First Aid Endocrine Flashcards
In addition to congenital cause, name 3 causes of nephrogenic diabetes
MC congenital (mutation in ADH receptor rendering it nonresponsive)
Others
- Lithium toxicity
- hypercalcemia (chronic Ca over 11)
- demeclocycline: abx that reduces responsiveness of collecting tubules to ADH (used in the tx of SIADH)
Key feature to distinguish primary hyperparathyroidism and familial hypocalciureic hypercalcemia
FHH = defect in calcium sensor in the parathyroid glad => PTH levels are normal despite hypercalcemia
In FHH urine calcium is low, while hypercalciuria in primary hyperPTH
What are the anterior vs. posterior pituitary derived from?
Anterior pituitary derived from oral ectoderm (Rathke pouch)
Posterior pituitary derived from neuroectoderm (connected to hypothalamus by neurophysis)
Describe vitamin D’s impact on serum Ca+2 and PO4-3
Vit D increases intestinal absorption of both Ca and phosphorus
Vit D also stimulates bone breakdown => increases both Ca and PO in serum
Desmopressin
(a) What is it
(b) Indication
Desmopressin = ADH analog
(a) Vasopressin/ADH analog
(b) Used to tx diabetes insipidus
How may IgG4 related disease present w/ thyroid manifestation?
Ridel Thyroiditis = chronic thyroiditis that can be a manifestation of IgG4-related systemic disease
Causes normal thyroid tissue to be replaced by fibrous tissue => dense, fixed thyroid gland (painless goiter)
MC hormone deficiency in congenital adrenal hyperplasia
21 hydroxylase
Analogs of what hypothalamic hormone can be used to treat acromegaly
Somatostatin analog b/c somatostatin inhibits GH and TSH secretion
Clinical presentation of glucagonoma
Very high glucagon: 4 D’s
- dermatitis (necrolytic migratory erythema)
- diabetes (hyperglycemia)
- DVT
- depression
MC cause of acromegaly
(a) Serum marker
Acromegaly = effect of elevated growth hormone in adults, MC 2/2 pituitary adenoma
(a) Elevated IGF-1 (insulin growth factor 1) whose release is stimulated by GH
How does pH affect serum calcium levels
(a) Basic or acidic environment cause muscle cramps/paresthesias?
40% of serum calcium exists bound to albumin, pH can change conformation/affinity of albumin
(a) Increased pH (basic) makes albumin more negative (fewer H+ around) => albumin has higher affinity for Ca2+ => less free (unbound) serum calcium => symptoms of hypocalcemia such as muscle pain, cramps, and paresthesias
Name 4 genetic syndromes w/ pheochromocytomas
Pheo found in
- MEN2A
- MEN2B
- von Hippel Lindau (pheo, b/l renal cell carcinoma, retinal and intracranial hemangioblastoma
- NF1
Name the d/o of vit D deficiency in
(a) Children
(b) Adults
Vit D deficiency in
(a) Children = Rickets
(b) Adults = osteomalacia
Which GLUT receptor is insulin sensitive?
(a) Where are they located?
GLUT4 is insulin sensitive
(a) Insulin sensitive tissues = striated muscle, adipocytes, cardiomyocytes
Clinical features of cretinism (congenital hypothyroidism)
Either thyroid agenesis or iodine deficiency =>
Severe MR (poor brain development) Large protruding tongue Protruding umbilicus (ventral hernia)
MC adrenal tumor in
(a) Adults
(b) Children
MC adrenal tumor in
(a) Adults = pheochoromocytoma (nonmalignant tumor of adrenal medulla)
- p/w episodic HTN
(b) Children = neuroblastoma (malignant tumor of neural crest cells anywhere along sympathetic chain)
Presentation of nonfunctional pituitary adenoma
Mass effect => bitemporal hemianopsia (visual field deficits), headache, symptoms of hypopituitarism
Adrenal medulla
(a) Type of cells
(b) Secretory product
(c) Control system
Adrenal medulla
(a) Cromaffin cells
(b) Secrete catecholamines: epi and norepi
(c) Controlled by sympathetic fibers
Function of the posterior pituitary
Posterior pituitary stores ADH and oxytocin produced by hypothalamus
Name the 3 complications of thyroidectomy surgery
Thyroidectomy complications
- Hoarseness 2/2 damage to recurrent larygneal nerve
- Hypocalcemia 2/2 accidental removal of parathryoid glands
- Airway compromise of b/l transection of superior laryngeal nerve
What type of hypersensitivity is Hashimoto’s thyroiditis?
