Thyroid Diseases Flashcards
What are the main thyroid hormones?
T3 (triiodo-thyronine) and T4 (tetraiodo-thyronine/thyroxine)
T4 is 93% of thyroid hormones, while T3 is 7%.
What is the primary function of thyroid hormones?
Regulation of metabolic rate, growth, development, neurologic function, reproduction, cardiovascular system, skeletal muscle, and bone remodeling
Thyroid hormones affect body heat and oxygen consumption.
What is the T4/T3 ratio released in blood?
Approximately 13:1
T4 is converted to T3 mostly in peripheral tissues.
What is the role of the Sodium-Iodide Symporter (NIS)?
Iodine trapping in the thyroid gland
It concentrates iodide from the blood by 30 times.
What is organification in the thyroid gland?
The incorporation of I2 (inorganic iodine) into thyroglobulin (TG)
It involves iodination and coupling catalyzed by Thyroid Peroxidase (TPO).
What is the dietary iodine requirement?
1 mg I-/week (50 mg/year)
Needs increase with body mass, pregnancy, and lactation.
What is the half-life of free T4 and T3 in serum?
Free T4 ~1 week, Free T3 ~1 day
Only free T4 and T3 are considered biologically active.
What is the function of peripheral deiodinases?
Regulation of thyroid hormone bioavailability
D1, D2, and D3 are the main types, converting T4 to T3 and rT3.
What are the two mechanisms of thyroid hormone action?
Genomic and non-genomic mechanisms
Genomic involves binding to nuclear receptors; non-genomic effects occur rapidly.
What are the physiological effects of elevated thyroid hormones?
Increased heart rate, weight loss, heat intolerance, anxiety, and tremors
Symptoms include exophthalmos in Graves’ disease.
What is the hypothalamus-pituitary-thyroid axis?
TRH → TSH → T3/T4 with negative feedback inhibition
TRH is produced in the hypothalamus and stimulates TSH release from the anterior pituitary.
What are stimulatory factors for thyroid hormone secretion?
- TSH
- Thyroid-stimulating antibodies
- Increased thyroid-binding globulins
- Pregnancy
These factors promote hormone synthesis and secretion.
What are inhibitory factors for thyroid hormone secretion?
- Iodine deficiency
- Excessive iodine intake
- Perchlorate
- Thiocyanate
- Propylthiouracil
- Methimazole
- Decreased TBG
- Liver disease
These factors can suppress thyroid function.
What are the common causes of hyperthyroidism?
- Graves’ disease
- Thyroid adenoma
- Excessive TRH/TSH secretion
- Exogenous thyroid hormone
Graves’ disease is the most common cause.
What are the symptoms of hypothyroidism?
- Decreased heart rate
- Cold intolerance
- Goiter
- Myxedema
- Fatigue
- Digestive issues
- Reduced brain function
- Unexplained weight gain
- Depression
- Hair loss
- Muscle weakness
- Dry itchy skin
Hashimoto’s thyroiditis is a common cause.
What is cretinism?
Congenital hypothyroidism often due to iodide deficiency
Symptoms include pot-bellied appearance, pale skin, puffy face, protruding umbilicus, and protruberant tongue.
What is Non-thyroidal Illness Syndrome (NTIS)?
Low T3 levels with normal TSH in severe illness
It complicates treatment decisions due to overlapping symptoms.
What is the main treatment for hypothyroidism?
T4 (Synthroid), T3 (Cytomel), Armour (T3/T4 extracted from pig thyroid glands)
These treatments help restore normal hormone levels.
What is the primary treatment for hyperthyroidism?
Propylthiouracil (PTU) and Methimazole
These medications block thyroid hormone production and peripheral conversion.
What are the main treatments for hypothyroidism?
T4 (Synthroid), T3 (Cytomel), Armour (T3/T4 extracted from pig thyroid glands)
These treatments aim to replace or supplement the deficient thyroid hormones.
What are the main treatments for hyperthyroidism?
propylthiouracil (PTU), Methimazole, radioactive iodine, thyroid gland surgery
PTU and Methimazole block thyroid hormone production.
