Patient was apparently well 1 days back when she started
having abnormal movements of body in form of tonic clonic
movements associated with tongue bite, bladder bowel
this episode last for 2-3 min followed by confusion in form
reduced responsiveness, decreased communication ,
unsteadiness of gait.
With these complaints patient is brought to IGMC shimla.
Patient had similar episode during hospital stay.
No history fever, rash , trauma ..
No significant history of similar complaints in past. no history
of ATT intake. HTN, DM in past.
No family history of similar complaints
Patient is non alcohlic, non smoker, vegitarian ,house wife
educated up to 10th standard
Menstrual history is normal
Pt is cooperative, well oriented to time and person but
not to place.
PR 80/min, BP 108/78mm hg , RR 24/min.
no Pallor no icterus
No clubbing, pedal edema ,cyanosis, icterus ,LAP.
Wt. 46kg,ht. 158 cm, BMI 18.42
no neck rigidity no kernig sign
During B.P monitoring it was noted that there was
flexion at the MP joints
extension of the IP joints
I. S1 and S2 normal. no mumur .
Trachea central. both sides moving equally with
respiration. Bilatral vesicular breath sounds . No added
HMF, cranial nerves, speech –normal
motor system, sensory system- normal
no kernig sign, no neck rigidity .
Inj. Lopez 4mg .
calcium gluconate 10ml (1amp) 10% w/v in 50ml of
D5 over 5mins under strict vital monitoring
followed by calcium gluconate infusion for 24 hours
(mix 5 ampoules of calcium gluconate in 500 ml of D5
start at 10 udrops/min to be completed in 12 hours
followed by same infusion for another 12 hours)
Oral calcium 1gm bd with meals
oral calcitriol 0.25ugm/day
patient improved symptomatically
after treatment calcium increases to 7.90 mg/dl and
phosphorus decreases to 3.70mg/dl.
QTc comes to normal 0.41
Patient discharged on oral calcium and vitamin D
Renal effects (steady state maintenance)
◦ Inhibition of phosphate transport
◦ Increased reabsorption of calcium
◦ Stimulation of 25(OH)D-1alpha-hydroxylase
Bone effects (immediate control of blood Ca)
◦ Causes calcium bone release within minutes
◦ Chronic elevation increases bone remodeling and increased
osteoclast-mediated bone resorption
◦ However, PTH administered intermittently has been
shown to increase bone formation and this is a potential
new therapy for osteoporosis
Promote absorption of Ca++
Effect is primarily mediated through increased levels of 1,25-
Normal serum calcium (Ca) levels range between 2, 25
– 2,75 mmol/l (8.8 – 10.4 mg/100 ml.
Approximately 40 % of the total blood Ca is bound to
serum proteins while the remaining 50 % is
ultrafilterable and includes ionized Ca plus Ca
comlexed with phosphate and citrate.
The ionized Ca fraction (about 50 % of the total blood
Ca) is influenced by pH changes.
Acidosis is associated with decreased protein - binding
and increased ionized Ca and alkalosis with a fall of
ionized Ca due to increased protein – binding.
These pH – induced changes in ionized Ca occur
independently of any change in total blood Ca
ionized calcium increases by 0.2mg/dl for each 0.1
decrease in PH
PTH is 84 amino acid single chain peptide with amino and
Amino terminal PTH(1-34) is highly conserved biologic
ionized calcium is important determinant of hormone
secreation most rapid method of increase in serum PTH by
release of preformed hormone within minutes
Peripheral proteolysis of hormone occurs in liver and kidney
results in biologically inactive fragments so called middle and
Rate of clearance of secreted 84 amino acid peptide from
blood is more rapid than biologically inactive fragments
that are middle and carboxyl terminal of PTH.
Consequently interpretation of result obtained with
earlier PTH radioimmunoassays is influenced nature
peptide fragments detected by antibodies.
Second generation assay are double antibody
immunometric assay. These assay beside detecting intact
PTH(1-84) , also detects amino truncated forms PTH(7-
84). These amino truncated forms are present in normal
and uremic persons in additional to intact PTH(1-84).
