Endocrinology 4

within 15 min of meal; as rescue: w/o regard to meals

Available for use in insulin pumps up to 48 hours

15 min prior to meal OR within 20 min after starting a meal

Better in obese patients?

within 30 min of meal; as rescue: w/o regard to meals

x2 / day (depending on meal schedule)

bound to albumin; good for 42 days out of refrigerator

peakless insulin; acidic pH; provides 24 hr coverage in most pts

Reduce TDD by 20%; administer total dose QD

unit-to-unit

NovoLog 70/30 (30 Aspart & 70 Protamine); Humalog 75/25 (25 Lispro & 75 Protamine); Humalog 50/50 (good for pt eating 2 big CHO meals/ day)

Regular insulin (30) & NPH (70)

Basal: 50% of TDD; Bolus: 50% of TDD (divided into mealtime doses)

Decrease amt used as bolus by 20%

2/3 of TDD in AM (1/3 short acting; 2/3 intermed); 1/3 of TDD in PM (1/2 short acting, 1/2 intermed)

50mg/dL

25-30 mg/dL

as much as 70- 100mg/dL

blood sugar level

1800 / TDD = x (mg/dL changed by 1 unit insulin) = correction factor

(FSBS) – (goal) / correction factor

CHO intake

500 / TDD = x gm CHO covered by 1 unit insulin

decrease by 0.5 units

hypoglycemia triggers counter-reg hormones; causes hyperglycemia; manage insulin to prevent hypoglycemia

d/t waning insulin levels; causes hyperglycemia; manage with insulin, or move peak to more physiologic time

beta cell hormone co-secreted w/ insulin; suppresses glucagon secretion from panc; regulate gastric emptying; enhances satiety

Sticky; adheres to surfaces; forms aggregates & insoluble particles; Half-life is minutes, must be given IV

1 unit = 6 mcg

5 mL vial; 60 mcg T1DM pens (15-30-45-60); 120 mcg T2DM pens (60-120)

15mcg (2.5 units) before meals; decrease meal-time insulin by 50%; Increase pramlintide dose by 15mcg (2.5 units) q 3-7 days as tolerated to 60 mcg (10 units)

Nausea & anorexia (T1 > T2); Black Box: severe insulin-induced hypoglycemia, usu within 3 hrs of dosing

Take immed prior to meal of 30 gm or more of CHO; injection technique & admin site (abdomen or thigh); do not mix with insulin

Unopened vial/pen: refrigerated; Opened vial: refrig or rm temp; Opened pen: rm temp

Oral agent needing rapid onset (analgesics); meds needing threshold conc for efficacy (Abx, contraceptives); Administer oral med at least 1 hr prior

Severe GI disease (diagnosed gastroparesis)

insulin (& diet & exercise); then adjunct oral tx (biguanide / TZD); then Inj Adjunct (amylin)

diet & exercise (& metformin?); oral mono or combo tx (TZD / sulf; then poss alpha-gluc inhib or meglitinide or DPP4); incretin mimetics (GLP-1); insulin; amylin [insulin may be started at any time]

if pt is producing insulin

Sulfonylureas; meglitinides; insulin

biguanides; TZDs

GLP-1 agonist; DPP4 inhib; amylin agonist

Sulfs (Glyburide, Glipizide, Glimepiride: hugs panc all day); meglitinides (Repaglinide, Nateglinide: quick panc hug to cover meal)

Replace 1stG; 2ndG do not work better but fewer DI and no sulfa allergy concerns

initial med: start low / slow; titrate q3-4 wks as poss, adjust for hep/renal dysfn; pt ed re: hypoglycemia; consider combo tx when tx nears max dose

Glipizide may be used in renal impairment; glyburide may worsen renal dysfn

Liver / renal dz; elder / debilitated; Severe trauma / infxn; PG/ BF

at 1 wk by doubling dose up to 4 mg

Inhibit hepatic glu O/P; Promote glu uptake by fat & mx; Decreases intestinal absorption of glucose (minor)

Kidney / Liver dz (Scr: M 1.5, F 1.4); Elderly; Alcohol Abuse; Unstable Heart Failure; IV Contrast Media

