Week 7 Flashcards
(119 cards)
1
Q
What is the location of the thyroid in the body?
A
- Two lobe located in lower neck, anterior and anterolateral to the trachea
2
Q
Blood supply of the thyroid?
A
- Blood supply
- R + L superior thyroid arteries (from external carotid arteries)
- R + L inferior thyroid arteries (from thyrocervical trunks)
3
Q
Venous drainage of the thyroid
A
- Venous drainage
- R + L superior thyroid veins (into IJ veins)
- R + L middle thyroid veins (into IJ veins)
- R + L inferior thyroid veins (into brachiocephalic veins)
4
Q
What is important to know about the recurrent laryngeal nerves? Also what is their function?
A
- R+L Recurrent laryngeal nerves
- Sensory below the vocal cords and motor function to all intrinsic muscles of the larynx
- Risk of damage during thyroidectomy
5
Q
How many parathryoid glands are there? Where are they located?
Blood supply of parathyroid?
A
Parathyroid Glands
- 4 glands (2 on each side) located in posterior region of each thyroid lobe
- Inferior thyroid arteries supply 100% of the inferior parathyroid glands and 85% of superior parathyroid glands
- Superior thyroid arteries supply 15% of the superior parathyroid glands
6
Q
What is the pathway of the hypothalamic-pituitary-thyroid axis?
How does negative feedback occur?
A
Regulation of Hypothalamic-Pituitary-Thyroid Axis
- Pathway: Hypothalamus releases TRH → anterior pituitary release TSH → TSH stimulates gland growth → TSH stimulation + dietary iodine → T4 and T3 (less) release
- Negative inhibition: TRH and TSH release inhibited by high levels of T3 and T4
7
Q
How is the thyroid hormone synthesized? Provide a detailed pathway!
A
- Pathway:
- TSH binds to TSH receptor (basolateral) → activates Na-I symporter (basolateral) → iodine enters cells → iodine exits cell at apical side via Pendrin
- Synthesis of thyroglobulin (Tg) in ER of cell → Tg secreted at apical side of cell → thyroid peroxidase (TPO) located on apical surface catalyzes reaction between iodine and Tg → Tg-T3/4 → Tg-T3/4 enters cells → exits basolateral side of cell as T3 or T4
8
Q
Know this image.
A
yeah.
9
Q
How much of thyroid hormone is bound? What is it bound by?
A
- BOUND (99.95%) – to serum carrier proteins, which are made by the liver
- Thyroxine-binding globulin (TBG) – principle binding protein
- Thyroxine-binding prealbumin (transthyretin)
- Albumin
10
Q
How much of thyroid hormone is free? What functions and actions does free thryoid hormone have?
A
- FREE (0.05%) – metabolically active form responsible for hormonal activity
- Available to peripheral tissues for intracellular transport
- Participates in negative feedback regulation
- Undergoes degradation and excretion
11
Q
How does the conversion of T4 to T3 occur? What enzyme is involved? What’s so special about T3?
A
Peripheral Conversion of T4
- Serum T4 converted to T3 by intracellular 5’-deiodinase (D1) enzyme in many peripheral tissues
- Accounts for 85% (most) of body’s T3
- T3 is the biologically active and most potent form of thyroid hormone
- T4 converted to inactive reverse T3 (rT3) by peripheral tissues
12
Q
What is the general mechanism of thyroid hormone? How does it act on peripheral tissue?
Give some examples of what would occur when thyroid hormone acts (hypothalamus, pituitary, beta receptors)
A
- MOA: binding to nuclear receptor at target tissues → interact with thyroid hormone response elements (TREs) sequences upstream of target gene promoters → regulation of gene expression
- Ex: T3 decreases gene transcription of TRH (hypothal) and TSH (pituitary) = gives NEGATIVE FEEDBACK
- T3 increases gene transcription of b-adrenergic receptors in heart, liver, muscle, adipocytes
13
Q
What effects does thyroid hormone have on the following:
- BMR?
- O2/CO2
- Carbs/lipids/proteins
- Bones, intestines
A
- Metabolic
- Overall, increases Basal Metabolic Rate (BMR) and affects oxidative metabolism
- Increase O2 consumption, CO2 production, thermogenesis
- Affects Carbohydrate, lipid, and protein metabolism
- Increases glycogenolysis, gluconeogenesis, lipolysis, proteolysis
- Increase bone turnover, intestinal motility, erythropoiesis
- Normal CNS function
14
Q
What effects does thyroid hormone have on the following:
- adrenergic?
- Brain?
- Bones?
- Sexual characteristics?
A
- Potentiates adrenergic stimuli/catecholamines
- Positive chronotropic and inotropic effect – increases HR and CO; decreases SVR
- Promotes normal Growth and Development
- Brain development and maturation
- Skeletal and muscle growth and maturation
- Sexual maturation
15
Q
What is the best way to test your thyroid initially?
