Thyroid Pathology Flashcards
Follicular Cell Anatomy and Functions (4)
Surround colloid which makes Thyroglobulin
Have TSH receptors that stimulate TG synthesis
Transport Iodide for TG synthesis
Cleave TG to form T3 and T4 hormones
Parafollicular Cells (C cells) Functions (2)
Synthesize and secrete Calcitonin
Calcitonin inhibits osteoclasts and promotes skeletal calcium absorption
Thyroid Hormone Actions (5)
*Essential action is to increase the basal metabolic rate
Increase Cholesterol/Fat/Glucose synthesis
Increase heart rate
Increase Growth Hormone
Increase protein/fat/carbohydrate use in muscles
Goiterogens Mechanisms of Action
Propylthiouracil (2) and Iodide (2)
Propylthiouracil:
Inhibits Iodide oxidation to block T3/T4 synthesis
Iodide:
Blocks Thyroglobulin proteolysis to blockT3/T4 release
Thyrotoxicosis
Definition, Primary (5) and Secondary (1) Etiologies
Hypermetabolic state from excess T3/T4
Primary: Diffuse hyperplasia from Graves disease Multinodular goiter Thyroid adenoma Iodine Induced Neonatal (from maternal Graves disease)
Secondary:
Pituitary adenoma secreting TSH
Hyperthyroidism Physiological Mechanisms (2) and Clinical Features (7)
Excess thyroid hormone induces hypermetabolic state
Increased Beta-adrenergic tone causes SNS overactivity
Perspiration Facial Flushing Nervous/Excitable/Restless/Emotional unstable Insomnia Exophthalmos Palpitations/Tachycardia Tremor
Hyperthyroidism
Diagnosis (6) and Treatment (5)
Measure T3/T4 and TSH:
TSH low and T3/T4 elevated, primary hyperthyroidism
T3/T4 and TSH all elevated, secondary hyperthyroidism
Radioactive iodine uptake by Thyroid:
Diffuse points to Graves disease
Uptake by single nodule points to adenoma
High doses of iodine (Wolff-Chaikoff effect) Thionamide Radioiodine ablation Surgical resection Beta blockers and NSAIDs for symptoms
Graves Disease Clinical Features (3), Pathogenesis and Morphology (2)
Hyperthyroidism with gland enlargement
Infiltrative opthalmopathy
Pretibial myxedema
TSH receptor antibodies (TSI Abs)
Diffusely enlarged thyroid
Bubbly colloid from droplet resorption
Thyroid Storm
Definition, Symptoms (4) and Precipitating Events (3)
abrupt onset of life threatening thyrotoxicosis
Fever
Tachycardia
Congestive Heart Failure
Jaundice
Pregnancy
Hemithyroidectomy
Amiodarone
Hypothyroidism
Prevalence (3) Etiologies: Primary (6) and Secondary (2)
Common Disease (.3-4%)
More common in women
Prevalence increases with age
Genetic thyroid development defect Iatrogenic - Postablative Thyroid hormone resistance syndrome Autoimmune Iodine deficiency (congenital cretinism) Dyshormonogenetic goiter (congenital)
Pituitary failure
Hypothalamus failure
Cretinism
Etiologies (2) Pathogenesis (2) Clinical Features (4)
Maternal iodine deficiency
Genetic alterations in normal thyroid metabolic pathways
Lack of maternal T3/T4 crossing placenta early in pregnancy leading to abnormal brain development
Mental retardation Growth retardation Coarse facial features, protruding tongue Umbilical hernias Short stature
Iatrogenic Hypothyroidism
Etiologies (3)
Thyroidectomy
Radioiodine/Exogenous irradiation
Drugs: methimazole, propylthiouracil, lithium, p-aminosalicyclic acid
Myxedema (Hypothyroidism) Clinical Features (7) and Lab Values (2)
Mental/physical sluggishness Weight gain Cold intolerance Low cardiac output Hypercholesterolemia Brittle nails Hair loss
Elevated TSH
Decreased T4/T3
Hashimoto Thyroiditis
Prevalence (2) Pathogenesis (2) Morphology (3)
Clinical Features (4) Associated Diseases (2)
