Flashcards in Endocrine Deck (128):
Which HLA is associated with T1DM?
DR3 and DR4
How do Beta Blockers cause worsening hyperglycemia in DMs?
BBlocks mask the warning signs of hyperglycemia such as tachycardia.
What step in the steroid hormone mechanism immediately precedes DNA binding within the nucleus?
Conformation change of the hormone-receptor complex
After binding, the conformation change reveals the DNA binding domain and is able to bind the DNA enhancer element
What changes are seen in thyroid hormone levels in a pregnant woman?
Increased thyroid-binding globulin, increased total T4, unchanged free T4
Increased estrogen -> increased synthesis of thyroid binding globulin -> increased total T4 to maintain a normal level of T4
Which GLUT is in the hepatocyte and describe its Affinity, Km, and insulin responsiveness
Glut 2 (liver, pancreatic B cells, renal tubular cells, small intestinal epithelial cells)
Decreased Glucose affinity (prevents saturation at high glucose levels)
Not responsive to insulin
What is the pathology of T2DM?
Decreased uptake of glucose into muscle cells
What is the pathology of T1DM?
Decreased secretion of insulin
A 45 y/o presents with light headedness, back pain, muscle weakness, fatigue. PE - dark buccal mucosa and hypotensive. Pt recently stopped taking his medication. Dx?
Insufficient production of adrenal hormones (cortisol, androgens, aldosterone)
Syx = hyperpigmentation, hypotension, muscle weakness, salt craving
Tx - po hydrocortisone
How do you differentiate addisons from adrenal crisis?
Addisons will have hyperpigmentation
When do you give dehydroepiandrosterone?
androgen replacement therapy
Can be given in addison's, but withdrawl doesn't result in hyperpigmentation
A teenager was found unresponsive after reporting that he has been fatigued and drinking lots of water. He is hyponatremic with an anion gap. Normal urine sodium. Dx?
Hyperglycemia causes osmotic diuresis
He appears hyponatremic because the hyperglycemia is pulling fluid into the plasma and makes his salt levels look lower than they are
What labs would be seen in DI that would make it unique from T1DM DKA?
hypernatremia, hyperosmotic urine.
Risk factor for spontaneous achondroplasia in a fetus with negative family history?
Advanced paternal age
Normal trunk length but short limbs
defect in fibroblast growth receptor 3 - abn cartilage formation.
A 23 y/o male with marfanoid habitus with pectus excavatum presents with being awakened at night by HA, anxiety, and heart palpitations. Dx?
MEN 2B (1P)
Medullary thyroid carcinoma
Oral or gastrointestinal neuromas
Look for neuromas in the oral mucosa and elevated calcitonin level
Pt presents with a thyroid nodule. Bx = hypochromic ground-glass nuclei, intranuclear pseudoinclusions, and nuclear grooves. What else would be seen on histology?
Extracellular, calcified, spherical bodies
Papillary carcinoma of the thyroid is the most common thyroid carcinoma and has the best prognosis
"ground glass" or "Orphan Annie" nuclei, psammoma bodies
Dx thyroid nodules on fine-needle aspiration
What lab findings would be seen in Sheehan syndrome (aka postpartum hypopituitarism)
decreased TSH and ACTH results in decreased thyroxine and cortisol
syx = fatigue, anorexia, poor lactation, loss of pubic and axillary hair.
Order of hormone loss = GH, FSH/LH, ACTH, and TSH
Tx - replace all the deficient hormones
A SLE pt taking prednisone increases risk of what type of syx?
Cushing-like syx - increased infection, cataracts, acne, HTN, hyperglycemia, peptic ulcers, osteoporosis, and psychosis.
Recommend vitamin D
Which type of study has subjects randomly assigned to a sequence of treatments with a washout between the treatment interval? (ie control group undergoes washout and switches to treatment group)
Allows the subjects to serve as their own controls
Drawback - washout may not be long enough
A pt has no change in urine osmolality during water restriction, but they do have an increase in osmolality following vasopressin administration. Dx and where is the damage??
Central DI - low ADH production
Nephrogenic would not respond to aDH administration
Damage to the hypothalamic nuclei
Damage to PP - transiet DI
Damage to hypothalamus - permanent DI
Where is ADH synthesized and stored?
