Endocrinology

rare

papilledema is ____ (rare/common) in pituitary tumors

suprasellar

papilledema, diabetes insipidus, & neurologic symptoms are common with _______ tumors

Foster-Kennedy Syndrome

one eye has optic atrophy and the other has papilledema

diabetes insipidus

• chronic excretion of large amounts of pale urine w/ low specific gravity up to 6L/day

• sx: polyuria & polydipsia

  • HA, VF defects, seizures

• can also be CNS or nephrogenic

Wolfram syndrome

diabetes insipidus, optic atrophy, & deafness

inadequate ADH

what is the CNS type of diabetes insipidus caused by?

kidneys do not respond to ADH

what is the nephrogenic type of diabetes insipidus caused by?

prolactin hypersecretion

what is the most common type of all pituitary adenomas?

prolactin, GH, corticotropin

what are the types of hypersecretion tumors?

amenorrhea

what is the most common symptom of pituitary prolactinoma?

amenorrhea

absence of menses of more than 6mo in females older than 16yo that have previously had a normal menstrual cycle

pituitary prolactinoma

amenorrhea w/ galactorrhea is highly suggestive of _______

serum prolactin, serum FSH & LH

what lab tests are done in the work-up for a pituitary prolactinoma?

primary gonadal failure

if serum FSH & LH are high on the lab workup for a pituitary prolactinoma, what does this indicate?

acromegaly/gigantism

• due to hypersecretion of GH

• changes are very slow and progressive

• s/sx:

  • broadened hands, fingers & feet

  • coarse facial features

  • enlarged nose

  • pronounced jaw → malocclusion & widely spaced teeth

  • thickened skin

• HTN common

• DM in 25% of cases

HA, loss of VA, bitemporal hemianopsia

what are the common optometric ccs for acromegaly?

oral glucose tolerance test, IGF-1, FBS, serum T4, serum testosterone, X-ray, MRI

what are the lab tests for acromegaly work up?

increased

_______ blood glucose causes the body to stop making GH

elevated

FBS will be _________ in acromegaly

low

serum T4 is ____ in acromegaly

low

serum testosterone is ____ in acromegaly

>10ng/mL

dx of acromegaly is confirmed by finding elevated fasting blood levels of GH _______

enlarged pituitary fossa & jaw, lips & hooks on finger tips

what are some acromegaly findings seen on X-ray?

1. trans-sphenoidal microsurgery

2. radiotherapy

3. somatostatin injection, GH receptor antagonists

what are some of the tx for acromegaly?

trans-sphenoidal microsurgery

which tx for acromegaly has the highest cure rate?

CN3 palsy

what is a potential sequela of trans-sphenoidal microsurgery for acromegaly?

Cushing’s disease, ectopic ACTH syndrome

what can ACTH hypersecretion lead to?

cortisol

excessive production of ACTH will act upon the adrenal glands to produce excessive levels of ______

Cushing’s disease

• hypercortisolism caused by bilateral adrenal hyperplasia due to a pituitary lesion

• pathophysiology:

  • pituitary tumor (80%)

  • sarcoid

  • infections

  • Sheehan’s syndrome

• females makeup more than 70% of cases

• onset: 20-40yo

• s/sx:

  • truncal obesity

  • moon facies

  • dorsal hump

  • protein wasting w/ thin skin

  • bruising

  • violaceous striae

  • muscle weakness

  • osteoporosis & compression fractures

  • HTN & diabetes

  • mental changes

  • hirsutism & menstrual irregularity in females

Cushing’s syndrome

any disorder of glucocorticoid excess (not due to a tumor)

Sheehan’s syndrome (pituitary apoplexy)

• ischemic necrosis or hypovolemic shock during/after childbirth

• life-threatening, acute infarction of the pituitary gland

• s/sx:

  • sudden decrease in VA

  • ophthalmoplegia

  • sudden HA/nausea & vomiting

  • sensory perception changes

  • seizures/hemiplegia

24hr urine free cortisol, late night salivary cortisol, midnight plasma cortisol x 3 nights

what are the initial labs for Cushings?

8am, 11pm, 50%

when is urine cortisol highest? lowest? normal expected ___ drop

positive

if urine free cortisol measures the same at 8am and 11pm, this is a _____ finding

>7.5ug/dL

midnight plasma cortisol x 3 nights is positive for Cushings if ______

pituitary dependent tumor

if plasma ACTH >52pg/mL, there is a 90% chance that there is a ________

ectopic ACTH

if plasma ACTH >400pg/mL, this indicates an ______

primary adrenal disease

if plasma ACTH is <5pg/mL, this indicates _________

no, plain X-rays do not often show the tumor because it is small & CT/MRI are only positive 50% of the time w/ 10-15% of normal brains showing similar changes

is special imaging good for finding a pituitary tumor?

