6-9 291 - Endo - Path

Increased cortisol die to variety of causes

Exogenous steroids cause low cortisol by suppressing ACTH

1. Cushing's disease (70/100
2. Ectopic ACTH (15/100)
3. Adrenal causes (15/100)

This is specifically due to an ACTH secreting pituitary adenoma
Increased ACTH leads to increased cortisol

A nonpituitary tissue making ACTH
Increased ACTH leads to increased cortisol

1. Small cell lung cancer
2. Bronchial carcinoids

1. Adrenal adenoma
2. Adrenal carcinoma
3. Nodular adrenal hyperplasia
Cortisol is primarily increased and thus ACTH is low

1. HTN
2. Weight gain
3. Moon facies
4. Truncal obesity
5. Buffalo hump
6. Hyperglycemia due to insulin resistance
7. Thinning and striae in the skin
8. Osteoporosis
9. Amenorhea
10. Immune suppression

Dexamethasone is a synthetic glucocorticoid.
It is used diagnostically in the dexamethasone supression test (DST) where a patient is given a low and high dose each followed by a cortisol measurement

In a normal patient administered low-dose dexamethasone feeds back negatively and appropriately to the pituitary to supress ACTH
Thus, the normal response after low dose dexamethasone is low cortisol

Cushing's disease = ACTH increased due to pituitary adenoma
After low dose - cortisol will still be high like at baseline
After high dose - ACTH supression is achieved and cortisol will be low

Ectopic ATCH producing tumors don't respond to dexamethasone
Therefore, cortisol will remain high after both the low and high dose

ACTH is not involved in production of cortisol here, so dexamthasone will have no effect
Therefore, cortisol will remain high after both the low and high dose

Conn's syndrome is the eponym for primary hyperaldosteronism

Aldosterone secreting tumor such as adrenal carcinoma

1. HTN (salt retention)
2. Potassium wasting (hypokalemia)
3. Proton wasting (metabolic alkalosis)
4. Low plasma renin

Spironolactone
Competitive aldosterone antagonist

This is where the kidneys think they are being underperfused and so they jack up the renin-angiotensin-aldosterone pathway
Renin is high here

1. Renal artery stenosis
2. Chronic renal failure
3. Congestive heart failure
4. Nephrotic syndrome

Chronic adrenal insufficiency that is due to adrenal atrophy or destruction
This affects all adrenal cortex layers and so it leads to primary insufficiency of aldosterone and cortisol

1. Autoimmune
2. Tuberculosis
3. Metastasis

1. Low aldosterone
2. Low cortisol
3. Hypotension (salt-wasting)
4. Hyperkalemia
5. Elevated ACTH leads to skin hyperpigmentation

POMC is the precursor protein for both ACTH and MSH. So if one is increased, the other is increased.

Secondary adrenal insufficiency would be a hypo-secreting pituitary
Thus aldosterone would not be involved, so potassium would be normal
There would also be no hyperpigmentation

Acute adrenocortical insufficiency due to adrenal hemorrhage

1. Neisseria meningiditis septicemia
2. DIC
3. Endotoxic shock

Most common adrenal medulla tumor in adults

Chromaffin cells which are dervied from neural crest

Dopamine, NE and Epi leads to eposodic hypertensive spells, with other related symptoms

High urinary levels of HVA, VMA and metanephrine

1. NF1
2. MEN IIA
3. MEN IIB

With nonselective alpha blockers
1. Phenoxybenzamine: irrervible blocker used for pre-op control
2. Phentolamine: reversible blocker used for intra-op contral (more controllable)

1. Pressure
2. Pain (headache)
3. Perspiration
4. Palpitations
5. Pallor

10 percent:
malignant
bilateral
extra-adrenal
calcify
affect kids
run in families

Phenylalanine --> tyrosine --> L-dopa --> dopamine --> NE --> Epi
Dopamine converts to HVA (homovanillic acid)
NE converts to VMA (vanillylmandelic acid)
Epi converts to metanephrine