A
- Measurement of TSH level (highly sensitive; best initial test for primary thyroid dysfunction)
16
Q
What are two other measurements of thyroid (other than TSH)?
A
- Measurement of circulating thyroid hormone levels
- FREE serum T4 (FT4) and free T3 (FT3) = most important
- TOTAL serum T4 (TT4) and T3 (TT3)
17
Q
What are some things that can increase your total serum T4? How does this occur?
A
- Increase thyroid hormone binding proteins (increase total hormone levels):
- Hyperestrogenic states (estrogen Tx, pregnancy)
- Drugs (heroin, methadone, clofibrate, 5FU, major tranquilizers)
- Acute hepatitis
- Congenital TBG excess
18
Q
What are some things that can decrease your total serum T4? How does this occur?
A
- Decrease thyroid hormone binding proteins (decrease total hormone levels due excessive negative feedback):
- Drugs (androgenic steroids, glucocorticoids, L-asparaginase)
- Protein malnutrition or loss (nephrotic syndrome, protein losing enteropathy)
- Cirrhosis
- Major systemic illness
- Congenital TBG deficiency
19
Q
For the following conditions, know concentration of binding proteins, total plasma T4/T3, free plasma T4/T3, plasma TSH, and clinical thyroid state:
- Hyperthyroidism
- Hypothyroidism
- Estrogens, methadone, heroin, etc
- Glucorticoids, androgens, danazol
A
20
Q
Describe thyrotoxicosis.
A
- Description: hypermetabolic state and increased sympathetic tone due to excessive thyroid hormones
21
Q
List symptoms/signs of thyrotoxicosis.
A
- Clinical features: heat intolerance (due to high BMR), tachycardia/palpitations, arrhythmias (A-fib), weight loss (high BMR), nervous/tremor (increased sympathetic), warm/moist skin, excessive sweating, proximal weakness (proteolysis), frequent bowel movements, oligomenorrhea (prolactin induced), bone resorption, hypocholesterolemia (increased LDLr), hyperglycemia (gluconeogenesis)
22
Q
What are labs of thyrotoxicosis?
A
- Dx: decreased TSH, increased T4
23
Q
What are some treatments of thyrotoxicosis?
A
- Treatment: beta blockers, thionamides (methimazole, propylthiouracil), radioactive iodine (I-131 ablation), surgery (thyroidectomy)
24
Q
What is the biggest complication of thyrotoxicosis? List pathophys, labs, and treatment for this.
A
- Complication: thyroid storm
- Pathophysiology: underlying hyperthyroidism + acute stress → elevated catecholamines → hormone excess → arrhythmias/hyperthermia/hypovolemic shock/coma
- Labs: increased LFTs
- Tx (4 Ps): propranolol, propylthiouracil, prednisolone, potassium iodide
25
List classifications of thyrotocicosis with different diseases listed.
* High/normal iodine uptake
* Production (primary hyperthyroidism)
* Grave’s Disease
* Multinodular goiter
* Toxic adenoma
* Suppressed iodine uptake
* Destructive thyrotoxicosis
* Subacute Granulomatous (De Quervain) Thyroiditis
* Subacute Lymphocytic (Silent) Thyroiditis/Postpartum thyroiditis
* Exogenous (factitious or iatrogenic)
* Iodine-induced thyrotoxicosis
* Exogenous ingestion of thyroid hormone
26
For Grave's
* Epidemiology
* Pathophys
* Dx
**Classifications of Thyrotoxicosis**
* High/normal iodine uptake
* Production (primary hyperthyroidism)
* Grave’s Disease
* Epidemiology: females, 20-40s, HLA DR3 or B8
* Pathophysiology (type II hypersensitivity): TSH-receptor IgG autoantibody (TSI) → stimulates TSH receptor → increased synthesis of TH due to thyroid cell growth
* Dx: iodine uptake scan (diffuse increased iodine uptake)
* Histology: crowded epithelial follicular cells with scalloped colloids
27
For Grave's
* Histology
* Unique features
**Classifications of Thyrotoxicosis**
* High/normal iodine uptake
* Production (primary hyperthyroidism)
* Grave’s Disease
* Histology: crowded epithelial follicular cells with scalloped colloids
* Unique features: diffuse, symmetric goiter, myxedema (swelling of dermofibroblasts), Graves’ opathalomopathy (exophthalamos)
* Exopthalamos: infiltration of retroorbital space by T-cells → increased cytokine release → increased fibroblast release of hydrophilic glycoaminoglycans → increased osmotic edema → bulging of eyes anteriorly
28
For multinodular goiter:
* Description
* Pathophys of two subtypes
* Diagnosis
* Micropathology
* Multinodular goiter
* Description: enlarged thyroid with multiple nodules due to iodine deficiency or TSH receptor mutations
* Can be toxic or non-toxic
* Toxic: leads to excessive T4 release → hyperthyroidism
* Diagnosis:
* Iodine uptake scan (focalized areas of increased uptake → multinodular goiter)
* Micropathology: distended colloids
29
For toxic adenoma:
* Descirbe it
* Diagnosis
* Toxic adenoma
* Description: benign hyperplasia of thyroid glands
* Dx: iodine uptake scan (singular hot nodule → focalized area of increased uptake)
* If malignant: nodule is hypoechoic or “cold” on iodine uptake scan
30
For subacute granulomatous thyroiditis:
* Whats another name for this?
