THYROID - medicine.tamhsc.edu•Glucagonoma •Presents with: necrotizing migratory erythematous...
Transcript of THYROID - medicine.tamhsc.edu•Glucagonoma •Presents with: necrotizing migratory erythematous...
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THYROID
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Hypothalamic-Pituitary-Thyroid Axis Regulation
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T3 and T4 Metabolism
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Thyroxine Metabolism• T4 produced only in thyroid
• T3 is produced by deiodination of T4 (80%)/Thyroid (20%)
• Enzymes made in multiple tissues:• Type I – PTU sensitive
• Liver, kidney, thyroid
• rT3>T4>T3
• Type II – PTU insensitive
• Muscle, brain, pituitary, skin and placenta
• T4>rT3
• T3 most biologically active but degraded quickly
• rT3 degraded even faster than T3 (but is biologically inactive)
• T4 and T3 are protein bound• FREE molecules are the players
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Laboratory Testing Options
• TSH
• T3
• T4
• Free T4
• Anti-thyroglobin
• Anti-thyroid peroxidase
• Also have more esoteric testing that is sent out• Takes a long time
• More expensive
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Thyroid Function Laboratory Testing
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Laboratory Testing
• First Test Always!!!!!• TSH
• If elevated TSH:• Hypothyroid state
• Clinical TSH > 10
• Subclinical TSH 5-10
• If decreased TSH:• Hyperthyroid state
• Endogenous Graves’ disease, multinodular goiter, thyroid producing neoplasm
• Exogenous Taking oral thyroxine
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Laboratory Testing
• If normal TSH:• EuthyroidMaybe, maybe not
• Important to keep in mind whether there is an appropriate response versus an impaired response!!!!!!
• Free T4
• Elevated despite normal TSH hyperthyroid state
• Depressed despite normal TSH hypothyroid state
• TRH stimulation test• Used to help determine whether pituitary-associated hyperthyroidism
• Normal: Following TRH injection TSH rise
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Radioiodine Uptake Testing
• Increased uptake: • Solitary
• Toxic adenoma
• Diffuse• Graves’ disease
• Decreased uptake:• Thyroiditis
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Fine Needle Aspiration
• Biopsy superficial masses to determine their significance.
• Cytology: The appearance of the cells themselves and the context of the background help determine a diagnosis.
• Pros: On-site evaluation, quick, no need for surgery, you get to visit with your friendly pathologist
• Cons: Cannot definitively diagnose follicular lesions, cannot always get diagnostic material
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FNA Procedure
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Entities that can be diagnosed by FNA
• Non-neoplastic• Acute thyroiditis• Subacute thyroiditis• Hashimoto’s thyroiditis• Reidel’s thyroiditis• Graves’ disease• Amyloid goiter
• Neoplastic• Follicular carcinoma• Hurthle cell carcinoma• Papillary thyroid carcinoma• Poorly differentiated carcinoma• Undifferentiated carcinoma• Medullary thyroid carcinoma• Metastatic neoplasms• Lymphoma
Screening
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Disease
Neoplastic
Benign
Cyst Nodule Adenoma Hurthle cell
Malignant
Papillary
Tall cellFollicular variant
Etc
Follicular Anaplastic
Non-neoplastic
Inflammatory Autoimmune Goiter
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Disease
Thyrotoxicosis Hypothyroid Euthyroid
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Graves’ Disease
• Hypermetabolic state• Decreased TSH
• Increased T4, T3
• Overactivity of the SYMPATHETIC nervous system
• Symptoms• General: Inability to gain weight, sweating, ex ophthalamos
• Skin: Dry skin
• CV: Palpitations, tachycardia, cardiomegaly, arrhythmia
• CNS: Anxiety, tremor, insomnia, emotional lability
• GI: Hypermotility, diarrhea
• Musculoskeletal: Osteopenia/porosis, loss of muscle tone
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Graves’ Disease
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Graves’ Disease
• Diffuse hyperplasia and hypertrophy of epithelial cells• Looks papillary
• NO fibrovascular cores
• Scalloped colloid
• Inflammatory infiltrate –lymphocytes, plasma cells
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Normal Thyroid
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Graves’ Disease
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Multinodular Goiter
• Asymmetric enlargement of the thyroid• Can involve one or all aspects of the gland
• Can reach >2000g
• Can degenerate and form scar, calcifications, and hemorrhage
• Microscopic: • Colloid-rich follicles lined by flattened, inactive epithelium with follicular
hyperplasia
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Multinodular Goiter
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Benign Thyroid Nodule
Sheets of follicular cells with NO overlapping, round nuclear borders, possible nucleoli
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Thyroid Storm
• Abrupt onset of hyperthyroidism
• DANGEROUS!• Arrhythmia leading to death
• Sx:• Febrile
• Tachycardia
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Disease
Thyrotoxicosis Hypothyroid Euthyroid
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Thyroiditis
• Disease of the thyroid that includes inflammation
• Two typical presentations• Painful
• Infectious thyroiditis
• Subacute granulomatous thyroiditis
• Thyroid dysfunction• Hashimoto’s thyroiditis
• Subacute lymphocytic thyroiditis
• Fibrous (Reidel) thyroiditis
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Hashimoto’s Thyroiditis
• Common cause of hypothyroidism in US
• Women 10-20:1
• Benign
• Inflammatory!!!! Autoimmune destruction!• Anti-Thyroglobulin
• Anti-thyroperoxidase
• Description: Extensive lymphoctyic infiltrate with plasma cells. Well developed germinal centers. Breakdown of thyroid colloid. Hurthlecell change.
