Thyroid Disorders Flashcards
Each lobe of the thyroid has a
Upper middle and lower pole
The right and left lobes of the thyroid gland are connected by a?
Isthmus
The thyroid epithelium is composed of?
Simple cuboidal to low columnar epithelium
Parafollicular cells (clear cells) are located where?
At the periphery
Do the parafollicular cells contact the colloid?
No
The parafollicular cells secrete what?
Calcitonin
Subclinical hypothyroidism is…?
Increased TSH and free T4 level remains in the lower-normal to normal range
Primary hypothyroidism means there is a problem with what structure?
The thyroid itself
Seconday hypothyroidism is…?
An inadequate stimulation by TSH that ends up in a deficient thyroid gland function
What is the most common cause of primary hypothyroidism in North America?
Hashimotos thyroiditis
What are other causes of primary hypothyroidism?
Thyroid agenesis
Inborn errors of thyroid metabolism
Anti-microsomal, antithyroid peroxidase, and antithyroglobulin
Surgical/radiation/drugs
What germline mutations are associated with primary hypothyroidism?
FOXE1, PAX8, and THRB
What gene increases the risk for follicular carcinoma?
PAX8
Cretinism is mostly associated with?
Endemic iodine deficiency
What are some clinical features of children with cretinism?
Growth retardation, mental retardation, proturding tongue, umbilical hernia, coarse facial features
What other symptoms can children with hypothyroidism exhibit?
Pseudohypertrophy of the muscle (it is really fat)
Precocious or delayed puberty
Myxedema can be found in?
Hypothyroidism
Myxedema is due to?
Deposition of glycosaminoglycans
Overt primary hypothryroidism is characterized by an elevated TSH level of what?
More than 10 mIU/L and free T4 levels below the lower limit of the reference range
T4 levels in subclinical hypothyroidism remain where?
Low normal to normal range
In secondary or central hypothyroidism deficient thyroid gland function is due to
Inadequate stimulation of TSH
In secondary or central hypothyroidism we are going to have a low or normal what
TSH
What is the most common cause of primary hypothyroidism in developed countries?
Hashimotos thyroiditis?
Hashimotos thyroiditis may occur in association with?
Autoimmune polyendocrine syndrome types 1 and 2
Does Hashimotos thyroiditis have a strong genetic component?
Yes
In Hashimotos thyroiditis there are circulating autoantibodies that are called?
Anti thyroglobulin and anti thyroid peroxidase
Autoantibodies against the sodium iodide symporter and pendrin have been found in a minority of patients with?
Hashimotos thyroiditis
What are some non endocrine disorders associated with Hashimotos ?
SLE, myastenia gravis, Sjogern syndrome
Which polymorphomisms in immune regulation-associated genes increase a persons susceptibility for Hashimotos?
CTLA4 and PTPN22 (polymorphomisms in these genes)
In Hashimotos disease there is a transient what?
Hyperthyroidism initially
In Hashimotos disease there is destruction of the follicular cells by what cells?
CD8+ T cells
In Hashimotis disease there is production and release of inflammatory cytokines by what?
Activated CD4+ T cells
In Hashimotos disease, painless enlargment of the thyroid may precede what?
Systemic manifestations
In Hashimotos disease, enlargment of the thyroid gland is?
Symmetric and diffuse
In ultrasound diffuse heterogeneity suggests what?
Autoimmune thyroiditis
In Hashimotos thyroiditis, the gland tends to enlarge in what way?
Symmetrically
Epithelial cells in Hashimotos thyroiditis undergo what?
Hurthle cell change
What lymphocytes can be found in Hashimotos thyroiditis?
CD8 and CD4 T cells
Also germinal centers
Painless and postpartum thyroiditis are variants of what?
Autoimmune thyroiditis
what is an important difference between Hashimotos disease and subacute lymphocytic painless thyroiditis?
Fibrosis and Hurthle cell metaplasia are not prominent in lymphocytic painless thyroiditis
In subacute granulomatous thyroiditis there is painful ….
Enlargement of the gland
In granulomatous thyroiditis there is transient inflammation and…
Hyperthyroidism
In subacute granulomatous thyroiditis there is decreased what?