Synthesized - paraventricular and supraoptic nuclei of the hypothalamus
Stored - posterior pituitary
Injury to posterior pituitary = transient DI, but if the hypothalamic tract is intact axonal regeneration and hypertrophy will allow adequate ADH realse
Where are the different versions of Vit D synthesized?
7-dehydrocholesterol -> cholecalciferol in the skin
Cholecalciferol -> 25OHvitD in the liver
1,25dihydoxyvitD in the kidney
A pt taking lots of vitamin and mineral supplements presents with stupor and dry mucous membranes. What's going on?
Hypercalcemia due to excessive vitamin D (muscle wakness, constipation, mental status changes, polyuria/polydypsia)
Also see hypercalcemia in granulomatous dz (sarcoidosis, TB) due to PTH independent conversion due to over expression of 1-alpha-hydroxylase in active macrophages. High vit D synthesis = high intestinal calcium absorption. Similar process is seen in Hodgkin dz
13 yr old presents with difficulty breathing, hoarseness, dysphagia. Large red lingual mass. Bx = normal thyroid follicles with colloid Dx?
Thyroid gland is derived from evagination of the pharyngeal epithelium and descends to the lower neck.
If migration fails the thyroid can reside anywhere along the thyroglossal duct's pathway including the tongue (lingual thyroid)
What is the pathology behind Sheehan Syndrome?
Pt presents with painful rash of the groin and perineum x 2 weeks. PMH DM, normochromic normocytic anemia both dx'd less than a year ago. PE = coalescing erythematous lesion with crusting and scaling at the borders and central area of bronze-colored induration. Bx = superficial necrolysis. Dx?
Glucagonoma (from alpha cells)
Presents with necrolytic migratory erythema usually affecting the mucus membranes (glossitis, cheilitis, blepharitis)
Also hyperglycemia (DM),GI syx, and anemia of chronic dz.
Dx - elevated glucagon in the serum
A 46XY newborn is born with hypospadias and a small phalus. Testes are well developed but stuck in the inguinal area. Serum testosterone is WNL. Dx?
5alpha-reductase deficiency type II
Converts testosterone to dihydrotestosterone (more potent version)
Born with feminized external genitalia that masculinize at puberty
A SLE pt continues taking prednisone following surgery. How would this medication affect her levels of: Corticotropin-releasing hormone, ACTH, and cortisol?
All 3 will be decreased
Acute adrenal insufficiency (adrenal crisis) due to suppresion of the hypothalamic-pituitary adrenal axis
steroid blocks CRH release -> low ACTH release -> low cortisol
HPA axis will atrophy with long term steroid use
If a prolactinoma is left untreated, what other syx are likely to develop?
Loss of bone mass
Hyperprolactinemia causes suppression of GnRH causing reduced estrogen in women. Low estrogen -= RF for osteoperosis
Syx of androgenic steroid abuse?
Virilization in women (cliteromegaly, hirsutism)
A pt with estrogen receptor + but HER2 - breast cancer is given anastrozole. What is its MOA?
Decreased androgen aromatization
Aromatase inhibitors (anastrozole, letrozole, exemestane) decrease the synthesis of estrogen from androgens. Decreasing the levels of estrogen will slow the progression of ER positive tumors
Less effective in premenopausal women b/c ovarian aromatase is upregulated in response to gonadotropins
A T2DM is found unresponsive because she failed to adjust her DM medication despite being very active and skipping dinner. She is given a bolus of dextrose but hours later becomes confused again and her blood glucose is 49. What medication is she likely taking?
Sulfonylurea - bind receptor on pancreatic beta cells to inhibit the ATP dependent K+ channel and increases insulin secretion from pancreatic beta cells independent of glucose concentration
Sulfonylureas have a high incidence of hypoglycemia especially in the elderly
What should be checked prior to initiating long-term amiodarone therapy?
Amiodarone is 40% iodine by weight - can cause hypothyroidism due to decreased production of thyroid hormone. Can also cause hyperthyroidism due to increased hormone synthesis or destructive thyroiditis with release of preformed thyroid hormone
In the presence of insulin, D-glucose transports across the plasma membrane of adipocytes much faster than L-glucose. Which transport process best describes the mechanism of gluocse entry into the cells?