Hashimoto’s thyroidism = combined type II and type IV hypersensitivity reaction
Type II = 2/2 preformed antibodies (anti-TSH receptor antibodies)
Type IV = direct destruction of thyroid tissue by CD8 (cytotoxic killer T cells) and by CD4-attracted macrophages
Waterhouse-Friderichsen
(a) What is it?
(b) Classic cause
(c) Physical exam
Waterhouse-Friderichsens
(a) Acute adrenal insufficiency 2/2 b/l adrenal hemorrhage/infarct
(b) Classically caused by neisseria meningitides septicemia 2/2 endotoxicemia and DIC
(c) Meningitis and petechiae
Tx of DKA
DKA tx
-IV fluids (b/c pt is wildly dehydrated and hyperosmolar)
-IV insulin (need to get that glucose into the cells!! cells are starving)
-give glucose as well b/c the amount of insulin you’ll need to give, need to prevent hypoglycemia
-K+ b/c as you give insulin this will push K+ into cells and pt will get hypokalemic
-
Distinguish MEN1, MEN2A, MEN2A
MEN 1 (3 P’s): parathyroid carcinoma, pancreatic adenoma (gastrinoma => Zollinger-Ellison), pituitary adenoma (prolactinoma)
Is serum CK elevated in hypo or hyperthyroidism?
Hypothyroidism myopathy
-about 80% of pts w/ chronic hypothyroidism have some muscle/weakness complaint
Elevated CK seen in hypothyroidism
DKA
(a) Triggers
(b) Explain where the ketones come from
DKA
(a) Increased insulin requirement in times of stress: such as infection, MI, drugs, also med noncompliance or undiagnosed
(b) Lipolysis reved up to make more substrate, producing ketones (mostly beta-hydroxybutyrate)
Describe the effect of thyroid hormone on serum cholesterol?
(a) Hypercholesterolemia seen in hyper or hypothryoidism?
Thyroid hormone induces LDL receptor expression => increased cholesterol uptake by cells
(a) So hypercholesterolemia (more chol left in blood) 2/2 reduced LDL receptor expression seen in hypothyroidism
Hyperaldosteronism
(a) Clinical features
(b) pH abnormality
(c) Tx
Hyperaldo: high aldo causes retention of Na+ while dumping up K+
(a) Hypokalemia (=> weakness, tetany), sometimes HTN 2/2 hypernatremia, but often pt is normonatremic 2/2 compensatory diuresis
(b) Metabolic alkalosis
(c) Tx = Spironolactone = aldo receptor antagonist
What part of the hypothalamus produces
(a) ADH
(b) Oxytocin
Hypothalamic nuclei
(a) Supraoptic nuclei contains osmoreceptors that secrete ADH in response to low osmolality
(b) Oxytocin produced in paraventricular nuclei
How does 21-hydroxylase deficiency present in
(a) infancy
(b) childhood
21-hydroxylase (congenital adrenal hyplerplasia): low aldo, low cortisol, high androgens
(a) Infancy presents w/ salt wasting (2/2 low aldo)- extreme thirst and salt cravings, polyuria, hypotension => syncope or orthostatic symptoms
(b) presents w/ precocious puberty in childhood 2/2 high androgens
Can the following agents be used w/o any islet cell function?
(a) Metformin
(b) Glyburide
(c) Exenatide
(d) Sitagliptin
Islet cell function
(a) Metformin can be used in pts w/o islet function b/c it increases glucose uptake peripherally (improves insulin sensitivity)
(b) Glyburide (sulfonylurea) works to stimulate endogenous release of insulin => requires some islet fxn (useless in type 1)
Differentiate primary and secondary adrenal insufficiency
(a) Cause
(b) Clinical presentation
Primary adrenal insufficiency
(a) Due to adrenal damage (ex: Addison’s disease) where adrenal gland isn’t producing cortisol
(b) Presents w/ skin hyperpigmentation (2/2 elevated melanocyte secreting hormone as byproduct of ACTH), hypotension 2/2 hyponatremic volume contraction (b/c low aldo), hyperkalemia (b/c low aldo), metabolic acidosis
Secondary adrenal insufficiency
(a) pituitary reduced release of ACTH (so the adrenal gland itself is fine)
(b) No hyperpigmentation (b/c ACTH is reduced not elevated) and no hyperkalemia/hypotension (b/c aldo secretion is normal since controlled by RAS system)
- so just the symptoms of hypocortisol = fatigue, weakness, GI symptoms, wt loss
DKA ketones
(a) Ketone produced in the highest amount
(b) How ketones are measured
DKA ketones: 3 are produced- acetoacetate, beta-hydroxybutyric acid, and acetone
(a) Beta-hydroxybutyrate is produced in the highest amount
- accounts of the anion gap
(b) First start w/ urine dipstick that uses nitroprusside tablet just to see if there are ketones present, if positive can then do direct beta-hydroxybutyrate serum test to quantify
Diabetes drugs: wt loss of wt gain?
