Part 26 Flashcards
Blood calcium levels range to determine treatment
- Asymptomatic or mildy symptomatic <12mg/dL does not require immediate treatment
- 12-14mg/dL may be tolerated well if chronic but not if acute
- > 14mg/dL requires urgent treatment regardless of symptoms
Hypercalcemia treatment (4)
- Isotonic saline to correct for volume depletion and vomiting
- Exogenous salmon calcitonin for rapid short term treatment but wears off (tachyphylaxis)
- Biphosphonates (takes a few days to activate but eventually take over from the calcitonin)
- Calcimimetics such as cincalcet in patients in parathyroid dz
3 types of hyponatremia and common causes
Hypovolemia - GI losses, renal losses from thiazide diuretics
Euvolemia - SIADH, primary polydipsia
Hypervolemia - heart failure, cirrhosis
Most common endocrine disorder of women and most common cause of infertility
PCOS
PCOS pathophysiology
Hypothalamic pituitary abnormalities resulting in altered LH action increasing the LH:FSH ratio >2 and increased sensitivity to androgens (hyperandrogenism) including androstenedione, DHEA-S, and testosterone, and also see insulin resistance (50-70% are hyperinsulinemic and at risk for pre-diabetes and overt type 2 diabetes
PCOS and insulin
Due to genetic and environmental factors, ovaries and thecal cells in ovaries that make estrogen and a little bit of testosterone are very sensitive to higher insulin levels and insulin serves as a co-gonadotropin so that instead of LH stimulating these cells insulin does instead to see increased androgen production by the ovaries
High risk groups for PCOS (4)
- oligo-ovulatory infertility
- obesity and insulin resistance
- diabetes type 2 (typically)
- family members with pcos
PCOS presenting signs/symptoms (9)
- Secondary amenorrhea (rule out pregnancy)
- other menstrual irregularities
- androgen excess (hirsutism, acne, male pattern baldness)
- obesity
- cystic ovaries (usual but not diagnostic)
- glucose intolerance
- metabolic syndrome
- Nonalcoholic steatohepatitis (NASH) (very common cause of cirrhosis in US)
- miscarriage risk
PCOS diagnostic criteria NIH (3)
- Menstrual irregularity
- clinical or biochemical evidence of hyperandrogenism
- ruling out other causes of menstrual irregularity
PCOS diagnostic criteria Rotterdam
2 of the following
- Evidence of androgen excess
- Ovulatory dysfunction
- polycystic ovaries
Most sensitive test for hyperandrogenism in PCOS eval
Free testosterone first thing in morning
Look for other causes than PCOS when you have these 3 things
- Sudden onset or worsening of symptoms
- onset 3rd decade of life or later
- signs of virilization (frontal balding, severe acne, clitoromegaly, muscle mass, deepening voice)
Test to rule out acquired congenital adrenal hyperplasia in a suspected PCOS patient
Test for 17 hydroxyprogesterone elevation
PCOS therapeutic options (6)
- Birth control pills to lower free testosterone (Yaz)
- Antiandrogens (spironolactone)
- Metformin
- weight loss
- clomiphene (80% ovulate in response to this allowing almost 50% to conceive)
- bariatric surgery (curative)
First trimester, third trimester, adolescence, and adult consequences of impaired testosterone secretion
1st trimester - female external genitalia, partial virilization
3rd trimester - micropenis
Adolescence - incomplete puberty
Adult - energy, libido, decreased hair, loss of muscle mass, severe osteoporosis
Kallmann’s syndrome
Male individuals who have lifelong hypogonadism and also have anosmia due to deficient secretion of GnRH
Klinefelter’s syndrome
Genetic abnormality of two x chromosomes on a male patient resulting in infertility and hypogonadism
Eunuchoid proportions
Measured when floor to pubis are measured as 2cm longer than pubis to crown of a patient indicative of male hypogonadism
