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
What is the most common cause of thyroid pain
granulomatous thyroiditis
Describe the diffuse sclerosing variant of papillary carcinoma
- unusual
- younger
- prominent papillary growth pattern intermixed with solid areas containing nests of squamous metaplasia
- extensive diffuse fibrosis throughout the thyroid gland, often associated with a prominent lymphocytic infiltrate, simulating hashimoto thyroiditis
- Lymph node metastases are present in ALMOST ALL cases
- lack BRAF but RET/PTC in half
Riedel thyroiditis is associated with fibrosis elsewhere such as where?
retroperitoneum
Death in anaplastic carcinoma is usually from what?
compromise of vital structures in the neck
Skin of thyrotoxic patient
- soft
- warm
- flushed
- due to increased blood flow and peripheral vasodilation
Exposure to ionizing radiation early in life leads to increased risk of what type of thyroid carcinoma
Papillary
Genetics of medullary thyroid carcinoma
Familial: MEN-2 . . . germiline RET mutations
Sporadic: RET in about half . . . RET/PTC NOT seen in medullary tho . . those would be papillary
Describe the thyroid gland grossly in Hashimoto?
- diffusely enlarged . . symmetric
- capsule intact: gland well demarcated from adjacent structures
- cut surface: pale, yello-tan, firm, somewhat nodular
Clue that lead you to POSSIBILITY of benign nodules
- multiple
- older
- females
- functional nodules that take up radioactive iodine (“hot” nodules
What is the most sensitive screening test for hypothyroidism?
should be what for primary causes?
- TSH level
- increased . . loss of feedback inhibition
Gross appearance of subacute lymphocytic thyroiditis
-except for possible mild symmetric enlargement . . . normal
in fine needle aspiration biopsy, what is characteristic of hashimoto
presence of Herthle cells in conjunction with heterogeneous population of lymphocytes
The thyroid gland follicle also contain a population of parafollicular cells, or C cells, which synthesize and secrete what?
calcitonin
what is the most common cause of hypothyroidism in iodine sufficient areas of the world
autoimmune hypothyroidism: Hashimoto thyroiditis
what are the subtypes of thyroid carcinoma and the % prevalence?
- Papillary (>85%)
- Follicular (5-15%)
- Anaplastic (undifferentiated) (<5%)
- medullary (5%)
radioactive iodine uptake in Graves?
toxic adenoma?
Thyroiditis?
- diffusely increased in whole gland
- increased uptake in solitary nodule
- decreased uptake
Treatment of papillary carcinoma
- total thyroidectomy
- Radioactive iodine or external radiation
- Chemo, hormone, and targeted therapy
What is the most useful single screening test for hyperthyroidism
-serum TSH concentration because its levels are decreased even at the earliest stages when disease is subclinical
Genetics of medullary carcinoma
- Familial: germline RET mutations
- RET also in 1/2 of sporadic
Enlargement of the thyroid, or goiter, is caused by impaired synthesis of thyroid hormonewhich is most often the result of what?
dietary iodine deficiency
Secondary (or central) hypothyroidism is caused by deficiencies of what?
TSH or, far less commonly, TRH . . . any of the causes of hypopituitarism
Describe the age and gender correlation of thyroid carcinomas
- W>M: early and middle adult years
- W=M: childhood and late adult life
What does a medullary carcinoma secrete that helps in diagnosis and can also be used to follow patients after surgery
calcitonin
if suspecting an thyroid adenoma and do a ultrasonagraphy and fine needle aspiration . . what is differential diagnosis
we just know it is a follicular neoplasm
- follicular adenoma
- follicular carcinoma
- follicular variant of papillary carcinoma
Do thyroglossal duct cysts give rise to cancer
rarely
What is the thyroid typically like in Hashimoto
enlarged or goitrous
age and gender for Granulomatous thyroiditis (De Quervain thyroiditis?
