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Repro/Endo flashcards > Endo > Flashcards

Endo Flashcards

1
Q

Fasting glucose criteria for DM (normal vs DM)

A

Normal fasting glucose < 100 mg/dL
Diabetes= 126 mg/dL or greater
Impaired fasting glucose (pre-diabetes)= 100-126 mg/dL

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2
Q

Oral glucose tolerance testing criteria

A

75 gm glucose in fasting state
Diabetes: Glucose >= 200 mg/dL at 2 hrs
Impaired glucose tolerance: glucose= 140-199 at 2 hours
Normal: glucose < 140 at 2 hours

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3
Q

HbA1c

A

Normal < 5.7%
Risk: 5.7-6.4%
Diabetes >= 6.5%
* Study show dramatic increase in retinopathy above HbA1c level of 6.5%

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4
Q

Criteria for diagnosis of diabetes

A

A: fasting glucose >= 126 mg/dL
B: 2 hr OGTT >= 200 mg/dL
C: random plasma glucose >= 200 mg/dL with symptoms
D: A1c >= 6.5%
* criteria A, B, D should be confirmed by repeat testing

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5
Q

Effects of insulin on liver

A

Inhibits glucose output, gluconeogensis, glycogenolysis

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6
Q

Effects of insulin on Skeletal muscle

A
  • Stimulates glucose uptake/metabolism
  • Stimulates amino acid uptake, protein synthesis
  • Inhibits protein degradation
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7
Q

Effects of insulin on adipose tissue

A

stimulates glucose uptake, metabolism; decreases hydrolysis of triglycerides, release of FFA

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8
Q

Type 2 DM requiring insulin

A
  • Hyperglycemia despite maximum effective oral agents
  • Significant hyperglycemia at presentation
  • Acute injury, stress, infection
  • High plasma glucose, unexpected weight loss (insulin deficiency)
  • Surgery
  • Pregnancy (only insulin indicated)
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9
Q

Disadvantages of insulin

A

Injections
Hypoglycemia
Weight gain (esp. with decreased exercise)

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10
Q

Basal insulin delivery effects

A
  • Suppresses ketogenesis, hepatic glucose output
    Constant levels
    ~50% of insulin requirements
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11
Q

Bolus insulin delivery effects

A
  • Limits hyperglycemia after meals
  • 10-20% daily insulin requirement (depending on carb levels in meal)
  • Rapidy delivers to bloodstream, rapidly goes down as blood glucose falls post-prandially
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12
Q

Rapid acting insulin analogs

A

Lispro, aspart, glusisine

  • 15 minute onset
  • 1-2 hour peak
  • 3-5 hour duration
  • don’t need to dose long before eating
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13
Q

Short-acting insulin

A

Regular (soluble, crystalline)

  • 30-60 min onset
  • 2-4 hours peak (can cause hypoglycemia)
  • 6-8 hour duration
  • not used as commonly, but cheaper (needs to be taken longer before eating)
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14
Q

Intermediate insulin

A

Neutral protamine Hagedorn (NPH)

  • 2-4 hour onset
  • 4-10 hour peak (can cause mid-day or night time hypoglycemia)
  • 12-16 hour duration
  • not used as commonly due to hypoglycemia, weight gain
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15
Q

Basal insulin analogs

A

Glargine, Detemir

  • 2-3 hour onset
  • peakless- mimics basal insulin secretion
  • 20-24 hour duration (Glargine), 14-18 hour duration (detemir)
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16
Q

Premixed insulin formulations

A

Stable premixed insulin formulations for patients who do not want to do 4 shots per day (delivered as 2 shots)
Less ideal- does not mimic insulin secretion

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17
Q

Continuous subcutaneous infusion of insulin

A

Programmable mechanical pump:

  • Basal insulin adjusted over 24 hour period
  • Bolus easily delivered at mealtimes/snacks
  • Rapid-acting insulin
  • Subcutaneous catheter is changed 48-72 hours
  • does NOT replace need for glucose testing (open loop system), pump is expensive
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18
Q

Non-fasting glucose criteria for Diabetes

A

Random glucose >= 200 mg/dL

  • Without regard to meals/time of day
  • Associated with symptoms of diabetes
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19
Q

Metformin

A

Oral agent for T2DM

  • improves insulin sensitivity at the liver
  • reduces hepatic glucose production
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20
Q

Thiazolidinediones

A

Oral agent for T2DM

  • improves insulin action in peripheral tissues
  • Changes composition of adipose tissue (visceral–> subcutaneous) via action on PPAR-gamma
  • Enhances glucose uptake
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21
Q

Sulfonylureas/Repaglinide/Nateglinide

A

Oral agent for T2DM

- Enhances meal-mediated insulin release

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22
Q

Alpha-glucosidase inhibitors

A

Oral agent for T2DM

- decreases post-prandial glucose absorption

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23
Q

Causes of altered mental status in diabetic patients

A
  • Hypoglycemia
  • Hyperosmolar, hyperglycemic, non-ketotic state (HHNK)
  • Diabetic ketoacidosis (DKA)
  • Lactic acidosis
  • Alcoholic ketoacidosis (EtOH blocks gluconeogenesis, but glucose lower than in DKA)
  • CNS events (drugs, stroke)
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24
Q

Precipitating factors for hyperglycemia/DKA

A
  1. Insulin (lack of insulin), insufficiency= 40%
  2. Infection (anywhere)- pneumonia, UTI= 30%
  3. Ischemia (CNS, CVS, GI)
  4. Infarction (anywhere- MI, stroke)
  5. Drugs (steroids increase peripheral insulin resistance, diuretics block insulin secretion, antidepressants, cocaine)
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25
Q

Insulin deficiency and ketoacidosis

A

Low insulin–> hyperglycemia (increased hepatic glucose production, decreased peripheral glucose uptake)
* Body perceives state of hypoglycemia (though opposite occuring)–> increased generation of glucose, breakdown of fats

Ketoacidosis: increased lipolysis, FFA released from adipose tissue, increased ketogenesis, decreased peripheral utilization of ketone bodies

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26
Q

Clinical spectrum of DKA/HHNK

A

In T1DM, stopping insulin for 1 day can lead to DKA. Not as common in T2DM as suppression of ketogenesis is 10x more sensitive to insulin than glucoregulation (therefore even small amounts of endogenous insulin prevent DKA)

HHNK (pure hyperosmolar state) has slower onset as it takes long time to develop significant dehydration

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27
Q

Hormonal abnormalities responsible for hyperglycemia and DKA

A
  1. Absence of insulin/resistance

2. Glucagon excess (unopposed by insulin)

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28
Q

Anion gap and DKA

A

Serum (Na+) - (Cl- + HCO3-)
Normal= 8-16

DKA= 21+; ketone bodies (acetoacetate= AcAc, beta-hydroxybutyrate= beta-OHB) anions. Ratio of beta-OHB/AcAc increases in DKA. **Diagnose DKA by measuring beta-OHB.

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29
Q

Etiology of DKA

A
  • Beta cells fail to make insulin (initial presentation of T1DM often DKA)
  • Dehydration: glycosuria (dump water with glucose)–> seen in elderly, ill
  • Drug therapy (glucocorticoids, diuretics/K+ depleting drugs)
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30
Q

Clinical manifestations of DKA

A
  • Polyuria, nocturia
  • Thirst (polydypsia)
  • Nausea/vomiting (excess sugar decreases GI motility)
  • Malaise, weakness
  • Fruity breath smell (ketones)
  • Deep sighing (Kussmaul’s) to blow off CO2
  • Abdominal pain mimicking pancreatitis, surgical abdomen
  • Dehydration: decreased pulse, BP, skin turgor
  • Changes in consciousness (due to hyperosmolarity)
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31
Q

Lab findings in DKA

A

Hyperglycemia (blood glucose < 800 mg/dL in T1DM)

  • Acidosis (ketone bodies): pH < 7.3, HCO3 < 15
  • Hyperkalemia (K+ moves out of cells, decreased RBF)- monitor K when beginning hydration
  • Elevated WBC: 15,000 (without infection, or + fever= infection)
  • Elevated lipids
  • Plasma Na+ falsely lowered due to glucose/lipid excess in blood
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32
Q

Ketogenesis

A

Blood glucose low/ can’t be used as fuel (starvation, DKA), liver converts FFA to ketones so brain can use as energy source

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33
Q

Treatment of DKA

A
  • Flow sheet to track vitals, labs
  • FLUIDS: vigorous replacement in DKA and HHNK (up to 10L)
  • INSULIN: early, with fluids (immediate in DKA)
  • Ions: early replacement of K+ to avoid hypokalemia with reversal of acidosis (K+< 3.3mEq/L)
  • NG suction (atonic stomach in DKA emptied to avoid aspiration)
  • Resolve precipitating factors
  • Bicarbonate therapy in severe acidosis (pH<7)- seen in coma
  • Monitor for late complications
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34
Q

Complications of DKA/treatment

A
  • Cerebral edema (rehydration–> hypoosmolar state–> swelling in brain)
  • Adult respiratory distress syndrome (ARDS) due to cerebral edema or blowing off excess CO2
  • Aspiration of vomit
  • Thromboembolism
  • Death
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35
Q

Patient characteristics in DKA

A
  • Usually < 40 (can be any age with T1DM, but this is usually first incidence)
  • Patient walks into ER
  • Symptoms for < 800 mg/dL
  • pH < 330 mOsm/kg
  • High ketone
  • < 5% mortality
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36
Q

Patient characteristics in HHNK Coma

A
  • > 40 years
  • Found comatose (homeless, lives alone)
  • Symptoms > 5 days
  • Glucose > 800 mg/dL
  • Normal pH
  • Serum osmolality > 300 mOsm/kg
  • may have ketones
  • > 50% mortality
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37
Q

Symptoms of Hypoglycemia due to adrenergic response

A 
Sweating
Tremulousness
Palpitations
Anxiety and confusion
Hunger
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38
Q

Symptoms of hypoglycemia due to neuroglycopenia

A 
Confusion, irritability
Psychotic behavior
Diplopia
Motor incoordination
Paresis
Coma
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39
Q

Whipple’s triad for hypoglycemia

A

Symptoms/signs of hypoglycemia
Blood glucose < 50mg/dL
Recovery by glucose administration

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40
Q

Glucose threshold for decreased insulin secretion

A

80 mg/dL

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41
Q

Glucose threshold for increased glucagon, epineprine, cortisol, GH

A

65 mg/dL

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42
Q

Glucose threshold for symptoms for hypoglycemia

A

55 mg/dL

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43
Q

Glucose threhold leading to cognitive dysfunction

A

45 mg/dL

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44
Q

Fasting hypoglycemia: causes

A
  • Insulin overtreatment
  • Oral drugs for T2DM (sulfonylureas, insulin secretion enhancers)
  • Islet cell tumor (insulinoma)
  • Endocrine deficiencies (GH, cortisol)
  • Advanced liver disease (poor glycogen storage/gluconeogenesis)
  • Rare causes: autoimmune (antibodies to insulin receptor, large non-islet cell tumor producing insulin-like hormones)
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45
Q

