Endocrine Flashcards
storage form of insulin?
proinsulin
normal fasting blood glucose? diabetic?
4-6 mmol/L
>7 (126 mg/dL)
normal random blood glucose? diabetic?
< 9 mmol/L
>11.1 (200 mg/dL)
name 3 endogenous hormones that antagonize insulin
cortisol
growth hormone
catecholamines
name 2 genetic diseases associated with diabetes
Down’s
Turner’s
what is the differential age for onset between diabetes type I and II?
40
< 40 = type 1
> 40 = type 2
which type of diabetic presents with ketoacidosis? why doesn’t the other type?
type 1
type 2 have insulin which is very antiketogenic
Which type of diabetes has an established HLA link? what is the HLA involved?
type 1
HLA-DR3 & HLA-DR4
DQA1 & DQB1
coxsackie B4 virus is associated with what disease?
Diabetes Type I
Rubella and mumps are associated with what disease?
Diabetes Type I
which type of diabetes has a long pre-diabetic phase? What symptoms do they exhibit? What is found in their blood?
Type I
asymptomatic
islet cell antibodies (ICA)
name 2 possible etiologies of type I diabetes
viral infection and molecular mimicry
direct damage to beta cells
which type of diabetes has the strongest genetic component?
type II
name 2 compounds found in obese patients and explain how they lead to the development of diabetes
Obese patients have high levels of FAs and TNF (both produced by adipose tissue) and they are both insulin antagonists
which diabetes is associated with amyloid? why?
Type II
it is secreted with insulin and type I diabetics don’t produce insulin
explain vomiting in diabetes
in type I diabetics, production of ketone bodies is high, ketones stimulate the area postrema responsible for vomiting
is high urine glucose diagnostic for diabetes? why or why not?
No, used for screening only
Diagnosis is based off of HbA1C > 6.5%
how could a severely diabetic patient present with normal HbA1C levels?
If they have HbS or HbF from sickle cell or thalassemia the % of HbA will be skewed
explain the term “impaired fasting glycemia” (IFG)
prediabetic state where fasting glucose levels are above normal but below diabetic range (between 5.6 and 6.9 mmol/L)
explain the term “impaired glucose tolerance” IGT
prediabetic state where the 2h value of the OGTT (oral glucose tolerance test) is above normal, but below diabetic range (between 7.8 and 11.1mmol/L)
explain how hyperglycemia can lead to dehydration
glucose is freely filtered, but cannot all be reabsorbed like it is normally. It is osmotically active and draws water into filtrate -> polyuria, dehydration
explain how diabetics can develop lactic acidosis
caused by dehydration and vasoconstriction by stress hormones (from cellular starvation and hypovolemia)
what two substances do you give to someone with ketoacidosis? why?
insulin to encourage cellular uptake of glucose
potassium to fix electrolyte imbalance from vomiting and osmotic diuresis
75 year old, very dehydrated woman presents to the ER in a comatose state, there is no sign of ketoacidosis. explain her situation and what is characteristic of her blood work?
She is a type 2 diabetic in a hyperosmolar nonketotic coma. She has enough insulin to suppress ketosis, but cannot suppress hyperglycemia. Her blood will show VERY high glucose levels which is causing the dehydration by glucose’s osmotic action in the renal filtrate
what is the first long term complication of diabetes to present in microangiopathy? what are 3 common complications of diabetic microangiopathy?
thickening of the basement membrane
retinopathy, nephropathy, neuropathy
what is the most common complication of diabetic macroangiopathy and how does it present?
atherosclerosis
ischemic heart disease, stroke, peripheral vascular disease
most important treatment in long term diabetics is?
prevention of vascular accidents, even more important than controlling blood glucose
list the first functional change, first biochemical sign, and first morphological signs seen in diabetic nephropathy
functional: hyperfiltration
biochemical: microalbuminuria
morphological: thickening of basement membrane and mesangial expansion
what is the most common cause of blindness in adults 30-65 years old?
