Endocrine - Pathology

Question 1

Insulin Physiology - Transports (4)

Answer 1

GLUT-4 - Insulin Dependent - Skeletal Muscle/Adipose + Increase glucose uptake with insulin via lipogenesis + potein synthesis + glycogen synthesis

GLUT-1 (Brain/RBC/Eye) - Non-Insulin Dependent
GLUT-2 (B-Cells + Liver) - Non-Insulin Dependent
GLUT-3 (Brain) - Non-Insulin Dependent

Question 2

Type I vs. Type II DM - Histology

Answer 2

Type 1 - Islets with lymphocytic infilitrate

Type II - Islets with amyloid depostion + kidney with hyaline arteriosclerosis + Kimmelstiel-Wilson Nodules

Question 3

Type I DM Genetics

Answer 3

Not Strong Genetic Link - HLA-DR3/4

Question 4

MEN 1 - 3 Diseases + Genetics

Answer 4

Parathyroid Hyperplasia/Tumor

PEN - Pancreatic Endocrine Tumor (Insulinoma)

Pituitary Adenoma

MEN1 Tumor Supressor Gene Knockout

Question 5

MEN 2A/2B - 3 Diseases + Genetics

Answer 5

2A
Medullary Thyroid Cancer
Pheocromocytoma
Parathyroid Hyperplasia

2B
Medullary Thyroid Cancer
Pheocromocytoma
Ganglioneuromas of mucosal sites

RET Oncogene Mutation

Question 6

Insulinoma - Key Findings (3)

Answer 6

1) Eposodic hypoglycemia episodes (confusion/stupor/LOC)
2) Histology shows amyloid deposition
3) Increased C-Peptide

Question 7

Signs/Symptoms of Hypoglycemia (6)

Answer 7

1) Neurogenic - Excess Epi/NE

Neuroglycopenic

1) Blurred Vision
2) Confusion
3) Aggression
4) Seizures
5) Memory Loss

Question 8

Common Causes of Hypoglycemia

Answer 8

1) Facticious
2) Insulinoma
3) Excess Diarrhea (no absorption)
4) Ketoisic (active child uses up all their glycogen)
5) Alcoholic Induced
6) GIST Tumor Producing IFG-1

Question 9

Hypoglycemia Causing Drugs (3)

Answer 9

1) Diabetes Tx
2) Alcohol
3) Sulfonamide Antibiotics

Question 10

General Rules of Endocrine Testing (2)

Answer 10

1) Hyposecretion - Stimulation Test - Missing Cortisol? Run stimulation test to see if ACTH increases it or not (if yes then the issue is low ACTH production, if no then the adrenal isn’t responding to the ACTH = Primary)
2) Hypersecretion - Suppression Test - E.g. give dexamathsone overnight - Should result in less morning ACTH (since coritsol is elevated all night) - No suppression = ACTH secreting tumor = Secondary

Question 11

Prolactinoma - Findings (4)

Answer 11

1) Increased Prolactin + Decreased FSH/LH
2) Galactoria
3) Amenorrhea
4) Male loss of libido

Question 12

GH Adenoma - Key Findings (2)

Answer 12

1) Secondary diabetes via GH/IGF-1

2) Often with co-secretion of prolactin (glactoria)

Question 13

Sheehan Syndrome - Pathophysiology + Presentation (3)

Answer 13

Increased hormone demand of pregnancy - leads to enlargement of the Pituitary - Blood loss in birthing triggers infarction of the pituitary

Presentation

1) Poor Lactation
2) Loss of Pubic Hair
3) Fatigue in Postpartum Stage

Question 14

Kallman’s Syndrome - Pathophyisology

Answer 14

Failure of GnRH cells to migrate from olfactory region - Anosmia + failure of GnRH to develop (low FSH/LH)

Question 15

Cortisol Testing - Most Sensitive + Most Specific

Answer 15

Most Sensitive - 24 Hour Free Cortisol

More Specific - Low Dose Dexy Test

Question 16

Adrenal Cortex Layers (3)