(a) metformin
(b) pioglitazone
(a) Metformin causes modest wt loss
(b) Pioglitazone (PPAR-alpha agonist) can cause wt gain
- also hepatotoxic
What is a craniopharyngioma?
(a) Presenting feature
Craniopharyngioma = Rathke pouch tumor arising from the pituitary stalk
(a) Presenting feature of bitemporal hemianopsia from mass effect causing compression of the optic nerve
What are Hurthle cells?
(a) 2 associated conditions
Hurthle cells = type of thyroid cell
(a) Associated w/ Hashimoto’s thyroiditis (autoimmune hypothyroidism) and follicular thyroid carcinoma
Hashimoto’s thyroiditis
(a) Symptoms- early vs. late in disease course
(b) Physical exam of thyroid
(c) Tx
(d) Increased risk of what malignancy?
Hashimoto’s thyroiditis
(a) In beginning may have hyperthryoid as follicular cells rupture and release contents, then hypothyroid as cells die off and are no longer producing hormone
(b) Moderately enlarged, non-tender gland
(c) Tx = thyroid hormone supplementation
(d) Increased risk of thyroid lymphoma, particularly B-cell non-Hodgkin’s lymphoma
GLUT2 receptors
(a) Function
(b) Location
GLUT2 receptors are low affinity
(a) Fxn to safe glucose for more vital tissues during fasting (so places like adipocytes and hepatocytes don’t uptake glucose during starvation)
- Also fxns to mediate glucose storage in hepatocytes during surplus
- Stimulate insulin release from beta-islet cells
(b) Hepatocytes, kidney, small intestines, beta-islet cells
What cells produce
(a) PTH
(b) Calcitonin
(a) PTH produced by chief cells of the parathyroid gland
(b) Calcitonin produced by parafollicular (C-cells) cells of the thyroid gland
Hormone reduced in congenital obesity
Congenital obesity: decreased levels of leptin
Clinical features of Cushing’s syndrome
(a) Main features
(b) Changes in appearance
Cushing’s syndrome = clinical findings of high cortisol levels
(a) HTN, Flushing, palpitations, wt gain, depression, weakness (2/2 catabolism of muscle for gluconeogenesis)
(b) Buffalo hump, striae, moon facies, truncal obesity, hirsuitism, easy bruising and thin skin (2/2 weakened collagen)
Also: immunosuppression, osteoporosis, hyperglycemia, amenorrhea
Causes of SIADH
Causes of SIADH
- head trauma, CNS disorder
- Ectopic ADH secretion (ex: small cell lung cancer)
- pulmonary disease
- drugs (ex: cyclophosphamide)
Name 3 clinical features of hypocalcemia
- tetancy
- ‘C’hvostek’s sign = ‘c’ontraction of facial muscles when tapped rapidly
- ‘T’rousseau’s sign = carpal sapsm following occlusion of brachial artery (‘t’ricep) w/ BP cuff
MC cause of secondary hyperparathyroidism
Chronic renal failure
-kidneys can’t reabsorb Ca2+ => hypocalcemia causes high PTH secretion
Which hypothalamic hormone secretion is regulated by prolactin
Prolactin regulates GnRH secretion from hypothalamus
-therefore prolactin regulates FSH/LH release (so ovulation/puberty etc)
How to treat pheochromocytoma
Pheo- imperative to first give alpha blockage, then give beta-block prior to tumor resection
-if give beta-block first then unopposed alpha-action can cause hypertensive crisis
How does calcium travel in serum?
Calcium travels
45% ionized (active form)
40% bond to albumin
15% bound to anions
Describe how demeclocycline can help in the tx of SIADH
Demeclocycline (tetracycline abx) works as an ADH antagonist => helps in SIADH
-but if not used in SIADH, can cause nephrogenic DI
Name congenital d/o w/ increased ghrelin production
Ghrelin production pathologically increased in Prader-Willi (paternal chromosome 15 microdeletion)
SIADH
(a) How is euvolemia maintained?
(b) Na+ status
SIADH = too much ADH produced => can’t get rid of excess water and pee out too much salt
End up with euvolemic (b) hyponatremic state
(a) Euvolemia b/c aldo secretion decreased in response to hyponatremia, maintaining a rather euvolemic state
Name 2 malignancies associated w/ hypercalcemia
- Small cell lung cancer- PTHrP secretion
- Multiple myeloma
- CRAB (calcium, renal insufficiency, anemia, bone breakdown)
- IL-1 production activates osteoclast-driven bone resoprtion
Differentiate etiologies of primary and secondary hyperaldosteronism
Primary hyperaldo = adrenal cortex overproducing aldo
-adrenal adenoma = Conn’s
Secondary hyperaldo = overstimulation by overactive RAS system (aka too much renin) 2/2 renal artery stenosis or CHF
-chronically high renin b/c kidneys seeing low flow despite normal/high flow elsewhere
What is a pituitary apoplexy?
