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Endocrinology Review Thyroid, pituitary, adrenal

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Title: Endocrinology Review Thyroid, pituitary, adrenal


1
Endocrinology ReviewThyroid, pituitary, adrenal
bone
  • Dora Liu, MD FRCPC

2
Basic thyroid physiology
3
Hypothalamic-Pituitary-Thyroid Axis
4
Thyroid hormones
From UpToDate
5
Thyroid hormone transport
  • Three major transport proteins
  • Thyroxine-binding globulin (TBG)
  • Thyroxine-binding prealbumin (TBPA)
  • Albumin
  • Free (unbound) hormones are active
  • Proportion of free hormones
  • 0.04 of T4
  • 0.4 of T3

6
(No Transcript)
7
Thyrotoxicosis
8
Clinical features of thyrotoxicosis
  • Weight loss
  • Increased appetite
  • Heat intolerance
  • Anxiety, irritability
  • Fine tremor
  • Fatigue
  • Thyroid stare
  • Systolic HTN
  • Tachycardia
  • Palpitations
  • Atrial fibrillation
  • Frequent BMs
  • Proximal weakness
  • Diaphoresis
  • Moist skin
  • Fine hair

9
Thyrotoxicosis - Investigations
  • Primary
  • Low TSH
  • Increased fT3 and/or fT4
  • Thyroid uptake and scan to determine etiology of
    1o hyperthyroidism
  • Secondary
  • TSH elevated or not suppressed
  • Increased fT3 and/or fT4

10
Causes of 1o thyrotoxicosis
  • Graves disease
  • Toxic adenoma or toxic multinodular goitre
  • Thyroiditis
  • Jod-Basedow (iodine-induced)
  • Exogenous thyroid hormone
  • Gestational hyperthyroidism (hCG-induced)

11
Graves disease
  • Autoimmune disorder
  • Thyroid stimulating immunoglobulin binds TSH
    receptor
  • F gt M
  • Any age with peak in 3rd-4th decade
  • Diffusely enlarged meaty goitre

12
Graves Hyperthyroidism
13
Graves ophthalmopathy
14
Pretibial myxedema
15
Graves diseaseIncreased homogeneous uptake
16
Treatment of Graves disease
  • Methimazole or propylthiouracil (PTU)
  • Radioactive iodine therapy
  • Thyroidectomy
  • Temporary measures
  • ?-blockade
  • Steroids (decrease T4 to T3 conversion)
  • Iodine (Wolff-Chaikoff effect)

17
Toxic adenoma
  • Solitary thyroid nodule produces excess hormone
  • Accounts for lt 5 of hyperthyroidism
  • Frequency increases with age
  • F gt M
  • Treatment of choice radioactive iodine therapy

18
Toxic adenoma
19
Toxic multinodular goitre
20
Toxic multinodular goitre
  • ? 2 nodules producing excess hormone
  • In Canada, most patients are gt 50 yrs old
  • Younger patients in areas of iodine deficiency
  • Compressive symptoms can occur
  • Treatment of choice I-131

21
Toxic multinodular goitre
22
Thyroiditis
  • Destruction of thyroid cells causes release of
    hormones
  • Autoimmune, infectious and toxic causes
  • Can occur in post-partum period
  • Can be associated with fever, painful tender
    gland

23
Diagnosis treatment of thyroiditis
  • Low uptake on thyroid scan
  • NSAIDs for painful inflammation
  • ?-blockers to control symptoms
  • Steroids for severe cases
  • Often followed by hypothyroid phase

24
Gestational hyperthyroidism
  • hCG mimics TSH and stimulates thyroid hormone
    production
  • Associated with hyperemesis gravidarum, multiple
    gestation
  • Improves by 2nd trimester
  • Must differentiate from Graves disease
  • ?-blocker PTU can be used during pregnancy

25
Extrathyroidal sources of thyroid hormone
  • Exogenous sources
  • Exogenous thyroid hormone
  • Hamburger thyrotoxicosis
  • Endogenous sources
  • Struma ovarii
  • Functioning thyroid cancer

