What type of gynecomastia reflects the imbalance between estrogen and androgen action on the breasts caused by increased sex steroid production, may be unilateral/bilateral, presents as a tender discoid enlargement of breast tissue 2-3 cm in diameter beneath the areola, and usually subsides within a year?
How does aging cause gynecomastia?
Testosterone levels decrease
Sex hormone biding globulin levels increase
This process reduces the amount of free testosterone levels
Defect in androgen action: elevated testosterone, elevated LH/FSH (insensitivity)
What laboratory tests should be performed when evaluating hypogonadism?
Serum total testosterone: 60-75% bound to sex-hormone binding globulin (SHBG)
Serum free testosterone: 1-2% of total testosterone lvl (biologically active portion)
LH and FSH: low lvls warrant further evaluation of pituitary function
What are the levels of testosterone by age group?
20-30 yrs: highest
30-40 yrs: lvls begin to decrease
>40 yrs: lvls continue to fall gradually
What are the causes of primary hypogonadism?
Klinefelter's syndrome: most common congenital cause of hypogonadism (seminiferous tubule dysgenesis)
Acquired gonadal failure
Other etiologies: lymphoma, anti-tumor chemo, radiation therapy, testicular trauma
What is the most common genotype in Klinefelter's syndrome? What is the phenotype?
What are the puberty findings in a pts with Klinefelter's syndrome?
Small, firm testes <2cm
Testes were normal size during childhood
Body hair & external genitalia mature to varying degrees
Gynecomastia, impotence, infertility
Testosterone decreased, estradiol increased
Eunuchoidal proportions, tall stature
47 XXY may be fertile
Osteopenia/osteoporosis if not treated
Karyotype required to confirm dx
What are the characteristics of cryptorchidism?
Occurs in 3% of full-term male infants
0.75% are still affected after 1 yr of age
Undescended testes may become cancerous after several years if not removed
What are the characteristics of bilateral anorchia (vanishing testicle syndrome)?
Testes are present 1st 14-16 weeks of gestation
Scrotum is empty at birth
Growth & development normal until secondary sexual development fails to occur @ puberty
Diagnose with hCG stimulation test: no increase in testosterone after injection with hCG confirms dx
What causes acquired gonadal failure at the level of the seminiferous tubules and Leydig cells?
Mumps, gonorrhea, leprosy
FSH level is usually elevated, but may be normal
Leydig cells: same as above plus aging (LH lvl usually elevated)
What is the treatment for primary hypogonadism?
Testosterone IM every 2-3 weeks: transdermal patches (testoderm, androderm) used on scrotal and non-scrotal areas (shoulder, upper arm/ abdomen); 1% testosterone gel (androgen) on same areas as patch; or oral agents (methyltestosterone, fluoxymesterone) just not as effective as IM therapy
Prostate cancer screening prior to therapy is appropriate for older men (DRE & PSA)
What are the contraindications to using IM testosterone for primary hypogonadism treatment?
Boys <13 y/o to avoid premature epiphyseal closure and short stature
What are the side effects if IM testosterone therapy?
decreased HDL levels
What is the follow-up procedure when treating primary hypogonadism?
Check testosterone @ 1 month, then every 6 months
Check lipid levels and Hgb/Hct at 3 months
DRE every 6 months, PSA
What are the causes of secondary hypogonadism?
What is the most common form of secondary hypogonadism?
What are the characteristics of Kallmann's syndrome?
5-alpha-reductase deficiency: variable degrees of gynecomastia, hypospadias, cryptorchidism
What are the characteristics of testicular feminization (genetic male)?
Testes function normally but are located intra-abdominally
Abnormal receptors in the pituitary gland don't recognize testosterone, development proceeds is if there is a lack of testosterone
External female genitalia observed with no uterus or fallopian tubes
No male accessory sex organs
Testes are cryptorchid
Child has appearance of normal pre-pubertal girl
At puberty testes secrete large amounts of testosterone that gets converted into estrogens by adipose tissue resulting in a phenotypic female with well developed breasts that never menstruates
What are the characteristics of incomplete testicular feminization?
Mixed pattern of virilization and feminization.
What is the treatment for testicular feminization?
There are NO treatments that can restore androgen receptors.
Pt's phenotype and gender assignment are female.
Intra-abdominal testes must be removed to avoid malignancy.
Estrogen treatment is provided to develop secondary female sexual characteristics.
What are the characteristics of 5-alpha-reductase deficiency (DHT deficiency)?
