parathyroid & calcium disorders
TRANSCRIPT
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Parathyroid DisordersOsteomalacia & Osteoporosis
Professor Tariq Waseem
Dr. Hina Latif
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Botanical Garden Sydney
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CASE SCENARIO: 1
A 20yr old girl presented in E.R with h/o of convulsions for the last 3 hrs. Examining her the house officer noticed a stridor and observed spasm of her hands while he was recording her blood pressure.
What is the working diagnosis?Which 3 bed side tests can be performed to confirm the diagnosis?
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• Tetany.• Hypocalcemia.
• Trosseou’s sign• Chvostek’s sign• Brisk tendon Reflexes
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Hypoparathyroidism
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Parathormone(PTH)
PTH is an 84-amino acid polypeptide derived from a prohormone.
It is the major hormone in Ca++ homeostasis.
NORMAL Ca LEVELS9 to 10.5mg/dl
2.2 to 2.6 mmol/L
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ACTIONS OF PTH
BONE RESORPTION
PHOSPHATURIC
REABSORPTION OF DIETARY Ca++
DISTAL RENAL TUBULAR REABSORPTION OF Ca++
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HYPOPARATHYROIDISM
• Iatrogenic• Idiopathic (auto immune)• Pseudohypoparathroidism (autosomal dominant)• Pseudo pseudo hypoparathyroidism (normal Ca levels)
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Albright’s Syndrome (Pseudohypoparathyroidism)
Short 4th & 5th metacarpels
Low Serum Calcium, Normal PTH. PTH receptor deficiency
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HYPOCALCEMIA
LARYNGOSPASM
CHVOSTEK SIGN
CONVULSIONS, MENTAL
RETARDATION
PROLONGED QT INTERVAL
HYPER REFLEXIA
TROUSSEAU’S SIGN
CATARACT PAPPILOEDEMA
SKELETAL DEFORMITIES
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DIFFERNTIAL DIAGNOSISCa IONIZED Ca PO4 PTH
HYPOALBUMINEMIA L N N N
ALKALOSIS N L N N/H
VIT D DEFICIENCY L L L H
HYPO- PARATHYROIDISM
L L H L
PSEUDO HYPO PARATHYROIDISM
L L H H
ACUTE PANCREATITIS L L L/N H
RENAL FAILURE L L H H
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MANAGEMENT
• Treat alkalosis (Rebreathing exhaled air through a bag)• Inj calcium gluconate 10mg in 10ml over 10 mins.• Magnesium sulphate• 1 alpha hydroxy cholecalciferol
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CASE SCENARIO: 2
A 55 yr old male presented in E.R holding his right flank. He complains of a severe right sided lumbar pain , excessive vomiting & constipation for 2days. He has a dry tongue with vitals of B.P 150/110mmHg, pulse 110/min . On USG KUB radio opaque stones are seen in the right kidney.
Give a list of differential diagnosis?What investigations will you request?
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HYPERCALCEMIA
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HYPERCALCEMIA
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CAUSES OF HYPERCALCEMIA
• Primary or tertiary hyperparathyroidism• Familial hypocalciuric hypercalcemia
• Malignancy• Multiple myeloma• Milk alkali syndrome• Diuretics• Paget’s disease• Vitamin D intoxication• Addison’s disease
NORMAL OR ELEVATED PTH
LOW PTH
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TYPES OF HYPERPARATHYROIDISMTYPES Ca PTH PO4 ALP URINE
Ca/PO4
PRIMARY H N/H L H H
SECONDARY L H H H L
TERTIARY H N/ H H H
MALIGNANCY H L/N L H
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INVESTIGATIONS….
• Screen for malignancy• Chest X ray, bone scan, X ray hands• CT neck• Rule out Multiple Myeloma.
Serum protein electrophoresis, benze jones
proteins,immunoglobulins• Sarcoidosis ( ACE levels)
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IMAGING
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IMAGING…
SUB PERIOSTEAL RESORPTION BROWN TUMOR
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MEDICAL MANAGEMENT
REHYDRATE WITH 4-6 LITRES OF SALINE
BISPHOSPHONATESPRAMIDRONATE 90mg I.V over 4 hrs till cause is removed.
