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Flashcards in Endocrine Pathology Deck (77):
1

Anterior Pituitary

glandular organ --> arises from Rathke's pouch
- secretes GH, PRL, FSH, LH, ACTH, TSH
- all hormones are controlled by hypothalamus (stimulatory except PRL which is inhibited by dopamine)

2

Posterior Pituitary

Neural ectoderm -> from diencephalon
- doesn't make hormones, it stores hormones (oxytocin and ADH)
- extension of hypothalamus

3

Acidophils

secretes GH and PRL

4

Basophils

secretes FSH, LH, ACTH, TSH

5

Oxytocin

Labor induction
Milk let down
Cuddle hormone
Monogamy
Trust

6

Hyperpituitarism

too much of one or more anterior pituitary hormones
- most common cause = pituitary adenoma
- endocrine abnormalities occur when adenomas secrete hormones, otherwise it can be latent until growth becomes big enough to cause mass effect

7

Mass Effect

Visual field abnormalities - bitemporal hemianopsia (optic chiasm)
Symptoms of increased cranial pressure
Compression of pituitary -> HYPOpituitarism

8

Functional vs. Nonfunctional pituitary adenomas

functional = produces pituitary hormone
non-functional = doesn't produce hormone -> becomes really big (mass effect)

9

Epidemiology of pituitary adenomas

occurs most common in adults
3% arise from multiple endocrine neoplasia
- can cause "pituitary apoplexy" --> sudden bleeding that is BAD

10

Microscopic appearance of pituitary adenoma

can't tell type of hormone from histology --> need special stains
- most commonly involve one cell type, can be pleomorphic
MOST COMMON - prolactin-producing
LEAST COMMON - thyroid-stimulating hormone producing

11

Molecular mutations in pituitary adenomas

mutated G-proteins -> GNAS1 gene
- alpha subunit doesn't turn off -> GTP constantly causing cAMP and PKA pathways
- some can cause activating mutation of RAS oncogene or overexpression of c-MYC oncogene

12

Prolactin-producing adenoma

MOST COMMON type of pituitary adenoma
- secretes prolactin efficiently -> causes symptoms (amenorrhea, galactorrhea, infertility, loss of libido)
- drugs that interfere with dopamine action can also cause increased prolactin
Tx = bromocriptine (D2 receptor agonist)

13

Growth hormone producing adenoma

Gigantism = GH adenoma BEFORE puberty
Acromegaly = GH adenoma AFTER puberty (changes can happen subtly so that patient doesn't realize)
Lab - GH unreliable because of pulsatile secretion, check IGF-1
- can also perform glucose test (administer glucose should decrease GH but it won't)
Tx = get GH back to normal (surgery/radiation)

14

ACTH producing adenoma

makes ACTH --> revs up adrenal glands which make cortisol
Cushing Syndrome -> too much cortisol
Cushing Disease -> ACTH producing adenoma that causes cushing syndrome
Nelson Syndrome -> removal of adrenals with cushing syndrome -> BAD (no inhibition of pituitary)

15

FSH and LH producing adenomas

secrete FSH and LH very inefficiently
- mass effect brings it to attention rather than endocrine abnormalities

16

TSH-producing adenomas

RARE!!!!!

17

Non-functioning adenoma

secretes no hormones --> gets BIG and causes mass effect

18

Hypopituitarism

decreased secretion of pituitary hormones
Causes:
1. Pituitary destruction --> more than 75% (surgery, radiation, tumor compressing it)
2. Ischemic Necrosis -> Sheehan syndrome (pregnancy), pituitary increases in size but not blood supply, hemorrhage of shock during delivery infarcts the pituitary
3. Empty Sella syndrome -> arachnoid membrane and CSF herniate down into sella turcica (more than 75%)
4. Pituitary Apoplexy -> sudden, spontaneous infarct of pituitary (symptoms of severe headache, stiff neck, N/V) -> bad bleeding

19

Clinical finding of hypopituitarism

insidious, chronic onset (need 75% or more of pituitary affected)
Order of Loss of Hormones = GH, FSH/LH, TSH, ACTH
GH -> dwarfism (childhood), muscle atrophy and weakness (adulthood)
FSH/LH -> menstrual abnormalities
PRL -> prevents lactation
TRH -> secondary hypothyroidism
ACTH -> adrenal insufficiency

20

Posterior Pituitary Syndromes

Diabetes Insipidus and Syndrome of Inappropriate ADH Secretion

21

Diabetes Insipidus

central or nephrogenic decrease in ADH secretion
- ADH deficiency leads to dilute, massive amounts of urine
- increase in serum osmolality
- head trauma, tumors, or ethanol
Tx = increase water intake and give ADH (vasopressin)