* Decription
* Pathophys
* Findings
* Treatment
* Destructive thyrotoxicosis
* Subacute Granulomatous (De Quervain) Thyroiditis
* Description: tender, PAINful (QuerVAIN), enlarged thyroid
* Pathophysiology: viral infection → granuloma of thyroid
* Early, transient hyperthyroidism → late hypothyroidism
* Findings: increased ESR, jaw pain, negative antibodies, +/- fever
* Treatment: NSAIDS, salicylates, beta blockers
31
For subacute lymphocytic thryoiditis:
* What are some other names for it?
* Description
* Pathophys
* Findings
* Dx
* Subacute Lymphocytic (Silent) Thyroiditis/Postpartum thyroiditis
* Description: autoimmune, painless, enlarged thyroid
* Pathophysiology: autoimmune attack on thyroid
* Common post-partum when immune system is quickly picking back up (often recurs with subsequent pregnancies)
* Early, transient hyperthyroidism → late hypothyroidism
* Findings: antibodies positive (anti-TPO), no fever
* Dx: low iodine uptake (distinguishes from Grave’s disease)
32
For iodine induced thyrotoxicosis:
* Pathophys
* Risk factors
* Iodine-induced thyrotoxicosis
* Pathophysiology: excessive exogenous iodine → negative feedback on thyroid → decreased iodine uptake (Jod-Basedow effect)
* Risk factors: previous thyroid disease (Grave’s disease, MNG)
33
For exogenous ingestion of thyroid hormone:
* Pathophys
* Exogenous ingestion of thyroid hormone
* Pathophysiology: over-ingestion of thyroid hormone → decreased serum thyroglobulin levels (high in other causes of hyperthyroidism)
34
Descirbe hypothyroidism
**Hypothyroidism**
* Description: disorder in which the thyroid gland fails to secrete adequate amounts of thyroid hormone
35
What are the symptoms of hypothryoidism?
**Hypothyroidism**
* Signs/symptoms:
* Cold intolerance, weight gain (low BMR), decreased appetite, constipation, decreased reflexes (slowed sympathetic), muscle cramps (increased creatinine kinase), myxedema (accumulation of glycoaminoglycans → severe edema), anemia, hyponatremia, hypercholesterolemia (decreased LDLr), constipation, bradycardia, dyspnea, oligomenorrhea (prolactin-induced)
36
What is the outline of hypothryoidism with the diseases?
* Primary: diseases or treatments that destroy thyroid tissue or interfere with thyroid hormone synthesis (increased TSH, decreased T4)
* Chronic Lymphocytic Thyroiditis (Hashimoto’s thyroiditis)
* Neonatal hypothyroidism (cretinism)
* Riedel thyroiditis
* Others: radiation injury, post-thyroidectomy, thyroid gland agenesis, idiopathic hypothyroidism, iodine deficiency, acute iodine excess in thyroid disease, meds
* Central: results from pituitary (secondary) or hypothalamic (tertiary) disease
37
For chronic lymphocytic thyroiditis:
* What is another name?
* Epidemiology
* Pathophys
* Labs
* PE
* Complications
* Chronic Lymphocytic Thyroiditis (Hashimoto’s thyroiditis)
* Epidemiology: female, HLA DR5, most common cause of hypothyroidism (presents as hyperthyroidism early)
* Pathophysiology: chronic antibodies against thyroglobulin or TPO → thyroid destruction
* Labs: anti-TPO, firm goiter
* PE: enlarged, non-tender thyroid
* Complications: increased risk of B-cell lymphoma
38
For neonatal hypothyroidism:
* Another name?
* Etiologies (two groups)
* Findings
* Screening
* Tx
* Neonatal hypothyroidism (cretinism)
* Etiologies:
* Permanent hypothyroidism: thyroid dysgenesis, thyroid hormone defects, TSH/TRSH defects/deficiencies, TSH/TRH unresponsiveness
* Transient hypothyroidism: extreme prematurity, maternal anti-thyroid meds, iodide deficiency (maternal/newborn), maternal TSHr antibodies, maternal hypothyroidism
* Findings (6 P’s): Pot-bellied, Pale, Puffy-faced, Protruding umbilicus, Protuberant tongue, Poor brain development
* Lack of epiphyseal growth and patent fontanelle
* Screening: heel prick (day 2-5)
* TT4 strategy: may miss compensated hypothyroidism due to normal TT4 levels, but high TSH
* TSH strategy: TSH deficiency due to central hypothyroidism will be missed due to normal TSH levels
* Tx: thyroxine immediately, monitor
39
For Riedel thyroiditis:
* Pathophys?