(a) Presentation
Pituitary apoplexy = bleeding into an abnormal blood supply of the pituitary region, usually 2/2 underlying pituitary adenoma (often not previously diagnosed)
(a) Presents w/ sudden onset headache and visual symptoms
Location of both steps of vitamin D activation
Vit D –> 25-OH, Vit D in liver
Then activated into 1,25(OH)2, Vit D in kidney
Metformin
(a) Activity
(b) Contraindication
Metformin = first line oral diabetes agent
(a) Exact mechanism unknown, but increases insulin sensitivity
- decreases gluconeogenesis, increases glycolysis and peripheral glucose uptake
(b) Contraindicated in renal insufficiency b/c can cause lactic acidosis
Graves disease treatment
(a) First line meds
(b) Monitor what on these meds
(c) Definitive management
(d) Meds for extra-thyroid manifestation
(f) Which during pregnancy
Treating Graves’ disease (autoimmune hyperthyroid)
(a) Propranolol (beta-blocker) + thionamide (PTU, methimazole) to decrease hormone synthesis
(b) Beware of agranulocytosis w/ PTU
(c) Definitive management = radioactive iodine ablation in general, or thyroidectomy in extreme cases (pregnancy)
(d) Steroids for exophthalmus
(f) Use PTU during pregnancy
- methimazole is a possible teratogen
MC pituitary adenoma
(a) Tx
Prolactinoma
a) Bromocriptine = dopamine agonist (b/c DA inhibits prolactin release
- also transphenoidal resection of pituitary
Features of malignant thyroid nodule
Cold (low 131-I uptake indicating low T3/T4 production)
Bad prognostic factors: men and children (women more likely to have benign cysts or follicular adenoma)
Name 2 things that
(a) Stimulate growth hormone release
(b) Inhibit growth hormone release
(a) GH release stimulated by exercise and sleep
(b) GH inhibited by glucose and somatostatin
What is Addison’s disease?
(a) Name other causes besides AI
(b) Clinical features
(c) Lab findings
Addison’s disease = autoimmune destruction of adrenal cortex => low aldo, cortisol, and androgens
(a) 80% autoimmune, can also be congenital or caused by Tb/AIDS
(b) Clinically:
-low cortisol => weakness, fatigue,
-low aldo => 2/2 hyponatremic volume contraction
-high MSH => hyperpigmentation (MC seen in mouth)
-low androgens => amenorrhea
(c) Labs
Low cortisol => hypoglycemia, eosinophilia/leukocytosis (b/c usually are suppressed)
Low aldo => hyperkalemia, hyponatremia
Metabolic acidosis 2/2 bicarbonate
Sheehan’s syndrome
(a) What happens?
(b) MC initial symptom
Sheehan’s syndrome
(a) Ischemic infarct of the pituitary gland 2/2 hypovolemia/blood loss during childbirth
(b) Failure (or trouble w/) to lactate
- then amenorrhea
- cold intolerance
Effect of glucagon on
(a) Gluconeogenesis
(b) Lipolysis
(c) Ketone production
Glucagon (catabolic hormone) release stimulated by hypoglycemia
(a) Stimulates gluconeogenesis
(b) Stimulates lipolysis (lipid break down)
(c) Stimulates ketone production
What is osteitis fibrosa cystica?
(a) Etiology
Osteitis fibrosa cystica = skeletal d/o caused by (a) primary hyperparathyroidism
- chronically high PTH stimulates osteoclast bone resorption, so calcified supporting structure of bone gets replaced w/ brown fibrous tissue
- see cyst-like brown ‘tumors’ in and around bone
Clinical features of carcinoid syndrome
(a) MC
(b) pulm
(c) cards
Carcinoid syndrome clinically
(a) Diarrhea (2/2 bowel motility) and flushing
(b) Asthmatic wheezing 2/2 bronchospasm
(c) Right sided heart murmurs- ‘TIPS’
Tricuspid insufficiency, pulmonary stenosis
Graves disease
(a) What type of hypersensitivity?
(b) Exact antibodies
(c) Physical exam finding
Graves disease
(a) Type II hypersensitivity due to pre-formed antibodies
(b) Antibodies that stimulate TSH-receptor (TSH stimulating antibodies)
(c) Non-tender, symmetrically and diffusely enlarged thyroid
Which two types of GLUT receptors are present in the brain?