Carrier proteins undergo conformation changes as the substrate is transported.
Facilitated diffusion - no ATP
GLUT 2 and 4
Which side effects are expected when initiating pioglitazone therapy?
Weight gain and edema
Both are due to fluid retention and can exacerbate underlying congestive heart failure
Fluid retention is often worse when TZD is given with insulin
Also causes adipose weight gain
A pt reports a history of having a problem metabolizing sugar but is on no dietary restrictions. Urine shows positive copper reduction test, but glucoase oxidase dipstick is negative.
Urine is testing postivie for a reducing sugar due to the presence of unmetabolized fructose
A pt with a pituitary adenoma (HA, bitemporal hemianopsia) becomes hypotensive and loses consciousness shortly after admission
Acute hemorrhage into the pituitary most often occurs in pts with preexisting pituatary adenomas
Acute bleed = severe HA, cardiovascular collapse (ACTH deficiency leads to adrenocortical insufficiency)
Tx - emergency neurosurgery and gluccocorticoids
A pt with fatiguability and weight gain presents with elevated creatine kinase. PE - lump rises at the site where the reflex hammer was used. What should be done next?
Hypothyroidism is a common cause of elevated CK due to hypothyroid myopathy.
Other causes of elevated CK = autoimmune, muscular dystrophies, and statins
Following a thyroidectomy a pt presents with muscle cramps, parethesias, twitching of his facial muscles. Dx?
Post operative hypoparathyroidism
Decreased calcium and phosphate resorption from bone, and decreased calcium reabsorption from urine
Following a Thyroidectomy a pt presents with hypocalcermia. What tx should be given?
Calcitriol = active form of bit D
Post op supplementation with po calcium and Vit D can treat and prevent post op hypocalcemia
Do NOT give calcidiol because the conversion to the active form (calcitriol) depends on PTH
A male pt with 1 testes in his scrotum is found to have elevated FSH but normal LH. Production of which substance is impaired?
Produced by the sertoli cells and inhibits FSH secreation
Sertoli cells are in the seminiferous tubules of the testes. If a pt has only one testicle then they are only able to produce half of the Inhibin B as a normal male
Which hormone provides negative feedback for LH?
A T1DM pt is found in a store unconscious and hypoglycemic. Best way to normalize her blood sugar?
Use in a nonmedical settive
Increase hepatic glycogenolysis and gluconeogenesis
Takes 10-15 min
Can try sublingual glucose (sugar packets etc) but mucosal absorption is erratic
When is fruit juice an appropriate tx for T1DM related hypoglycemia?
When the pt has acute syx of hypoglycemia (anxiety, tremor, sweating) but still concious
How would you tx a unconscious T1DM pt with hypoglycemia in a medical setting?
How does propranolol correct hypothyroidism?
Decreases peripheral conversion of T4 to T3
Decrease symphathetic adrenergic impulses on target organs
Following metyrapone stimulation there is a spike in 17-hydroxycorticosteroid in the urine. Why?
Metyrapone causes a decrease in cortisol synthesis by inhibitin 11-b-hydroxylase. IF the HPA axis is intact there will be an increase in ACTH, 11-deoxycortisol, and urinary 17-hydroxycorticosteroid levels
Pt presents to ED with abdominal pain and vomitting. BMI 37 and fasting labs show triglyceride of 1500. After being stabilized what long term tx should he receive?
TGs are metabolized to FFa's by pancreatic lipases causeing acute pancreatitis in pts with severe hypertriglyceridemia. Fibrates are the most effective tx
MOA for fibrates?
Activate peroxisome proliferator activated receptor alpha (PPAR-a) which increases lipoprotein lipase activity. Can rapidly lower TGs by 25-50%
Surgical removal of brown fat around the adrenals in a neonate would cause?
Contains more mitochondira and produces heat by uncoupling oxidative phosphorylation with the protein thermogenin
Brown fat has higher oxygen requirement and more vascularization
MOA of flutamide in prostate cancer?