GI (30%); Lactic acidosis; anorexia; Vit B12 depletion

GI effects should resolve within 14 days; Take with meals

d/c drug 24 hr before procedure, restart 48 hrs after, or labs prove kidney fn is back to nml

500 – 850 QD or 500 BID; titrate 500 q7d & 850 q14d (no benefit >2000 mg / day)

use XR if GI AE concerns; 500 QD w/ PM meal; titrate q7d

Promotes glu uptake by fat & mx; Inhibits hepatic glucose output

Liver dz; Heart failure (Black Box); PG & Lactation

Liver tox; Fluid retention (not resolved by diuretics); Wt gain (20-30 lb?); HA, fatigue

Patience: 6-12 weeks for max efficacy; may have noticeable wt gain; Report to provider SOB with any activity

No sooner than 4 weeks

cause CHO to be absorbed more slowly

IBD / UC / obstruct bowel disorders; Liver / renal impairment; PG/BF

Flatulence, GI distress, diarrhea; Jaundice, elevated LFTs (acarbose)

Pancreatic enzymes

Take w/ meal; If have hypoglycemic event, must tx w/ glucose (tablet) or lactose (milk), not complex CHOs; GI AE will lessen over time

Peptide hormones released by the gut to normalize glucose profile; include GLP-1; GIP (no effect if given exogenously)

Rapid inactivation by DPP-IV; Requires continuous SQ injection

GLP-1 Agonist: Modify protein to prevent breakdown; DPP-4 inhib: Limit enzyme activity

urticaria & angioedema; poss severe pancreatitis

metformin and/or TZDs (address impaired insulin secretion, insulin resistance, and dec glucagon suppression); can give to pt w/ impaired hepatic / renal fn

Peripheral edema (in combo w/ TZD); HA; UTI; Hypoglycemia with sulfonylureas

metformin and Actos

Biguanide

meglitinides; alpha-gluc inhibs

TZDs; DPP-4 inhibs; Meglitinides; Glipizide IR; Glimepiride; Tolbutamide

metformin, insulin, sulfs (TZDs effective but expensive)

inc glucose-dept insulin secretion; dec glucagon secretion; dec rate of nutrient absorption (so improved gastric emptying); inc satiety

5 or 10 mcg pens; SQ; thigh, abd, upper arm

At least 6 hrs apart; Inc dose after 30d, as tolerated, prn; Decrease sulf dose by half to reduce hypoglycemia risk; Must be on 5 for 30 d, before consider inc to 10 mcg; Take before meals

Sig reduction in A1c; wt loss

Injxn technique (1 time prime); Take within 60 min of meal (if skip meal, skip dose); Storage: Unopened: refrigerate; Opened: refrig rm temp (to 30 days)

Oral agent needing rapid onset (analgesics); meds needing threshold conc for efficacy (Abx, contraceptives); Administer oral med at least 1 hr prior

0.6, 1.2 (after 1 wk), 1.8 pen; once daily, independent of meals; 0.6 mg not effective for glycemic control (only minimizes GI sx); Decrease sulf dose by half to reduce hypoglycemia risk; poss sig DI

Inc hypoglycemia risk if combo w/ sulf; N/V; Diarrhea; Anxious / jittery; Pancreatitis; Wt loss; Thyroid C-cell tumors (liraglutide)

After oral agents have failed; HbA1c from 7-11%

T1DM; ESRD / CrCl <30 ml/min; Pancreatitis; Severe GI dz; h/o medullary thyroid ca or Multiple Endocrine Neoplasia Syndrome (liraglutide only)

60mcg (10 units) before meals; Decrease meal-time insulin by 50%; Increase to 120mcg (20 units) in 3-7 d, as tolerated

NPH; mixes

Regular

Regular; NPH; Novolin 70/30; Humulin 70/30

CRH, GHRH, GnRH, TRH, DA, SS

Prolactin; GH; ACTH; ADH; TSH; LH/FSH

Epinephrine; Cortisol; Aldosterone

produced by pit; neg inhib by DA (so the more DA, less prolactin)