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Hashimoto Thyroiditis
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Hashimoto’s Thyroiditis FNA
Hurthle cells with abundant eosinophilic cytoplasm
Lymphocytes
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Subacute Granulomatous Thyroiditis
• AKA: De Quervain thyroiditis
• Etiology: viral illness
• Painful thyroid
• Transient condition but will be hyperthyroid• ↓ TSH, ↑ T3 , ↑ T4
• Description: Look for neutrophils and microabscesses destroying the follicles early in the disease course. Later, see multinucleated giant cells, histiocytes, lymphocytes, and plasma cells.
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Subacute Granulomatous Thyroiditis
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What’s at the solid arrows?
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What is within the dashed circles?
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What are the dashed arrows pointing to?
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What do the boxes enclose?
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Subacute Lymphocytic Thyroiditis
• Painless
• Sx:• Mild hyperthyroidism
• Diffuse thyroid enlargement
• Description: hyperplastic germinal centers within the thryoid parenchyma and patchy disruption of colloid follicles. Hurthle cell metaplasia, fibrosis NOT prominent.
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Thyroid Follicular Neoplasms
BenignMalignant
Criteria to distinguish benign versus malignant thyroid FOLLICULAR neoplasms:
1)Capsular invasion2)Lymphovascular invasion3)Metastasis
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Follicular Adenoma
• Typically solitary, well-encapsulated nodule
• Can see hemorrhage, fibrosis, calcifications, cystic change
• Microscopically: Uniform appearing cells that contain colloid. Looks different from the normal thyroid (more densely crowded, but still bland). Mitotic figures are rare.• NO lymphovascular or capsular invasion
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Follicular Adenoma
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Follicular Carcinoma
• Similar to Adenoma BUT:• Capsular invasion +/- lymphovascular invasion
• Pleomorphic nuclei
• Mitoses
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Follicular Carcinoma
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Papillary Thyroid Carcinoma
• Most common thyroid carcinoma (85%)
• Younger women
• Metastasis common
• Microscopic: • Papillary architecture – look for fibrovascular cores
• Psammoma bodies – laminated calcified structures
• Cytology – EXTREMELY important• Nuclear inclusions
• Nuclear grooves
• Powdery chromatin
• Overlapping cells
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Papillary Thyroid Carcinoma
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PTC
Nuclear grooves
Fine chromatin
Inclusion
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Medullary Carcinoma
• Arise from C cells• Identified by calcitonin
• Sporadic • Solitary nodule
• MEN2A or MEN2B syndrome• Bilateral, multinodular
• Microscopic: polygonal to spindle-shaped cells, form nests or trabeculae, amyloid deposits
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Medullary Carcinoma
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Medullary Carcinoma
Left: Spindled, bland appearing hypercellularsmear.
Below: spindled cells with amorphous amyloid deposits.