Radioactive iodine uptake when compared to Graves disease
In subacute granulomatous thyroiditis there is…
Unilateral or bilateral glandular growth
What can be found in the early inflammatory phase of subacute granulomatous thyroiditis?
Scattered follicles may be disrupted and replaced by neutrophils forming microabscesses
What can be found in the later phase of subacute granulomatous thyroiditis?
Aggregates of lymphocytes, activated macrophages, and plasma cells associated with collapsed and damaged thyroid follicules, multinucleated giant cells surround fragments of colloid, chronic inflammatory infiltrate and fibrosis may replace the foci of injury
Thyrotoxicosis is caused by?
Excessive thyroid hormone
Hyperthyroid disorders can be classified into what categories?
Primary and secondary
What are some primary causes of hyperthyroidism?
Graves disease, hyper-functional toxic multinodular goiter, hyperfunctional toxic adenoma
What are some secondary causes of hyperthyroidism?
TSH secreting pituitary adenoma, ingestion of thyroid hormone
Graves disease is characterized by?
Hyperthyroidism, opthalmopathy, and dermopathy (pretibial myxedema)
Graves disease is the most common cause of?
Endogenous hyperthyroidism
Graves disease is more common in women or men?
Women
What is the pathogenesis of Graves disease?
The production of thyroid-stimulating immunoglobulins that bind to and activate TSH receptors
What are some characteristics of opthalmopathy in Graves disease?
Eyelid retraction, perioribital edema, episcleral vascular injection, conjunctival swelling, proptosis (exopthalmos)
Pretibial myxedema happens when?
There is a deposition of glycosaminoglycans in the dermis of the skin
How does pretibial myxedema look like?
Mildly pruritic, orange peel-like thickening of the skin along the anterior aspects of the shins
What is an important diagnosis when it comes to Grave’s disease?
Fractional 24 hour radioiodine uptake
What diagnostic method can confirm the presence of solitary or multiple thyroid nodules?
Thyroid ultrasonography
In Grave’s disease the thyroid enlargment is…?
symmetrical and secondary to diffuse hypertrophy and hyperplasia of thyroid follicular epithelial cells
The thyroid of someone with Grave’s disease has a
meaty apperance on a cut section
In Grave’s disease, what can be found in the microscopic morphology?
Tall, crowded follicular cells, pale colloid centers, presence of small clear vacoules on the edge of the colloid
Colloid goiter is known as ?
Diffuse nontoxic simple goiter
How are the TSH, T3 and T4 levels of someone with colloid goiter?
Normal
Most symptoms of colloid goiter arise from the?
Mass effect
A toxic multinodular goiter is charcaterized by the presence of
Multiple autonomous functioning thyroid nodules which are capable of synthesizing and secreting excessive amounts of thyroid hormone
Toxic multinodular goiter tends to be more common in?
Older individuals
The enlargment of multinodular goiter is
Assymetrical
Most patients with multinodular goiter become
Euthyroid
What does “hot nodules” mean in multinodular goiter?
increased activity on radionuclide scintigraphic scanning
Most thyroid nodules represent
Small, benign adenomatoid nodules or cysts
Does a personal family history of therapeutic neck irradiation in childhood presents a risk for malignancy?
Yes
Medullary thyroid cancer is familial in
50% of cases
Medullary thyroid cancer is associated with?
Multiple endocrine neoplasia type 2 (MEN-2) syndromes
Papillary thyroid cancers are familial in
10% of cases
Malignancy of thyroid nodules is suggested by?
Fixation and ipsilateral regional adenopathy or vocal cord paresis
Multinodularity of the gland may reflect a
Benign process
Low/undetectable levels of TSH may reflect a
Toxic adenoma
What can an ultrasound of a thyroid do?
Confirm that a mass is within a thyroid, accurately defines its size, classifies it as cystic or solid, and determines whether additional nodules are present
What is the most accurate test to exclude or confirm malignant disease in patients with a nodule and a normal TSH level?
Fine-needle aspiration biopsy
Thyroid adenomas are also known as
Follicular adenomas
In most cases thyroid adenomas are
Discrete, solitary masses derived from follicular epithelium
In most cases thyroid adenomas are not precursos of carcinomas
In most cases thyroid adenomas are not precursos to
Carcinomas
Most thyroid adenomas are not
Functional
What does a functional adenoma mean?