Answer 16

GFR + Salt, Sugar, Sex
Glomerulosa = Mineralcorticoids
Fasicular = Glucocorticoids
Reticularis = Androgens

Question 17

Signs/Symptoms of High Cortisol (9)

Answer 17

1) Hyperglycemia/DM
2) HTN (Increased A1 Receptros from Epi)
3) Moon Facies
4) Central Obesity
5) Violaceous Straie
6) Menstrual Irregularities
7) Osteoporosis
8) Muscle Wasting/Weakness
9) Immune Suppression

Question 18

Pathophysiology of Glucocorticoid Immune Suppresion (3)

Answer 18

1) Inhibit Phospholipase A2 - No Arachodonic Acid Metabolites (E.g. PGE2)
2) Inhibit IL-2 (T-Cell Growth)
3) Decreased Mast Cell Degranlation

Question 19

CT Differential of Cushings

Answer 19

Primary Disease = Unilateral hypertrophy + atrophy of contralateral
Secondary Disease = Bilateral hyperplasia

Question 20

Primary Mineral Corticoid Excess - Name + MCC (2) + Presenting S/Sx (5)

Answer 20

Conn Syndrome

Bilateral Adrenal Hyperplasia = Adolsterone Secreting Adenoma

S/Sx

1) High Aldosterone
2) HTN
3) Hypernatremia
4) Hypokalemia
5) Metabolic Alkalosis

Question 21

Signs/Symptoms of Primary Adrenal Insufficiency (6)

Answer 21

1) Hypotension (Low Cortisol)
2) Weakness (Low Cortisol
3) Weight Loss (Low Cortisol
4) Hyperkalemia (Low Aldosterone)
5) Metabolic Acidosis (Low Aldosterone)
6) Hyperpigmentation (High ACTH)

Question 22

Pheochromocytoma - S/Sx (5) + Diagnosis

Answer 22

1) Pressure (HTN)
2) Pain (Headache)
3) Perspiration
4) Palpitation
5) Paroxysmal (On/Off for 20 minutes)

Urine Metanephrines + Vaillymandelic Acid

Question 23

Pheochromocytoma - Treatment

Answer 23

Step 1 - 1-2 Weeks Prior - Alpha Block (Phenoxybenzamine + Prazosin)
Step 2 - 2-3 Days Prior - Beta Block (Propranolol + Atenolol)

Question 24

Adrenocortical Carcinoma - Classic Presentation + S/Sx (3)

Answer 24

Female with rapid onset oily skin + hirtuism from excess andersteindione

1) Mass Effect (Abdominal Pain
2) Metastasis
3) Rapid Onset hormone secretion (any layer)

Question 25

Congenital Adrenal Hyperplasia - Pathophysiology + Genetics + Types (2)

Answer 25

Missing steroidogenesis enzyme - Results in deficiencies + bilateral adrenal hyperplasia Autosomal Recessive 21-Oh Deficiency - No MC/GC + Excess Sex Steroids 17-Oh Deficiency - No GC/Sex with Excess Aldosterone

Question 26

21-Hydroxylase Deficiency - Key Findings (6)

Answer 26

1) High Sex Steroids 2) Hypotension 3) Hyperkalemia (Low Alodosteone) 4) Addison's S/Sx 5) Big Penis (Male) + Ambiguous Genitalia (Female) 6) 17-OH Build Up

Question 27

17-Hydroxylase Deficiency - Key Findings (3)

Answer 27

1) Low Cortisol + Sex Steroids 2) HTN (High Aldosterone) 3) Hypokalemia (High Aldosterone)

Question 28

Hashimoto's Thyroiditis - Pathophysiology

Answer 28

Auto-immuno destruction of TPO - Produces iodized TH - Loss leads to hypothyroid Associated with lymphocytic infiltration and the HLA-DR5 subtype which causes CD8 mediated cell death

Question 29

Drugs Inducing Hypothyroid (3)

Answer 29

1) Amiodorone 2) Lithum 3) Iodide Dyes

Question 30

Hypothyroid S/Sx (7)

