Term
| In a pediatric patient with T2DM, what should their drug regimen include? |
|
Definition
Metformin only
NO sulfonylureas
+/- insulin |
|
|
Term
| In an old patient with cirrhosis and CHF with T2DM, drug regimen? |
|
Definition
Best treatment = INSULIN
No metformin because of predisposition to lactic acidosis |
|
|
Term
| #1 cause of adrenal insufficiency worldwide? |
|
Definition
|
|
Term
| Best test for thyroid dysfunction? |
|
Definition
|
|
Term
| What would urine look like for PRIMARY HYPERALDOSTERONISM (Conn's)? |
|
Definition
|
|
Term
MIS is released by ______ cells
Testosterone is released by _______ cells |
|
Definition
MIS = Sertoli
Testosterone = Leydig |
|
|
Term
| What is the best test to rule out pheochromocytoma? |
|
Definition
Plasma metanephrines, but not always available
Most practical = urine fractionated metanephrines + catechol |
|
|
Term
| What kind of drugs can be used to suppress GH-secreting tumors? |
|
Definition
Octreotide - somatostatin analog; decrease GH release
Pegvisomant - GH-R antagonist |
|
|
Term
| An increase in _______ secretion will lead to an increase in PRL secretion |
|
Definition
| TRH - also stimulates PRL release from pituitary |
|
|
Term
| Paget's disease a what kind of bone disease? |
|
Definition
| "Localized disorder of bone remodelling" |
|
|
Term
| What happens to insulin requirements in the 1st trimester of pregnancy? |
|
Definition
|
|
Term
| What kind of tumour responds best to medical treatment? |
|
Definition
Prolactinoma
Rx - bromocriptine, cabergoline, quinagolide |
|
|
Term
| Why do GnRH secretions decrease after birth? |
|
Definition
| Because of GABA inhibition of GnRH neutrons |
|
|
Term
| Mechanism of action of the thioamides (MMI, PTU) |
|
Definition
Inhibit TPO function - decreased iodination of Tyr
Blocks coupling with MIT and DIT - decrease in free T4/T3 |
|
|
Term
| #1 cause of hypothyroid in N. America? |
|
Definition
| Hashimoto's - anti-TPO Ab's |
|
|
Term
| How to differentiate hyperthyroid vs. thyrotoxicosis, viral etc.? |
|
Definition
|
|
Term
| Types of AA Derivative hormones? |
|
Definition
Catecholamines - E, NE, DA
Thyroid hormones - Tyr derivatives |
|
|
Term
| Parvicellular neurons release trophic hormones into ______ pituitary |
|
Definition
ANTERIOR
Parvicellular = short neutrons, release trophic hormones into hypophyseal portal system |
|
|
Term
| Magnocellular neurons act on _____ pituitary |
|
Definition
POSTERIOR
Magnocellular = longer, release hormones directly onto posterior; from PVN, SON |
|
|
Term
| PRL is inhibited by ____ and stimulated by _____ |
|
Definition
Inhibition = DA
Stimulation = TRH |
|
|
Term
| Where is thyroglobulin (Tg) located in the thyroid gland? |
|
Definition
|
|
Term
| Iodine Trap = which two components? |
|
Definition
1) NIS = Na, I symporter on basolateral
2) Pendrin = I transporter on apical membrane |
|
|
Term
| What are the two functions of TPO? |
|
Definition
1) Iodination of Tyr residues
2) Coupling of Tyr residues
Occurs at microvillus surface of follicular cell |
|
|
Term
| 3 actions of TSH on follicular cells... |
|
Definition
1) Increased NIS activity - more iodine into cell
2) Increased production of Tg
3) Increased TPO activity - more iodination and coupling |
|
|
Term
| In the blood _____% of thyroid hormone is bound to TBG |
|
Definition
|
|
Term
Transthyretin (TTR) binds how much T4 vs. T3
HSA binds how much T4 vs. T3 |
|
Definition
TTR - 20% T4, 5% T3
HSA - 20% T3, 5% T4 |
|
|
Term
| How much T4 vs. T3 is secreted? |
|
Definition
90% T4, 10% T3
But T3 is 10x more potent; T4 has longer half life |
|
|
Term
| Deiodinases - D2 vs. D3 function |
|
Definition
D2 is activating - converts T4 to T3 in target cells
D3 is inactivating - converts T4 to rT3, T3 to T2 |
|
|
Term
| Thyroid hormone receptor is located in |
|
Definition
| CYTOPLASM, but acts as a NUCLEAR RECEPTOR |
|
|
Term
|
Definition
1) Early development - need for neural and GH development
2) Increase mitochondrial activity - increase BMR
3) Increase Na/K ATPase - increase metabolism of cells
4) Increase transcription of metabolism ENZ
5) Permissive for induction of PRL, GH, surfactant, NGF |
|
|
Term
| All active thyroid hormones are in which enantiomeric form? |
|
Definition
L-enantiomers
L-thyroxine, for example |
|
|
Term
Synthetic T4 = ?