diabetic retinopathy
name 3 long term complications involving the eye in diabetics
retinopathy
cataracts
glaucoma
explain AGE and give a complication
advanced glycosylation end products in diabetics
high blood glucose leads to glycosylation of basement membranes capillaries and structural proteins -> retinopathy
explain why cataracts form in diabetics
lens does not require insulin for glucose uptake, gets a lot, glu is shuffled into minor metabolism pathways because glycolysis is overwhelmed. Gets converted into sorbitol which is highly osmotically active and accumulation leads to discoloration of lens
explain the major differences of a histo section of the pancreas between type I and type II diabetes. What is common to both?
type I: lymphocytic infiltration
type II: amyloid deposition
both: pancreatic hyalinization
give 3 early changes in the kidney with diabetes
basement membrane thickening
mesangial cell proliferation
hyaline arteriolosclerosis of afferent and efferent
give 2 later appearances of the kidney associated with diabetes. Which is more specific for diabetes? In what other pathology can the other change be seen?
diffuse mesangial sclerosis
nodular glomerulosclerosis
Nodular is specific to diabetes, diffuse can be seen in old age and hypertension
on histology of a kidney biopsy you find spherical deposits of laminated matrix. what are these deposits? How do they stain? What disease are they associated with?
Kimmelstiel wilson lesions
PAS+
diabetes
your kidney biopsy is described as having a finely granular cortical surface. What pathology is involved? Associated with what disease?
this describes a scarred kidney caused by long term ischemia. Commonly seen in nodular glomerulosclerosis of diabetics
what is the hallmark of proliferative retinopathy in diabetics?
neovascularization and fibrosis
explain the pathogenesis of microaneurysms in diabetic retinopathy
loss of pericytes (sorbitol is toxic to them and glucose freely enters pericytes) that provide structural support to capillaries leads to ballooning and possible rupture of the vessels of the eye
why would a diabetic present with hyperkalemia? When would you see hypokalemia?
insulin drives K+ into cells, so type I diabetics have no insulin so K+ stays in blood
hypokalemia is seen after treatment with insulin and a reversal of acidosis. K+ is driven into the cells and patient can become hypokalemic without supplementation
explain how type II diabetics can present with coma
high glucose leads to life-threatening diuresis and if dehydration is severe enough, the hypotension can result in coma
explain the pathogenesis behind peripheral neuropathy in diabetics
glucose can freely enter Schwann cells which myelinate peripheral nerves. Production of sorbitol leads to osmotic damage and death of schwann cells
explain the importance of the blood supply to the anterior pituitary
Not very well oxygenated - very susceptible to infarct
which hormones are produced by acidophils in the ant. pituitary? name the ones produced by the basophils
Acidophil: growth hormone - prolactin
Basophil: TSH - ACTH - LH - FSH
GnRH triggers the release of what hormones?
LH and FSH
CRF triggers the release of what hormones?
ACTH
TRH triggers the release of what hormones?
TSH and prolactin
TRH = thyrotrophin releasing hormone
which molecule inhibits the release of growth hormone?
somatostatin
what molecule triggers the release of growth hormone?
GH-RH (growth hormone releasing hormone)
What is the functionality of the most common pituitary disorder? What causes it? How?
hypopituitarism
pituitary adenoma - as it expands, it destroys other secreting cells
a woman has a complicated pregnancy and loses a lot of blood during birth and becomes severely hypovolemic. what is she at risk for? what is this called? why?
hypopituitarism
Sheehan’s syndrome
pituitary enlarges during pregnancy and becomes even more vulnerable to ischemia/infarct
a woman experiences low milk production after giving birth - give a possible differential
Sheehan’s syndrome - hypopituitarism due to infarct from loss of blood during delivery
name two diseases associated with hypopituitarism
sarcoidosis
hemochromatosis
pt seems to be experiencing symptoms of hypopituitarism but her LH is normal. what does this tell you? why?
probably not hypopituitarism because LH and GH are the first deficiencies to appear in hypopituitarism
List the hormones of the anterior pituitary in the order that they present in deficiency. Starting with the one that generally becomes deficient first
disappears first: LH, GH
next: FSH
last: ACTH, TSH
a female presents with menstrual disturbances and delayed puberty - give a differential
loss of gonadotrophins - LH and FSH
hypopituitarism
a male is experiencing loss of libido, loss of facial and body hair, and impotence - give a differential
loss of gonadotrophins - LH and FSH
hypopituitarism
what is a complication of panhypopituitarism?