What is a notable concern regarding patients treated with Synthroid?
About 1/5 of patients remain symptomatic and are not happy
This indicates a growing concern in the treatment of hypothyroidism.
What is the structure of thyroid hormones?
Two linked tyrosines with attached iodine molecules
This structure is essential for their function in regulating metabolism.
How are thyroid hormones transported in the blood?
Bound to proteins
This binding is crucial for their stability and transport in the circulation.
What is the mechanism of thyroid hormone function?
Mediated through intracellular nuclear receptors and non-genomic mechanisms
This dual mechanism allows for a wide range of physiological effects.
How should thyroid hormones be administered?
Orally, on an empty stomach or >1 hour after eating, avoiding antacids
This ensures optimal absorption of the hormones.
What axis regulates thyroid hormone production?
Hypothalamus (TRH) - pituitary (TSH) - thyroid (T3, T4) axis
This axis is critical for maintaining thyroid hormone levels.
Which gender is more commonly affected by thyroid disorders?
Females (1/8 in lifetime)
This prevalence highlights the need for awareness and screening in women.
Which type of thyroid disorders are more common?
Primary thyroid disorders
Primary disorders involve the thyroid gland itself, while secondary and tertiary involve the pituitary and hypothalamus, respectively.
What are the diagnoses to make with serum values for T3/T4, TRH, and TSH?
Hyperthyroidism, Hypothyroidism, Non-thyroidal Illness Syndrome, Subclinical hypothyroidism, Subclinical hyperthyroidism
Understanding these conditions is crucial for proper management of thyroid health.
True or False: Hormone changes with thyroid dysfunction are diagnostic.
True
These changes provide essential clues for diagnosing thyroid disorders.
Fill in the blank: Thyroid hormones are stored in _______.
follicles
Follicles are the structures in the thyroid gland where hormones are synthesized and stored.
T or F: T3 & 4 increased the BMR?
True
T 3 & 4 are synthesized from what molecules?
Iodine (3 atoms in T3; 4 atoms in T4)
Tyrosine
compare and contrast the PK-PK profiles of T3 & T4
T3:
more potent, shorter duration of action; active TH hormone
T4:
less potent, longer duration of action, pro-TH hormone
T or F: The thyroid produces most of the active TH T3
False
most of the active T3 form are produced from T4 in the periphery through a process called deiodination
what are the differences b/t T3 & rT3
The emphatical formula remains unchanged; however the arrangements are different
T3: much more active due to cleavage of iodine from the tyrosine residue at the carboxyl-terminal end of Triiodothyronine
rT3: way less active and more inert due to cleavage of iodine from the linked tyrosine residue in triiodothyronine
Amount of dietary iodine positively correlates w/ what
body mass
what food source has the highest I content
salt
most thyroid hormones bind to what?
TBG
T or F: TBG has a much higher affinity for T4 than T3
True
T or F: T3 is an intracellular peptide-hormone that targets nuclear receptors to alter gene expression
True
Injection of a high does of T4 is administered to a pt. w/ hyperthyroidism. 2 weeks later, he is brought back to the clinic for monitoring and the lab tech. makes note that the pt.’s BMR is still to high. How would you as the physician explain this to the lab tech.
T4 has a relatively long half-life in serum. It can linger in the bloodstream for several days before being taken up by tissue.
In this clinical vignette, the pt. already had a high BMR to begin with, so the exogenous T4 will not be taken up by tissue.
The goal of this therapy is to steadily decrease BMR as the T4 gradually decreases to normal levels. This is why reevaluating the BMR does not become clinically significant until 6 weeks-post injection
T or F: the neurohypophysis is basically an extension of the hypothalamus.
True
The neurohypophysis does not actually produce its own endogenous hormones. The hormones are actually produced in the hypothalamus and then travel to the posterior pituitary to be stored
What is the normal weight range of the thyroid gland?
5 – 25 grams
What are the two main lobes of the thyroid gland connected by?
