Endocrine - Pathology Flashcards
Insulin Physiology - Transports (4)
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
Type I vs. Type II DM - Histology
Type 1 - Islets with lymphocytic infilitrate
Type II - Islets with amyloid depostion + kidney with hyaline arteriosclerosis + Kimmelstiel-Wilson Nodules
Type I DM Genetics
Not Strong Genetic Link - HLA-DR3/4
MEN 1 - 3 Diseases + Genetics
Parathyroid Hyperplasia/Tumor
PEN - Pancreatic Endocrine Tumor (Insulinoma)
Pituitary Adenoma
MEN1 Tumor Supressor Gene Knockout
MEN 2A/2B - 3 Diseases + Genetics
2A
Medullary Thyroid Cancer
Pheocromocytoma
Parathyroid Hyperplasia
2B
Medullary Thyroid Cancer
Pheocromocytoma
Ganglioneuromas of mucosal sites
RET Oncogene Mutation
Insulinoma - Key Findings (3)
1) Eposodic hypoglycemia episodes (confusion/stupor/LOC)
2) Histology shows amyloid deposition
3) Increased C-Peptide
Signs/Symptoms of Hypoglycemia (6)
1) Neurogenic - Excess Epi/NE
Neuroglycopenic
1) Blurred Vision
2) Confusion
3) Aggression
4) Seizures
5) Memory Loss
Common Causes of Hypoglycemia
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
Hypoglycemia Causing Drugs (3)
1) Diabetes Tx
2) Alcohol
3) Sulfonamide Antibiotics
General Rules of Endocrine Testing (2)
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
Prolactinoma - Findings (4)
1) Increased Prolactin + Decreased FSH/LH
2) Galactoria
3) Amenorrhea
4) Male loss of libido
GH Adenoma - Key Findings (2)
1) Secondary diabetes via GH/IGF-1
2) Often with co-secretion of prolactin (glactoria)
Sheehan Syndrome - Pathophysiology + Presentation (3)
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
Kallman’s Syndrome - Pathophyisology
Failure of GnRH cells to migrate from olfactory region - Anosmia + failure of GnRH to develop (low FSH/LH)
Cortisol Testing - Most Sensitive + Most Specific
Most Sensitive - 24 Hour Free Cortisol
More Specific - Low Dose Dexy Test
Adrenal Cortex Layers (3)
GFR + Salt, Sugar, Sex
Glomerulosa = Mineralcorticoids
Fasicular = Glucocorticoids
Reticularis = Androgens
Signs/Symptoms of High Cortisol (9)
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
Pathophysiology of Glucocorticoid Immune Suppresion (3)
1) Inhibit Phospholipase A2 - No Arachodonic Acid Metabolites (E.g. PGE2)
2) Inhibit IL-2 (T-Cell Growth)
3) Decreased Mast Cell Degranlation
CT Differential of Cushings
Primary Disease = Unilateral hypertrophy + atrophy of contralateral
Secondary Disease = Bilateral hyperplasia
Primary Mineral Corticoid Excess - Name + MCC (2) + Presenting S/Sx (5)
Conn Syndrome
Bilateral Adrenal Hyperplasia = Adolsterone Secreting Adenoma
S/Sx
1) High Aldosterone
2) HTN
3) Hypernatremia
4) Hypokalemia
5) Metabolic Alkalosis
Signs/Symptoms of Primary Adrenal Insufficiency (6)
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)
Pheochromocytoma - S/Sx (5) + Diagnosis
1) Pressure (HTN)
2) Pain (Headache)
3) Perspiration
4) Palpitation
5) Paroxysmal (On/Off for 20 minutes)
Urine Metanephrines + Vaillymandelic Acid
Pheochromocytoma - Treatment
Step 1 - 1-2 Weeks Prior - Alpha Block (Phenoxybenzamine + Prazosin)
Step 2 - 2-3 Days Prior - Beta Block (Propranolol + Atenolol)
Adrenocortical Carcinoma - Classic Presentation + S/Sx (3)
Female with rapid onset oily skin + hirtuism from excess andersteindione
1) Mass Effect (Abdominal Pain
2) Metastasis
3) Rapid Onset hormone secretion (any layer)
Congenital Adrenal Hyperplasia - Pathophysiology + Genetics + Types (2)
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
21-Hydroxylase Deficiency - Key Findings (6)
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
17-Hydroxylase Deficiency - Key Findings (3)
1) Low Cortisol + Sex Steroids
2) HTN (High Aldosterone)
3) Hypokalemia (High Aldosterone)
Hashimoto’s Thyroiditis - Pathophysiology
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
Drugs Inducing Hypothyroid (3)
1) Amiodorone
2) Lithum
3) Iodide Dyes
Hypothyroid S/Sx (7)
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
Hashimoto’s Exam Findings (1) + Histology (2) + Extra S/Sx
Moderatly enlarged non-tender thyroid
Hurthle cells + lymphoid aggregates with germinal centers (increased B-Cell Lymphoma Risk)
Increased TSH Response = Increased Prolactin = Galacturia + Amenoreahhea
Thyrotoxicosis - Signs/Symptoms (7)
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
Graves Disease - Signs/Symptoms (4)
1) Normal Hyperthyroid (anxiety, heat intolerance etc.)
