Endocrine Flashcards
Cushing’s disease vs Cushing’s syndrome
The disease is the most common cause of Cushing’s syndrome
Disease is ACTH-secreting pituitary adenoma that causes increase in cortisol
Syndrome is hypercortisol state
Causes of Cushing’s Syndrome
Cushing’s disease (pituitary adenoma, most common cause)
Chronic steroid use
Adrenal tumor
Ectopic production by ACTH-secreting tumor (often small lung cell carcinoma)
Patients most commonly affected by Cushing’s Syndrome
premenopausal women
Hallmark findings of Cushing’s Syndrome
buffalo hump moon face proximal muscle weakness pigmented striae obesity - centrally located with skinny limbs
Best lab to dx Cushing’s Syndrome
24 hr urine for free cortisol
> 125 is diagnostic
How does overnight dexamethasone suppression test help dx Cushing’s Syndrome?
Distinguishes pituitary vs ectopic cause of cortisol elevation
Patient gets 1 mg of dexamethasone at 12pm. 8am plasma ACTH measured
Pituitary tumor (Cushing's Disease) - low ACTH; negative feedback Ectopic tumor - no ACTH change
How is Cushing’s Disease treated?
transsphenoidal resection with hydrocortisol replacement, but if tumor cannot be removed chemo or radiation therapy useful
How is Cushing’s Syndrome treated?
Metyrapone and Ketoconazole may suppress hypercortisolism
Parenteral octreotide may suppress ACTH
Often patients treated for Cushing’s syndrome will go into cortisol withdraw and require steroid tapering therapy with hydrocortisone or prednisone
Clinical findings of Addison’s Disease
Sparse axillary and pubic hair
Hyperpigmentation of skin, esp. creases or pressure areas (waist band/bra line)
Hypotension and small heart
What chemicals/lytes are low in Addison’s Disease? which are elevated?
Low – Na and glucose
Elevated – K+, Ca2+ and BUN
Diagnostic lab test for Addison’s disease
low plasma cortisol and aldosterone with elevated ACTH
Treatment of Addison’s disease
Replacement with oral hydrocortisone or prednisone
Fludrocortisone also useful for sodium retention
DHEA may also be given
Difference between pathophysiology of primary and secondary hyperthyroidism
Primary hyperthyroidism: problem with thyroid
Secondary hyperthyroidism: problem with pituitary
___________ is the most common cause of hyperthyroidism. It is an autoimmune disease in which the body creates antibodies that bond to the TSH receptors and force excessive T3/T4 production.
Graves’ disease
20-40% of patients with Grave’s disease have what findings that can distinguish from other hyperthyroid issues?
conjunctivitis
exophthalmos (bulging of eyes)
pretibial myxedema (non-pitting edema of knee)
thyroid bruit
Some of the many symptoms of hyperthyroidism
Eyes: stare, lid lag, diplopia
CV: Tachycardia, A-fib, palpitations, chest pain
Skin: Fine hair, warm/moist skin, onycholysis
Mental changes: irritability, Nervousness, fatigue
Heat intolerance, sweating
Weight loss, increased appetite
Hyperreflexia
Goiter
What is a thyroid storm?
very rare but severe form of hyperthyroidism
risk factors include stressful illness, thyroid surgery, radioactive iodine treatment
symptoms: fever, tachycardia, vomiting/diarrhea, dehydration, muscle weakness, confusion
How does hyperthyroidism affect TSH, T3, T4
TSH decreased (primary) or elevated (secondary)
T4 elevated
T3 elevated
What is specifically elevated in Graves’ disease?
anti-TSH receptor antibodies
Radioactive iodine uptake scan results of Graves disease
thyroid has increased iodine uptake
First line treatment for acute hyperthyroidism and thyroid storm? Long term control?
Acute: beta blockers (especially propanol)
Long term: Methimazole and propylthiourcial (PTU)
Definitive tx: Radioactive iodine ablation
How to treat A-fib of hyperthyroidism?