Factitous hypoglycemia

A

Artifactual: test shows low glucose but patient has no symptoms. Could be due to leukemia (metabolism in test tube), or hemolytic anemia

Factitious: self-administered insulin or errors in medications (patient given wrong med that lower blood sugar/enhances insulin)

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46
Q

Postprandial hypoglycemia

A

Symptoms of hypoglycemia within 4 hours of eating a large meal: thought to be due to excess insulin release in response to high-carbohydrate meal
- Mixed meal (complex carbs/proteins) reduce symptoms

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47
Q

Hormonal response to hypoglycemia

A
  1. Glucagon
  2. Epinephrine
  3. Growth hormone
  4. Cortisol
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48
Q

Idiopathic postprandial syndrome

A

Normal blood glucose with hypoglycemic symptoms due to overactive counter-regulatory mechanisms

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49
Q

Management of idiopathic postprandial syndrome

A

Dietary adjustment:

  • Avoid simple sugars
  • Complex carbs, proteins
  • Reducing meal size
  • Increasing meal frequency
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50
Q

Insulinomas: incidence

A

Diagnosis of insulinoma- keep in mind this is RARE condition causing hypoglycemia

  • 5-10% malignant
  • Associated with MEN (multiple endocrine neoplasia), therefore look for pituitary and PTH adenomas
  • Symptoms present for many years, masquerading as neurologic (seizures) or psychiatric disease
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51
Q

Insulinomas: biochemical diagnosis

A

Elevated insulin:glucose ratio (insulin > 6mU/mL when glucose < 45 mg/dL

  • Prolonged fasting test (72 hours) will show:
    • increased c-peptide
    • elevated proinsulin (not processed by tumor cells)
    • Reduced beta-OHB level (suppressed by insulin)
    • Enhanced glucose production in response to glucagon injection
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52
Q

Biochemical markers in fasting hypoglycemia: insulinoma

A
  • Increased plasma insulin
  • Increased c-peptide
  • Increased proinsulin (tumor doesn’t process)
  • decreased beta-OHB
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53
Q

Biochemical markers in fasting hypoglycemia: sulfonylurea

A

increased plasma insulin
increased c-peptide
decreased beta-OHB (decreased ketogenesis)
Positive sulfonylurea screen

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54
Q

Biochemical markers in fasting hypoglycemia: exogenous insulin injection

A

Increased plasma insulin
Decreased beta-OHB (decreased ketogenesis)
NO c-peptide/proinsulin increases

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55
Q

Biochemical markers in fasting hypoglycemia: multi-organ failure

A

decreased plasma insulin

decreased c-peptide

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56
Q

Biochemical markers in fasting hypoglycemia: tumor causing hypoglycemia

A

decreased plasma insulin (tumor eating up sugar?)

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57
Q

Symptoms of hypothyroidism

A
  • Feeling cold (hypothermic)
  • Constipation, “bloated” feeling
  • Mild/modest weight gain
  • Skin: myxedema (puffy), capillary fragility (bruising)
  • Fatigue, depression
  • Alopecia, coarsening of hair
  • Queen Anne’s sign= lateral eyebrow hair loss
  • Bradycardia
  • Musculoskeletal: Symmetric decrease in proximal muscle power, DELAY IN RELAXATION PHASE of ankle reflex
  • Snoring
  • Menstrual changes
  • Erectile dysfunction, oligospermia
  • Nervous system: lethargy, somnolence, confusion, paranoia, severe agitation, sensory deficits, cerebellar ataxia. Mucinous accumulations in cerebellum and nerve fibers.
  • Cardiovascular - cardiac output decrease, myxedema heart (dilated
    cardiomyopathy) , peripheral vascular resistance increased
  • GI: decreased peristalsis with constipation, myxedema megacolon

Rare= Myxedema coma: hypothermia, hypoventilation, hyponatremia, depressed mental status

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58
Q

Causes of hypothyroidism

A
  • Endemic goiter (iodide deficiency)
  • Defective synthesis of TH with compensatory goiter
  • Inadequate function due to decreased gland mass
    • “burned out” Hashimoto’s
    • Thyroidectomy (mantle radiation–> xerostomia= kill thyroid gland tissue)
  • Inadequate TSH, TRH
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59
Q

Symptoms of hyperthyroidism

A
  • Warm/hot (increased sweating)
  • Neurologic: Anxiousness, agitation, tremor, emotional lability
  • GI: mild/modest weight loss (>10% body mass over 2 months), hyperdefecation/ diarrhea
  • CV: palpitations, slight tachycardia at rest (irregularly irregular rhythm= concerning), Afib
  • diffuse alopecia with fine, thin hair
  • Dermopathy: Plummer’s nails= distal onycholysis, acropachy (diagnostic for graves= clubbing of fingers), pretibial myxedema
  • Musculoskeletal: Brisk DTR, proximal myopathy
  • Lid lag (NOT exopthalmos) due to spasm of eyelid elevator muscles
  • GU: oligomenorrhea
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60
Q

Causes of exopthalmos

A
  • Infection (orbital cellulitis)
  • trauma
  • Tumor
  • Grave’s disease (unilateral)
  • NOT caused by thyroid hormone excess
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61
Q

Symptoms of Hyperthyroidism due to Grave’s disease

A
  • Diffuse goiter with bruit
  • Hyperthyroidism
  • Opthalmopathy (non-specific): grittiness, photophobia, lid lag & retration
  • Specific opthalmopathy: proptosis (see upper AND lower sclera), exopthalmos, (diagnose with Moebius sign), ophthalmoplegia
  • Dermopathy: acropachy (clubbing)
  • Elevated T3, T4, increased radioactive iodide uptake

** Can cross placenta and cause fetal hyperthyroidism

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62
Q

Moebius sign

A

test to RULE OUT exopthalmos:

  • Patient asked to converge eyes- observe for smooth ocular motion
  • Weakness/odd movement seen in early exopthalmos
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63
Q

Apathetic hyperthyroidism

A

Seen in older patients: autonomic degeneration prevents patient from developing classic symptoms of hyperthyroidism
- Can see plummer’s nails, hair changes

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64
Q

Symptoms of acute hypoglycemia

A

Glucose < 60 mg/dL

Tachycardia, diaphoresis, tremor, confusion, delirium, intoxicated appearance
** everything but confusion is catecholamine mediate- therefore if on beta-blocker, patient may have no symptoms of hypoglycemia

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65
Q

Symptoms of acute hyperglycemia

A

Not noticeable until glucose > 300 mg/dL
Changes in vision (changes to hydration in lens, polyuria, polydipsia, nocturia, decreased conciousness, hyperventilation in state of acidosis

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66
Q

Physical exam for DM

A

Examine feet, skin, fundus, peripheral/central arterial system:

  • Feet: look for tinea infections, acanthosis nigricans; sensory exam
  • External genitalia: balanitis (scrotum), vulvovaginitis candida infections
  • Skin: Anterior tibial skin breakdown
  • Opthalmoscopic: hard/soft exudates, bleeds, neovascularization
    • Exudates- albumen spillage: hard= smaller, soft= larger patches
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67
Q

Pathophysiology of Type 1 DM

A

< 10% of all DM patients

  • Autoimmune disorder: destruction of beta cells in Islets of Langerhaans–> depleted insulin secretion (symptomatic at < 90% function- typically presents with DKA)
  • Genetic susceptibility: defects in immune recognition of beta-cell antigens (insulin and GAD65)
  • Environmental trigger (viral infection–> overactive immune system)
  • Insulinitis: lymphocytic inflammatory reaction in islets
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68
Q

Pathophysiology of Type 2 DM

A

90% forms of DM

  • Complex metabolic disturbance
  • High levels of hereditary patterning
  • Insulin resistance (changing glucose/lipid metabolism) due to lipotoxicity
  • Failure of beta-cell insulin secretion (lipo and glucotoxicity effects), amylin decreased
  • Excessive alpha-cell glucagon secretion
  • Deficient secretion of incretins
  • Frequently asymptomatic (develops over years) > 50% have complications at diagnosis
  • “Pre-diabetes”= intermediate diagnosis (Impaired glucose tolerance/fasting glucose)
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69
Q

Gestational diabetes

A

Develops in pregnancy (~6% of pregnancies)

  • Insulin resistance characteristic of normal pregnancy + inadequate insulin secretion by beta cells
  • Increased fetal morbidity and mortality (macrosomia)
  • 30-40% develop T2DM in 5-10 years
  • Women at risk screened between weeks 24-28 with oral glucose tolerance test (OGTT)
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70
Q

Pancreatic disease causing DM

A
  • Pancreatic disease (hemochromatosis, pancreatitis)–> islet cell destruction
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71
Q

Endocrinopathies causing DM

A

Excess secretion of hormones antagonizing insulin

  • Cushings= excess cortisol (peripheral insulin resistance)
  • Acromegaly= excess GH (enhances gluconeogenesis, glycogen breakdown)
  • Pheochromocytoma= excess catecholamines (enhances blood glucose)
  • Glucagonoma= excess glucagon–> increased blood glucose
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72
Q

Genetic mutations causing DM

A
  • Insulin receptor mutation

- Beta-cell mutation: glucokinase mutations

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73
Q

Acute symptoms of diabetes mellitus

A

Failure to utilize calories in diet:

  • weight loss with good appetite
  • increased food intake
  • Diuretic effect of glucose: polyuria, nocturia, dehydration, polydipsia
  • Other: vaginal infections, blurred vision, altered mental status
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74
Q

Microvascular Complications of chronic DM

A

Microvascular disease:

  • Retinopathy
  • Nephropathy: nodular diabetic glomerulosclerosis–> renal failure
  • Peripheral neuropathy (depends on length of nerve- longer= worse)
  • Autonomic nerve dysfunction (decreased GI motility
  • Ulcers, gangrene, poor wound healing
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75
Q

Charcot joint

A

Neuropathy leading to excess joint damage (can’t sense arthritis development)

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76
Q

Cardiovascular complications of chronic DM

A

Accelerated atherosclerosis

Autonomic nerve dysfunction–> decreased sensation during MI

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77
Q

Immune dysfunction in chronic DM

A

Leukocyte dysfunction

Decreased immune response, Mucomycosis (fungus)–> blindess–> stoke

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78
Q

Opthalmic complications of chronic DM

A 
Glaucoma
Cataracts
Corneal disease
Infections
Retinopathy
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79
Q

