Endocrine Flashcards
Typical T4 replacement dose
1.6 mcg/kg
Clinical Presentation of Hypothyroidism
Extreme fatigue, Weight gain, depression, cold intolerance, dry skin/loss of hair, constipation, irregular, heavy menses, decreased concentration, forgetfulness, bradycardia, hypothermia, hoarseness, hyperlipidemia.
Hypothyroidism Lab Values
High TSH typically 5-10 mIU/ml. Treat > 5 w/symptoms and > 10 w/o sx.
Low TT4 (normal 5-12 mcg/dl)
Low free thyroxine (FT4) (normal 0.7-1.9)
Low TT3 (normal 80-180 ng/dl)
Thyroid antibodies present in Hashimoto dz
Low RAI uptake (RAIU)
True or False…All adults 18 y/o and older should be screened for thyroid disease every 5 years.
False. The US Preventative Services Task force found insufficient evidence to recommend for or against routine screening for thyroid disease in adults.
However the American Thyroid Association does recommend everyone older than 35 y/o be screened with a TSH test every 5 years.
Levothyroxine Treatment
Typically begins with TSH greater than 5 mIU/L
stable, pure, predictable potency
serum T3 is controlled physiologically
long half life, allows daily dosing
DOC American Thyroid Association/American Association of Clinical Endocrinologists.
Take on empty stomach but some studies show bedtime versus morning with improved levels.
Titrate dose to normalization of TSH , check TSH 6-8 weeks after each dose change then every 3-6 months during first year of diagnosis, and annually thereafter.
Thyroid Dz and Pregnant Women
Pregnant Women- treat even mildly elevated TSH
Increase T4 replacement by 30% with first detection of pregnancy
Monitor TSH monthly and adjust dose accordingly
Typically wil need a 40-50% increase in T4 dose.
Some evidence that T4 is a better marker in pregnancy vs TSH.
Cardiac Disease and Thyroid Treatment
Start low 12.5 mcg and go slow in 12.5 mcg increments every 6-8 weeks.
Drug Interactions with Levothyroxine
- Decrease in T4 absorption , take T4 2 hours before or 4 hours after. Cholestyramine, Calcium, Ferrous sulfate, sucralfate, aluminium hydroxide.
- Increase in T4 metabolism. Rifampin, Phenytoin, Phenobarbital, Sertraline
- Pharmacodynamic interactions. Warfarin, Digoxin.
Hyperthyroidism Causes/Clinical Presentation
Causes: Toxic diffuse goiter (graves dz), toxic adenoma, toxic multinodular goiter, subactute thyroiditis, silent thyroiditis, iodine-induced, excessive ingestion of thyroid hormone, drugs (amiodarone), tumor
Clinical Presentation: Heat intolerance or increased sweating. Tremor Palpitations and tachycardia Nervousness and irritability Frequent bowel movements or diarrhea less frequent, shorter, lighter menses fatigue and muscle weakness thyroid enlargement weight loss despite and increased appetite Exopthalmos and/or pretibial myxedema (in graves dz only) insomnia Elderly may have minimal s/s.
Diagnosis of Hyperthyroidism
PE: Increase HR, Thyroid palpation, eye exam, dermatologic exam
Labs: Low TSH (in primary dz, could be high in secondary dz but rare) High TT4 High FT4 High TT3 Thyroid antibodies High RAIU Thyroid scan
Treatment for HTR- Radioactive iodine
Most common tx of HTR in US
C/I in pregnancy and breastfeeding
Very high risk of subsequent HoTR
Treatment for HTR- Surgery
TOC for thyroid cancer, respiratory, or swallowing difficulties
find an experienced surgeon
hypothyroidism
Treatment for HTR- Thioamides
Medications are noninvasive, minimal risk of HoTR but potential for ADRS and need long term adherence.
MOA: inhibits organification and coupling; PTU also inhibits the peripheral conversion of T4 to T3. DELAYED EFFECT (weeks)
PTU: 300-600 mg/day in 2 or 3 doses, preferred in 1st trimeter of pregnancy, lactation and thyroid storm.