Evidence suggest that these amino truncated forms are
inhibitor of intact PTH action and are clinically significant in
renal failure, efforts to prevent secondary HPT ( due to over
detection PTH(7-84) BY 2nd generation assay) by certain
measures results in over suppression of intact PTH secreation
which further results in ADYNAMIC BONE DISEASE
The measurement of PTH by3rd generation immunometric
assay which use detection antibodies directed against
extreme amino terminal of PTH epitope detect only full length
intact PTH(1-84) so prevents bone disease in CKD.
blood transfusion with citrated blood ,
acute renal failure
Patients with severe sepsis may have decreased ionized
calcium. But in other severely ill patient
hypoalbuminemia is primary cause of reduced
Alkalosis increases calcium binding to proteins in this
setting ionized calcium should be measured
medications protamine glucagon heparin causes
Corrected total calcium = measured total calcium+ 0.8
(4.0 − serum albumin),
where calcium is measured in milligrams per deciliter
and albumin is measured in grams per deciliter.
1) DiGeorge syndrome-
Heterozygous Deletion Of chromosome 22q11.2
may include conotruncal cardiac defects,
parathyroid thymic hypoplasia,
palatal, renal, ocular, and skeletal anomalies;
hypocalcemia (in 50–60% of patients) can be transient or
permanent and can develop in adulthood; microarray analysis
performed as an initial diagnostic screening test, with the
deletion confirmed by FISH
Heterozygous gain-of-function mutations in the CaSR .
These receptors senses ambient calcium levels as
excessive and suppresses PTH secretion leading to
hypocalcemia and hypercalciuria
Mutation in GATA 3 which is required for kidney otic
vesicle parathyroid development
Progressive external ophthalmoplegia, pigmentary
retinopathy, heart block or
cardiomyopathy, diabetes, and hypoparathyroidism).
MELAS with diabetes and hypoparathyroidism
short stature, osteosclerosis, cortical bone
thickening, calcification of basal ganglia, ocular
abnormalities, and hypoparathyroidism that is
probably due to agenesis of the glands.
parathyroid aplasia, growth failure, ocular
PGA type 1 usually recognized in first decade of life
and requires two of three components for diagnosis i.e
mucocutaneous candidiasis, adrenal insufficiency and
Acquired hypoparathyroidism is most commonly the result of
inadvertent removal or irreversible damage to the
glands, usually to their blood supply, during
thyroidectomy, parathyroidectomy, or radical neck dissection.
Definitions of permanent postsurgical hypoparathyroidism
vary, but the definition is generally accepted to be insufficient
PTH to maintain normocalcemia 6 months after surgery.
Hypoparathyroidism is estimated to occur after approximately
0.5 to 6.6% of total thyroidectomies;
Immune-mediated destruction of the parathyroid glands can be
either isolated or part of autoimmune polyendocrine syndrome
type 1 (APS-1).
Hypoparathyroidism may also be caused by accumulation in
the parathyroid glands of iron (hemochromatosis or
transfusion-dependent thalassemia) or copper (Wilson’s
disease) in rare cases by iodine- 131 therapy for thyroid
diseases or metastatic infiltration
Severe hypomagnesemia <0.8meq/l associated with
hypocalcemia by two mechanism of action.
1) Impaired PTH secretion
2) reduced responsiveness of PTH
drugs (aminoglycoside, cisplatin, diuretics, cyclosporine,
renal disorders :RTA, Post obstructive nephropathy
It may be difficult to rule out hypomagnesemia as the
cause of or a contributor to hypocalcemia because the
serum magnesium level may be normal, even when
intracellular magnesium stores are reduced.
In general, if the primary disturbance is magnesium
depletion, serum calcium levels are only slightly
Intact PTH is often undetectable or inappropriately low.
phosphate levels are not elevated as in case of idiopathic
PTH is ineffective when there is
1) defect in PTH receptor i.e pseudohypoparathyrodism
2)when PTH action to promote calcium absorption from diet is
impaired due to vitamin D deficiency or because vitamin D is
3) chronic renal failure
PTH binds to PTH receptor which acts through G
PHP results from some form of disruption in this
Type 1a Reduction in activity of the stimulatory protein
G (Gs), limiting AMPc synthesis, patients are not only
resistant to PTH, but to other peptide hormones like
TSH, gonadotrophins, and glucagon.Transmission is
Type 1 b normal Gs activity, and isolated resistance to
PTH. Molecular studies do not show an intrinsic defect
in the PTH receptor, and present normal Gs function.