GLUT1 and GLUT3 are in the brain (both are high affinity uptake)
GLUT1 is high-affinity for glucose => saturated at normal levels of serum glucose
GLUT3 only in brain and neurons, high affinity uptake
Insulin’s effect on
(a) TG synthesis
(b) Renal sodium
(c) K+
Insulin
(a) Stimulates TG synthesis
(b) Increases renal sodium excretion
(c) Increases cellular uptake of K+
- hence why giving insulin in hyperkalemia pushes K+ intracellularly
Explain the extra-thyroid manifestations of Graves’ disease
Anti-TSH antibodies also stimulate
(a) Retro-orbital fibroblasts => exopthlamus
(b) Dermal fibroblasts => pretibial myxedema
Embryologic origin of the pyramidal lobe of the thyroid
Pyramidal lobe of the thyroid is persistent from the thyroid’s descent (it’s a remnant of the thyroglossal duct which connects the thyroid’s original and final location)
PTH’s effect on
(a) Bone
(b) Renal Ca2+
(c) Renal PO4-3
(d) Vit D
PTH
(a) Stimulates bone resorption => releases Ca and PO4 into serum
(b) PTH stimulates Ca2+ reabsorption in distal convoluted tubule
(c) PTH inhibits PO4 reabsorption in proximal convoluted tubule
- ‘PTH as phosphate trashing hormone’
(d) PTH stimulates 1-alpha hydroxylase in the kidney to activate more vitamin D
How does MEN1 present?
MEN1 presents w/
- gastric ulcers from gastrinoma (pancreatic islet cell cancer)
- kidney stones from chronic hypercalcemia from PTH (parathyroid cancer)
Tx options for SIADH
SIADH tx
- fluid restriction, IV hypertonic saline
- ADH receptor antagonists = conivaptan, tolvaptan
- deemeclocycline
Explain how deficiency in an enzyme to make cortisol causes bilateral adrenal enlargement
Low cortisol gives negative feedback to ACTH, high ACTH secretion further stimulates both adrenal glands (hyperplasia)
Tx for Addison’s disease
Addison’s = autoimmune destruction of adrenal cortex => low aldo, cortisol, and androgens
Tx by replacing mineralocorticoid and glucocorticoid (and sex hormones as needed), and by providing stress-dose steroids when needed (ex: severe illness, surgery)
How to differentiate primary and secondary hyperparathyroidism
Primary hyperparathyroidism (parathyroid adenoma or hyperplasia) = high PTH, high Ca, low PO4
Secondary hyperparathyroidism (chronic renal disease) = low Ca2+ and high PO4 causes high PTH
What differentiates toxic multinodular goiter from iodine deficiency thyroid hyperplasia?
Toxic multinodular goiter is when the TSH receptors mutate (increased risk from iodine-deficiency induced hyperplasia) to be constitutively active => TSH receptors no longer depend on signal => hyperthyroidism
What is Cushing’s disease?
(a) Name two other causes of Cushing’s syndrome
Cushing’s disease is specifically hypercortisol 2/2 ACTH secreting pituitary adenoma
(a) While the constellation of symptoms caused by high cortisol can also be induced by
- exogenous corticosteroids (MC)
- primary adrenal adenoma/hyperplasia/carcinoma
Explain how high cortisol levels can lead to a reactivation of Tb
Cortisol inhibits the inflammatory and immune response by inhibiting leukotriene, prostaglandin, and IL-2 production
Inhibited immune response = more susceptible to Tb and candidiasis reactivation
Function of ADH
ADH upregulates aquaporin channels on principle cells of renal collecting duct => increase water reabsorption by the kidneys
Released in response to hypothalamus sensing high serum osmolality
Name the 6 hormones secreted by the anterior pituitary
Anterior pituitary 'FLAT PiG' FSH LH ACTH TSH Prolactin Growth hormone
Are the following found in hyper or hypo- thyroidism?
