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103 Cards in this Set

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  • Back
Primary cause: of Hypothyroidism
failure of thyroid gland to secrete hormone
Secondary causes: of Hypothyroidism
failure of pituitary gland to secret TSH or hypothalamus to secrete TRH
TSH stimulates pituitary thyroid _____
T4- 5 deiodinase activity


Above stimulates pituitary gland to release additional T3
Heart problems assoc with Hypothyroidism
Heart: myxedematous heart disease: decreased contractility, cardiac enlargement, pericardial effusion, decreased pulse, decreased cardiac output
GI probs assoc with Hypothyroidism
achlorhydria, decreased intestinal transit with gastric stasis
Sexual dys funcs of Hypothyroidism
Delayed puberty, anovulation, amenorrhea, infertility
Nutritional problems with Hypothyroidism
Hypercholesterolemia with increased levels of LDL

Insulin resistance
Classic Signs & Symptoms of Hypothyroidism
Cold intolerance
Puffiness
Decreased sweating
Coarse skin
Above reported in 90-97% of patients, more common in elderly, 50-64% in younger pts.
Definition of Myxedema
Severe form of hypothyroidism associated with:
Altered mental status

Hypothermia

Bradycardia
Myxedema coma: occurs in pts with myxedema who are subjected to ________
external stress
Worldwide, ________remains as foremost cause of hypothyroidism
iodine deficiency
In the US and other areas of adequate intake, _______is most common cause of hypothyroidism
autoimmune thyroid disease
Most Common Cause of Acquired Hypothyroidism
Most frequent cause is autoimmune thyroiditis

Up to 95% of affected pts have thyroid autoantibodies (antimicrosomal & antiperoxidase, most common)
Up to ___% of post-partum women develop lymphocytic thyroiditis
10
Up to 10% of post-partum women develop lymphocytic thyroiditis

With women with type 1 diabetes, the percentage rises to ___%
25
High titers of _______antibodies reported as 97% sensitive and 91% specific for post-partum autoimmune thyroid disease
anti-TPO
Hypothyroidism associated with the following drugs:
Amiodarone
Interferon alpha
Thalidomide
Stavudine
Radioactive Iodine (RAI) for treatment of Graves disease generally results in permanent hypothyroidism within (how long) after therapy
one year


(Frequency much lower in pts with toxic nodular goiters and solitary “hot” nodules)
A solitary thyroid nodule is detected by palpation
A more direct approach to determine the nature of the nodule is the ______
fine needle aspirate
Thyroid gland, radionuclide scan, solitary cold nodule
?
Thyroid gland, radionuclide scan, cold nodule
?
Thyroid gland, radionuclide scan, multiple cold nodules
?
Nearly all of the cold nodules, when removed, have proven to be _____(benign or malig).
benign
Remember: Nearly all solitary thyroid nodules are ____.
cold
Of the cold solitary nodules, only 10% are _______
malignant
Prior to the introduction of FNA, the decision to remove a solitary nodule because it was cold, depended on clinical factors, such as, ____ (4)
sex, palpatory findings, family history, exposure to radiation
Thyroid gland, FNA, follicular cells, Wright stain
?
The reliability of the FNA resides in the ______
competency of the aspirator in obtaining a good specimen


(The aspirate should then be interpreted by an equally competent pathologist)
FNA is reliable in the detection of papillary, medullary & anaplastic carcinomas.

However, with ______ carcinomas, FNA is less dependable
follicular
Thyroid gland, unifocal medullary carcinoma of sporadic type
?
Thyroid gland, papillary carcinoma
?
Thyroid gland, follicular adenoma
?
Thyroid gland, follicular carcinoma in nodular goiter
?
A solitary nodule which is more active in concentrating radionuclide and results in a ____ nodule, usually with suppression of the remainder of the thyroid parenchyma
“hot”
The hot nodule can be the cause of ____
hyperthyroidism
Thyroid gland, solitary hot nodule, with suppression of remainder of gland
?
Thyroid gland, multiple hot nodules, nodular goiter
?
Thyroid gland, radionuclide scan, multiple hot nodules
?
The consensus is that solitary hot nodules are nearly all benign.

However, they can be the cause of _____
hyperthyroidism
Thyroid Neoplasms
Benign: called what?
adenoma
Thyroid Neoplasms
Carcinomas: (4)
Papillary
Follicular
Medullary
Anaplastic
Thyroid Neoplasms
another malignant type (not carcinoma)
Malignant lymphoma
What Thyroid Neoplasm?

Solitary nodule
Normal or goitrous background
Encapsulated
Interior of adenoma, differs histologically from surrounding parenchyma
Adenoma
Thyroid gland, follicular adenoma
?
Follicular adenoma
?
What type of thyroid neoplasm?