22

SIADH

ADH excess causes kidneys to excrete SUPER concentrated urine --> lots of water retention (decrease serum osmolality)
Most common cause -> ectopic ADH producing tumor (small-cell lung cancer)
Tx = restrict water intake

23

Thyroid Embryology

thyroid develops from pharyngeal epithelium from back of tongue -> descends anterior portion of neck
- remnants = thyroglossal duct cyst
- bilobed structure with isthmus, follicles contain colloid

24

Thyroid Physiology

hypothalamus secretes TRH --> anterior pituitary secretes TSH --> thyroid synthesizes and releases T3 and T4, grows, uptakes iodine

25

Thyroid Hormone Function

increase fat breakdown, decrease carb utilization, stimluate protein synthesis, increased BMR

26

Thyroid Lab Testing

TSH -> amount of TSH in blood, VERY sensitive (even a small fluctuation in T4 causes a rapid, inverse change in TSH)
Free T4 -> tells how much active, free T4 patient has (don't confuse with total T4 which is bound, inactive)
Free or total T3 -> how much free or total T3 patient is making
TBG - measures thyroglobulin (carrier for thyroid hormone)
Anti-thyroid antibody test - Graves'

27

Radioiodine thyroid screening

123-I radiolabeled is taken up by thyroid
- evaluate thyroid nodules or determine appropriate dosing
Hot -> almost always benign because cancer doesn't make hormones
Cold -> occasionally malignant because cancer doesn't make hormone

28

Hyperthyroidism

HYPERMETABOLIC state caused by increased thyroid hormone levels
Primary -> thyroid over-functioning because of intrinsic problem
Secondary -> thyroid over-functioning because too much TSH (pituitary problem)

29

Signs and Symptoms of hyperthyroidism

Cardiac -> rapid pulse, cardiomegaly, arrhythmias
Neuro -> nervous, tremor, emotional
Eye -> lid lag, wide-staring gaze
Skin -> warm, moist, flushed skin
GI -> diarrhea, weight loss
Skeletal -> osteoporosis
Thyroid Storm --> BAD SHIT -> coma and death

30

Causes of hyperthyroidism

Graves' disease --> MOST COMMON CAUSE
- goiter, thyroid adenoma, thyroiditis, ingestion of thyroid hormones, pituitary adenoma, struma ovarii, factitious

31

Diagnosis of hyperthyroidism

TSH and free T4
Primary -> high T4 and low TSH
Secondary -> high T4 and high TSH

32

Hypothyroidism

HYPOMETABOLIC state by decreased levels of thyroid homrones
Primary -> under-functioning because of intrinsic problem
Secondary -> under-functioning because of low TSH (pituitary problem)

33

Signs and Symptoms of Hypothyroidism

Slowing of mind and body -> fatigue, mental slowness, irritability, loss of interest
Myxedema -> accumulation of ground substance in tissues -> not fluid
Cardiac -> slow pulse, diminished contractility
GI - > constipation
Skin -> dry, cool, pale
Cold Intolerance
Delayed deep tendon reflexes
Myxedema Coma -> opposite of thyroid storm

34

Causes of Hypothyroidism

Congenital (Cretinism) -> iodine deficiency, developmental or genetic
- symptoms reflect impaired development = short, mental retardation (range of severities)
Acquired (adulthood) -> Hashimoto thyroidits (autoimmune), iatrogenic (surgery or radiation), goiter, amyloidosis, sarcoidosis, thyroiditis

35

Diagnosis of Hypothyroidism

TSH and free T4
Primary -> low T4 and high TSH
Secondary -> low T4 and low TSH

36

Thyroiditis

inflammation of thyroid gland
- Hashimoto is most common
- may be euthyroid, hypothyroid, or hyperthyroid (colloid spilling out)
- radioactive uptake is decreased ("cold" thyroid tissue)

37

Hashimoto thyroiditis

MOST COMMON thyroiditis (F>M)
- Primary Hypothyroidism (T4 low, TSH high)
- enlarged, non-tender thyroid (gradually hypothyroid)
Lab Testing = thyroid tests reflect thyroid status
- anti-peroxidase antibodies (detected by immunofluorescence)
Patho = autoimmune destruction of thyroid gland (T-cells attack thyroid AND stimulate B-cells) --> anti-TSH receptor antibody

38

DeQuervian thyroiditis

occurs after upper respiratory infection (viral infection)
- many patients have HLA-B35 antigen
- painful, enlarged thyroid (abrupt)
- self-limiting disease
- damaged, disrupted follicles and multinucleate giant cells