- 40-50
- W>M
Describe a thyroglossal duct cyst
- may not become evident until adulthood
- cysts can collect mucinous, clear secretions
- midline of the neck, anterior to the trachea
How do patients with thyroid storm present
- febrile
- tachycardia out of proportion to fever
- medical emergency
A low TSH value is usually confirmed with measurement of what?
free T4 which is predictably increased
describe the papillary microcarcinoma variant of papillary carcinoma
- an otherwise conventional papillary carcinoma less than 1 cm in size
- most commonly come to attention as incidental finding in patients undergoing surgery
Morphology of a thyroid adenoma
- made up of uniform appearing follicles that typically contain colloid
- follicular growth pattern is usually quite distinct from adjacent thyroid
- cells are uniform and bland . . look like surrounding follicular epithelial cells
- occasionally the cells have eosinophilic granular cytoplasm (oxyphil or Hurthle cell change) . .called Hurthle cell adenoma
Iodide, when given in LARGE doses to individuals with thyroid hyperfunction, also blocks the release of thyroid hormones by do what?
inhibiting the proteolysis of thyroglobulin . . . thyroid hormone is synthesized and incorporated into colloid but it is not released into blood
Presentation of sporadic medullary carcinoma?
- mass in the neck sometimes associated with dysphagia or hoarseness
- Some cases initially present with paraneoplastic syndrome caused by secretion of a hormone (diarrhea due to secretion of VIP)
- Hypocalcemia is NOT a prominent feature despite elevated calcitonin levels
- Carcinoembryonic antigen (CEA) is also secreted by many tumors . . useful tumor marker for disease burden and follow up
What is key in distinguishing follicular adenoma from follicular carcinoma
- Integrity of the capsule
- follicular adenoma: intact, well-formed capsule encircling the tumor
- follicular carcinoma: capsular and/or vascular invasion
Papillary carcinomas typically present as what?
asymptomatic thyroid nodules
-sometimes presents as a mass in a cervical lymph node
Virtually all long standing simple goiters convert into what?
multinodular goiters
What type of cells do medullary carcinomas come from?
What do all others come from
- C cells
- thyroid follicular epithelium
The dominant clinical features of multinodular goiters are those caused by what?
- mass effects
- cosmetic
- Airway obstruction and dysphagia
- compression of large vessels in neck and upper thorax (superior vena cava syndrome)
malignancy and multinodular goiters .
low. . <5%
- concern arises when they demonstrate sudden changes in size or symptoms (hoarseness)
patients with unexplained increases in body weight or hypercholesterolemia whould be assessed for what?
hypothyroidism
epidemiology of hypothyroidism
- prevalence increases with age
- W»>men . . 10x
What does Riedel thyroiditis mimic
hard and fixed thyroid mass clinically mimics thyroid carcinoma
describe the resolution of granulomatous thyroiditis
self limited
Treatment of Graves
- B-blocker: treats tachy, palpitations, tremulousness and anxiety
- Decrease thyroid hormone synthesis with: Thionamides (propylthiouracil), radioiodine ablation, thyroidectomy
- Surgery typically only those with large goiters that are compressing surrounding structures
Clinical course of anaplastic carcinoma
- usually present as a rapidly enlarging bulky neck mass . . . at presentation most hve spread beyond the thyroid capsule and/or metastasized to the lungs
- symptoms of dyspnea, dysphagia, hoarseness, and cough . . compression
In Graves Disease, the protrusion of the eyeball is associated with what?
- increased volume of retroorbital connective tissues and extraocular muscles
- Marked infiltration by mononuclear cells (T cells)
- inflammation with edema and swelling of extraocular muscles
- accumulation of extracellular matrix components, specifically hydrophilic glycosaminoglycans such as hyaluronic acid and chondroitin sulfate
- increased number of adipocytes
What % of cold nodules are malignant
10%
prognosis of papillary carcinoma
- excellent
- 10 year survival >95%
Describe the epithelium of a thyroglossal duct cyst?
Location dependent?
- subjacent to the lining epithelium, there is an intense lymphocytic infiltrate
- High in neck: stratified squamous epithelium resembling covering of posterior portion of tongue in the region of the foramen cecum
- low in neck: epithelium resembling the thyroidal acinar epithelium
Morphology of Follicular carcinoma
- Single nodules that may be well circumscribed or widely infiltrative
- sharply demarcated lesions are very difficult to distinguish from follicular adenomas . . may require examining the entire capsule microscopically to find invasion
- small follicles with colloid with uniform cells
- Hurthle cell (oncocytic) variant: cells with abundant granular, eosinophilic cytoplasm
- NUCLEI: lack the features typical of papillary carcinoma
What do thyroid follicular cells produce?
