Endocrinology Flashcards
Most common 2nd messenger system
cAMP (e.g. glucagon)
2nd messenger system of insulin
tyrosine kinase (also used by IGF-1, EPO)
2nd messenger system of thyroid hormone
none (acts like steroids)
Hormones derived from proopiomelanocortin (POMC)
MSH, ACTH, B-lipoprotein, B-endorphin
Other name for growth hormone
somatotropin
Other name for insulin-like growth factor 1 (IGF-1)
somatomedin
Antagonizes prolactin
dopamine (and analogs like bromocriptine)
Main site of ADH/vasopressin synthesis
supraoptic nuclei of the anterior hypothalamus
Main site of oxytocin synthesis
paraventricular nuclei of the anterior hypothalamus
Site of ADH and oxytocin storage and secretion
posterior pituitary
Predominant form of thyroid hormone in the blood
T4
Active form of thyroid hormone
T3
3 parts of the adrenal cortex from outer to inner
Glomerulosa –> Fasciculata –> Reticularis (salty, sweet, sex)
2 products of the adrenal medulla
epinephrine (80%), norepinephrine (20%)
Increased adrenal androgens, decreased aldosterone, decreased cortisol
21-beta hydroxylase deficiency (virilizing)
Increased aldosterone, decreased adrenal androgens, decreased cortisol
17-alpha hydroxylase deficiency (non-virilizing)
Effect of insulin on potassium
increased uptake in muscles and adipose (decreased plasma K)
Marker for endogenously produced insulin
c-peptide
Responsible for tensile strength of the bone
collagen fibers (95% of organic amtrix)
Responsible for compressional strength of the bone
bone salts
Decreases calcium and phosphate excretion but increases urinary calcium, increases intestinal calcium absorption
vitamin D
Decreases calcium excretion, increases phosphate excretion, increases 1-alpha hydroxylase, increases bone resorption
PTH
Stimulated by LH, releases the “libido” hormone testosterone
Leydig cells (LLL: LH, Leydig, Libido)
Stimulated by FSH, nurse cell for sperm
Sertoli Cells
Sperm formation
seminiferous tubules
Sperm motility
epididymis
Sperm storage
vas deferens
Production of fructose and prostaglandins for sperm
seminal vesicle
Semen alkalinity
prostate
Supplies mucus to semen for lubrication
Cowper’s glands/bulbourethral glands
Main hormone for the follicular phase
estrogen
Main hormone for the luteal phase
progesterone
Causes ovulation
LH surge
Cells of the blastocyst that digests and liquefies the endometrium for invasion
trophoblast
Nutrient-rich endometrium invaded by trophoblast
decidua
B-HCG source
syncytiotrophoblast
Promotes growth fo the fetus, insulin resistance in the mon, lipolysis in the mother, index fo fetal well-being
human chorionic somatomammotropin (HCS), formerly known as human placental lactogen (HPL)
Prevents pregnancy during breastfeeding
prolactin inhibition of GnRH
Peak GH response to hypoglycemia of
adult growth hormone deficiency
Failure of GH suppression to
acromegaly
GH receptor antagonist via blocking peripheral GH binding to its receptor
pegvisomant
Pituitary corticotrope adenoma causes?