Synthetic T3 = ? |
|
Definition
T4 = Levothyroxine (Synthroid)
T3 = Liothyronine (Cytomel)
T4>T3 because more predictable, slower metabolism
Only use T3 when rapid action needed - myxoedema coma |
|
|
Term
|
Definition
| Reduction in thyroid hormone levels due to ingestion of large iodine load; increased accumulation of intracellular iodine leads to inability to form thyroid hormone properly, impaired transport (iodine limits its own transport) |
|
|
Term
| Serious adverse effects of MMI, PTU? |
|
Definition
Agranulocytosis
Hepatitis
Arthralgia
*Fulminant hepatitis is a risk |
|
|
Term
|
Definition
Opposite of WC Effect
When large iodine load is given to someone with toxic nodules, subclinical Graves' or autonomous thyroid tissue - end up with hyperthyroid/thyrotoxicosis
Iodine load induced hyperthyroidism |
|
|
Term
| What type of iodine is used in radioactive ablation? |
|
Definition
Iodine-131
*iodine-123 is used only for iodine scans, due to short half life |
|
|
Term
| Which two anions can compete with iodine for transport into thyroid cells? |
|
Definition
| Perchlorate and thiocyanate; because they have similar hydrated radius to iodide anions |
|
|
Term
| Which vegetables have a compound that mimics thioamide functions? |
|
Definition
| Kale, turnips, cabbage - have goitrin, mimics thioamides; can cause goitres in rabbit |
|
|
Term
| What is the most sensitive test for thyroid function? |
|
Definition
|
|
Term
| What happens to BP in hyper vs. hypothyroid? |
|
Definition
Hyper - get systolic HTN - wide pulse pressure
Hypo - get diastolic HTN - narrow pulse pressure |
|
|
Term
| What are the general eye symptoms of thyrotoxicosis vs. Graves' exophthalmos? |
|
Definition
General - lid lag, lid retraction, increased stare
Graves - proptosis, periorbital edema, diplopia |
|
|
Term
| #1 cause of hyperthyroid = ? |
|
Definition
Graves' disease
More common in women, eye symptoms may precede dx |
|
|
Term
| Why do you get exophthalmos in Graves'? |
|
Definition
| Anti-TSH-R Abs cross react with extra ocular muscles and retro-orbital CT - maturation of fat cells and mucoid production; stimulate fibroblast proliferation |
|
|
Term
| What happens to the thyroid gland in Graves'? |
|
Definition
| Becomes DIFFUSELY ENLARGED |
|
|
Term
| What happens to the thyroid gland in Graves'? |
|
Definition
| Becomes DIFFUSELY ENLARGED |
|
|
Term
| What happens to the thyroid gland in Graves'? |
|
Definition
| Becomes DIFFUSELY ENLARGED |
|
|
Term
| 3 histological features of Graves' disease? |
|
Definition
Hyperplastic follicles
Papillary projections
Scalloping of the colloid |
|
|
Term
| When are TBII tests useful for Graves'? |
|
Definition
TBII = Thyrotropin Binding Inhibitory Ig's
Useful in pregnancy because you cannot do a RAI U&S due to damage to fetal thyroid
**NEED to Dx Graves' in pregnancy because it can damage fetal thyroid as well |
|
|
Term
| Most common treatment for Graves' in N. America vs. Europe? |
|
Definition
N. America = radioactive ablation
Europe = thyroidectomy |
|
|
Term
| How to differentiate between Graves' and thyroiditis on RAI U&S? |
|
Definition
Graves = see diffuse spread of RAI throughout thyroid
Thyroiditis = see very little uptake due to poor uptake; appears as "no thyroid present" |
|
|
Term
|
Definition
Wait & watch
Rx symptoms - B-blockers (for palpitations, HTN) |
|
|
Term
| In what condition is there slowed relaxation phase of deep tendon reflexes? |
|
Definition
HYPOTHYROID