Lab tests for male hypogonadism (4)
- Serum total testosterone (most important test avoid when hospitalized or on steroid therapy)
- LH and FSH
- serum free testosterone (binding protein abnormality suspected)
- Prolactin levels
Diurnal fluctuation of testosterone
Highest in the morning, lowest in the evening
Primary hypogonadism causes (4)
- Congenital abnormalities such as klinefelters
- Bilateral cryptorchidism (undescended testes)
- varicocele
- Infection such as mumps
Secondary hypogonadism causes (4)
- Kallmann’s syndrome (deficient secretion of GnRH)
- isolated hypogonadotropic hypogonadism
- systemic illness and long term steroid treatments
- chronic opiate administration
Issue with oral preparations of testosterone
Almost impossible to maintain normal levels with them, also liver toxic due to first pass effect
Male hypogonadism testosterone treatment options (2)
- Injectable Tetosterone 100mg weekly or 300 every 3 weeks (fluctuations occur)
- transdermal patch or gel
Undesirable effects of testosterone treatment (5)
- acne
- gynecomastia over first few months (body converts to estrogen initially)
- physically aggressive behavior
- PSA level increases but should remain in normal range (BPH isn’t a problem)
- 2ndary polycythemia vera
Gynecomastia pathogenesis
- Decreased androgen production
- Increased estrogen production
Testosterone variation with age
100 ng/dl DECREASE from age 20-80 especially in free testosterone, will see symptoms comparable to hypogonadism
Type 1.5 diabetes
Adult onset that appears initially like type 2 diabetics but are usually healthy, fit, and thin and then over time progresses into type 1 diabetes
For sliding scale insulin dosing, 1 unit acting insulin corresponds to ingestion of ___ g of carb
12-15
Thyroid hormone mech of action
- T3, the only active form enters the cell and binds specific receptors located in the cell’s nucleus
- induces transcription of specific DNA segments which ultimately results in altered protein synthesis in the cell
Plummer’s disease/toxic nodular goiter
Recult of thyroid adenoma that clinical manifestts similar to graves disease but without exopthalmos, requires surgery and radiation
Desiccated thyroid (Thyroid USP/armour thyroid)
Obsolete treatment for hypothyroidism only still used in those who have been on it for years derived from porcine, has higher T3:T4 ratio which can lead to fluctuating levels of T3
Propylthiouracil (PTU) function and ADR’s (3)
- Used alone as sole source of treatment in graves disease or employed as adjunct to radiation therapy
- Agranulocytosis, hypothyroidism, liver injury (sudden onset)
Potassium iodide (thyro-block)
PO to protect thyroid in event of radiation emergency (such as a nuclear accident) that prevents uptake of radioactive iodide preventing harm to thyroid gland
Radioactive iodine 131 I
Radioactive isotope of stable iodine to produce clinical remission in hyperthyroid patients by destroying the gland without damaging surrounding tissue
Aldosterone physiologic effects
Acts on the collecting ducts of nephron to promote Na+ resorption in exchange for K+ or H+ excretion (without it see hyponatremia and hyperkalemia, and acidosis), regulated by angiotensin II not ACTH
Adrenal adenoma and carcinoma causing hypersecretion of glucocorticoids is cushings….
….syndrome
Hypersecretion of ACTH by pituitary adenomas resulting in excess glucocorticoids is cushings…
….disease
Primary hyperaldosteronism results in these 3 things and can be treated with what drug?
- Causes hypokalemia, metabolic alkalosis, and hypertension
- Aldosterone antagonist spironolactone
Secondary and tertiary adrenocortical insufficiency does not effect ____ because…
mineralcorticoid secretion
….they are managed by the angiotensin II aldosterone system!