Most common adrenal medulla tumor in kids

Anywhere along the sympathetic chain

Elevated urinary HVA or VMA

Neuroblastomas don't cause HTN

N-myc

hypo

hyper

hypo

hyper

hypo

hypo

hyper

hyper

hyper

hypo

hypo

hypo

hypo

hyper

hyper

hypo

hyper

hyper

hypo

hyper

TSH

1. Increased TSH
2. Decreased total T4
3. Decreased free T4

1. Decreased TSH
2. Increased total T4
3. Increased free T4

Hashimoto's thyroiditis

Autoimmune process where the thryoid follicles are slowly destroyed
Patient may be hyperthyroid early in the course (thyrotoxicosis)
Patient will eventually become hypothyroid

Thryoid will be moderatley enlarged and non-tender

1. Lymphocytic infilatrate with germinal centers
2. Hurthle cells - enlarged epithelial cells that are eosinophilic and stain pink

1. Anti-thyroglobulin
2. Anti-microsomal

HLA-DR5

a syndrome due to severe fetal hypothyroidism

anywhere where there is a lack of dietary iodine which leads to endemic goiter

China

1. Due to defect in T4 production
2. Develepmental defect in thyroid gland formation

1. Pot-belly
2. Pale
3. Puffy face
4. Protruding umbilicus
5. Protuberant tingue
6. Mental retardation

Christlike - those who were affect were thought to be so mentally retarded that they were incapable of sin

Subacute thyroiditis

May initially by hyperthryoid
Self-limited hypothyroidism often following a flu-like illness

1. High ESR (inflammation)
2. Jaw pain
3. Very tender thyroid

Granulomatous inflammation (multi-nucleated giant cells)

Hashimoto's is also called chronic lymphocytic and it is painless
Subacute lymphocytic is also painless and it tends to happen post-partum
de Quervain's is also subacute but very painful

This is a type of chronic hypothyroidism where the thyroid tissue is replaced with fibrous tissue.

Fixed and rock-hard but painless goiter

Autoimmune - type II hypersensitivity

Auto-antibodies which bind and stimulate TSH receptors leading to hyperthyroid

1. Proptosis and EOM swelling
2. Pretibial myxedema
3. Diffuse goiter

During times of stress like childbirth

Hyperthyroidism of any kind increases to density of beta-1 receptors on the heart
Therefore, a stress induced catecholamine surge is a potential cause of death in any hyperthyroid patient

There are focal patches of hyperfunctioning follicular cells which are working independentally of TSH because they are mutated

Even though this sounds cancerous - no they are not malignant

A patient who has iodine deficiency goiter who is suddenly made iodine replete will become thyrotoxic

Papillary carcinoma

excellent

1. Ground glass nuclei (orphan annies)
2. Psammoma bodies
3. Nuclear grooves

Radiation in childhood

good

Uniform follicles

Parafollicular C cells

calcitonin

sheets of cells in amyloid stroma

MEN IIA and IIB

very poor

older folks

Hasimoto's thyroiditis

CHIMPANZEES
C = calcium ingestion (milk-alkali syndrome)
H = hyperPT or thryoid
I = iatrogenic
M = muliple myeloma
P = paget's disease
A = addison's disease
N = neoplasm
Z = zollinger ellison
E = Excess vitamin D
E = Excess vitamin A
S = sarcoidosis

thiazide diuretics

they usually have normal calcium but become hypercalcemic when immobalized

Usually a PTH secreting parathyroid adenoma

Stones, bones and groans
1. Hypercalcemia
2. Hypercalciuria (stones)
2. Hypophosphatemia
3. Increased PTH
4. Increased alk phos (bones)
5. Increased urinary cAMP
6. Weakness and constipation (groans)

The parathryoid glands are over active leading to painful cystic bone spaces that are filled with fibroous tissue.

von Recklinghausen's diesase
This is not NF1 which is von recklinhausen syndrome

the PT glands become hyperplastic because there is decreased gut calcium absorption and increased phosphorus levels

chronic kidney disease - so the whole process is secondary to decreased vitamin D