Cannot get enough ATP, need ATP for uncoupling of filaments; have brisk contraction, slow return to rest |
|
|
Term
| What condition is also known as chronic lymphocytic thyroiditis? |
|
Definition
| Hashimoto's thyroiditis - #1 cause of hypothyroid in N. America |
|
|
Term
| What are 3 histological features of hashimoto's thyroiditis? |
|
Definition
1. Chronic inflammatory cells - lymphocytes, plasma cells
2. Hurthle cells - epithelial cells w/ granular cytoplasm
3. Fibrosis |
|
|
Term
| Acutely, what happens to the thyroid gland in Hashimoto's thyroiditis? |
|
Definition
| Acute enlargement, rubbery, nodular |
|
|
Term
| What is the #1 thyroid disease in N. America? |
|
Definition
| Simple, multinodular sporadic goitre |
|
|
Term
| What is the #1 thyroid disease in N. America? |
|
Definition
| Simple, multinodular sporadic goitre |
|
|
Term
| Enlargement of the thyroid in multi nodular goitre vs. Graves? |
|
Definition
Goitre = ASYMMETRIC ENLARGEMENT
Graves' = SYMMETRIC ENLARGEMENT (diffuse) |
|
|
Term
| What test do you not use to dx multi nodular goitre? |
|
Definition
|
|
Term
Always biopsy thyroid nodule if > ___ cm
Do not need to biopsy if < ___ cm |
|
Definition
If > 2 cm then FNAB
If < 1 cm then no |
|
|
Term
| Only do RAI U&S if you see low ____ with multi nodular goitre? |
|
Definition
| LOW TSH - suspect hot nodule then |
|
|
Term
| What is the most common type of thyroid cancer? |
|
Definition
| Papillary carcinoma (80% of all follicular cell cancers) |
|
|
Term
| What is the most fatal type of thyroid cancer? |
|
Definition
| Anaplastic carcinoma (follicular cell cancer) |
|
|
Term
| What is diagnostic of a papillary carcinoma of the thyroid? |
|
Definition
NUCLEAR FEATURES on histology
- Enlargement, notched membranes, inclusions, clear nuclei
- Psammoma bodies - concentric calcifications |
|
|
Term
| What condition are Psamomma bodies seen in? |
|
Definition
Seen in PAPILLARY CARCINOMA of the thyroid
Psammoma = concentric intracellular calcifications |
|
|
Term
| Can FNAB separate adenoma from follicular carcinoma? |
|
Definition
NO
Dx is based on presence or absence of vascular invasion through capsule
- Adenoma = no invasion
- Carcinoma = invasion |
|
|
Term
| Majority of medullary thyroid cancers are familial or sporadic? |
|
Definition
|
|
Term
| What is the lab diagnosis of medullary thyroid cancer? |
|
Definition
|
|
Term
| 99% of body Ca2+ is located where? |
|
Definition
|
|
Term
| What two cell types are present in PT glands? |
|
Definition
Chief cells - secrete PTH in response to low Ca2+
Oxyphil cells - more mitochondria, for energy production
*Cells arranged into nests via fibrotic tissue |
|
|
Term
|
Definition
1) Increased osteoclast activity
2) Increased Ca2+ renal reabsorption, decreased phosphate reabsorption
3) Increased 1 alpha hydroxylase activity - more calcitriol |
|
|
Term
| Where do we get Vit D2 vs. D3? |
|
Definition
D2 - from plants
D3 - from animals, from skin (cholecalciferol) |
|
|
Term
| Primary hyperparathyroid is almost always due to? |
|
Definition
Benign adenomas of the PT glands
2nd most common = idiopathic PT hyperplasia |
|
|
Term
| Secondary hyperparathyroidism is almost always due to? |
|
Definition
Renal deficiencies (chronic renal failure)
Secondary due to low levels of calcitriol |
|
|
Term
| What are calcium levels in primary vs. secondary hyperparathyroidism? |
|
Definition
Primary - HYPERCALCEMIA
Secondary - NO hypercalcemia because not enough activated Vit D (cannot absorb Ca from gut) |
|
|
Term
| What are two disorders of the PTH receptor? |