Metabolic syndrome criteria

A 
At least 3 of the following:
Abdominal obesity (>35 for women, >40 for men)
Fasting triglycerides (> 150 mg/dL)
HDL Cholesterol < 40 (men), < 50 (women)
BP >= 130/85
Fasting glucose >= 100 mg/dL
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80
Q

Acanthosis nigracans

A

Velvety skin with darkening at creases: clinical sign of insulin resistance (inflammatory state, elevated insulin–> excess skin growth)

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81
Q

Glucotoxicity

A

Elevated glucose levels impair insulin secretion

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82
Q

Lipotoxicity

A
  • High FFA and islet accumulation of lipids–> impaired insulin secretion
  • Lipid accumulation in liver/skeletal muscle impairs insulin action
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83
Q

Incretins and DM

A

Incretins= intestinal hormones released after meal ingestion: help with normal glucose homeostasis, regulate insulin release in glucose-dependent manner

  • GLP-1= glucagon-like peptide-1
    • stimulates insulin secretion, suppresses glucagon secretion
  • GIP= Gastric inhibitory polypeptide
  • Incretin effect decreased in T2DM (study shows enhanced insulin secretion with oral vs IV glucose in HEALTHY individuals–> delayed/diminished in T2DM)
  • Incretins degraded by DPP-4–> Gliptins (drugs) block DPP-4 to enhance incretin effect
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84
Q

GLP-1

A

Glucagon-like peptide-1

  • Released from L cells in ileum and colon
  • Stimulates insulin response from beta cells in glucose-dependent manner
  • Inhibits glucagon secretion from alpha cells in glucose-dependent manner
  • Inhibits gastric emptying
  • Reduces food intake and body weight
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85
Q

GIP

A

Gastric inhibitory peptide

  • Released from K cells in duodenum
  • Stimulates insulin response from beta cells in glucose-dependent manner
  • Does NOT inhibit glucagon secretion
  • No effects on gastric emptying
  • No effects on satiety/body weight
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86
Q

Amylin

A

Co-secreted with insulin from beta cells, helps regulate post-prandial glucose.
Actions:
- Suppresses inappropriately elevated glucagon secretion
- Slows gastric emptying
- Promotes satiety/reduces caloric intake
- Reduces blood glucose peak after meals

  • Amylin secretion deficient in T2DM
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87
Q

Adiponectin

A

Hormone secreted from adipose tissue (subcutaneous) that enhances insulin sensitivity

  • Vascular protective effects
  • Adiponectin levels reduced with visceral adiposity (insulin resistance further enhanced, more atherosclerosis)
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88
Q

Beta cell impairment in T2DM

A

Glucotoxicity
Lipotoxicity
Deficient secretion of incretins (GLP-1, GIP)
Amylin deficiency

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89
Q

Dyslipidemia in metabolic syndrome

A
  • Low HDL
  • High triglyceride
  • Changes in LDL particle size (small and dense–> atherogenic)
  • FFA and TNF-alpha (cytokine) contribute toward insulin resistance
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90
Q

Metabolic syndrome

A

Visceral obesity, insulin resistance:

  • Glucose intolerance
  • Dyslipidemia
  • Abnormal thrombolysis (increased levels of plasminogen activator inhibitor-1)
  • Endothelial dysfunction (vascular reactivity, inflammatory changes)
  • Hypertension (mild)
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91
Q

Screening for diabetic retinopathy

A

T1DM: within 5 years of onset, then annually
T2DM: at onset, annually

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92
Q

Treatment of diabetic eye disease

A

Improve glucose control: transient worsening of retinopathy (blurry vision) due to fluid shifts

  • Laser photocoaguation therapy (for proliferative stages)
  • In pregnancy, symptoms worsen (due to systemic BP decreases, hormonal changes causing fluid shits/ischemia)–> reverses after delivery
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93
Q

Systemic polyneuropathy

A

Most common type of neuropathy= “stocking glove”

  • Burning/tingling in feet
  • Loss of sensation
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94
Q

Autonomic neuropathy

A 
Gastroparesis (slowed gastric emptying, N/V)
Postural hypotension (abnormal CV response)
Bladder dysfunction (urinary incontinence, retention)
Erectile dysfunction (caused by vascular disease as well)
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95
Q

Screening for diabetic neuropathy

A

Peripheral: monofilament/vibration testing; all T1 and T2 at diagnosis, yearly

Autonomic neuropathy:
T1 5 years after diagnosis, T2 annually
take BP in supine and standing
- Change >20/10= orthostatic hypotension.
- Drop in BP NOT accompanied by HR change= autonomic neuropathy

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96
Q

Diabetic foot/Charcot arthropathy

A

Diabetic neuropathy and PVD (peripheral vascular disease)

Charcot= neruopathy, force, PVD–> osteoarthropathy destruction of bone in foot

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97
Q

Treatment of diabetic neuropathy

A

Glycemic control

Meds: pregabalin (lyrica), duloxetine (cymbalta)

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98
Q

Pathophysiology of diabetic nephropathy

A

Alteration in glomerular filtration barrier due to:
- Thickening basement membrane (glycosylation)
- Podocyte injury
Leads to protein in urine–> glomerulosclerosis–> end stage renal disease

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99
Q

Macrovascular complications in DM

A

80% diabetics die from CVD
No evidence of glycemic control lowering macrovascular risk
- Screening for PVD and CAD has not improved M&M, but it is still recommended
- Decrease risk multifactorial: glycemic, BP, hyperlipidemia, smoking cessation, weight managment

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100
Q

Goals/Therapy for DM pts with CAD

ADA guidelines

A

LDL: < 100 in DM; < 70 in CAD + DM patients

HbA1c ~7%, but AVOID intensive therapy in patients with established CAD

BP: < 130/ < 80

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101
Q

False changes in HbA1c

A

Elevated: low RBC turnover (iron deficiency anemia–> decreased RBC production)- blood cells older, making HbA1c appear higher than may be after treatment

Low: accelerated RBC turnover (sickle cell anemia). Treatment lowers glucose levels but not seeing long-term glucose levels as only measuring new RBCs

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102
Q

Albumin/Creatinine ratio: normal, micro- and macroalbuminuria

A

Normal: < 30 microgram albumin /mg creatnine
Micro: 30-299 mg albumin/24 hours
Macroalbuminuria: 300 mg+ albumin/24 hours
Nephrotic syndrome: > 3000mg / 24 hours

  • Serum creatinine rises in later stages of diabetic nephropathy (after established macroalubimuria)- systemic hypertension elevates rate of development; see impaired glomerular filtration
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103
Q

Albumin/creatinine screen

A

Urine: T1: 5 years after diagnosis; T2: at diagnosis, yearly

Serum creatinine: everyone yearly

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104
Q

Treatment of diabetic nephropathy

A

Type 1: ACE- I for an albuminuria
Type 2: ACE-I for micro-, ARB for macro/renal insufficiency (Cr > 1.5mg/dL)

* ARB with patients who develop cough
Additional: 
- Decrease protein intake
- Monitor Cr and K if using ACE-I/ARBs
- Adequate BP and glucose control
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105
Q

Hyperglycemia–> tissue damage (3 pathways)

A
  1. Increased aldose reductase–> NA/K ATPase activity changes—> sorbitol accumulation in nerve tissue
  2. Increased DAG and B2 protein kinase C–> vascular smooth m. dysfunction, altered endothelial cell permeability
  3. Accelerated glycosylation–> advanced glycosylation end product (AGE) receptor activation–> cell lipoprotein alteration, matrix/basement membrane protein alteration
    * All processes increase inflammatory cytokines–> oxidative stress
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106
Q

Effects of glycemic control on vasculature

A

MICROvascular complications rates decrease with intensive control (HbA1c ~ 7.2%)

NO significant improvement in MACROvascular complications with intensive HbA1c control

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107
Q

Metabolic memory and glucose control

A

Protective effects of intensive therapy persist over time when glycemic differences disappear. Get glucose under good control immediately- body “remembers” even if not controlled later

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108
Q

Hypothalamic control of pituitary gland

A

“Master of the master gland”

  • CRH= corticotropin releasing hormone
  • TRH= thyrotropin releasing hormone
  • GHRH= Growth hormone releasing hormone
  • LHRH= luteinizing hormone-releasing hormone
  • GnRH= Gonadotropin releasing hormone
  • Dopamine-prolactin INHIBITORY factor
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109
Q

Adenohypophysis

A

Anterior pituitary: derived from ectoderm of oral cavity (Rathke’s pouch). Secretes:

  • ACTH
  • GH
  • TSH
  • LH
  • FSH
  • prolactin
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110
Q

Neurohypophysis

A

Posterior pituitary

  • Contains axon terminals from paraventricular and supraoptic nuclei of hypothalamus
  • Vasopressin (ADH) and oxytocin secretion
111
Q

Hypopituitarism: causes

A
  • Tumor compression
  • Sheehan syndrome
  • Pituitary apoplexy
  • Trauma (shear stress)
  • Iatrogenic
  • Inflammatory process (lymphocytic hypophysitis)
  • Hemochromatosis
  • Genetic
  • Empty sella syndrome
  • Isolated hormone deficiencies
  • Kallmann syndrome
  • Laron syndrome
112
Q

Sheehan syndrome

A

Postpartum hemorrhage–> hypotension and ischemic necrosis of pituitary gland (enlarged in pregnancy). Evidenced by mother unable to lactate post-partum

113
Q

Pituitary apoplexy

A

hemorrhage/infarction of pituitary (could be due to endocrinologically inactive tumors)

  • Presentation: headaches, change in mental status, ophthalmoplegia/visual loss
  • Treatment: surgical decompression
114
Q

Lymphocytic hypophysitis

A

Autoimmune damage of one endocrine organ leading to attach of another organ

115
Q

Laron syndrome

A

End organ resistance to GH: administration of GH will not help. See in Sephardic jews (dwarfism), pygmies

116
Q

Pituitary adenoma

A

Sporadic, may be associated with MEN

  • Most common= prolactinoma
  • May secrete more than one hormone
  • Rare malignancy (must metastasize to be laeled malignant); can invade hypothalamus, cavernous sinus, sphenoid bone

Symptoms:
Microadenomas (< 10mm): symptoms seen due to hormone secretion
Macroadenomas: > 10 mm= cause problems due to compression (impinge optic chiasm–> bitemporal hemianopsia), oculomotor palsies

117
Q

Prolactinoma (pituitary adenoma) symptoms

A

Lactotrope adenoma: most common type
Symptoms:
- Females= amenorrhea, infertility, galactorrhea (nursing mom= amenorrhea + lactation); tend to have microadenomas
- Males= decreased libido, erectile dysfunction; tend to have macroadenomas
- Peripheral vision defects (bitemporal hemianopsia), oculomotor palsy