A well demarcated nodule in one lobe.

The remainder of the thyroid gland appears normal, or it may have changes of a nodular goiter
Follicular adenomas
Follicular adenomas usually do not develop into ______
follicular carcinomas
What type of carcinoma?

Solitary nodule, in background of normal parenchyma

More common in iodine-sufficient areas

Affects any age, not unusual in children or young adults

Predisposing factors: radiation is the most important factor

Not encapsulated, well demarcated

Invasive microscopically

Prone to metastasize to regional lymph nodes

Distant metastases to lungs and bones
Papillary Carcinoma
Cellular

No nuclear pleomorphism, no increased mitoses

No vascular or capsular invasion
in some cases, like this one,
if invasive growth were present, a diagnosis of well differentiated follicular carcinoma or minimally invasive follicular carcinoma would be made
?
Usual papillary carcinoma
Size, 2 cm
Well demarcated but not encapsulated when viewed microscopically
?
Papillae, papillary carcinoma
Papillae present

Psammoma bodies, laminated & calcified

Nuclear changes
Clear nuclei
Nuclear grooves (nuclear membrane folds)
Intranuclear inclusions (of cytoplasm)
?
Psammoma body, papillary carcinoma
?
Psammoma body in smear
of aspirated material
?
.
?
Clinical Features of papillary carcinoma
Presence of thyroid nodule

Aspiration cytology: should be diagnostic

Distant metastases: recognized in radiographs or total body radionuclide scans

Palpatory findings may be suggestive
Thyroid gland, FNA, papillary carcinoma
?
Papillary carcinoma, follicular variant. Note: nuclear changes
?
Treatment of pap carcinoma
Thyroidectomy, ranging from lobectomy to total thyroidectomy; Lymph node dissection, when indicated

Postoperative RAI, when indicated
Prognostic Factors of pap carcinoma
Age: the older the patient the worse the prognosis. Children & adolescents associated with a good prognosis
Metastases: distant metastases, i.e., to lung and/or bones predict a bad prognosis. However, metastases to regional lymph nodes does not
Extension of neoplasm across the capsule of the thyroid gland forebodes a bad prognosis
Size: the larger the tumor the worse the prognosis

Metastases to regional lymph nodes do not affect prognosis
Lymph node, metastatic papillary carcinoma of thyroid gland
?
Papillary thyroid carcinoma
Invading adjacent skeletal muscle
?
By definition, smaller than 1 cm
Like all papillary carcinomas, tumors can be bilateral, multifocal
Such tumors, previously considered as metastatic foci, now accepted as primary lesions
Easily metastasizes to regional lymph nodes

Early metastases to regional lymph nodes

Not unusual for pt to present with enlarged lymph nodes without a palpable thyroid lesion
Papillary Microcarcinoma
US incidence: of Papillary Microcarcinoma
6-9%

With such high frequencies, the rate of clinically significant thyroid cancers should be higher, but it is not
Papillary microcarcinoma, note invasive borders
?
Thyroid gland, multiple foci, papillary y carcinoma.
?.Intrathyroidal metastasis or multiple primary neoplasms
?
Papillary Carcinoma Predisposing Factors
There is only one predisposing factor and that is radiation.
Thyroid Carcinoma:
A rate of _?_%, in a population exposed to radiation for benign conditions: enlarged thymus, tinea capitis, chronic sinusitis. This rate is for an American population
9
Radiation and Chernobyl:
Genetic studies reveal that a large proportion of thyroid glands showed rearrangements of ______ type.
RET/PTC3
Chernobyl Accident:
majority were _____ carcinomas
papillary
RET protooncogene has become a factor in developing familial forms of ______ carcinoma
medullary
In medullary carcinomas, germline point mutations of ____ are involved
RET
RET also has a role in ____ carcinomas.
papillary
The changes are gene rearrangements resulting in oncogenes, RET/PTC1 to _____.
RET/PTC4
____-more common in irradiated thyroid glands from Chernobyl
RET/PTC3
What carcinoma?