(a) Constipation
(b) Wt loss
(c) Hyperreflexia
(d) Diarrhea
(e) Facial/peri-orbital myxedema
(f) Pretibial myxedema
(g) Osteoporosis
(h) HTN
(i) Cold, dry skin
(j) CP/palpitations
(a) Constipation = hypothyroid
(b) Wt loss = hyper
(c) Hyperreflexia = hyper
(d) Diarrea = hyper
(e) Facial/peri-orbital myxedema = hypo
(f) Pretibial = hyper
(g) Osteoporosis = hyper
(h) HTN in both
- diastolic HTN in hypo, systolic HTN is hyper
(i) Cold dry skin in hypo
- vs warm moist skin in hyper
(j) CP/palpitations in hyper
How does thyroid hormone increase metabolic rate
Thyroid hormones stimulate activity of Na/K ATPase => increasing metabolic rate
Diabetes insipidus
(a) Main clinical features
(b) Treatment: central vs. nephrogenic
DI
(a) Polyuria and polydipsia
(b) Tx
- central = hydration and desmopressin (ADH analog)
- nephrogenic = HCTZ, amiloride (K+ sparing diuretic), hydration, indomethacin
Pt p/w enlarged and tender neck w/ fever, malaise, and myalgia 1 week s/p URI
(a) Dx
(b) Tx
(a) Subacute thyroiditis (de Quervain’s thyroiditis) = painful acute enlargement of thyroid gland s/p viral infection
(b) Tx = just pain management (NSAID)
- self limited and rarely recurs => don’t need to treat the thyroid symptoms (early hyperthyroidism, late hypothyroid)
42 yo obese F p/w diastolic HTN and menstrual irregularities
- On exam: full, plethoric face w/ facial hair, truncal obesity, and purple stria around the abdomen
- Labs: Hb 18, WBC 18k
- Normal CXR
(a) Dx?
(b) MC cause
Dx = Cushing's syndrome 2/2 hypercortisolism -wt gain -leukocytosis 2/2 marginalization by cortisol -striae 2/2 weakening of collagen
(a) MC cause = pituitary adenoma secreting ACTH (Cushing’s disease)
- but can be 2/2 exogenous steroids, ectopic ACTH production (ex: small cell lung cancer), adrenal hyperplasia/carcinoma
Why is DKA so dangerous?
aka what are the serious complications
Complications of DKA
- mucormycosis (rhizopus) infection: thrive in ketoacidotic state
- cerebral edema
- arrhythmias 2/2 electrolyte abnormalities
- HF due to hypovolemia
Neuroblastoma
(a) Presentation
(b) Clinical hallmark
(c) Associated genetic issue
(d) UA finding
(e) Tx
Neuroblastoma = malignant adrenal tumor in kids
(a) Unilateral, off-centered irregular abdominal mass in children under 4 yoa
- while Wilm’s tumor is smooth and midline)
(b) Opsoclonus-myoclonus = dancing eyes, dancing feet
(d) Elevated HVA (DA breakdown product) and VMA (epi and norepi breakdown product) in urine
(e) Tx = surgical removal
What are the adrenal cortex and adrenal medulla derived from?
Adrenal cortex derived from mesoderm
Adrenal medulla derived from neural crest cells (forms neuroblastoma in children, secretes epi and norepi)
2 consequences of persistent thyroid gland tissue
- pyramidal lobe of the thyroid
2. thyroid duct cyst
Exact mechanism of sulfonylureas
Sulfonyulreas (glyburide, glimepiride) close K+ channels on beta-islet cell membranes => depolarizing the cell (causing Ca2+ influx) => induces insulin release
Useless in type 1 b/c needs functional beta-islet cells, only acting to stimulate endogenously produced insulin (doesn’t work peripherally to improve sensitivity)
Explain iatrogenic adrenal insufficiency
Tertiary/iatrogen adrenal insufficiency: abrupt withdrawal from exogenous steroids
This is why you need to taper prednisone- exogenous corticoids suppress ACTH release => adrenal gland isn’t being stimulated to make any
Fxn of calcitonin
Calcitonin works to counteract PTH, doesn’t have much of a function in overall Ca2+ homeostasis
-inhibits bone resorption
What is thyroid storm?
a) Clinical presentation
(b) Tx (3 Ps
Thyroid storm = large release of thyroid hormone that causes systemic effect
(a) Hyperpyrexia (like over 104F, 40C, super high), tachyarrhythmia, N/V, coma, hypotension
- what can be fatal is the arrhythmias
(b) Tx:
- Propranolol (beta-blocker) for HR
- PTU to decrease hormone synthesis
- Prednisone: decreases peripheral conversion of P4 to P3
- Anti-pyretic, fluids, supportive measures (cooling blanket)
Name 3 electrolytes whose levels can stimulate PTH secretion
PTH release stimulated by
- hyperphosphatemia (high PO4)
- hypocalcemia (low Ca)
- hypomagnesemia (low Mg)
Compare tonic and pulsatile GnRH
Tonic GnRH suppresses the HPA axis
While pulsatile GnRH (yay) leads to puberty and fertility (by correct secretion of FSH/LH)
Primary energy source and source during starvation
(a) RBC
(b) Brain
(a) RBC don’t have mitochondria => can’t do aerobic glycosis so only can use glucose for energy (even in starvation)
(b) Brain primarily uses glucose, can use ketones during starvation
Differentiate central from nephrogenic diabetes insipidus
(a) ADH level
(b) Urine specific gravity
(c) Serum osmolality
(d) Test used to differentiate
Central DI = brain (hypothalamus) not making ADH. Nephrogenic DI when sufficient ADH is produced by kidneys are not responsive to it (ex: mutated receptor)
(a) ADH low is central, ADH normal in nephrogenic
(b) Urine SG low in both b/c peeing out all water (SG under 1.006)
(c) Serum osmolality high in both (over 290) b/c can’t retain water
(d) Give ADH analog (desmopressin acetate) and see if urine osmolality increases
- Uosm increases = central, Uosm nonresponsive (doesn’t increase) = nephrogenic
Is it the glucose or the insulin that is harmful to the fetus in maternal diabetes?