Answer 30

1) Intolerance to cold 2) Fatigue Weakness 3) Modest weight gain 4) Loss of lateral eyebrows 5) Dry brittle hair/nails 6) Hypercholesterolemia 7) Constipation

Question 31

Hashimoto's Exam Findings (1) + Histology (2) + Extra S/Sx

Answer 31

Moderatly enlarged non-tender thyroid Hurthle cells + lymphoid aggregates with germinal centers (increased B-Cell Lymphoma Risk) Increased TSH Response = Increased Prolactin = Galacturia + Amenoreahhea

Question 32

Thyrotoxicosis - Signs/Symptoms (7)

Answer 32

1) Anxiety 2) Increased NE/Epi Signs 3) Heat Intolerance 4) Increased Bowel Movement 5) Hyper-reflexive 6) Increased A-Fib 7) Bone resportion with hypercalcemia

Question 33

Graves Disease - Signs/Symptoms (4)

Answer 33

1) Normal Hyperthyroid (anxiety, heat intolerance etc.) 2) Pretibial myxedema (edema via glycosaminoglycans) 3) Opthalmopathy 4) Scalloping of follicle on histolgoy

Question 34

Graves Disease - Pathophysiology

Answer 34

Ab (IgG) that stimulates the TSH Receptor (Thyroid Stimulating Antibody = TSI)

Question 35

Multinodular Goiter - Pathophysilogy

Answer 35

Heterogenous follicles - Hot (active) + cold (possibly malignant) - Focal patches operate independent of TSH = hyperthyroid

Question 36

Goiter Classification - Use TSH

Answer 36

Low TSH (Thyrotoxic) - Diffuse = Goiter vs. Irregular = Multinodular Hypothyroid - Iodine Deficiency of Hashimoto's Euthyroid - Iodine Deficiency + Solitary Nodule (Adenoma, Cyst, Cancer) -- Check Calcatonin (Elevated = Medullary)

