Systems - Endocrine

• 1) hypothalamus makes TRH stimulates anterior pituitary to make TSH
• 2) TSH increases the production of T3 and T4
• 3) Rising levels of T3 and T4 inhibits TRH release by the hypothalamus and TSH levels by the anterior pituitary

• 1) PE (HR, sweating, fine tremor, hair loss)
• 2) Palpation of thyroid 
• 3) Labs (fT3, fT4, TSH, thyroid autoantibodies)
• 4) U/S
• 5) Iodine uptake scan

• 1) increases synthesis of Na-K-ATPase pumps
• 2) Increases SNS by increasing expression of Beta1 receptors

• 1) Autoimmune: Graves (most common; TSH receptor antibodies), Hashimoto's (transient; anti Tb and Tg antibodies)
• 2) autonomy of the thyroid (not TSH dependent; uptake scan, absence of abs)
• 3) Exogenous hyperthyroid (too many pills; Hx)
• 4) Thyroid cancer (rare; uptake, U/S)
• 5) Pituitary dysfunction (high TSH)
• 6) Amiodarone therapy

• 1) initial hyperthyroid (release of stored T4) and then hypo (tissue is destroyed)
• 2) Look for high antithyroglobilin (Tg-abs) and anti-thyroperoxidase (TPO-abs) (these are the destructive antibodies causing the damage)
• 3) infiltration of lymphocytes
• 4) Heurthel cells

IgG (TSI) stimulates the TSH receptors which causes the overproduction of thyroid hormone in the thyroid. In addition it increases GAG production in fibroblasts behind the eyes and on the shins causing the proptosis and tibial myxedema, respectively.

• Decreased TSH, increased fT3 and fT4
• TSH-receptor abs are increased
• anti-TPO and anti-Tg abs are increased. 
• Diffuse increased RAIU (radioactive iodine uptake)

With the exception of the TSH-receptor abs and the these results are the same as what you would see in early Hashimoto's thyroiditis

• -Hot: autonomous adenomas
• -diffuse increase: disseminated autonomy and Graves

• Pressure - HTN (90%)
• Pain - headache (80%)
• Perspiration (70%)
• Palpitations (65%)
• Pallor (40%)

The 6th P is paroxysmal. These events are severe and transient (some insult causing release)

• 1) Hashimoto's: chronic lymphocytic infiltration
• 2) de Quervain's (subacute thyroiditis): tender, granulomatous infiltration
• 3) Post partum: subacute
• 4) Riedel: hard a wood, nontender

• Primary: thyroid
• Secondary: pituitary
• Tertiary: hypothalamus

• -empty sella
• -pituitary adenoma
• -post hypophyseal surg
• -post traumatic brain injury
• -apoplexy (Sheehan-syndrome)

• 1) increased TSH levels cause cell hypertrophy
• 2) decreased Iodine in thyrocytes causes cell hyperplasia

both of these lead to goiter. Normal TSH, fT3, and fT4

• bradycardia
• cardiac and lipid abnormalities
• cold intolerance
• delayed reflexes
• goiter
• hair and skin changes

• THYROIDISM mnemonic
• Tremor
• Heart rate up
• Yawning (fatigued)
• Restlessness
• Oligomenorrhea/amenorrhea
• Intolerance to heat
• Sweating
• Muscle wasting/weight loss

lifetime f/u. routine TSH, fT4, fT3, thyroid autoantibodies

autonomous adenoma (multinodular goitre)

• 1) Thionamines: Methimazole (longer half life, usually preferred, teratogenic); Propylthiouracil (PTU, use in 1st trimester of preg)
• 2) Symptom tmt with beta blockers
• 3) Thyroid ablation with radioactive iodine
• 4) Thyroidectomy
• 5) Use steroids for extreme exopthalmos

This is a medical emergency. Bascially stress in a hyperthyroid patient has caused a huge hormone release.

Treat the same as graves, but with higher doses. give supportive tmt. Treat precipitant. Give dexamethasone to decrease inflammation and stop peripheral conversion of T3->T4.