Cushing’s disease (Cushing’s syndrome is nonspecific to just increased cortisol)
Syndrome of abnormally large volumes of dilute urine (> 50 mL/kg 24-hr urine volume, urine osmolality
Diabetes Insipidus
Venous distention over the neck and difficulty breathing especially when the arms are raised
Pemberton’s sign (large retrosternal goiter)
Rule of 10s in pheochromocytoma
10% bilateral, extra-adrenal, malignant, calcify, in children, familial
Rule of 1/3 in carcinoid syndrome
1/3 metastasize, present with 2nd malignancy, multiple
Screening for DM
age > 45 q3 years (screen earlier if BMI > 25 and with 1 risk factor for DM)
Corrected serum sodium regards to glucose administration
Add 1.6 meq for each 100 mg/dL rise in serum glucose
Microvascular manifestations of DM
retinopathy, neurophaty, nephropathy
Macrovascular manifestations of DM
coronary heart disease, peripheral arterial disease, cerebrovascular disease
Treatment for proliferative retinopathy
panretinal laser photocoagulation
Treatment for macular edema
focal laser photocoagulation
Microalbuminuria
30-299 mg/day in a 24-hr collection OR 30-299 ug/mg creatinine in a spot collection
Diabetic dermatopathy
pigmented pretibial papules aka diabetic skin spots
Normal ejaculate values
2-6 mL, sperm count > 20M/mL, motility > 50%, > 15% normal morphology
True gynecomastia value
glandular breast tissue > 4cm diameter
Infertility definition
inability to conceive after 12 months of unprotected sexual intercourse
Precocious puberty in boys age cutoff
development of secondary sexual characteristics before age 9
Delayed puberty in boys age cutoff
development of secondary sexual characteristics after age 14
Precocious puberty in girls age cutoff
development of secondary sexual characteristics before age 8
Delayed puberty in girls age cutoff
absence of secondary sexual characteristics by age 13
Cause of humoral hypercalcemia of malginancy
overproduction of PTH-related peptide (PTHrP) by cancer cells
Potent inhibitor of renal 1A-hydroxylase
fibroblast growth factor 23 (FGF-23), suppresses ability of kidneys to activate vitamin D and impairs calcium absorption
WHO definition of osteoporosis
Bone density with 2.5 standard eviations below the mean for young healthy adults of same sex
Diagnosis of osteoporosis
T score below -2.5 in lumbar spine, femoral neck or total hip
Monoclonal antibody to RANKL, used for osteoporosis
denosumab
Exogenous PTH analogue
teriparatide
Excessive urination due to insensitivity of renal tubules to ADH
nephrogenic Diabetes Insipidus
Excessive urination secondary to lack of ADH
central Diabetes Insipidus
Excess ADH causing excessive resorption of water in hyponatremia
SIADH
Most common cause of hypopituitarism in children associated with WNT signalling pathway
craniopharyngioma
Hypothyroidism in infancy or early childhood leads to?
cretinism
Tapping facial nerve induces contractions of the muscles of eye, mouth, or nose
Chvostek’s sign (hypocalcemia)
Carpal spams produced by occlusion of the circulation to the forearm
Trosseau sign (hypocalcemia)
Most common functioning pituitary adenoma
prolactinoma
Second most common pituitary adenoma
somatotroph adenoma
Postpartum necrosis of anterior pituitary gland
Sheehan syndrome (presents with sudden cessation of lactation)
Sudden headache, diplopia, and hypopituitarism
Pituitary apoplexy
Papillary thyroid CA patho
Orphan Annie eye nuclei
Follicular thyroid CA patho
Hurthle cells, invades blood vessels
Medullary thyroid CA patho
C cells, MEN-associated
Apalstic thyroid CA patho
giant cells, spindle cells
Most common cause of hypothyroidism in iodine sufficient areas
Hashimoto’s thyroiditis
Most common casue of hypothyroidism worldwide
iodine deficiency
Most common casue of painful thryroid gland; associated with viral infection
De Quervain
Condition where thyroid tissues are replaced by fibrous tissue
Reidel thyroiditis
Hyperthyroidism + ophthalmopathy + dermopathy = ?
Graves disease
Histologic finding of Grave’s disease
diffuse thyroid hypertrophy and hyperplasia
Most common primary thyroid cancer
papillary thyroid CA
Diseases with Psammoma bodies
papillary thyroid CA, serous cystadenoma of ovaries, mesothelioma, meningioma
Most common cause of primary hyperparathyroidism
parathyroid adenoma
Osteoporosis
decreased bone mass
Osteopetrosis
thickened, dense bone
Osteomalacia/rickets
soft bones
Osteitis fibrosa cystica
“Brown tumors”
Paget’s disease in bone
abnormal bone architecture
Hypertension with hypokalemia not controlled by monotherapy
hyperaldosteronism
Most common cause of primary hyperaldosteronism
idiopathic hyperaldosteronism
Adrenals are converted to sacs of clotted blood, obscuring all details
Waterhouse-Friderichsen syndrome (causes acute adrenal insufficiency)
Neoplams composed of chromaffin cells, which release catecholamines
pheochromocytoma
Trophic hormone failure associated with pituitary compression or destruction, occurs in what sequence of hormones?