Upper cortical inputs (CNS); Autonomic NS; environmental cues (light & temp); Peripheral endocrine FB

Estrogen (F); Spermatogenesis (M) [if no estrogen prod: FSH increases]

regulates ovulation; stimulates testosterone in men [if no testosterone prod: LH increases]

increases thyroid hormone production [if no TH prod: TSH increases]

induces lactation

controls acral growth

stimulates cortisol production

Thyroid gland fails to make T4; TSH is HIGH; FREE T4 is LOW

Pituitary gland fails to make TSH; TSH is inappropriately LOW; FREE T4 is LOW; Other Pit Hormone Deficiencies; cannot follow TSH (must also follow Free T4)

Cold intolerance; Fatigue; Heavy Menstrual Bleeding; Wt Gain; Myxedema Coma

Much rarer than primary

Follow TSH to adjust thyroid hormone replacement

panhypopituitarism

hypothyroidism & low normal TSH, low normal t4

replete thyroid hormone before repleting cortisol; if pt adrenal/ cortisol deficient, & replete TH first, revs up metab, can lead to adrenal crisis (wont have enough cortisol to support metabm)

Sx of Hypothyroidism; Low TSH; Low T4; Other Sx to suggest Pan-Hypopituitarism

Cortisol Deficiency

Addison Dz; adrenal gland does not respond to ACTH & not make adrenal hormones

Pit does not make ACTH; adrenal is not stimulated to make cortisol

Suppression of CRH & ACTH by exogenous cortisol use

Sx based on hypocortisolism & hypoaldosteronism: Fatigue & Hyponatremia (most important); Hypotension; Hyperkalemia; Hyperpigmentation (from ACTH); Death

Low morning cortisol <5

Failure of pit to secrete ACTH; caused by the same causes of Pan-Hypopituitarism

b/c secondary & tertiary adrenal insuff only involve low ACTH levels, the RAAS is still intact; Only cortisol is deficient.

Hyperkalemia & Hypotension are rarely seen; hyperpigmentation is not seen

Low morning cortisol <5; Low ACTH in setting of low cortisol; No Response to synthetic ACTH (cortrosyn) stim test; Insulin Tolerance Test; Metyrapone Test

baseline cortisol, then: 250 mcg IM Cortrosyn; cortisol s/b over 18 (if adrenal gland is working)

ACTH stims adrenal to make 11-deoxycortisol (which makes cortisol); Nml pit will drive up 11-d, if 11-d goes up & ACTH goes up, then pt has nml pit-adrenal axis;

Give metyrapone: blocks cortisol prodn, cortisol goes down, FB to hypo-pit, if pit working, more ACTH to inc cortisol

F: Amenorrhea/Infertility; M: Erectile Dysfunction/ Infertility; Inappropriately Low FSH/LH for low estrogen or testosterone

Hx (congenital or acquired); MRI Pituitary to assess for cause; Labs (prolactin; Iron/TIBC (Hemachromotosis); other Hormonal Work-Up; if estrogen level low, do Provera challenge); Give Hormone Replacement

No ADH; unable to conc urine; Polyuria; Polydipsia (esp night); UOP: 5-20 L / d; U spec grav < 1.0006; Hypernatremia; Normal Glucose

Follow every 1-2 hrs: Na; UOP, Urine Osmo; Wt; BP & HR (Lying / Standing); Once serum osm >300 & urine osm has not increased, give 10 ug of vasopressin and follow urine osm

distinguish btw central and (nephrogenic) DI; Nephrogenic: give AVP, kidney wont respond, urine remains dilute; Central: give AVP, later serum osm changes?

