Endocrine

Question 1

Pituitary Adenoma

Answer 1

Benign tumor anterior pituitary
functional if it secretes hormones, nonfunctional if it is silent
Nonfunctional tumors can present as mass effect (compress optic chiasm get bitemporal hemianopsia, compress ituitary = hypopituitarism, headache)

Question 2

Prolactinoma

Answer 2

Pituitary Adenoma that secretes prolactin
galactorrhea and ammenorhea in females
decreased libido and headaches
Treat with dopamine agonists like bromocriptine or cabergoline

Question 3

Growth Hormone Cell adenoma

Answer 3

Pituitary Adenoma that secretes GH
Children = gigantism
Adults = acromegally (large hands, feet, and jaw), growth of visceral organs leads to dysfunction (heart failure) and enlarged tongue
Also get secondary DM (GH decreases glucose uptake in cells)
Treat with ostreotide (somatostatin that supresses release of GH), GH Receptro antagonists, or surgery

Question 4

ACTH Cell Adenomas

Answer 4

Pituitary Adenoma that secretes ACTH

Get Cushing Syndrome

Question 5

Hypopituitarism

Answer 5

Insufficeint production of hormones by the anterior pituitary
Causes include
1) pituitary adenomas or craniopharyngioma with mass effects or pituitary apoplexy (bleeding into an adenoma)
2) Sheehan syndrome = pregnancy related infarction of the pituitary gland
3) Empty Sella Syndrome - herniation of the arachnoid and CSF into the sell compresses and destroys the pituitary gland

Question 6

Sheehan Syndrome

Answer 6

Pituitary gland doubles in size during pregnancy but vasculature cannot keep up , blood loss during parturition precipitates infarction and leads to hypopituitarism

Question 7

Hormones in Posterior Pituitary

Answer 7

ADH - acts on distal tubules and collecting ducts to promote free water retention
Oxytocin = mediates uterine contraction and release of breast milk
both are made in hypothalmaus and then transported to posterior by axonal transport

Question 8

Central Diabetes Insipidus

Answer 8

ADH deficiency due to hypothalamic or posterior pituitary pathology
Get loss of free water leading to
1)polyuria and polydipsia with dangerous dehydration
2)hypernatremia and high serum osmolarity
Water deprivation test fails to increase urine osmolality
Treatment is desmopressin (ADH analog)

Question 9

Nephrogenic Diabetes insipidus

Answer 9

Impaired renal response to ADH
Due to inherited mutations or drugs (lithium and demeclocycline)
Get loss of free water leading to
1)polyuria and polydipsia with dangerous dehydration
2)hypernatremia and high serum osmolarity
Does not respond to desmopressin treatment

Question 10

Syndrome of Inappropriate ADH Secretion

Answer 10

Excessive ADH secretion
Usually due to ectopic production (small cell carcinoma of lung), CNS trauma, pulmonary infection, COPD, drugs like cyclophosphamide.
Retention of free water leads to
1) hyponatremia
2)Mental status change and seizures since hyponatremia leads to neuronal swelling and cerebral edema
treatment is free water restriction or democlocycline

Question 11

Thyroglossal Duct Cyst

Answer 11

Cystic dilation of thyroglossal duct remnant which is supposed to normally involute.
Presents as an anterior neck mass

Question 12

Lingual Thyroid

Answer 12

Persistence of thyroid tissue at the base of the tongue

Presents as a base of tongue mass

Question 13

Mechanism and Symptoms of hyperthyroidism

Answer 13

Increased levels of circulating thyroid hormone 1) increases basal metabolic rate (by increasing synthesis of Na-K-ATPase) 2) Increases sympathetic nervous system activity (due to icnreased expression of Beta1 adrengergic receptors)
SYMPTOMS
weight loss, heat intolerance, tachycardia, arrythmia, tremor, anxiety, insomnia, diarrhea, oligomennorhea, bone resoprtion (hypercalcemia and osteoperosis), decreased muscle mass, HYPOCHOLESTEROLEMIA, HYPERGLYCEMIA