2) Pretibial myxedema (edema via glycosaminoglycans)
3) Opthalmopathy
4) Scalloping of follicle on histolgoy
Graves Disease - Pathophysiology
Ab (IgG) that stimulates the TSH Receptor (Thyroid Stimulating Antibody = TSI)
Multinodular Goiter - Pathophysilogy
Heterogenous follicles - Hot (active) + cold (possibly malignant) - Focal patches operate independent of TSH = hyperthyroid
Goiter Classification - Use TSH
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)
Radioactive Iodine Test - Hot vs. Cold
Hot = Graves or Goiter Cold = Limited Uptake = Adenoma or Carcinoma
Papillary Thyroid Cancer - Key Points (4) + Histology
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)
Follicular Thyroid Cancer - Key Points (4) + Histology
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
Anaplastic Thyroid Cancer - Key Points (3) + Histology
1) Poor Prognosis
2) Painful (like subacute thyroiditis)
3) Dysphagia common
Histology
Highly invasive dysmorphic cells
Medullary Thyroid Cancer - Key Points (4) + Histology
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
Levothyroxine - Dosing + Toxicities (3)
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
Propythiouracil - Use + Mechanism + Toxicity (3)
PTU = Anti-Thyroid - Used for 1st 3 Months of Pregancy
Mechanism - Inhibits T4-T3 Conversion
Toxicity - Liver Failure + Agranulocytosis + Rash
Methamazole - Use + Mechanism + Toxicity (3)
MMI = Anti-Thyroid for any time but 1st Trimester
Mechanism - Inhibits TPO
Toxicity - Less Liver Failure (vs. TPU) + Agranulocytosis + Rash
Constitutional Growth Delay - Key Points (3)
1) Normal “Late Bloomer)
2) Delayed Puberty + Bone Age
3) Will Reach Target Height (Mid-Parental)
Dysmorphic Causes of Short Stature (3)
1) Turner’s
2) Trisomy 21
3) DiGeorge
Turner’s Syndrome - Key Findings (5) + Genetics
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
Non-Dysmorphic Causes of Short Statue (5)
Normal Weight
1) Chronic Illness
2) Eating Disorder
Increased Weight
1) GH Deficiency
2) Hypothyroidism
3) Cushing
Congenital GH Deficiency S/Sx (3)
1) Micropenis
2) Hypoglycemia
3) Look younger than natural age
GH Treatment - Side Effects (4)
1) Pseudotumor
2) Hyperglycemia
3) Thyroid Dysfunction
4) Malignancy
Tall Stature - Causes - (5)
1) GH Excess (MEN1 = Pituitary Adenoma)
2) GH Excess (McCune Albright Syndrome)
3) Genetics - Klinefleter
4) Genetics - Marfan
5) Genetics Homocytinuria
McCune Albright Snydrome - S/Sx (3)
1) Precocious Puberty
2) Cafe-Au-Lait- Macules + Increased Gs Activity
Klinefelter Syndrome - Key Points (4)
1) XXY
2) Gynecomastia
3) Small Testes + Absent Spermatogenesis
4) Tall Stature
Premature Adrenarch - Subpopulation + Predisopistion
Black Girl - PCOS Risk
Familial Male Limited Precocious Puberty - Key Points (3)
1) LH Receptor Mutation causes precocious puberty
2) Autosomal dominant + Male
3) Premature leydig cell maturation with small testes
Hypthalamic Hamartoma - Key Points (2)
1) Benign tumor causing precocious puberty
2) Gelastic Seizures (laughing seizures)
Hyperthyroid Impact on Testosterone
Increases SBHG = Less Free Testosterone
5-Alpha-Reductase - Function + Key Role
Converts Testosterone to Dihydrotestosterone
DIT = Key for External Genital = Pubic Hair Growth in Male + BPH
DDx of Low Serum Testosterone - Next Step + Differential by 2 Groups
Check LH/FSH
Elevated = Karotype Issue (Primary Gonad Issue) = Klinefelter’s
Low = Secondary = Measure Prolactin + Pituitary Functino
Klinefelter’s - Key Feautures (4)
1) XXY
2) Genetically Male with Less Puberty Development
3) Gynecomastia
4) Low Testosterone + High FSH/LH
Kallman’s Syndrome - Key Features (5)
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)
Complete Androgen Insensitivity - Key Features (3)
1) Male’s present as females with normal appearing breasts + female genitalia
2) High Testosterone trying to activate insensitive receptors
5-Alpha Reducatase Deficiency - Key Features (4)
1) Bifid Scrotum
2) Hypospadias
3) Variable Childhood Phenotype
4) Virilization at puberty