Digoxin
Warfarin to prevent possible clotting
Pathway of T3/T4 production from hypothalamus signaling
Hypothalamus → thyroid releasing hormone → pituitary → thyroid stimulating hormone → thyroid → T3 and T4
Why might a patient have hypothyroidism?
Thyroiditis
Patient doesn’t have thyroid
Meds: amiodarone, lithium, PTU & Methimazole
Iodine deficiency
Some of the many hypothyroidism symptoms:
cold intolerance, puffy face, fatigue, pale/cool skin, thin brittle nails, depression, dementia, weakness, anorexia, constipation, weight gain, bradycardia, hyporeflexia
+/- Goiter
TSH, T3, and T4 levels in hypothyroidism
- TSH elevated (primary) or decreased/normal (secondary)
- T4 decreased
- T3 may be normal
Treatment of hypothyroidism
Thyroid hormone replacement: Levothyroxine (synthetic T4)
Treatment is for life
Thyroid levels checked yearly
Watch for signs of hyperthyroidism
thyroid storm : hyperthyroidism
__________ : hypothyroidism
myxedema
Patients with myxedema will have symptoms of hypothyroid as well as what?
mental changes ranging from confusion to coma convulsions hypotension hypothermia hypoventilation rhabdomyolysis and AKI hyponatremia
Treatment of myxedema
IV levothyroxine
intubation prn
slow warming with warm blankets prn
What is Hashimoto’s thyroidits?
- Autoimmune disease causing partial or complete impairment of thyroid gland; hypothyroid sx’s
- Typically occurs with other autoimmune problems like Sjorgren’s, MG, DM-I, celiac disease, Addison’s, etc.
Clinical presentation of thyroiditis
enlarged, firm, nodular thyroid
dysphagia
+/- pain
What condition has increased anti-thyroperoxidase and anti-thyroglobulin antibodies?
Hashimoto’s thyroiditis
What imaging is used to differentiate thyroiditis from nodular goiter or malignancy?
Thyroid U/S
Radioiodine uptake scan
Why is a fine needle aspiration done for patients with Hashimoto’s or thyroid nodule?
significant risk of thyroid cancer
Why is a fine needle aspiration done for patients with suppurative thyroiditis?
suppurative thyroiditis is likely bacterial infection, so FNA can be helpful for gram stain and culture
How is postpartum thyroiditis treated?
self-limiting
symptomatic treatment prn
How is subacute thyroiditis treated?
Aspirin first line for pain and inflammation
Propranolol for hyperthyroid sx’s
Levothyroxine for hypothyroid sx’s
How is Hashimoto’s thyroiditis treated?
If patient hypothyroid -> Levothyroxine
If patient has large goiter -> Levothyroxine in effort to shrink goiter
Otherwise monitor for hypothyroid
Which thyroiditis is due to a bacterial infection?
Suppurative thyroiditis
How can you tell if Hashimoto’s thyroiditis has Sjogren’s as well?
dry eyes
dry mouth
** 33% of Hashimoto’s will also have Sjogren’s syndrome
You believe a patient presenting to you has relatively severe hypothyroidism. You send off a thyroid panel as well as CBC and BMP. What abnormality do you expect to find on BMP?
decreased sodium
Different types of thyroiditis
Hashimoto’s - autoimmune issue (most common) Suppurative - bacterial infection Subacute/ de Quervain's - viral Riedel - fibrous infiltration Postpartum
3 hormones that regulate calcium levels in the blood?
PTH and Vit D increase calcium
Calcitonin decreases calcium
Primary hyperparathyroidism typically caused by what?
adenoma in 1 of 4 parathyroid glands
could also be from hyperplasia or carcinoma
What is secondary hyperparathyroidism caused by what?
overstimulation of parathyroid glands
- Chronic renal failure and poor Vit D production which decreases calcium
- Malignant tumor (breast, lung, pancreas)
- Calcium deficiency
“moans, (abdominal) groans, stones, and bones” =
hyperparathyroidism
What lab value differentiates primary and secondary hyperparathyroid?
serum phosphate low in primary and elevated in secondary
both have elevated serum PTH
Because serum calcium is high in hyperparathyroid, what is low?