coma
name the stress hormones released by the anterior pituitary. How do you asses their release?
prolactin
GH
ACTH
induce a stress, hypoglycemia, by injecting patient with insulin and measure levels released
antipsychotics and oral contraceptives have what affect on the pituitary?
hyperprolactinemia
what is the most common pituitary tumor?
prolactinoma
renal failure has what effect on the pituitary? why?
hyperprolactinemia excess release (its a stress hormone) and reduced clearance because its usually metabolized in the kidney
female presents with amenorrhea, infertility, and galactorrhea - differential?
hyperprolactinemia
patient presents with frontal bossing, hypertension, arthritis, loss of libido, and symptoms of diabetes mellitus - differential? cause? explain
Acromegaly - excess GH release after childhood due to adenoma
diabetes: GH antagonizes insulin
GH inhibits action of what other hormone?
insulin
When would you measure IGF-1 levels and why?
insulin-like growth factor-1
acromegaly - GH acts on liver to produce IGF-1 and it is more stable than GH so easier to measure
What should happen to GH levels after the administration of oral glucose? Failure of this to happen suggest what?
normal person should show undetectable levels of GH following glucose (GH antagonizes insulin which needs to be high, so GH release is inhibited)
if GH levels are normal or paradoxically rise -> acromegaly (ant. pituitary adenoma)
When is ADH secreted (2)?
What does it cause? How?
secreted in response to decreased blood volume or raised plasma osmolality
causes water retention by increasing permeability in the distal convoluted tubules and collecting ducts in the kidney
patient presents with polyuria and polydipsia, and is extremely dehydrated - differential? causes (2)?
diabetes insipidus
Central: lack of ADH
Nephrogenic: resistance to ADH action
name 2 metabolic causes of diabetes insipidus
hypokalemia
hypercalcemia
explain the water deprivation test and what disease it’s used to diagnose
fluid restriction for 8 hours, pee every hour, measure urine volume and osmolality and body weight - if the urine does not become concentrated, indicates diabetes insipidus
how can you differentiate between central and nephrogenic diabetes insipidus?
after fluid deprivation and the urine osmolality stays low, give ADH - urine osmolality will increase if central, and won’t change if nephrogenic
patient presents with coma, water retention, and hyponatremia - differential?
SIADH - excess secretion of ADH with no feedback
what hormone is most responsible for reabsorbing sodium in the collecting tubule?
aldosterone
explain why patients with SIADH have hyponatremia yet still lose it in their urine
excess ADH leads to water retension -> hypervolemia. The main hormone responsible for reabsorption of sodium in the collecting tubule is aldosterone, but it is only released during hypovolemia, so sodium is lost in urine
what hormone suppresses prolactin production?
dopamine
prolactin inhibits synthesis and release of what? associated symptoms?
GnRH so no FSH or LH -> amenorrhea
explain the relationship between GH adenoma and secondary diabetes mellitus
GH decreases glucose uptake by cells but also induces liver gluconeogensis -> high blood glucose
desmopressin is an analog of what? used to treat what?
analog of ADH
treats central diabetes insipidus
Male with a history of smoking presents with a poorly differentiated, centrally located tumor in his lungs. What other disease can be associated with this condition?
Small cell carcinoma, releases ADH -> SIADH
name the 2 thyroid hormones and which is produced in greater abundance?
Most: T4 - thyroxine
T3 - tri-iodothyronine
name two major functions of thyroid hormones
stimulate basal metabolic rate
inc. sensitivity of CVS and nervous system to catecholamines by upregulating B1 receptors
what two hormones are necessary for release of thyroid hormone? also give their locations of production
TRH from hypothalamus
TSH from pituitary
Pt presents with infertility, arrythmias, osteoporosis and muscle weakness - differential? other associated symptoms?