1. Hypocalcemia
2. Hyperphosphatemia
3. Increased alk phos
4. Increased PTH

Renal disease --> low vitamin D --> low calcium --> high PTH --> high bone turnover --> bone lesions

1. Accidental excision when doing a thyroid surgery
2. Autoimmune destruction
3. DiGeorge's syndrome

Hypocalcemia which is famous for causing tetany

A sign that indiciates hypocalcemia:
tapping on the facial nerve ellicits facial muscle twitching

A sign that indiciates hypocalcemia:
occlusion of brachial artery with BP cuff ellicits carpal spasms

an autosomal dominant kidney condition where the kidney doesn't respond to PTH

Albright's hereditary osteodytrophy

1. Hypocalcemia
2. Shortened 4th and 5th digits
3. Short-stature

prolactinoma

1. Bitemporal heminopsia due to compression of the optic chiasm
2. Amenorrhea - hypogonadism
3. Low libido - hypogonadism

Dopamine agonist drugs cause tumor shrinkage: Bromocriptine and cabergoline

Excess GH in adults

1. Large tongue with deeps furrows
2. Deep voice
3. Large, doughy hands and feet
4. Coarse facies
5. Insulin resistance (GH increases glucose)

Gigantism because excess GH accelerates linear bone growth

Pituitary adenoma resection followed by octreotide administration (somatostatin analogue)

1. Stress
2. Exercise
3. Hypoglycemia

1. Increased serum IGF-1
2. Serum GH does not fall after administering glucose load

Postpartum hypopituitarism

During pregnancy, the anterior pituitary gets bigger due to lactotroph hyperplasia. However, the blood suppply does not change. At delivery, if there is severe bleeding the enlarged pituitary is now at increased risk of being infarcted

1. Fatigue
2. Anorexia
3. Poor lactation
4. Loss of pupic and axillary hair

Constant thrist and polyuria
Cannot concentrate urine due to malfunction in ADH pathway

1. Central - lack of ADH production
2. Nephrogenic - ADH cannot bind to the kidneys

1. Pituitary tumor
2. Trauma
3. Surgey
4. Histiocytosis X

1. Hypercalcemia - messes with tubular transport
2. Lithium - famous for this
3. Demeclocycline - a tetracycline abx that antagonizes ADH

1. Water deprivation test - urine osmolality does not increase (urine doesn't concentate)
2. Central DI: desmopressin adminstration causes urine to concetrate
3. Nephrogenic: desmopressin administration yields no change

Dilute urine with SG < 1.006
Serum is hypertonic > 290

Intranasal desmopressin

1. Indomethacin
2. HCTZ
3. amilioride

It's complicated but the overall effect is to decrease:
1. Decrease water loss
2. Prevent hypokalemia

Anything whereby there is too much ADH acting in the body:
1. Excessive water retention - leads to hypotnic serum
2. Hyponatremia
3. Urine is more concentrated than the serum

Hyponatremia can lead to seizures
However, the levels must be corrected slowly because central pontine myelysis occurs if corrected too rapidly

1. H20 restriction
2. Demeclocycline

1. Ectopic ADH - small cell lung cancers
2. CNS disorder
3. Head trauma
4. Pulmonary disease
5. Drugs - cyclophosphamide

1. Polydipsia - drink lots
2. Polyuria - pee lots
3. Polyphagia - eat lots
4. Weight loss
5. DKA in type I
6. Hyperosmolar coma

1. Glucagon
2. GH
3. Epinephrine
4. Cortisol

Dehydration and acidosis which lead to coma and death

Insulin shortage (and unopposed other hormone excess) lead to:
1. Decreased glucose uptake
2. Increased protein breakdown
3. Increased lipolysis

Basically, hyperglycemia contributes to an osmotic diuresis where excess water is pulled into the tubules because there is so much solute

Protein breakdow creates lots of free AA which are lost as nitrogen in the urine. This process also contributes to osmotic diuresis