26
Other causes of hyperthyroidism
  • TSH-secreting tumour
  • Iodine load (Jod-Basedow phenomenon)
  • Pituitary resistance to thyroid hormone

27
Hypothyroidism
28
Hypothyroidism
  • 2-3 of population
  • FM 101
  • 1o hypothyroidism (90)
  • Autoimmune (e.g., Hashimotos)
  • Iatrogenic (surgery, RAI, drugs, iodine)
  • Congenital, intrinsic defect of hormone synthesis
  • Infiltrative (amyloid, progressive systemic
    sclerosis)
  • 2o hypothyroidism - TSH deficiency
  • 3o hypothyroidism - TRH deficiency

29
Clinical features of hypothyroidism
  • Fatigue
  • Cold intolerance
  • Slow mental physical performance
  • Hoarse voice
  • Bradycardia
  • Diastolic hypertension
  • Edema
  • Weight gain
  • Constipation
  • Menorrhagia
  • Dry skin
  • Macroglossia
  • Muscle cramps
  • Delayed DTR
  • Dyslipidemia

30
Hypothyroidism - Lab tests
  • 1o hypothyroidism
  • Elevated TSH
  • Low fT4 and/or fT3
  • Central hypothyroidism
  • Low fT4 and/or fT3
  • TSH not reliable

31
Treatment of hypothyroidism
  • Typical levothyroxine (LT4) dose 50 - 200 mcg
  • Start low dose (25 mcg) and titrate up slowly in
    elderly
  • R/O adrenal insufficiency
  • Check TSH 6-8 wk after dose change titrate to
    normalize TSH for 1o hypothyroidism
  • Titrate to normalize fT3 for central
    hypothyroidism

32
Myxedema coma
  • Severe hypothyroidism
  • Precipitating event (e.g., trauma, sepsis, cold
    exposure, MI, narcotics)
  • Clinical features Hypothermia, hypoglycemia,
    hypotension, bradycardia, hypoventilation
  • Mortality up to 60
  • Treatment
  • ABCs
  • Stress-dose steroids
  • L-T4 0.2-0.5 mg IV then 0.1 mg daily

33
Non-thyroidal illnessSick euthyroid syndrome
34
Non-thyroidal illness
  • Change in thyroid hormone levels related to
    serious illness
  • Abnormalities in TSH secretion, hormone binding
    metabolism
  • Decreased T4 to T3 conversion
  • Typically see low fT3 high rT3
  • More severe illness fT3, fT4 TSH can all be
    low
  • Rx Treat underlying illness

35
Thyroid nodules and malignancies
36
Thyroid nodules
  • 4 prevalence
  • 5 malignant
  • If nodule is identified, check TSH
  • Low TSH ? Thyroid scan
  • Low probability of malignancy with hot nodules
  • FNAB if cold nodule is present (15-20 malignant)
  • Normal or high TSH ? FNAB if palpable or gt 1 cm
    in diameter

37
Thyroid malignancies
  • Well-differentiated thyroid carcinomas
  • Papillary
  • Follicular
  • Medullary thyroid carcinoma
  • Familial forms MEN IIa IIb, familial
    medullary carcinoma
  • Calcitonin is a tumour marker
  • Anaplastic thyroid carcinoma
  • Very poor prognosis

38
Well-differentiated thyroid carcinoma
  • Total thyroidectomy
  • I-131 therapy if higher risk
  • Multifocal
  • Large tumour
  • Capsular invasion
  • Lymph node or distant metastases
  • TSH suppression
  • Follow thyroglobulin level

39
Medullary thyroid CA
  • Look for other features of MEN IIa IIb
  • R/O pheochromocytoma
  • R/O 1o hyperparathyroidism
  • RET protooncogene mutation
  • Treatment
  • Surgical resection for cure
  • Some respond to MIBG or octreotide
  • Prophylactic thyroidectomy in affected relatives