Stored?
Convert it to what?
thyroglobulin
- stored in follicles (colloid)
- T4 (thyroxine) and T3 (triiodothyronine)
How do you distinguish papillae in papillary carcinoma from those seen in areas of hyperplasia
the ones in papillary carcinoma are more complex and have a dense fibrovascular core
The definite diagnosis of adenomas can be made only after what?
careful histologic examination of the resected specimen
-so we need surgery
Hashimoto thyroiditis is associated with polymorphisms in what immune regulation associated genes?
These same genes make u susceptible to what?
- CTLA-4
- PTPN22
- type 1 diabetes
What cardiac morphological changes can be seen in thyrotoxicosis
- focal lymphocytic and eosinophilic infiltrates
- mild fibrosis
- myofibril fatty change
- increase in size and number of mitochondria
contast a hyperplastic nodule from a multinodular goiter and follicular neoplasms
a prominent capsule between a hyperplastic nodule and residual compressed thyroid parenchyma is NOT present
Abrupt onset of severe hyperthyroidism is know as what?
occurs most commonly in what pts?
acute elevation in what levels?
Encountered why?
- thyroid storm
- those with underlying Graves disease
- catecholamine levels
- infection, surgery, cessation of antithyroid meds, any form of stress
Presentation of familial medullary carcinoma
- Symptoms localized to the thyroid
- Endocrine neoplasms in other organs (adrenal or parathyroid)
- Medullary carcinomas in MEN-2B patients are more aggressive
a condition caused by a structural or functional derangement that interferes with the production of thyroid hormone
hypothyroidism
How does an isolated cervical nodal metastasis affect prognosis of papillary carcinoma?
Where else can it metastasize?
Does not have significant influence
-lung
Histology of subacute lymphocytic thyroiditis
- lymphocytic infiltration with large germinal centers within parenchyma
- patchy disruption and collapse of thyroid follicles
- UNLIKE HASHIMOTO: fibrosis and Hurthle cell metaplasia NOT prominent
What levels are increased in individuals with hypothyroidism of ANY ORIGIN
T4 levels
What is the most common clinically significant congenital anomaly of the thyroid
thyroglossal duct cyst
3 most common and clinically significant subtypes of thyroiditis?
- Hashimoto thyroiditis
- granulomatous (de Quervain thyroiditis)
- subacute lymphocytic thyroiditis
What is the most common cause of thyrotoxicosis
hyperfunction of thyroid gland . . hyperthyroidism
describe the radionuclide of follicular carcinomas
- typically “cold” nodules
- rarely hyperfunctional and appear “warm”
What is offered in MEN-2B patients with medullary carcinoma
prophylactic thyroidectomy
describe the onset symptoms in an adult with hypothyroidism
insidious and may take years to manifest clinical signs
are thyroid adenomas typically functional or nonfunctionaly
- Nonfunctional
- if functional then toxic adenomas
what things can cause sporadic goiters
- ingestion of substances that interfere with thyroid hormone synthesis
- Hereditary enzymatic defects that interfere with thyroid hormone synthesis: all autosomal recessive .. dyshormonogenetic goiter)
- mostly unkown
Most common cause of endogenous hyperhyroidism
Graves Disease
Exophthalmus after treatment of thyrotoxicosis in Graves
may persist or progress
familial medullary carcinomas are associated with what syndromes
MEN 2A or 2B or without syndrome . . FMTC (familial medullary thyroid carcinoma)
Diagnosis of papillary carcinoma
- Radionuclide scan: cold nodules
- Fine needle aspiration cytology: nuclear features
What refers to thyrotoxicosis occurring in older adults, in whom advanced age and various co-morbidities may blunt the features of thyroid hormone excess that typically bring younger patients to attention
apathetic hyperthyroidism
epidemiology of hashimoto thyroiditis
- most prevalent b/t 45 and 65
- 10-20x more common in women
- can occur in children
The severity of mental retardation in cretinism seems to be related to what?