* Findings
* Complications
* Riedel thyroiditis
* Pathophysiology: chronic inflammation → fibrosis of thyroid gland → hypothyroidism
* Findings: VERY hard non-tender thyroid gland
* Complications: fibrosis may spread to esophagus and trachea
40
What are some other causes of primary hypothyroidism?
* Others: radiation injury, post-thyroidectomy, thyroid gland agenesis, idiopathic hypothyroidism, iodine deficiency, acute iodine excess in thyroid disease, meds
41
What are the labs associated with central hypothyroidism?
* Central: results from pituitary (secondary) or hypothalamic (tertiary) disease
* Low T4 with a low-normal TSH
42
For nonthyroidal illness syndrome
* What are two other names?
* Pathophys?
* Treatment?
**Nonthyroidal illness (NTI) syndrome/Euthyroid sick syndrome/Low T3 syndrome**
* Pathophysiology: severe illness → alterations in peripheral TH metabolism and transport → low T3
* These changes are a “protective mechanism”
* Treatment: NONE, do not assess thyroid function unless strong suspicion of disease
43
Describe PTH. What is it increased by?
* Parathyroid hormone (PTH)
* Description: protein secreted by the chief cells to regulate serum calcium levels
* Increased by: decreased serum Ca (via Ca-sensing receptor), decreased active Vit D, increased phosphate, and decreased Magnesium/Aluminum/Strontium
44
What are 4 main actions of PTH? Understand the pathophys of each.
* Actions
* Increases bone osteoclast activity → releases Ca and PO4
* Continuous PTH → RANKL release from osteoblasts → RANKL binds RANK on osteoclasts → stimulation of osteoclast activity → bone resorption → increased serum Ca
* Intermittent PTH → bone formation
* Activates Vit D via 1-alpha-hydroxylase → increases calcitriol → increased small bowel absorption of Ca and PO4
* Increased renal calcium reabsorption at distal tubule
* Decreased phosphate reabsorption at proximal tubule (balances increased PO4)
45
For primary hyperparathyroidism
* Etiologies (3)
* Labs
* Complication
* Treatment
* Primary hyperparathyroidism
* Etiologies: adenomas (majority), glandular hyperplasia, carcinomas
* Labs: increased PTH, increased Ca, decreased phosphate, increased urinary cAMP, increased alkaline phosphate, decreased bone density
* Complication: nephrogenic diabetes insipidus due to hypercalcemia (polyuria, polydipsia)
* Treatment: parathyroidectomy, denosumab (RANKL inhibitor), bisphosphonates, cinacalcet (activates Ca-sensing receptors → decreases PTH secretion)
46
What are the clinical findings associated with primary hyperparathyroidism? Explain each one.
* Clinical: bone pain, kidney stones, polyuria, abdominal pain, and depression (bones, stones, thrones, groans, and psychiatric overtones)
* Bones: osteitis fibrosa cystica (brown fibrous tissue consisting of osteoclasts and deposited hemosiderin → lytic lesions and eating away of bones), osteomalacia, and osteoporosis
* Stones: hypercalciuria → calcium oxalate and phosphate stones → nephrocalcinosis/renal insufficiency (due to damage)
47
For secondary hyperparathyroidism
* Clinical
* Labs
* Tx
* Secondary hyperparathyroidism
* Clinical: renal osteodystrophy (osteitis fibrosa cystica, osteomalalcia), deformities, fractures
* Labs: increased PTH, decreased Ca,
* Tx: Ca, Vit D replacement, phosphate binders (indicated for CKD/ESRD)
48
Explain the etiologies associated with secondary hyperparathyroidism and why they cause the disease
* Secondary hyperparathyroidism
* Etiologies: Celiac’s, pancreatitis, antiseizure meds, vit D dependent rickets (1-alpha-hydrxylase mutation), vit D resistance
* CKD/ESRD or nutritional deficiency/malabsorptive state: decreased 1-alpha-hydroxylation of Vit D → decreased calcium absorption from GI tract/decreased phosphate clearance from urine → hypocalcemia, hyperphosphatemia, hypomagnesemia, hypovitaminosis D
49
For tertiary hyperparathyroidism:
* Etiology
* Labs
* Clinical signs
* Treatment
* Tertiary hyperparathyroidism
* Etiology: chronic ESRD → prolonged stimulation of parathyroid glands → glandular hyperplasia → increased PTH → hypercalcemia, decreased calcitriol, increased phosphate
* Labs: VERY high levels of PTH (\>800pg/mL), hypercalcemia, hyperphosphatemia
* Clinical: osteitis fibrosa cystica, bone pain, fractures, extraskeletal calcification
* Treatment: parathyroidectomy
50
For hypoparathyroidism:
* What are clinical signs?
* Labs?