|
Definition
Jansen's - activating mutation of PTH-R; dwarfism from bone resorption
Blomstrand's - inactivating mutation of PTH-R; advanced bone maturation, early death |
|
|
Term
| What is Familial Hypocaluric Hypercalcemia? |
|
Definition
FHH due to impaired Ca2+ sensing receptor mutation (activating mutation)
Get more PTH for any given level of Ca2+ in body
Are hypercalcemic, but low Ca2+ in urine |
|
|
Term
| What is pseudohyperparathyroid? |
|
Definition
Humoral Hypercalcemia of Malignancy
Due to PTHrP (peptide; cross reactive with PTH-R)
Produced in prostate cancers, breast cancers, lymphomas, multiple myeloma, leukemias |
|
|
Term
| PT Glands develop from the _________ |
|
Definition
Branchial pouches
3rd pouch - inferior PT glands
4th pouch - superior PT glands |
|
|
Term
| What is the normal range of serum calcium? |
|
Definition
|
|
Term
| Ca2+ is tightly regulated by which 3 factors? |
|
Definition
|
|
Term
|
Definition
Increased Ca2+ absorption from gut
Increase bone resorption (w/ PTH)
Increase Ca2+ and phosphate reabsorption from kidney (opposes PTH effects on phosphate) |
|
|
Term
| When is Vit D toxicity a real threat? |
|
Definition
In patients on DIGOXIN
Recall that Digoxin inhibits Na/K ATPase; cause Na+ accumulation in cell; increased intracellular Ca2+
Vit D can exacerbate this accumulation |
|
|
Term
| What are some INHIBITORS of BONE RESORPTION? |
|
Definition
Bisphosphonates - inhibit osteoclasts
SERMs - estrogen receptor modulators
RANK-L inhibitors - denosumab |
|
|
Term
| How much of Ca2+ is ionized vs. bound? |
|
Definition
50% ionized
40% bound to albumin; 10% bound to other |
|
|
Term
| Albumin, Ca2+ correction? |
|
Definition
| For every 1 g/L change in albumin (normally 40), increase Ca2+ by 0.02 mM |
|
|
Term
| #1 cause of hypercalcemia? |
|
Definition
Hyper PTH (primary), usually incidental finding
#2 cause = malignancy |
|
|
Term
| What happens to PTH levels in Hypercalcemia of Malignancy? |
|
Definition
LOW
Because it is the PTHrP stimulating PTH-R, so lots of negative feedback to keep PTH low |
|
|
Term
| Rx of Acute Hypercalcemia? |
|
Definition
Fluids + diuresis (loop + K+ replace)
Bisphosphonates - pamidronate
Calcitonin
Prednisone |
|
|
Term
| What two signs are seen in hypocalcemia? |
|
Definition
Chvostek - CN VII; look at corner of mouth and eye ipsilaterally
Trousseau's - inflate BP cuff; get carpal spasm sustained |
|
|
Term
| What features are indicative of PTH deficiency vs. PTH resistance? |
|
Definition
Deficiency = low Ca2+, high PO4, normal ALP, low PTH
Resistance = low Ca2+, high PO4, HIGH PTH
- Resistance; inherited; short, round facies, short metacarpals and metatarsals |
|
|
Term
| PTH deficiency vs. PTH resistance vs. Vit D deficiency |
|
Definition
PTH deficiency - low Ca, high PO4, normal ALP, low PTH
PTH resistance - low Ca, high PO4, high PTH
Vit D deficiency - low Ca, low PO4, high ALP, high PTH |
|
|
Term
| Osteomalacia is a defect in ___________ |
|
Definition
| BONE MATRIX MINERALIZATION - get soft bones |
|
|
Term
| #1 etiology of osteomalacia? |
|
Definition
|
|
Term
| What are Vit D requirements? |
|
Definition
1-70 yo = 600 IU
70+ yo = 800 IU |
|
|
Term
| What are Looser-Milkman pseudo fractures? |
|
Definition
| Micro fractures seen on XR in OSTEOMALACIA |
|
|
Term
| Temperature of affected bones in Paget's Disease? |
|
Definition
| WARMER - due to increased vascularity |
|
|
Term
| What is a urinary marker of bone resorption? What condition can this be useful in? |
|