Hyperthyroidism
exophthalmos, lid lag, weight loss, tachycardia, sweating, diarrhea
what do the C cells of the thyroid produce? what is its function?
calcitonin - reduces serum calcium, opposes PTH
pt. presents with hypocholesterolemia, hypercalcemia, and hyperglycemia - differential?
hyperthyroidism
35 year old female presents with a diffuse enlargement in her neck and periorbital edema - what is characteristic on histology (2)?
graves disease - hyperthyroidism
scalloping of colloid, chronic inflammation
pretibial myxedema - diagnosis? what type of hypersensitivity? explain pathogensis
Grave’s disease - hyperthyroidism
type II hypersensitivity
IgG autoantibodies that stimulate TSH receptor
elevated T4
decreased TSH
hypocholesterolemia
hyperglycemia
Graves disease - hyperthyroidism
following viral infection, patient presents with weight loss, exophthalmos, pain, tenderness in neck, and fever - explain current symptoms and course of his illness
Subacute DeQuervain’s thyroiditis
inflammation post viral infection destroys acini of thyroid gland leading to release of premade thyroid hormone and hyperthyroidism symptoms. It is self limiting, does not progress to hypothyroidism
patient presents with multinodular, nontoxic goiter - differential? cause?
euthyroid enlargement due to iodine deficiency
decreased T4
elevated TRH
elevated TSH
iodine deficiency
patient presents with carpal tunnel syndrome, infertility, and hyperprolactinemia - differential? cause for hyperprolactinemia?
hypothyroidism
thyroid hormone is not being produced, no negative feedback on hypothalamus, leading to increased TRH which is responsible for release of both TSH and prolactin
HLA-DR5 - disease?
Hashimoto thyroiditis (hypothyroidism)
thyroid biopsy shows fleshy, soft, pale, lobular nodules protruding above the cut surface with areas of depression between the nodules - disease? what is the explanation for the areas of depression? what is an important disease association with this condition?
Hashimoto’s thyroiditis (hypothyroidism)
depressed areas are fibrosis from autoimmune destruction of the gland
association: increased risk for B-cell (marginal zone) lymphoma
how do you differentiate between the early stages of Hashimoto’s thyroiditis and subacute De Quervain thyroiditis based on symptoms alone?
Both present initially as hyperthyroidism due to destruction of the gland and release of preformed thyroid hormone. However, Hashimoto’s will progress to hypothyroidism whereas De Quervain’s is self limiting and will not progress
neonate presents with a protruding tongue, umbilical hernia, and shows signs of mental retardation - diagnosis? give 3 possible causes
Cretinism - hypothyroidism
maternal hypothyroidism during pregnancy thyroid agenesis (DiGeorge!) iodine deficiency
patient presents with muscle weakness, bradycardia, hypercholesterolemia and constipation - diagnosis? 3 possible causes?
hypothyroidism
iodine deficiency, Hashimoto’s thyroiditis, radioablation of thyroid
On serology you find anti-TPO and antithyroglobulin antibodies from your patient’s blood. Diagnosis? what is characteristic of this condition on histology? describe
Hashimoto’s thyroiditis
germinal centers and Hurthle cells (eosinophilic metaplasia of cells that line follicles)
what two values do you need to investigate to fully analyze the state of thyroid function?
TSH and T4
46 year old woman complains of hot flushes and presents with diffusely enlarged thyroid.
TSH levels are high, and T4 levels are on the low end of normal. Differentials?
Early hypothyroidism (presents with hyperthyroid symptoms first from release of thyroid hormone from destruction of follicles)
mild iodine insufficiency
elderly woman is noted to have high TSH levels but normal levels of T4/T3 and is otherwise asymptomatic - diagnosis? 2 complications
sub-clinical hypothyroidism (usually in elderly - page 32 of class notes)
can convert to hypothyroidism
associated with endothelial dysfunction -> atheroma
what is the effect of GH on blood glucose levels?
GH inhibits uptake of glucose by cells -> high blood sugar
patient presents with hyperglycemia, hypertension, osteoarthritis, headache, and prognathism - diagnosis? most common cause of death?
acromegaly
death due to cardiac failure (GH leads to organ enlargement too)
explain “hot” vs “cold” nodules - which is associated with adenoma? Grave’s? carcinoma?
hot nodule actively produces thyroid hormone so shows increased uptake of radioactive iodoine. cold nodules dont produce hormone and so decreased uptake of radioactive iodine
hot nodules: Grave’s
cold nodules: adenoma (but can rarely secrete thyroid hormone) and carinoma
Patient with a history of ionizing radiation exposure presents with mass in his neck and enlargement of several cervical lymph nodes. Diagnosis? What is characteristic on histo? Prognosis?