Impaired androgen-recepter interaction
Use in conjunction with long acting GnRH agonist (down regulates LH and therefore testosterone)
A pt presents with hyperthyroidism syx and pain at the front of her neck that radiates to her ears with swallowing. Notes syx started following a URI. Higher ESR but low iodine uptake. Dx and histology?
de Quervain Thyroiditis
Mixed, cellular infiltration with occasional multinucleated giant cells
A teenager is tall but lacks secondary characteristics. Also unable to distinguish scents. Dx and pathology?
KAL-1 or FGFR1 mutation
No GnRH secretory neurons in the hypothalamus due to defective migration from the olfactory placode
Central hypogonadism, anosmia, and delayed puberty
At what age is puberty officially delayed?
Boys - 14
Girls - 12
First sign of puberty in each sex
Boys - testicle enlargement
Girls - breast enlargement
In a pt with hypothyroidism that starts on liothyronine (T3) supplementation, how does it change their labs for: TSH, T3, Reverse T3, T4
Decreased - TSH Reverse T3, and T4
Increased - T3
The HPA is negatively regulated by T3 so exogenous T3 suppresses TSH which in turn decreases T4 and r T3
However liothyronine is not used for long term mangement of hypothyroidism because of its short half life
MOA of pioglitazone
Thiazolidinediones bind to peroxisome proliferator-activated recepto-gamma (PPAR-g), an intracellular nuclear receptor that acts as a transcriptional regulator of many genes involve din glucose and lipid metabolism (adioponectin improves insulin sensitivty)
In a pt with hyperlipidemia, which drug is most likely to increase triglyceride levels as a monotherapy?
Bile acid binding resins inhibit the enterhepatic circulation of bile acids causing diversion of hepatic cholesterol to synthesis of new bile acids, uncreased uptake of cholesterol from circulation, and reduced LDL.
But, bile acid-binding resins increase hepatic production of triglycerides and can cause hypertriglyceridemia
Prior to initiating canagliflozin therapy in a DM pt, what labs should be checked?
BUN and Cr
SGLT 2 inhibitors (liflozin) decrease PCT reabsorption of glucose and promote glucose loss.
2nd or 3rd line drugs
AE's = UTI and genital mycotic infections due to glucosuria. Increased osmotic diuresis -> hypotension
Avoid in pts with moderate to severe renal ipairement
Describe the levels of extracellular and intracellular K+ in a pt with DKA
Extracellular K+ = jogh
Intracellular K+ = low
Insulin makes K+ go in, so in DKA the low insulin lets K+ escape
What happens when insulin binds its receptor?
The alpha subunits of insulin receptor bind insulin and the intracellular beta units contain a tyrosine kinase which becomes activated on insulin binding to alpha. IR becomes autophosphorylated -> Glut 4 is translocated to the cell membrane
How does TNF alpha affect insulin binding?
Proinflammatory cytokine that induces insulin resistance through activation of serine kinases which phosphorylates serine residues on the besta subunits of insulin receptor. this inhibits tyrosine phosphorylation and hinders all downstream signaling causing a resistance to insulin through decreased GLUT4 translocatoin
Phosphorylation of thronine residues has similar effects
Catecholamines, gluccocorticoids, and glucagon all induce insulin resistance through this mechanism
What are the 4 erythropoietin secreting tumors that can cause polycythemia?
Renal Cell carcinoma
How do you treat Pheochromocytoma acutely?
alpha blocker (phenoxybenzamine)
Never give a beta blocker by itself because you'll have unopposed alpha 1 activity
features of adrenal neuroblastoma
Tumor of sympathetic ganglion cells
Most common adrenal medulla tumor in kids
Causes mild HTN and monitor with HVA and VMA
Describe MEN 1
Pacreatic tumor (Gastrinoma, insulinoma, glucagonoma, VIPoma)
Describe MEN 2A
2P + 1M
Medullary thyroid cancer
Describe MEN 2B
1P + 2M
Prolactinomas are derived from which cell type?
Presents with HA's , bitemporal hemianopsia from compression of the optic chiasm
A pt presents with muscle cramps, tingling around his mouth, sensation of choking, and twitching of the perioral muscles when tapped (Chvostek sign). What is the cause?
Hypocalcemia = muscle cramps, perioral parathesia, hypotension, and neuromuscular hyperexcitability
Injury to the parathyroid during thyroid surgery is a common cause of hypothyroidism and hypocalcemia.
