Endocrine Pathology Flashcards
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)
Posterior Pituitary
Neural ectoderm -> from diencephalon
- doesn’t make hormones, it stores hormones (oxytocin and ADH)
- extension of hypothalamus
Acidophils
secretes GH and PRL
Basophils
secretes FSH, LH, ACTH, TSH
Oxytocin
Labor induction Milk let down Cuddle hormone Monogamy Trust
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
Mass Effect
Visual field abnormalities - bitemporal hemianopsia (optic chiasm)
Symptoms of increased cranial pressure
Compression of pituitary -> HYPOpituitarism
Functional vs. Nonfunctional pituitary adenomas
functional = produces pituitary hormone non-functional = doesn't produce hormone -> becomes really big (mass effect)
Epidemiology of pituitary adenomas
occurs most common in adults
3% arise from multiple endocrine neoplasia
- can cause “pituitary apoplexy” –> sudden bleeding that is BAD
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
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
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)
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)
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)
FSH and LH producing adenomas
secrete FSH and LH very inefficiently
- mass effect brings it to attention rather than endocrine abnormalities
TSH-producing adenomas
RARE!!!!!
Non-functioning adenoma
secretes no hormones –> gets BIG and causes mass effect
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
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
Posterior Pituitary Syndromes
Diabetes Insipidus and Syndrome of Inappropriate ADH Secretion
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)
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
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
Thyroid Physiology
hypothalamus secretes TRH –> anterior pituitary secretes TSH –> thyroid synthesizes and releases T3 and T4, grows, uptakes iodine
Thyroid Hormone Function
increase fat breakdown, decrease carb utilization, stimluate protein synthesis, increased BMR
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’
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
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)
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
Causes of hyperthyroidism
Graves’ disease –> MOST COMMON CAUSE
- goiter, thyroid adenoma, thyroiditis, ingestion of thyroid hormones, pituitary adenoma, struma ovarii, factitious
Diagnosis of hyperthyroidism
TSH and free T4
Primary -> high T4 and low TSH
Secondary -> high T4 and high TSH
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)
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
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
Diagnosis of Hypothyroidism
TSH and free T4
Primary -> low T4 and high TSH
Secondary -> low T4 and low TSH
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)
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
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
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)
Reidel’s thyroiditis
Rock-hard, woody neck mass –> fibrosis
- fibrosis may progress and put pressure on trachea
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
Treatment of Graves’
decrease symptoms of hyperthyroidism (beta-blocker)
decrease synthesis of thyroid hormones = PTU, radioiodine ablation
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)
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
Neoplastic thyroid disease
most thyroid bumps are non-neoplastic –> but need to aspirate/biopsy to make sure
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
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
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
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
Anaplastic thyroid carcinoma
rapidly-enlarging bulky neck mass –> often metastasized already upon presentation
Anaplastic cells –> VERY undifferentiated = bad prognosis
Parathyroid Gland
4 glands in 2 pairs Upper lobes -> 4th pharyngeal pouch Lower lobes -> 3rd pharyngeal pouch - chief cells -> PTH - oxyphil cells -> unknown function
Parathyroid Physiology
Chief cells secrete proparathyroid -> cleaved to PTH -> binds to PTH receptors -> stimulate AC -> PLC -> IP3 and DAG
PTH Actions
- Stimulate osteoblasts -> stimulate osteoclasts -> increase blood calcium
- Increase renal absorption of calcium
- Increase renal conversion of Vit D to active form
- Increase urinary excretion of phosphate
- Absorb gut calcium
What controls PTH release?
serum calcium –> NOT pituitary
serum calcium increases -> PTH decreases
serum calcium decreases -> PTH increases
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
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)
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
Causes of primary hyperparathyroidism
- Parathyroid Adenoma -> most common
- composed mostly of chief cells
PRAD1 -> genetic alterations in sporadic cases
MEN1 or RET -> genetic alterations in familial cases - Parathyroid Hyperplasia -> normal looking cells, just a lot of them, some MEN1 syndromes
- Parathyroid Carcinoma -> abrupt onset of pain bain, usually just one gland affecteed, tumors are well-differentiated
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
Hypoparathyroidism
Iatrogenic, congenital (DiGeorge’s -> thymic aplasia, absence of parathyroids), familial
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
Adrenal Anatomy and Histology
paired gland at top of kidneys, cortex has 3 zones, medulla has chromaffin cells
Adrenal Cortex and Medulla and hormones
Zona glomerulosa -> mineralocorticoids
Zona fasciculata -> glucocorticoids
Zona reticularis -> sex steroids
Medulla -> Catecholamines
Cushing Syndrome
increased glucocorticoids (cortisol) in blood - stable BP, decreased Bone, decreased inflammation, decreased immunity, increased gluconeogenesis
Signs of Cushings
HTN and weight gain adipose tissue distributed truncally, moon facies, buffalo hump - weakness - glucose intolerance - thin fragile skin - infections
Labs for Cushing
24 hr urine free cortisol –> diagnosis
ACTH level, dexamethasone test –> cause
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
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
Adrenogenital syndromes
VIRILIZATION
Primary gonadal disorders, primary adrenal disorders
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
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
Primary Acute adrenal insufficiency
adrenal SUDDENLY aren’t releasing their stuff
Addisonian crisis, steroid withdrawal, massive adrenal hemorrhage
Massive Adrenal Hemorrhage
newborns following difficult delivery
anticoagulated patients
DIC
following bacterial infection (WFS)
Waterhouse-Friderichsen syndrome
overwhelming bacterial infection (N. meningitidis)
hypotension and shock
DIC
rapidly progressive massive adrenal hemorrhage
Secondary Adrenal Insufficiency
low ACTH -> low adrenal products
Causes = pituitary insufficiency, hypothalamic insufficiency
Features = symptoms of low cortisol and low sex steroids
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
Neuroblastoma
neoplasm derived from neural crest cells -> common childhood tumor
- round, blue rosette cells
- N-myc amplification associated with bad prognosis