* Hypoparathyroidism
* Clinical: tetany (muscle spasms), prolonged QT interval/arrhythmia/HF, paresthesias/tingling (circumoral: around mouth)
* **Ch**vostek’s sign: tapping on facial nerve (**Ch**eek) → contraction of facial muscles
* **Tr**ousseau’s sign: occlusion of brachial artery (**Tr**icep) with BP cuff → carpal spasms
* Labs: hypocalcemia, hyperphosphatemia, low PTH
51
What are etiologies of hypoparathyroidism? What is one syndrome?
For that syndrome, describe it, provide genetic etiology, and clinical signs.
* Hypoparathyroidism
* Etiologies: surgical removal/radiation of parathyroid gland, autoimmune destruction, infiltrative diseases/metastatic cancer, DiGeorge syndrome
* DiGeorge syndrome:
* Description: abnormal development of third and fourth branchial pouches
* Etiology: deletion of chromosome 22q11
* Clinical: hypocalcemia, thymic aplasia, cardiac defects, developmental delay, characteristic facial appearance (flat bridge of nose, low set ears, small jaw, cleft lip/palate)
52
For psuedohyperparathyroidism:
* Etiologies (name a disease)
* gentic mutation
* Clinical signs
* * Labs
* Complications
* Treatment
* Pseudohypoparathyroidism
* Etiologies: end-organ resistance to PTH (affecting kidneys, bones are spared)
* Albright’s Hereditary Osteodystrophy (inherited **_maternal_** allele)
* Autosomal dominant mutation in GNAS1 gene → failure to encode for PTH protein G receptor
* Clinical: shortened 4th/5th digits, short stature
* Labs: hypocalcemia, hyperphosphatemia, elevated PTH
* Complications: end organ resistance in thyroid and gonads
* Treatment: replace Ca, calcitriol, replaced respective hormones
53
For pseudopsuedohyperparathyroidism:
* Etiologies (name a disease)
* gentic mutation
* Clinical signs
* labs
* Pseudopseudohyperparathyroidism
* Etiologies: NO end-organ resistance to PTH
* Albright’s Hereditary Osteodystrophy (inherited **_paternal_** allele)
* Clinical: shortened 4th/5th digits, short stature
* Labs: normal lab findings (only physical exam findings)
54
For MEN-1:
* Genetics
* Epidemiology
* What do they present with?
* Dx
* Management
**MEN-1**
* Genetics: associated with autosomal dominant mutation of menin (tumor suppressor on chromosome 11) – need two hits for inactivation
* Epidemiology: rare, peak age (men: 4th decade/women: 3rd decade), high mortality
* Mortality due to: malignant islet cell tumor, malignant carcinoid tumor
* Clinical presentation (3 P’s): must have 2/3 for diagnosis
* **P**arathyroid (90%): primary hyperparathyroidism
* **P**ancreatic islet cell (70%): gastrinoma, insulinoma, non-functioning tumor, VIP-oma, glucagonoma, somatostatinoma
* **P**ituitary (anterior) (20%): prolactinoma, pituitary tumors (GH, TSH, GnRH, ACTH)
* Dx/screening: imaging, somatostatin-receptor scintigraphy, endoscopic US, labs annually (calcium, PTH, gastrin, pancreatic polypeptide, prolactin, IGF-1)
* Management: treat underlying tumors
* Will always remove parathyroid before treatment of gastrinoma → will decrease Ca++ and reduce size of gastrinoma
55
For MEN-2A:
* What is another name?
* Genetics?
* Epidemiology?
* Clinical presentation?
**MEN-2A (Sipple’s Syndrome)**
* Genetics: associated with autosomal dominant mutation in proto-oncogene RET (codes for receptor tyrosine kinase)
* Gain of function → MEN syndromes; loss of function: Hirschprung’s disease
* Epidemiology: peak incidence in 30s
* Clinical presentation (2 P’s + MTC):
* Medullary thyroid carcinoma (90%) – neoplasm of C-cells that produce calcitonin
* **P**heochromocytoma (50%)
* **P**arathyroid hyperplasia (10%)
56
For MEN-2B:
* Genetics
* Clinical presentation
**MEN-2B**
* Genetics: associated with autosomal dominant mutation in proto-oncogene RET (codes for receptor tyrosine kinase)
* Clinical presentation (1 P + others)
* Medullary thyroid cancer (100%)
* **P**heochromocytoma (50%)
* Mucosal ganglioneuromas (oral/intestinal)
* Marfanoid habitus (75%)
57
What action needs to be taken for someone with either medullary thyroid cancer or pheochromocytoma?
* Any patient with pheochromocytoma or medullary thyroid cancer should be referred to geneticist to check for MEN
58
What are the treatments/management for pheochromocytoma? For medullary thyroid carcinoma?
* Treatments
* Pheochromocytoma: surgical resection with possible partial adrenalectomy
* Medullary thyroid carcinoma:
* Evaluate for possible medullary thyroid carcinoma
* Total thyroidectomy and resection of all involved structures (i.e. trachea)
59
What are the prophylactic treatments indicated for MEN-2a and MEN-2b? By what ages do these need to be completed?
