1
Q
Describe the development of the thyroid gland…
A
- derived from median endodermal thickening near the foramen cecum. It later descends into the neck and forms gland - parafollicular C cells are derived from the ultimobranchial body
2
Q
Congential abnormalities of Thyroid gland
A
- agenesis - lingual thyroid (problems with descent during development) - heterotopic thyroid tissue (pockets in neck) - thyroglossal duct cyst (neck cysts with thyroid tissue inside)
3
Q
T/F thyroid pathology is more common in females than males
A
True!
4
Q
A
Normal thyroid
5
Q
Nontoxic Goiter
Causes…
Tx?
A
- -enlargement that is not associated with functional, inflammatory, or neoplastic alterations
- neither hyperthyroid nor hypothyroid (T4, T3, TSH usually normal)
- Usually asymptomatic except for presence of neck mass or local pressure on adjacent structures
- Thyroid growth may be related to an exaggerated response to normal TSH levels
- Treatment includes thyroid hormone–decreases TSH (feedback inhibition on pituitary)
- Radioactive iodine or surgery for local compressive symptoms
6
Q
subtypes of non-toxic goiter
A
- Diffuse-more common in adolescence and during pregnancy
- Multinodular form more common > 50 years
- Both nontoxic and toxic multinodular goiter are much more common in females
- Many patients will progress to toxic multinodular goiter
7
Q
A
nodular thyroid
8
Q
A
nodular goiter histo
compressed normal gland
9
Q
Causes of Hypothyroidism
A
- defective synthesis of thyroid hormone with compensatory goiter (endemic)
- inadequate function due to decreased gland mass (surgery, inflammation, radiation therapy)
- inadequate TSH (pituitary), TRH (hypothalamus)
10
Q
Systemic effects of hypothyroidism
A
- *Skin** – myxedema (puffy appearance), capillary fragility, i.e. easy bruising
- *Nervous System** - lethargy, somnolence, confusion, paranoia, severe agitation (myxedema madness), sensory deficits, cerebellar ataxia. Mucinous accumulations in cerebellum and nerve fibers.
- *Cardiovascular** - cardiac output decrease, myxedema heart (dilated cardiomyopathy), peripheral vascular resistance increased
Gastrointestinal - decreased peristalsis with constipation, myxedema megacolon
Reproductive
females- anovulatory failure, menstrual cycle disturbances
males - erectile dysfunction and oligospermia
11
Q
Sx: 3 week old baby with apathy, lethargy, enlarged abdomen, decreased body temperature, refractory anemia, dilated heart, mental retardation (irreversible) and stunted growth
Dx?
Tx?
Causes?
Prognosis?
A
Dx? congenital hypothyroidism (cretinism)
Tx? prompt thyroid hormone replacement therapy
Causes? endemic (insufficient iodide in diet), sporadic, familial, secondary to thyroid dysgenesis
Prognosis? if not treated promptly, irreversible brain damage and dwarfism
12
Q
Causes of goitrous hypothyroidism…
A
- Enlargement of thyroid due to inadequate thyroid hormone production
- Dietary iodine deficiency (Antithyroid agents–lithium, phenylbutazone, p-aminosalicylic acid or Foods with goitrogens–Rutabagas, turnips, cassava)
- Iodide induced goiter–Excessive dietary iodide (seaweed, supplements)
- High dose iodine in pregnancy can produce goitrous infants
- Hereditary defects in thyroid hormone synthesis
13
Q
Causes of hyperthyroidism…
A
- may occur secondary to increased TSH production (rare)
- abnormal stimulation of thyroid (Graves)
- extrinsic production from ectopic thyroid tissue, i.e. struma ovarii (rare)
- Thyroiditis (early stages, thyroid follicles destroyed and excessive TH released into blood)
- -may or may not cause goiter
14
Q
Features of toxic multinodular goiter
A
- development of functional autonomy of a nodule(s) from a nontoxic goiter
- unresponsive to thyroid hormone administration
- Uptake of iodine may be diffuse or only within hyperfunctioning nodules. Other more normal follicles are suppressed.