the time at which thyroid deficiency occurs in utero
Clinical course of diffuse nontoxic goiter
- majority are euthyroid . . although TSH elevated
- symptoms of mass effect
genes involved in rare genetic defects in thyroid development
- PAX8
- FOXE1
- TSH receptor mutation
What is the most common form of thyroid cancer
papillary carcinoma
hypothyroidism that develops in infancy or early childhood
cretinism
Skeletal system symptoms of thyrotoxicosis
- thyroid hormone stimulates bone resorption (osteoporosis and risk of fracture)
- increase porosity of cortical bone
- reduces volume of trabecular bone
- atrophy of skeletal muscle, with fatty infiltration and focal interstitial lymphocytic infiltrates
Describe how autoimmunity plays a role in Graves ophthalmopathy?
- orbital preadipocyte fibroblasts, which express the TSH receptor, appear to stimulate the autoimmune reaction
- activated CD4+ helper T cells secrete cytokines that stimulate fibroblast proliferation and synthesis of extracellular matrix proteins
Pathogenesis of Graves disease
-production of autoantibodies against multiple thyroid proteins, most importantly TSH receptor
The 3 most common causes of thyrotoxicosis are associated with hyperfunction of the gland and include what?
- diffuse hyperplasia of the thyroid associated with Graves disease (85%)
- Hyperfunctional multinodular goiter
- hyperfunctional thyroid adenoma
Iatrogenic hypothyroidism can be caused by what
surgical or radiation induced ablation
a vestige of the tubular development of the thyroid gland
thyroglossal duct cyst
Goiters can broadly be divided into what two types
- diffuse nontoxic
- multinodular
Thyroid hormones regulate the trancription of several sarcolemmal genes, such as what, so lowered expression results in decreased cardiac output
- calcium ATPases
- b-adrengergic receptors
In rare, cases of pituitary-associated (secondary) hyperthyroidism, TSH levels are either normal or raised. . . Give thyrotropin-releasing hormone (TRH stimulation test) . . what excludes secondary hyperthyroidism?
a normal rise in TSH after administration of TRH
A disease process resembling painless thyroiditis that can occur during the postpartum period in up to 5% of women?
postpartum thyroiditis
prognosis of follicular carcinomas depends on what?
extent of invasion and stage at presentation
A palpably discrete swelling within otherwise apparently normal thyroid gland
solitary thyroid nodule
many follicular adenoma present as what?
unilateral painless masses
-larger masses may produce symptoms like difficulty swallowing
Dietary iodine deficiency is linked with a higher freqyency of what type of thyroid carcinoma
follicular
What does cassava contain that is goitrogenic
thiocyanate that inhibits iodide transport within the thyroid
What do T4 and T3 bind to in circulation
circulating plasma proteins such as thyroxine-binding globulin and transthyretin
In contrast to papillary carcinomas, follicular carcinomas are associated with acquired mutations that activate what?
- RAS or
- PI-3K/AKT arm
- Loss of function in PTEN
The degree of thyroid enlargement in a goiter is proportionate to what?
the level andduration of thyroid hormone deficiency
What are the 2 phases in the evolution of diffuse nontoxic goiters
- hyperplastic phase
- phase of colloid involution
Autoimmune hypothyroidism can occur in isolation or in conjunction with what?
autoimmune polyendocrine syndrome (APS) types 1 and 2
What are the circulating autoantibodies in Hashimoto thyroiditis?
- antimicrosomal
- antithyroid peroxidase
- antithyroglobulin
describe what hashitoxicosis is
hashimoto patient that the HYPOthyroidism is preceded by transient thyrotoxicosis caused by disruption of thyroid follicles leading to release of thyroid hormones
- T3 and T4 elevated
- TSH diminished
- radioactive uptake is decreased
The presence of this genetic alteration in papillary carcinoma correlates with adverse prognostic factors like metastatic disease and extrathyroidal extension
BRAF mutation
The diagnosis of thyrotoxicosis in individuals with apathetic hyperthyroidism is often made during laboratory work up for what?
- unexplained weight loss
- worsening cardiovascular disease
about 70% of medullary carcinomas are ______.
