absent PTH

1
????? ???????????

• ?"? ????? ?????
• ?????? ?'
• ????? ?????? ????
• ??"? ????

2
?????????? - ???? ??????

• ?????? ?????
• ???????
• ?????????
• absent PTH
• resistance PTH
• PTH overwhelmed
• ????? ???????????

3
?????? ??????

• ???? ?? 70
• Ca 8 mg/dl
• ???? ????? ????? ????? ???????????????
• ?????? ?????? ??????
• ?????? ?? ???? ????? ??????
• Alb-4, ALP-156

• ???? ?? 60
• Ca 6.4 mg/dl
• ??????? ? ?.?.?. ???? ????? ????? ????? ???
  ?????? ????
• ??????? ?? ????? ?????? ?????? ???? ?????? ?????
• Alb 3

• ?? ?????? ??? ??????
• ?? ???????

4
Calcium Homeostasis
5
Correction of Total Calcium According to Albumin

• ? 40 of circulating calcium is bound to
• albumin
• ? Correction for hypoalbuminemia
• Each 1 g/dL reduction in serum albumin
• results in 0.8 mg/dL reduction in serum
• calcium without affecting ionized calcium

6
?????? ??????

• ???? ?? 70
• Ca 8 mg/dl
• ???? ????? ????? ????? ???????????????
• ?????? ?????? ??????
• ?????? ?? ???? ????? ??????
• Alb-4, ALP-156
• ??? ???? ??????

• ???? ?? 60
• Ca 6.4 mg/dl
• ??????? ? ?.?.?. ???? ????? ????? ????? ???
  ?????? ????
• ??????? ?? ????? ?????? ?????? ???? ?????? ?????
• Alb 3
• ???? ?????
• 6.40.87.2 mg/dl

• ?? ?????? ??? ??????
• ?? ???????

7
HypocalcemiaClinical Manifestations

• Determined by the serum ionized calcium level and
  the rate of development

8
HypocalcemiaNeuromuscular Symptoms

• ? Numbness, paresthesias, muscle cramps
• Carpopedal spasm, facial grimacing
• Tetany, seizures
• Laryngospasm, bronchospasm
• ? Fatigue, irritability, anxiety, depression
• ? Some patients do not have neuromuscular
• symptoms (even with severe hypocalcemia)!

9
HypocalcemiaNeuromuscular Symptoms

• Chronic untreated hypocalcemia
• ? Mental retardation in children (irreversible)
• ? Extrapyramidal disorders
• ? Basal ganglia calcifications
• ? Papilledema- with or without high CSF
• pressure, reversible

10
Trousseaus sign
Induction of carpal spasm by inflation of a
sphynfomanometer above systolic BP for 3 min
11
Chvosteks and Trousseaus signs
Contraction of the ipsilateral facial muscles
(mouth, nose, eye) elicited by tapping on the
facial nerve
12
Prolonged QT
13
Pathogenesis of Hypocalcemia

• Failure to secrete PTH
• Failure to respond to PTH
• Vitamin D Deficiency/resistance
• PTH overwhelmed

14
Etiology of Hypocalcemia

• Low PTH levels
• (Hypoparathyroidism)
• Hereditary
• Hypomagnesemia
• Parathyroid destruction
• post-surgery
• autoimmune

15
PTH Deficiency -Hypoparathyroidism

• Laboratory
• Calcium ?
• Phosphate ?
• PTH ?

16
PTH Deficiency Hereditary Hypoparathyroidism

• Isolated
• Polyglandular endocrinopathy type I
• Addison disease
• Hypogonadism
• Autoimmune thyroid disease
• D.M. type 1
• Mucocutaneous candidiasis
• Alopecia, vitiligo
• Acquired age 2-10
• Defected protein AIRE autoimmune regulator

17
Post Surgical Hypoparathyroidism

• The most common cause of hypoparathyroidism in
  adults
• Presumptive diagnosis for hypocalcemia for any
  patients with a surgical scar on the neck
• Occurs after total thyroidectomy for cancer or
  after parathyroidectomy
• Causes edema, destruction of blood supply
• Usually transient (more than 50), reversible
• Sometimes permanent

18
PTH Deficiency HypoMagnesemia

• Severe hypomagnesemia is associated with
  hypocalcemia (lt0.8 meq/L)
• Impaired PTH secretion
• Reduced responsiveness to PTH
• The cellular mechanism is unknown
• Repletion of Mg leads to PTH recovery

19
????? ????? 1

• ???? ?? 60
• Ca 6.4 mg/dl
• Phosphate 6.1 mg/dl (2.5-4.5)
• ??????? ? ?.?.?. ???? ????? ????? ????? ???
  ?????? ????.
• ?????? ?? ????? ????? ??????. ???? ?????? ?????.
• Alb 3 g/dl
• Corrected Ca 6.40.87.2 mg/dl

?? ???????
20
????? ????? 1

• PTH 5 pg/ml (12-72)
• Diagnosis hypoparathyroidism post surgical
• Treatment oral or intravenous calcium Vitamin
  D alpha D3 1(OH)D3
  calcitriol 1,25(OH)2D3
  

21
Etiology of Hypocalcemia

• Low PTH levels
• (Hypoparathyroidism)
• Hereditary
• Hypomagnesemia
• Parathyroid destruction
• post-surgery
• autoimmune

• PTH ineffective
• High PTH levels
• Vitamin D deficiency
• Renal failure
• Vitamin D resistance
• PTH resistance

22
Vitamin D Metabolism
7-dehydrocholesterol
The major circulating storage form
23
Vitamin D Deficiency

• Vitamin D deficiency is common because
• of decreased solar exposure, 25 in
• elderly patients
• The most specific screening test for
• vitamin D deficiency is a serum 25(OH)D
• Normal vitamin D gt20 ng/dl
• Vitamin D deficiency lt8 ng/dl

24
Vitamin D Deficiency Etiology

• Cutaneous
• Clothes, sunscreens
• Highly pigmented skin
• Latitude
• Winter season
• Aging
• Reduced dietary intake
• Malabsorption
• Inflammatory bowel Disease
• Celiac disease

25
Vitamin D Deficiency - Clinical Features

• 1. ?????? ?????? - ??????????
• 2. ????????? ?? ???????? ????? ?????
  ?????? ????? ?????? ???????????
• ???? ?????, ???? ?????
• 3. ????????? ?? ??????????
• 4. ????? ????? ????? ???????????
• ????????????
• ??????????????, ?????

