Bone case scenarios

Rasha Odeh

Serum Ca:

45% is present in physiologically active ionized Calcium (Ca++)

40% is bound to albumin (ca : albumin 0.8:1)15% circulates as complexes with other molecules

(such as citrate and sulphate)

Serum Calcium concentration is influenced by:

• Intestinal Ca ++ absorption

• Ca deposition in bone & mobilization of Ca following bone

resorption

• Renal tubular Ca reabsorption

• Parathyroid hormone (PTH) – increases reabsorption of calcium and excretion of phosphorus from

distal tubules

– During hypocalcemia, mobilizes calcium from bone through stimulating osteoclast activity

– Enhances 1hydroxylase activity and calcitriol production in proximal tubules

– Bicarb and aminoacid excretion.

• 1,25(OH)2D (vitamin D) – accelerates calcium absorption from the intestine and stimulates bone

resorption

• Calcitonin– inhibits osteoclastic bone resorption stimulated by PTH

Which hormones regulate calcium homeostasis?

Primary function of PTH prevent hypocalcemia

Within minutes changes in PTH

increasing Ca abs & P exc.

Osteoclastic bone resorption

Over a period of 1-2 days,by stimulating synthesis of

1,25(OH)2D3

increase intestinal Ca abs

CaSR

PTHR1

Gs,

PTH

Serum Ca++

Par

ath

yro

id

glan

d

Target organs•Kidney

•Bone

Hypocalcemia Hypercalcemia

Autosomal dominant hypocalcemia (CaSR activating mutation)

Famil benign Hypocalciu/ hypercalcemia

(CaSR inactivating mutation)

Hypoparathyroidism(XLR,AR)•Di George Syndrome•SYNDROMES(Sanjad Sakati)•APECED Syndrome / mitochondrial•Infiltrative disease (thalasemia)•Parathyroid surgery

Hyperparathyroidism

•MEN-1, MEN 2a

•Sporadic parathyroid adenomas

•Tertiary hyperparathyroidism

Blomstrand’s chondrodysplasia(inactivating mutation)

Jansen disease

Pseudohypoparathyroidism•Type Ia•Type Ib•Type Ic•Type II

McCune–Albright syndrome

Chronic renal failure Hypophosphatasia

Modified from Allgrove J. In: Brook CGD, Clinical Pediatric Endocrinology, 5th edn. Oxford:

AR, AD familial isolated hypopa Sporadic parathyroid tumors

Stage Ca P Alk P PTH Events

Stage 1 N to

Low

N N to

high

N to

high

Poor Ca absorption from

gut

Stage 2 N Low High High Secondary hyperPTH, bone

loss

Stage 3 Low Very

low

Very

high

Very

high

Ca stores depleted, severe

hypocalcemia, seizures

Biochemical Stages of Nutritional Rickets

Case 1

• Ca 6.8 mg/dL

• P 7.6 mg/dL

• Mg 3.7 mg/dl

• ALP 333 U/L

• PTH 4 pg/mL (low)

• Albumin 3.7 mg/dl

• 25 (OH)D 55 ng/ml

How to approach

• Low calcium

• High phosphate

• ?? MG and albumin

• KFT

• Vit D

• PTH level

• Cause

Answer

• Primary hypoparathyroidism due to SanjadSakati Syndrome

3 year old with delayed walking and bowing of lower limbs

• Ca 6.5 mg/dL

• P 2.3 mg/dL

• Mg 2.5 mg/dl

• ALP 720 U/L

• PTH 500 pg/mL.high

• Albumin 3.7 mg/dl

• 25 (OH)D 3 ng/ml

Answer

• (nutritional) rickets

• Ca 6.5 mg/dL

• P 7 mg/dL

• Mg 2.5 mg/dl

• ALP 220 U/L

• PTH 500 pg/mL (high)

• Albumin 3.7 mg/dl

• 25 (OH)D 38 ng/ml

AHO Phenotypic features

• Syndromes are associated with specific dysmorphic features

• Round face• Short neck• Short stature

• Shortened fourth metacarpal & metatarsal

Answer

• Pseudohypoparathyroidism, type 1a or 1c

Case presentation:

8month old female baby presented with:

• poor appetite

• decreased activity

• Preference of water over milk

• Polyurea and polydipsia

• symptoms increased in severity in the last 2months

• Incidental finding of hypercalcemia

• (ca=16.5 mg/dl)

• Vaccination up to age

• Day care attendance

• not on medication nor supplemental vitamins

• Feeding regular formula

• Bowel motion once daily

• First alive baby In the family(first trimester abortion and 2ed baby was IUFD)

• parents are cousins

• Mother had celiac and protein c deficiency

P/E:

• V/S :

HR 126 RR 35 BP90\50

• Growth parameter

HT 65 10th centile WT 6.8 kg 10th centile

• Sunken eyes, dry lips

• GAEB with normal heart sounds

• Soft lax abdomen

• No organomegally

Routine Labs:platlymphneutwbcrdwmcvhtchb

27770.720.79.1115.283.733.611.3

Alka.pho

rbsmgcaclphosBUNcrkna

82921.6819.51085.643.60.434.7141

LDHastAltalbumT.prot

402.831144.16.4

problem list:

1.Hypercalcemia

2.Dehydration

Management

1.correct dehydration with 7%

2.treat hypercalcemia with hydration and furosamide

3.strict urin output u.o=5-8ml\kg\hr

4.look for causes

5.complications of hypercalcemia

VITA-DTSHT4PTH

57.6(nl)4.612.33.4 (low)

SPOT CR-URIN

SPOT CA-URIN

URIN OSMOLSERUM OSMO

0.076392274.8

BEHCO3CO2PH

-320307.44

• Hypercalcemia NOT due to vit D intoxication or hyperparathyroidism

• No evidence for granulomatous disease

• No evidence of malignancy

• The hypercalcemia was due to the fact that the patient has Williams syndrome

• Hypercalcemia can occur in these patients and it usually is transient and mild, but can also be severe as in this patient.

Thank you