- The clinical presentation may be similar to a toxic (functioning) adenoma (but adenoma is generally solitary)
- Hyperthyroidism not as severe as in Grave’s (no exophthalmos)
- T4, T3, only minimally elevated or normal
- Treatment: radioactive iodine after anti-thyroid therapy.
15
Q
Sx: nervousness, tremor, weakness, wt loss, heat intolerance, palpitations
PE: hyperthyroidism, diffuse goiter with bruits, exopthalmos, dermopathy
Tests: increased radioactive iodine uptake and elevated T3 and T4
Dx?
Causes?
Tx?
A
Dx: Grave’s disease
Cause: autoimmune–anti-TSH receptor stimulating antibodies
Tx:
- antithyroid medications
- radioactive iodine, along with corticosteroids and adrenergic
antagonists - exophthalmos does not resolve with treatment and may worsen
- thyroid failure may ensue
16
Q
A
Grave’s disease
-Diffusely hyperplastic thyroid
17
Q
A
Grave’s disease histo
- Papillary projections of epithelium into follicles with scalloped borders
- lymphoplasmacytic infiltrate (not shown)
18
Q
A
- treated graves disease
- Diffusely hyperplastic with numerous papillary projections and little colloid
19
Q
Toxic adenoma
A
- cause of hyperthyroidism
- hyperfunctioning, autonomous “hot” nodule
- infrequent cause of hyperthyroidism
- treated with radioactive iodine and/or surgery
20
Q
Hypersecretion of TSH
A
- cause of hyperthyroidism
- thyrotropin adenoma
- TSH-like substances secreted by trophoblastic tumors
21
Q
Dx?
Histo?
clinical features?
Tx?
A
Dx: hashimotos thyroiditis histo
histo: lymphoplasmacytic infiltrate, destruction and atrophy of follicles, Hurthle (Askanazy) cell metaplasia
Clinical features: gradual development goiter, hypothyroidism, elevated TSH, circulating antibodies
Tx: hormone replacement
22
Q
subacute thyroiditis
A
-painful
- DeQuervain, Granulomatous, or giant cell thyroiditis
- follows URI, caused by viral infection (influenza, adenovirus, echo, coxsackie, possibly mumps)
- granulomatous inflammation (not lymphoplasmocytic)
- transient hyperthyroidism with destruction of follicles
- euthyroid state restored upon recovery
histo: DeQuervain’s thyroiditis with giant cells
23
Q
silent thyroiditis
A
- painless subacute thyroiditis
- Lack of anti-thyroid antibodies or autoimmune thyroiditis
- affects mostly post-partum females
- typically resolves over several months
24
Q
What type of thyroiditis?
Features?
Histo?
A
- *Riedel Thyroiditis**
- dense fibrosis of thyroid
- associated with extrathyroidal fibrosis including:
- retroperitoneum
- mediastinum
- not related to other thyroiditides
- *Histology**
- dense hyalinized tissue with chronic inflammatory infiltrate
25
follicular adenoma
* benign neoplasm with follicular differentiation (looks like small thyroid follicles)
* most common tumor of thyroid
* “cold” solitary circumscribed nodule (not hyperfunctional)
* When multiple are often a component of multinodular goiter where referred to as dominant or hyperplastic nodules
26
Papillary thyroid carcinoma
Pathogenesis?
Histo?
Prognosis?