39

Silent thyroiditis

painless, slightly enlarged thyroid (asymptomatic)
- middle age or after pregnancy
- transient and self-limiting
- abundant lymphocytes (like Hashimoto but none of the features of Hashimoto)

40

Reidel's thyroiditis

Rock-hard, woody neck mass --> fibrosis
- fibrosis may progress and put pressure on trachea

41

Graves' Disease

MOST COMMON cause of hyperthyroidism (F>M)
- Classic Triad = hyperthyroidism, ophthalmopathy, dermopathy
Labs = high T4, low TSH, high uptake of iodine
- Autoimmune disease with anti-TSH receptor antibodies (opposite effect of Hashimoto)
- eye muscles and skin has TSH receptors --> that's how those symptoms occur

42

Treatment of Graves'

decrease symptoms of hyperthyroidism (beta-blocker)
decrease synthesis of thyroid hormones = PTU, radioiodine ablation

43

Goiters

big thyroid gland
low T4 --> high TSH --> BIG THYROID
Simple --> first stage (smooth)
Multinodular --> second stage (bumpy and big)
Labs = euthyroid
Histo --> hyperplastic cells, then cells become exhausted and involute (oversized colloid)

44

Cause and Treatment of Goiters

Lack of iodine, diet rich in goitrogen
Tx = levothyroxine --> suppress TSH and shrink goiter
- be careful of Jod-Basedow phenomena --> giving iodine to patient --> acute hyperthyroidism

45

Neoplastic thyroid disease

most thyroid bumps are non-neoplastic --> but need to aspirate/biopsy to make sure

46

Thyroid Adenoma

euthyroid patients, commoner in adults
- Labs = normal T4 and TSH, cold thyroids
Solitary nodules, encapsulated, and generally not invasive
Tx = surgical removal
- need to look at capsule to see if there is tumor cells --> that means it's invasive

47

Papillary Adenocarcinoma

most common cause of thyroid carcinoma (best prognosis too)
- papillary growth pattern
- nuclei look empty (Orphan Annie's eyes), nucelar pseudoinclusions, psammoma body

48

Follicular Adenocarcinoma

follicular growth pattern, well-differentiated
Hard to identify from thyroid adenoma
- look for vascular invasion and tumor cells extending into thyroid capsule
Tx = surgical excision, look for metastasis

49

Medullary Carcinoma

endocrine tumor
- thyroid C-cells --> makes calcitonin -> creates amyloid deposits (congo red stain)
- vague nests
Tx = anyone suspected of MEN II or familial thyroid

50

Anaplastic thyroid carcinoma

rapidly-enlarging bulky neck mass --> often metastasized already upon presentation
Anaplastic cells --> VERY undifferentiated = bad prognosis

51

Parathyroid Gland

4 glands in 2 pairs
Upper lobes -> 4th pharyngeal pouch
Lower lobes -> 3rd pharyngeal pouch
- chief cells -> PTH
- oxyphil cells -> unknown function

52

Parathyroid Physiology

Chief cells secrete proparathyroid -> cleaved to PTH -> binds to PTH receptors -> stimulate AC -> PLC -> IP3 and DAG

53

PTH Actions

1. Stimulate osteoblasts -> stimulate osteoclasts -> increase blood calcium
2. Increase renal absorption of calcium
3. Increase renal conversion of Vit D to active form
4. Increase urinary excretion of phosphate
5. Absorb gut calcium

54

What controls PTH release?

serum calcium --> NOT pituitary
serum calcium increases -> PTH decreases
serum calcium decreases -> PTH increases

55

Hypercalcemia

Lots of things can cause it:
M alignancy
D iuretics
P arathyroid
I diopathic
M egadose of Vit D
P aget's disease
S arcoidosis
M ilk-alkali syndrome
E ndocrine

56

Hyperparathyhroidism

Primary -> over-functioning because of intrinsic problem
Secondary -> over-functioning because of something else causing chronic hypocalcemia
Pseudohyperparathyroidism -> hypercalcemia caused by production of PTH related protein by cancers (squamous cell lung carcinoma)

57

Primary Hyperparathyroidism

Stone -> kidney stones (hypercalcemia)
Bone -> bone pain (osteoclasts erode bone)
- brown tumors -> microfractures and hemorrhage
Groan -> GI problems (constipation, ulcers, nausea)
Moan -> mental changes (depression, lethargy)
Labs = increased PTH, increased Ca, decreased PO4, increased 24-hr urine Ca, increased urine cAMP