Methimazole (Tapazole): 30-60 mg/day in 1 or 2 doses, longer half-life, better adherence, LESS HEPATOTOXICITY, recommended thiamide unless first trimester of pregnancy.
Often used before RAI therapy, may use for 18-24 months in Graves Dz.
ADRs Rash, fever, arthralgias, severe agranulocytosis, hepatitis.
Need to get CBC on patients before they start therapy.
Treatment for HTR- Iodides
MOA: block thyroid hormone release, inhibit organification, inhibit peripheral conversion of T4 to T3. Decrease gland size/vascularity, Rapid onset (days)
Dose:
Saturated solution of potassium iodine (38 mg/drop): 1-5 drops in juice 3/day.
Lugol’s solution (6 mg/drop): 3-5 drops in juice 3times/day
Radiographic iodinated contrast agents (1 gram daily)
Most often used in graves dz patients before surgery and in thyroid storm.
ADRs:
Allergic reactions, dose-related toxicity, metallic taste, “escape” phenomenon.
CI:
Pregnancy
Before RAI therapy
Patients with nodular goiter or adenomas.
Treatment for HTR- Beta Blockers
MOA: selective inhibitor of B1 adrenergic receptors (manages sympathetic-mediated hyperthyroid symptoms)
Inhibit T4 conversion (propranolol, nadolol)
Quick onset, (hours)
Propranolol 120-160 mg/day in 3-4 divided doses
Nadolol 80mg/day in 1 or 2 doses.
Used until more specific thyroid therapy can take effect.
ADRS
Hypotensio/Bradycardia/Fatigue.
PCOS Causes/Clinical Presentation/DX
Excess androgen production in the ovaries..leads to insulin resistance. Excess insulin also decreases hepatic synthesis of sex hormone- binding globulrin (SHBG) which normally binds free T, resulting in increased hirsutism.
CP: Chronic anovulation Hirsutism Acne Male pattern hair loss Hyperandrogenemia Insulin Resistance Acanthosis nigricans, overwieght/obese IGT, nonalcoholic steatohepatitius, abdominal obestiy.
Dx: Two of the following
Oligovulation or anovulation, elevated circulating androgens, Polycystic ovaries 12 or more 2-9mm diameter follicles in each ovary or increase ovariam volume
PCOS Treatment
Weight reduction (5-7% ) has shown improvement in androgen levels Exercise decreases insulin resistance.
Infertility: Weight loss, clomiphene, metformin
Hyperandrogenism/hirsutisim: OCs
Other:
Sprionolactone,
Elfornithine (Vaniquia) reduces hair growth
Flutamide (potent nonsteroidal antiandrogen, 250 mg daily, hepatotoxicity conerns, CI in liver dz/pregnancy)
Cyproterone: Antiandrogen often used in combo with OCs.
Topical Minoxidil for alopecia
Insulin Resistance: metformin, pioglitazone
Menstrual Irregularities/endometrial hyperplasia/OCs
See chart Table 1 on page 183 of chapter.
Prolactinoma What is it? Causes?
Pituitary tumor, that secretes excessive amounts of prolactin, most common type of pituitary tumor
Prolactin levels >30 ng/ml
Normal 15-25 ng/dml
Causes:
Levels > 200 ng/ml are usually associated with a tumor.
Modest prolactin elevation 30-100 ng/ml Pregnancy Stress Hypothyroidism Kidney failure Liver faitlure Medications "Stalk effect" any dz within or near the pituitary that interferes with delivery of dopamine from hypothalamus to prolactin secreting cells. No longer under chronic inhibition.
Drug Induced Hyperprolactenemia Causes
Dopamine antagonists: (phenothiazine, TCS, metoclopramine) SSRIs, estrogen-progesterone, Methyldopa, Verapamil, Gondadotropin-releasing hormone analogs.
Clinical Presentation of Prolactinomas
Women: Reproductive age, irregular periods, infertility, galactorrhea, reduction in sex drive, vision loss/ha, osteoporosis.
Men: 50-60’s, decreased libido, erectile dysfunction, loss of body hair. Vision loss/ha, osteoporosis.