Papillary carcinoma of the thyroid
Orphan Annie eye nuclei (clear) and psammoma bodies
excellent prognosis even with lymph node involvement
on histology of thyroid biopsy you see outpouchings of the stroma lined by cells showing finely dispersed chromatin - diagnosis? how common?
Papillary carcinoma of the thyroid
most common thyroid carcinoma, but thyroid adenoma is far more common
On fine needle aspiration of a singular nodular lesion of the thyroid, you find well differentiated follicles. Patient also shows masses in lung and liver - diagnosis? what is unique? treatment
Follicular carcinoma of the thyroid
carcinoma that spreads hematogenously (other 3 exceptions are renal cell, hepatocelluar, and choriocarcinoma)
responds to TSH so give thyroid hormone to inhibit release of endogenous TSH
nodule of the thyroid shows increased uptake of radiolabeled iodine. Should you be concerned? Why or why not?
No, carcinoma usually results in loss of function (cold nodules) so uptake of iodine indicates a functioning gland and is less likely to be cancer
on biopsy of thyroid you find concentric layers of calcification and extensions of stroma with a fibrovascular core with multiple layers of cuboidal and columnar cells - diagnosis? mutation involved?
Papillary carcinoma of the thyroid
RET and RAS pathway mutations
where does papillary carcinoma of the thyroid commonly spread? how?
cervical lymph nodes via lymph
where does follicular carcinoma of they thyroid common spread? how?
liver, bone, lung
hematogenously
patient presents with mass in his neck and hypocalcemia - diagnosis? what cells are involved? pathogenesis of the hypocalcemia?
Medullar carcinoma of the thyroid
parafollicular C cells - they secrete calcitonin which is inactive at normal physiological levels, but increased levels from tumor can lead to hypocalcemia by increasing renal excretion of calcium
biopsy of the thyroid gland shows sheets of malignant cells on a glassy pink background - diagnosis? most common hereditary cause? mutation? treatment?
medullary carcinoma of the thyroid
MEN 2A and 2B
RET mutation
detection of RET mutation -> prophylactic thyroidectomy (also treatment)
what feature is most important in diagnosis of follicular carcinoma of the thyroid? why?
must do biopsy to find capsular invasion - otherwise, the stroma looks like normal thyroid gland
on histo of thyroid biopsy you see nests of polygonal to spindle-shaped cells - diagnosis?
medullary carcinoma of the thyroid
patient presents with moon face, buffalo hump, watery diarrhea, and cervical lymphadenopathy - diagnosis? explain the pathogenesis of this condition? what is another possible association?
Medullar carcinoma of the thyroid
ACTH is also secreted by the tumor along with calcitonin resulting in cushing’s symptoms
patient could also present with carcinoid syndrome due to tumor producing serotonin as well
patient presents with flushing, watery diarrhea, and a mass in her neck - diagnosis? what is found in urine?
medullary carcinoma of the thyroid causing paraneoplastic syndrome (carcinoid syndrome from production and release of serotonin)
5-HIAA is found in urine - breakdown product of serotonin
(flushing is key feature of carcinoid syndrome)
73 year old woman presents with dysphagia and trouble breathing and a firm, bulky, enlarging mass in her neck - diagnosis? prognosis? how do cells appear on histo?
anaplastic carcinoma of the thyroid
very poor prognosis, most malignant tumor in the body (only in people over 60)
cells are undifferentiated, pleomorphic, anaplastic
scalloping of colloid is involved with which type of nodule in the thyroid? hot or cold? why is this important?
only seen in hot - malignancy is virtually nonexistent in hot nodules
most common swelling of thyroid gland?