• Anti-TPO Abs
• Anti thyroglobulin Abs
• Uptake scan
• U/S

• HIS FIRM CAP mnemonic
• Hypoventilation
• Intolerance to cold
• Slow HR
• Fatigue
• Impotence
• Renal impairment
• Menorrhagia/amenorrhea
• Constipation
• Anemia
• Paresthesia

Six weeks, because it has a one week half life and it takes this long to reach SS in the body

Increase the levothyroxine dose as pregnant women need more in order to stay euthyroidic.

a medical emergency! Hypothyroid complicated by some kid of acute stressor. Treat the same as hypothyroidism with supportive care.

• -different T3/T4 ratio in animals
• -a lot of variability between batches

FNA

DKA

-Insulin receptors on all tissues.

-induce uptake of glucose into cells

-Increase storage of glucose (glycogen, protein, and fat production)

-Decreases gluconeogenesis by liver

-Inhibits glucagon

• 1) relative insulin deficiency
• 2) Excess hepatic glucose production
• 3) Insulin resistance (due to obesity and inactivity)

• DM II - 90-95%
• DM I - 5-10%

We cannot prevent it once it is underway

• >40 or part of a high risk group
• HR Groups
• -History: 1st degree rel with DM, HR population (e.g. aboriginal), IGT or IFG (pre-diabetes), Hx of GDM or macrosomia
• -Clinical: DM complications, HTN, dyslip, fat, PCOS, acanthosis nigricans, chronic use of corticosteroids

Lifestyle changes. 60% reduced risk with 5% weight loss in people with prediabetes.

Medications can give some prophylaxis, but are not as good

Diabetes: presence of hyperglycemia

pre-diabetes: abnormal blood glucose, but not to the levels of diabetes. Includes Impaired fasting glucose (b/n 6.1-6.9), Impaired glucose tolerance (b/n 7.8-11.0), of HbA1c 6.0-6.5

DMI: young, usually no FHx, usually thin, sudden onset (DKA)

DM II: usually older adults, commonly a +ve FHx, fatty, gradual onset

• Any one of these will diagnose (confirm on a later date usually)
• 1) fasting glucose >= 7 
• 2) random gucose > 11.1 + Sx of hyperglycemia (Polydipsia, polyuria, weight loss)
• 3) 75 g OGTT: fasting >= 7 and 2hr blood > 11.1
• 4) HbA1c >= 6.5%

Unless one test is SUPER sky high, confirm the next day with any of the above tests (does not need to be the same one)

• 1) ketonemia
• 2) ketouria
• 3) increased ion gap metabolic acidosis

• 1) A1C: <= 7 (7.1-8.5 in elderly)
• 2) FPG or pre prandial: PG 4-7
• 3) 2 hr post-prandial: 5-10

Achieve one in 3-6 months

• carbs: 40-60%
• protein: 15-20% protein
• fat: <35% fat

5-10%

metformin

CI's: renal failure or CHF

• -thiazolidinedione
• -insulin
• -sulphonylurea (glyburide)
• -meglitinide

We want to use the ones that cause weight loss first (usually metformin to start)

• 1) insulin secretagogues (sulphonylureas, meglitinides
• 2) Insulin sensitizers (metformin
• 3) Impair carb absorption (acarbose)
• 4) Incretin analogues (GLP, or DPP agonists)
• 5) pee out glucose (SGLT inhibitors)
• 6) insulin

• 1) rapid acting (10-15 mins onset, 1 hr peak): humalog, novorapid
• 2) short acting ( 30 min onset, 2-5 hr peak): humulin-R, toronto
• 3) Intermediate (1-3 hr onset, 5-8 hr peak): humulin-N, NPH
• 4) long acting (90 min onset, lasts 16-24 hrs): Lantus

• 1) A1c < 7
• 2) BMI < 25
• 3) aggressive BP management (<130/80): protect kidney, brain, heart and BVs
• 4) Aggressive cholesterol management: Target LDL < 2

ACEi or ARB

absolute insulin deficiency and a trigger (e.g. infection, trauma, etc)

triggers high counterregulatory hormone production (cortisol, glucagon, etc) which breaks down glycogen, proteins, fats which produces ketones and acids.