Question 14

Grave Disease

• mechanism
• symptoms
• Path
• Labs
• Treatment
• Complications

Answer 14

M = Autoantibody (IgG) that stimulates the TSH receptor (type II hypersensitivity) leads to increased synthesis and release of thyroid hormone.  Classically seen in women of childbearing age.
S = Get hyperthyroidism, diffuse goiter, exophthalmos and pretibial myxedema (fibroblasts behind the orbit and overlying the shin express the TSH receptor, activation results in GLYCOSAMINOGLYCAN buildup, inflammation, fibrosis, and edema)
P = irregular follicles with scalloped and chronic inflammation
L = Increased total and free T4, decreased TSH, hypocholesterolemia, increased serum glucose
T = Beta blockers, thioamide, and radioiodide ablation
C= Thyroid storm (elevated catecholamines and massive hormone excess, arrythmia, hyperthermia, and vomitting with hypovolemic shock) treat with propylthiouracil (inhibits peroxidase and peripheral conversion of T4 to T3), beta blockers, and steroids

Question 15

Multinodular Goiter

Answer 15

Enlarged thyroid gland with multiple nodules
Due to relative iodine deficiency
Usually nontoxic
Rarely regions become TSH-independent leading to T4 release and hyperthyroidism (toxic goiter)

Question 16

Cretinism

Answer 16

Hypothyroidism in neonates and infants
Characterized by mental retardation, short stature, caorse facial features, enlarged tongue, and umbilical hernia
Can be casued by maternal hypothyroidism in early pregnancy, thyroid agenesis, dyshormonogenetic goiter, and iodine deficiency (peroxidase mutation)

Question 17

Myxedema

Answer 17

hypothyroidism in older children and adults
Clinical features based on decreased metabolic rate and decreased sympathetic nervous system activity
Get myxedema (results in DEEP VOICE and ENLARGED TONGUE), weight gain, slowing of mental activity, ,muscle weakness, cold intolerance, bradycardia, oligomenorrhea, HYPERCHOLESTEROLEMIA, constipation
Usually due to iodine deficiency, hashimoto thyroiditis, lithium, or surgical removal

Question 18

Hasimoto Thyroiditis

Answer 18

Autoimmune destruction of thyroid gland, associated with HLA-DR5
Clinical presents intially as hyperthyroidism as preformed follicles release their T3, T4, but eventually progresses to hypothyroidism (decreased T4 and Increased TSH)
See Chronic inflammation with germinal centers and hurthle cells
Increased risk for B-Cell (marginal zone) lymphoma

Question 19

Subacute Granulomatous (De Quervain) Thyroiditis

Answer 19

Granulomatous thyroiditis that follows a viral infection

Presents as tender thyroid with transient hyperthyroidisim. Usually self limited but may progress to hypothyroidism

Question 20

Reidel Fibrosing Thyroiditis

Answer 20

Chronic Inflammation with extensive fibrosis of the thyroid gland
Hypothyroidism with a “HARD AS WOOD” nontender thyrid gland
Fibrosis may extend to involve local structures such as airways
See in YOUNG patients (40s)

Question 21

“Hot” vs “Cold Nodule

Answer 21

I radioactive uptake studies are useful to charcteriz thyroid nodules.
Take up lots of I = hot = seen in graves disease or nodular goiter
Take up little I = cold = seen in adenoma and carcinoma, often warrants biopsy

Question 22

How to biopsy Thyroid

Answer 22

Fine Needle Aspiration since it is highly vascualr and would bleed to much if do actual biopsy

Question 23

Follicular Adenoma

Answer 23

Benign proliferation of follicles surrounded by a fibrous capsule.
Typically nonfunctional but can secrete thyroid hormone

Question 24

Papillary Carcinoma

Answer 24

Most common thyroid carcinoma
Exposure to ionizing radiation in childhood is major risk factor
See papillae lined by cells with clear “orphan annie eye” nuclei and nuclear grooves, papillae are often associated with psammoma bodies
Often spreads to cervical lymph nodes

Question 25

Follicular Carcinoma

Answer 25

Malignant proliferation of follicles SURROUNDED by a fibrous capsule with INVASION through the capsule(unlike follicular adenoma) Have to examine entire capsule not just a FNA Mets HEMATOGENOUSLY (like chorio, renal, and hepatocellular carcinomas)