Vit D
Possible XR findings of hyperparathyroid
demineralization
subperiosteal bone resorption, especially fingers
cysts of jaw
salt and pepper skull
What is the recommended definitive treatment for symptomatic and some asx hyperparathyroidism?
- parathyroidectomy (94% success rate)
- monitor complications of hypocalcemia with Ca2+ supplements and hyperthyroidism with propranolol
How can one acquire hypoparathyroidism?
*Post thyroidectomy Heavy metal damage Low magnesium Granulomas Infection
Congenital cause of hypoparathyroidism
DiGeorge Syndrome (chrom 22 defect) and other genetic disorders
Acute hypoparathyroid symptoms
Irritability
Tetany - involuntary contractions
Carpopedal spasms
Tingling (circumoral, distal extremities)
Chronic hypoparathyroid symptoms
Lethargy Parkinsonism Mental retardation Anxiety Cataracts Dry skin, brittle nails
What is Trousseau sign?
blood pressure cuff placed around arm and inflated to pressure > systolic BP and held in place for 3 min to occlude brachial artery -> spasm of hand and forearm
observed in patient’s with low calcium
What is Chvostek sign?
sign of existing tetany seen in hypocalcemia
facial muscles contract when facial nerve tapped at masseter
What do a positive Trousseau and Chvostek signs indicate?
hypocalcemia
What labs values are low in hypoparathyroidism?
Serum and urinary Ca
PTH
Magnesium
ECG findings of hypocalcemia
prolonged QT
T wave abnormalities
Emergency treatment of hypoparathyroidism
Airway maintenance
IV calcium gluconate
How is hypoparathyroidism managed long term?
Calcium and Vit D supplements
Magnesium if appropriate
Close monitoring of calcium
What is pseudohypoparathyroidism?
patient makes enough PTH, but receptors don’t respond
presents just like hypoparathyroidism except PTH is elevated
Non-surgical treatment of hyperparathyroidism and high calcium
Fluids!!!! (1st line if extremely high Ca levels)
IV Bisphosphonates
Cinacalcet (calcimimetic)
Vit D
Estrogen to decrease Ca in postmenopausal woman
Propranolol to protect heart from elevated Ca
What is the most common and least aggressive type of thyroid cancer?
papillary carcinoma (80%)
What is the second most common thyroid cancer that is more aggressive and may secrete enough T4 to cause thyroid storm?
Follicular thyroid cancer
Thyroid cancer that may be associated genetics or MEN type 2
Medullary thyroid cancer
What characteristics of thyroid suggest malignancy?
single palpable nodule
painless neck swelling
may cause dysphagia, hoarseness, dyspnea, or hyperthyroid sx’s
How are suspicious thyroid nodules diagnosed?
Fine needle aspiration
TSH and T4 are normal in all thyroid cancers except for _______.
follicular cancer; produces excess T4 which suppresses TSH
Best to image metastasis in lungs with _____ and metastasis in bone with _____.
CT
MRI
Treatment of thyroid cancer
Total or near total thyroidectomy
Neck dissection and lymph node removal if indicated
Post op:
Levothyroxine (synthetic T4) if thyroidectomy
Radioactive iodine ablation for residual dz, metastatic dz and to prevent recurrence
Monitor with whole body radioactive iodine scans and monitor TSH for levothyroxine dose
Which type of thyroid cancer is least common but most aggressive?
anaplastic
How is thyroid cancer remission defined?
Two consecutive negative whole body radioisotope scans
Leading cause of blindness in U.S.
diabetes
Type I DM is secondary to autoimmune disease affecting what in body?
islet beta cells of pancreas, so patient can’t produce enough insulin
What gene is a risk factor for DM-I?