Question 37

Radioactive Iodine Test - Hot vs. Cold

Answer 37

``` Hot = Graves or Goiter Cold = Limited Uptake = Adenoma or Carcinoma ```

Question 38

Papillary Thyroid Cancer - Key Points (4) + Histology

Answer 38

1) Most common thyroid cancer 2) Age 25-50 3) Good Prognosis 4) Associated with radiation exposure (E.g. Hodgkin's Tx or Radioactive Disaster) Histology = Psammoma bodies + finger like projectsion with ground glass nuclei (orphan annie cells)

Question 39

Follicular Thyroid Cancer - Key Points (4) + Histology

Answer 39

1) Most common in areas of iodine deficiency 2) Tyrosine Kinase gain of function 3) Hematogenous spread (not normal for carcinoma) 4) Peak Age = 40-60 Malignant proliferation through the follicle and into the basement membrane

Question 40

Anaplastic Thyroid Cancer - Key Points (3) + Histology

Answer 40

1) Poor Prognosis 2) Painful (like subacute thyroiditis) 3) Dysphagia common Histology Highly invasive dysmorphic cells

Question 41

Medullary Thyroid Cancer - Key Points (4) + Histology

Answer 41

1) C-Cell Proliferation (Calcatonin Production) 2) RET Mutation (MENA/B) + Familial (Later Onset) 3) Calcitonin lowers serum calcium levels Histology Hylanizng amyloid stroma with polygonal cells in nest + apple green biferingence on congo-red staining

Question 42

Levothyroxine - Dosing + Toxicities (3)

Answer 42

Dose 30 Minutes Before Meal, Iron, Soy, Ca all interfere with absorption 1) TSH Suppression causes cardiotoxic affects (A-Fib) 2) Overdose Risk 3) Allergic Reaction

Question 43

Propythiouracil - Use + Mechanism + Toxicity (3)

Answer 43

PTU = Anti-Thyroid - Used for 1st 3 Months of Pregancy Mechanism - Inhibits T4-T3 Conversion Toxicity - Liver Failure + Agranulocytosis + Rash

Question 44

Methamazole - Use + Mechanism + Toxicity (3)

Answer 44

MMI = Anti-Thyroid for any time but 1st Trimester Mechanism - Inhibits TPO Toxicity - Less Liver Failure (vs. TPU) + Agranulocytosis + Rash

Question 45

Constitutional Growth Delay - Key Points (3)

Answer 45

1) Normal "Late Bloomer) 2) Delayed Puberty + Bone Age 3) Will Reach Target Height (Mid-Parental)

Question 46

Dysmorphic Causes of Short Stature (3)

Answer 46

1) Turner's 2) Trisomy 21 3) DiGeorge

Question 47

Turner's Syndrome - Key Findings (5) + Genetics

Answer 47

Loss of part of an X Chromosome Findings 1) Webbed Feet 2) Floppy Skin 3) Shortened IVth Metacarpal 4) Coartation of the Aorta 5) Hashimoto's

Question 48

Non-Dysmorphic Causes of Short Statue (5)

Answer 48

Normal Weight 1) Chronic Illness 2) Eating Disorder Increased Weight 1) GH Deficiency 2) Hypothyroidism 3) Cushing

Question 49

Congenital GH Deficiency S/Sx (3)

Answer 49

1) Micropenis 2) Hypoglycemia 3) Look younger than natural age

Question 50

GH Treatment - Side Effects (4)

Answer 50

1) Pseudotumor 2) Hyperglycemia 3) Thyroid Dysfunction 4) Malignancy

Question 51

Tall Stature - Causes - (5)

Answer 51

1) GH Excess (MEN1 = Pituitary Adenoma) 2) GH Excess (McCune Albright Syndrome) 3) Genetics - Klinefleter 4) Genetics - Marfan 5) Genetics Homocytinuria

Question 52

McCune Albright Snydrome - S/Sx (3)

Answer 52

1) Precocious Puberty | 2) Cafe-Au-Lait- Macules + Increased Gs Activity

Question 53

Klinefelter Syndrome - Key Points (4)

Answer 53

1) XXY 2) Gynecomastia 3) Small Testes + Absent Spermatogenesis 4) Tall Stature

Question 54

Premature Adrenarch - Subpopulation + Predisopistion

Answer 54

Black Girl - PCOS Risk

Question 55

Familial Male Limited Precocious Puberty - Key Points (3)

Answer 55

1) LH Receptor Mutation causes precocious puberty 2) Autosomal dominant + Male 3) Premature leydig cell maturation with small testes

Question 56

Hypthalamic Hamartoma - Key Points (2)

Answer 56

1) Benign tumor causing precocious puberty | 2) Gelastic Seizures (laughing seizures)

Question 57

Hyperthyroid Impact on Testosterone

Answer 57

Increases SBHG = Less Free Testosterone

Question 58

5-Alpha-Reductase - Function + Key Role

Answer 58

Converts Testosterone to Dihydrotestosterone DIT = Key for External Genital = Pubic Hair Growth in Male + BPH

Question 59

DDx of Low Serum Testosterone - Next Step + Differential by 2 Groups

Answer 59

Check LH/FSH Elevated = Karotype Issue (Primary Gonad Issue) = Klinefelter's Low = Secondary = Measure Prolactin + Pituitary Functino

Question 60

Klinefelter's - Key Feautures (4)

Answer 60

1) XXY 2) Genetically Male with Less Puberty Development 3) Gynecomastia 4) Low Testosterone + High FSH/LH

Question 61

Kallman's Syndrome - Key Features (5)

Answer 61

1) Low GnRH + FSH/LH 2) Due to Olfactory Migration Issue 3) Anosmia 4) AD or AR 5) Pubic Hair Still Present (No Adrenal Androgen Production Inhibition)

Question 62

Complete Androgen Insensitivity - Key Features (3)

Answer 62

1) Male's present as females with normal appearing breasts + female genitalia 2) High Testosterone trying to activate insensitive receptors

Question 63

5-Alpha Reducatase Deficiency - Key Features (4)

Answer 63

1) Bifid Scrotum 2) Hypospadias 3) Variable Childhood Phenotype 4) Virilization at puberty