* Prophylactic treatments
* Prophylactic thyroidectomy indicated for MEN-2a (by 5-6 y/o) and MEN-2b (by 6 mo)
60
Normal gross and microfeatures of thyroid
* Gross: homogenous red surface with fibrous septae
* Micro: Lobules (divided by fibrous septae) containing 20-40 follicles (functional unit of the thyroid)
Follicles are filled with colloid (blue arrow) and lined by cuboidal follicular cells (red arrow)
61
Nodular hyperplasia
presentation and pathophys
* Single to multinodular thyroid
* Increased radioactive iodine uptake
* Endemic – lack of iodine in diet, goitrogens
* Sporadic
62
Nodular hyperplasia
gross and micro features
Gross: Multiple variably sized heterogenous nodules
Micro: fibrotic changes (yellow), calcifications (blue), variable sized follicles (resembles normal)
63
Lymphocytic Hyperplasia/ Hashitmoto’s Thyroiditis
presentation and pathophys
and micro features
Multinodular thyroid
Autoimmune (T-cell mediated)
Micro: Lymphocytic infiltration with germinal center formation, destruction of follicular cells, Hurthle cells (light pink blob – blue arrow)
64
follicular ademonas
presentation, causes, genetics
65
follicular ademonas
gross and micro features
Gross: completely encapsulated nodule
Micro: fibrous capsule (yellow), compression of normal parenchyma (blue), benign proliferation (uniform growth, but different from surrounding)
66
Papillary thyroid carcinoma
presentation, causes, genetics
67
Papillary thyroid carcinoma
micro?
Micro: Papillary architecture, empty-appearing nuclei (Orphan Annie – blue arrow), nuclear grooves (yellow arrows), psammoma bodies (calcifications – orange arrow)
68
follicular carcinoma
presenation, causes, genetics
69
Follicular carcinoma
gross and micro features
Gross:
* Encapsulated nodule
* Invasion through capsule (differentiates from follicular adenoma)
* Poorly circumscribed tumor
Micro: proliferation of follicles with possible vascular invasion
70
Medullary carcinoma
presentation, causes, genetics
71
anaplastic carcinoma
presentation, causes, genetics
72
Medullary carcinoma
gross and micro features
Gross: poorly-defined tan mass
Micro: Hyperplasia of c-cells and amyloid stroma (calcitonin deposits seen on Congo red stain – blue arrow)
73
Anaplastic carcinoma
micro features
Micro: Large bizarre malignant cells with prominent mitotic activity and necrosis; no resemblance to any other structures
74
normal thyroid
75
normal thyroid
76
nodular hyperplasia
77
Lymphocytic Hyperplasia/ Hashitmoto’s Thyroiditis
78
Lymphocytic Hyperplasia/ Hashitmoto’s Thyroiditis
79
follicular adenoma
80
follicular adenoma
81
papillary carcinoma
82
papillary carcinoma
83
follicular carcinoma
84
follicular carcinoma
85
Medullary carcinoma
86
Anaplastic carcinoma
87
**Hypoglycemia**
clinical, labs, associated cancers, tx
* **Clinical:** Sweating, anxiety, tremors, palpitations, hunger, weakness, seizures, confusion, coma
* **Labs**
* ***Non-islet* cell tumor:**
* low glucose, low insulin, low c-peptide, elevated IGF-2:IGF-1 ratio
***Islet cell tumor:***
low glucose, elevated insulin and c-peptide; normal IGF-2:IGF-1 ratio
* **Cancers:**
Mesothelioma, sarcomas, lung cancer, hepatocellular carcinoma
* **Tx:**
Tumor resection;
glucose infusion, corticosteroids, glucagon, diazoxide, octreotide, HGH
88
**Ectopic Cushing’s**
clinical, labs, associated cancers, tx
* **Clinical:**Muscle weakness; peripheral edema, hypertension weight gain
* **Labs:**
* Hypokalemia
* Metabolic alkalosis
* Elevated serum cortisol (\>29 µg/dL)
Not suppressed by high dose dexamethasone
* **Cancers:**
_Small cell lung_; bronchial carcinoid; others: thymoma, medullary thyroid CA, GI, pancreatic, adrenal, ovarian
* **Tx:**
* * Steroid synthesis inhibitors: ketoconazole, metyrapone, mitotane, aminoglutethimide, etomidate
* Blocks ACTH release: octreotide
* Binds glucorticoid receptor: mifepristone
Adrenalectomy
89
**Hypercalcemia**
clinical, labs, associated cancers, tx
* **Clinical:**Altered mental status, weakness, ataxia, lethargy, renal failure, nausea/vomiting, hypertension, bradycardia, coma
* **Labs:**