LH, FSH & testosterone levels are normal
Internal sex organ develop normally
Cryptorchid (intra-abdominal) testes present
Dihydrotestosterone-dependent structures fail to develop (prostate, external genitalia are poorly developed)
Individual appears female or has ambiguous genitalia at birth
At puberty testosterone levels rise dramatically to overcome the defect and secondary sexual characteristics develop (external genitalia becomes masculinized, penis develops, "guevedoce"=penis at 12)
What do osteoclasts and osteoblasts do?
-clasts: dissolve bone
-blasts: build new bone
How much of the total body calcium circulates in the blood? Of that how much calcium circulates as free (ionized) calcium, how much bound to proteins and how much bound to bicarb, citrate and phosphate?
1% total body calcium circulates in blood
50% circulates as free/ionized (active) calcium
40% is bound to proteins (albumin, globulin)
10% is bound to bicarb, citrate, phosphate
What are the primary regulators of serum calcium?
Parathyroid Hormone (PTH)
What is a very potent hormone that exerts major control over the plasma calcium concentration?
What are the actions of parathyroid hormone?
Stimulates resorption (or dissolution) of bone by osteoclasts, increasing delivery of calcium and phosphorus to the circulation.
Increases renal tubular reabsorption of calcium.
Stimulates renal activation of vitamin D which enhances intestinal absorption of calcium.
What stimulates PTH secretion from the parathyroid?
Falling free (ionized) calcium levels.
Stimulating suppressed by rising free (ionized) calcium levels.
How is vitamin D synthesized by the action of sunlight on the skin?
7-DHC (dehydrocholesterol) present in the epidermis is exposed to UV B light.
UV B-exposed 7-DHC continues to be transformed by the liver and kidney into the active form of vitamin D.
What is the action of vitamin D on calcium levels?
Vitamin D increases calcium and phosphate absorption from the intestines.
What hormone is produced by the parafollicular cells of the thyroid gland in response to an elevated serum calcium level and plays a minor role in plasma calcium concentration?
What is the action of calcitonin in regards to calcium levels?
Inhibits calcium resorption from bone (inhibits osteoclasts).
Increases calcium storage in bone.
Increases renal excretion of calcium.
When the serum calcium level decreases, what response will you see with PTH and calcitonin?
When the serum calcium level increases, what response will you see with PTH and calcitonin?
What are the three failures of calcium homeostasis?
Overtones: depression, memory loss, confusion, lethargy, coma
What are the etiologies of primary hyperparathyroidism?
Benign parathyroid adenoma (80%)
Parathyroid hyperplasia (20%)
What is the pathophysiology of primary hyperparathyroidism?
Excess PTH causes hypercalcemia
Much of the excess calcium is present in the glomular filtrate
Much of the excess in the glomular filtrate is excreted due to overwhelming the renal tubular reabsorption capacity resulting hypercalciuria
What are the signs and symptoms of hyperparathyroidism?
Most pts are asymptomatic
Total serum calcium >10.5 mg/dl (corrected)
Free (ionized) calcium level is elevated (>5.3 mg/dl)
Serum phosphate level is low (<2.5 mg/dl)
Hypercalciuria or normal urine calcium excretion occurs
Shortened QT interval on ECG may be observed
If total calcium is >14 mg/dl, pt may be confused, weak, and lethargic
What are the characteristics of parathyroid adenoma?
Common, esp in middle-aged women
Most presentations are mild/asymptomatic
24-hr urine calcium and phosphorus is increased
20% of pts develop kidney stones
X-rays are not required for diagnosing hypercalcemia but instead to check cortical bone mineral density (may be low) or to observe possible changes in distal finger tufts
How is hypercalcemia associated with a parathyroid adenoma treated?
Maintain good hydration
Surgery considered if: serum calcium is markedly elevated w/ symptoms, there is hx of prior life-threatening hypercalcemia, kidney stones present by abdominal Xray, 30% reduced creatinine clearance, 24-hr urine calcium >400 mg/24 hours, evidence of severe osteoporosis, pt is less than 50 yrs old, pregnancy (2nd tri), medical follow-up or pt compliance issues present.
How should you observe a parathyroid adenoma in an otherwise asymptomatic patient?
Follow up every 6 months
Ask about symptoms of hypercalcemia at each visit
What are some complications associated with hypercalcemia with increased PTH?
Pathologic fractures (more common)
Urinary tract infections from stones/obstruction may lead to renal failure and uremia
Parathyroid hyperplasia may be associated with what other endocrine disorder?
What is the clinical/lab presentation and treatment of parathyroid hyperplasia?
Presentation: same as parathyroid adenoma
Treatment: subtotal parathyroidectomy
What is the presentation of hypercalcemia with parathyroid cancer? How is it treated?
Severe hypercalcemia with very high PTH levels
Tumor resection along with affected thyroid lobe
What conditions cause hypercalcemia with increased PTH?