118
Q

Somatotrope pituitary adenoma

A

Growth hormone excess
Prior to epiphyseal plate closure= gigantism:
- rapid, sustained growth
- coarse features, frontal bossing, broad nasal bridge, prognathism
- excessive sweating, voracious appetite
- enlargement of hands, feet

After epiphyseal plate closure= acromegaly

119
Q

Acromegaly: signs and symptoms

A

Excess GH after epiphyseal plate closure

Symptoms:

  • Coarse facies, acral (head) enlargement, enlarged hands, feet, head, internal organs (w/o increased height)
  • Arthralgias/ carpal tunnel syndrome
  • Joint changes (bony changes irreversible)
  • Heel pad thickness > 22mm
  • Prognathism (jaw pushed forward)/ malocclusion
  • Headache,
  • Peripheral neuropathy
  • Diabetes
  • Skin tags/ greasy, oily skin
  • Excessive sweating
  • Obstructive sleep apnea
  • Hypercalciuria, hyperprolactinemia, HTN
120
Q

Corticotroph pituitary adenoma

A

Produces ACTH
Precursor cleaved to ACTH, lipocortin, MSH, endorphins
- Cushing’s disease
- Nelson’s syndrome: rapidly growing corticotroph adenoma after bilateral adrenalectomy (patient had excess cortisol–> remove adrenals–> corticotroph adenoma causing excess cortisol no longer inhibited–> grows)

121
Q

Gonadotrope pituitary adenoma

A

Produces FSH and LH in continuous stream (NOT pulsatile)
- “Nonfunctioning” adenomas: may not see any symptoms

Larger tumor:

  • Mass effects: headache, abnormal visual fields
  • Hypopituitarism (deficiency of other hormones due to obstruction from excess cells)
  • More common in men, see suppression of testosterone and hypogonadism as continuous stimulation has paradoxical inhibitory effect
122
Q

Thyrotropin pituitary adenoma

A

Least common type of adenoma
Produces TSH

Symptoms: Hyperthyroidism (high T4/T3) with inappropriately normal/elevated TSH (vs primary hyperthyroidism- TSH suppressed), goiter, pituitary lesion mass effects: headache, abnormal visual fields

Treatment: surgery

123
Q

Pituitary adenoma: order of hyposecretion of pituitary hormones

A
  1. GH
  2. LH/FSH
  3. TSH
  4. ACTH
  5. ADH
124
Q

Functions of oxytocin

A

Released by neurohypophysis. Causes:

  • uterine contractions
  • milk let down
  • pair bonding
  • mother/child bonding (uterine contractions/nursin)
  • Released from stimulation of nipples, cervix
125
Q

Functions of vasopressin

A

Released from neurohypophysis. Acts on V2 receptors–> increases cAMP in distal tubules/collecting ducts–> increases water permeability

Functions:

  • Anti-diuretic hormone (prevents dehydration)
  • Pair bonding in males?
  • Variation in AVPR1A (receptor gene) correlates with infidelity, spousal dissatisfaction)
  • Excess= SIADH (syndrome of inappropriate secretion of antidiuretic hormone)
  • Deficiency= central diabetes insipidus
126
Q

Causes of Central diabetes insipidus

A

Polydipsia/polyuria secondary to ADH deficiency
Causes:
- idiopathic sporadic mutations
- familial causes
- tumors
- post-surgical (pituitary adenomas)
- Inflammatory processes: sarcoidosis, tuberculosis (lives at base of brain)

127
Q

Corticotropin (ACTH) excess and deficiency

A
  • regulated by corticotropin-releasing hormone (CRH)–> anterior pituitary (ACTH)–> adrenal glands–> cortisol synthesis
  • Cortisol= negative feedback on ACTH secretion
    Excess= Cushing’s syndrome
    Deficiency= adrenal insufficiency
128
Q

Causes of Cushing’s syndrome

A
  • Most common etiology= corticosteroid use

ACTH-dependent causes:

  • Cushing’s disease (most common cause= excess ACTH–> bilateral adrenal hyperplasia and excess cortisol)
  • Ectopic ACTH syndrome
  • Ectopic CRH syndrome

ACTH-independent causes:

  • Adrenal adenoma, carcinoma
  • Micro/macronodular hyperplasia

Pseudo-Cushing’s syndrome:

  • Major depressive disorder (hard to rule out what caused what
  • Alcoholism
129
Q

Cushing’s syndrome signs/symptoms

A

Constellation of clinical signs and symptoms due to chronic glucocorticoid excess

Symptom/sign:

  • Central obesity, supraclavicular fat pad, buffalo hump, moon face
  • Easy bruising
  • Proximal weakness
  • Facial plethora (flushing)
  • Amenorrhea, hypogonadism
  • Purple striae on abdomen
  • Excess urination
  • Hyperpigmentation
  • Exopthalmos
  • Psych changes (hard to rule out what caused what)
130
Q

Diagnosis of Cushing’s

A

24-hour urine collection (BEST): free cortisol at least 3x upper limit of normal. Must be confirmed at least two times

First test: Overnight dexamethasone suppression test:

  • Cushing’s patients will NOT suppress morning serum cortisol below 1.8ng/dL after 1 mg dexameth the night before
  • 10-20% false-positive results due to pseudo-cushing’s (obesity, depression, alcoholism)- abnormal test MUST be confirmed by urine free cortisol
  • Check for loss of diurinal variation (salivary cortisol at 11pm- normally lowest at night)- cortisol constantly high in Cushing’s
131
Q

TSH (thyroid stimulating hormone): excess and deficiency

A

TRH (hypothalamus)–> TSH (ant. pit)–> TH (thyroid gland)–> negative feedback on TSH

  • Excess= hyperthyroidism (central)
  • Deficiency= hypothyroidism (central)
132
Q

GH (growth hormone): excess and deficiency

A

GHRH (+) and somatostatin (-) (hypothalamus)–> GH (ant pit)–> IGF-1 (Liver)–> target bones, muscle (* single transmembrane receptor)+ negative feedback to GH

  • Excess= gigantism, acromegaly
  • Deficiency= growth retardation, adult clinical syndrome
133
Q

ID etiology of Cushings

A
  • ACTH-independent (adrenal)= plasma ACTH < 5 pg/mL + CT scan of adrenals
    • Treatment= adrenalectomy
  • ACTH-dependent (pituitary/ectopic)= plasma ACTH > 20pg/mL
    • Treat pituitary Cushing’s with transphenoid surgical removal (or remove ectopic tissue)
  • Not definitive between 5 and 20 pg/mL
134
Q

Gonadotropins: excess and deficiency

A

GnRH (hypothalamus)–> LH and FSH (ant. pit)–> testosterone+ spermatogenesis/ estradiol+ gametogenesis (testes/ovaries)

  • Excess= precocious puberty
  • Deficiency= hypogonadism
135
Q

Pituitary vs ectopic Cushings

A

Ectopic Cushings= much higher ACTH than pituitary

  • Neuroendocrine tumors secrete ACTH, mimicking pituitary disease (bronchial carcinoids= most common)
  • Other tumors= small cell lung, islet cell, pheochromocytoma, medullary carcinoma
  • High dose dexamethasone suppression test: people with pituitary Cushing’s will suppress ACTH after high dose dexamath (ectopic ACTH do not)
  • Petrosal sinus sampling: catheter drains pituitary venous system (pituitary Cushing’s disease= high ACTH)
  • Perform MRI AFTER testing positive for pituitary Cushing’s (10-20% incidentalomas in general population)
136
Q

Prolactin (PRL): excess and deficiency

A

Dopamine (-) (Hypothalamus)–> PRL (ant. pit)–> lymphokines and lactation (lymphocytes and breast) * single transmembrane receptor

  • Excess= galactorrhea, amenorrhea
  • Deficiency= inability to lactate after delivery
137
Q

Diagnosis and Treatment of Acromegaly

A

Diagnosis:

  • IGF-1: high
  • OGTT (gold standard): glucose remains high after administering glucose due to excess GH (no suppression)

Treatment: Somatotrope (GH) adenoma treated surgically
Medically:
- Somatostatin= inhibits GH release- (octreotide, lanreotide)
- Pegvisomant= GH receptor antagonist
- Radiation (if not amenable to surgery)
- Surgery= transsphenoidal surgery: 50% curative

  • Screen for colonic polyps/cancer
138
Q

Risk of long-term exposure to elevated GH

A
  • Joint/bony changes (permanent)
  • HTN
  • GH effect on heart–> cardiomyopathy
  • Sleep apnea (hypoxemia)
  • Colon polyps, cancer (increased risk)
  • Diabetes (improves once GH excess treated)
139
Q

Diagnosis of acromegaly

A
  • IGF-1 (somatomedin C): high, BEST screening test (false negative 10-15%
  • Failure of GH to suppress after OGTT (GOLD standard)
    • Oral glucose–> suppress GH: measure every 30 min for 2 hours. Acromegaly=GH does not suppress to < 1 ng/mL
  • MRI of pituitary (macroademona)
140
Q

Prolactinomas: diagnosis

A

High prolactin with abnormal pituitary MRI
Need to exclude other etiologies (10-20% incidentalomas)
- Nonfunctioning pituitary macroadenoma (compression of stalk–> no dopamine suppression from hypothal)
- Infiltrative disease of hypoth/pit axis
- Primary hypothyroidism (low T4/T3–> high TSH–> high TRH–> stimulate PRL release)
- Renal failure, cirrhosis
- Pregnancy, stress
- Drugs: dopamine antagonists (antipsychotics)

141
Q

Prolactinoma treatment

A

Preferred to use medical treatment (even with abnormal visual fields):
Bromocriptine or cabergoline (dopamine agonist) to shrink tumor (can be stopped after 1-2 years)

  • Surgery/radiation for patients non-responsive to drugs
142
Q

Diabetes insipidus etiology

A
  • insufficient ADH secretion (central): acute onset

- resistance of kidney to ADH (nephrogenic): slow onset- ISSUES with kidney

143
Q

Causes of nephrogenic diabetes insipidus

A
  • Congenital (x-linked)
  • Acquired:
    • Renal disease (sickle cell disease, polycystic kidney, amyloidosis, obstructive uropathy)
    • Electrolyte disorders (hypokalemia, hypercalcemia)
    • Drugs (lithium, demeclocycline)
144
Q

Diagnosis and treatment of Diabetes insipidus

A

Diagnosis: Polyruria + urine specific + gravity 1.005 or less+ urine osmolality 200 mmol/L or less

Treatment:

  • Central DI responds to ddAVP
  • Nephrogenic DI responds to NSAIDs
145
Q

Hypopituitarism

A

Clinical syndrome from deficienc from 1+ pituitary hormones:

  • GH, FSH, LH lost first
  • TSH, ACTH, ADH lost last

Cause:

  • Pituitary macroadenoma (most common)
  • Sheehan’s syndrome
  • Pituitary apoplexy
146
Q