Isthmus
What are C cells in the thyroid gland responsible for secreting?
Calcitonin
What congenital anomaly is the most common clinically significant issue of the thyroid?
Thyroglossal duct cyst
Which hormone stimulates thyroid growth and hormone synthesis?
TSH (Thyroid-stimulating hormone)
What are the two primary thyroid hormones produced by the thyroid gland?
- Thyroxine (T4)
- Triiodothyronine (T3)
What is thyrotoxicosis?
Hypermetabolic state caused by elevated circulating levels of free T3 and T4
What is the most common cause of thyrotoxicosis?
Graves disease
What is the primary characteristic of hyperthyroidism?
Excess thyroid hormone synthesis and secretion
What is the key clinical feature of thyroid storm?
Abrupt onset of severe hyperthyroidism
What is the most common cause of primary hyperthyroidism?
Graves disease
What are the symptoms of hyperthyroidism related to the sympathetic nervous system?
- Tremor
- Hyperactivity
- Emotional lability
- Anxiety
- Insomnia
True or False: Hyperthyroidism is associated with weight gain.
False
What is the typical lab finding for diagnosing hyperthyroidism?
Low TSH value with increased free T4
What is the treatment for hyperthyroidism?
- β-blockers
- Thionamides (e.g., methimazole)
- Iodine solution
- Radioactive iodine
What autoimmune disorder is the most common cause of endogenous hyperthyroidism?
Graves disease
What is the clinical triad associated with Graves disease?
- Hyperthyroidism
- Infiltrative ophthalmopathy
- Localized, infiltrative dermopathy
What is the most common antibody subtype found in Graves disease?
Thyroid-stimulating immunoglobulin (TSI)
What causes exophthalmos in Graves disease?
Increase in volume of retro-orbital connective tissues and extraocular muscles
What is pretibial myxedema?
Thickening of the dermis associated with Graves disease
What is Hashimoto’s thyroiditis?
An autoimmune disorder causing hypothyroidism
What is the characteristic change in thyroid tissue in Hashimoto’s thyroiditis?
Lymphocytic infiltrate
What is the main pathological feature of subacute granulomatous thyroiditis?
Viral infection
What is the primary feature of myxedema?
Severe hypothyroidism
What is the function of calcitonin?
Promotes absorption of calcium by skeletal system and inhibits breakdown of bone
What is the typical age range for peak incidence of Graves disease?
20 - 40 years
What is the risk associated with thyroid hormone binding to nuclear receptors in target cells?
Increased transcription of target genes
Fill in the blank: The presence of _______ at the base of the tongue may indicate ectopic thyroid tissue.
Lingual thyroid
What do T cells secrete that stimulates fibroblast proliferation?
Cytokines
What is the most common area affected in infiltrative dermopathy associated with Graves disease?
Shins
What is the characteristic thickening of the dermis in Graves disease called?
Pretibial myxedema
What is the appearance of the thyroid in Graves disease?
Diffuse hypertrophy and hyperplasia of thyroid follicular epithelial cells
In Graves disease, what is the appearance of colloid within the follicle lumen?
Pale with scalloped margins
What type of cells infiltrate the interstitium in Graves disease?
Lymphocytes
What is the term for the bulging eyes seen in Graves disease?
Exophthalmos
What is the treatment option for large goiters in Graves disease?
Thyroidectomy
What laboratory finding is most likely present in a patient with Graves disease?
Anti-TSH receptor antibodies
What is the primary cause of hypothyroidism?
Structural or functional derangement that interferes with production of thyroid hormone
What is the most common cause of hypothyroidism in iodine-sufficient areas?
Hashimoto thyroiditis
What is the prevalence of hypothyroidism in women compared to men?
About 10-fold more common
What is the most sensitive screening test for hypothyroidism?
Measurement of serum TSH level
What is myxedema?
Hypothyroidism in older child or adult
What skin changes occur in myxedema?
Cool and pale due to decreased blood flow
What are the clinical features of infantile hypothyroidism?