ACTH syndromes

• make up 10% of ACTH elevations, often secondary to small cell lung CA

• M=F

• s/sx:

  • muscle weakness

  • weight loss

  • hypokalemic alkalosis

panhypopituitarism

• destruction of the pituitary due to hemorrhage, tumors, postpartum, trauma/shock, or DM

• s/sx:

  • loss of eyebrows/lashes

  • dry, scaling lids

  • depigmentation of the uvea

  • hypoadrenalism

  • hypothyroidism

  • hypogonadism

inflammation (sarcoidosis), toxic (vincristine)

hypothalamic disease can be secondary to __________ or ______

florid myxedema

• subcutaneous infiltrative skin condition of the face & hands associated w/ severe hypothyroidism

• common

pretibial myxedema

• infiltrative skin condition of the lower extremities associated w/ hyperthyroidism

• rare

diffuse/smooth symmetrical gland often w/ bruit & hyperthyroidism

describe the goiter seen in Graves’ disease

nodular gland w/ hypothyroidism & positive antibodies

describe the goiter seen in Hashimoto’s thyroiditis

longstanding multi-nodular gland in older pts, often accompanied by CHF, arrythmias, & high iodine uptake

describe an endemic goiter

hypothalamus releases TRH → anterior pituitary releases TSH → thyroid makes T3 & T4 → T3>T4 inhibits hypothalamus & anterior pituitary output

describe the hypothalamus, pituitary, thyroid feedback loop

2nd gen serum thyrotropin assay

what is the current best single screening thyroid test?

<0.1mU/L

what is the critical value for the 2nd gen serum thyrotropin assay?

hyper

a 2nd gen serum thyrotropin assay result of <0.4mU/L TSH indicates ___thyroidism

hypo

a 2nd gen serum thyrotropin assay result of >5.2mU/L TSH indicates ___thyroidism

2nd gen serum thyrotropin assay, FreeT4 assays, serum T3 & T4 resin uptake, thyroxine-binding globulin, thyroid antibodies

what are some thyroid function lab tests?

high serum sTSH >14mU/L, positive antithyroid microsomal antibodies

what are 2 findings that predict progression from subclinical to overt thyroid disease?

euthyroid

having a normally functioning thyroid gland w/ signs or symptoms of thyroid dysfunction

thyroxine binding globulin, Werner T3 suppression test, thyrotropin releasing hormone

what are the tests for euthyroid?

ultrasonography, fine needle aspiration, radio-nuclide scans

what are the tests for thyroid nodules?

Hashimoto’s thyroiditis

what is the most common cause of adult hypothyroidism?

adult hypothyroidism

• 3rd most common disease in US

• s/sx:

  • hoarseness

  • lethargy, fatigue, muscle aching

  • constipation

  • cold intolerance

  • dry skin

  • vitiligo

  • slowing of intellectual functioning

  • depression, mood swings

  • slowing of motor function & reaction time

  • menstrual dysfunction

  • decreased appetite

  • weight gain

  • peripheral edema

  • alopecia & prematurely gray hair

  • periorbital puffiness

florid myxedema, cardiomegaly, CHF, hypothermia, myxedema coma, death

what are the side effects of unmanaged hypothyroidism?

Graves’ disease, subacute thyroiditis, painless thyroiditis, postpartum thyroiditis

what are the causes of hyperthyroidism?

hyperthyroidism

• most common cause is Graves’ disease

• s/sx:

  • emotionally labile, nervousness, sleeplessness

  • heat intolerance, sweating

  • weight loss

  • muscle weakness

  • goiter

  • amenorrhea

  • shortness of breath

  • palpitations, tachycardia

  • tremor of hands & tongue

  • hyperreflexia

  • thyroid bruit

  • warm, moist, velvety skin

  • palmar erythema

  • fine, silky hair

  • onycholysis

Kocher sign, Dalrymple sign, van Graefe’s sign, brow does not wrinkle on upward gaze, infrequent blinking

what are some common eye signs of hyperthyroidism?

Kocher sign

stare/frightened appearance w/ fixation in a pt w/ hyperthyroidism

Dalrymple’s sign

widened palpebral fissure in a pt w/ hyperthyroidism

van Graefe’s sign

lid lag on downgaze seen in a pt w/ hyperthyroidism

hyperthyroidism, dermopathy, ophthalmopathy

what is the triad of Graves’ disease?

>99mg/dL

what is the normal blood sugar for an adult?

90-180mg/dL

what is the normal blood sugar for a 6-12yo?

90-150mg/dL

what is the normal blood sugar for a 13-19yo?

100-200mg/dL

what is the normal blood sugar for a 7day-6yo?

<140mg/dL

what is the normal blood sugar for a pregnant person?