\*most common variant
Pathogenesis: mostly sporadic but assoc with iodine excess, regions endemic for goiter, radiation
Histo:
* variable morphology with some papillary areas
* pseudonuclear inclusions (clear nuclei), nuclear grooves (invagination of cytoplasm into nucleus)
* psammoma bodies (calcospherites)—rounded spherical calcified structure
spreads predominately by lymphatics
Genetics: Increased risk among first degree relatives, RET oncogene rearrangement
Prognosis: excellent, relatively normal life expectancy even with lymph node metastases at the time of initial surgery. Overall \> 90% survival
27
Follicular thyroid carcinoma features
* purely follicular, no papillary carcinoma features
* resembles follicular adenoma but invades a thickened capsule
* blood borne metastases
* _minimally invasive_ form extends into but not through capsule (good prognosis – at least 90% at 10 years)
* _widely invasive_ form invades through capsule and/or vascular invasion--50% at 10 years
* **Tx:** with surgery, radioactive iodine as with papillary carcinoma
28
follicular thyroid carcinoma capsular invasion
29
follicular thyroid carcinoma capsular invasion (high power)
Well differentiated follicular appearance
30
follicular thyroid carcinoma bone metastasis
31
follicular thyroid carcinoma vascular invasion
32
Medullary thyroid carcinoma
* derived from C cells, C cell hyperplasia is precursor lesion
* 20% are familial and associated with MEN 2
* RET oncogene mutations
* composed of solid sheets of polygonal granular cells with amyloid deposition (procalcitonin)—resemble islet cell tumors
* produces calcitonin (may also produce ACTH, glucagon, insulin, HCG, VIP, serotonin)
* Invasive and metastatic
* 60-70% 5 year survival
33
Anaplastic thyroid carcinoma
* rapidly fatal
* -50% of patients have a history of longstanding goiter
* many had prior lower grade thyroid neoplasms
* RET activation not observed
34
medullary thyroid carcinoma with amyloid deposition
35
lymphoma
* - 95% are B cell tumors
* - most arise in the setting of chronic thyroiditis
36
Parathyroid gland general features
* derivatives of the 3rd and 4th branchial pouches
* usually 4 glands
* chief cells secrete parathormone (PTH)
* clear cells - chief cells with abundant glycogen
* oxyphil cells - packed with mitochondria-nonsecretory
* Parathyroid glands respond to levels of ionized calcium and magnesium.
* Histo: normal parathyroid, fat (clear areas) comprise 30-50% of gland
37
Sx: tinging, muscle cramps, convulsions, neuropsychiatric--depression, psychosis, paranoia
Tests: dec. serum calcium, decreased PTH
Dx?
Causes?
Tx?
Dx: hypoparathyroidism
Causes:
* most common cause is iatrogenic
* familial forms may be autoimmune and polyglandular
* idiopathic
* Agenesis – DiGeorge syndrome
Tx: Ca and vitamin D
38
Pseudohypoparathyroidism
* hypocalcemia secondary to end organ resistance
* Elevated PTH
* Mutation of Gs protein gene (GNAS1) results in diminished cAMP response to PTH
39
Albright’s Hereditary Osteodystrophy
* More generalized end organ resistance to several cAMP-coupled hormones (PTH, TSH, glucagon, FSH, and LH).
* short stature, obesity, mental retardation, subcutaneous calcification, congenital abnormalities of bone
40
Pseudopseudohypoparathyroidism
* similar phenotype as Albright’s Hereditary Osteodystrophy
* Reduced Gs activity but no GNAS1 mutation
* No abnormal cAMP response to PTH
41
Signs/Sx:increased serum Ca and decreased phosphate
* nephrocalcinosis, renal stones
* osteitis fibrosa cystica
* bone pain, cysts, fractures
* polyuria secondary to hypercalciuria
* mental status changes
* muscle weakness secondary to peripheral neuropathy
* peptic ulcer
* chronic pancreatitis
* hypertension
Dx?
Causes?
Dx:Hyperparathyroidism
Causes:
* parathyroid hyperplasia
* parathyroid adenoma
* parathyroid carcinoma
42
Dx? parathyroid-\_\_\_\_?
Features?
Dx: parathyroid hyperplasia
Lack of adipose tissue. Gland is 100% cellular
**1/3 associated with MEN1 and 2A
1/3 demonstrate monoclonality
lack of cellular pleomorphism**
43
parathyroid ?
Dx: Parathyroid Adenoma
hypercellular parathyroid tissue (no fat)
* sporadic or as part of MEN1
* usually sheets of chief cells with rim of normal tissue
* other glands tend to be atrophic
* May show considerable atypia
44
Secondary Hyperparathyroidism
* chronic renal failure - renal osteodystrophy
* vitamin D deficiency, intestinal malabsorption, renal tubular acidosis
45
Tertiary Hyperparathyroidism
* autonomous parathyroid hyperfunction following chronic renal failure which persists even after renal transplantation
* evidence of monoclonality in some cases
46
Osteitis Fibrosa Cystica
Histo: Numerous multinucleated osteoclasts reabsorbing bone
47
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