Question 26

Medullary Carcinoma

Answer 26

Malignant proliferation of parafollicular C cells C Cells are neuroendocrine cells that secrete calcitonin which lowers serum calcium by increasing renal calcium excretion. Calcitonin can also deposit within a tumor as an amyloid Biopsy reveals sheets of malignant cells in an amyloid stroma Familial cases are often due Mutliple Endocrine Neoplasasia (MEN) 2A and 2B which are associated with mutations in RET oncogene MEN 2 results in medullary carcinoma, pheochromocytoma, and parathyroid adenomas (2A) or ganglioneuromas of the oral mucose (2B) RET mutation warrants prophylactic thyroidectomy

Question 27

MEN 2A and2B

Answer 27

Mutations in RET oncogene MEN 2 results in medullary carcinoma, pheochromocytoma, and parathyroid adenomas (2A) or ganglioneuromas of the oral mucose (2B) RET mutation warrants prophylactic thyroidectomy

Question 28

Anaplastic Carcinoma

Answer 28

Undifferentiated malignant tumor of the thyroid, usually seen in ELDERLY Often invades local structures, leading to dysphagia or respiratory compromise Poor prognosis

Question 29

Parathyroid Gland

Answer 29

Its Chief Cells regulate free ionzied calcium via PTH 1) Increases osteoclast activity (indirectly by activating osteoblasts) releasing calcium and phosphate 2) Increases small bowel absorption of calcium and phosphate (indirectly by activating vitamin D) 3) Increases renal calcium absoprtion (distal tubule) and decreases phosphate reabsorption (Proximal tubule)

Question 30

Primary Hyperparathyroidisim | Symptoms and labs

Answer 30

Excess PTH due to Parathyroid gland itself Major cause is parathyroid adenoma but also sporadic parathyroid hyperplasia and parathyroid carcinoma Usually asymptomatic hypercalcemia but can get 1) Nephrolithiasis 2) Nephrocalcinosis = metastatic calcification of renal tubules 3) CNS disturbance such as depression or seizures 4) Constipation, peptic ulcer disease, or Acute pancreatitis Osteitis fibrosa cystica Labs = Increased serum PTH, Ca2+, urincary cAMP, and serum alkaline phophatase, and decreased serum phosphate

Question 31

Secondary Hyperparathyroidisim

Answer 31

Excess Production of PTH due to disease extrinsic to parathyroid gland such as chronic renal failure With chronic renal failure see decreased phosphate excretion which will increase serum phosphate that will bind calcium and therefore decrease serum free calcium. This will stimulate all 4 parathyroid glands to increase PTH to breakdown bone to increase calcium and lead to renal osteodystrophy See increased PTH, serum phosphate, alkaline phosphate, and decreased serum calcium

Question 32

Hypoparathyroidisim

Answer 32

Low PTH. Causes include autoimmune damage, surgical excission or Digeorge syndrome (failure to develop parathyroid since 3rd and 4th pharyngeal pouch were missing) Presents with low serum calcium that leads to numbness and tingling and muscle spasms that may be elicitied by filling up blood pressure cuff (trousseau sign) or tapping on the facial nerve (chvostek sign) Labs show decreased PTH and serum calcium

Question 33

Troussea Sign

Answer 33

Muscle spasm upon filling up blood pressure cuff. | Can be sign of hypocalcemia due to hypoparathyrodisim

Question 34

Chvostek sign

Answer 34

Muscle spasm illicited by tapping on facial nerve | Can be sign of hypocalcemia due to hypoparathyrodisim

Question 35

Pseudohypoparathyrodisim

Answer 35

End organ resistance to PTH Labs show hypocalcemia with increased PTH levels Autosomal dominant form where GS is mutated and patients also are short in stature and have short 4th and 5th digits.