Increased fat breakdown leads to increased free fatty acids in the blood. This triggers ketogenesis which is a starvation reponse. So ketone levels in the blood and urine are high. They also cause the blood pH to drop and so this is called DKA

1. Non-enzymatic glycosylation
2. Osmotic damage

1. Small vessel disease - the BM is diffusely thickened
2. Retinopathy
3. Glaucoma
4. Nephropathy
5. Large vessel artherosclerosis (and the following sequelae)

1. Neuropathy
2. Cataracts due to sorbital accumulation

Type 1: viral or immune destruction of beta cells
Type II: body becomes resistant to insulin

Type 1: always
Type II: sometimes

Type 1: < 30 (with exceptions)
Type II: > 40 (with exceptions)

Type 1: no
Type II: yes

Type 1: weak
Type II: strong

Type 1: HLA-DR 3 and 4
Type II: no

Type 1: severe
Type II: mild

Type 1: common
Type II: rare

Type 1: decreased in number
Type II: amyloid is present

Type 1: decreased
Type II: variable

Type 1: yes
Type II: sometimes

Type 1

1. Due to not taking insulin (non-compliance or non-treated)
2. Complaint patient has increased insulin demands due to a physiologic stress like infection

Hyperglycemia without insulin ramps up lipolysis which then triggers ketogenesis from free FFA
This leads to ketone body formation (beta-hydroxybutyrate in greater concentrations then acetoacetate)

1. Kussmaul breathing (deep and rapid)
2. N&V
3. Abdominal pain
4. Psychosis
5. dehydration
6. Fruity smalling breath due to exhaled acetone

1. Hyperglycemia
2. High AG acidosis
3. Decreased bicarb
4. High blood ketones
5. High leukocytes
6. Hyperkalemia - due to K+ shift from inside cells which happens sue to low insulin

1. Mucormysosis
2. Rhizopus infections
3. Cerebral edema
4. Arrhythmias and heart failure

1. Fluids
2. Insulin
3. Potassium
4. Glucose on standby if hypoglycemia ensues

Hyperkalemia from DKA is because lack of insulin causes K+ to shift out of cells into the serum
When insulin is given, the K+ gets sucked back into cells and hypokalemia ensues
Therefore, K+ must be co-administered to correct this treatment related hypokalemia

rare

neuroendocrine cells

small bowel neuroendocrine tumors that metastasize to elsewhere
these tumors secrete 5-HT

when they are confined to the small bowel, secreted seratonin is metabolized in the liver

1. Diarrhea
2. Flushing
3. Asthmatic wheezing
4. Right sided valvular disease

carcinoid tumors are the most common tumor of the appenidix

increased 5-HIAA in the urine
this is the metabolic product of serotonin

1/3 of these tumors:
1. Metastasize
2. Present with a 2nd malignancy
3. are multiple

octreotide is a somatostatin analougue

gastrin secreting tumor of the pancreas or duodenem

recurrent ulcers

MEN I - this is one of the possible pancreatic tumors

1. MEN I
2. MEN IIA
3. MEN IIB

Wermer's

Sipple's

there is none

All MEN syndromes are AD

The ret gene is associated with MEN IIA and IIB

3PUST 2PM 1PMMG

3PUST
P = pituitary tumor
P = Parathyroid tumor
P = Pancreatic neuroendocrine tumors
U = ulcers
S = stones (from high PTH)
T = thyroid adenoma

Prolactin or GH

PTH --> hypercalcemia --> kidney stones

1. Zollinger Ellison - secretes gastrin which causes ulcers
2. Insulinomas
3. VIPoma
4. Glucagonoma

2PM
P = pheochromocytoma
P = Parathyroid tumors (high PTH)
M = medullary thyroid carcinoma (secreting calcitonin)

1PMMG
P = pheochromocytoma
M = medullary thyroid carcinoma (secreting calcitonin)
M = marfinoid habitus
G = ganglioblastomas in the mouth and intestine