FORCED DIURESIS (FUROSEMIDE)GLUCOCORTICOIDSCALCITONINDIALYSIS
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Botanical Gardens Sydney
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• A 40yrs old female, known epileptic, presented with 4months history of generalized muscular discomfort particularly in her shoulders. The symptoms don’t worse in the morning with non-specific relieving factors. Her weight is stable.
• Examination reveals only mild proximal weakness in both arms and legs with preserved reflexes
Case scenario: 3
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• Hb…10.9g/dl• ESR…16mm/h• Plasma glucose(post-parandial) ….7.6mmol/l• HbA1C….5.6%• S.calcium…7.4mg/dl• Phosphate…2.5mg/dl• Alkaline phosphatase…198 IU/L
• DIAGNOSIS??????
Subsequent investigations revealed:
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• This Patient’s presentation with myalgia associated with a combination of mild hypocalcemia, hypophosphatemia and elevation of alkaline phosphatase is strongly suggestive of OSTEOMALACIA.
OSTEOMALACIA
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• Rickets and osteomalacia are conditions characterized by pathological defects in bone matrix mineralization. Rickets refers specifically to osteomalacia, where the defect occurs in growing bone.
• The aetiological factors are diverse, but the end result is an increased quantity of unmineralized bone matrix (osteoid).
RICKETS AND OSTEOMALACIA
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The conditions may arise in three distinct
situations:• Deficiency or abnormal metabolism of vitamin D• Phosphate depletion• Chronic metabolic acidosis…RTA
Etiology
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Causes of Osteomalacia:
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• Bone pain• Backache• Muscle weakness…proximal myopathy• Vertebral collapse…kyphosis, loss of height• Deformities and stress fractures• Difficulty in rising from a chair• Difficulty in walking• Waddling gait…sometimes
Sign & Symptoms:
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Clinical presentation:
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Laboratory tests:
• Increased serum alkaline phosphatase• Plasma calcium…usually normal but decreased in
severe disease• Low serum phosphate• Serum 25OHD….low
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X-RAYS:• May show defective mineralization in pelvis, long bones
and ribs, with pseudofractures and LOOSER’S zones• Linear areas of low density
surrounded by sclerotic
bone.
Imaging
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X-ray findings:
Loosers zones - incomplete stress # with healing lacking calcium, on compression side of long bones
Codfish vertebrae due to
pressure of discs
Trefoil pelvis, due to indentation of acetabulae stress #s
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Looser Zones
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Looser Zones
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• Illiac crest biopsy….necessary if biochemical tests are equivocal
• Serum fibroblast FGF-23….sometimes elevated in tumor associated osteomalacia.
Further Diagnostic tests:
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Depends on the underlying cause;
• Vitamin D supplementation• Phosphate supplements if required• Calcium supplements for isolated calcium deficiency• Bicarbonate if chronic acidosis
Treatment:
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• Vitamin D : 400-800IU/day for nutritional deficiency.
• Higher doses or parenteral administration in pts with gastrectomy, liver disease, on epileptic medications
• Calcitriol or alfacalcidol
For defective 1a-hydroxylation…CKD,
Vit. D dependency,
Hypophosphatemic rickets with osteomalacia
Treatment:
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• Correction of the fracture• Deformities stabilization• DIET THERAPY:
• Milk, yogurt, cheese• Dark green leafy vegetables, okra, broccoli• Fish and seafood• Almonds
Treatment:
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• Monitoring of serum calcium, alkaline phosphatase…to screen for hypercalcemia
• Normalization of alkaline phosphatase…good measure of healing
Monitoring:
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Case Scenario: 4
• A 65 year old lady on long term steroids for bronchial asthma is brought to ER after she fell in wash room and could not stand up due to severe pain in and around her left hip and lower back.
• X-rays showed fracture on left femoral neck and markedly reduced density of Lumber vertebrae.
• What bone disease she has?• What are risk factors for this disease?
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Osteoporosis
Under diagnosed
Under reported
Inadequately researched
Challenges of Osteoporosis
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Risk Factors Being female
Older age
Family history of osteoporosis or broken bones
Being small and thin
History of broken bones
Low sex hormones
• Low estrogen levels in women, including
menopause
• Missing periods (amenorrhea)
• Low levels of testosterone and estrogen in men
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Risk Factors… Diet• Low calcium intake • Low vitamin D intake • Excessive intake of protein,
sodium and caffeine Inactive lifestyle Smoking , Alcohol abuse Certain medications
• steroid , anticonvulsants etc Certain diseases
• anorexia nervosa, rheumatoid arthritis, gastrointestinal diseases and others
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Definition of OsteoporoisNational Osteoporosis Foundation: a disease characterized by low bone
mass an micro-architectural deterioration of bone tissue, leading to bone fragility and an increased susceptibility to fractures.”