Severe cognitive impairment, short stature, coarse facial features, protruding tongue, umbilical hernia
What characterizes autoimmune hypothyroidism?
Presence of circulating autoantibodies against thyroglobulin and thyroid peroxidase
What is the role of CD8+ cytotoxic T cells in Hashimoto thyroiditis?
They may destroy thyroid follicular cells
What type of thyroiditis is associated with viral infections?
Subacute (granulomatous) thyroiditis
What is the typical demographic affected by subacute thyroiditis?
Women aged 40 - 50 years
What triggers subacute thyroiditis?
Viral infection
What is the histological feature of Hashimoto thyroiditis?
Extensive infiltration of thyroid parenchyma by mononuclear inflammatory infiltrate
What is the autoimmune disease characterized by thyroid gland destruction?
Hashimoto thyroiditis
What type of thyroiditis is fibrous in nature?
Fibrous thyroiditis (Reidel)
What is the most common demographic affected by subacute granulomatous thyroiditis?
Women aged 40 - 50 years, with a ratio of 4:1 compared to men.
What often triggers subacute granulomatous thyroiditis?
Viral infection.
What is the typical duration for hyperthyroidism associated with subacute granulomatous thyroiditis?
Transient, usually decreases in 2 - 6 weeks.
What is the pathogenesis of subacute granulomatous thyroiditis believed to involve?
Virus-induced host tissue damage stimulating cytotoxic T-lymphocyte response.
What are the histological features of early subacute granulomatous thyroiditis?
Scattered follicles disrupted/replaced by neutrophils forming microabscesses.
What characterizes the later stages of subacute granulomatous thyroiditis?
Chronic inflammatory infiltrate and fibrosis may replace areas of injury.
What is Riedel (Fibrous) Thyroiditis?
A rare condition with extensive fibrosis involving thyroid and contiguous neck structures.
What disease does Riedel thyroiditis clinically simulate?
Thyroid carcinoma.
What is the characteristic histological feature of Riedel thyroiditis?
Atrophic thyroid follicles with dense inflammatory infiltrate and fibrosis.
What is the typical presentation of subacute lymphocytic thyroiditis?
Painless goiter, mild transient hyperthyroidism, or both.
What demographic is more commonly affected by subacute lymphocytic thyroiditis?
Middle-aged adults, more common in women.
What antibodies are often present in subacute lymphocytic thyroiditis?
Antithyroid peroxidase antibodies.
What is a potential progression of subacute lymphocytic thyroiditis?
Hypothyroidism in 1/3 of patients over 10 years.
What is the typical symptom duration for subacute lymphocytic thyroiditis?
Symptoms for about 2-8 weeks.
What are the key features of Hashimoto’s thyroiditis?
Autoantibodies, lymphoid follicles, and Hurthle cell metaplasia.
What is the definition of hyperthyroidism?
Increased thyroid hormone leading to a hypermetabolic state.
What is a thyroid storm?
Abrupt onset of hyperthyroidism with fever, considered an emergency.
What does Graves’ disease involve?
Hyperthyroidism, diffuse hyperplasia, infiltrative ophthalmopathy, and dermatopathy.
What is the definition of hypothyroidism?
Decreased thyroid hormone levels.
What is the common cause of thyroid pain?
Subacute granulomatous thyroiditis.
Fill in the blank: The presence of large foreign body giant cells with inflammatory destruction of thyroid follicles is characteristic of _______.
Riedel thyroiditis.
What is the typical thyroid presentation in an infant with growth restriction, dry skin, and a protuberant abdomen?
Infantile hypothyroidism.
What histological findings are associated with subacute granulomatous thyroiditis?
Multinucleate giant cells enclosing pools of colloid.
What is a goiter?
Enlargement of the thyroid gland
Can be diffuse non-toxic or multinodular
What are the causes of diffuse non-toxic goiter?
Dietary iodine deficiency, ingestion of goitrogens, hereditary enzymatic defects
Goitrogens include cabbage, cauliflower, Brussels sprouts, turnips, and cassava
What is the hyperplastic phase of diffuse non-toxic goiter?