* * Hypercalcemia (nl 8.5-10.2 mg/dL)
* PTH: Low to normal (\<20 pg/mL)
Elevated PTHrP
* **Cancers:** Breast, myeloma, renal cell, squamous cell (PTHrP), ovarian, endometrial, Hodgkin’s lymphoma (Vit D secretion)
* **Tx:** Saline; furosemide (after hydration); pamidronate/zoledronate (bisphosphonates); calcitonin, gallium nitrate (osteoclast inhibitor); hemodialysis; treat underlying malignancy
90
SIADH
clinical, labs, associated cancers, tx
* **Clinical:**
Abnormal gait, headache, nausea, fatigue, muscle cramps, confusion, seizures, coma, respiratory depression
* No* orthostasis, *No* edema
* **Labs:**
* Decreased serum Na+(nl ~ 135-145 mEq/L)
* Decreased BUN/uric acid
Decreased, but concentrated urine
* **Cancers:** Small cell lung; squamous cell, lung; mesothelioma, GU, GI, brain, head/neck, prostate
* **Tx:** Restrict fluids; encourage salt and protein intake; demeclocycline (interferes w/ renal response to ADH); Conivaptan/tolvaptan (vasopressor receptor antagonists); hypertonic saline
91
**Define “paraneoplasia”**
* Ectopic production of humoral factors (hormones, peptides, or cytokines) – by tumor cells, causing secondary disease, remote from the tumor itself
92
**Identify a cell type responsible for ectopic hormone peptide synthesis and secretion by some tumors**
* Both endocrine cells and non-endocrine tumor cells can secrete polypeptide hormones *or* inappropriately express a hormone’s receptor
* Inappropriate repression or expression of certain genes → paraneoplasia
93
APUD
* APUD (amine precursor uptake and decarboxylation) cells: cells of neural crest or endodermal region that can produce, store, and secrete peptide hormones
* Occur in clusters in normal and malignant tissues
94
**Growth Hormone Axis**
* GHRH → binds GPCR (GS) → release of GH at anterior pituitary → binds to Jak/Stat tyrosine kinase at peripheral tissues
95
**Thyroid Hormone Axis**
## Footnote
**also how does lithium, amiodarone, corticosteroid effects this**
* TRH from hypothalamus → Gq activation → TSH release at anterior pituitary → Gs activation → release of TH
* Lithium decreases synthesis and release of thyroid hormone → hypothyroidism
* Amiodarone is similar to TH → negative feedback → hypothyroidism
* Can also cause hyperthyroidism (be careful in patients with existing arrhythmias)
* Corticosteroid cortisol and glucocorticoids inhibits iodinase → decreased conversion from T4 to T3
96
Liotrix
MOA, SE, Use, other fun facts
**MOA:** T4/T3
**SE:** Cardiac events
**USE:** Hypothyroidism
**OTHER:** EXPENSIVE
97
Liothyronine (Ctyomel)
MOA, SE, Use, other fun facts
**MOA:** Synthetic T3 (fast onset, not protein bound)
**SE:** Cardiac events
**USE:** Hypothyroidism, myxedena
**OTHER:** higher cost
98
Natural desiccated thyroid
MOA, SE, Use, other fun facts
**MOA:** Animal T4
**SE:** Allergic reactions
**USE:** Hypothyroidism
**OTHER:**
Drug interactions: warfarin (TH reduces clotting factors), beta blockers
Increased T4 clearance by: Rifampin, Phenytoin
99
Synthroid, Levothroid, Levothryxine
MOA, SE, Use, other fun facts
**MOA:** Synthetic T4 (protein bound, can be converted to T3, slow onset)
**SE:** Cardiac events
**USE:** Hypothyroidism
**OTHER:**
Drug interactions: warfarin (TH reduces clotting factors), beta blockers
Increased T4 clearance by: Rifampin, Phenytoin
100
Methimazole
MOA, SE, Use, other fun facts
**MOA:** Substrate for TPO, inhibits MIT/DIT coupling to thyroglobulin,
**SE:** Hypothyroidism, rashes, arthralgias, SLE-like syndrome, hypersensitivity reactions, birth defects
**USE:** Hyperthyroidism
**OTHER:**
101
Propylthiouracil (PTU)
MOA, SE, Use, other fun facts
**MOA:** Substrate for TPO, inhibits MIT/DIT coupling to thyroglobulin, blocks peripheral conversion of T4/T3
**SE:** Hypothyroidism, rashes, arthralgias, SLE-like syndrome, hypersensitivity reactions, hepatotoxicity
**USE:** Thyroid storm, hyperthyroidism, when methimazole is not tolerated
**OTHER:** Indicated: pregnancy
102
Iodides
MOA, SE, Use, other fun facts
**MOA:** Iodine analog → negative feedback of T3/T4 synthesis
**SE:** Hypothyroidism SE
**USE:** Short term hyperthyroidism (pre-operatively)
**OTHER:**
103