GH > FSH > LH > TSH > ACTH (1st sign in childhood = growth retardation; in adults = hypogonadism)
ACTH reserve most reliably assessed by
ACTH and cortisol levels during insulin-induced hypoglycemia
Most common cause of pituitary hormone syndromes in adults
pituitary adenoma
Size of microadenoma
Mechanism which suprasellar extension can lead to bitemporal hemianopsia
compression of optic chiasm
Early sign of optic tract pressure
loss of red perception
Desired surgical approach for pituitary tumors
transsphenoidal surgery
Most common pituitary hormone hypersecretion syndrome
hyperprolactinemia
Hallmarks of hyperprolactinemia
amenorrhea, glactorrhea, infertility
Mainstay therapy for micro/macroprolactinemia
dopamine agonist (cabergoline and bromocriptine)
Most abundant anterior pituitary hormone
GH
Major source of circulating IGF-1
liver
Major determinant of hepatic IGF-1 synthesis
GH
GH excess causes most significant clinical impact on which system?
cardiovascular system
Screening measure when raising possibility of acromegaly
IGF-1 levels
Initial treatment for most patients with acromegaly
Surgical resection of GH secreting adenoma
Side effect of somatostatin analogues (used in acromegaly)
drug-induced suppression of GI motility and secretion
Accounts for 70% of patients with endogenous casues of Cushing’s syndrome
pituitatry adenoma
Most common cause of Cushingoid features
iatrogenic hypercortisolism
Primary cause of death in Cushing’s
cardiovascular disease
Precise screening test for Cushing’s syndrome
24-hr urine free cortisol
Most common presenting feature of adult hypopituitarism
hypogonadism
What test differentiates central vs peripheral Diabetes Insipidus
Fluid deprivation test
Thyroid hormone synthesis normally begins at?
11 weeks AOG
Subunit unique to TSH
beta subunit (alpha subunit is common to FSH, LH, and hCG)
First step in thyroid hormone synthesis
iodide uptake
Most common cause of preventable mental deficiency
iodine deficiency
Method of choice in determining thyroid size accurately
ultrasound
1st test in thyroid testing, using a logical approach
TSH levels
Most common symptom of hypothyroidism
tiredness, weakness
Most common sign of hypothyroidism
dry coarse skin, cool extremities
Autoimmune hypothyroidism is primarily mediated by
CD8+ cytotoxic T cells
Major role in pathogenesis of myxedema coma, leading to hypoxia and hypercapnia
hypoventilation
Thyrotoxicosis via hyperthyroidism have what major etiologies?
Graves’ disease, toxic multinodular goiter, toxic adenoma
Most common symptom of hyperthyroidism
hyperactivity, irritability, dysphoria
Most common sign of hyperthyrdoidism
tachycardia, atrial fibrillation in the elderly
Minor risk factor for Graves’ disease
smoking
Major risk factor for Graves’ ophthalmopathy
smoking
Most common cardiovascular manifestation of hyperthyroidism
sinus tachycardia
Earliest manifestations of Graves’ ophthalmopathy
eye discomfort, grittiness and excess tearing
Most serious manfiestation of Graves’ ophthalmopathy
compression of optic nerve at apex of the orbit
Most frequent site of thyroid dermopathy
pretibial myxedema
Time of major risk of relapse in Graves’ disease in pregnancy
postpartum period
Prior to radioiodine therapy, carbimazole or methimazole should be stopped when?
2 days before
Prior to radioiodine therapy, PTU should be stopped when?