Majority of cases are sporadic.
Type 1 c Albright’s phenotype and resistance to
multiple hormones. Gs activity is normal, Studies
show reduced activity of the membrane’s adenyl
cyclase catalytic subunit.
Type 2 associated with defects in stages posterior to
AMPc formation, because Gs activity is normal.
AHO Resistance to
PHP 1 A Yes yes yes yes
PHP1 B Yes No No rare
PHP 1C Yes No yes yes
PHP-II Yes Normal No No No
ALBRIGHT’S HEREDITARY OSTEODYSTROPHY
short, stocky build,round face
low, flat nasal bridge,
Brachymetaphalangism-short 4th and 5th metacarpal and
developmental delay, with or without endocrine
Intracranial calcification (commonly involving the basal ganglia )
MENTAL RETARDATION :
Seizures, usually grand mal, occur in AHO and may be independent of
Sensorineural hearing loss and impaired olfaction has been identifed in
Cataracts and lenticular opacities are common in these patients.
THYROID: Hypothyroidism secondary to TSH resistance is common.
GONADAL : Gonadal dysfunction, particularly menstrual irregularity is
Short stature &
Round, flat face
-vitamin D deficiency
impaired cutaneous production
accelerated loss of vitamin d
increased metabolism(phenytoin rifampicin )
impaired enterohepatic circulation
impaired 25 hydroxylation
liver disease isoniazid
1@ hydroxylase mutations
target organ resistance-vitamin D resistance mutation
Vitamin D dependent
rickets type 1
Vitamin D dependent
rickets type 2
Also called psedovitamin D
1@hydroxylase. no partial
or total alopecia.
physiological amount of
calcitriol cure the disease
Also called true vitamin D
resistant rickets due to end
organ resistant active met
or total alopecia.requires
nocturnal calcium infusions
Delayed closure of fontanels
Delayed eruption of teeth
Splaying of distal ends of
long bones bones
Recurrent chest infections
CLINICAL FEATURES OF vitamin D
Bone pain and pathologic fractures. proximal myopathy is
striking feature severe vitamin D deficiency both in childrens
Decreased bone density osteopenia
Hypophosphatemia, increase in alkaline phosphatase and
serum PTH levels
Mild hypocalcemia ,secondry hyperparathyrodism , severe
Conditions causing severe hyperphosphatemia like in
rhabdomyolysis tumour lysis syndrome there is
severe hypocalcemia can occur quickly PTH rises in
response to hypocalcemia but does return blood
calcium to normal.
◦ When nerves are exposed to low levels of
calcium they show abnormal neuronal function
which may include decrease threshold of
excitation, repetitive response to a single
stimulus and rarely continuous activity.
◦ Adrenergic symptoms
◦ Convulsion (More common in young people and it can
take the form of either generalized tetany followed by
prolonged tonic spasms or the typical epileptiform
◦ Signs of latent tetany
Extrapyramidal signs (due to basal ganglia calcification)
A blood pressure cuff is inflated to a pressure above the patients
Pressure is continued for 2-3 minutes.
flexion at the wrist
flexion at the MP joints
extension of the IP joints
bradycardia or ventricular arrhythmias, cardiovascular collapse,
hypotension that is non-responsive to fluids and vasopressors.
A decrease in myocardial contractility occurs,
ECG: corrected QT interval (QTc) prolongation
Hypocalcaemia leads to decreased myocardial
Although the mechanism is undefined, calcium plays
a critical role in excitation-contraction coupling and
is required for epinephrine-induced glycogenolysis in
clinically this may present as congestive heart failure.