Diffuse, symmetric enlargement of the thyroid with crowded columnar cells
Follicles may vary in size, some being distended and others small
What is multinodular goiter?
Irregular enlargement of the thyroid due to recurrent episodes of hyperplasia and involution
May be mistaken for neoplasm
What are common clinical manifestations of multinodular goiter?
Airway obstruction, dysphagia, compression of major vessels
Can lead to superior vena cava syndrome
What characterizes a solitary thyroid nodule?
Palpably discrete swelling within a normal thyroid gland
Incidence in the US is 1-10%, more common in women
What is the prognosis for solitary thyroid nodules?
1% are malignant; >90% of patients are alive 20 years after diagnosis
Nodules in younger patients and males are more likely to be neoplastic
What defines a follicular adenoma?
Discrete, solitary masses derived from follicle epithelium
Majority are nonfunctional; some may cause thyrotoxicosis
What mutations are associated with toxic adenomas?
Gain-of-function mutations in TSH receptor pathway
Most commonly in TSH receptor (TSHR) or GNAS
What is the average size of follicular adenomas?
About 3 cm in diameter, some larger than 10 cm
May show areas of hemorrhage, fibrosis, calcification
What is the most common type of thyroid carcinoma?
Papillary thyroid carcinoma (PTC)
Accounts for 80-85% of cases
What are the genetic characteristics of conventional PTC?
Translocations resulting in RET or NTRK gene fusions; BRAF mutations
BRAF mutations are associated with reduced expression of thyroid differentiation markers
What are the precursor lesions recognized for thyroid carcinomas?
Papillary microcarcinoma, noninvasive thyroid neoplasm with papillary-like nuclear features (NIFTP), nonfunctioning follicular adenoma
These lesions can progress to invasive forms
What mutation is frequently found in follicular neoplasms?
Gain-of-function mutations in RAS
Found in 20-40% of follicular adenomas and 30-50% of follicular carcinomas
What is the prognosis for thyroid carcinomas?
5-year survival greater than 98% for most cases
Mortality is one of the lowest among solid tumors
What are the pathological features of medullary carcinoma?
Derived from parafollicular C cells, associated with endocrine neoplasia syndromes
Accounts for 5% of thyroid carcinomas
What are the characteristics of anaplastic carcinoma of the thyroid?
Poorly differentiated and aggressive form of thyroid cancer
Typically arises from well-differentiated thyroid cancers
What percentage of follicular carcinomas exhibit a translocation?
20% to 50%
Translocation is a common genetic alteration in follicular carcinomas.
What are the gain-of-function mutations associated with follicular carcinomas?
PIK3CA mutations
PIK3CA encodes the enzyme PI3K, which plays a role in cell growth and division.
What gene is commonly mutated in poorly differentiated and anaplastic thyroid carcinomas?
TP53
TP53 is a tumor suppressor gene that regulates the cell cycle.
What is the most common form of thyroid cancer?
Papillary Thyroid Carcinoma
It accounts for nearly 85% of thyroid cancer cases in the US.
What is a major risk factor for thyroid carcinomas?
Exposure to ionizing radiation
Particularly significant during the first two decades of life.
What is the prognosis for papillary thyroid carcinoma?
Generally good to excellent
Presence of isolated cervical nodal metastases does not worsen prognosis.
What histological feature is characteristic of papillary thyroid carcinoma?
Branching papillae with fibro-vascular stalks
Nuclei exhibit optical clarity, described as ‘ground glass’ or ‘Orphan Annie eyes’.
What is the typical age range for patients diagnosed with papillary thyroid carcinoma?
25 to 50 years
The incidence has increased markedly in the last 30 years.
What are psammoma bodies?
Concentrically calcified structures usually within papillary cores
They are often found in various tumors, including papillary thyroid carcinoma.
What is the typical presentation of follicular carcinoma of the thyroid?
Slowly enlarging painless nodules
These nodules are usually cold on scintigrams.
What is the characteristic pattern of spread for follicular carcinoma?