Chvostek sign and Trousseau sign are neuromuscular hyperexcitability due to?
Which 3 pt demographics are at the same risk for cardiovascular events (MI, Stroke) as pts with known coronary dz?
Noncoronary atherosclerotic dz
Chronic kidney dz
Most common cause of death in DM pts?
Coronary heart dz
During hospitalization a DM pt alternates between euglycemic and hypoglycemic. When he is hypoglycemic the only syx he experiences are sweating and hunger. Which medication is causing this?
Propranolol, timolol, nadolol
Non-selective beta blockers exacerbate hypoglycemia and mask adrenergic syx mediated by NE and Epi.
Use a selective Beta block instead (pindolol, acebutolol)
When a pt is started on high dose steroids what changes are seen on CBC differential?
Acute effects of corticosteroids in WBCs are increased PMNs and decreased lymphocyte, moocyte basophil, and eos counts.
PMNs increase due to"demargination" of PMNs previously attached to the vessel walls
A pts presents with general weakness and parathesia x 3 weeks. She has reported 2 visits of HTN (190/100). Labs show low renin and normal creatinine. Dx and what levels would be expected for Na, K, and bicarb?
Severe HTN in a young pt + weakness and parathesia suggests an electrolyte and acid-base disturbance.
Primary hyperaldosteronism causes increased renal sodium reabsorption leading to HTN, hypokalemia, and metabolic alkalosis
Why are pedal edema and hypernatremia rarely observed in primary mineralcorticoid excess (hyperaldosteronism)?
The increased intravascular volume causes increased RBF and augments release of ANP. this limits sodium retention and prevents the development of overt volume overload and significant hypernatremia
They will be eunatremic
How do Calcium sensing receptors work?
transmembrane G-protein-coupled receptors that regulate the secretion of parathyroid hormone in response to changes in circulating calcium levels.
A teenager is found to have incidental mild hypercalcemia on his labs but there are no syx of hypercalcemia. His family confirms that there are many relatives with mild hypercalcemia. Vit D level is WNL.
Familial hypocalciuric hypercalemia is benign AD disorder caused by defective calcium sensing receptors in the parathyroid gland and kidneys
An alcoholic presents with hypoglycemia after 5 days of binge drinking and his urine is strongly positive for ketones. Suppression of which metabolic process is responsible for his hypoglycemia?
Ethanol causes hypoglycemia once hepatic glycogen stores are depleted
Ethanol causes an increase in the NADH/NAD+ ratio - this inhibits all pathways that require NAD+
Inhibits: pyruvate to lactate, malate to oxaloacetate. These are both intermediates in gluconeogenesis
Glucogenolysis is not inhibited and keeps the pt euglycemic while hepatic stores last.
A pt being treated for prostate cancer develops gynecomastia. Which medication if initiated early would have prevented this?
SERMs inhibit the effect of estrogen on breast tissue that can develop while this pt is on androgen-deprivation therapy
What is the histology of gynecomastia?
Ductal epithelial hyperplasia surrounded by dense stromal fibrosis.
Acinar development is not seen because it is driven by progesterone.
Which medications can cause central SIADH?
Carbamazepine (seizure meds)
Which endocrines are synthesized within the neurons found in the paraventricular and supraoptic nuclei of the hypothalamus?
Which endocrines are released from the posterior pituitary (neurohypophysis)?
Vesicles in the PP contain neurohypophysis proteins that are involved in posttranslational hormone processing and stabilization during axonal transport.
Which medication inhibits cholesterol absorption at the brush bored of the small intestine?
Decreased intestinal absorption -> decreased vholesterol reaching the liver -> increased expression of LDL receptors -> further draws cholesterol out of the circulation
Pt with cushing like syx undergoes dexamethasone test. Cortisol levels are suppressed with high levels of dexamethasone, but not low levels. ACTH are borderline elevated. Dx?
ectopic adenoma would not respond to either dose of dexamethasone
Adrenal adenoma or exogenous glucorticoid intake would respond to low dose dexamethasone
Describe the characteristics of mealtime insulin analogs
Lispro, aspart, glulisine
Amino acid substitution at the C terminal end of the B chain have a rapid onset of action mimicking postprandial insulin secertion.