What conditions cause hypercalcemia with suppressed PTH?
Malignancies (other than parathyroid)
Excess vitamin D
High bone turnover
What are some other malignancies besides parathyroid cancer that can cause hypercalcemia?
Squamous cell cancer of lung, esophagus, head and neck, renal, bladder, ovarian, breast cancer.
What are the major mechanisms of malignancies that cause hypercalcemia?
Tumor production of PTHrP (PTH related protein)
Localized bone destruction (multiple myeloma, breast cancer, lymphoma)
Tumors may produce calcitriol causing hypercalcemia (Hodgkin's disease, non-Hodgkin's lymphoma)
How does PTHrP produced by malignancies cause hypercalcemia?
Causes bone resorption and hypercalcemia similar to the action of PTH.
High doses of exogenous vitamin D or excess endogenous production of vitamin D (excess vitamin D) cause hypercalcemia with suppressed PTH. What are some diseases that cause excess vitamin D production?
If pt is asymptomatic: annual alkaline phosphatase level and X-rays of lytic lesions
Treat complications (orthotics as needed)
Medications to decreased bone resorption by osteoclasts: bisphosphonates (tx of choice) given clinically until alkaline phosphatase level normalizes then is discontinued for 3 months, nasal calcitonin-salmon (not used often but still effective for some pts)
What is the leading cause of blindness in adults?
What is the normal fasting glucose range?
140 mg/dl on 2 hr OGTT
What is the impaired fasting glucose (IFG) range?
What is the impaired glucose tolerance (IGT) range?
OGTT level >/= 140-199 mg/dl @ 2 hr
What is the general age, weight, insulin requirement, ketone prone-ness, pathogenesis, fasting C-peptide level and percentage affected in type 1 diabetes mellitus?
Neuroglycopenic: behavior/cognitive changes, drowsiness, confusion, blurred vision, HA, amnesia, seizures, coma
What are the common causes for hypoglycemia?
Too much insulin: most common complication of insulin therapy
Insulinoma: otherwise healthy ppl
Too little food
Too much activity
Oral hypoglycemic agents
Gastroparesis (nerve damage delays stomach emptying, food is absorbed slower)
What is the treatment for mild to moderate hypoglycemia (BS <50)?
2-3 glucose tabs/gel (dextrosol)
4-6 oz OJ
4-6 oz reg soda
1/4-1/3 cup of raisins
5 lifesaver candies
Follow with complex carbs (milk/sandwich)
Glucagon if responsive but very symptomatic
What is the treatment for severe hypoglycemia/patient is unresponsive (BS <20)?
Home treatment glucagon kit: contains 1 ampule (1 mg), should be provided to every pt receiving insulin therapy, pt and fam/friends should be instructed on use
ER treatment: insure adequate airway, give IV glucose (50 ml of 50% solution), once pt is conscious they can sip fruit juice, if IV glucose isn't available, give glucagon 1 mg IM
What is the incidence of DKA?
5-8 episodes/1000 type 1 pts annually, may occur in type 2 esp during acute illness
Accounts for 20-40% of new pts
50-60% of children will have at least 1 episode
3-5% of events occur in infants < 1 yr
What are the risk factors for diabetic pts developing DKA?
Lapse in insulin administration: 15-41%
Recent onset diabetes: 17-25%
Medical illnesses: 10%
Trauma, ETOH, steroid use: 10-20%
What are the symptoms of DKA?
Polyuria, polydipsia for 1-2 days progressing to fatigue, nausea, vomiting, and mental stupor that can progress to coma.
What are the signs of a pt suffering from DKA?
Dehydration in stuporous patient
Rapid, deep breathing (Kussmaul's respirations)
"Fruity" breath odor (acetone)
May have abdominal pain/tenderness
What are the laboratory findings in pts with DKA?
Hyperglycemia (>250 mg/dl): due to decreased glucose uptake plus hepatic gluconeogenesis
Ketonemia (elevated serum acetone): elevated lvl of GH, catecholamines, and glucagon increase lipolysis from adipose and liver ketone production
Low arterial blood pH: <7.3
Low plasma bicarb: <15 mEq/L
Elevated serum potassium (may not reflect potassium depletion- dehydration)
Elevated serum osmolality
How is DKA managed?
Restore circulating plasma volume: there is 4-5 liter fluid deficit in most pts, use IV NS for 4 hrs then 1/2 NS for 4 hrs then consider D5 1/2 NS (glucose <250 mg/dl), avoid excess fluid replacement (>5 L/8 hrs), can cause ARDS or cerebral edema
Regular insulin: 10 U IV after 30 min or 0.1 U/kg/hr, goal is to maintain glucose lvl of 250-300 mg/dl to decrease risk of cerebral edema & hypoglycemia
If pH <7.0 give 100 ml bicarb over 45 min
Give potassium chloride 10-30 mEq/L during 2nd & 3rd hrs of fluid resuscitation as acidosis starts to resolve
Monitor serum osmolality
Search for precipitating cause
What are the sick day rule guidelines for preventing DKA?