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ENDOCRINE PANCREAS
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Endocrine Pancreas Function
• Hormones• Insulin
• Glucagon
• Incretins
• Somatostatin
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Insulin
• Pre-proinsulin insulin + C-peptide • [C-peptide] in serum is much higher than insulin
• Insulin has high hepatic clearance
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Insulin
• Hyperinsulinemia• Cirrhotic
• High insulin and High C-peptide
• Exogenous• High insulin and Low/Absent C-peptide
• Neoplasm• Insulinoma
• High insulin and High C-peptide
• Profound hypoglycemia
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Endocrine Pancreas
ALPHA CELLS BETA CELLS
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Diabetes
• Diabetes Type 1• Insulin DEPENDENT
• DKA
• Lifelong
• Autoimmune
• Destruction of Beta islet cells
• Diabetes Type 2• Insulin Resistance
• Hyperosmolar
• Can be prevented
• Multifactorial• Genetics
• Environmental
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Diabetes Continued
• Gestational Diabetes• Pregnant women
• Leads to increased risk of Type 2 diabetes later on (within 5-10 yrs)
• Requires very close follow-up during the course of the pregnancy
• Very strict glucose control throughout pregnancy
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Ketone Bodies
• Products of fatty acid degradation:• Acetone
• Beta-hydroxybutyrate (BH)
• Acetoacetic acid (AA)
• BH:AA in serum• Normal: 1:1
• DKA: ↑ ↑BH:AA
• Urine test strips are frequently used to ID ketosis:• Test strips DO NOT test for BH
• AA and acetone levels increase during therapy
• Do not use strips to monitor treatment of DKA
• Follow electrolytes and BH assays for treatment!• BH assays can be enzymatic, colorimetric, etc.
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Hypoglycemia
• Glucose levels < 55 mg/dL (healthy person)
• Two types:• Neurogenic
• Tremulousness, diaphoresis, anxiety, palpitations
• Neuroglycopenic• Dizziness, tingling, blurred vision, alterations of mentation
• Severe, prolonged hypoglycemia can lead to BRAIN DEATH!
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Hypoglycemia
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Glucagon• Produced by Alpha cells
• Stimulates glucose production• Important for glycogenolysis, gluconeogenesis and ketogenesis
• Diabetes:• Gradual decrease in alpha cells occurs in Type I
• Glucagon deficiency
• Increasing glycemic fluctuations
• Difficulty recovering from hypoglycemia
• Glucagonoma• Presents with: necrotizing migratory erythematous rash, stomatitis, glossitis, weight
loss, anemia and mild DM
• Increased levels in cirrhosis, pancreatitis, Cushing’s syndrome, acromegaly, and renal insufficiency
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Somatostatin
• Made in DELTA cells• 5-10% of islet cells
• Inhibits:• Pituitary
• GH and thyrotropin
• Gastrointestinal• Gastrin, secretin, VIP
• Pancreatic hormones• Insulin
• Glucagon
• Non-endocrine function• Gastric acid secretion
• Gastric emptying
• Pancreatic enzyme release
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Pathology of Diabetes
Every Organ System can be Affected!
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Diabetes Pathophysiology
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Diabetes Effects on Pancreatic Islet Cells
Type I Type II
Inflammatory infiltrate composed of lymphocytes: INSULITIS
Hyalinization with deposition of AMYLOID
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Diabetic Complications
Vasculature• Atherosclerosis
• Peripheral vascular disease
• Erectile dysfunction
• Why?