Treatment of Prolactinomas
Transsphenoidal surgery
Radiotherapy
Drug Therapy: TOC D2 receptor agonists, stimulate postsynaptic dopamine receptors in the hypothalamus.
- Bromocritine Dose start at 1.25 mg once daily or BId and increase weekly up to 15 mg/day (preferred for fertility),
- Cabergoline 0.25 mg Bid, maximal dose of 1 mg BID. Drug interactions with 3A4 inhibitors, less nausea.
Growth Hormone Excess-Acromegaly, Causes/CP
Causes: pituitary adenoma, rarely cuased by tumors of the pancrease, lung, ovary, or breast.
CP: Enlarged hands and feet excessive sweating coarse facial features several skin tags deepened voice osteoarthritis sleep apnea increased risk of DM, colonic polyps, colon CA, CAD
Growth Hormone Excess-Acromegaly Dx
Elevated serum GH level in the fasting state and after an OGTT
Elevated IGF-1 (somatomedia C) ideal screening test
MRI with special cuts of pituitary
Growth Hormone Excess-Acromegaly- Treatment
Transsphenoidal sugary (TOC) Stereotactic radiosurgery Drug Therapy (when surgery has failed or is contraindicated) Dopamine agonists (bromocriptine, cabergoline) relative lack of efficacy
Octreotide and ocreotide LAR (Sandostatin)
Lanreotide
Pegvisomant
Octreotide
MOA: Bind to somatostatin receptors and cause directo inhibition of GH secretion.
Long term use can cause some soft tissue manifestations of disease
Reduces tumor size
Dosing 50-100 mcg sub-q every 8-12 hours. LAR version, 20mg IM every 4 weeks.
Dose to GH levels less than 1 ng/ml, and IGF-1 levels less than 2 units/ml
ADRs Diarrhea Nausea GI cramps Fever Dizziness Hyper- and hypoglycemia Cholelithiasis Hypothyroidism
Drug Interactions: Cyclosporin, B-blockers, CCBs
Efficacy 95% symptom relief, 2/3 of patients will normalize IGF-1 levels.
Lanreotide SR and Lanreotide Autogel) Somatuline Depot)
Synthetic octapeptide analog of somatostatin
Slow real ease: start with 60 mg IM every 2 weeks and titrate
Depot 90 mg sub-q every 4 weeks for 3 months, then adjust dose on the basis of GH and IGF-1 levels.
Pegvisomant (Somavert)
Consider in patients with high IGF-1 levels unresponsive to somatostatin analog therapy.
MOA: GH-receptor antagonists; blocks the binding of endogenous GH leading to decreased IGF-1 levels.
used in patients resistant or intolerant to ocreotide
No associated with reduction in tumor size.
Dosing: 40 mg sub-Q loading, then 10mg Sub-Q daily. Increase by 5 mg increments at 4-6 week intervals on basis of IGF-1 levels. maximal dose 30mg/day.
ADRs
HA, Diarrhea, Nausea, Increase in LFTS, Hyperglycemia, Flulike Sx
95% of patients with sx relief, 95% with normalized IGF-1, use may be associated with increase in tumor size.
GH Deficiency Causes/CP/DX
Causes: Congenital & Pituitary injury (tumor, surgery, radiation therapy, trauma, infection)
CP Delayed growth of child, height of 2 STD or more below age, central obesity lethargy and fatigue, decreased strength.
Dx
Rule out other causes of growth delay (malnutrition, HoTR), low GH levels despite insulin challenge or arginine challenge.
Treatment of GH Deficiency
Recombinant GH (somatropin- Genotropin , Humatrope, Norditropin, Nutropin, Omnitrope, Sizen, Serostim, Tev-Tropin)
Administer in the evening
ADRs Fluid retention Carpel tunnel Arthralgias Myalgies
Montior Growth curve LFTs, glucose IGF-1 levles, Funduscopic exams Height
Obesity Definition
BMI of 30 kg/m2 or greater
Overweight is BMI 25-29.9 kg/m2
Waist circumference may be a better way to measure risk for obestiy related health proems, men >40 inches, women over 35 inches
Obesity Treatment- Diethlpropion
Brand- Tenuate
MOA; Sympathomimetic increases norepi and dopamine
Efficacy short term 3-4 kg weight loss, 25 mg TID with meals or 75 mg controlled release in the morning.