Question 36

Endocrine Pancreas | Cells and their functions

Answer 36

functional endocrine portion is the islets of langerhans Beta cells lie in the center and secrete insulin which upregulates GLUT4 therefore increasing glucose uptake into cells and decreasing serum glucose Alpha cells on the periphery secrete glucagon which increases serum glucose levels by stimulating glycogenolysis and lipolysis

Question 37

Type 1 Diaebtes Mellitus

Answer 37

Insulin deficiency leads to hyperglycemia Results from autoimmune destruction of beta cells by T lymphocytes (type IV hypersensitivity). See inflammation of islets, HLA-DR3 and HLA-DR4, autoantibodies against insulin often present Manifests in childhood with 1)High serum glucose 2)Weight loss, low muscle mass and polyphagia (eat a lot) 3) Polyuria, polydispsia, and glycosuria. Treatment is lifetime replacement of insulin High risk for DKA

Question 38

Diabetic Ketoacidosis

Answer 38

Condition seen in DM1. Characterized by excessive ketones, often arises with stress such as infection where epinephrine levels are high and stiulate glucagon to exacerbate already high glucose levels. There is increased lipolysis to increase free fatty acids that are converted to ketone bodies by the lvier. See hyperglycemia (>300), anion gap metabolic acidosis, and hyperkalemia (that will be lsot in urine) Present with Kussmaul respirations to breathe off acidosis, dehydration, nausea, vomiting, mental status changes, fruity breath Treat with fluids, insulin, and replacement of electrolytes (potassium)

Question 39

Type 2 Diabetes Mellitus

Answer 39

End organ insulin resistance leading to metabolic disorder characterized by hyperglycemia See in middle aged, obese (obesity decreases insulin receptors on cells), adults, with strong genetic predisposition Insulin levels initially rise early in disease but beta cells become exhausted and insulin levels die down. See amyloid deposits in these islets. Clinically silent but when do present they have polyuria, polydipsia, and hyperglycemia Treat with weight loss, solfonylureas or metformin, or exogenous insulin. Risk for hyper-osmolar non-ketoic coma = glucose above 500 leads to life threatening diuresis with hypotension and coma

Question 40

hyper-osmolar non-ketoic coma

Answer 40

Deadly complication of DM2 | glucose above 500 leads to life threatening diuresis with hypotension and coma

Question 41

Long term consequences of Diabetes

Answer 41

Nonenzymatic glycosylation (NEG) of vascular basement membranes. 1) large and medium sized vessels = cardiovascular leads to death and peripheral vascular leads to need for amputations 2) small vessels = hyaline arterolosclerosis = renal arterioles leads to glomerulosclerosis with small scarred kidneys with a granular surface. Preferntial involvement of efferent arterioles leads to glomerular hyperfiltration with microalbuminuria that eventually progresses to nephrotic syndrome that is characterized by Kimmelstiel-Wilson Nodules Osmotic Damage Glucose freely enters schwann cells, pericytes of retinal blood vessels, and the lens Aldose reductase converts glucose to soribtal, resulting is osmotic damage Leads to peripheral neuropathy, impotence, blindness, and cataracts

Question 42

Tumors of Islet Cells

Answer 42

often a component of MEN1 along with parathyroid hyperplasia and pituitary adenomas

Question 43

Insulinomas

Answer 43

Episodic hypoglycemia with mental staus changes that are relieved by administration of glucose. Diagnose by seeing decreased serum glucose, increased insulin, AND increased C-peptide

Question 44

Gastrinomas

Answer 44

Present as treatment resistant peptic ulcers (Zollinger-Ellison syndrome)

Question 45

Somatostatinomas

Answer 45

Achlorhydia (due to inhibition of gastrin) and cholelithiasis (gall stones) with steatorrhea (excess fat in feces) (both due to inhibition of cholecystokinin)

Question 46

VIPomas

Answer 46

Secrete excessive vasoactive intestinal peptide leading to watery diarrhea, hypokalemia, and achlorhydria (lack of gastric acid production)

