APIRADEE SRIWIJITKAMOL

DIVISION OF ENDOCRINOLOGY AND METABOLISM

DEPARTMENT OF MEDICINE
FACULTY OF MEDICINE SIRIRAJ HOSPITAL
CALCIUM
HOMEOSTASIS
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Review 2014

VITAMIN D PATHWAY
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Review 2014

 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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Review 2014

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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Review 2014

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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Review 2014

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
 S2iriraj Board
Review 2014

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 S2iriraj Board
Review 2014

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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neurogenicReview 2014

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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Review 2014

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