Glucose can cross the placenta while insulin can’t. Problem is that high maternal glucose causes the fetus to overproduce its own insulin
Growth hormone
(a) Intermediate molecule
(b) Effect on diabetes
(c) Frequency of release
Growth hormone
(a) GH stimulates linear growth and muscle mass thru IGF-1 (somatomedin)
(b) Growth hormone is diabetogenic, it stimulates insulin resistance
(c) GH released in pulses in response to GHRH
What differentiates toxic vs. nontoxic thyroid goiter?
Nontoxic goiter meaning the tissue is dependent on TSH stimulation, hyperplasia is 2/2 T3/T4 deficiency
-compensatory hyperplasia from low thyroid hormone levels systemically
While toxic goiter is when the hyperplasia becomes independent of TSH
DKA clinically
(a) Symptoms
(b) Signs
(c) Odor of breath
Clinical picture of DKA
(a) Abdominal pain, N/V
(b) Physical exam signs
- Kussmal respirations 2/2 metabolic acidosis
- delirium
- dehydration (2/2 polyuria and high serum osmolality from hyperglycemia), coma
(c) Fruity breath odor 2/2 exhaled acetone (one of three ketone bodies that accumulate)
Explain how cortisol can cause an increase in BP
Cortisol upregulates alpha1 receptors on arterioles to increase their sensitivity to epi and norepi
Give examples of each type of insulin
(a) Rapid acting
(b) Short acting
(c) Intermediate acting
(d) Long acting
Insulinnnn
(a) Rapid acting = aspart (Novolog), glulisine, lispro (Humalog): work in like 15 mins
(b) Short acting = regular insulin (Humulin, novolin)
(c) Intermediate acting = NPH: works in 1-2 hrs
(d) Long acting = glargine (Lantus) and detemir (Levemir)
Describe how the following impact prolactin release
(a) bromocriptine
(b) hypothyroidism
Prolactin release
(a) Bromocriptine is a dopamine agonist, dopamine inhibits prolactin release => use bromocriptine to treat prolactinoma medically
(b) TRH increases prolactin secretion, so hypothyroid => high TSH => galactorrhea/amenorrhea
Changes in thyroid hormone levels w/
(a) OCP use
(b) hepatic failure
(c) PTU
Thyroid hormone: free levels decrease it TBG (thyroid binding globulin) concentration increases
(a) OCPs/estrogen increase TBG synthesis => hypothyroid (b/c less free thyroid hormone since more is bound)
(b) Estrogen breakdown occurs in the liver => during hepatic failure estrogen levels rise => increased TBG (hypothyroid)
(c) PTU inhibits peroxidase (oxidizes I- –> I2) and enzyme that combines MIT and DIT to form T3/T4 in lumen => PTU decreases thyroid hormone synthesis
- used in Graves
Explain the lab findings in DKA
(a) CBC abnormality
(b) pH abnormality
(c) Explain K+ levels
DKA lab abnormalities
(a) Leukocytosis 2/2 stress-induced cortisol release
(b) Metabolic acidosis 2/2 accumulate of ketones and lactate
(c) Need insulin to push K+ into cells, also K+ exchanged out for extra H+ to get into cells => serum hyperkalemia but intracellular K+ deficit
Clinical features of hyperparathyroidism
High PTH => hypercalcemia, hypercalciura, hypophosphatemia
Symptoms of hypercalcemia: “stones, bones, groans, psychiatric overtones”
- kidney stones 2/2 hypercalciuria
- bone weakening due to loss of calcified supporting structures
- constipation
- depression
Pt p/w diarrhea and facial flushing, murmur of tricuspid regurg: describe how you would screen for carcinoid syndrome
Carcinoid syndrome
- first can screen urine for 5-HIAA (breakdown product of 5-HT)
- then CT scan abdomen for tumor
Pharmacologic tx of hyperparathyroidism
Treating hypercalcemia: give tons of fluids
- furosemide to increase renal Ca excretion
- bisphosphonates
- Cinacalcet sensitizes the CaSR (calcium sensing receptor) in the parathyroid gland => works to make parathyroid cells more sensitive to high serum calcium and decrease PTH production
Tx for carcinoid syndrome if tumor is non-resectable
Octreotide = somatostatin analog
-somatostatin decreases 5-HT production
Appetite regulation
(a) Which hormone stimulates appetite
(b) Which hormones reduces appetite
Appetite regulation
(a) Appetite stimulated by ghrelin
(b) Appetite suppressed by leptin
Pheochromocytoma
a) What is it?