DM; Primary Polydipsia; CHF; Prostate Hypertrophy; Cushing syn (Excess Glucocorticoids); Other Osmotic Load (Calcium); Lithium; Parkinson Dz

Panhypopituitarism (often have intact ADH secretion with deficient ant pit hormones); Sarcoidosis/ Infiltrative Dz; Tumor; Trauma; Image Pituitary to Dx

Secondary Hypothyroidism; Hypocortisolism (secondary adrenal insuff); Amenorrhea, Menopause, Erectile Dysfunction, Infertility; Polyuria/Polydipsia

Investigate / Tx Underlying Cause (MRI pit); Replace Hormones (unless CI); Cortisol First; Thyroid Hormone; Sex Steroids: Estrogen (unless postmenopause); Testosterone

Galactorrhea; Amenorrhea; Infertility

ED; Infertility; HA; Mass Effect (eg, from tumor in head); Galactorrhea

Galactorrhea

Hyperprolactinemia; Pit Adenoma; Renal Fail; PG

Hyperprolactinemia; Pit Adenoma; Renal Fail; PG; Drugs; Other Pit Tumors; Hypothal Tumors; Chest Wall Stimulation

Anti-DA (Anti-psychotics; Reglan); TCAs; SSRI; Verapamil; Alcohol, esp Beer; Heroin; Cocaine

medical mgmt first (before surg); tumor size (< 1 cm: microadenoma; >1 cm: macroadenoma & must tx); mass effect or visual field disturbance? Is estrogen / testost prodn disrupted? Is fertility desired?

Dopaminergic Drugs if: Macroadenoma; Mass Effect; Visual Field Deficit; Fertilty Desired

No Fertility Desired; Microadenoma; Visual Field Full; No Mass Effect; Estrogen or Testosterone is low

Tx w/ Dopaminergic Drugs; DA inhib fx on prolactin; shrink tumor; Cabergoline / Bromocriptine; AE: nausea, hypotension

Acromeg: pit tumor secreting GH in adulthood; Gigantism: pit tumor secreting GH during puberty before epiphyseal plate fusion; rapid linear growth, heights up to 8ft 11

Arthropathy, neuropathy, CVD; HTN; resp dz; malig; CHO intol/DM

MEN-1 / other FH; Prominent Brow; Enlarged soft tissue of hands / ft; Teeth Splaying; DM; HTN/ LVH; Can be Subtle

Elevated IGF-1; GH Fails to Suppress <2 ng/mL after 75 g CHO load

Surgical; Somatostatin Analogs: Sandostatin; XRT

Too much Cortisol Prodn; Exogenous (Use of synthetic Glucocorticoids); Endogenous = Cushing Dz

DM; HTN; Osteoporosis; Psychosis; Easy Bruising; Truncal Obesity; Hyponatremia; Moon Facies; Buffalo Hump; Mx Wasting; Hirsutism; Purple Striae; Supraclavicular Fat; Infections

Pit ACTH overprodn; Ectopic ACTH Prodn; or Pit/Adrenal Adenoma producing cortisol; 75-80 % of cases with endogenous cortisol excess; elevated cortisol levels do not suppress hypothalamic & ant pit secretion of CRH & ACTH

Nonpituitary Tumors secrete ACTH and do not respond to negative inhibition of high cortisol levels

Small Cell Lung Ca; Carcinoid Tumors; Pheochromocytoma; Thymoma; Pancreatic Cell tumors; Medullary Ca of the Thyroid

ACTH & CRH are suppressed; Caused by: Adrenal Adenomas; Adrenal Ca; Micronodular or Macronodular Hyperplasia

24 hr urine for free cortisol (if >100, prob Cushing, if >300, def Cushing; Check Cortisol at night; Suppressing Cortisol with oral dex; checking ACTH levels

if suppress to <2, then do not have Cushing (dex provided enough glucocorticoid to pit, signals need not prod cortisol); if ACTH >2, prob has tumor that does not respond to dex

Do not do radiographic studies prior to lab studies (poss Incidental Tumors, False Negative Scans)

destn of primary gland: auto-immune (addison, thyroiditis) or surgical removal

Pituitary (PanHypopituitarism); Hypothalamus (Stress, Tumor)

Autonomous Fn of Primary Gland (Thyroid Toxic Adenoma); Autonomous Fn of Gland making Stim Hormone (Cushing Dz: ACTH); Ab’s that Stim Hor Receptor (Graves / TSI); Ectopic Prod Stim Hormone (Ectopic ACTH)