Onset is 0-4 hours vs regular insulin is 0-7 hrs
Following exposure to radioactive iodine pt should be given what to prevent tissue damage?
Competitively inhibits thyroid uptake of radioactive iodine isotopes and is given after exposure to radiation to protect the thyroid and prevent development of radiation induced thyroid carcinoma
What is the function of the thyroid peroxidase enzyme?
Ab against thyroid peroxidase in Hashimoto's thyroiditis
MOA of methimazole?
Coupling of iodotyrosines
Thionamides (methimazole and propyltiouracil) decreases formation of thyroid hormones via inhibition of thyroid peroxidase which is the enzyme responsible for both iodine organificaiton and coupling of iodotyrosines.
Propylthiouracil also decreases peripheral T4 conversion to T3
An unconscious T1DM pt is given glucagon. Metabolic changes in which organ allow for his recovery?
Glucagon increases hepatic glycogenolysis and gluconeogenesis
Stimulates insulin secretion from the pancreas
Insignificant effect on glucose homeostasis in the skeletal muscle, adipose, and renal cortex (whihc is unlike epinephrine)
An neonate is born with hypoglycemia. His mom has gestational DM. Why is he hypoglycemic?
Beta cell hyperplasia
Maternal hyperglycemia causes increased transplacental glucose delivery to the infant, fetal hyperglycemia and beta cell hyperplasia. This hyperinsulinemia causes islet cell hyperplasia and is associated with fetal macrosomia and hypoglycemia after delivery
Female child is brought in with syx of elevated estrogen. She is tall now but will likely stop growing and become short. Why?
Estrogens effect on the long bone epiphyseal plate
Promotes plate closure
Precocious puberty causes shorter stature despite and intitial growth spurt.
Gigantism is caused by excessive secretion of?
Excessive GH and IGF-1 does not cause premature closure of the epiphysis
What electrolyte changes can be seen in a pt with celiacs?
Vitamin D deficiency via malabsorption
Decreased phosphorus, calcium
syx of bone pain and muscle weakness
The adrenal medulla (chromaffin cells) release catecholamines (Epi, Ne) following stimulation from?
ACh from sympathetic preganglonic neurons
If a pt has persistant central DI following a MVA, where is the damage?
The hypothalamic nuclei damage causes permanent central DI
Damage to the posterior pituitary causes only transient DI
Pt presents with hypoglycemia, high insulin, and high C peptide. Dx?
Excess endogenous insulin due to use of secretagogues (ie sulfonylurea) or insulinoma
Sunlight exposure catalyzes which step in the conversion of Vit D?
7-dehydrocholesterol to cholecalciferol (vit D3)
Occurs in the skin
25 hydroxylation occurs in the liver
1 hydroxylation occurs in the kidney to produce active 1,25 dihydroxyvitamin D
Binding of which molecule induces closure of the K+ channels in GLUT-2 to release insulin?
ATP binds to the K+ channels -> membrane depolarization -> insulin release
Derivatives of neural crest tissue?
Adrenal medulla (pheochromocytoma)
Parafollicular C cells of the thyroid (Medullary thyroid cancer)
Parafollicular cells of the thyroid
Pt with orotic acid crystals and megaloblastic anemia benefits from supplementation with?
Disorder of de novo pyrimidine synthesis
Defect in uridine 5'-monophosphate (UMP) synthase
Meningococcal septicemia can cause?
Bilateral hemorrhagic infarction of the adrenal glands
Waterhouse-Friderichsen syndrome (low platelets, petechial rash, ABN bleeding, DIC)
What is at risk of damage during a thyroidectomy
External branch of the superior laryngeal nerve
inn cricothyroid m.
Tissue with high levels of smooth ER is likely to respond to which hormone?
because SER contains enzymes for steroid and phospholipid biosynthesis
G6P DH is the RLS in the pentose phosphate pathway. It is required for
G6P -> Ribulose-5-P
Major source of NADPH necessary to reduce glutathione (protects RBCs from oxidative stress).
Also essential for biosynthesis of cholesterol, fatty acids, and steroids
A T2DM pt is found unconscious. Her blood glucose is corrected, but within hours she is hypoglycemic again. What med does she take?