40
MEN syndromes
MEN 1 MEN 2A MEN 2B
Parathyroid adenoma Enteropancreatic tumour Foregut carcinoid Anterior pituitary tumour Adrenal cortex Medullary thyroid cancer Pheochromo-cytoma Parathyroid tumours Cutaneous lichen amyloidosis Medullary thyroid cancer Pheochromo-cytoma Marfanoid habitus Mucosal neuromas
41
Medullary thyroid CA
  • Look for other features of MEN IIa IIb
  • R/O pheochromocytoma
  • R/O 1o hyperparathyroidism
  • RET proto-oncogene mutation
  • Treatment
  • Surgical resection for cure
  • Some respond to MIBG or octreotide
  • Prophylactic thyroidectomy in affected relatives

42
Pituitary - Adrenal Disorders
43
Basic pituitary adrenal physiology
44
Hypothalamic anterior pituitary hormones
  • GHRH ? Growth hormone (GH)
  • TRH ??TSH
  • Somatostatin ? ? GH TSH
  • TRH Prolactin-releasing factors ? Prolactin
  • Dopamine ? ? Prolactin
  • CRH ? ACTH
  • GnRH ? LH FSH

45
Pituitary hormones
  • Anterior
  • Growth hormone
  • ACTH
  • LH
  • FSH
  • TSH
  • Prolactin
  • Posterior
  • ADH (arginine vasopressin)
  • Oxytocin

46
Hyperprolactinemia
47
Causes of hyperprolactinemia
Physiologic Medications Pathologic
Pregnancy Nipple stimulation Sleep Stress Exercise Estrogen Anti-psychotics MAOI Opioids Cimetidine Licorice Pituitary tumours Stalk compression Chest wall lesions Hypothyroidism Renal failure Severe liver disease
48
Hyperprolactinemia
  • Clinical features
  • Galactorrhea, gynecomastia, infertility, low bone
    density
  • Headaches, bitemporal hemianopsia (if
    macroadenoma affects optic chiasm)
  • Treat underlying cause, if present
  • 1o Rx for prolactinoma
  • Dopamine agonist (e.g., bromocriptine or
    cabergoline)

49
Acromegaly
50
Clinical features of acromegaly
  • Coarse facial features
  • Acral enlargement
  • Hyperhidrosis
  • Heat intolerance
  • Oily skin
  • Fatigue
  • Weight gain
  • HTN
  • Goitre
  • Cardiomegaly
  • Insulin resistance
  • Arthralgias
  • Parasthesias
  • Hypogonadism
  • Headaches

51
Acromegaly
  • Diagnostic tests
  • Glucose suppression test
  • IGF-1 level
  • Treatment
  • Surgery
  • Somatostatin analogues (Octreotide)
  • Radiotherapy
  • GH receptor antagonist (Pegvisomant)

52
Posterior pituitary disorders
53
SIADH Diagnostic criteria
  • Plasma osmolality lt 275 mOsm/kg H2O, excluding
    pseudohyponatremia or hyperglycemia
  • Inappropriate urine concentration (UOsm gt 100
    with normal renal function)
  • Clinical euvolemia
  • Elevated urine sodium excretion with normal salt
    and water intake
  • Absence of other potential causes of euvolemic
    hypo-osmolality (hypothyroidism, adrenal
    insufficiency, diuretic use)

54
Treating SIADH
  • Fluid restriction
  • Loop diuretics
  • Hypertonic saline if urgent correction needed
  • Demeclocycline, lithium (rarely used)
  • Do not correct Na too quickly
  • Treat underlying cause

55
Diabetes insipidus
  • Clinical features
  • Polyuria, polydispsia
  • Hypernatremia, dehydration
  • Low urine Na osmolality
  • Treatments
  • Oral IV fluids
  • dDAVP
  • For nephrogenic DI
  • Na restriction, thiazides PG inhibitors

56
Hypothalamic Pituitary Adrenal Axis
From Williams Textbook of Endocrinology
57
POMC synthesis and cleavage
From Williams Textbook of Endocrinology
58
Retroperitoneal Anatomy
59
Microscopic anatomy
Zone Hormone
Glomerulosa Aldosterone
Fasciculata Cortisol
Reticularis Androgens
Medulla Catecholamines
From Williams Textbook of Endocrinology
60
Adrenal steroid function
  • Glucocorticoids
  • Affects fuel metabolism, responses to injury and
    general cell function
  • Mineralocorticoids
  • Control body Na and K content
  • Androgens
  • Similar function to male gonadal hormones