126mg/dL or more at 2 different visits or 200mg/dL or more w/ symptoms

what constitutes elevated plasma glucose?

<40 or >470mg/dL

what are the critical values for plasma glucose?

type 1A DM

• most pts are <40yo

• M>F

• autoimmune in >90% of cases

  • 48% show enterovirus antibodies

  • HLA markers

type 1B DM

• idiopathic DM

• no B cell autoimmunity

• 4% of population & most are Asian or West African

type 2 DM

• most pts are >65yo

• F>M

• 18 different genome links

• greatest risk factor: obesity

prediabetes

• impaired glucose tolerance

  • F>M

• impaired fasting glucose, b/t 110-126

  • M>F

estrogen protects & maintains insulin sensitivity & secretion, so when it drops at menopause this protection/maintenance is lost

why does the female risk for type 2 diabetes increase at menopause?

testosterone is converted into estrogen & androgen receptors in beta cells help cells produce more insulin

why are men with low testosterone predisposed to type 2 at any age?

70

the risk of developing T2DM is up to ___% of prediabetics

2nd trimester, FBS >140 &/or baby weight >9.5lbs

in what trimester is gestational diabetes most likely to develop & what increases the risk?

type 1.5 DM (latent autoimmune of adulthood)

late onset T1DM who become obese & insulin resistant

maturity onset diabetes of the young

5 types of AD, genetic insulin resistance, appears before age 25

metabolic syndromes

• not a subclass of diabetes but common in DM pts

• 1/3 adults in the us

• cluster of clinical findings associated w/ high risk of atherosclerotic vascular disease

  • abdominal obesity

  • HTN

  • glucose intolerance

  • insulin resistance

  • T2DM

  • dyslipidemia

  • increase clotting factors

  • hyperuricemia

  • systemic inflammation

polyuria, polydipsia, polyphagia, ketonuria, rapid weight loss

what are the classic symptoms of hyperglycemia?

1. >200mg/dL w/ symptoms

2. FPG of 126mg/dL or more on 2 testing days

3. FPG of 140mg/dL or more and an oral glucose tolerance 2hr test of >200

what are the 3 conditions that constitute elevated plasma glucose?

3

FBS screening is routinely recommended for all people over age 45 every ___ years

every year

FBS screening is routinely recommended for all people with high risk characteristics how often?

obesity, HTN/vascular disease, +FHx, hx of gestational diabetes or baby w/ a birthweight of >9.5lbs, high risk ethnic populations, primary relative w/ DM, elevated triglycerides >250, HDL cholesterol <35

what are the high risk characteristics that warrant yearly screening for FBS?

1. African American, Native American, Mexican Americans

2. +FHx

3. obesity (especially if weight is gained in early teens/20s)

4. >40yo

5. sedentary lifestyle

6. vascular disease

7. HLA & Islet antibodies

8. history of gestational DM

what are the risk factors of DM?

diabetic ketoacidosis, hyperosmolar coma, hypoglycemia

what are the acute complications of DM?

accelerated arteriosclerosis → CVD & polyneuropathy, retinopathy → blindness, nephropathy → kidney failure

what are the long term complications of DM?

diabetic ketoacidosis

• most common endocrine emergency

• low mortality

• build up of ketones in the blood

• usually seen in pts that do not know they have DM yet or are poorly controlled

• clinical sx:

  • thirst & dry mouth

  • polyuria

  • weight loss

  • dyspnea

  • nausea

  • weakness

  • muscle aches

  • HA

  • abdominal pain

  • CNS depression w/ drowsiness

  • stupor progressing to coma

hyperosmolar coma

• often seen in elderly undiagnosed diabetics

• common to have a recent illness hx

• high mortality rate (CHF, stroke, renal failure)

• prolonged osmotic diuresis → dehydration → mental obtundation → convulsions → coma

induced hypoglycemia (insulin reaction)

• plasma glucose levels drop below 60mg/dL

• most commonly due to errors in insulin dosing/injection technique

• can also be due to failure to maintain diet

• can be life threatening if the glucose level falls below 20mg/dL

insulin lipodystrophy (atrophy)

• 28-35% of pts

• F>M

• can happen over 6mo-2yrs after starting insulin injection tx

• subcutaneous fat seems to melt away at injection sites

• most often seen in the upper arm or thigh

insulin lipodystrophy (hypertrophy)

• M>F

• most often found on anterior & lateral thigh

• spongy, localized anesthetic hypertrophic scar tissue secondary to prolonged & constant use of the same site

• insulin absorption is slowed if continuing to use that site

accelerated arteriosclerosis, peripheral arterial insufficiency, nephropathy, neuropathy

what are the chronic microvascular complications of DM?

2x risk of MI, 3x risk of stroke

accelerated arteriosclerosis seen w/ DM leads to what?