Increases insulin secretion from pancreatic beta cells independent of blood glucose
Long acting - glyburide glimepiride have high incidency of hypoglycemia in the elderly
Short acting - glipizide
MOA of meglitinides
Close the ATP-dependent K+ channel in the pancreatic beta cell membrane -> depolarization -> insulin release
Given with meals to reduce post prandial glucose excursions
Histology of the thyroid shows intense lymphocytic infiltrate with germinal centers. Dx?
Progressive fatigue, weight gain, constipation, and diffuse goiter
Most common cause of hypothyroidism in iodine sufficient regions
A MSUD infant would respond to supplementation with?
Branched chain alpha-ketoacid dehydrogenase requires Thiamine, Lipoate, Coenzyme A, FAD, NAD as cofactors
Dietary restriction of ILV is the best tx
What residues are often seen in the alpha helices of transmembrane dz?
Hydrophobic amino acids
Ala, Val, Leu, ILU, Phe, Tryp, Meth, Pro, Gly
Transmembrane domain anchors the protein to the phospholipid bilayer of the cell membrane
A pt presents with acute hypotension, shock and general hyperpigmentation. Dx and Tx?
Primary adrenal insufficiency (Addison's dz)
Tx - Dexamethasone, hydrocortisone, fluids
Pt is not able to increase glucocorticoid in response to acute stress. look for hx of auto immune endocrine dz (hypothyroidism, T1DM) or other endocrine dz
What serum electrolyte values would be expected in a pt with Primary adrenal insufficiency?
Low - Na, Bicarb
High - K+, Cl-
Adrenal insufficiency = hyponatremia, hyperkalemia, hyperchloremia, non anion gap metabolic acidosis
Pt presents with sudden severe HA, bitemporal hemianopsia, and defective EOM. Dx?
Acute hemorrhage of the pituitary
Usually have chronic syx of a pituitary tumor (bitemporal hemianopsia, decreased libido)
If no bitemporal hemianopsia - think subarachnoid hemorrhage
MOA of thizolidinediones (-glitazones)
Activated PPAR-gamma, a nuclear receptor that alters transcription of
GLUT 4 and Adiponectin
Decreases insulin resistance
Insulin increases glycogen synthesis in hepatocytes by activating?
Tyrosine kinase -> PI3 kinase -> Protein phosphatase -> dephosphorylates (activates) glycogen synthase
A T1DM presents with elevated blood glucose due to increased activity of?
In liver and kidney cells, uses glycerol from adipose tissue to synthesize glucose during gluconeogenesis
Which drug can cause a flair of gout?
Decreases hepatic synthesis of triglycerides, VLDL, and clearance of HDL (used in dyslipidemia)
Can cause decreased renal excretion of uric acid -> gouty arthritis
Where is PPAR-gamma located?
Intracellular nuclear receptor
Target of thiazolidinediones
Codes for GLUT 4 and adiponectin (cytokin secreted by fat that enhances insulin sensitivity and fatty acid oxidation; low in pts with obesity and T2DM)
Pharmacokinetics of mealtime insulins?
Sharp quick pick (left side of the house)
Lads and Girls
Lispro, aspart, Glulisine
Amino acid substitution at the Cterm end of the B chain allows for rapid onset and offset of action to mimic postprandial insulin
Deficient enzyme in Pmpe dz?
Cardiomegaly, macroglossia, muscle hypotonia in early infancy.
ABN glycogen accumulation within lysosomal vesicles on muscle bx
Virilized female at birth
Defect in progesterone (17-hydroxyprogesterone) -> 11-deoxycorticosterone
Males will have normal genetalia with salt-wasting or precocious puberty
Dx - high 17-hydroxyprogesterone
5-alpha reductase catalyzes?
Test -> DHT
ABN development of external genetalia in a male (feminized genitalia that will masculinize at puberty)
LH, FSH, testosterone, sperm count in a Klinefelter pt (47 XXY)?
Testosterone negatively inhibits?
Inhibin negatively inhibits?
Levels of CRH, ACTH, and cortisol in a pt that takes chronic prednisone?
Prednisone caan cause adrenal insufficiency due to depression of HPA
Adrenal crisis in stressful situations (hypotension, shock)