ADRs
Dry mouth, constipation, insomnia, asthenia
CI:
MAO-I use w/i 14 days, Pulmonary HTN, HTR, CAD, Gluacoma, Hx of substance abuse
High abuse potential. FDA schedule IV.
Obesity Treatment- Phentermine
Brand: Adipex P
MOA: Sympathomimetic; suppresses appetite
Short term efficacy 3-4 kg weight loss.
Dose 15-37.5 mg TID before meals
ADRs
Palpitations, tachycarida, HTN, Dry mouth, Constipation, Insomnia, Asthenia, Pulmonary HTN and Valvular Heart dz
CI:
MAO-I use in the last 14 days, Hx of heart failure, CV dz, arrhythmia, stroke, or glaucoma
Not evaluated in children less than 16
High Abuse potential, only allowed for 12 weeks, then must be off for 6 months. FDA schedule IV.
Obesity Treatment: Orlistat
Brand names, Xenical, Alli
Only drug approved for long term use
MOA: gastric and pancreatic lipase inhibitor, reduces absoprtion of dietary fat (around 30%)
Dose over 60 mg (OTC) or 120 mg (Rx) TID with meals containing fat.
ADRs
GI adverse effects caused by malaborption of fat (oily spotting, flatus with dischrage, fecal urgency, fecal incontinence- but no diarrhea), bloating, cramping.
CI:
Chronic malabsoprtion syndrome
Cholestatis
Safety not established in pregnant or lactating women (I don’t’ know why someone would use this during pregnancy and I would say unsafe…baby needs fat for brain development!)
Drug-Interactions
Fat-soluble vitamins
Cyclosporine
Warfarin
Must take MVI with ADEK 2 hours before, 30-40 % discontinuation rate.
Obesity Treatment- Phentermine/Topiramate
Qsymia-Brand name
Initial Dose: Phentermine 3.75 mg/topiramate 23 mg once daily for 14 days, then dose gets doubled for 12 weeks.
Same CI as Phentermine alone.
ADRs Renal caclus with topiramate.
C-IV
Obesity Treatment- Surgical Intervention
Gastric Bypass: 30-40 Kg weight loss maintained for 10 years, decreased morbidity and mortality, serous nutritional deficiencies associated iron, B12, folate, calcium
Laparoscopic adjustable Gastric Banding:
20-30 Kg weight loss maintained for 5 years, decreased morbidity and mortality
Liposuction: No long term reduction in weight, no significant improvements in metabolic or cardiac risk factors, not recommended for weight loss.
The 5 S’s of adrenal crisis managment are….
- Salt
- Sugar
- Steriods
- Suppot
- Search (for underlying cause)
Causes of Addison Dz
a. Primary: The adrenal gland (audoimmune, drug induced,)
b. Secondary: Pituitary or hypothalamic problem
(abrupt discontinuation of exogenous corticosteriod therapy, pituitary dz, drug-induced (medroyprogesterone, megestrol)
Clinical Presentation of Addison Dz
Autoimmune cause seen in women 2-3 fold more often than men, primary dz most common in 20’s-40’s.
Weakness Fatigue Anorexia Nausea Salt craving (in primary dz loss of aldosterone production) Dizziness Hypotension/Hypovolemia Dehydration Weight Loss Decreased axillary/pubic hair Tan appearence
Physical Exam: Low BP, Orthostatis, Hyperpigmentation
Labs: Low plasma cortisol (less than 5 mcg/dl) Cosyntropin (cortrosyn) stimulation test Hyperkalemia (less than 50% of cases) Hyponatremia (80%) Hypoglycemia
Glucocorticoid Preparations
Equivelent Doses and Mineralocorticoid Activity
Cortisone Equivelent Dose 25mg- Mineralocorticoid Activity 2+
Hydrocortisone ED 20mg MCA 2+
prednisone ED 5mg, MCA 1+
Methylprednisolone ED 4 mg MCA 0
Dexamethasone 0.75 mg, MCA 0
Adrenal Crisis Treatment
Hydrocortisone 100mg IV for 8 hours for 24 hours, then 50mg every 6-8 hours after hemodynamic stability, tapered to maintenance dose after 4-5 days.