Diagnosis and treatment of hypopituitarism

A
  • MRI of hypothalamus, pituitary
  • Endocrine testing (PRL, TSH + free T4, cortisol + ACTH, testosterone/menstrual history, GH dynamic testing

Treatment: neurosurgery, hormone replacement

147
Q

Pituitary incidentalomas: causes

A

Pituitary tumor found incidentally by imaging (with no suspicion of pituitary disease)

  • 10-20% people
  • Most common= pituitary adenoma (micro)
  • Other causes: craniopharyngioma, germ-cell tumor, glioma, meningioma, granuloma, infection, metastases
148
Q

Pituitary incidentalomas: diagnosis and treatment

A

Exclude hormonal hypersecretion:
- PRL, IGF-1, TSH, free T4, overnight dexamethasone suppression, LH, FSH, alpha-subunit

  • Macroadenoma: rule out hypopituitarism, visual field testing
  • Testing normal: follow with periodic MRI (6 months, 1, 2, 5 years)
149
Q

Congenital hypothyroidism (cretinism)

A

Endemic, sporadic, familial forms
- 90% of cretinism in non-endemic area are secondary to thyroid dysgenesis

Clinical features (within a few weeks postnatally):

  • apathy, lethargy, enlarged abdomen, decreased body temperature, refractory anemia, dilated heart, mental retardation and stunted growth.
  • prompt thyroid hormone replacement prevents irreversible brain damage and dwarfism
150
Q

Goitrous hypothyroidism

A

Enlargement of thyroid due to inadequate thyroid hormone production:

  • Dietary iodine deficiency
  • Antithyroid agents: lithium, phenylbutazone, p-aminosalicylic acid
  • Foods with goitrogens: Rutabagas, turnips, cassava
  • Iodide induced goiter: Excessive dietary iodide (seaweed, supplements); High dose iodine in pregnancy can produce goitrous infants
  • Hereditary defects in thyroid hormone synthesis
151
Q

Causes of Grave’s disease

A
  • Autoimmune (ANTI-TSH RECEPTOR stimulating antibodies, autoreactive cytotoxic antibodies)
  • Family history increases risk (no genetic marker)
  • molecular mimcry due to yersinia enterocolitica?
152
Q

Hashimoto’s thyroiditis causes

A

End-stage autoimmune thyroiditis= cell mediated (CD8+ cells) and humoral:

  • circulating antibodies directed against thyroid microsomal peroxidase (ANTI-TPO ANTIBODIES), thyroglobulin, TSH receptor (antagonist)
  • genetic predisposition
  • may be associated other systemic autoimmune disease
153
Q

Hashimoto’s thyroiditis: clinical presentation and treatment

A

More common in women in 50s-60s

  • gradual development of goiter
  • hypothyroidism
  • rarely hyperthyroidism (Hashitoxicosis)
  • elevated TSH
  • circulating antibodies
  • high prolactin (elevated TRH–> can stimulate Prolactin release)- see amenorrhea and galactorrhea

Treatment: hormone replacement (damage to gland generally irreversible by the time they present)

154
Q

Pretibial myxedema

A

Sign of hyperthyroidism:

red patches/plaques on anterior tibia

155
Q

Thyroiditis

A

Hyperthyroidism with LOW uptake of radioactive iodine (diagnostic difference from Grave’s) that progresses to hypothyroid and then euthyroidism

Painful= DeQuervains/granulomatous (subacute)

  • Following URI- ESR> 80 (elevated c-reactive protein)
  • LOW 24-hour radioiodine uptake
  • Hyperthyroidism–> hypothyroidism–> euthyroid

Painless= Hashimoto’s (post-partum)

  • Elevated TPO (thyroid peroxidase) antibodies
  • LOW 24-hour radioiodine uptake
  • Hyperthyroid–> hypothyroid (may be permanent)–> euthyroid
156
Q

Disorders associated with Hashimoto’s hypothyroidism

A 
Organ-specific autoimmune disorders: 
- Chronic active hepatitis
- Primary biliary cirrhosis
- Dermatitis herpetiformis
- Idiopathic chronic urticaria and angioedema
Rheumatologic disorders
- Rheumatoid arthritis
- SLE
- Sjögren's
- Polymyalgia rheumatica
- Temporal arteritis
- Relapsing polychondritis
- Systemic sclerosis
Autoimmune Polyglandular Syndrome
- Autoimmune thyroid disease
- DM type I
- Addison’s
- Premature ovarian failure
- Celiac disease
- Myasthenia gravis
- Pernicious anemia
- Vitiligo/Alopecia
157
Q

Diagnosis of Hypothyroidism

A
  • Clinical findings
  • TFT: TSH, free T4
  • TPO: thyroid peroxidase antibodies
158
Q

Fine Needle Aspiration Biopsy

A

Gold standard for IDing thyroid pathology

  • ~95% sensitivity and specificity (must be done by expert)
  • Increases cancer yield at surgery
  • Decreases surgery rates, cost (75% of biopsies result in conservative management)
  • If results indeterminate, perform genetic marker testing- only 5% malignancy in negative tests
159
Q

Incidentaloma of Thyroid

A 
Assess function (TSH and TPO antibodies)
Assess structure:
< 1cm+ low cancer risk= ultrasound every 6-12 months
< 1 cm+ high cancer risk= needle biopsy
> 1cm= needle biopsy
160
Q

Cancer risks of thyroid

A 
Pathology
Clinical
- Old age (>45/60 years)
- Size (>4 cm)
- Male sex
- Metastases
- Rapid growth
161
Q

Iodide intake–> colloid

A 
Adult= 150 mcg/day (thyroid removes 75 mcg, remainder goes to urine)
Pregnancy= 200 mcg/day

Iodide converted to Iodine by TPO:
2 Iodine= DIT
1 Iodine= MIT

2 DIT + TBG= T4
1 MIT + 1 DIT + TBG= T3

162
Q

High TBG States

A

Liver secretes more TBG, binds more T3/4–> decreased free TH levels–> increased TSH

  • Estrogens (OCP, pregnancy)
    • High total T3/T4 but normal free T3/T4
  • Acute/chronic active hepatitis
  • Acute intermittent porphyria
  • Hereditary
163
Q

Low TBG states

A

Lower TBG levels due to decreased liver production (or kidney loss of proteins)–> see elevated free T3/T4 levels–> decreased TSH–> low total T3/T4 but normal free T3/T4

  • Androgens
  • Glucocorticoids
  • Nephrotic syndrome
  • Hereditary
164
Q

Metabolism of Thyroid hormone

A

Deiodination of T4 to T3

  • Occurs in liver, kidneys, target cells
  • T3 is 3-4 times more potent than T4
  • Severe illness, may have rT3 product which is inactive, leading to symptoms of hypothyroidism
165
Q

Diagnosis of hyperthyroidism

A

1: Free T4 and TSH test
2: 24 hour Iodide uptake and scan
- Thyroiditis= NO uptake
- Grave’s disease= high levels of uptake

166
Q

Criteria for pre-diabetes/glucose impairment

A

Fasting glucose: 100-125
HbA1c: 5.7-6.4
OGTT: 140-199

167
Q

Thyroid gland development/abnormal development

A

Derived from endodermal thickening of foramen cecum–> descends into neck–> gland
- Parafollicular c-cells from ultimobranchial body

Anomalies (congenital):

  • Agenesis
  • Lingual atrophy
  • Heterotrophic thyroid tissue
  • Thyroglossal duct cyst
168
Q

Nontoxic Goiter: symptoms and treatment

A

Enlargement with no funcitonal, inflammatory, neoplastic alterations

  • Diffuse= adolescence, pregnancy
  • Multinodular= more common in older women (over 50)–> more likely to progress to toxic multinodular goiter
  • Euthyroid
  • Asymptomatic (except presence of neck mass/local pressure)

Treatment: TH (to decrease TSH causing goiter), radioactive iodine/surgery for compressive symptoms

169
Q

Symptoms of hypercalcemia

A

Most commonly a LAB finding

  • Neuro-muscular: proximal muscle weakness, hypotonia (decreased DTR)
  • Neurologic (CNS depression due to dehydration): lethargy, confusion, forgetfulness, blurred vision, coma
  • Cardiac: shortened QT interval, bradycardia, arrhythmias
  • GI (dehydration): dry mouth, thirst, anorexia, N&V, constipation
  • Renal: elevated serum calcium impairs kidney’s ability to concentrate urine (polyuria/polydipsia, hyperchloremic acidosis, nephrocalcinosis, kidney stones, reversible renal failure)
170
Q

Physical findings in hypercalcemia

A

USUALLY nothing special

  • depressed mental status
  • decreased DTRs
  • neck mass (rare)
  • quadriceps weakness
171
Q

Pathophysiology of hypercalcemia

A
  • Increased bone resorption
  • Increased gut absorption of calcium
  • Excessive renal re-absorption
172
Q

High calcium with high PTH

A
  1. Primary hyperparathyroidism= most common cause
  2. Tertiary hyperparathyroidism
  3. Familial hypocalciuric hypercalcemia (FHH)
  4. Multiple endocrine neoplasia type 1 (MEN-1)
  5. MEN-2
  6. Rare ectopic PTH production
  7. lithium
173
Q

Adjusted Calcium calculation

A

Serum calcium + 0.8( 4- serum albumen)

174
Q

High calcium with low PTH hypercalcemia

A
  1. Malignancy related hypercalcemia (seen with INPATIENT):
    - Humoral hypercalcemia of malignancy (HHM) (PTHrP mediated-squamous cell cancer)
    - Local osteolytic hypercalcemia; myeloma, solid breast cancer tumors
    - Lymphoproliferative disorders (1,25 D mediated lymphoma)
  2. Vitamin D intoxication
  3. Milk alkali syndrome
  4. Vitamin A intoxication
  5. Drugs: thiazide diuretics, TPN
175
Q

Uncommon causes of hypercalcemia

A
  1. Granulomatous disorders: sarcoid/TB granulomas synthesize 1-alpha-hydroxylase enzyme–> increased 1,25-dihydroxy-vitamin D levels
  2. Immobilization
  3. Non-parathyroid endocrinopathies (hyperthyroidism, pheochromocytoma, acromegaly, adrenal insufficiency)
176
Q

Familial hypocalciuric hypercalcemia (FHH)

A

Decreased perception of calcium by CaSR (calcium-sensing receptors) on Parathyroid glands/kidney due to inactivating mutation–> hypercalcemia, low urine calcium

177
Q

Primary hyperparathyroidism: incidence

A

1/1000 individuals, 3:1 female:male ratio

Surgery is ONLY definitive treatment- 95% successful

178
Q

Indications for parathyroid removal in hyperparathyroidism

A

Indications for surgery:

  1. Serum Ca > 1mg/dL above upper limit normal or previous episode of life-threatening hypercalcemia
  2. Signs or symptoms (kidney stones)
  3. Creatinine clearance below 60 ml/min
  4. BMD at spine, hip, radius shows osteoporosis
  5. Age < 50 years
  6. Medical surveillance not possible
  7. Onset of menopause
179
Q

Medical treatment of hyperparathyroidism

A
  • Check serum calcium, creatinine yearly
  • DXA scan 1-2 years
  • Avoid dehydration, diuretics/HCTZ (increase Ca reabsorption), immobilization, lower dietary Ca, Vit D
  • Sensipar= mimics calcium, lowering PTH
180
Q

Malignancy-associated hypercalcemia

A

Cancers can cause hypercalcemia:

  • Direct bony metastases
  • release of PTHrP
  • cytokine (lymphotoxin, transforming-growth factors, interleukins, TNF) production–> osteoclast activation
  • Increased 1,25-OH D production (lymphomas)
181
Q

Lab evaluation of hypercalcemia

A
  1. Serum calcium (correct low/high albumin)
  2. PTH level
  3. 24-hour urine calcium
182
Q

Medical treatment of hypercalcemia

A
  1. Hydration
  2. Block calcium release from skeleton (bisphosphonates- Zoledronic acid)
  3. inhibit gut absorption of calcium (glucocorticoids)
  4. Others: calcitonin (binds osteoclasts to inhibit resorption), mithramycin (antibiotic= inhibits RNA synthesis in osteoclasts), oral phosphates (normal renal funciton), hemodialysis
183
Q

Milk Alkali Syndrome

A
  1. Hypercalcemia
  2. Systemic alkalosis
  3. Renal insufficiency

Most common agent= calcium carbonate intake in setting of volume contraction (taking Tums while dehydrated from vomiting/diarrhea)

  • Alkalosis impairs renal ability to excrete calcium
  • Low PTH
184
Q

Symptoms of hypocalcemia

A
  • Parasthesias
  • Muscle cramps
  • NM excitation (tetany)
  • Bronchospasm
  • Laryngeal stridor
  • Seizures
  • Basal ganglia calcifications–> Parkinson’s disease (over years)
185
Q

Signs of hypocalcemia

A
  • Cataracts
  • Chvostek’s sign
  • Trousseau’s sign
  • Hyperreflexia
  • Prolonged QT
186
Q

Chvostek’s sign

A

Tap on facial nerve- see spasm in facial muscles (sign of hypocalcemia)

187
Q

Trousseau’s sign

A

Hold BP cuff 20 mm Hg above systolic BP for 3 min–> see spasm of hand muscles

188
Q

Causes of hypocalcemia:

Low Calcium, Low PTH

A
  • Surgical removal of parathyroid gland (MOST common)
  • Functional (severe hypomagnesemia- Mg needed to absorb Ca)
  • Idiopathic
  • Autoimmune, infiltrative (hemochromatosis), Congenital (Di George= no parathyroid glands)
  • “hungry bone syndrome”
189
Q

Causes of hypocalcemia:

Low calcium, High PTH

A
  1. Vitamin D deficiency (MOST common)
    - lack of sunshine
    - dietary
    - malabsorption (sprue, Bowel surgery)
    - Cholestatic liver disease (deficient 25-OH D production)
    - advanced renal failure (deficient 1 alpha hydroxylase)
    - anticonvulsants (phenytoin)
    - Vitamin D dependent Rickets (type 1), resistance (type 2)
  2. Pseudohypoparathyroidism (end-organ PTH resistance due to mutation of GNAS1)
  3. Other:
    - Acute pancreatitis
    - Tumor lysis syndrome, rhabdomyolysis
    - Acute hyperphosphatemia
    - Low serum albumin
    - Hypocalcemic agents- bisphosphonates
    - Osteoblastic metastases- prostate cancer/breast cancer 50% (ONLY cancers to cause HYPOcalcemia)
    - Hungry bone syndrome
    - Acute severe illness
  4. Pseudohypocalcemia= due to gadolinium for scans interfering with Ca assay
190
Q

Ricket’s

A

Type 1: ineffective 1-alpha hydroxylase–> Vit D deficiency
Type 2: Vitamin-D receptor defect (resistance)
Symptoms:
- bowing deformities
- frontal bossing
- softening of skull (craniotabes)
- Muscular hypotonia + weakness

191
Q

Osteomalacia

A

Defect in bone mineralization AFTER cessation of growth (in adults) due to deficiency in Vitamin D or phosphate (intestinal malabsorption of Ca/D= #1 cause in US)

  • Skeletal pain and weakness without bony abnormalities
  • decreased bone density, coarsened bone trabeculae, pseudofractures

*Pseudofractures/Looser’s zones/ milkman’s fractures= pathognomic for osteomalacia

192
Q

Secondary reactions to hypocalcemia

A

Hypocalcemia–> secondary hyperparathyroidism

Low vit D–> hypocalcemia + hypophosphatemia*
* in renal failure, kidneys won’t produce 1,25-OH D and won’t excrete phosphate–> see low D, hyperphosphatemia

Increased alkaline phosphatase due to secondary hyperparathyroidism–> increased osteoblast/clast activity

193
Q

Treatment of hypocalcemia

A
  1. Keep serum calcium at lower range of normal (asymptomatic)
  2. Check serum magnesium (replace before calcium)
  3. Symptomatic? Calcium gluconate
  4. Oral calcium, vitamin D (secondary hyperparathyroidism)
  5. Renal failure/hypoparathyroidism: active 1,25-OH D replacement
  6. Hydrochlorothiazide–> improve renal calcium absorption
194
Q

Osteoporosis

A

Decreased bone mass
- Skeletal disorder of low bone mass, microarchitectural disruption leading to fragility fractures

Risk factors:

  • Family Hx
  • Slender build
  • Hypogonadism (post-menopausal)
  • Smoking
  • Inadequate dietary Ca
  • Alcoholism
195
Q

Etiology of osteoporosis

A
  • Post-menopausal: trabecular bone degeneration (loss of estrogen)
    Senile/age related: hip/femur fractures due to loss of trabecular and cortical bone
  • Hypogonadism: trabecular bone loss
  • Glucocorticoids: inhibit bone formation
  • Immobilization: increase bone turnover/loss
  • Hyperthyroidism/ hyperparathyroidism: increased bone turnover/loss in cortical bone
  • Heparin: poor bone quality
  • Multiple myeloma: increase bone loss/weak bone formation
  • Estrogen affects trabecular bone more
  • Parathyroid hormone affects cortical bone more
196
Q

Causes of low Vitamin D

A
  1. Calciopenic disorders:
    - Dietary Vit D deficiency (nutritional)
    - Vit D malabsorption (post bypass or celiac)
    - VDDR= vit D-dependent rickets= defective renal 1 alpha hydroxylase
    - VDDR II= hereditary resistance of 1,25-vit D
    - Enhanced metabolism of 1,25-OH D (anticonvulsants, rifampin)
    - Chronic renal disease
  2. Low phosphorous (RARE)
  3. Normal mineral availability (Ca, PO4)= VERY RARE
    - abnormal matrix synthesis or mineralization defect
197
Q

Osteogenesis imperfecta

A

Brittle bone disease= primary osteoblast disease due to mutation in Type 1 collagen.
VERY RARE
- See osteopenia, fragile bones, hyperextensible joints, dental abnormalities, bluish discoloration of sclera, adult-onset hearing loss

198
Q

Osteopetrosis

A

Primary osteoclast disease (skeletal fragility)

- Carbonic anhydrase deficiency: can’t breakdown/remodel effectively

199
Q

Paget’s disease

A

Rare before age 60

  • Disorder of bone remodeling: abnormal bone formation
  • Symptoms of bone pain, bowing deformities, enlargement of skull, increased bone vascularity
  • Common fractures
  • Most asymptomatic- discovered by isolated elevations in serum alkaline phosphatase

Treatment= pulse therapy with bisphosphanates

200
Q

Calcium in body

A 
99% in bone
1% in serum:
- 50% ionized (active form)
- 40% bound to albumin
- 10% complexed with citrate and phosphate
201
Q

PTH: physiologic effects

A

Parathyroid Hormone: determines serum calcium
- Glands in neck (4) secrete PTH from chief cells. Calcium-sensing receptors (CaSR) regulate hormone secretion based on serum calclium levels

Bone: PTH binds to osteoclasts–> increases resorption–> calcium to circulation

Kidney: Ca resorption in distal tubules, inhibit phosphate resorption in proximal tubules, stimulate 1-alpha-hydroxylase to form 1,25-OH D

Intestine: indirect (via 1,25-OH D) increase of calcium, phosphate absorption

202
Q

Vitamin D: Metabolism and physiology

A

Orally ingested or created in skin from 7-dehydrocholesterol (UV light)

  • Converted by 25-hydroxylase in liver to 25-OH D
  • Converted by 1-alpha hydroxylase in kidney to 1,25-OH D (kidney stimulated to convert by PTH or decreased serum phosphate)
  • Increases calcium, phophate absorption in GI tract
  • Decreases PTH synthesis
203
Q

PTHrP

A

PTH-related polypeptide: acts like PTH (increases calcium uptake)–> humoral hypercalcemia of malignancy

  • See suppressed PTH for level of hypercalcemia (indicating not primary hyperparathyroidism)
  • Does NOT convert 25-OH to 1,25-OH D
  • accounts for 80% of humoral hypercalcemia of malignancy (HHM)
204
Q

Parathyroid glands: general

A

Derivatives of 3rd/4th branchial pouches (4 glands)

  • Seen in thyroid, but can be in mediastinum, etc.
  • Chief Cells secrete PTH
  • Clear cells= glycogen
  • Oxyphil cells= mitochondria
  • Glands respond to ionized Ca and Mg
205
Q

Albright’s hereditary osteodystrophy

A

End-organ resistance to cAMP-coupled hormones (PTH, TSH, glucagon, FSH, LH)
- Results in short stature, obesity, mental retardation, subcutaneous calcifications, congenital bone abnormalities

206
Q

Symptoms and signs of hypoparathyroidism

A

Similar to hypocalcemia:

  • Tingling, muscle cramps, convulsions
  • Neuropsychiatric manifestations (depression, psychosis)
  • Lab: decreased serum Ca, decreased PTH
207
Q

Symptoms and signs of hyperparathyroidism

A

Similar to hypercalcemia:

  • increased serum Ca, decreased phosphate
  • Nephrocalcinosis, renal stones
  • Osteitis fibrosa cystica: bone pain, cysts, fractures (bone turnover–> decreased bone mass)
  • Polyuria (secondary to hypercalciuria)
  • Mental status changes
  • Muscle weakness (peripheral neuropathy)
  • Peptic ulcer (increased calcium)
  • Chronic pancreatitis (increased calcium)
  • Hypertension
208
Q