HLA
Signs of DKA
N/V
polyuria and polydipsia
change in mental state
fruity breath
Clinical findings of Type 1 DM
Signs of ketoacidosis Weight loss despite normal diet Blurry vision Poor wound healing Acanthosis nigricans Neuropathy
Ways to dx diabetes
1) fasting blood glucose levels >126 mg/dL on more than one occasion
2) non-fasting blood glucose of >200 mg/dL
3) oral glucose tolerance; fasting patient consumes 75 g oral glucose and 2 hrs later glucose level > 200 mg/dL
What is hemoglobin A1c? What is normal?
indicates sugar levels over previous 3 months and is used for monitoring glucose control
Normal is 3.8-6.3%
Diet and Education for diabetes management
Increase fiber and complex carbs
Monitor carb intake
Monitor glucose
Eat snacks and meals at regular intervals
Examples of rapid acting insulin
Lispro, Humalog, Novolog
Onset, peak, and effective duration of rapid acting insulin?
Onset: 5-15 minutes
Peak: 1-1.5 hours
Duration: 3-4 hours
Examples of short acting insulin
Human Regular
Onset, peak, and effective duration of short acting insulin?
Onset: 30-60 minutes
Peak: 2 hours
Duration: 6-8 hours
Examples of intermediate acting insulin
Human NPH (Neutral protamine hagedorn) and Lente
Onset, peak, and effective duration of intermediate acting insulin?
Onset: 2-4 hours
Peak: Flat
Duration: about 24 hours
Examples of long acting insulin
Lantus, Ultralente
Onset, peak, and effective duration of long acting insulin?
Onset: 30-180 minutes
Peak: Lantus no peak, Ultralente 10-20hrs
Duration: 20-36 hrs
Which type of insulin is used before meals?
Short acting insulin, Human Regular
Which insulin is typically two doses daily and used in conjunction with a short acting insulin?
Intermediate acting insulin, Human NPH
What are routine exams all diabetic should have?
Regular visits to podiatrist for foot care
Regular diabetic eye exams
How many units of regular or Lispro insulin should be used based on carbs eaten?
1 unit for every 10-15 grams
How does DM-2 present differently than DM-1?
dx'd later in middle age or later insidious onset (usually asx) abdominal obesity functioning pancreas that produces insulin, but receptors and tissues do not respond (insulin resistance)
Type of neuropathy in diabetes
stocking-glove distribution
What races are more susceptible to DM-2?
African American, Hispanic, Pima Indians
Lipid panel changes in DM-2?
Elevated triglycerides 300-400 mg/dl
Low HDL
Most common drug class used to stimulate insulin secretion
sulfonylureas (glypburide, glipizede, glimepiride)
First line therapy for DM-2
Metformin
Meds that lower glucose? How?
Metformin – reduces hepatic glucose production
alpha-Glucosidase inhibitors (Acarbose)– decrease carb absorption from intestines
Thiazolidinediones MOA for treating DM-2
increase tissue sensitivity to insulin
ex: rosiglitazone and pioglitazone
Treatment of DM-1
NEED INSULIN
Treatment of DM-2
1) Diet and exercise to improve insulin resistance
2) Oral meds: Metformin 1st line; others are sulfonylureas, alpha-glucosidase inhibitors, thiazolidinediones
3) Insulin therapy
Patients with metabolic syndrome are at higher risk for what?
DM 2 Elevated triglycerides Lower HDL Elevated LDL HTN Blood clots Atherosclerosis
What is clinical definition of metabolic syndrome?
3 or more of following:
BP > 130/85 Fasting glucose > 100 Waist circumference - M > 40 inches - W > 35 inches Low HDL - M less than 40 - W less than 50 Triglycerides > 150
What is postprandial hypoglycemia?
blood sugar drop after eating
Early = 2-3 hours after Late = 3-5 hours after
Causes of hypoglycemia
Exogenous insulin overdose Insulinoma Addison’s disease (hypopituitarism) Renal failure Liver problem Glycogen storage Alcohol related
How can alcohol cause hypoglycemia?