61
Adrenal steroidogenesis
From Williams Textbook of Endocrinology
62
Sites of glucocorticoid action
From Williams Textbook of Endocrinology
63
Cushings syndrome
64
Features of Cushings
  • Moon facies
  • Facial plethora
  • Dorsal supraclavicular fat pads
  • Mental status change
  • HTN
  • Visceral adiposity
  • Muscle wasting
  • Ecchymoses
  • Thin skin
  • Purple striae
  • Osteoporosis
  • Avascular necrosis
  • Insulin resistance

65
Screening tests for Cushings syndrome
  • 24 hr urinary free cortisol
  • Low-dose dexamethasone suppression test
  • Evening cortisol
  • Salivary cortisol (2300)

66
Working up Cushings
Diagnose Cushings
ACTH gt 2
ACTH lt 2
High-dose DST
Adrenal Imaging
Ectopic Cushings or Cushings disease
Cushings disease
Adrenalectomy
MRI Pituitary
Inferior petrosal sinus sampling
Pituitary surgery
Cushings disease
Ectopic Cushings
CT Chest/abdo Octreotide scan
MRI Pituitary
Pituitary surgery
67
Adrenal insufficiency
68
Clinical features of adrenal insufficiency
  • Addisons
  • Hyperpigmentation
  • Volume depletion
  • N/V, abdo pain
  • Hyperkalemia
  • Weight loss
  • Fatigue
  • Weakness
  • Hypoglycemia
  • Hyponatremia
  • Anemia

69
Adrenal insufficiency
  • Treatment
  • IV fluids
  • Glucocorticoid therapy
  • Mineralocorticoid therapy for Addisons
  • Diagnosis
  • ACTH stimulation test
  • Insulin tolerance test for central disease

70
Primary hyperaldosteronism
71
Aldosterone secretion action
Hypotension Low Na
Renin
Angiotensinogen Angiotensin I
Aldosterone
ACE
Angiotensin II
? Na reabsorption
? Blood pressure
72
Control of renin secretion
  • Promoters
  • Low perfusion pressure
  • Low tubular Na
  • Hemorrhage
  • Renal artery stenosis
  • Dehydration
  • Salt loss
  • Hyperkalemia
  • Norepinephrine
  • Suppressors
  • High-salt diet
  • Elevated BP
  • Hypokalemia
  • Beta-blockers
  • Indomethacin

73
Assessment of renin-angiotensin-aldosterone axis
  • Random plasma renin activity not reliable
  • Plasma aldosterone gt 695 pmol/L
  • Aldosteronerenin ratio
  • 24 hr urinary aldosterone
  • Normal 14-56 nmol
  • Aldosterone-producing adenoma 125 ? 9 nmol
  • Idiopathic hyperaldosteronism 75 ? 5 nmol
  • Adrenal vein sampling

74
From UpToDate
75
Adrenal androgens
76
Adrenal androgen secretion
  • gt 50 of circulating androgens in premenopausal
    females
  • Relative contribution smaller in males
  • Stimulated by ACTH
  • DHEA and androstenedione levels demonstrate
    circadian rhythm (but not DHEAS)

77
Congenital adrenal hyperplasia
X
X
78
Congenital adrenal hyperplasia
  • Autosomal recessive disorder
  • Presentations of CAH
  • Female neonates Ambiguous genitalia
  • Male neonates Adrenal crisis
  • Non-classic Hirsutism infertility in females
  • Treatment
  • Glucocorticoid therapy
  • Mineralocorticoid for salt-wasting varieties

79
Pheochromocytoma
80
Clinical features of pheochromocytoma
  • Paroxysmal or sustained HTN
  • Triad H/A, palpitations/tachycardia,
    diaphoresis
  • Postural drop in BP
  • Dilated cardiomyopathy
  • Tremor, anxiety
  • Chest pain
  • Papilledema, blurry vision

81
Pheochromocytoma
  • Diagnosis
  • Urine metanephrines or plasma catecholamines
  • MIBG, octreotide scan
  • Treatment
  • ?-blockade or CCB (not ?-blocker 1st!)
  • Volume restoration
  • Adrenalectomy