Test urine ketones every 2-4 hours
Pt is to call if their blood glucose >250 for >6 hrs
Pt is to call if there are + urine ketones for >6 hrs
Pt is to continue taking insulin
Pt should eat and drink fluids if possible
If pt can't eat, they should drink carb containing liquids
What are the characteristic of hyperglycemic hyperosmolar nonketotic syndrome?
What are the signs and symptoms of hyperosmolar nonketotic syndrome?
Insidious onset of polyuria, polydipsia, and weakness over several days or weeks
Lethargy, confusion, coma
ABSENCE of Kussmall's respiration
NO acetone breath odor
Why is there such a high mortality rate (10x mortality rate of DKA) in hyperosmolar nonketotic syndrome?
Due to the insidiousness, organ dysfunction, and delayed diagnosis.
What are the laboratory findings in a pt with hyperosmolar nonketotic syndrome?
Severe hyperglycemia: BS 600-2400 mg/dl common
Elevated serum osmolality
Moderate to severe dehydration common
Hyponatremia initially, then a gradual increase
Elevated serum urea nitrogen (dehydration)
How are pts suffering from hyperosmolar nonketotic syndrome treated?
Fluid replacement (important!): 4-6 liters over 8-10 hrs, is pt is hypovolemic NS (0.9%) is used, if pt is not hypovolemic, 0.45% saline is used, once glucose level <250 mg/dl give 5% dextrose in water (D5W), 0.45% saline or 0.9% (decreases risk of cerebral edema and hypoglycemia)
Insulin: lower dose than DKA
Potassium replacement: 10 mEq/L given during initial IV fluid admin if potassium is not elevated
Look for underlying cause
What are microvascular chronic complications of diabetes mellitus?
Retinopathy: leading cause of blindness ages 20-74 in developed world
Erectile dysfunction: medical therapy includes viagra (50-60% improvement) and intracavernous injection of vasoactive drugs (papaverine), mechanical therapy (external vacuum), surgical therapy (implant of penile prostheses)
What are the cardiovascular (macro vascular) complications that occur with diabetes mellitus?
What are the cerebrovascular (macrovascular) complications that occur with diabetes mellitus?
Transient ischemic attacks (TIA)
How are macrovascular complications managed?
Keep BP less than 130/80
ACE inhibitor therapy
Angiotensin II receptor blocker (ARB)
BB may mask hypoglycemia!
Manage obesity and dyslipidemia: GOALS= LDL <100 mg/dl (<70 mg/dl for pts with CAD), HDL >40 mg/dl (males) HDL >50 mg/dl (females), trig <150 mg/dl (fasting), STATINS are the drug of choice for lipid control in diabetics
Regular exercise program
What are the factors responsible for diabetic foot problems?
Peripheral artery disease (PAD): often asymptomatic, sometimes presents as intermittent claudication; signs include absence of pedal pulses, poor ABI scores, absence of hair growth on lower legs
What are the steps to take for preventing diabetic foot problems in pts?
Comprehensive foot exam annually: visually check skin and tissue integrity, look at shoes for wear patterns, observe biomechanical integrity (gait, deformities), check pedal pulses, test sensation (vibration/pin prick/ankle reflexes)
Categorize findings as "low risk" or "at risk": pt at risk with loss of protective sensation, absent pedal pulses, foot deformity, hx of foot ulcer, prior amputation, smokes, hx of retinopathy, nephropathy, those on anticoagulant, those who can't see, feel or reach their feet (refer to podiatrist)
What are the essentials of patient education of foot care?
Shoes: wear them, diabetic shoes available through medicare, be sure shoes fit, shake them, NO SANDALS
Foot hygiene: wash and inspect daily, moisturize, toenail care
Avoid trimming corns and calluses: can cause infections or wounds (advise foot clinic!)
What are skin conditions that diabetic patients develop?
Fungal infections (thrush)
Necrobiosis lipoidica diabeticorum
What is the summary of "P" (diabetic management)?
Diabetes education classes
BP, pulse, ht and wt at every visit
Foot exam (including pulse) at every visit, monofilament exam annually
FBS (110-120 mg/dl), UA, Chem 10, HbA1C (<7%, ideally <6.5%) at every visit (2-4 times yearly for stable pts)
Serial microalbumin at initial diagnosis and annually (type 2 DM)