Causes dehydration due to diuresis

• 1) hyperglycemia (>14)
• 2) Ketoacidosis: Increased Ion gap metabolic acidosis; ketonemia; ketonuria
• 3) Dehydration electrolytes: elevated Cr/urea; usually hyperkalemia due to insulin deficiency

• IV fluids (NS; they are dehydrated)
• potassium (prevent hypokalemia as the insulin drives the K intracellularly; wait until urine is being produced)
• insulin (to correct hyperglycemia; wait until K levels are 3.3-5.5 before giving; usually in conjunction with IV glucose once stabalized)

• Stop Insulin when:
•  -Anion gap normal
•  -patient is eating/drinking without vomiting
•  -Kenotemia/ketonuria is resolved

similarities: severe volume depletion; hyperglycemia

difference: no ketoacidosis (no DKA manifestations, no increased ion gap MA, no ketonuria/ketonemia); K+ is usually normal (both due to this only being a RELATIVE insulin deficiency); patients are usually 2x as dehydrated

PG < 4

adrenergic sx (1st): palpatations, tremors, anxiety, sweating, tachycard

neuroglycopenic Sx (2nd): dizzyness, dullness, confusion, seizures, coma

1) macro: CAD, PAD, CVD

2) micro: retinopathy, neuropathy, nephropathy, gastroparesis, erectile dysfunction

anion gap = [Na] - ([HCO2-]+[Cl-])

Normal is 12+-2

Statins

• -no cortisol, no aldo, lots of sex steroids
• -no cortisol: hypotension, excess ACTH makes both glands big, N/V
• -no aldo: salt waste (hypovol) with hyperkalemia
• -excess sex steroids: clitoromegaly and precocious puberty

• it gets better as you get deeper (GFR):
• -outermost (granulosa): aldo
• -middle (fasciculata): cortisol
• -deepest (reticularis): sex steroids

• -muscle atrophy: increased m. breakdown for gluconeogenesis
• -weird fat deposition: increased insulin causes fat storage
• -abdominal striae: cortisol decreases collagen prod, causing BV rupture
• -HTN: cortisol increases alpha1 receptors
• -Osteoporosis (decreased bone prod, increased resorption)
• -Immunosuppression

• 1) 24 hour urine free cortisol and Cr: should not be 3x normal upper limite
• 2) Low dose dex suppression test: 1 mg dex at 11pm should suppress cortisol at 8am (< 50). Dex is not detected in assay. If it is still high then cortisol levels are TRULY elevated and this is not just regular variability

• 1) What is causing this excess production
•  -Adrenal source (ACTH < 5)
•  -ACTH-dependent (ACTH >15)
• 2) If ACTH-dependent use high dose dex test and imaging to figure out pituitary or ectopic source (high dose dex will slap the pituitary and decrease ACTH levels, no response in tumor)
• 3) Manage Sx: Blood sugars, BP, infections, bone health

hyperaldosteronism due to an adrenal adenoma

• sodium reabsorption (water follows)
• potassium excretion
• H+ excretion

• -Severe HTN on 3 agents or hypokalemia (Use the BP Cuff in Conn's)
• -electrolyte changes: hypernatremia, met alk, ALMOST ALWAYS HYPOKALEMIA
• -There will be high aldo and low renin

• 1) low sodium
• 2) dehydration
• 3) decreased renal blood flow
• 4) low aldo

• 1) salt loading test: sodium bolus decreases aldo in a normal person but does not change anything with someone with primary hyperaldosteronism. Confirm with MRI.
• 2) Too many people have adrenal incidentalomas (10%) which will give falkse +ves

• Definitive tmt is surgery
• Medically manage with spirinolactone (aldo antagonist)

• -androsenedone
• -DHEAS
• -testosterone

MRI of adrenals after biochemical suspicion

important to diagnose early because hair that has converted to dark terminal hair will not revert back after tumor is excised.

