APIRADEE SRIWIJITKAMOL
DIVISION OF ENDOCRINOLOGY AND METABOLISM
DEPARTMENT OF MEDICINE
FACULTY OF MEDICINE SIRIRAJ HOSPITAL
CALCIUM
HOMEOSTASIS
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VITAMIN D PATHWAY
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APPROACH TO HYPERCALCEMIA
-Hyper PTH -Malignancy -Vitamin D intake
-Lithium - PTHrP: -Granulomatous
-Familial hypocalciuric - Sq cell CA disease
hypercalcemia - Breast, lymphoma
- Humoral: NHL
- LOF: MM, Breast
-Endocrine dis.
-Drugs: vit A, thiazide
-Others
TYPES OF HYPERCALCEMIA
ASSOCIATED WITH CANCER
Stewart AF. N Engl J Med 2005;352:373-379.
TREATMENT OF HYPERCALCEMIA
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Mild Moderate Severe
Symptom - - + -/+
Identify cause
Supportive
IV fluid*
I/O > 3L/D
IV Furosemide
Bisphosphanate**
Calcitonin***
Hemodialysis
* Be careful in elderly and heart disease patients
** Do not use in patient with acute kidney injury
*** A few days of treatment
APPROACH TO HYPOCALCEMIA
-Low PTH: -Vit D def.
-Critical illness - Malabsorption
- Hypoparathyroidism
- Hyperphos. - Liver and renal
-Low Mg - Rhabodmyolysis
-PTH resistance - Anticonvulsant
- Tumor lysis synd
- Pseudohypo PTH - Elderly
- Phosphate Rx
- Others: -Vit D resistance
-Drugs: - Ricket type II
- P450: INH, rifam, - Phenytoin Rx
anticonvulsant ,gllucocorticoid
- Citrate
METABOLIC BONE DISEASES
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Mineralization
Osteomalacia/rickets
Low bone mineral content
Osteoporosis
High bone turnover
Hyperparathyroidism
OSTEOMALACIA
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vInadequate MINERALIZATION of normal
osteoid tissue
vDifferent expressions of the same disease
v Rickets
vAreas of endochondral growth
v Osteomalacia
vAll skeleton is incompletely calcified
OSTEOMALACIA
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Symptoms and Signs
v
v Bone pain, backache
v Muscle weakness
v Vertebral collapse
vKyphosis
vloss of height
v Deformities & stress fractures
Bone pain
Pathological fracture!
Generalized muscle weakness
Disability!
Others Metabolic Bone Disease
Metastasis bone
Rheumato
Hematologic: Osteoporosis! Pagets!
MM
Osteomalacia!
Osteomalacia Osteoporosos
Clinical Pain, muscle weakness -
Lab Ca , P , Alk -
X-ray Osteopenia, looser zone Osteopenia
BMD Decrease Decrease
Bone pain
Pathological fracture!
Generalized muscle weakness
Disability!
Others Metabolic Bone Disease
Metastasis bone
Rheumato
Hematologic: Osteoporosis! Pagets!
MM
Osteomalacia!
Vit D def.! Fanconis! Hereditary TIO!
Hypophosphatemia!
-RTA
-Glycosuria
-hypophosphatemia
OSTEOMALACIA
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v Defect in Vitamin D metabolism
vNutritional
vUnderexposure to sunlight
vIntestinal malabsorption
vLiver & kidney diseases
vAnticonvulsant use
v Hypophosphataemia with renal phosphate wasting
vRTA
vTumor-induced ostemalacia
vHereditary hypophosphatemic osteomalacia
OSTEOMALACIA
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v Investigation
v Blood chemistries
vCalcium, Phosphate, Albumin, Alkaline
phosphatase
vRenal function and Elyte
v25-OH vitamin D
viPTH
v Urine calcium/phosphate
v Film bone survey
v Bone biopsy
PSEUDOFRACTURE
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PSEUDOFRACTURE
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PSEUDOFRACTURE
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HYPOPHOSPHATEMIA VS.