thyroid adenoma - benign
name the 3 zones of the adrenal gland and the major hormone produced by each
glomerulosa: aldosterone (mineralcorticoids)
fasiculata: cortisol (glucocorticoids)
reticularis: testosterone (androgens)
17-alpha hydroxylase deficiency leads to a decrease in the production of what? increase in what? give characteristics
decrease in: androgens and cortisol
increase in: aldosterone
feminine, hypertension
21-beta hydroxylase deficiency leads to a decrease in the production of what? increase in what? give characteristics
decrease in: aldosterone and cortisol
increase in: androgens
masculinity, hyponatremia, hyperkalemia, hypovolemia, hypotension
which hormone is an insulin antagonist and an anti-inflammatory?
cortisol
which hormone increases sodium reabsorption in the kidney in exchange for potassium and hydrogen ions?
aldosterone
which group of hormones leads to precocious puberty in boys and masculinization of females?
androgens
release of cortisol from adrenal glands is regulated by the action of what two hormones?
hypothalamus: CRH
pituitary: ACTH
what hormone’s release follows the circadian rhythm? when are concentrations highest? lowest? what can override this pattern?
cortisol
highest: morning
lowest: midnight
stress can override
name the two physiological conditions that lead to release of aldosterone
hypotension sodium loss (hyponatremia)
what hormone controls the release of androgens?
ACTH
young child presents with very high fever, tachypnea, and petechiae on his extremities - diagnosis? associated pathological process? complication from this associated process?
sepsis (most commonly N. meningitidis)
Waterhouse-Friderichsen syndrome
W-F syndrome leads to hemorrhagic necrosis of the adrenal glands bilaterally which leads to a lack of cortisol - lack of cortisol exacerbates hypotension from sepsis and can lead to death
patient presents with hypotension, hypovolemia, hyperkalemia and hyperpigmentation - diagnosis? most common cause in developed world? developing world? other?
adrenal insufficiency
developed: autoimmune destruction (Addison’s)
developing: TB
other: metastasis from lung cancer (lung cancer loves to go to adrenals)
which hormone is associated with hyperpigmentation? is it due to lack of or excess hormone?
ACTH
excess (increased ACTH by-products stimulate melanocytes)
what cancer has a common metastasis to the adrenal gland?
lung cancer
patient presents with tiredness, anorexia, abdominal pain, hyperpigmentation and postural hypotension - diagnosis?
Addison’s
how do you tell the difference between primary adrenal insufficiency (Addison’s) and secondary adrencortical insufficiency (pituitary problem) based on presentation?
secondary does not present with hyperpigmentation (no ACTH) and, initially, no electrolyte disturbances due to presence of aldosterone (released from renin-angiotensin system, not pituitary)
explain the synacthen test - what is it testing?
give 2 conditions it used for
you give ACTH analog (synacthen) to see if cortisol is produced - tests residual capacity of the adrenal gland
- it can differentiate between addisons and secondary adrenal insufficiency based on whether the gland responds to ACTH with cortisol production or not
- it can be used to test for 21-hydroxylase deficiency - if it is deficient, the ACTH analog will lead to production of excess androgens so you would see elevated 17-alpha hydroxyprogesterone in blood
patient presents with hypertension, frequent colds, muscle weakness and abdominal striae - diagnosis? explain the pathogenesis behind each of the presenting symptoms
hypercortisolism (cushings)
hypertension: cortisol upregulates alpha-1 receptors on arterioles (inc. peripheral resistance)
frequent colds: cortisol is an immune suppressant
muscle weakness: cortisol breaks down muscles for gluconeogensis
striae: cortisol inhibits collagen synthesis
explain the mechanism behind the moon facies, buffalo hump, and truncal obesity (what disease?)
cushing’s
cortisol breaks down muscle for gluconeogenesis leading to hyperglycemia - this stimulates production of insulin which increases storage of fat
name two important sources of ectopic ACTH
small cell lung carcinoma steroid usage (iatrogenic)
briefly explain the low-dose dexamethasone suppression test - what is it used for?
dexamethasone is a cortisol analog that suppresses ACTH production, used to diagnose the potential cause of hypercortisolism
dexamethasone suppression test shows no suppression at low levels, but suppression at high levels - what does this indicate?
Cushing’s disease (pituitary tumor)
dexamethasone suppression test shows no suppression at low or high levels - what does this indicate?