82
Bone calcium disorders
83
PTH-Ca2 feedback loop
-
Parathyroid glands
PTH
PTH
-
GI Tract
1,25 D
Ca2
Ca2
Ca2
-
ECF Ca2
84
Vitamin D
7-dehydrocholesterol
Cholecalciferol
25-OH vitamin D
PTH
Calcitriol
24,25(OH)2 - D
?Intestinal Ca PO4 absorption
  • PTH
  • secretion

Multiple effects in bone
Effects in muscle
85
Hypercalcemia
86
Clinical manifestations of hypercalcemia
  • General Weakness
  • CVS HTN, valve arterial calcification
  • GI Constipation, anorexia, N/V, pancreatitis
  • Renal Stones, DI (polyuria), renal
    insufficiency
  • MSK Bone pain
  • CNS Altered mental status

87
Mechanisms for hypercalcemia
  • Increased bone resorption
  • Increased gastrointestinal absorption of calcium
  • Decreased renal excretion of calcium

88
Increased bone resorption
  • Hyperparathyroidism (usually 1o)
  • Malignancies
  • PTHrP (solid tumours, leukemia)
  • 1,25(OH)2D (lymphomas)
  • Ectopic PTH (rare)
  • Osteolytic lesions
  • Hyperthyroidism
  • Immobilization
  • Pagets disease (usually with immobilization)
  • Estrogen, tamoxifen
  • Hypervitaminosis A

89
More causes of hypercalcemia
  • Increased calcium absorption
  • Increased calcium intake
  • Hypervitaminosis D
  • Lithium
  • Thiazide diuretics
  • Pheochromocytoma
  • Adrenal insufficiency
  • Rhabdomyolysis
  • Theophylline
  • Familial hypocalciuric hypercalcemia

90
Ways to lower calcium
  • IV fluids
  • Furosemide
  • Calcitonin
  • Steroids
  • Bisphosphonates
  • Dialysis

91
Management Increase Renal Excretion of Calcium
  • IV fluids
  • NS 200-300 cc/hr or as tolerated
  • Maintain urine output 100-150 cc/hr
  • Furosemide IV q4-6h
  • Start when volume replete
  • Watch for and correct hypomagnesemia, hypokalemia

92
Management Inhibit bone resorption
  • Calcitonin
  • Decreases Ca by up to 0.3-0.5 mmol/L in 4-6 hrs
  • Efficacy limited to first 48 hours
  • Most effective in cases assoc. with
    hyperphosphatemia
  • Indicated when volume and diuretics ineffective
  • Bisphosphonates
  • Pamidronate 30-90 mg IV
  • Zolendronate 4 mg IV most effective for
    malignancy
  • Works in 2-4 days
  • Gallium nitrate
  • 200 mg/day IV by continuous infusion over 5 days
  • Potentially nephrotoxic

93
Management Decrease intestinal calcium
absorption
  • Glucocorticoids
  • Hydrocortisone 3-5mg/kg/day IV or prednisone
    20-40 mg/day
  • Effective for breast CA, myeloma, sarcoidosis,
    vit D intoxication
  • Decrease calcitriol production by activated
    mononuclear cells
  • Effect occurs in 48-72 hours
  • Oral phosphate binds calcium in GI tract

94
Other management strategies
  • Chelators
  • EDTA
  • IV phosphate
  • Not used due to toxicity
  • Hemodialysis or peritoneal dialysis

95
Hypocalcemia
96
Clinical features of hypocalcemia
  • Paresthesia
  • Laryngospasm
  • Seizures
  • Carpopedal spasm
  • Chvosteks sign (CN VII)
  • Trousseaus sign (carpal spasm)
  • Hyperreflexia
  • Mental status changes

97
Causes of hypocalcemia
  • Low PTH
  • Hypoparathyroidism
  • Hypomagnesemia
  • Vitamin D related
  • Vitamin D deficiency
  • 1?-hydroxylase activity (renal failure, vit D
    dependent rickets)
  • Vitamin D resistant rickets
  • Pseudohypoparathyroidism (PTH resistance)
  • Drugs (calcitonin, furosemide)