Definition
Marker = hydroxylated Proline
Elevated in PAGET'S |
|
|
Term
| What drug can inhibit osteoclast activity? |
|
Definition
| BISPHOSPHONATES ("----dronates") |
|
|
Term
| What is the Ca2+ threshold for fracture? |
|
Definition
| << 500 g Ca2+ (bone mass) |
|
|
Term
|
Definition
RANK-L released by osteoblasts, initiates osteoclast maturation
Normally bound and inhibited by estrogen; that's why increased osteoporotic risk after menopause |
|
|
Term
| What does long term bisphosphonate do to bone mineralization? |
|
Definition
|
|
Term
|
Definition
| INCREASES RANK-L release from osteoblasts to increase osteoclast # and function |
|
|
Term
| Most useful imaging test for osteoporosis? |
|
Definition
| Bone Densitometry - DEXA (Dual XR Absorptiometry) |
|
|
Term
| What type of osteoporosis occurs post-menopause? |
|
Definition
|
|
Term
|
Definition
| Monoclonal Ab against RANK-L |
|
|
Term
| Intermittent PTH use (teriperatide) can be used in... |
|
Definition
| Osteoporosis - use it to increase osteoblast activity - increase bone mass |
|
|
Term
| Cell type that makes catecholamines? |
|
Definition
| CHROMAFFIN cells in adrenal medulla |
|
|
Term
| Main functions of CORTISOL? |
|
Definition
Gluconeogenesis
Lipid and muscle catabolism
GLUT4 inhibition (block insulin effects)
Enhanced lyte/H2O balance - cross-react w/ mineralocorticoid receptor |
|
|
Term
| What type of receptor is ACTH-R in adrenal cortex? |
|
Definition
GPCR
Increased activity CEH to elevate cholesterol levels; increased cholesterol transport into mitochondria (via StAR) |
|
|
Term
| What is the treatment for Paget's disease? |
|
Definition
ABC
Analgesia for pain
Bisphosphonates for bone mineralization
Calcitonin for shits and giggles |
|
|
Term
| What is the largest receptor of steroid hormones? |
|
Definition
Mineralocorticoid-R
Get cross reactivity with cortisol |
|
|
Term
| Where is the glucocorticoid receptor expressed? |
|
Definition
|
|
Term
|
Definition
Inactivates cortisol in the kidneys, activates it in the liver
Isoform 1 = liver; isoform 2 = kidneys |
|
|
Term
| 11BHSD mutations lead to... |
|
Definition
Syndrome of Apparent Mineralocorticoid Excess
Due to cortisol cross-reactivity with mineralocorticoid-R
Also caused by black liquorice - inhibits ENZ as well |
|
|
Term
| What type of 11BHSD is located in the placenta? |
|
Definition
Isoform 2 - inactivates cortisol to cortisone
Important to prevent growth restriction, pre-eclampsia |
|
|
Term
|
Definition
Steroid inhibitor
Used to treat Cushing's
Normally anti fungal, but also can inhibit adrenal and gonadal steroidogenesis by inhibiting P450 ENZ |
|
|
Term
|
Definition
| Causes destruction of adrenal cortex tissue |
|
|
Term
| What are the symptoms of adrenal overproduction in Cushing's? |
|
Definition
Glucocorticoid excesss - moon face, central obesity, fat pads, hyperglycaemia, lipolysis, proximal muscle wasting, paper thin skin, ecchymoses, striae
Mineralocorticoid excess - HTN, hypernatremia, hypokalemia, edema
Androgen excess - hirustism, oligomenorrhea |
|
|
Term
| What symptoms of Cushing's have the highest likelihood ratios for the Dx? |
|
Definition
Ecchymoses
Proximal muscle weakness
HTN
Osteopenia/fracture |
|
|
Term
| What are the 3 key features of cortisol dysregulation in Cushing's and how do you test for each? |
|
Definition
Loss of diurnal variation - 11 PM saliva cortisol
Cortisol excess - 24 hr UFC
Non-suppressability - 8AM cortisol after 1 mg dexameth suppression
Need 2/3 to be positive for the dx |
