory findings in Graves
- low TSH
- high free T4 and T3
- radioiodine scans show a diffusely increased uptake
Long laundry list of symptoms of Myxedema
- slowing of physical and mental activity
- initial: generalize fatigue, apathy, and mental sluggishness which may mimic depression
- speech and intellectual functions are slowed
- listless, cold intolerant, and frequently overweight
- decreased sympathetics: constipation and decreased sweating
- skin: cool and pale
- Heart: reduced CO so shortness of breath and decreased exercise capacity
- increase in total cholesterol and LDH . . increases cardiovascular mortality
Hashimoto is caused by what?
breakdown in self tolerance of thyroid autoantigens
clues that lead you to POSSIBILITY of neoplastic nodule
- solitary
- younger
- males
- history of radiation to head and neck
Describe gross appearance of a thyroid adenoma
solitary, spherical, encapsulated lesion that is demarcated from the surrounding thyroid parenchyma by a well define intact capsule . .. helps distinguish from multinodular goider
Binding of thyroid hormone to its nuclear thyroid hormone receptor results in the assembly of what
a multiprotein hormone-receptor complex on thyroid hormone response elevements (TREs) in target genes
Ocular changes in thyrotoxicosis
- Wide staring gaze and lid lag (sympathetic overstimulation of superior tarsal muscle) . . also known as Muller’s muscle
- True thyroid opthalmopathy associated with poptosis ONLY in Grave’s disease
therapies for anaplastic carcinomas
No effective therapies
What does calcitonin do?
promotes the absorption of calcium by the skeletal system and inhibits the resorption of bone by osteoclasts
What drugs can cause primary hypothyroidism
- Lithium
- iodines
- methimazole
- propylthiouracil
- p-aminosalicylic acid
explain the pathogenesis of Granulomatous thyroiditis
- believed to be from an immune response triggered by a viral infection
- Majority of pts have hx of URI just before onset
- Seasonal incidence: peaking in summer
epidemiolgy and stats about thyroid nodules
- 1-10% of US adults
- significantly higher in endemic goitrous regions
- W>M
- incidence increases throughout life
- overwhelming are benign
- <1% of solitary thyroid nodules are malignant . . and most of the cancers are indolent
neuroendocrine neoplasm derived from the parafollicular cells (C cells)
medullary carcinoma
If a multinodular goiter grows behind the sternum and clavicles what is it called
intrathoracic or plunging goiters
Maternal thryoid hormone deficiency later in pregnancy?
does not affect normal brain development
What is the unique translocation and fusion gene found in 1/3 to 1/2 of follicular carcinomas
(2;3): PAX8-PPARG fusion
describe the radinuclide scan for follicular adenoma
-nonfunctioning adenoma take up less radioactive iodine than the normal thyrod parenchyma: “COLD NODULES”
What manifestations are among the earliest and most consistent features of thyrotoxicosis
cardiac manifestations
- elevated contractility and output
- tachycardia, palpitations, and cardiomegaly are common
- Arrythmias, particularly Afib, occur frequently but more common in older patients
- congestive heart failure may develop
Where is cretinism found
- regions where dietary iodine deficiency is endemic
- Himalayas, inland China, Africa, Mountainous areas
What are some factors that affect prognosis of papillary carcinoma
- Age (less favorable for those > 40)
- Extrathyroidal extension
- Presence of distant metastases
Morphology of medullary carcinoma
- Sporadic: typically a solitary nodule
- familial: often bilateral with multiple nodules
- tumor positive for calcitonin by immunohistochemistry
- Familial medullary cancers: multicentric C CELL HYPERPLASIA in the surrounding thyroid parenchyma
- Acellular AMYLOID DEPOSITS derived from calcitonin polypeptides are present in the stroma in many cases
Clinical findings of Graves
- some associated with thyrotoxicosis
- unique to Graves: The triad
- increased blood flow through the hyperactive gland can produce an audible bruit
controversial link b/t Hashimoto disease and what thyroid cancer
papillary
hypothyroidism developing in the older child or adult
myxedema
Lymph system in Graves pts
generalized lymphoid hyperplasia and lymphadenopathy
therapy for hyperthyroidism and mechanism: B-blocker?
- Thionamide?
- iodine solution?
- Radioiodine?
- control symptoms induced by increased adrenergic tone
- block new hormone synthesis
- block release of thyroid hormone
- incorporated into thyroid tissues, resulting in ablation of thyroid function over period of 6-18 weeks
-Also can use agents that inhibit peripheral conversion of T4 to T3
T4 and T3 levels in granulomatous thyroiditis?