Question 47

Layers of The Adrenal Cortex

Answer 47

``` Glomerulosa = mineralcorticoids = aldosterone Fasciculate = glucocorticoids = cortisol Reticularis =sex steroids = testosterone Kidney "Sweeter as you go deeper" "when thinking of kidney think of GFR" ```

Question 48

Symptoms and diagnosis of Hypercortisolism

Answer 48

Excess cortisol clinically presents as 1)muscle weakness with thin extremities 2) Moon facies, buffalo hump, and truncal obesity cus the high insulin increases storage of fat 3) Absominal striae from impaired synthesis of collagen 4) Hypertension 5) Osteoperosis 6) Immune Supression Diagnose by increased 24hr urine cortisol levels

Question 49

Causes of Hypercortisolism

Answer 49

1) Exogenous corticosteroids = bilateral adrenal atrophy since steroids supress ACTH secretion 2) Primary adrenal adenoma, hyperplasia, or carcinoma = atrophy of uninvolved adrenal gland 3) ACTH-secreting pituitary adenoma = bilateral adrenal hyperplasia. High dose dexamethesaone supresses ACTH production by a pituitary adenoma and the cortisol levels derease 4) Paraneoplastic ACTH Secretion (small cell carcinoma of the lung) = bilateral adrenal hyperplasia = not responsive to high dose dexamethesaone and ACTH and cortisol levels remain high

Question 50

Hyperaldosteronism | -primary vs secondary

Answer 50

Excess aldosterone presents as hypertenion from sodium retention, hypokalemia, and metabolic alkalosis. Primary = most commonly due to adrenal adenoma but also from spradic adrenal hyperplasia or adrenal carcnimoa. Characterized by high aldosterone and low renin Secondary = seen in the activation of renin-angiotensin system (renovascular hypertension or CHE). See high aldosterone and high renin

Question 51

Congenital Adrenal Hyperplasia

Answer 51

Excess sex steroids with hyperplasia of both adrenal glands. Inherited 21-hyroxylase deficiency is most common cause. It is required for production of aldosterone and cortisol so cholesterol shifts towards making all that it can now which is sex steroids. Lack of cortisol leads to increased ACTH scretion which causes the bilateral adrenal hyperplasia. Clinically see Salt wasting with hyponatremia, hyperkalemia, and hypovolemia, life threatening hypotenison from lack of cortisol that activates alpha 1. See clitoral enlargmenet in women or precocious puberty in males

Question 52

Adrenal Insufficiency

Answer 52

Lack of adrenal hormones Acute insufficiency may arise with Waterhouse-Friderichsen syndrome = hemmorhagic necrosis of the adrenal glands following DIC in young children with N meningitidis. The lack of cortisol exacerbates hypotension and leads to death Chronic insufficiency = addison disease = progressive destruction of the adrenal glands by autimmune, TB, or metatastic carcinoma. Clinically see hypotension, hyponatremia, hypovolemia, hyperkalemia, weakness, hyperpigmentation (especially in oral mucosa) vomitting and diarrhea

Question 53

Waterhouse-Friderichsen syndrome

Answer 53

adrenal insufficiency caused by hemmorhagic necrosis of the adrenal glands following DIC in young children with N meningitidis. The lack of cortisol exacerbates hypotension and leads to death Clinically see hypotension, hyponatremia, hypovolemia, hyperkalemia, weakness, hyperpigmentation (especially in oral mucosa) vomitting and diarrhea

Question 54

addison disease

Answer 54

Chronic adrenal insufficiency from progressive destruction of the adrenal glands by autimmune, TB, or metatastic carcinoma. Clinically see hypotension, hyponatremia, hypovolemia, hyperkalemia, weakness, hyperpigmentation (especially in oral mucosa) vomitting and diarrhea

Question 55

Pheochromocytoma

Answer 55

Tumor of chromaffin cells of the Adrenal Medulla. Get increased serum catecholamines (epi and norepi) leads to episodic hypertenison, headache, palpitations, tachycardia, and sweating Diagnose with increased serum metanephrins and increased 24hr urine metanephrines and vanillylmandelic acid. Treat with surgical excision but first give them PHENOXYBENZAMINE (irreversible alpha blocker) to prevent a hypertensive crisis in middle of surgery Rule of 10s = 10% bilateral, 10% familial, 10% malignant, 10% located outside of the adrenal medulla (bladder wall or organ of zuckerlandl) Assoicated with MEN2A or MEN2B (RET mutations), Von-hippel-lindau, and neurofibromatosis type 1

Question 56

MEN 2A

Answer 56

RET mutation so Increased risk for medullary carcinoma of thyroid Pheochromocytoma Parathyroid Adenoma

Question 57

MEN 2B

Answer 57

RET mutation so Increased risk of medullary carcinoma of thyroid Pheochromocytoma Mucosal ganglioneuroma (especially in oral mucosa)

Question 58

von Hippel Lindau

Answer 58

Increased risk for hemangioblastoma of the cerebellum Renal cell carcinoma Pheochromocytoma