|
|
Term
| Causes of false positives on screening tests for Cushing's? |
|
Definition
| Obesity, depression, alcohol use, OCP |
|
|
Term
| #1 cause of ACTH dependent Cushing's? |
|
Definition
| Cushing's DISEASE - pituitary adenoma |
|
|
Term
| If you have hypokalemic HTN, think _________ |
|
Definition
| Conn's syndrome - primary hyperaldosteronism |
|
|
Term
| Dx test for Conn's syndrome? |
|
Definition
| Elevation of the aldosterone:renin ratio |
|
|
Term
| Suppression test for Hyperaldosteronism? |
|
Definition
| Fludrocortisone/saline infusion |
|
|
Term
| Episodic triad of PHEOCHROMOCYTOMA? |
|
Definition
| Palpitations, sweating, headache (last 30 minutes to 2 hours) |
|
|
Term
| 1st line Rx for pheochromocytoma? |
|
Definition
SURGERY
Do alpha block before beta block - prevent HTN crisis |
|
|
Term
| What symptoms are present in almost all cases of Addison's? |
|
Definition
| Weight loss, fatigue, anorexia |
|
|
Term
| Acute adrenal crisis is most commonly caused by |
|
Definition
| Infection (e.g. Meningococcemia) |
|
|
Term
| If unexplained fever + hypoglycaemia - think... |
|
Definition
ADRENAL CRISIS
Check for hypotension, dehydration, shock |
|
|
Term
|
Definition
|
|
Term
| Measurements diagnostic for insufficiency in 8 AM cortisol test? |
|
Definition
<100 - likely AI
>500 - exclude dx of insufficinency
*if 100-500, then do ACTH stimulation test |
|
|
Term
| 24 hr UFC is positive in Cushing's? |
|
Definition
|
|
Term
|
Definition
|
|
Term
| Positive threshold for positive test in 1 mg dexameth suppression? |
|
Definition
|
|
Term
| cause of secondary hyperaldosteronism? |
|
Definition
Renal artery stenosis
Normal aldosterone:renin ratio, just both are elevated |
|
|
Term
| What does SRY gene trigger? |
|
Definition
Stroll cell formation - epithelial cells of the seminiferous tubules
SRY gene located on short arm of Y char |
|
|
Term
|
Definition
| Chromosomal sex determines gonadal sex determines phenotypic sex |
|
|
Term
| What does 5alpha reductase do? |
|
Definition
| Converts tesotsoterone to DHT - need DHT for external genitalia development |
|
|
Term
| What is Primary Sex Reversal? |
|
Definition
Due to crossing over during meiosis
XX individual phenotypically male
XY phenotypically female; 1/20k live births |
|
|
Term
| Relationship between SRY, DAX-1 and SOX9? |
|
Definition
SRY inhibits DAX-1
DAX-1 inhibits SOX9
So male - SRY inhibits DAX1 which allows SOX9 to support Sertoli cells
Female - no SRY so DAX1 inhibits SOX9 |
|
|
Term
| When do primordial germ cells migrate into the embryo from yolk sac? |
|
Definition
| 4th week; by 5th week have primordial gonad |
|
|
Term
| Wolffian structures vs. Mullerian structures - which ducts? |
|
Definition
Wolffian - mesonephric duct
Mullerian - paramesonephric duct |
|
|
Term
| How do males with 5alpha reductase deficiency present? |
|
Definition
Pseudovagina - have no DHT
Internally have male structures due to testosterone, but no DHT so no external genitalia
Girls turn to boys at puberty because testosterone surge can get enough DHT then |
|
|
Term
| How do males with 5alpha reductase deficiency present? |
|
Definition
Pseudovagina - have no DHT
Internally have male structures due to testosterone, but no DHT so no external genitalia
Girls turn to boys at puberty because testosterone surge can get enough DHT then |
|
|
Term
| What biomarker is diagnostic of CAH? |
|
Definition
| 17-OHP (for 21hydroxylase deficiency) |
|
|
Term
| 2nd most common form of CAH? |
|
Definition
|
|