VITAMIN D DEFICEINCY
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Hypophosphatemic Vit. D Deficiency
Osteomalacia Osteomalacia
Calcium Normal Normal. (Low)
Phosphate Low Low
ALP High High
Elyte In RTA -
25-OH vitamin D Normal Low
iPTH Normal, Nornal, (High)
Urine phosphate High Normal
*Urine phosphate > 100 mg/D , FE phosphate > 5% = high
PRIMARY HYPERPARATHYROIDISM
vHistory vPhysical examination
vAsymptomatic vNeck mass
v50% of symptomatic: vBasic lab
vRenal calculi vCBC, UA
vBone pain or fracture vCa, P, Alk, Alb
vOther symptoms vElectrolyte, BUN, Cr
vPU, Pancreatitis vSpecial test
vNeuromuscular and vBone survey
vNeuropsychiatric vBMD
vEndocrine syndrome: vMIBI scan
vMEN I or MEN IIa
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Film HAND
v Acro-osteolysis
v Generalized osteopenia
v Subperiosteal
resorption of the radial
aspect of the middle
phalanges of index and
middle fingers
FILM BONE SURVEY
A: Subperiosteal distal clavicular resorption
B: Brown tumor, the osseous expansion
and lucency of the proximal humerus
FILM SKULL
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Trabecular bone
resorption resulting in
the salt-and-pepper
appearance
FILM SKULL
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vBrown tumor
vLoss of lamina dura
RENAL OSTEODYSTROPHY
v Characteristic endplate
sclerosis
v Rugger-jersey spine
RENAL OSTEODYSTROPHY
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vMultifocal, large, amorphous
calcific deposits
vTumoral calcinosis
RECOMMENDATIONS FOR THE
EVALUATION OF ASYMPTOMATIC PHPT
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v Biochemistry panel
v Ca, P, ALP, BUN, Cr, 25(OH)D
v PTH level
v BMD by DXA
v Lumbar spine, hip, and distal 1/3 radius
v Vertebral spine X-ray or VFA by DXA
v 24-h urine for:
v Ca, Cr, CCr
v Stone risk profile esp. Ur Ca >400 mg/D
v Abdominal imaging by x-ray, ultrasound, or CT scan
Bilezikian et al,. J Clin Endocrinol Metab, October 2014, 99(10):35613569
PRIMARY HYPERPARATHYROIDISM
v Symptomatic: surgery
v Asymptomatic: ?Indication
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Measurement 1990 2002 2008 2013
Serum Ca 1-1.6 mg/dl 1 mg/dl 1 mg/dl 1 mg/dl
(>upper NL)
Renal
24-h Ur Ca >400 mg/D >400 mg/D -
Ccr by 30% by 30% < 60 mL/min < 60 mL/min
Others Ca-stone
risk
Skeletal
BMD Z-score <-2.0 in T-score <-2.5 at T-score <-2.0 at T-score <-2.5 at
forearm any site any site* any site*
Others Vertebral #
Age <50 <50 <50 <50
*Z-score in premenopausal women and in men under 50
INDIVIDUALIZED GLYCEMIC
TARGET
Diabetes Care 2017;40(Suppl. 1):S48S56 | DOI: 10.2337/dc17-S009
IDF GUIDELINE 2013
A1C
INCRETIN-BASED THERAPY
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DPP-IV Inhibitor GLP-1 receptor agonist
glucose dependence glucose dependence
insulin secretion insulin secretion
A1C ~0.5-0.8% A1C ~0.5-1.0%
GFR >30
GFR
?
SGLT2 INHIBITION
Advantage Disadvantage
o Insulin independence Polyuria
action
Urine output
o A1C ~0.7%
400-600 ml
o Low risk of hypoglycemia
Electrolytes
o BW reduction
abnormalities
o glycosuria 75 g/D =
Not found in the study
300 kcal/D
o 3-4 . UTI
o BP reduction Genital tract infection
o ~4-5 mmHg Euglycemic DKA
o CV death
Update ADA 2017
WHIPPLES TRIAD
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Symptoms consistent with hypoglycemia Review 2014
Neurogenic manifestation
Neuroglycopenic manifestation
Low plasma glucose
Non-diabetic subject <55 mg/dl
Diabetic subject <70 mg/dl
Relief of symptoms when plasma glucose concentration is
raised to normal level
SEVERITY OF HYPOGLYCEMIA
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MILD
Autonomic symptoms are present
Individual is able to self-treat
MODERATE
Autonomic and neuroglycopenic symptoms are present
Individual is able to self-treat
SEVERE
Unconsciousness may present
Individual requires assistance of another person
Plasma glucose is typically < 50 mg/dl
HYPOGLYCEMIC
UNAWARENESS
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MANAGEMENT OF HYPOGLYCEMIA
qIs it true hypoglycemia?
qWhat is its cause?
qTreatment of hypoglycemia
qPrevention
MANAGEMENT OF HYPOGLYCEMIA
qIs it true hypoglycemia?
qWhat is its cause?
qTreatment of hypoglycemia
qPrevention
MANAGEMENT OF HYPOGLYCEMIA
qIs it true hypoglycemia?
qWhat is its cause?
qTreatment of hypoglycemia
qPrevention
APPROACH TO HYPPGLYCEMIA
COMMON DRUG OTHER THAN
SU/INSULIN THAT CAUSED HYPOGLYCEMIA
Gatifloxacin Chloroquine ACEI/ARB
Pentamidine Artesunate Levofloxacin
Quinine Lithium Bactrim
Indomethacin Heparin
INVESTIGATION IN SEEMINGLY WELL
NON-DM
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Repeat plasma glucose
Plasma insulin, C-peptide, cortisol, ketone during
hypoglycemia
Sulfonylurea level
Insulin C-peptide Cortisol SU Ketone
Endogenous hyperinsulinemia -
Insulin injection -
SU intake -
Adrenal insufficiency
MANAGEMENT OF HYPOGLYCEMIA
Capillary blood glucose
Confirmed venous blood glucose
Identify cause of hypoglycemia*
Retest BG after 15-20 min
Check for recovery
Retest BG in 15 min
Repeat treatment
if BG still < 70 mg/dl Repeat treatment