TSH?
radioactive iodine uptake?
- high
- low
- diminished . . unlike graves
Overactivity of the sympathetic nervous system in thyrotoxicosis causes what symptoms?
- Tremor
- hyperactivity
- emotional lability
- Anxiety
- inability to concentrate
- insomnia
- Proximal muscle weakness and decreased muscle mass are common (thyroid myopathy)
- hyperstimulation of the gut (DIARRHEA and malabsorption)
Where do you find endemic goiters
geographic areas where soil, water, and food supply contain low levels of iodine
Triad of clinical findings in Graves
- Hyperthyroidism associated with diffuse enlargement of the gland
- Infiltrative ophthalmopathy with resultant exophthalmos
- localized, infiltrative dermopathy, sometimes called pretibial myxedema (only in minority of patients)
If there is maternal thyroid deficiency before the development of what then mental retardation is severe
fetal thyroid gland
in children, dyshormonogenetic goiter, caused by a congenital biosynthetic defect, may induce what
cretinism
Painless and postpartum thyroiditides are variants of autoimmune thyroiditis so most patients have what?
- circulating antithyroid peroxidase
- or a family history of other autoimmune disorders
complete absence of thyroid parenchyma
thyroid agenesis
This is a hypermetabolic state caused by elevated circulating levels of free T3 and T4
thyrotoxicosis
If compensation of hormone deficiency isn’t enough in a goiter then what do you get
goitrous hypothyroidism
Primary hypothyroidism can be from what 3 general causes
- congenital
- autoimmune
- iatrogenic
With time, recurrent episodes of hyperplasia and involution combine to produce a more irregular enlargement of the thyroid, termed what?
multinodular goiter
Gross appearance of granulomatous thyroiditis
- unilateral or bilaterally enlarged
- firm with intact capsule but may be stuck to surrounding structures
Describe the somatic mutations in a “toxic” adenoma . . . this just means is functional
- mutations of TSH receptor signaling pathway
- gain of function most often in TSHR or GNAS
- causes follicular cells to secrete thyroid hormon independent of TSH stimulation (thyroid autonomy)
- leads to hyperthyroidism and “hot” nodule
epidemiology of Graves
- about 2% of US women
- women»_space;» men
- peak at 20-40 years
Hashimoto thyroiditis most often comes to clinical attention as what?
PAINLESS enlargement of the thyroid, usually associated with some degree of hypothyroidism in a middle aged woman
explain the epidemiology of multinodular goiters
Because they derive from simple goiter, they occur in both sporadic and endemic forms. same F:M ratio . . older individuals because they are a late complications
A significant number of untreated thyroid storm patients die of what?
cardiac arrhythmias
Can thyroglossal duct cysts become infected?
yes and may form abscess cavities
What are the disorders of thyrotoxicosis NOT associated with hyperthyroidism
- Granulomatous (de Quervain) thyroiditis (painful)
- Subacute lymphocytic thyroiditis (painless)
- Struma ovarii (ovarian teratoma with ectopic thyroid)
- Factitious thyrotoxicosis (exogenous thyroxine intake)
Morphology of papillary carcinoma
- solitary or multifocal
- can be well circumscribed, encapsulated or infiltrative
- usually has areas of fibrosis and calcification
- Nuclei (key for diagnosis): Large and overlapping. Finely dispersed chromatin, giving them an optially clear or empty appearance .. Ground glass or ORPHAN ANNIE EYE nuclei. Nuclear groove. invaginations of cytoplasm give appearance of intranuclear inclusion (“PSEUDO-INCLUSIONS)
- PSAMMOMA BODIES
radioiodine scan in a multinodular goiter
uneven iodine uptake including the occasional “hot” autonomous nodule
-from an admixture of hyperplastic and involuting nodules
What inhibits the oxidation of iodide and thus blocks the production of thyroid hormones and also inhibits the peripheral deiodination of circulating T4 into T3
propylthiouracil
The clinical manifestation of thyrotoxicosis are due to overactivity of what?
- sympathetics
- increase in B-adrenergic tone
Worldwide, congenital hypothyroidism is most often the result of what?
endemic iodine deficiency in the diet
what are the two subtypes of diffuse nontoxic (simple) goiters
endemic and sporadic
Treatment of follicular carcinoma?