ACTH production by small cell lung carcinoma
or cortisol secreting tumor of adrenal gland
what is the only cause of hypercortisolism in which you seen unilateral atrophy of the adrenal gland? explain
primary cortisol secreting tumor of the adrenal gland - excess cortisol inhibits ACTH release from pituitary thus leading to down regulation of cortisol production by functional adrenal gland, eventually leading to atrophy
what is the only cause of hypercortisolism where you see bilateral atrophy of the adrenal gland? explain
exogenous use of corticosteroids - steroids suppress ACTH secretion via negative feedback, leading to down regulation of cortisol production by the adrenal glands, eventually leading to atrophy
patient presents with hypertension, hypernatremia, hypokalemia, and metabolic alkalosis - diagnosis?
hyperaldosteronism (Conn syndrome)
explain aldosterone’s actions on the kidney
increases sodium absorption, potassium secretion and hydrogen ion secretion at the distal tubules and collecting duct
patient presents with hypertension. Plasma cortisol in the morning is 470 nmol/L and at midnight is 110 nmol/L - what can you rule out as the cause of her hypertension and why
cannot be due cushings because the cortisol levels follow the circadian rhythm - they would always be high in cushings
girl presents with enlarged clitoris and partially fused labia - diagnosis?
21-beta hydroxylase deficiency
congenital adrenal hyperplasia
female patient presents with hirsutism and infertility - diagnosis?
21-beta hydroxylase deficiency
late onset congenital adrenal hyperplasia
teenage girl presents with delayed puberty, no breast development, and amenorrhea - diagnosis? what would be an associated symptom? why?
17-alpha hydroxylase deficiency
(congenital adrenal hyperplasia)
hypertension due to excess mineralocorticoid production
what is the breakdown product of catecholamines? what two enzymes are used to degrade them?
VMA (Vanillyl mandelic acid)
COMT and MAO
from what cell type are chromaffin cells produced? where are they found? what do they produce?
neural crest cells
adrenal medulla
catecholamines
what are the 3 tumors associated with MEN2a? what gene is mutated?
medullary carcinoma of the thyroid
pheochromocytoma
parathyroid adenoma
RET
what are the 3 tumors associated with MEN2b? what gene is mutated?
medullary carcinoma of the thyroid
pheochromocytoma
ganglioneuromas of the oral mucosa
RET
explain the rule of 10s
pheochromocytoma 10% inherited (90% sporadic) 10% malignant (90% benign) 10% bilateral (90% unilateral) 10% component of MEN2a/MEN2b 10% in childhood (90% in adulthood) 10% found outside adrenal medulla 10% have no assoc. hypertension
pheochromocytoma presents with vascular invasion. Is it malignant? why or why not?
you can’t tell, benign pheochromocytomas can invade vasculature - would need evidence of metastasis to confirm malignancy
explain MIBG scintigraphy
inject radio labeled catecholamine precursors and image the person - in a pheochromocytoma you would see an accumulation of these labeled precursors in the area of the tumor
patient presents with hypertension, wt loss, headache, hyperglycemia, and sweating - diagnosis? what is unique about the onset of symptoms?
pheochromocytoma
5 H’s: HTN, hyper-metabolism, headache, hyperhydrosis, hyperglycemia
onset of symptoms is episodic
what is produced in pheochromocytomas?
mostly epi and NE, little dopamine (rarely)
5 year old presents with tumor in his adrenal gland - give 2 differentials and how would you tell them apart?
neuroblastoma (major product is dopamine)
one of the 10% of pheochromocytomas that presents in childhood (produces epi and NE)
to differentiate, look at breakdown products in urine:
if neurblastoma: elevated homovanillic acid HVA (dopamine metabolite)
if pheochromocytoma: elevated Vanillyl mandelic acid VMA (epi and NE metabolite)
what are the 3 tumors associated with MEN1? what gene is mutated? association?
pituitary gland, parathyroid and pancreas
MEN1 gene
Zollinger-Ellison syndrome (peptic ulcers)
patient presents with high cortisol levels that are suppressed with low dose dexamethasone - diagnosis? causes?