Adrenal crisis
Hypotension, dehydration, weakness, lethargy, and GI symptoms that can progress into shock and death caused by adrenal failure, pituitary failure, or failure to replace/sudden withdrawal from glucocorticoid therapy
Fludrocortisone function and ADR’s (3)
Only mineralocorticoid available to mimic the body’s natural conc. and used for chronic replacement
-Excessive salt and h2o retention, cardomegaly, hypokalemia
Drug of choice for chronic adrenal insufficiency
Cortisone and hydrocortisone
Whipple’s triad and what is it pathognomonic for
- Fasting hypoglycemia symptoms
- Serum glucose <50
- symptoms improve with sugar
Insulinoma presence
Honeymoon phenomenon type 1 diabetes
Period shortly after type 1 diabetes diagnosis in which not very large dosages of insulin are needed to treat because the pancreas is still making its own to an extent, does not occur in all patients and is temporary but can be prolonged with certain lifestyle modifications
The dawn effect
Abnormal high early morning (2-8am) early morning glucose in patients with diabetes
The somogyi effect
high blood sugar in AM as a response to rebound low blood sugar at night
Metabolic syndrome diagnostic criteria
3 or more of the 5 following
- waist circumference >35in in women and >40 in men
- triglycerides >150
- Low HDL <50
- High BP > 135/85
- fasting glucose >110
Pemberton sign
Test for venous obstruction due to a goiter, positive when bilateral arm elevation causes facial erythema and cyanosis compressing the thoracic inlet indicating goiter presence
The right adrenal gland’s main vein (right suprarenal vein) drains directly into the ___, the left drains ___
- vena cava
- renal vein
Layers of the adrenal gland and hormones secreted in each (4)
Zona Glomerulosa - aldosterone
Zona fasciculata - cortisol
Zona reticularis - androgens
Medulla - catecholamines
4 common extramedullary locations of pheochromocytoma (catecholamine secreting paragangliomas that only secrete norepi)
- Organ of Zuckerkandl (near bifurcation of abdominal aorta along spine)
- neck
- upper abdomen (most common)
- bladder
Classic triad of pheochromocytoma and another pathognomonic finding
- palpitations
- sweating
- headache
-feeling of impending doom
Pheochromocytoma treatment options (1) and what is the pre op prep?
- surgical resection only (dissection with minimal tumor manipulation to prevent catecholamine surge, venous drainage first*** then arterial)
- Pre op prep involving preventing hypertension and tachycardia beginning 1 week before (alpha adrenergic antagonist like phenoxybenzamine THEN B receptor antagonist like propranolol
Aldosteronoma pathognomonic findings (2)
- hypertension
- hypokalemia (not on diuretics)
Recall the RAAS system
- at the level of the kidneys hypovolemia causes release of renin from juxtaglomerular aparatus
- angiotensinogen released from liver is converted by renin to angiotensin I
- angiotensin I is converted by lungs that release ACE into angiotensin II
- angiotensin II causes aldosterone secretion at the adrenal gland and has peripheral vasoconstriction effects
- aldosterone causes retention of sodium and therefore water but loss of potassium
Diagnostic labs of aldosteronoma (4)
- increased plasma aldosterone but decreased plasma renin (inappropriate release of aldosterone)
- rule out bilateral adrenal hyperplasia (unknown cause) via CT scan
- oral sodium loading (should suppress aldosterone secretion)
- captopril administration test (should cause decrease in adlosterone and increased renin but in primary hyperaldosteronism there is no change)
Cushing syndrome vs cushing dz
Syndrome is signs and symptoms associated with elevated cortisol level vs in cushing dz see pituitary tumor hypersecreting ACTH resulting in excess cortisol
Glucocorticoid producing tumor diagnostic studies (3)
- increased 24 hr urine free cortisol
- dexamethasone suppression test
- CT scan
Cushing syndrome signs and symptoms (8)
- weight gain
- peripheral muscle wasting
- hirsutism
- buffalo hump
- moon face
- menstrual irregularity
- amenorrhea
- impotence
Cortisol release pathway
- cortosol levels sensed in hypothalamus and releases CRH when low
- Anterior pituitary receives CRH and this stimulates release of ACTH
- this acts at the adrenal gland increasing cortisol in the blood stream to be sensed in hypothalamus
Cushings disease has __ ACTH and ___ cortisol, noncushings disease cushings syndrome has ___ ACTH and ___ cortisol
Elevated, elevated, low, elevated
Dexamethasone suppression test
-24 hr urine for 3 consecutive days, .5 mg of dexamethasone given every 6 hours on day 2 and 3, urinary free cortisol should be <10mcg/day on day 2, if not suppressed then must have adenoma
Adrenal cortex incidentaloma