(Mineralocorticoid replacement need not be added in the acute setting as long as the total daily hydrocortisone dose is > 50mg )
Also give Normal Saline/5%dextrose: several liters (the Salt and Sugar of the 5 S’s)
Adrenal Crisis Maintaince Therapy
Hydrocortisone 20mg QAM, 10mg late afternoon
Fludrocortisone 0.05-0.2 mg every morning
On Sick days, double or triple their GC replacement dose.
Cushing Syndrome Causes
Pituitary (65-75% of cases), Adrenal (15-20%) adrenal adenoma and carinoma, Ectopic, iatrogenic (most common)
Clinical presentation: Central obesity with moon face, buffalo hump, ecchmoses, facila plethora, hypertension, glucose intolerance, myopathy with or without proixmal muscle weakness, neuropsychiatric symtpoms, back pain, oligo/amenorrhea, straie, hirsutisim, acne, funal infections, hypokalemia.
Cusing Syndrome Diagnosis
24 hour free cortisol, 1 mg overnight dexamethasone suppression test.
Cusing Syndrome Treatment
Surgical in TOC if the tumor can be localized and no CIs.
Irradiation of the pituitary 6-12 month lag time, high incidence of pan hypopituitarism (reserved for sergical failures)
Drug InducedL Taper and DC GC as soon as possible.
Medical (only used in patients with unlocalized of unresectable tumors, not surgical candidates, etc.)
Cusing Treatment-Ketoconazole
400-1200 mg/day in divided doses, start at 200mg/day and increase by 200mg/day every 2-3 days. ADRs Nausea, Hepatotoxicity, Gynocomastia, Adrenal insufficiency
Cusing Treatment-Metyrapone
Metyrapone steriodgenic inhibitors MOA: inhibits the final step in cortisol synthesis. Dose 1-4 grams/day divided every 6 hours. Must give GC replacement. ADR, N/V Anorexia, Dizziness, HA, Sedation, Hirsutisim and acne, Hypokalemia and HTN
Cusing Treatment-Aminoglutethimide
Brand Name Cytadren
MOA: Steroidogenic inhibitors, blocks the conversion of cholesterol to pregnenolone, therby inhibiting the synthesis of all steriod-derived hormones.
Dose: 500-2000 mg/day divided every 6-12 hours.
GC replacement is required
Often used with metyrapone in pituitary Cusing
ADRs Anorexia, NV, lethargy, drowiness, dizziness, Hepatotoxicity, Rash
Cusing Treatment- Mitotane
Brand- Lysodren
Adrenolytic, inhibits 11B-hydroxylaste and adrenal cholesterl synthesis. Adrenolytic agent at higher doses cuasing adrenocortical atrophy.
Dose 2-12 g/day didvided every 6 hours. Requires GC dose for life (50% permanent hypoadrenalism if treated. 6 months, consider hospitalization before initiatinon)
ADR
Anorexia, NVD, Lethary, somnolence, Rash, Hypercholesterolemia.
Other Drug Treatment Cusing Syndrome
Etomidate
Spironolactone
Etomidate, anesthic parenteral use only , use limited to patients awaiting surgery
Spironolactone, someones used to treat the HTN and hypokalemia in Cushing Syndrome.
Hyperaldosteronism- Cause/Clinical Presentation/DX
Excessive production of aldosterone , primary from adrenal cortex, bilateral adrenal hyuperplasia and aldosterone-producing adenoma, and secondary bilateral adrenal hyperplaisa, aldosterone-producing adenoma, adrenal carcinoma, licorice ingestion, pseudohyperaldosteronism.
CP: Weakness Muscle cramping Paresthesias Headache Fluid retention Polyuria, polydipsia HTN Lab tests: Hypokalemia, hypernatremia, hyperglycemia, metabolic alkalosis
DX Elevated plasma aldosterone-plasma renin activity ration >20, 24 hour urine for aldosterone more than 12 mg/day, CT scan adrenal venous sampling.