Liver problems
Alcohol inhibits gluconeogenesis
N/V – gastritis
How does Addison’s disease cause hypoglycemia?
hypopituitarism -> adrenal insufficiency -> low cortisol
no cortisol to break down glycogen in liver into glucose and no cortisol to convert fats, proteins, and carbs into glucose
Clinical presentation of hypoglycemia
Often symptoms occur after missing a meal Sweating Palpitations Anxiety Blurred vision Weakness Light headed Slurred speech Loss of consciousness
Clinical definition of hypoglycemia
low blood sugar below 70 mg/dl
What blood sugar levels can cause someone to lose consciousness?
about 50 mg/dl
Whipples Triad
1) history of hypoglycemia
2) low serum glucose at time of event
3) immediate recovery on administration of glucose
suggest a patient’s symptoms are due to hypoglycemia; or may indicate insulinoma
How to treat hypoglycemia based on cause?
Exogenous insulin overdose – eat a cookie :)
Insulinoma – surgically resect if possible
Postprandial hypoglycemia – small meals every 2-3 hours
Addison’s – oral steroid
What is ACTH? and what does it do?
adrenocorticotropic hormone; stimulates increased production and release of corticosteroids by adrenal glands
What are hormones released by posterior pituitary? What are their functions?
ADH (antidiuretic, vasopressin) – increases water absorption in kidneys
Oxytocin – increases uterine contractions, milk release
Pathophysiology of acromegaly
usually a pituitary adenoma which secretes excess GH
Acromegaly vs Gigantism
excess GH during child before epiphyses closure -> Gigantism
excess GH as adult after epiphyses closure -> Acromegaly
____ levels 5x higher than normal in Acromegaly and Gigantism.
IGF-1
MRI will show _________ in about 90% of patients with Acromegaly.
pituitary adenoma
Treatment of Acromegaly and Gigantism
Primary treatment is trans-sphenoidal resection of pituitary adenoma
Dopamine agonist (Cabergoline) to help normalize GH Somatostatin analog (Octreotide, Lanreotide acetate) GH receptor antagonist (Pegvisomant)
Diabetes insipidus is a deficiency in what?
ADH
Signs of Diabetes Insipidus
THIRSTY!!! 2-20 Liters per day
Polyuria
What is the vasopressin challenge test and how does it help determine cause of DI?
Urine volume for 12 hours
Desmopressin acetate is given
Urine volume over next 12 hours
if urine volume improves with Desmopressin then pituitary or hypothalamus issue = central
if no improvement, kidney tubules = nephrogenic
Treatment of diabetes insipidus
Central DI (Pituitary/Hypothalamus decreased ADH production)
Desmopressin Acetate
HCTZ
Nephrogenic DI (ADH resistance) Indomethacin HCTZ
__________ is abnormal mineralization of bones AFTER closing of epiphyseal plates. __________ is abnormal mineralization BEFORE closing of plates.
Osteomalacia
Rickets
Causes of Rickets
Vit D deficiency - sun exposure, nutrition, malabsorption, chronic renal failure
Calcium or phosphate deficiency
Phenytoin – seizure med
Location of bone pain in Rickets and Osteomalacia mostly where?
pelvis
Classic XR findings of Rickets and Osteomalacia
Decrease in bone density
Milkman lines
Looser zones
Treatment of Rickets and Osteomalacia
Ergocalciferol (as Vit D supplement)
Phosphate supplement
Calcium supplement
Patient comes in c/o deafness and arthralgia. XR shows bony lesions with hyper-density and bowing. Serum calcium and phosphate normal, but alk phos elevated. Likely dx?
Paget’s Disease
Paget’s Disease treatment
1st line: Oral bisphosphonates (Alendronate, Tiludronate, Risedronate)
IV Bisphosphonates (Zoledronic acid or Pamidronate)
Most common cause of secondary hyperthyroidism?
pituitary tumor
Anti-arrhythmic drug that can cause hyper or hypothyroidism?
Amiodarone
“iod” = iodine, thyroid
What are 3 zones of the adrenal cortex and what does each secrete?
zona glomerulosa - aldosterone
zona fasciculata - glucocorticoids (cortisol)
zona reticularis - sex hormones
What does the adrenal medulla secrete?
epinephrine and norepinephrine with sympathetic stimulation
What stimulates aldosterone secretion from adrenal gland?
Hypotension (renin -> angiotensin -> ADH)
Hyperkalemia
Hyponatremia
______ prevent angiotensin-stimulated aldosterone release.
ACE inhibitors
Why is there hyperpigmentation in Addison’s disease?