Seen in patients often getting CT or screening for something else, if it isn’t presenting symptomatic then don’t need surgical intervention, can do fine needle aspiration after ruling out a pheo*** to determine cause
Most common functional pancreatic endocrine tumor
Insulinoma
Diagnosis of insulinoma (3)
- insulin and glucose determinations during a 72 hr fast
- insulin to glucose ration >.3 after overnight fast
- elevated c peptide and proinsulin levels
Proinsulin is cleaved to insulin from removal of a free ___, measuring this rules out ___ insulin as a source
C peptide, exogenously injected
Zollinger Ellison syndrome/gastrinoma suspicious findings (5)
- ulcers in unusual locations (not antrum or prepyloric area)
- persistent ulcers despite medical management and chronic diarrhea
- ulcers and manifestations of other endocrine tumors
- strong family history of ulcer dz
- recurrent ulcers after antiulcer surgery
Gastrinoma diagnostic studies (2)
- fasting gastrin >200 or >1000 highly suspicious
- secretin stimulation increasing gastrin levels >200 is diagnostic***
Gastrinoma treatment options (2)
- control gastric hypersecretion (gastrin, Ach from vagus, histamine all contributors) so give PPI
- surgical localization, assess for mets, and remove
Pyramidal lobe of the thyroid
Remnant of thyroglossal duct sometimes present extends upward torward cricoid cartilage from isthmus
Thyroid arterial supply (3)***
- Inferior thyroid artery from the thyrocervical trunk
- Superior thyroid artery off carotid
-rarely thyroid ima artery
Thyroid venous supply (3)***
- Inferior thyroid vein draining into subclavian
- middle thyroid vein (has NO arterial equivalent)
- superior thyroid vein draining into jugular
Hemopoiesis definition
Production of formed elements of blood (erythrocytes, leukocytes, thrombocytes)
Red marrow location in children vs adults
Nearly all marrow in children is red, in adults it is confined to specific areas (skull, ribs and sternum, pelvis primarily) of bone, with yellow marrow replacing it in other locations (although it can convert back)
Hemocytoblast
Stem cells that form all elements of blood, also known as a pluripotential stem cell
Differentiation of stem cells occurs when they develop surface receptors for a specific 1 of 3 of these growth factor’s in which they are then committed for life to that line
- erythropoietin (transforms an uncommitted potential cell to a committed proerythroblast)
- thrombopoietin
- CSF’s
Erythrocyte differentiation pathway (5)
Hemocytoblast Proerythroblast Erythroblast Reticulocyte (enters circulation) mature RBC
Erythrocyte homeostasis mechanism of action
- Drop in O2 content detected by receptors in kidney
- increases output of erythropietin by kidneys
- 3-4 days later, RBC rises and compensates for dropped O2 content
Major requirements for erythropoiesis to occur and what function do they serve(2)
- Iron (form hemoglobin)
- B12 and folic acid (proper cell division)
Iron metabolism and storage in the liver mechanism of action pathway
- Fe3+ is converted to Fe2+, or ingested Fe2+ sits in the gut
- Only Fe2+ can be absorbed by small intestine binding gastroferrin produced by stomach
- Dissociates from gastroferrin and binds transferrin to deliver to tissues of the body
- liver binds any excess iron to apoferrin, the iron storage complex becoming ferritin
- Ferritin releases stored Fe2+ converting itself back to apoferrin, iron goes into circulation as needed
3 differentiated types of WBC progenitors from the hemocytoblast
- B progenitors
- T progenitors
- granulocytes/macrophage colony forming units
When thrombopoietin binds to a hemocytoblast, what happens?
It becomes a megakaryoblast by replicating DNA without nuclear or cytoplasmic cytokinesis
How long to platelets survive in the circulation
5-9 days
Erythropoietic growth factors/erythropoiesis stimulating agents function
Allow the patient to see increase in RBC count in patients with CRF and cancer patients undergoing chemotherapy
Erythropoietic growth factors/erythropoiesis stimulating agents ADR’s (5)
- Hypertension is most significant
- Increased risk of DVT when used before elective surgery
- Can worsen some cancers
- cardiac arrest
- autoimmune pure red cell aplasia (PRCA)
Epoetin alfa (Epogen, procrit) class, therapeutic use,
- Erythropoietic growth factor
- can reverse anemia associated with CKD virtually eliminating need for transfusion
Procrit indications (2)
- treats chemo induced anemia in patients with nonmyeloid malignancies reducing need for transfusions
- undergoing elective surgery when significant blood loss is expected
Autoimmune pure red cell aplasia (PRCA) and treatment