It means that the adenoma is able to increase the thyroid hormone levels independant of TSH
Functional adenomas clinically present as
Thyrotoxicosis
What gain of function mutations are present in thyroid toxic adenomas?
TSHR and GNAS mutations
The gain of function mutations TSHR and GNAS lead to…
Autonomous secretion of thyroid hormone by follicular cells independant of TSH
How does a thyroid adenoma look macroscopically?
Solitary, spherical, encapsulated well defined lesion
How does a thyroid adenoma look like microscopically?
Presence of recognizable follicles that are small and packed closely
What is the hallmark of all follicular adenomas?
Presence of intact well formed capsule encircling the tumor
Which two types of thyroid cancer are well differentiated?
Papillary carcinoma
Follicular carcinoma
Which two types of thyroid carcinomas are not well differentiated?
Anaplastic
Medullary carcinoma
Papillary carcinomas involve a gain of function mutation in which genes?
RET or NTK1 receptor tyrosine kinase
Serine/threonine kinase BRAF
Both mutations set off a signaling cascade down the MAPK pathway
Follicular carcinomas are associated with point mutations where?
RAS and PI3K which increase PI3K/AKT/mTOR pathway
Loss of function mutations in which gene salso play a role in the pathogenesis of follicular carcinoma?
PTEN
Follicular carcinomas are associated with what type of mutations?
Point mutations in RAS and PI3K which increase the PI3K/AKT/mTOR pathway
Loss of function mutations in which gene play a role in the pathogenesis of follicular carcinomas?
PTEN
Anaplastic carcinomas may arise
De novo
Anaplastic carcinomas have mutations in
RAS or PIK3CA mutations
In anaplastic carcinomas there is a loss of function of which gene?
TP53
Anaplastic carcinomas have activating mutations of
Beta-catenin
Medullary carcinomas occurr in
Multiple endocrine neoplasia type 2
What type of mutations are present in medullary carcinomas?
Germline RET mutations
Papillary carcinomas are the most
Popular type of thyroid carcinoma
Previous exposure to ionizing radiation is the main risk factor for?
papillary carcinoma
Papillary carcinomas have an excellent
Prognosis with a 10 year survival rate
Most papillary carcinomas present as
Asymptomatic thyroid nodules
In some people, the first manifestation of papillary carcinoma may be
A mass in a cervical lymph node
In papillary carcinomas, does the presence of isolated cervical nodal metastases have a significant influence on prognosis?
No
What are some symptoms of advanced papillary carcinoma?
Hoarseness, dysphagia, cough, and dyspnea
Which thyroid carcinoma are cold masses on scintiscans?
Papillary carcinoma
What are some morphological characteristics of papillary carcinoma?
Some are well demarcated and capsulated
Some are infiltrative to the adjacent parenchyma and unevely formed
Fibrosis, calcifications, and cystic changes may be present
Microscopically, papillary carcinomas have a branching papillar with a
Fibromuscular stalk
The branching papillae in papillary carcinoma are covered with
single to multiple layers of cuboidal epithelial cells
The nuclei of papillary carcinomas contain finely disperesed
Chromatin
How does the nuclei of papillary carcinoma cells look like?
Optically clear or empty apperance
-Orphan Annie eye
In papillary carcinoma, invaginations of the cytoplasm
may give the apperance of nuclear inclusions
Papillary carcinomas have what type of bodies?
Psamomma bodies
Follicular carcinomas are associated with increased incidence of
Iodine deficiency
Follicular carcinomas are more common in
Older patients
The prognosis of follicular carcinoma depends on
The extent of invasion and stage at presentation
Widely invasive follicular carcinomas are usually accompanied by
Metastases
How do follicular carcinomas typically present?
Slowly enlarging painless nodules
Are regional lymph nodes rarely involved in follicular carcinomas?
Yes
Is hematogenous dissemination common in follicular carcinomas?
Yes
To which organs do follicular carcinomas spread to?
Bone, lungs, liver and elsewhere
Follicular carcinomas typically present as
Cold nodules , however better differentiated lesions may be hyperfunctional