ACTH and MSH (melanocyte stimulating hormone) share common precursor POMC
When ACTH increases so does MSH
Aldosterone production in primary and secondary adrenal insufficiency
Primary - aldosterone and cortisol decrease since whole adrenal gland not working
Secondary - aldosterone normal since its stimulate by RAAS; only cortisol decreases
Over-secretion of epinephrine occurs in __________.
pheochromocytoma
Location of tumors of MEN 1
3 P’s: parathyroid, pituitary, pancreas
What does MEN stand for?
= multiple endocrine neoplasia
Which endocrine hormone is not regulated by the pituitary?
PTH; secretes from parathyroid in response to low calcium
How does PTH increase calcium?
- stimulates osteoclasts to break down bone
- increases reabsorption of calcium by kidneys
- decreases reabsorption of phosphate by kidneys
- increases conversion of inactive Vit D to active form (absorption of calcium in GI tract)
PTH and Vit D effects on phosphate levels
Vit D increases serum phosphate
PTH decreases serum phosphate
How does calcitonin decrease calcium levels?
secreted by thyroid when calcium blood levels high
increases bone absorption of calcium and decreases renal absorption of calcium
Serum and urine findings in primary hyperparathyroidism
Serum: calcium and PTH high, phosphate low
Urine: calcium, phosphate, and cAMP high
Pathologies that cause elevated Vitamin D
TB, sarcoidosis, lymphoma, Milk-Alkali syndrome
How does elevated PTH affect Vit D?
increase conversion of 25-vit D to 1,25-vit D = increased Vit D
How does elevated Vit D affect PTH?
increased Ca2+ = decreased PTH
What is DiGeorge Syndrome?
congenital absence of parathyroids and thymus
Causes of Vitamin D deficiency
decreased UV exposure
inadequate dietary intake
malabsorption
liver or renal disease
What is Hungry Bone Syndrome?
sudden decrease in PTH after hyperparathyroid treatment causes bones to be “hungry” for calcium
How do calcium levels affect ECG readings?
high calcium shortens QT
low calcium prolongs QT
Hormone/chemical issues that cause osteoporosis
low estrogen
high cortiso
low calcium/Vit D
Genetic pathology with osteoclast dysfunction and uncontrolled bone formation?
Osteopetrosis
Hormones released by anterior pituitary?
“FLAT PEG”
FSH LH ACTH TSH Prolactin * Endorphins GH
The pituitary gland sits beneath the ________ attached to the brain.
optic chiasm
Why is GH level not a reliable dx test? What is measured instead?
GH has pulsatile release
IGF-1 used instead (stimulated by GH)
Dx tests for suspected GH-secreting tumor?
IGF-1 level
Glucose challenge test (high glucose normally decreases GH)
How is prolactin secretion controlled?
dopamine released from hypothalamus inhibits prolactin release from anterior pituitary until postpartum when high estrogen levels stimulate its secretion for lactation
Sheehan’s syndrome
postpartum hemorrhage in mother results in hypovolemia and subsequent pituitary damage (hypopituitarism)
Effects of insulin and glucagon on blood sugar levels
Insulin: glucose into cell (lowers sugar)
Glucagon: glucose to blood (raises sugar)
- “Is your glucose gone? Get glucagon!”
- INsulin sugar goes IN
What other hormones, apart from glucagon, raise blood sugar levels?
cortisol
GH
Nor/epinephrine
How does insulin reduce glucose levels?
increases glycogenesis (glycogen storage) and glycolysis (glucose breakdown)
How does glucagon lower glucose levels?
decreases glycolysis increases gluconeogenesis (glucose formation) and glycogenolysis (glycogen breakdown into glucose)
cosyntropin (ACTH) stimulation test =
Addison’s
dexamethasone suppression test =
Cushing’s Syndrome
vasopressin challenge test =
Diabetes Insipidus
Side effects of Methimazole
rash
agranulocytosis
lupoid hepatitis
renal failure
PTU instead of Methimazole in what patients?
pregnancy