Most common cause of iodine sufficient hypothyroidism
Most common in women aged 45-65
CTLA4 and PTPN22 defects cause loss of tolerance
Autoantibodies to Tg and TPO made
Lymphocytic infiltrate forming germinal centers
Follicular cell atrophy and Hurthle cell metaplasia
Diffuse, painless thyroid enlargement
Initial Hashitoxicosis (hyperthyroidism)
Eventual hypothyroidism
Elevated TSH, decreased T4/T3
Many other Autoimmune diseases
Thyroid B cell Lymphoma
Subacute Lymphocytic Thyroiditis
Pathogenesis, Morphology, Clinical Features (3) and Related Disease
Anti-TPO antibodies
Lymphocytic infiltrate with germinal centers
Painless goiter
Transient hyperthyroidism
Progression to overt hypothyroidism
Postpartum Thyroiditis
Granulomatous Thyroiditis
Demographic, Pathogenesis (2) Morphology (2) Clinical Feature and Lab Values (2)
Women aged 40 to 50
Triggered by viral infection
Associated with HLA B35
Multinucleated giant cells enclose colloid
Granulomatous formations\
Thyroid Pain
High T4/T3
Low TSH
Riedel Thyroiditis
Pathogenesis, Morphology (2), Lab Values (2)
IgG4 mediated thyroiditis
Fibrosis extending from thyroid into adjacent tissues
Lymphocytic and Plasma cell infiltration
Normal T4/T3
Normal TSH
Diffuse Goiters
Demographics (2) Etiologies (3) Morphology (3) Lab Values (2) and Clinical Features (4)
15-25 years old
Women (sporadic etiology)
Decreased thyroid synthesis from:
Insufficient dietary iodine
Goitrogens: cassava root, Brassicaceae vegetables
Sporadic
Diffuse and symmetrical thyroid enlargement
Follicular hyperplasia
Abundant colloid
Normal T4/T3
Normal TSH
Dysphagia
Hoarseness
Stridor
Superior Vena Cava Syndrome
Multinodular Goiters
Age Group, Etiology, Morphology (3), Lab Values (2) Clinical Features (4)
Ages 26+
Long standing simple diffuse goiter
Massively enlarged thyroid
Follicular hyperplasia
Substernal, intrathoracic growth
Normal-Raised T4/T3
Undetectable TSH
Dysphagia
Hoarseness
Stridor
Superior Vena Cava Syndrome
Thyroid Nodule Detection Lab Techniques
Radioisotope (2) and Fine Needle Aspiration (2)
Radioiodine Scanning:
Hot areas show hyperfunctioning nodules
Cold areas more likely to be neoplastic
Fine Needle Aspiration
Determines cellular components of nodule
Helps to determine neoplasm vs hyperplasia
Follicular Adenoma
Prognosis, Genetics (2) Morphology (2)
Presentation (2) and Diagnosis (3)
Benign
Somatic mutation of TSH receptor signaling pathway
Gain of function GNAS mutation
Solitary, spherical lesion
Well defined INTACT capsule
Unilateral painless mass
Mass effect if larger
Cold spot on radioisotope
FNA
Definitive requires surgical excision
Papillary Carcinoma
Prognosis, Age Group, Genetics (2) Morphology (3) Clinical Features (3)
Malignant (most common malignancy)
Ages 25-50
RET/PTC fusion gene
BRAF gain of function mutation
Well differentiated cells
Psammoma bodies
Orphan Annie eye nuclei (clear cytoplasm)**
Excellent prognosis
Asymptomatic
Palpable nodule
Papillary Carcinoma Subclasses with Descriptions
Follicular (2) Tall Cell (3) and Diffuse Sclerosing (3)
Follicular:
RAS Mutations
More aggressive and invasive
Tall Cell:
BRAF mutations
More aggressive
Seen in older patients
Diffuse Sclerosing:
RET/PTC translocations
Distant metastases
Presents in kids
Follicular Carcinoma
Prognosis, Demographics (2), Genetics (2) Invasive Features (2)
Malignant
More common in women
More common in areas of iodine deficiency
RAS mutation
PAX8/PPARG mutation
**Capsule invasion (mushroom shape)
Angioinvasion with Hematogenous metastasis