Treatment Hyperaldosteronism
Surgical for Adenomas
Drug Therapy
1. Spironoloactone (Aldactone) 25 -50 mg BID to start, max dose 400mg a day ADR Gynecomastia, Nausea, Impotenice, menstrual irregularities, Hyperkalemia.
Epleronone (inspra) Specific aldosterone antagonist with low affinity for androgen and progestrone receptors. Dose 50mg/day may increase to BID. ADR Gynecomastia only 1% vs. 9% with Spironolactone and Hyperkalemia.
Male Hypogonadism Causes/CP/DX
Causes- Primary Testicles, Secondary, Pituitary or hypothalamus or other
CP:Decreased sexual desire, ED, loss of body hair, loss of energy/fatigue, depression, loss of muscle mass with increased body fat, osteoporosis.
DX: Should only be sought in men with s/s then confirmed with low total T levels less than 300 ng/dl. Serum LH and FSH used to distinguish b/t primary and secondary causes.
Male Hypogonadism Treatment- Oral Androgens
methyltestosterone, Fluoxymesterone (hepatotoxic) oral T replacement products should not be used.
Male Hypogonadism Treatment- T esters
T enanthate (Delatestryl, T cypionate (depot T), Administred as a deep intramuscular injection, 200-400 mg eery 2-4 weeks, results in high peaks (fluid retention, polycytehmia) and low trough. (symptoms of T crash)
20% of patients are on this type of therapy.
Inexpensive
Male Hypogonadism scrotal patches
Good absorption and physiologic levels but require shaving of scrotal skin, apply daily. Testoderm 4 and 6 mg patches.
Male Hypogonadism, non-scrotal patches
Physiological levels of T but skin irritation (about 1/3) and limited flexibility in dosing.
Androderm (2.5, 5, 7.5 mg/day) once nightly new doses of 2mg and 4mg also available.
Testoderm TTS 2.5 and 5 mg patches, can apply to arm, back or upper buttocks.
Monitoring- measure T levels 3-12 hours after patch application.
Buccal Testosterone
Mucoadhesive tablet that provides controlled release of T through buccal mucosa, avoids first pass metabolism, gum irritation , gum tenderness, bitter taste ADR.
Dose 30 mg applied to the upper gum BID (Striant)
Measure T level immediately before or after application.)
Testosterone Gels
Patient Needs to allow to dry on skinb efore dressing, apply at least 2-6 hours before showering or swimming. most popular T-replacement products (70% of patient susing)
Hydroalcoholic 1 % or 2% gel
Physiologic levels of T
Precautions need to be taken to prevent transference to partner and exposure to children.
Dose 5-10 mg appplied once daily , preferably in the morning.
AndroGel, packets or pump
Testim 5 gram packets 30 ct box
Fortesta, pump
Measure T at least 2 hours after application after on treatment for a minimum of 14 days
Testosterone implantable pellets
Each pellet containes 75 mg of crystalline T, releases slowly over months.
150-450 mg implated Sub-Q every 3-6 months (Testopel)
Testosterone Solution
Hydroalcoholic 2% T soluation, physiologic levels of T, precautions to prevent tranference to partner (less likely than with gels)
Applied once daily in the morning. 60mg
Axiron comes in pump
ADRs & CI for Testosterone Therapy
Edemia, Acne, Gynecomastia, Polycythemia, dyslipidemia, worsened sleep apnea, HTN, hair loss/balding, infertility, site reactiosn (injections)
CI: Hx of breast or prostate cancer Enlarged prostate or palpable nodule (PSA > 3 ng/ml) Severe untreated BPH Erthrocytosis (HCT more than 50%) Untreated obstructive sleep apnea) Severe unctronlled CHF (class III or IV) pregnancy and breastfeeding.
Testosterone Monitoring
Baseline: Sx, BP, prostate examination, lab values
F/U 1 and 3 months, symptoms lab values (free T, DHT, SHBG, estradiol levels, hematocrit, PSA 1 and 3 months then annually) LFTs and cholesterole annual, DXA after 1-2 years,
PE: BP rectal exam, observe for acne, gynecomastia, hair loss, edema, local skin rxn