• 10% are extramedullary
• 10% in kids
• 10% bilateral
• 10% malignant
• 10% incidentally discovered
• 10% re-occur after removal
• 10% familial (more like 20%)

• -MEN 2A and 2B
• -von hippel-landau
• -NF 1

24 hour urine looking for metanephrines and chatechols. (+ve if >2x upper limit)

Drugs and stress (OSA included) can cause false +ves

• 1) MRI
• 2) CT
• 3) MIBG scan (attaches to these specific tumor cells)

Surgical excision

always give phenoxybenzamine (irreversible alpha blocker) so that when you disturb the gland and release all the catacholamines the patient doesn't die on you

If they cant tolerate surgery, give them beta blockers

Cancer is large (>4.5) adenoma is small (<4.5 cm)

Diagnose by biopsy, BUT MUST RULE OUT PHEO BEFORE JAMMING A NEEDLE IN THERE!!!

• non-functioning (most common)
• Cushings
• Pheo
• primary aldo

AI destruction cortical glucocorticoid and mineralocorticoid layers. People get hyperpigmentation and vitiligo (if they have concurrent hash. thyroiditis)

• Pull 8am cortisol levels ( best screening)
• if low then do a cosyntropin (ACTH analog) stimulation test. +ve test if no corresponding rise in cortisol (best diagnostic)

180/120

• 80%+ of pheo's are non-familial
• MEN is autosomal dominant, so she would need a parent with the disease

• -1-3 L of NS over 24 hours
• -glucocorticoids (e.g. dex) IV

DO NOT WAIT FOR TESTS TO COME BACK!

use mineralocorticoid replacement (fludrocortisone) for replacement

• ACTH: CRH (+ve), cortisol (-ve)
• GH: GRHR, somatostatin
• LH/FSH: pulsatile GnRH, constant GnRH, estrogen 
• TSH: TRH, T4, T3
• Prolactin: progesterone, under constant dopamine inhibition

bitemporal hemianopsia usually. can get a homonymous hemianopsia if post-optic chiasm compression

• If macroadenoma (>1cm):
• -evaluate for hyper/hypofunctioning
• -if <2cm and no Sx-> close followup

• If microadenoma (<1cm):
• -evaluate for hyper/hypofunctioning
• -followup if non-functioning
• -reassure patient (95% do not enlarge over 4-6 years of observation)

• -acute infarct/hemorrhage of pituitary tumor
• -sudden/severe headache
• -ophthalmoplegia
• -an emergency!!! need transphenoidal decompression

• Presentation:
• -Children: (justin fontaine), reduced muscle mass, chubby/cherubic facial features
• -adults: baldness, fatigue, reduced muscle/bone mass

• Investigate:
• -NOT random GH (pulsatile hormone)
• -IGF-1 (would be low)
• -Stimulated GH (Insulin Tolerance Test (hypoglycemia))

TSH (normal to low), free T4 (markedly low)

if this was primary hypothyroid TSH would be markedly elevated

• Peds: absent puberty (>16 w/o menarche), boys >15
• Adults: decreased libido, ED, amenorrhea, infertility

Genetic cause of this is Kallmann syndrome (XXY

• AM cortisol (screening test)
• Hypoglycemia (insulin tolerance test) gold standard

• No hyperkalemia (RAAS is still intact)
• No hyperpigmentation (no increase in POM-c)

• -Polyuria and polydipsia
• -hypernat and hyperosm (serum) only if water restricted
• -inappropriately dilute urine

We water restrict them and test urine OSM. If even in the presence of increase serum osmolality their urine is still dilute Uosm<300) it is diagnostic.

Give desmopressin (ADH) to distinguish (no response if nephrogenic, because of shitty kidney receptors)

• 1) 1-5 days of DI due to stunned pituitary
• 2) day 6-11 see heavy release of ADH from degenerating pituitary (SIADH)
• 3) third phase sees either resolution or permanent DI (almost all resolve (10% stay))

we replace the end organ hormones as needed

• -features of hypogonadism (prolactin inhibits GnRH release)
• -galactorrhea
• -may be asymptomatic in post-menopausal women

Dopamine agonists: Cabergoline, bromocriptine, pergolide (work in 90% of patients)

Trasphenoidal surgery if highly symptomatic and refractory to medical tmt

• Children: gigantism
• Adult (acromegaly): jaw growth, rings and shoes dont fit, coarse facial features, diabetes (GH impairs glucose uptake into cells), hyperhidrosis (lots of sweating), Body Odor