Kidney• Thickening of basement
membrane
• Kimmelstiel-Wilson nodules
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Glomerulus
Arteriole
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Kimmelstiel-Wilson Nodule
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Neuroendocrine Neoplasms of the Pancreas
• 1 - 2% of all pancreatic neoplasms
• Occur at any age but are rare in childhood (usually age 40-60), no sex predilection
• Approximately 10% are associated with a syndrome and will occur at a younger age • multiple endocrine neoplasia type 1 syndrome (60% of patients have
pancreatic neuroendocrine tumors and 80% have pancreatic microadenomatosis/hyperplasia)
• neurofibromatosis 1 syndrome (1% of patients have pancreatic neuroendocrine tumors)
• von Hippel-Lindau syndrome (16% of patients have pancreatic neuroendocrine tumors)
• tuberous sclerosis complex (rare)
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Neuroendocrine Neoplasms of the Pancreas
• Nonfunctional tumors are encountered incidentally and are usually larger at time of diagnosis
• Local obstruction/mass effect, if located in the pancreatic head
• Other clinical features of MEN1, VHL, NF1 or TSC if have syndrome
• Clinical hormonal syndromes in functioning tumors
• Elevated serum chromogranin A in 60-80%
• Solid or solid cystic lesion within any part of the pancreas on radiology
• Surgical resection is the predominant treatment with resolution of both mass effect symptoms and symptoms associated with hormone secretion. Chemotherapy has a limited role unless high grade or extensive disease
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Neuroendocrine Neoplasms of the Pancreas
• Insulinoma• Most common functioning pancreatic neuroendocrine tumor
• Insulin secretion
• Hypoglycemic syndrome
• Solitary tumor < 2 cm
• 5 - 10% of insulinomas are associated with MEN1 and are usually multiple
• Benign in 90%
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Neuroendocrine Neoplasms of the Pancreas
• Gastrinoma: • Second most common functioning pancreatic neuroendocrine tumor
• Gastrin secretion
• Zollinger-Ellison syndrome (peptic ulcers, gastroesophageal reflux, diarrhea)
• "Gastrinoma triangle" (common bile duct, duodenum, pancreatic head)
• Duodenum affected more than pancreas
• 20 - 30% of gastrinomas are associated with MEN1
• Malignant in 80%
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Neuroendocrine Neoplasms of the Pancreas
• Glucagonoma• 4Ds: diabetes, dermatitis (necrolytic migratory erythema), deep vein
thrombosis, depression
• Solitary, large
• Tail > head
• > 50% have metastasis at presentation
• VIPoma• Verner-Morrison syndrome: watery diarrhea, hypokalemia,
achlorhydria/hypochlorhydria
• Solitary, large
• Tail > head
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Neuroendocrine Neoplasms of the Pancreas
• Somatostatinoma• Diabetes mellitus, diarrhea or steatorrhea, anemia, malabsorption,
cholelithiasis
• Very rare
• Solitary, large
• > 50% have metastasis at presentation
• Ectopic hormone producing neuroendocrine tumor• ACTH (Cushing syndrome), serotonin, growth hormone
• Usually malignant
• Solitary, large
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Neuroendocrine Neoplasms of the Pancreas
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Neuroendocrine Neoplasms of the Pancreas
• Firm, commonly well circumscribed, homogeneous
• Tumors may have a cystic component
• Color varies according to the degree of vascularity and amount of stroma and ranges from white to pink to tan to brown; may be yellow if necrosis present
• "Pigmented black pancreatic neuroendocrine tumor" is composed of intracytoplasmic lipfuscin and mimics metastatic melanoma
• "Lipid rich" pancreatic neuroendocrine tumor mimics adrenal cortical neoplasia
• Features of malignancy: invasion of fibroadipose tissue (as satellite nodules), invasion of adjacent organs, invasion of large vessels
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Neuroendocrine Neoplasms of the Pancreas
• Well differentiated neuroendocrine tumors• Organoid architecture: solid nests, trabeculae, gyri, cords, festoons, ribbons,
glandular, acinar, cribriform • Small to medium cells with eosinophilic to amphophilic and finely granular
cytoplasm; nuclei are uniform, central, round/oval, with "salt and pepper" (finely stippled) chromatin; no/inconspicuous cytoplasm
• Rich vascular network • Amyloid deposition in insulinomas• Psammoma bodies in somatostatinomas• Hyaline globules
• Poorly differentiated neuroendocrine carcinomas• Sheets or nests of atypical cells with pleomorphic, hyperchromatic nuclei and
abundant mitotic figures • "Salt and pepper" chromatin is lost • Necrosis often present • May be small cell (molding nuclei, scant cytoplasm) or large cell (abundant
amphophilic cytoplasm; may also have visible nucleoli)
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Neuroendocrine Neoplasms of the Pancreas
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Neuroendocrine Neoplasms of the Pancreas
• Cytology description• Small / medium sized cells
• Amphophilic, finely granular cytoplasm (neurosecretory capability)
• Round / oval, uniform, centrally located nuclei without prominent nucleoli
• May be plasmacytoid
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Neuroendocrine Neoplasms of the Pancreas
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Neuroendocrine Neoplasms of the Pancreas
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Neuroendocrine Neoplasms of the Pancreas
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Neuroendocrine Neoplasms of the Pancreas
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Neuroendocrine Neoplasms of the Pancreas
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Neuroendocrine Neoplasms of the Pancreas
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Neuroendocrine Neoplasms of the Pancreas
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Neuroendocrine Neoplasms of the Pancreas
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Endocrine Syndromes