World Health Organization (1994) : bone mineral density T-score greater
than –2.5 standard deviations from the mean peak adult bone mass (ie. a woman in her 30’s).”
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Classification of Osteoporosis Primary osteoporosis
• Juvenile osteoporosis. • Idiopathic osteoporosis• Postmenopausal
osteoporosis• Age-related, or senile,
osteoporosis
• Secondary osteoporosis• Congenital• Diet• Drugs• Endocrine disorder• Other Systemic
Disorder
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Osteoporosis
Losing bone with years
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Prevalence…
Worldwide, over age of 50 1 in 3 women 1 in 8 men have osteoporosis. Caucacian and asian races..at risk
80 % of those suffering from osteoporosis are women. Affects 75 million persons in the US, Europe and Japan.
Over 50% of women aged 50 years or older and 20% of men will suffer an osteoporosis-related fracture within their remaining lifetime
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SECONDARY CAUSES OF OSTEOPOROSISEndorine disecase
1. Hypogonadism*
2.Hyperparathyroidism
3 .Hyperthyroidism
4.Cushing's syndrome
5. Type 1 diabetes mellitus
Inflammatory disease
1. Inflammatory bowel disease .
2.Ankylosing spondylitis
3.Rheumatoid arthritis .
Gastrointestinal disease 1. Malabsorption
2.Chronic liver disease
* Hypogonadism plays an important role in osteoporosis associated with these conditions.
Drugs 1.Corticosteroids
2.Gonadotrophin-releasing hormone (GnRH) agonists*
3.Aromatase inhibitors
4.Thyroxine over-replacement
5.Sedatives 6. Rosiglitazone
7.Anticonvulsants
8. Alcohol excess 9.Heparin .10. Cyclosporine
Miscellaneous 1.Myeloma
2.Homocystinuria
3.Anorexia nervosa*
4.Highly trained athletes*
5.Gaucher's disease
6.Systemic mastocytosis
7.Immobilisation
8.Poor diet/low body weight .
9. Osteogenesis imperfecta
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The “silent disease”
• Often called the “silent disease”
• Bone loss occurs without symptoms• First sign may be a
fracture due to weakened bones
• A sudden strain or bump can break a bone
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Presentation People may not know that they
have osteoporosis until they break
a bone.
Vertebral (spinal) fractures may
initially be felt or seen in the form
of
Persistent, unexplained back
pain
Loss of height
Spinal deformities such as
kyphosis or stooped posture.
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Diagnosis…
Plain radiographs…may reveal asymptomatic vertebral deformities
Dual-energy X-ray Absorptiometry (DXA) Scan
• “Gold-standard” for BMD measurement.• Measures “central” or “axial” skeletal sites: spine
and hip( proximal femur) • May measure other sites: total body and forearm.• Precise, accurate, uses low dose of radiations
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• Quantative ultrasound of the calcenum…screening procedure before DXA
• Quantative CT scanning…allows true volumetric assessment, and distinction b/w trabecular and cortical bone
Bone density:
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Diagnosis…
Dual-energy X-ray Absorptiometry (DXA) Scan
Classification T-score
Normal -1 or greater
Osteopenia Between -1 and -2.5
Osteoporosis -2.5 or less
Severe Osteoporosis -2.5 or less and fragility fracture
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Investigations (continued) INDICATIONS FOR BONE DENSITOMETRY :
Low trauma fracture (fall from standing height or less)
Clinical features of osteoporosis (height loss, kyphosis)
Osteopenia on plain X-ray
Corticosteroid therapy (> 7.5 mg prednisolone daily for > 3 months)
Family history of osteoporotic fracture
Low body weight (body mass index < 19)
Early menopause (< 45 years)
Diseases associated with osteoporosis
Assessing response of osteoporosis to treatment
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Complications:
FRACTURE ,
The most serious complication of
Osteoporosis that leads to
Increased morbidity Increased mortality
Decreased quality of life
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Complications:
Wrist fracturemen 1 in 40 (2.5%)
women 1 in 6 (16%)
Spinal fracturemen 1 in 20 (5%)
women 1 in 6 (16%)
Hip fracturemen 1 in 17 (6%)
women 1 in 6 (17.5%)
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Management principle
Decreased fracture risk
Life style modification Therapeutic Intervention
• Minimizing risk factors Slowing/stopping bone loss
• Minimizing factors that Contribute to fall
Maintaining or increasing bone density and
strength
Maintaining or improving bone microarchitecture
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• Symptomatic management…of vertebral fractures, bed rest for 1-2 weeks, analgesics
• Calcium and vitamin D• Exercise• Smoking cessation• Reduce falls…physiotherapy & home safety• Pharmacological intervention…anti-resorptive drugs,
bisphosphonates, SERM, HRT, calcitriol, calcitonin etc…
Treatment and prevention:
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Goal of treatment
Prevent further bone loss
Increase or at least stabilize bone density
Prevent further fractures
Relieve deformity (e.g., kyphoplasty)
Relieve pain
Increase level of physical functioning
Increase quality of life
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Pharmacologic management
Supplements which maintain bone mass Calcium ( 700-1000mg/day), Vitamin D( 400-800 IU/day)
Anti-resorptive agents which inhibit bone resorption Bisphosphonates
Anabolic agents, which stimulate bone formation and, in turn, increase
bone mass.