- Total thyroidectromy followed by the radioactive iodine: can be used to identify metastases and to ablate them
- Also treated with thyroid hormone to suppress endogenous TSH levels: residual follicular carcinoma may respond to TSH stimulation
- serum thyroglobulin levels are used for monitoring tumor recurrence
Liver and thyrotoxicosis
-minimal liver enlargement due to fatty changes in hepatocytes
what % of the population is affected in endemic goiters
> 10%
describe the thyroid hormone state in most individuals with a goiter
euthyroid
epidemiology of sporadic (less frequent than endemic) goiter
- F»>M
- peaks a puberty of in young adult life
As many as a third of cases of subacute lymphocytic thyroiditis can evolve to what? and resemble what?
overt hypothyroidism
-thyroid histology may resemble Hashimoto
What provides the most definite information about the nature of a thyroid nodule
fine needle aspiration and surgical resection
Histology of Hashimoto
- mononuclear inflammatory infiltrate containing small lymphocytes, plasma cells, and well developed GERMINAL CENTERS
- Follicles: atrophic/lost . . lined by epithelial cells with abundant eosinophilic, granular cytoplasm termed HURTHLE CELLS . . metaplastic response
Clinical features of Cretinism
- impaired development of skeletal system and CNS
- severe mental retardation
- short stature
- coarse facial features
- protruding tongue
- umbilical hernia
More advanced local papillary carcinoma can present as what?
- hoarseness
- dysphagia
- cough
- dyspnea
Genetic alterations found in anaplastic carcinomas
- also RAS and PIK3-
- unique to anaplastic: inactivation of TP53 or activation of B-catenin
Dominant nodules in a multinodular goiter can present as what?
a “solitary thyroid nodule) mimicking a thyroid neoplasm
Riedel thyroiditis appears to be a manifestation of what disease
systemic autoimmune IgG4-related sclerosing disease
describe the enlargement of a diffuse nontoxic (simple) goiter
enlargement of the entire gland without producing nodularity
Genetic alterations in the three follicular cell-derived malignancies are in what pathway?
growth factor receptor signaling
Hashimotos . . increased risk for what cancer?
Extranodal marginal zone B cell lymphoma
What is the most common antibody found in graves disease
thyroid-stimulating immunoglobulin (TSI) . . . almost never observed in other autoimmune diseases of thyroid
Clinically, follicular adenomas can be difficult to distinguish from what?
dominant nodules of follicular hyperplasia or from the less common follicular carcinomas
What is helpful to facilitate the distinction of follicular hyperplasia of a mutlinodular goiter from a thyroid neoplasm?
fine needle aspiration
Describe the follicular variant of papillary thyroid carcinoma
- has characteristic nuclear features of papillary carcinoma
- follicular architecture
- can be encapsulated (favorable) or poorly circumscribed and infiltrative (more aggressive)
Genetic pathogenesis in papillary carcinomas
- RET (RET/PTC fusion) or NTRK1: (translocations or inversion)
- BRAF (point mutations): valine to glutamate change in codon 600
in the usual case of hashimoto, hypothyroidism develops how?
gradually
prognosis of anaplastic carcinoma
-highly aggressive . . mortality rate essentially 100%
where is the thyroid gland located
below and anterior to the larynx
in general, follicular adenomas are NOT forerunners to what?
carcinoma
What is it called when in a substantial minority of patients with a mutlinodular goiter have an autonomous nodule that may develop within a long standing goiter and produce hyperthyroidism
toxic multinodular goiter . . . PLUMMER SYNDROME . . . about 10% of multinodular goiters over a 10-year follow up
describe the inflammation and hyperthyroidism of granulomatous thyroiditis
- transient
- usually diminshing in 2-6 weeks even without treatment
- normal thyroid function after 6-8 weeks
What other things can a medullary carcinoma secrete
- serotonin
- ACTH
- VIP
What specific viruses are mentioned to be associated with granulomatous thyroiditis
- coxsackievirus
- mumps
- measles
- adenovirus
Morphology of anaplastic carcinoma
- Large pleomorphic GIANT cells, including occasional osteoclast-like multinucleate giant cells
- Spindle cells with a sarcomatous appearance
Describe the Tall cell variant of papillary thyroid carcionoma
- has tall columnar cells with intensely eosinophilic cytoplasm lining the papillary structures
- Older have worse prognosis
- BRAF mutation in most
- often also have RET/PTC translocations
Morphology in Graves
- symmetrically enlarged
- Diffuse hypertrophy and hyperplasia of thyroid follicular epithelial cells
- Follicular cells are tall and more crowded. Can even form small papillae that project into lumen. . . they LACK FIBROVASCULAR core )in contrast to papillary carcinoma)
- colloid is pale with SCALLOPED margins
- inflammatory infiltrates of lymphocytes and plasma cells . . germinal centers are common
unlike Reidel thyroiditis, descrive the fibrosis in Hashimoto
does NOT extend beyond the capsule of the gland