58

Causes of primary hyperparathyroidism

1. Parathyroid Adenoma -> most common
- composed mostly of chief cells
PRAD1 -> genetic alterations in sporadic cases
MEN1 or RET -> genetic alterations in familial cases
2. Parathyroid Hyperplasia -> normal looking cells, just a lot of them, some MEN1 syndromes
3. Parathyroid Carcinoma -> abrupt onset of pain bain, usually just one gland affecteed, tumors are well-differentiated

59

Secondary Hyperparathyroidism

Due to chronic hypocalcemia -> renal failure, poor calcium, Vit D deficiency
Pathophysiology = chronic renal failure -> phosphate not excreted -> Ca goes down -> stimulates PTH to be secreted
Symptoms overshadowed by chronic renal failure

60

Hypoparathyroidism

Iatrogenic, congenital (DiGeorge's -> thymic aplasia, absence of parathyroids), familial

61

Signs and Symptoms of Hypoparathyroidism

TETANY -> tingling around mouth/extremities
- Chvostek's sign -> stroking/tapping cheeck induces eye, mouth, and nose contraction
- Trousseau's sign -> occluding forearm circulation induces carpal contraction
Mental Status changes
CV disease
Dental Abnormalities

62

Adrenal Anatomy and Histology

paired gland at top of kidneys, cortex has 3 zones, medulla has chromaffin cells

63

Adrenal Cortex and Medulla and hormones

Zona glomerulosa -> mineralocorticoids
Zona fasciculata -> glucocorticoids
Zona reticularis -> sex steroids
Medulla -> Catecholamines

64

Cushing Syndrome

increased glucocorticoids (cortisol) in blood
- stable BP, decreased Bone, decreased inflammation, decreased immunity, increased gluconeogenesis

65

Signs of Cushings

HTN and weight gain
adipose tissue distributed truncally, moon facies, buffalo hump
- weakness
- glucose intolerance
- thin fragile skin
- infections

66

Labs for Cushing

24 hr urine free cortisol --> diagnosis
ACTH level, dexamethasone test --> cause

67

Causes of Cushing

Iatrogenic -> drug ingestion (low ACTH, dex doesn't suppress cortisol)
Pituitary adenoma -> ACTH high, dex suppresses cortisol
Adrenal lesion -> ACTH low, dex doesn't suppress cortisol
Ectopic ACTH production -> ACTH high, dex doesn't suppress cortisol

68

Hyperaldosteronism

High Aldosterone, high Na/low K
Primary - high aldosterone -> low renin
- HTN, weakness, fatigue
- Labs = high aldosterone, low renin, high Na/low K, metabolic alkalosis
Secondary - high renin -> high aldosterone
- symptoms same
- Labs = high aldosterone, high renin, high Na/low K, metabolic alkalosis

69

Adrenogenital syndromes

VIRILIZATION
Primary gonadal disorders, primary adrenal disorders

70

Congenital Adrenal Hyperplasia

enzyme block in cortisol pathway (21-hydroxylase MOST COMMON)
- precursors are shunted to other pathways --> mostly to sex steroids (testosterone) --> turns females to have male features

71

Addison disease

Primary CHRONIC adrenal insufficiency -> intrinsic adrenal cortex problem leading to decreased cortisol and mineralocorticoids
Causes -> autoimmune, infections, metastatic carcinoma
Features -> chronic (takes a while for symptoms to appear), hypoglycemia, metabolic acidosis, skin hyperpigmentation from POMC -> makes both ACTH and MSH

72

Primary Acute adrenal insufficiency

adrenal SUDDENLY aren't releasing their stuff
*Addisonian crisis*, steroid withdrawal, massive adrenal hemorrhage

73

Massive Adrenal Hemorrhage

newborns following difficult delivery
anticoagulated patients
DIC
following bacterial infection (WFS)

74

Waterhouse-Friderichsen syndrome

overwhelming bacterial infection (N. meningitidis)
hypotension and shock
DIC
rapidly progressive massive adrenal hemorrhage

75

Secondary Adrenal Insufficiency

low ACTH -> low adrenal products
Causes = pituitary insufficiency, hypothalamic insufficiency
Features = symptoms of low cortisol and low sex steroids

76

Pheochromocytoma

Neoplasm of catecholamine producing cells derived from neural crest
Pressure (BP), Pain, perspiration, palpitations, pallor
10% tumor = extra-adrenal, bilateral, familial, malignant, don't have HTN

77

Neuroblastoma

neoplasm derived from neural crest cells -> common childhood tumor
- round, blue rosette cells
- N-myc amplification associated with bad prognosis