The congestive cardiac failure in hypocalcaemia is
refractory to diuretics and digitalis but rapidly
responds to restoration of calcium concentrations to
Review of the patient’s medical and family histories may
suggest the cause of hypocalcemia
A history of neck surgery suggests that parathyroid function
may have been compromised by the surgical procedure
A family history of hypocalcemia suggests a genetic cause
.history of excessive alcohol intake may suggest magnesium
congenital defects point to the DiGeorge
The skin should be examined carefully for a
neck scar (which suggests a postsurgical cause
for candidiasis and vitiligo (which are
suggestive of APS-1); and for generalized
bronzing and signs of liver disease (which are
suggestive of hemochromatosis).
Features such as growth failure, congenital anomalies,
hearing loss, or retardation point to the possibility of
Laboratory testing should include measurements of serum
total and ionized calcium, albumin, phosphorus,
magnesium, creatinine, intactPTH, and 25-
hydroxyvitamin D (25[OH] vitamin D) levels. Albumin-
corrected total calcium is calculated as follows:
Corrected total calcium = measured total calcium + 0.8
(4.0 − serum albumin
the intact PTH level is
normal or inappropriately
low in a patient with low
serum calcium and Serum
phosphorus levels are
usually high or at the high
end of the normal range.
PTH calcium phosphor
low High or at
. Patients with
sm have a laboratory
profile that resembles
that in patient with
, low calcium and high
but they have elevated
PTH CALIUM PHOSPHO
most specific screening test for
vitamin d deficiency is 25(OH)D
level .optimal vitamin d level
>32ng/ml. levels <15ng/ml
associated with increase PTH
level.PTH induced increase bone
turn over increases ALP
level.PTH promotes phosphaturia.
initially calcium levels may b
normal or there may be mild
renal 1@hydroxylase so levels of
1,25(OH)2D are nomal in severe
vitamin D deficiency. radiologic
features include widened
expanded growth plate that is
chracteristic of rickets
Mild decrease(7-8)mg/dl Severe hypocalcemia
Oral therapy with calcitriol
and calcium supplements
With symtoms and signs
If ECG changes or symptoms present begin with iv
a)consider early initiation of haemodialysis when caused
by severe hyperphosphatemia
b) bolos 2gm of mgso4 iv over 15 min if known
hypomagnesemia or empirically if renal functions are
c) bolus 2gm of calcium gluconate ( 20ml or 2 ampoules
if 10% w/v 1g contain 93mg elemental calcium ) in 50-
100 ml in D5 or NS iv over 15 mins
D) begin continuous calcium infusion dilute 6gm of calcium
gluconate in 500 ml of of D5 or NS and infuse at 0.5-1.5mg
e) follow ionized calcium or corrected calcium 6 hourly and
continue infusion until calcium normalizes for 24-48 hours
2) dose 1-2gm elemental calcium PO tid or qid separate from
3) add 0.25-4 ugm/day calcitriol
4) can add salt restriction and hydrochlorthiazide if
Continue infusion for 24-48 hours,
key complication of vit D inoxication (hypercalcemia and
hypercalciuria) and adverse effects on kidney .
Levels of serum calcium phosphorous monthly during initial
dose adjustment and then yearly as dose is stablized . Urinary
calcium should also measured yearly.
Calcitriol is preferred over Vitamin D2 and D3 as it
has high potency rapid onset and rapid offset of
hyperphosphatemia can be addressed by
decreasing patient dietary intake (eggs, milk
products cola ) if needed phosphate binders can be
albumin corrected serum calcium at lower end of
normal range (8-8.5)mg/dl
24 hr urinary calcium less than 300mg
calcium phosphorous product should be less than 55
annual slit lamp examination to rule out
development of cataract
calcium supplements (1000–1500 mg/d elemental
calcium in divided doses)
Vitamin D2 or D3 (cholicalciferol 60000 IU weekly
for 8-12 weeks) or calcitriol [1,25(OH)2D, 0.25–2 g/d
40% elemental calcium by weight; begin with 500–1000 mg of
elemental calcium (three times per day) and adjust the dose to
control symptoms and achieve the targeted calcium level; at least
1–2 g of elemental calcium (three times daily) generally required
and more frequent. Constipation is a common side effect;
calcium carbonate is best absorbed with acid present in the
Recommended in patients who have achlorhydria or who are
taking a proton-pump
inhibitor, in order to achieve sufficient absorption of calcium
.950-mg tablet (200 mg of elemental calcium)