Parathyroid hyperplasia

A
  • 1/3 Associated with MEN1 and 2A
  • 1/3 monoclonal
  • Lack of cellular pleiomorphism
209
Q

Parathyroid adenoma

A

Sporadic/part of MEN1

  • Sheets of chief cells with rim of normal tissue
  • Other glands may become atrophic
  • Show considerable atypia
210
Q

Parathyroid carcinoma

A

usually functional, cellular atypia often absent, mitoses, capsular and vascular invasion, metastases

211
Q

Secondary hyperparathyroidism

A

Due to several causes:

  • Chronic renal failure–> renal osteodystrophy
  • Vit D deficiency (can’t convert 25-OH D to 1,25 due to 1-alpha hydroxylase deficiency or low Vit D intake/synthesis)
  • Intestinal malabsorption of Ca
  • Renal tubular acidosis- spill Ca
212
Q

Tertiary hyperparathyroidism

A
  • Parathyroid hyperfunction following chronic renal failure- will persist even after transplantation
  • Monoclonality seen in some cases
213
Q

Adrenal Cortex

A

Derived from coelomic mesenchymal cells

Zona glomerulosa= ALDOSTERONE secretion

  • Stimulated by angiotensin, potassium
  • Inhibited by ANP and Somatostatin

Zona Fasciculata= GLUCOCORTICOIDS,
- Stimulated by ACTH

Zona Reticularis= dehydroepiandosterone secretion

214
Q

Causes of adrenal cortical insufficiency: Chronic vs Acute

A

Chronic:

  1. Addison’s disease (autoimmune)
  2. Tuberculosis
  3. Secondary: Pituitary damage/ Autoimmune-isolated corticotropin deficiency
    - ACTH decreased–> POMC decreased–> no hyperpigmentation as in primary adrenal cortical failure

Acute:

  1. Corticosteroid therapy withdrawal
  2. Waterhouse-Friderichson syndrome
215
Q

Treatment of Cushing’s

A
  • Remove ACTH-producing tumor
  • Decrease steroid therapy
  • Administer adrenal enzyme inhibitors: Aminoglutethimide, Ketoconazole, Metapyrone
216
Q

Polyendocrine deficiency syndromes: types I and II

A

BOTH characterized by:

  • Autoimmune thyroid disease
  • Hypoadrenalism
  • Type I diabetes (rare in Type I PGE)

Type I:

  • Peak onset at 12 years
  • Characterized by: hypoparathyroidism, hypogonadism, mucocutaneous candidiasis, alopecia

Type II:

  • Peak onset at 30 years
  • Higher incidence of Type I diabetes
217
Q

Treatment and follow-up of Thyroid Carcinoma

A 
12,000 cases/year in US- 1000 deaths
Treatment:
- Surgical removal
- radioiodine ablation with I131
- L-thyroxine suppressive therapy
* human recombinant TSH--> reduced morbidity with surveillance scanning (patient can remain on thyroid supplementation during whole body scan)
218
Q

Thyroid cancer types

A
  1. Papillary= 75% thyroid cancers
    - Women, 30s, excellent prognosis
  2. Follicular= 20% thyroid cancers
    - Diagnosis in 50s, more metastases (worse prognosis)
  3. Medullary cancer= MEN2 syndromes
    - 90% sporadic, cannot be treated with I131
  4. Anaplastic
    - Diagnosis in 70s, aggressive, fatal
  5. Lymphoma (rare, 5%)
    - associated with Hashimoto’s thyroiditis
    - large-cell type
219
Q

Primary adrenal insufficiency

A

Adrenal destruction leading to loss of glucocorticoids, mineralocorticoids, and to lesser extent, androgens due to:

  1. Autoimmune (anti-adrenal antibodies)= Addison’s disease
  2. Infectious
  3. Cancer
  4. Metastatic cancer
  5. Hemorrhage/infarction (Waterhouse-Friderichson)
  6. Drugs (ketoconazole, rifampin, phenytoin)
220
Q

Secondary adrenal insufficiency

A

Lack of glucocorticoid secretion due to break down in Pituitary-Adrenal axis (no ACTH stimulation). Caused by:
- Suppression of hypothalamic-pituitary-adrenal axis by chronic high-dose glucocorticoid therapy

221
Q

Polyglandular autoimmune syndrome Type 1

A

More common in children/teens:

  • Hypoparathyroidism
  • Chronic mucocutaenous candidiasis
  • Adrenal insufficiency
222
Q

Polyglandular autoimmune syndrome Type 2

A

More common in adults (30s)

  • Adrenal insufficiency
  • Autoimmune thyroid disease
  • Type 1 DM
223
Q

Symptoms of adrenal insufficiency

A

Weakness, tiredness, fatique
Anorexia
GI symptoms: N/V, diarrhea, constipation
Salt craving

224
Q

Signs of adrenal insufficiency

A 
Weight loss
Hyperpigmentation
Hypotension
Vitiligo (autoimmune)
Auricular calcification
225
Q

Labs in adrenal insufficiency

A

Electrolyte disturbances: hyponatremia, hyperkalemia, hypercalcemia
Azotemia (excess nitrogens in blood)
Anemia
Eosinophilia

226
Q

Symptoms of primary vs secondary adrenal insufficiency

A

Primary: hyperpigmentation or vitiligo (autoimmune), salt craving (low ADH), HYPERKALEMIA

Both: hyponatremia (primary= lose ADH, secondary= water retention due to low cortisol–> dump Na due to unregulated ADH)

Secondary: may see symptoms of other pituitary hormone deficiencies

227
Q

Lab evaluation of adrenal insufficiency

A

Morning serum cortisol of 3 mcg/dL or less–> adrenal insufficiency (19mcg/dL or more- excludes diagnosis)

Indeterminate value: dynamic testing with cosyntropin (synthetic ACTH)

  • 250 mcg given IV/IM- serum cortisol measured 30-60 minutes later
  • 18-20 mcg/dL= normal
  • less than 18-20= diagnostic

Serum ACTH determines primary vs secondary: above 100pg.mL= primary; low/normal values= secondary

228
Q

Treatment of adrenal insufficiency

A

Smallest dose to relieve symptoms:

  • Hydrocortisone 15-20 mg AM, 5-10 mg PM
  • Prednisone 5-7.5 mg daily
  • during stress/illness- double/triple dosage
    • Primary adrenal insufficiency: add fludrocortisone (mineralocorticoid)

Wear medic-alert bracelets

229
Q

Adrenal Cushing’s syndrome

A
  • Adenomas (< 4 cm)
  • Adrenocortical carcinomas (> 6 cm)
    Characterized by autonomous overproduction of cortisol–> ACTH suppression
230
Q

Treatment of adrenal Cushing’s

A

Surgery
- Adrenal carcinoma rarely cured by surgery- may need adjuvant treatment (adrenolytic like mitotane, chemotherapy)

  • Post-op: may take up to 1 year to recover adrenal function–> administer steroids immediately to ensure they don’t crash
231
Q

Primary hyperaldosteronism

A

Hypertension (1% of all hypertensives)
Hypokalemia
High aldosterone and LOW renin
- Tumor in adrenals overproduces aldosterone–> negative feedback on renin

232
Q

Secondary hyperaldosteronism

A

Renal stenosis
- High renin and high aldosterone (low perfusion of kidneys–> stimulates renin secretion–> aldosterone production–> can’t adequately perfuse kidneys still–> continues

233
Q

Conn’s syndrome

A

Primary hyperaldosteronism due to adenoma (70% cases)

  • Benign (rarely carcinoma)
  • Younger patient, more severe hypertension, profound hypokalemia
  • Symptoms: muscle weakness, cramping, polyuria, polydipsia (hypokalemia)
  • vs. hyperplasia in both adrenals–> 30%
234
Q

Screening test for hyperaldosteronism

A

Aldosterone/ Renin ratio > 20

  • measured randomly after diuretics, ACE-I, spironolactone stopped
  • ratio < 20 EXCLUDES primary hyperaldosteronism (100% sensitivity)
  • ratio > 20 needs confirmatory testing (80% specificity)

Confirmatory testing:

  • 9 salt tablets/day for 3 days; 24-hour urine aldosterone > 14 mcg/day confirms primary hyperaldosteronism
  • Saline infusion in hospital
235
Q

Adrenal adenoma vs adrenal hyperplasia

A
  1. CT scan of adrenals
  2. Adrenal venous sampling if inconclusive

Adenoma: surgical: correct BP, K before operation, 30% may have persistant HTN

Hyperplasia: Na-restricted diet, pharmacotherapy (K-sparing spironolactone, amiloride, triamterene; Ca-channel antagonists; ACE-I; HCTZ)

236
Q

Pheochromocytoma

A

Clinical syndrome from autonomous production of catecholamines from a tumor:

  • Usually in adrenals
  • Occasionally extra-adrenal= paraganglioma

Symptoms:

  • HTN
  • Spells/crises
237
Q

Pheochromocytoma “Rule of 10”

A

10% are:

  • Extra-adrenal (intra-abdominal, sometimes in thorax, urinary bladder, cervical
  • bilateral
  • Familial- bilateral more common, associated with Von Recklinghousen’s and Von Hippel Lindau’s
  • malignant
  • Occur in children
  • recur after surgery
238
Q

MEN 2A= Sipple’s syndrome

A

Autosomal Dominant: 95% of MEN2

  • Pheochromocytoma
  • Medullary thyroid carcinoma
  • Hyperparathyroidism (parathyroid hyperplasia, parathyroid adenoma)
  • Other neural crest-derived tumors (glioma, meningioma)
  • RET oncogene mutations
239
Q

MEN 2B

A

Autosomal Dominant:

  • Pheochromocytoma
  • Medullary thyroid carcinoma
  • Mucosal neuromas (neurofibromas with ganglion cells)
  • Marfanoid body habitus
240
Q

MEN 1= Wermer’s syndrome

A

Autosomal Dominant:

  • Pituitary adenoma
  • Hyperparathyroidism
  • Pancreatic islet cell tumors (usually gastrinomas)
  • mutations in Menin protein gene
241
Q

Clinical features of pheochromocytomas

A

Hypertension:
- The most common manifestation
- Sustained in 60% , half with paroxysms
- Only paroxysmal in 40%
Spells or Crises:
- Sudden onset, last few minutes to few hours
- Headache, Diaphoresis, Palpitations, Apprehension, Anxiety, Pallor, Blood Pressure often elevated, with Tachycardia

242
Q

Diagnosis of pheochromocytoma

A

95% sensitive during crisis

  1. 24-hour urine catecholamines (NE, epi, DA) AND their metabolites (metanephrines)
    - Catecholamines= 2X upper limit
    - Metanephrines= above upper limit
  2. Plasma free metanephrines= newer test, not specific, but sensitive
    * NEVER do plasma catecholamines
243
Q

Adrenal imaging

A

CT= most widely used for anatomic localization
MRI= distinguish pheo from other adrenal masses (pheo= hyperintense in T2)
* If CT/MRI negative, consider:
- Whole body MRI (expensive, time-consuming)
- I-123 MIBG scan: similar to NE, taken up by tumor

244
Q

Management of Pheochromocytoma

A

Surgical
- be careful in prepping patient to avoid hypertensive crises in surgery:

  1. start with alpha-blocker (phenoxybenzamine) to control BP, paroxysms (2 weeks pre-op)
  2. If patient becomes tachycardic–> add beta-blockers (propanolol)
    * NEVER add beta before alpha (could have unopposed alpha-adrenergic stimulation)
  3. Can also use Metyrosine= inhibits catecholamine synthesis–> better perioperative course
    - AEs: sedation, depression, anxiety, urea elevation
    - Therefore, used when resection difficult or radiofrequency destruction being used
  4. Two weeks post-op, re-check 24 hour catecholamines, metanephrines (yearly for 5 years)
    - 30% may remain hypertensive despite ressection
245
Q

Adrenal incidentaloma

A

Found in 1-4% patients undergoing CT scans- most nonfunctional, benign adrenal adenomas

Malignancy?