The other 30% are ______
- sporadic
- familial
the TSH is not increased in persons with hypothyroidism due to what?
primary hypothalamic or pituitary disease
what produce the most extreme thyroid enlargements and are more frequently mistaken for neoplasms than any other form of thyroid disease
multinodular goiter
undifferentiated tumors of the thyroid follicular epithelium
-anaplastic carcinoma
Adenomas of the thyroid are typically what?
discrete, solitary masses, derived from follicular epithelium, and hence they are also known as follicular adenomas
Once the diagnosis of thyrotoxicosis has been confirmed by a combo of TSH assays and free thyroid hormone levels, what can help determine the etiology?
measurement of radioactive iodine uptake by the thyroid gland
rare disorder characterized by extensive fibrosis involving the thyroid and contiguous neck structures?
Riedel thyroiditis
age for anaplastic carcinoma
mean of 65
ages for medullary carcinoma
- with MEN 2A and 2B: younger
- sporadic and familial medullary carcinoma: 40s and 50s
Primary hypothyroidism account for vast majority of cases and may be accompanied by what
Goiter
Subacute Lymphocytic (painless) Thyroiditis usually comes to attention because of what?
- Mild HYPERthyroidism and/or
- goitrous enlargement
age for papillary carcinoma
-peaks at 25-50 years . .can occur at any age tho
in Hashimoto, induction of thyroid autoimmunity is accompanied by what?
-depletion of thyroid epithelial cells by apoptosis and replacement of the thyroid parenchyma by MONONUCLEAR cell infiltration and fibrosis
follicular adenomas present as what?
slowly growing painless nodules
individuals with Hashimoto are at increased risk of developing what other autoimmune diseases?
- Type 1 diabetes
- autoimmune adrenalitis
- SLE
- Myasthenia gravis
- Sjogren syndrome
Some individuals with thyrotoxicosis develop reversible left ventricular dysfunction and “low-output” heart failure, so called, what?
thyrotoxic or hyperthyroid cardiomyopathy
What are the follicles of the thyroid lined by?
filled with?
cuboidal to low columnar epithelium
-PAS-positive thryroglobulin
histology of Granulomatous thyroiditis
- varies and can be patchy
- Early: Neutrophilic microabscesses in damaged follicles
- Later: aggregates of lymphocytes, macrophages, and plasma cells associated with damaged follicles
- MUTLINUCLEATE GIANT cells around colloid
- fibrosis may replace the foci of injury
- Different histologic stages are sometimes found in the same gland, suggesting waves of destruction over a period of time
what are goitrogenic foods
-Cruciferous veggies: cabbage, cauliflower, Brussels sprouts, turnips, cassava
Age for follicular carcinomas
older than papillary: 40-60
Histologically, Myxedema results in accumulation of matrix substances, such as glycosaminoglycans and hyaluronic acid, in skin, subcutaneous tissue, and a number of visceral sites. This results in what symptoms?
- nonpitting edema
- broadening and coarsening of facial features
- enlargement of tongue
- deepening of voice
prognosis of follicular adenoma
do not recur or metastasize and have excellent prognosis
Describe the levels of T3 and 4 and TSH after hashitoxicosis is over and hypothyroidism starts
- T3 and T4 fall
- TSH increases
Describe the spread of follicular carcinomas
- Don’t typically invade lymphatics
- Vascular dissemination is common . . metastasize to bone, lungs, liver, etc
Explain how anaplastic carcinomas arise
- de novo or by dedifferentiation of a well-differentiated papillary or follicular carcinoma
- 1/4 have past history of a well-differentiated thyroid carcinoma
- 1/4 have a well-differentiated tumor in the resected specimen
the function of the thyroid gland can be inhibited by a variety of chemical agents, collectively referred to as what?
TSH levels?
what happens to the gland?
goitrogens
- TSH increases
- hyperplastic enlargement of gland
What are the 3 immunologic mechanisms that may contribute to thyroid cell death in Hashimoto?
- CD8+ cytotoxic T cell-mediated cell death
- Cytokine-mediated cell death: CD4+–>IFN-gamma—>recruits macrophages
- antithyroid antibodies followed by antibody dependent cell mediated cytotoxicity
epidemiology of subacute lymphocytic thyroiditis
- can at any age
- most common: middle ages women