several weeks before (sorry several talaga nakasulat)
Absolute contraindications to radioiodine
pregnancy and breastfeeding
Most common clinically apparent cause of chronic thyroiditis
Hashimoto’s thyroiditis
Major cause of sick euthyroid syndrome
relase of cytokines
Clinical manifestations of most goiters
asymptomatic
Most common malignancy of the endocrine system
thyroid CA
More common thyroid CA in iodine-deficient regions
follicular thyroid CA
Preferable treatment in almost all patients with well-differentiated cancer
near-total thyroidectomy
Mainstay of thyroid cancer treatment
levothyroxine suppression of TSH
Most common type of thyroid lymphoma
diffuse large-cell lymphoma
Provides a marker of residual or recurrent medullary thyroid CA
elevated serum calcitonin
Primary management of medullary thyroid CA
surgical
Size of most palpable thyroid nodules
> 1 cm
Most common cause of Cushing’s syndrome overall
medical use of glucocorticoids
Ectopic ACTH production is predominantly caused by
occult carcinoid tumors, most frequently lung
Source of ACTH-independent cortisol excess in majority
cortisol-producing adrenal adenoma
Most prominent features in Cushing’s are caused by
upregulation of gluconeogenesis, lipolysis and protein catabolism
Most important first step in management of suspected Cushing’s syndrome
extablish the correct diagnosis
Investigation of choice in ACTH-dependent cortisol excess
MRI fo the pituitary
Oral agents with established efficacy in Cushing’s syndrome
metyrapone and ketoconazole
Most common cause of mineralocorticoid excess
primary hyperaldosteronism (Conn’s syndrome)
Clinical hallmark of mineralocorticoid excess
hypokalemic hypertension
accepted screening test for primary hyperaldosteronism
concurrent measurement of plasma renin and aldosterone with calculation of aldosterone-renin ratio
Most straightforward test for primary hyperaldosterism
saline infusion test
Method of choice for adrenal imaging in hyperaldosteronism
fine-cut CT scan of adrenal region
Preferred appraoch for unilateral lesions in hyperaldosteronism
laparoscopic adrenalectomy
Medical management for hyperaldosteronism consists primarily of
spirinolactone
Most common cause of a malignant adrenal mass
metastatsis (from breast and lung)
Highly sensitive for detection of malignancy that may not be obvious on CT scan
18-FDG PET scan
Metastasis in adrenocortical carcinoma most frequently occurs to
liver and lungs
Most frequent origin of adrenal insufficiency
hypothalamic-pituitary
Most common cause of primary adrenal insufficiency
autoimmune adrenalitis
Distinguishing feature of primary adrenal insufficiency
hyperpigmentation
Characteristic feature of primary adrenal insufficiency (80%)
hyponatremia
Most prevalent cause of CAH (90-95% of causes)
CYP21A2 mutation (21-hydroxylase deficiency)
Marker for overtreatment of CAH
17-hydroxyprogesterone (17OHP)
Classic triad of pheochromocytoma
palpitations, headaches, profuse sweating
Dominant sign of pheochromocytoma
hypertension
Traditionally the 1st step in diagnosing pheochromocytoma
measure catecholamines
Cornerstone for diagnosing pheochromocytoma
elevated plasma and urinary catecholamines
Initial testing for pheochromocytoma
urinary test for VMA, metanephrine, catecholamines
Ultimate goal for pheochromocytoma
complete tumor removal
Before surgery for pheochromocytoma, BP should be
consistently below 160/90
Surgery of choice for pheochromocytoma
atraumatic endoscopic surgery
FIRST described pheochromocytoma-associated syndrome
neurofibromatosis type 1 (NF 1)
BEST KNOWN pheochromocytoma-associated syndrome
MEN 2A, MEN 2B
Leading causes of ESRD, nontraumatic lower extremity amputations and adult blindness
DM
Differentiate type 1a and 1b DM
1a is autoimmune, b is non-autoimmune destruction of Beta cells
Most reliable and convenient test for identifying DM in asymptomatics
HbA1C or FBS
Key regulator of insuling secretion
glucose
Glucose levels that stimulate insulin synthesis
glucose > 70 mg/dL (3.9 mmol/L)
Rate-limiting step that controls glucose-regulated insulin secretion
glucokinase (liver; higher Km; lower afinity, higher Vmax) and hexokinase (everywhere else; lower Km; higher affinity, lower Vmax)
Most potent incretin
glucagon-like peptide 1 (GLP-1)
Major portion of postprandial glucose is utilized by
skeletal muscle
Features of DM become evident when this % of Beta cells are destroyed
~80% destroyed
Major susceptibility gene in T1DM
HLA region on chromosome 6
Central to the development of T2DM
insulin resistance and abnormal insulin secretion
Predominantly accounts for increased FBS levels
increased hepatic glucose output
Results in postprandial hyperglycemia
decreased peripheral glucose usage
Classic signs of DKA
Kussmaul respirations and fruity odor (increased acetone and metabolic acidosis)
3 ketone bodies
acetone, acetoacetate, beta-hydroxybutyrate
Extremely serious complication of DKA, seen most frequently in children
cerebral edema
Conditions necessary for DKA to develop
both insulin deficiency and glucagon excess
Consistent finding in DKA (distinguishes from simple hyperglycemia)
ketonemia
Drug that causes false-positive reaction on nitroprusside tablet test for DKA
captopril or penicillamine
Central to successful treatment of DKA
monitoring and frequent reassessment for improvement
Potassium level in which you may start insulin in DKA
serum K
Underlying cause of hyperglycemic hyperosmotic state
relative insulin inefficiency and inadequate fluid intake
Leading casue of blindness between ages 20 and 74
DM
Hallmark of proliferative diabetic retinopathy
neovascularization in response to retinal hypoxia
Non-proliferative diabetic retinopathy is marked by
retinal vascular microaneurysms, blot hemorrhages and cotton wool spots
Best predictor of development of retinopathy
duration of DM and degree of glycemic control
Non-proliferative diabetic retinopathy is found in almost all with x years of DM?