  • 2-12% of incidentalomas, majority > 4 cm
  • 2/3 secrete hormones
  • FNA cannot distinguish benign from malignant
  • Metastases: without KNOWN extra-adrenal malignancy, risk of metastases in adrenal incidentaloma is LOW
  • Known extra-adrenal malignancy–> 8-38% chance this is metastasis (distinguish with FNAB, but exclude pheo first)
246
Q

Workup of adrenal incidentaloma

A

ALL patients with adrenal adenomas (even non-hypertensives) MUST be screened for pheos:

  1. 24-hour urine catechol/metaneph screen
  2. plasma free metanephrines

If hypertensive (plus hypokalemia), send random plasma aldosterone and plasma renin

1 mg overnight dexameth suppression in all patients- if abnormal, need another 24 hour urine collection

247
Q

Management of adrenal incidentaloma

A
  • Hormonally active= surgical removal (regardless of size)
  • > 4 cm= surgical removal (even if not active, due to higher carcinoma risk)
  • < 4 cm and non functional= observe biochemically every year for at least 4 years + repeat CT 3-6 months, 12 months, 24 months
  • Known or suspected extra-adrenal malignancy, perform FNA after pheo ruled out
248
Q

Zona Glomerulosa

A

Outermost layer of adrenal cortex

  • secretes Aldosterone
  • Stimulated by angiotensin, potassium
  • Inhibited by ANP and Somatostatin
249
Q

Zona Fasciculata

A

Intermediate layer of adrenal cortex

  • secretes Glucocorticoids (Cortisol)
  • Stimulated by ACTH
250
Q

Zona Reticularis

A

Inner cortex layer of adrenal- borders medulla

- secretes DHEA (sex steroids)

251
Q

Effects of glucocorticoids

A

Increases and maintains normal concentrations of glucose in blood (esp. in stress states):

  • Stimulates gluconeogenesis
  • Mobilizes aa from extrahepatic tissues
  • Inhibits glucose uptake in muscle, adipose tissue (insulin resistance)
  • Stimulates fat breakdown–> FA release
252
Q

Paraganglioma

A

Extra-adrenal pheochromocytoma–> excess catecholamines

253
Q

Congenital Causes of Primary Hypogonadism in Males

A
  • Klinefelter
  • Chromosomal
  • Mutation in FSH receptor gene
  • Cryptorchidism
  • Varicocele
  • Disorders of androgen synthesis
  • Myotonic dystrophy
254
Q

Acquired diseases causing primary hypogonadism in males

A
  • Infections (esp mumps)
  • Radiation
  • Alkylating agent
  • Suramin
  • Ketoconazole
  • Glucocorticoids
  • Toxins
  • Trauma
  • Testicular torsion
  • Autoimmune damage
  • Systemic illness (chronic)
  • Idiopathic)
255
Q

Causes of secondary hypogonadism

A
  • Same as hypopituitarism
  • Pituitary tumors/ apoplexy
  • Trauma/ XRT
  • Infiltrative diseases
  • Kallmann syndrom
  • Idiopathic
256
Q

In utero testosterone deficiency

A

If testosterone deficiency in the first trimester:

  • Male sexual differentiation is incomplete, resulting in pseudohermaphroditism
  • Complete lack of testosterone results in female external genitalia
  • Incomplete testosterone deficiency causes partial virilization with ambiguous genitalia

If testosterone deficiency after the first trimester:
- Normal male sexual differentiation but micropenis / cryptorchidism at birth

257
Q

Testosterone deficiency before puberty

A

Testosterone deficiency will result in delayed and incomplete puberty:

  • Small testes (<2.5cm; Normal: 4-7cm)
  • Short phallus
  • High voice
  • Decreased muscle mass
  • Decreased body hair
  • Delayed bone age
  • Eunuchoidal skeletal proportions
258
Q

Eunuchoidism

A

Lack of testosterone during puberty causes a delay in epiphyseal closure so that continued presence of growth hormone results in increased length of the long bones
Arm span is > 5 cm greater than height
Lower body segment (heel to pubis) is more than 5 cm longer than the upper body segment (pubis to crown)

259
Q

Hypogonadism after puberty

A

Normal skeletal proportions and penile length are found
Manifestations:
Decreased libido, soft testes and infertility
Fatigue, decreased strength and muscle mass
Decreased rate of hair growth (facial, pubic, axillary…)
Gynecomastia
Osteoporosis if chronic hypogonadism

260
Q

Workup of hypogonadism

A
  • Serum analysis: low sperm?
  • Low serum testosterone
  • Serum FSH/LH: high in primary, low or “normal” in secondary
  • Serum prolactin: rule out prolactinoma
  • Pituitary MRI (secondary hypogonadism- tumor/adenoma)
261
Q

Klinefelter syndrome

A
  • Congenital abnormality (47 XXY) causing PRIMARY hypogonadism (high FSH/LH, low Testosterone)
  • 1/1000 live male births
  • Signs: small firm testes, infertility, eunuchoidism, gynecomastia
  • Low T with high FSH/LH
262
Q

Kallmann syndrome

A

Isolated gonadotropin deficiency: GnRH neurons from hypothalamus fail to migrate to pituitary.

  • Congenital SECONDARY hypogonadism: deficient GnRH secretion (low FSH/LH)
  • Sporadic or inherited (X-linked) or AD/AR; males to females 4:1
  • Signs: anosmia, color blindness, cleft palate, urogenital tract abnormalities, neurosensory hearing loss
  • Low T/estradol, low/normal FSH/LH
263
Q

Testosterone replacement therapy

A
  • Transdermal (gel)
  • IM injections: testosterone enanthate, cypionate
  • Oral forms= dangerous (hepatic prob), scrotal patches= no longer used)
  • Regularly screen men on T: CBC (erythrocytosis), PSA (prostatic hyperplasia sensitive to T)
264
Q

Gynecomastia

A

Benign enlargement of male breast (proliferation of glandular tissue) due to estrogen: androgen imbalance

  • Unilateral (differentiate from carcinoma) or bilateral (asymmetric)
  • May be accompanied by mastodynia (breast tenderness)
  • Distinguish from pseudogynecomastia (lipomastia/fat deposition without glandular proliferation)
265
Q

Conditions associated with gynecomastia

A

Normal/Physiologic:

  • Neonatal (E production develops first in utero)
  • Pubertal (will resolve by puberty)
  • Involutional (aromatase breaks down T later in life–> imbalance)

Pathologic:

  • Neoplasma
  • Primary gonadal failure
  • Secondary hypogonadism
  • Enzyme, receptor defects
  • Drugs (marijuana)
266
Q

Evaluation of gynecomastia: labs

A

Testosterone

  • hCG: high? testicular or extragonadal neoplasm/ germ cell tumor
  • LH high/ T low: primary hypogonadism
  • low/nL LH, low T: secondary hypogonadism or prolactinoma (look for prolactin)
267
Q

Treatment of Gynecomastia

A
  • Watchful waiting
  • Treat underlying etiology
  • Chronic? (more than 12 months)- significant regression unlikely (fibrotic)–> cosmetic surgery
268
Q

Synthesis and secretion of testosterone

A

Men: 8 mg/day; 95% leydig, 5% adrenal
Women: equally from ovaries and adrenals

  • 65% boudn to SHBG
  • 33% bound to albumin
  • 2% free= active form
  • converted to DHT in target tissues (active form) by 5-alpha-reductase
  • Metabolized in liver to inactive forms
  • SHBG:
  • increased by estrogensm cirrhosis, hyperthyroidism
  • decreased by androgens, steroids, hypothyroidism, acromegaly, obesity
269
Q

Physiologic effects of Testosterone

A
  • Penile and scrotal growth
  • Body hair, beard, pubic and axillary hair
  • Sebaceous glands become more active => skin thicker and oilier
  • Growth of prostate and seminal vesicles
  • Vocal cords become thicker
  • Skeletal growth is stimulated
  • Epiphysial closure is accelerated
  • Increased lean body mass
  • Stimulates and maintains sexual function in men
270
Q

Clinical uses of Testosterone replacement

A
  • In patients with hypogonadism (primary, due to testicular failure, or secondary, due to hypothalamic/pituitary failure)
  • Testosterone is used to replace endogenous androgen production
  • In secondary hypogonadism, if fertility is desired, gonadotropins should then be used
  • Available in injections, patches, gel and oral forms (the latter not recommended due to liver damage)
271
Q

Adverse effects of Testosterone replacement

A

Adverse effects:

  • masculinization (females)= hirsutism, acne, amenorrhea, clitoral enlargement, deepening of voice, masculinization of female fetus (in utero exposure)
  • Hepatic dysfunctions: early in course
  • Sodium retention/edema (uncommon)
  • Sleep apnea
  • Gynecomastia (excess converted to estrogen)
  • Erythocytosis
  • Azoospermia/ decrease in testicular size due to suppression of endogenous LH/FSH production–> can take months to recover
  • Low HDL
  • Aggressiveness
  • AVOID in prostate cancer
272
Q

DiGeorge Syndrome

A

Agenesis of thymus, parathyroids; congenital heart defects, dysmorphic facial features

273
Q

Wiscott-Aldrich syndrome

A

X-linked recessive condition

  • thymic hypoplasia, eczema, thrombocytopenia
  • increased risk of lymphoma, autoimmunity
274
Q

Ataxia telangiectasia

A

Autosomal recessive

  • NO Hassall’s corpuscles or epithelial differentiation
  • Cerebellar ataxia, telangiectasias, risk of lymphoma

Repro/Endo flashcards (6 decks)

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