98
Treatment of hypocalcemia
  • ABCs
  • Replace calcium
  • Calcium gluconate IV
  • Oral calcium
  • Treat hypomagnesemia, if present
  • May require vitamin D
  • Correct underlying cause

99
Osteoporosis
100
What is osteoporosis?
  • Systemic skeletal disorder
  • Characterized by compromised bone strength
  • Leads to enhanced bone fragility and a consequent
    increase in fracture risk

101
What determines bone strength?
  • Bone density
  • Expressed in grams of bone mass over area or
    volume of bone
  • Determined by peak bone mass amount of bone
    loss
  • Bone quality
  • Refers to architecture, damage accumulation
    (e.g., microfractures) mineralization

NIH Consensus Statement 2000
102
Bone density quality determine bone strength
Normal bone Low BMD Poor
quality
103
Osteoporosis fractures
  • Osteoporosis is a significant risk factor for
    fractures
  • Fractures occur when a failure-inducing force is
    applied to osteoporotic bone

104
Indications for BMD 50 yrs
  • Age 65 yrs
  • Fragility fracture after age 40 yr
  • Prolonged glucocorticoid use
  • Use of other high-risk medications
  • Parental hip fracture
  • Vertebral or osteopenia on X-ray
  • Current smoking or high EtOH intake
  • Low weight (lt 60kg) or wt loss (gt10 of weight at
    age 25 yr)
  • Rheumatoid arthritis
  • Other disorder strongly associated with
    osteoporosis

CMAJ 2010
105
Indications for BMD lt 50 yrs
  • Fragility fracture
  • Prolonged use of glucocorticoid
  • Use of other high-risk medication
  • Hypogonadism or premature ovarian failure
  • Malabsorption syndrome
  • Primary hyperparathyroidism
  • Disorder strongly associated with rapid bone loss
    and/or fracture

CMAJ 2010
106
DEXA is used to measure BMD
  • The PROS of DEXA scanning
  • Quick, non-invasive
  • 1/10 radiation of CXR (background radiation
    exposure over 1 day)
  • Most accurate estimator of fracture risk
  • The CONS of DEXA scanning
  • Not a measure of bone strength (only accounts for
    70 of strength)
  • Inter-operator variability, lack of
    standardization

107
Who should be screened?
  • Indications for BMD scan
  • Patients with 1 major or 2 minor risk factors for
    osteoporosis
  • Age 65 years regardless of risk factors
  • Contraindications for BMD scan
  • Pregnancy
  • Recent GI study or nuclear medicine test (wait at
    least 72 hr up to 7 d for long-lived isotopes
    like gallium)

108
Interpretation of BMD measurements
  • T-score of SDs from average person of same
    gender at peak bone mass
  • Z-score of SDs compared to average person of
    same gender, age race

109
WHO diagnostic categories
Classification Criterion
Normal T-score - 1.0
Osteopenia T-score between -1.0 and -2.5
Osteoporosis T-score lt -2.5
Severe osteoporosis T-score lt -2.5 with Hx of fragility fracture(s)
110
Secondary causes of osteoporosis
Endocrine Metabolic Nutritional Drugs Collagen disorders Other
Hypogonadism Cushings Thyrotoxicosis Anorexia nervosa Hyperprolactinemia Porphyria Hypophosphatemia Diabetes Pregnancy Hyperparathyroidism Acromegaly Malabsorption Malnutrition Chronic cholestatic liver disease Gastric operations Vitamin D deficiency Calcium deficiency Alcoholism Glucocorticoids Excessive thyroid hormone Heparin GnRH agonists Phenytoin Phenobarbital Vitamin D toxicity Osteogenesis imperfecta Homocystinuria Ehlers-Danlos syndrome Marfan syndrome Rheumatoid arthritis Myeloma some cancers Immobilization Renal tubular acidosis Hypercalciuria COPD Organ transplantation Mastocytosis Thalassemia
111
Calcium vitamin D intake
Calcium Calcium
Children (4-8) 800 mg
Adolescents (9-18) 1300 mg
Premenopausal women 1000 mg
Men lt50 1000 mg
Menopausal women 1500 mg
Men gt 50 1500 mg
Pregnant or lactating women 1000 mg
Vitamin D Vitamin D
Age lt 50 400 IU
Age gt 50 800 IU
112
Fall Prevention
  • Risk Factors
  • Sedatives
  • Previous fall
  • Cognitive impairment
  • Visual impairment
  • Foot problems
  • Gait abnormalities
  • Lower extremity disability
  • Prevention measures
  • Bathroom lights on
  • Install grab bars
  • Avoid loose rugs
  • Remove clutter
  • Keep wires behind furniture