DM > 20 years
Most effective therapy for DM retinopathy
prevention
Fibrin caps, capsular drops, Kimmelsteil-Wilson nodules
DM nephropathy (nodular glomerulosclerosis)
Optimal therapy for DM nephropathy
prevention via control of glycemia
Preferred therapy for DM nephropathy
renal transpalnt
Most common form of DM neuropathy
distal symmetric polyneuropathy
Most commonly involved nerve in DM mononeuropathy
CN III- heralded by diplopia
Most prominent GI symptoms in DM
delayed gastric emptying, altered small- and large-bowel motility
Primary goal in GI and GU dysfunction in DM
improved glycemic control
Most common pattern of dyslipidemia in Dm
hypertriglyceridemia and reduced HDL
Drug that effectively raises HDL, but high doses (> 2 g/d) may worsen glycemic control
niacin/nicotinic acid
Most common site of foot ulcers
great toe or metatarsophalangeal areas
Optimal therapy for foot ulcers and amputation
prevention
Most common site of ulceration in DM
plantar surface of foot
Most helpful diagnostic for infected foot ulcer
culture of debrided ulcer base/purulent drainage/wound aspirate
Most specific modality for osteomyelities in DM
MRI of foot
Common denominator in DM infections
poor glycemic control
Most common skin manifestation in DM
protracted wound healing and skin ulcerations
Considered hypertension in DM
BP > 130/80
Confirms a patient’s need for insulin
low c-peptide levels
Symptoms of DM usually resolve in what glucose level?
Primary goal of treatment in DM is what HbA1c level?
HbA1c
Recommendations on exercise in Dm
150 min/week distributed over at elast 3 days of moderate aerobic physical activity
Standard of care in DM management
self-monitoring blood glucose
Standard method for long-term glycemic control
HbA1c
Primary predictor of long-term compliance in DM
HbA1c
Can be used as an alternative indicator of glycemic control when HbA1c is inaccurate (hemolytic anemia, hemoglobinopathies)
albumin
Major toxicity of metformin
lactic acidosis
Major side effects of GLP-1 agonist
nausea, vomiting, diarrhea
Major side effects of alpha-glucosidase inhibitors
diarrhea, flatulence, abdominal distention
Most serious complication of therapy for Dm
hypoglycemia
Preferred in ICU/unstable settings for DM
IV insulin infusion (SC insulin absorption is variable)
Preferred over insulin analogue for IV insulin infusion
regular insulin (less expensive and equally effective)
Pregnancy issues- most crucial period of glycemic control in pregnancy
soon after fertilization
Whipple’s triad
symptoms of hypoglycemia, low plasma glucose via precise method (not a glucose monitor) and relief of symptoms after glucose is raised
Lower limit of the fasting plasma glucose concentration
70 mg/dL (3.9 mmol/L)
Obligate metabolic fuel for the brain under physiologic conditions
glucose (ketones in prolonged fasting > 2 weeks)
Hepatic glycogen stores are usually sufficient to maintain glucose levels for how long?