Hematogenous spread
Unlike papillary carcinoma, lymphatic spread is uncommon.
What is a key histological feature of medullary thyroid carcinoma?
Polygonal to spindle-shaped cells
These cells may form nests, trabeculae, or follicles.
Which syndromes are associated with familial medullary thyroid carcinomas?
MEN-2A and MEN-2B
These syndromes involve specific germline mutations in the RET gene.
What is the typical age of onset for sporadic medullary thyroid carcinomas?
40s and 50s
This differs from familial cases, which can occur in younger patients.
What are the common symptoms of poorly differentiated and anaplastic thyroid carcinomas?
Dyspnea, dysphagia, hoarseness, cough
These symptoms result from compression and invasion of adjacent structures.
What is the expected survival rate for anaplastic thyroid carcinoma?
Approaching 100% mortality rate
Patients often die within less than one year.
What is a common feature present in familial medullary thyroid carcinomas?
Multicentric C-cell hyperplasia
This is not present in sporadic lesions and is believed to be a precursor lesion.
What is the treatment approach for most follicular carcinomas?
Total thyroidectomy followed by radioactive iodine
Serum thyroglobulin levels are monitored for tumor recurrence.
What type of cells are described as large, pleomorphic giant cells, including occasional osteoclast-like multinucleate giant cells?
Giant cells
These cells are often associated with certain types of tumors or inflammatory conditions.
What is the appearance of spindle cells in the context of sarcomatous lesions?
Sarcomatous appearance
Spindle cells are elongated cells typically seen in sarcomas.
What type of differentiation may be present in foci suggesting origin from well-differentiated carcinoma?
Papillary or follicular differentiation
This indicates a more organized structure that can be indicative of certain types of cancer.
What histological feature is associated with papillary thyroid carcinoma?
Optically clear nuclei
These nuclei are referred to as ‘Orphan Annie eyes’ due to their distinct appearance.
What is a common characteristic of psammoma bodies?
Presence in certain tumors
Psammoma bodies are calcified structures often found in papillary thyroid carcinoma.
What clinical presentation is associated with a solitary, nontender, firm nodule in the thyroid gland?
Potential thyroid pathology
This presentation may warrant further investigation for thyroid neoplasms.
What are the likely associated factors with the pathology of a 66-year-old man with a firm mass in the thyroid?
Low grade and stage, Previous follicular carcinoma
These factors can influence prognosis and treatment options.
What is the most likely diagnosis for a 32-year-old woman with a stony, hard thyroid gland replaced by dense fibrous tissue?
Riedel thyroiditis
This condition is characterized by fibrous tissue replacement in the thyroid.
What type of thyroiditis is characterized by granulomatous inflammation and giant cells?
DeQuervain thyroiditis
This type of thyroiditis is often self-limiting and can follow a viral infection.
What is the most common thyroiditis?
DeQuervain thyroiditis
It is often associated with viral infections and presents with neck pain.
What mutation is commonly associated with follicular carcinoma of the thyroid?
RAS mutations
These mutations are significant in the progression of thyroid tumors.
What is the prognosis for papillary thyroid carcinoma?
Usually very good – excellent prognosis
Factors such as staging and histological features can influence this prognosis.
What type of carcinoma is derived from parafollicular C cells and secretes calcitonin?
Medullary carcinoma
This type is often associated with familial syndromes and can form amyloid.
True or False: Anaplastic carcinoma has a poor prognosis.
True
This type of carcinoma is highly aggressive and undifferentiated.
Fill in the blank: Goiters are thyroid enlargement due to impaired synthesis of thyroid hormone usually because of _______.
Iodine deficiency
Iodine is essential for thyroid hormone production.
What is often the difference between benign and malignant thyroid nodules?
Hot vs. cold nodules
Hot nodules are usually benign and actively produce hormones, while cold nodules may indicate malignancy.
What are the histological features required for diagnosing papillary thyroid carcinoma?
Optically clear nuclei, intranuclear pseudoinclusions
These features help differentiate it from other thyroid lesions.