• 1) IGF-1 (would be high)
• 2) OGTT with GH tested (GH would not be successfully suppressed)

definitive tmt is surgery

if not resectable: give a somatostatin analog (Octreotide or lanreotide); or a dopamine agonist or a GH-receptor antagonist (not widely avail)

• The fat ones
• -moon facies
• -supraclavicular fat
• -dorsocervical fat (buffalo hump)

• Ovary: 40%
• Hypothalamus: 35%
• Pituitary: 19%
• Uterus: 5%
• Other: 1%

• -Prolactinoma can cause hypopit, which may cause low cortisol meaning hypotension and hypoglycemia
• -dopamine agonists can cause hypo or hypotension depending on the type or dose
• -NEED TO CAREFULLY MONITOR BLOOD PRESSURE INTRAOPERATIVELY!!!

• -try to avoid dopamine agonists
• -follow tumor size, if it starts enlarging (increased risk of sheehans) use bromocriptine in 1st trimester
• -Don't use if breast feeding because they decrease production

• heart: basically you get hypertrophy
• Joints: excess cartilage production, alters joint geometry, eventually causing osteoarthritis

• sensitive: IGF-1
• Specific: OGTT with reading of GH levels after

Yes, because of their presumed pituitary insufficiency they will likely not be able to make the cortisol they normally would to help during surgery.

• -excise adenoma from pituitary
• -radiation
• -drugs (e.g. ketoconazole, mitotaine) which decrease cortisol production by inhibiting adrenal enzymes
• -Remove adrenals then supplement cortisol
• -lifestyle: exercise, eat well

• -ensure adequate Vit D intake
• -follow current infant feeding guidelines: breastfeed for 6 months
• -avoid exposure to cow's milk proteins in high risk children (use casein formula instead)
• -avoid exposure to gluten before 6 months of age

GI: measure of blood glucose response to 50 g of carbohydrate from a paticular food

• GL = [GIx(g carbs per serving)]/100
•   -basically normalizes to carb density

• -slower stomach emptying (acids, protein, fat, soluble fibre)
• -amylose starch (legumes)
• -less geletanization of starch (cook pasta al dente)
• -physical barriers (whole grains)

• -mimic estradiol
• -induces hyperinsulinemia and insulin resistance

• -colon cancer
• -stroke
• -coronary heart disease
• -diabetes

• 1) maintain normal body weight
• 2) low GI/GL foods
• 3) high fibre diet
• 4) adequate vit C, D, magnesium
• 5) nuts, fatty fish
• 6) regular exercise
• 7) reduce exposure to environmental toxins (e.g. BPA)
• 8) reduce chronic stress

• -Gender: males>females
• -genetics
• -BMR decreases with age
• -higher % body fat means lower BMR
• -starvation decreases BMR

-as you lose weight you also lose lean tissue, when you regain the weight less lean tissue is regained

You never feel full and you keep eating

• -regular balanced meals and always eat breakfast
• - regular exercise
• - enough sleep (7-8 hours)
• -Reduce calories from liquids (other than milk)
• -increase fibre
• -take vit D (expecially in winter)
• -eat more slowly, chew more

PTH increases blood calcium level

• -resorption of bones
• -reabsorption from renal tubules (and excretion of PO4)
• -absorption from GIT

• CNS: lethargy, stupor, fatigue
• CV: short QT interval, HTN, bradycardia
• Renal: polyuria, stones
• GI: N&V

primary hyperparathyroidism (usually a single adenoma)

• -HYDRATION!!
• -furosemide
• -bisphosphonates
• -calcitonin acutely

• enhanced neuromuscular irritability
• -+ve Chovostek's and trousseau's signs

insufficient Vit D in children causes elastic bones that can bend.

Osteomalacia is the adult version of this and is seen in renal failure

• SPLATT
• S- symptoms
• P - previous falls
• L- location of the fall
• A - activity at the time of fall
• T - Time of fall
• T - Trauma

all men and women over 65

• Ca: 1200 mg/day
• Vit D: 1000-2000 IU/day

• Pituitary
• Pancreatic
• Primary hyperparathyroidism