8-12 hrs
Primary glucose regulatory factor (1st defense against hypoglycemia)
decrease insulin
Primary glucose counterregulatory factor (2nd defense against hypoglycemia)
increase glucagon
3rd defense against hypoglycemia
increase epinephrine
Limiting factor in the glycemic management of DM
hypoglycemia
In hospitalized patients, glycemic maintenance goals have been modified to fall between
140-180 mg/dL
Second only to drugs as causes of hypoglycemia
serious illnesses (renal, hepatic, cardiac failure, sepsis, inanition)
Major site of endogenous glucose production
liver
Hypoglycemia in non-beta cell tumors
Overproduction of insulin-like growth factor II (“big IGF-II”)
Prototypical cause of endogenous hyperinsulinism
insulinoma
Ingestion of an insulin secretagogue in relation to c-peptide levels
causes hypoglycemia with increased c-peptide levels
Exogenous insulin in relation to c-peptide levels
causes hypoglycemia with low c-peptide levels
Emerging as method of choice for testosterone measurement
liquid chromatography tandem mass spectrometry (LC-MS/MS)
Most important step in the evaluation of male infertility
semen analysis
Most common cause of androgen deficiency in acute illness
hypogonadotropic hypogonadism
Most common chromosomal disorder associated with testicular dysfunction and male infertility
Klinefelter syndrome (47 XXY)
Most effective therapy if gynecomastia is of long duration
surgery
Most common cause of female infertility
abnormalities in menstruation
Most widely used form of hormonal contraception
oral contraceptives
Primary regulator of calcium physiology
PTH, from chief cells of parathyroid
Primary function of PTH
maintain ECF calcium concentration
90% of all cases of hypercalcemia
hyperparathyroidism and cancer
Second most common cause of hypercalcemia in the adult
malignancy
Serum Ca levels for hypercalcemia symptoms (bones, groans, overtones, moans)
calcium > 11.5-12 mg/dL (> 2.9-3.0 mmol/L)
Serum Ca levels for severe hypercalcemia and medical emergency
Ca 15-18 mg/dL (3.7-4.5 mmol/L)
Parathyroid tumors are most often encountered in
isolated adenomas
Parathyroid adenomas are most often located in which parathyroid glands
inferior parathyroid glands
Predominant in both hyperplasia and adenoma of the parathyroid gland
chief cells
Hyperparathyroidism manifestations primarily involve which systems?
kidneys and skeletal system
Most prevalent form of hyperparathyroidism
asymptomatic hyperparathyroidism
Definitive therapy for hyperparathyroidism
surgical excision of the abnormal parathyroid tissue
Responsible agent in most solid tumors that cause hypercalcemia
PTHrP (in squamous cell lung CA, renal cell CA)
Striking feature of malignancy-associated hypercalcemia
rapidity in course
First principle of treatment of hypercalcemia
restore normal hydration
Treatment of choice for severe hypercalcemia complicated by renal failure
dialysis
Most frequent cause of acquired hypoparathyroidism in the past
surgery for hyperthyroidism
Currently the most frequent cause of acquired hypoparathyroidism
surgery for hyperparathyroidism
Chief clinical manifestations of osteoporosis
vertebral and hip fractures
Final common path in osteoclast development and activation
activation of RANK by RANKL
Age range after which resorption exceeds formation of calcium
after age 30-45
Most common estrogen-deficient state
menopause
Most common early consequence of estrogen deficiency
vertebral fractures
Most common cause of medication-induced osteoporosis
glucocorticoids
Standard for measuring bone density
Dual Energy X-Ray Absorptiometry (DEXA or DXA)
Preferred DXA sites of measurements
lumbar spine and hip
Can falsely increase bone density of the spine esp in the elderly
bone spurs
Guidelines further recommend that bone mass measurement be considered in
ALL women by age 65 (exact phrase of Q&A)
Preferred source of calcium
dairy products and other foods
Calcium carbonate requirements
best taken with food (require acid for solubility)
Primary therapeutic agent for prevention or treatment of osteoporosis
estrogen treatment
Approved for the prevention and treatment of breast cancer
tamoxifen (increased risk of uterine cancer in postmenopausal)
Osteonecrosis of the jaw in patients with cancer comes from being given high doses of
zoledronic acid or pmidronate
More severely affected bone in glucocorticoid-induced osteoporosis
trabecular bone (more than cortical bone)
Duration of steroids to have bone mass measurement via DEXA
> 3 months glucocorticoid therapy
If only one skeletal site can be measured for DEXA, where is it best taken?
spine in 60 years
Demonstrated to reduce the risk of fractures in patients being treated with glucocorticoids
only bisphosphonates