No distinctive histology like papillae, nuclear changes or psammoma bodies
Encapsulated tumors with well developed capsules
Most tumors, well-differentiated with well formed neoplastic follicles
May be difficult to differentiate from follicular adenoma
Follicular Carcinoma
2 divisions of Follicular Carcinoma
minimally or markedly invasive follicular carcinomas
Follicular Carcinoma:
Unlike papillary carcinomas, do not usually metastasize to ____
lymph nodes



(Prefers hematogenous spread to bones and lungs)
Follicular Carcinoma:
Usually arise in glands involved by _____ goiters
multinodular
Gross and microscopic look of Markedly invasive follicular carcinoma
Gross: diffuse infiltration of thyroid parenchyma or blood vessels by tumor

Microscopic: breach of capsule with extension of tumor into thyroid parenchyma and invasion of larger blood vessels
Follicular Carcinoma Clinical Features
Older females, with nodular goiter, perhaps, with a dominant nodule

Usually euthyroid

Distant metastases identified by chest x-ray films and radionuclide total body scans
Predisposing Factors for Follicular Carcinoma
No known predisposing factors, except for the possibility of iodine deficiency and nodular goiters
Prognostic Factors for Follicular Carcinoma
Like papillary carcinomas, age is a factor

Post-menopausal women harbor more aggressive tumors
Treatment for Follicular Carcinoma
Thyroidectomy: from lobectomy to total thyroidectomy
Radioactive iodine, postoperatively, when indicated.
Survival rate is worse than for papillary carcinomas
Medullary Carcinoma originates from __-cells.
C
Normal secretory product of Medullary Carcinoma
calcitonin
Multiple endocrine neoplasia syndromes assoc with 20% Medullary carcinoma
MEN IIa
MEN IIb
no stigmata of MEN II

Most difficult to detect

Most benign of medullary carcinomas
Familial Medullary Thyroid Carcinoma
Medullary carcinoma

Pheochromocytomas and/or adrenal medullary hyperplasia, bilateral, or mixtures of both

Parathyroid hyperplasia with hyperparathyroidism – 30% of patients
Multiple Endocrine Neoplasia IIa
Medullary carcinoma

Bilateral pheochromocytomas or adrenal medullary hyperplasia or mixtures of both

Other stigmata: facies, mucosal neuromas, colonic ganglioneuromatosis, Marfanoid habitus, hyperextensible joints, hypertrophic corneal nerves

Few associated with Hirschsprung disease

No parathyroid hyperplasia
Multiple Endocrine Neoplasia IIb
Medullary Carcinomas: Sporadic vs Familial Forms
Sporadic: unilateral and unifocal lesion, well demarcated, poorly encapsulated
May be associated with lymph node metastases that may be large and bulky.

Familial: bilateral, multifocal, well-demarcated, poorly encapsulated
Sporadic or non-familial medullary carcinoma
?
Thyroid gland, bilateral medullary carcinomas, of familial type
?
Two types of C-cell hyperplasia
Physiologic – associated with other lesions, like AIT, hyperparathyroidism
Pre-neoplastic-- associated with and gives rise to medullary carcinomas
Screening for Medullary Carcinomas
Present method: screen for RET protooncogene
method now used to follow pts postoperatively for persistent or recurrent Medullary Carcinomas
intravenous injection of pentagastrin and calcium

Positive test: elevated serum calcitonin
treatment of Medullary Carcinomas
Total thyroidectomy with dissection of regional lymph nodes, when indicated

Thyroid gland must be totally removed because any remaining C-cell is a potential source for carcinoma

When post-operative levels of calcitonin remain elevated, this indicates that pt is harboring more neoplasm, most likely in form of metastases
prognosis of Medullary Carcinomas
FMTC – best prognosis

MEN IIa – next best

MEN IIb – worst

Sporadic – 50% survival rate at 5 yrs.
pathology of MEN IIb
Microscopic: small neuroendocrine cells

Therefore: stain like neuroendocrine cells:
Chromogranin +
Neuron-specific enolase +
Synaptophysin +

Stains for calcitonin, CEA

Cells are versatile and may produce other peptides: CEA, VIP, serotonin, ACTH

Associated C-cell hyperplasia is found in familial forms

Amyloid is regularly produced by tumors
Anaplastic carcinoma points
Older patients, usually with long histories of goiters

Recent rapid growth of goiters, at times leading to respiratory distress, requiring tracheotomy

Large, hard, fixed mass in neck, vicinity of thyroid gland

Often, inoperable

Poor response to radiation or chemotherapy
Anaplastic Carcinoma – Pathology
Gross: extensively invasive, large white mass, may or may not see origin from thyroid gland.

Microscopic: Undifferentiated neoplasm, composed of spindle and giant cells, differentiated carcinomas often found within anaplastic areas.
Anaplastic tumors, often arise from differentiated carcinomas, most commonly ______ carcinomas
follicular
Anaplastic carcinomas, very rare in US, probably due to iodine sufficiency, lack of nodular goiters and _____ carcinomas
follicular
Clinical Features
of anaplastic carcinoma
Typically women

Older pts. (57-67 yrs)

Rapidly enlarging neck mass

Hoarseness & dyspnea