Hydrocortisone
MOA, SE, Use, other fun facts
**MOA:** Activates cytosolic glucocorticoid receptors → release of cortisol
**SE:** Cushingoid effects
**USE:** Adrenal insufficiency, inflammation, asthma, eczema, etc
**OTHER:** Metabolism slowed by estrogens, liver disease, age, pregnancy, hypothyroidism
104
Mifepristone
MOA, SE, Use, other fun facts
**MOA:** Progesterone and glucocorticoid receptor antagonist
**SE:** Vaginal bleeding, pregnancy termination, nausea
**USE:** Cushing’s syndrome
**OTHER:**
105
Mitotane
MOA, SE, Use, other fun facts
**MOA:** Causes degeneration of zona fasiculata and reticularis cells → atrophy of adrenal gland
**SE:** Lethargy and extreme sedation, CNS effects
**USE:** Cushing’s syndrome
**OTHER:** Use: Inoperable cortical carcinoma
106
Ketoconazole (antifungal)
MOA, SE, Use, other fun facts
**MOA:** Inhibits 11-hydroxylase activity
**SE:** Gynecomastia, low testosterone levels, elevates LFTs, CYP450 inhibitor
**USE:** Cushing’s syndrome
**OTHER:**
107
Metyrapone
MOA, SE, Use, other fun facts
**MOA:** Inhibits 11-hydroxylase activity
**SE:** Hirsutism (increased androgens), acne, HTN, N/V, sedation
**USE:** Cushing’s syndrome
**OTHER:**
108
Aminoglutethemide
MOA, SE, Use, other fun facts
**MOA:** Cholesterol desmolase inhibitor (rate-limiting step)
**SE:** Extreme sedation, nausea, severe skin rashes
**USE:** Cushing’s syndrome
**OTHER:**
109
Spironolact**_one_**, Epleren**_one_**
MOA, SE, Use, other fun facts
**MOA:** Aldo antagonist → blocks Na/H20 reabsorption
**SE:** Gynecomastia, menstrual issues (block androgen/ glucocorticoid receptors)
**USE:** HTN, hypokalemia
**OTHER:**
110
Fludrocortisone
MOA, SE, Use, other fun facts
**MOA:** Aldo agonist → Na/H20 reabsorption
**SE:** Fluid retention, hypokalemia
**USE:** CAH: 11-beta hydroxylase deficiency, adrenal insufficiency
**OTHER:**
111
Mecasemerin
MOA, SE, Use, other fun facts
**MOA:** Exogenous IGF-1 → acts at insulin-like receptor → growth
**SE:** Tonsillar hypertrophy, lipohypertrophy, hypoglycemia
**USE:** IGF-1 deficiency in children (not GH deficient, but resistant to effects of GH)
**OTHER:**
112
GHRH injection: Sermorelin
MOA, SE, Use, other fun facts
**MOA:** Exogenous GHRH → GH
**SE:**
Kids: elevated HbA1c, eosinophilia, increased risk of secondary malignancies
Adults: fluid retention, myalgia
**USE:** Dwarfism (GH deficiency)
**OTHER:** Drug interactions: estrogens, androgens, thyroid hormones
113
Growth hormone replacement: Somatotropin, Somatrem
MOA, SE, Use, other fun facts
**MOA:** Exogenous GH
**SE:**
Kids: elevated HbA1c, eosinophilia, increased risk of secondary malignancies
Adults: fluid retention, myalgia
**USE:** Dwarfism (GH deficiency)
**OTHER:** Drug interactions: estrogens, androgens, thyroid hormones
114
Pegvisomant (subQ)
MOA, SE, Use, other fun facts
**MOA:** Growth hormone receptor antagonist
**SE:** Infection (subQ), elevated LFTs
**USE:** acromegaly
**OTHER:**
115
Dopamine receptor antagonists: Metoclopramide
MOA, SE, Use, other fun facts
**MOA:** Inhibits dopamine → prolactin secretion occurs
**SE:**
**USE:** Hyperprolactinemia, acromegaly
**OTHER:**
116
Dopamine receptor agonists: Bromocriptine
MOA, SE, Use, other fun facts
**MOA:** Inhibits prolactin secretion and decreases GH release (unsure MOA)
**SE:** Postural hypotension, N/V (CTZ), hallucinations
**USE:** Hyperprolactinemia, acromegaly
**OTHER:**
117
Aquaretics: Coni**_vaptan_**
MOA, SE, Use, other fun facts
**MOA:** ADH antagonist → water excretion
**SE:**
**USE:** Hyponatremia (too much ADH)
**OTHER:** Used in patients with CHF
118
Desmopressin
MOA, SE, Use, other fun facts
**MOA:** ADH analog → fluid retention
**SE:** Rhinitis, hyponatremia
**USE:** Central diabetes insipidus (too little ADH)
**OTHER:** Contraindicated: HF, uncontrolled HTN
119
Oxytocin
MOA, SE, Use, other fun facts
**MOA:** Peptide binds Gq → release of Ca → contractions
**SE:** Mom: Fluid retention (vasopressin is structurally similar to oxytocin)
**USE:** Uterine contractions
**OTHER:** Fetus: Uterine rupture, distress