113
Who should receive pharmacotherapy?
114
10-yr fracture probability
Probability ()
T-score
Age (yrs)
Osteoporos Int 2001 12 989
115
FRAX Calculation tool
116
FRAX Calculation tool
117
Treat high risk patients
  • gt 20 10-yr fracture risk
  • Prior fragility of hip
  • Fragility of spine
  • gt 1 fragility

CMAJ 2010
118
Moderate risk (10-20 10-yr risk)
  • Consider treatment if
  • Prior wrist and age gt 65 yr
  • L-spine T-score ltlt femoral neck
  • Rapid bone loss
  • Androgen deprivation therapy or aromatase
    inhibitor
  • Long-term or repeated glucocorticoid use
  • Recurrent falls (gt 2 in 12 mos)
  • Disorder strongly associated with osteoporosis or
    rapid bone loss

CMAJ 2010
119
Bisphosphonates
  • Similar in structure to pyrophosphate in bone
  • Attaches to bone surface and inhibits
    osteoclastic resorption
  • PO Alendronate, risedronate
  • IV Pamidronate, zoledronic acid
  • Possible adverse effects Reflux, ONJ, atrial
    fibrillation, low-energy subtrochanteric fractures

120
Denosumab (Prolia)
  • Human monoclonal RANKL antibody
  • Inhibits osteoclastic activity
  • Pros
  • Convenient, 60 mg SC q6 mos
  • Reduces vertebral non-vertebral s
  • Well-tolerated
  • Cons
  • Lack of long-term data
  • Dermatologic side effects

121
Calcitonin
  • Inhibits bone resorption
  • Analgesic effect
  • No drug-drug interactions
  • Well-tolerated
  • Evidence for reduction in vertebral fractures,
    but not non-vertebral fractures

122
Hormone replacement therapy
  • The benefits
  • Decreases osteoclastic activity
  • Increases BMD lowers fracture risk
  • Treats symptoms of estrogen deficiency
  • Decreases colon cancer risk
  • The down side
  • Increased CVD, VTE PE risk
  • Increased breast cancer risk
  • Adverse effect on cognition

123
Selective Estrogen Receptor Modulator (SERM)
  • Binds to estrogen receptors
  • Produces an estrogen agonist effect in some
    tissues
  • Produces an estrogen antagonist effect in others
  • Examples Tamoxifen, raloxifene

124
Guidelines for Teriparatide
  • 1st line Rx for women 65 yrs with T lt -2.5 and
    Hx of vertebral fracture
  • Preferable to treat bisphosphonate naïve patients
  • Consider treating post-menopausal women with T lt
    -3.5 who continue to fracture despite adequate (2
    yr) trial of therapy
  • Discontinue bisphosphonate prior to PTH
  • Limit PTH Rx to maximum 24 mos
  • Administer bisphosphonate therapy after PTH course

CMAJ 2006 17548
125
Hip protectors
  • 1801 frail but ambulatory elderly adults, mean
    age 82 yrs
  • Hip protector control 1 2
  • 1 month F/U
  • Relative hazard of hip fracture 0.4 P0.008

NEJM 2000 343 1506
126
Vertebroplasty kyphoplasty
  • Vertebroplasty minimally invasive surgical
    procedure to relieve the pain of compression
    fractures
  • Kyphoplasty proprietary derivative procedure
    using polymethylmethacrylate (PMMA) to fix a
    vertebral body in place after balloon inflation
    of the body

127
Good luck!
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