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1.Bisphosphonates: synthetic analogues of bone
pyrophosphate, adher to hydroxyapatite and inhibit osteoclasts.
Alendronate: 70 mg orally once weekly (tablet or solution)
Risedronate: 35 mg orally once weekly
Ibandronate sodium:is taken once monthly in a dose of 150 mg orally .
Pharmacologic therapy:
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Management (continued)
Zoledronic acid: every 12 months in doses of 2–4 mg I/V over 15–30 minutes.
Pamidronate: an older parenteral bisphosphonate given in doses of 30–60 mg by slow i/V infusion in every 3–6 months
2. Hormone replacement therapy (HRT) : For oral estrogens, 0.3 mg/d for esterified estrogens, 0.625 mg/d for conjugated equine estrogens, and 5 g/d for ethinyl estradiol.
For transdermal estrogen, the commonly used dose supplies 50 g estradiol per day.
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3. Selective estrogen receptor modulators(SERMs): Raloxifene, 60 mg/d orally,Tamoxifen.
4. Calcitriol (1,25-(OH)2D3): may reduce vertebral fracture rate.
5. Calcitonin: binds to receptors on osteoclasts,dose is one puff (0.09 mL, 200IU) once daily, alternating nostrils.
Management (continued)
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Management (continued)
6. Parathyroid hormone (PTH): stimulate bone formation. Teriparatide daily s/c injection of 20 μg over a 12-18-month period. Increases BMD by 10% or more.
7. Strontium ranelate: weak anti-resorptive activity, 2 g daily
8. Denosumab: monoclonal antibody that inhibits osteoclast activation,60 mg s/c every 6 months.
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Nonpharmacologic Approaches:
a.Kyphoplasty and vertebroplasty
b. Measures…to avoid falls at home adequate lighting, handrails on stairs, handholds in bathrooms. Patients who have weakness or balance problems must use a cane or a walker.
Management (continued)
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Treatment Monitoring
• Response to treatment can be monitored either by repeated BMD measurement or by measuring biochemical markers of bone turnover.
• Changes must exceed ~4% in the spine and 6% in the hip to be considered significant in any individual.
• BMD should be repeated at intervals >2 years.
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• If bone turnover markers are used, a change in bone turnover markers must be 30–40% lower than the baseline to be significant.
• If neither BMD nor biochemical markers are available, treatment response can be assessed by monitoring changes in height and the occurrence of clinical fractures.
Treatment monitoring:
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Case Scenario: 5
• A 14 year old girl consults for fever which she has for 3 weeks. She has a history of recurrent fractures of long bones of forearm and legs since the age of Six on minor trauma. Latest fracture involving left mid femur was fixed through intramedullary rod insertion 6 months ago. Her IM rod was removed 4 weeks ago.Labs. Review: Normal calcium, phosphorus, vitamin D, parathormone.What bone disease she possibly has?What diagnostic test will help to reach a diagnosis?
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DEXA Scan
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DEXA Scan
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DEXA Scan
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Diagnosis
Osteogenesis Imperfecta
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“Three Sisters” Blue Mountains Australia