Rare condition where treatment with epoeitin leads to a condition characterized by severe anemia and complete loss of erythrocyte precursor cells in bone marrow due to production of Abs directed against epoetin and native endogenous erythropoietin, which causes RBC production to cease, treatment consists of transfusions for survival
Epoetin alfa administration and 2 drugs of this class
Injection
-epogen and procrit
Darbepoeitin alfa (ARANESP) function
Long acting erythropoietin approved by FDA for treatment of anemia that has a slower clearance making half life 2-3x longer
Darbepoeitin alfa (ARANESP) ADR’s (3)
- Hypertension
- MI
- thrombosis
Filgrastim (neupogen) OR Filgrastim-sndz (Zarxio) mechanism of action
Acts on cells of bone marrow to increase production of neutrophils using identical mechanism to G-CSF, and enhances phagocytic and cytotoxic actions of mature neutrophils
Filgrastim (neupogen) OR Filgrastim-sndz (Zarxio) therapeutic uses (3)
- Approved to reduce risk of infections in patients undergoing myelosuppressive chemotherapy (many chemotherapuetics suppress bone marrow, this leads to increased infection)
- also used in bone marrow transplants and harvesting bone marrow
- treats severe chronic neutropenia
Filgrastim (neupogen) OR Filgrastim-sndz (Zarxio) administration
Injection IV or SC
Pegfilgastrim (neulasta) characteristics
Long acting derivative of filgrastim (neupogen) that stimulates myeloid cells to increase neutrophil production, longer half life allows for treatment with one dose
Pegfilgastrim (neulasta) ADR
- devoid of serious ADR’s
- bone pain
Sargramostim (leukine, prokine) mechanism of action
Acts on cells in bone marrow to increase production of neutrophils, monocytes, macrophages and eosinophils by imitating a GM-CSF nearly identically
Oprelvekin (Neumega) mechanism of action
Nearly identical to interleukin 11, increasing platelet production
Romiplostim (Nplate) mechanism of action
Stimulates platelet production through acting as a thrombopoietin receptor agonist
Kostmann’s syndrome
A severe congenital neutropenia
Ferritin
Storage form of iron in mucosal and liver cells, apoferrin becomes this upon binding iron
Trasnferrin
Iron binding protein for distribution throughout body
Physiologic needs of iron require diet to contain ___ more iron than body needs because of how little is abosrbed (think about what the RDA represents)
10x
Ferrous sulfate info and what is it DOC for?
- Least expensive PO oral iron replacement therapy
- DOC for iron deficiency anemias or sometimes used prophylactically
Ferrous sulfate ADR’s (9)
- nausea
- heartburn
- bloating
- constipation
- diarrhea
- peptic ulcers
- dark green stool
- staining of teeth
- toxicity
Ferrous sulfate drug interactions (2)
- Antacids reduce absorption
- tetracyclines forms chelates decreasing absorption of both agents
PO iron administration recommendation
Recommended to administer between meals, every other day per latest guidelines
Ferrous gluconate/fumarate/aspartate function
Salts which are alternatives to ferrous sulfate, only difference is percent of iron content, produce same pharm effects, therapeutic responses, and ADRs
Carbonyl iron function
Pure elemental iron in microparticles to enhance bioavailability and can be administered at an increased dosage safely (good for children)
Iron dextran administration, function, indications
- IV or IM, preferabely IV, Iron preparation consisting of ferric hydroxide and dextrans
- reserved for those who cannot tolerate oral iron (such a those with intestinal disease or blood loss)
B12 essential metabolic functions (2)
- DNA synthesis
- catalyze folic acid allowing for cell growth and division
B12 absorption pathway
- Requires intrinsic factor secreted by parietal cells of stomach to form complex
- complex dissociates after absorption
- transported by transcobalamin II into tissues
- most B12 stored in liver, years to develop deficiency
2 major causes of B12 deficiency
- impaired absorption due to enteritis or celiac disease
- lack of intrinsic factor (perhaps from gastric bypass!)
Pernicious anemia
Atype of megaloblastic anemia where B12 deficiency due to lack of intrinsic factor resulting in low RBC count
Erythroblasts are different from proerythroblasts in that they have ____
hemoglobin
Anemia definition
Decrease in erythrocyte number, size, or hemoglobin content either due to blood loss, hemolysis, bone marrow dysfunction, or nutritional deficiences
During pregnancy, what happens to iron requirements?
They increase very high, often requiring supplementation
Vegans run the risk of this vitamin deficiency because it is only obtained from animal products or fortified foods
B12
Cyanocobalamin B12 function and DOC for what?
Purified crystalline form of vit B12 and DOC for B12 deficiency