(b) Clinical features (5 P’s
(c) Rule of 10s
Pheo
(a) Nonmalignant tumor of adrenal medulla that secretes epi, norepi, and dopamine
(b) Episodic symptoms:
Pressure (HTN)
Palpitations
Pain (headache)
Perspiration
Pallor
(c) 10% malignant, 10% bilateral, 10% extra-adrenal (bladder, organ of Zuckerkandl), 10% calcify, 10% in children (MC 40-50yoa)
2 functions of prolactin
(a) Use this to explain the clinical presentation of prolactinoma
Prolactin
- stimulates lactation
- inhibits GnRH release to inhibit ovulation and spermatogenesis
(a) Galactorrhea and loss of libido
Explain why a well controlled schizophrenic pt may exhibit galactorrhea
Many antipsychotics are dopamine antagonists, dopamine is needed to inhibit prolactin so w/o DA there is hyperprolactinemia => galactorrhea
Classic cause of Waterhouse-Friederichsen
Neisseria meningitides septicemia causing endotoxic shock and DIC => b/l adrenal hemorrhage and infarct
MC malignancy of the small intestines
Carcinoid tumor (neuroendocrine cells)
If MEN2A and MEN2B have different clinical features, why aren’t they separated into MEN2 and MEN3…?
B/c both caused by (or associated with) RET proto-oncogene
-therefore both have medullary thyroid carcinoma and pheo
MEN2A: + parathyroid cancer
MEN2B: + marfanoid body habitus, mucosal neuromas
Causes of hypoparathyroidism
(a) Genetic
(b) Iatrogenic
(c) Electrolyte abnormality
Hypoparathyroidism
(a) DiGeorge syndrome- congenital absence of parathyroid glands
(b) Accidental surgical removal during thyroidectomy
(c) Hypomagnesmia
Test used to differentiate Cushing’s disease vs. ectopic ACTH production
High dose dexa test
- if cortisol suppressed w/ high-dose dexa = Cushing’s disease = Cushing disease (ACTH secreting pituitary adenoma)
- if cortisol not suppressed by high-dose dexa = Ectopic ACTH production (ex: small cell lung cancer): ACTH source is resistant to negative feedback by dexa
Lab findings of pt w/ insulinoma
Elevated C-peptide, hypoglycemia
Does type 1 or 2 diabetes have a stronger genetic predisposition?
Type 2 has relatively strong (90% concordance in identical twins), while type 1’s genetic association is relatively weak (50% concordance in identical twins)
Possible toxicity of levothyroxine
Levothyroxine (T4) which is then converted to T3 (active form) can cause tachycardia, heat intolerance, tremors, arrhythmias
4 lesions in von-Hippel-Lindau syndromef
Von-Hippel Lindau
- b/l renal cell carcinoma
- pheochromocytoma
- retinal hemangioblastoma
- intracranial hemangioblastoma
Name two negative consequences of high cortisol levels
Cortisol causes decreased bone formation, increased insulin resistance (diabetogenic)
-also can be immunosuppressing (but sometimes this is what we use it for…)
Carcinoid syndrome
(a) Cause
(b) How does location of carcinoid tumor determine if pt gets syndrome or not
Carcinoid syndrome- clinical features of high serotonin 2/2
(a) Carcinoid tumor = neuroendocrine cell tumor that secretes tons of 5-HT
(b) Location, location, location
- carcinoid tumors only in the GI tract (w/o mets) don’t cause carcinoid syndrome b/c all the 5-HT they secrete gets metabolized during first pass metabolism thru the liver
- therefore causes carcinoid syndrome if blood drainage doesn’t go thru portal system => liver mets or extra-GI carcinoid tumors
Screening test used for Cushing’s syndrome
(a) Next step if screening test is positive
Screening test = low dose dexa test- this should suppress cortisol levels
Positive if low-dose dexa doesn’t suppress cortisol levels (aka the synthetic cortisol doesn’t inhibit ACTH or ACTH isn’t controlling cortisol production)
(a) If positive, measure serum ACTH
- Low serum ACTH = adrenal tumor
- High serum ACTH: use high-dose dexa test to differentiate Cushing disease (ACTH secreting pituitary adenoma) from ectopic ACTH production