pseudocushing’s syndrome
chronic stress, anorexia, chronic alcoholism, diabetes mellitus
Nests of polygonal spindle shaped cells surrounded by thin vascular stroma - pleomorphism and capsular invasion - diagnosis?
pheochromocytoma
66 year old lady fainted while grocery shopping. Her labs shows slightly elevated urea and calcium, elevated ALP, and slightly decreased phosphate - diagnosis?
hyperparathyroidism
what are hydroxyapatite crystals and where do you find them?
its the storage form of calcium in bone
name 3 ways PTH can regulate serum calcium and phosphate
- increases bone osteoclast activity (releases calcium and phosphate
- increases small intestinal absorption of calcium and phosphate (via activation of vit D)
- increases renal calcium reabsorption and decreases phosphate reabsorption (to balance out the gain of phosphate from the first 2)
1% of calcium is found extracellulary, name two functions of extracellular calcium
neuromuscular excitability
co-factor for clotting enzymes
only half of serum calcium is physiologically active, why?
other half is bound to albumin
what is the active form of calcium in blood? how does pH affect this?
active form is ionized calcium which is increased in acidosis and decreased in alkalosis
what is 1,25-dihydroxycholecalciferol? what does it do?
activated vit D
enhances absorption of calcium in gut and aids in bone resorption to release calcium
give the two main causes of hypercalcemia (95%)
hyperparathyroidism
malignancy
patient presents with hypercalcemia and normal levels of PTH - should you be concerned? what is one cause of this presentation?
yes, a patient with hypercalcemia should have low PTH - this is usually caused by an adenoma, but can be a carcinoma or hyperplasia
patient presents with polyuria, constipation, peptic ulcer disease, and acute pancreatitis - diagnosis? treatment?
hyperparathyroidism
remove affected gland (usually only 1)
what condition can cause total plasma calcium to be low, but ionized calcium to be normal?
hypoalbuminemia
explain the pathogenesis behind chronic renal failure leading to secondary hyperparathyroidism
renal insufficiency leads to decreased phosphate excretion. Increased serum phosphate binds free calcium. Decreased free serum calcium stimulates all four parathyroid glands -> bone resorption
child is born with a cleft palate, recurrent infections, and tetralogy of fallot - what do you expect his serum calcium levels to be? why?
low - he likely has Di George syndrome which results in hypoparathyroidism do to failure of the 3 and 4th pharyngeal pouches to form correctly (where the parathyroid glands develop from)
patient presents with numbness and tingling around the lips. Upon attempting to take their BP you notice muscle spasms - diagnosis?
hypoparathyroidism
patient presents with cataracts, mental retardation, psychosis, seizures and papilledema - diagnosis?
prolonged hypocalcemia
male presents with testicular atrophy, short stature, and short fingers and toes. His serum calcium levels are low - diagnosis? what do you expect his PTH levels to be? why is his calcium low?
pseudohypoparathyroidism (auto dominant)
PTH levels will be high
calcium is low due to end-organ resistance to PTH
30 year old man presents hypophosphatemia - lab work comes back unremarkable. What is the most likely cause?
chronic alcoholism
patient presents with hemolysis and rhabdomyolysis - this is the most serious complication of what disease? name a secondary complication of this presentation
hypophosphatemia
can lead to acute renal failure due to the myoglobin released from the muscle destruction
is phosphate predominantly an intra or extracellular ion? why is this important when handling blood samples?
intracellular
if blood is left sitting around too long in the lab, phosphate will leak out of the cells and result in falsely elevated phosphate levels
what deficiency is common with hypocalcemia and hypokalemia? name some effects of this deficiency
hypomagnesemia
tetany, agitation, ataxia, tremors
person with renal failure later presents with respiratory paralysis and cardiac arrest - what ion imbalance leads to this presentation?
hypermagnesemia
name 3 pancreatic endocrine tumors associated with MEN1. What are the other two organs involved with MEN1?
gastrinoma, insulinoma, glucagonoma
parathyroid, pituitary
give one explanation of why calcium levels might be high, but PTH levels low?
tumor secreting PTHrp (PTH related protein) - its a PTH agonist that has all the same functions as PTH