26
25(OH)D Deficiency - Laboratory
27
25(OH)D Deficiency - Laboratory

• 25(OH)Vitamin D ?
• Calcium ?
• P ?
• PTH ? - bone kidneys intestine
• ALP ?

28
????? 2

• ???? ?? 70
• Ca 8 mg/dl
• ???? ????? ????? ????? ???????????????
• ?????? ?? ???? ????? ??????
• Alb-4 g/dl, P 2.1 mg/dl (2.5-4.5)
• ALP-180 (45-115)
• GGT 15 normal
• Normal kidney function
• PTH 258 pg/ml (12-72)

?? ?????? ?????? ??????
29
????? 2

• PTH 238 pg/ml (12-72)
• 25(OH)D3 5 ng/dl (20-46)
• Diagnosis Vitamin D deficiency
• Secondary hyperparathyroidism
• Treatment ?

30
Etiology of Hypocalcemia

• Low PTH levels
• (Hypoparathyroidism)
• Hereditary
• Hypomagnesemia
• Parathyroid destruction
• post-surgery
• autoimmune

• PTH ineffective
• High PTH levels
• Vitamin D deficiency
• Renal failure
• Vitamin D resistance
• PTH resistance

31
Chronic Renal Failure Secondary
Hyperparathyroidism

• Hyperphosphatemia
• Decreased 1a hydroxylation
• decreased production of 1,25(OH)2D3
• Hypocalcemia
• Over many years
• Secondary hyperparathyroidism
• Bone disease

32
Hypocalcemia in chronic renal failure

1. 1,25(OH)2D ?
2. Phosphate ?
3. PTH ?

33
Treatment of Hypocalcemia in Chronic Renal Failure
Aim Restore normal calcium balance in order to
prevent Secondary hyperparathyroidism leading to
bone disease

• Restriction of phosphate in diet
• Adequate calcium intake per mouth
• Supplementation of alpha D3 or calcitriol

34
Etiology of Hypocalcemia

• Low PTH levels
• (Hypoparathyroidism)
• Hereditary
• Hypomagnesemia
• Parathyroid destruction
• post-surgery
• autoimmune

• PTH ineffective
• High PTH levels
• Vitamin D deficiency
• Renal failure
• Vitamin D resistance
• PTH resistance

35
Vitamin D Resistance

• Vitamin D-dependant rickets type 1
• Defective 1 hydroxylase
• Autosomal recessive
• Can be reversed by calcitriol
• Vitamin D-dependant rickets type 2 or
• Vitamin D-resistant rickets
• End organ resistance to 1,25(OH)2D3
• Treatment is difficult

36
PTH Resistance

• Pseudohypoparathyroidism
• ? PHP-1a
• Ca P PTH
• Patients have mutations in GNAS1
• Albright Hereditary Osteodystrophy round
  facies,
• short stature, short metacarpal and metatarsals
• Maternal transmission of GNAS1 is required for
  the full
• expression
• ? PHP-1b
• Biochemically identical but without the phenotype

37
Albright Hereditary Osteodystrophy
38
Etiology of Hypocalcemia

• PTH ineffective
• High PTH levels
• Vitamin D deficiency
• Renal failure
• Vitamin D resistance
• PTH resistance

• Low PTH levels
• (Hypoparathyroidism)
• Hereditary
• Hypomagnesemia
• Parathyroid destruction
• post-surgery
• autoimmune

• PTH overwhelmed
• Severe acute hyperphospatemia
• Acute pancreatitis
• Hungry bones

39
PTH Overwhelmed

• Increased loss of calcium from the circulation
• Hyperphosphatemia (severe, acute)
• Acute renal failure
• Tumor lysis (hematologic malignancies)
• Rhabdomyolysis
• Acute pancreatitis
• Precipitation of calcium soaps in the abdomen
• hungry bone syndrome

40
Hypocalcemia - Treatment

• Acute depends on symptoms I.V. calcium
  gluconate correct hypomagnesemia if diagnosed
• Chronic oral treatment calcium vitamin D
  vitamin D3 1-a- D3 (1a hydroxycholecalcifer
  ol) calcitriol

41
????? 2

• ???? ?? 70 ?? ?????????? ?? ??? ??? ?????? D
• ?????? ?? ???? ????? ??????
• ????? ?????? ?? ???? ?????? D ?????? 2000
  ?????? ????
• ????? ????? ??????? ????? ??????? ?????

42
Evaluation of Hypocalcemia
43
?????????? - ????? ??????

• ???????- ????????? ??????????????
• ?????? ??????
• ?????????
• absent PTH - ????????????????? ????
  ?????
• resistance PTH - ???? ?????? D, ???"?
  ?????
• PTH overwhelmed - ????? ?????? ?? ????? ????
• ????? ???????????
• ??"? ????? ??????????
• ???? ????? ????

44
???? ?? ??????
45
Etiology of Hypocalcemia

• PTH deficiency (hypoparathyroidism)
• Surgical
• Radiation
• Idiopathic
• Functional (low Mg)
• PTH resistance
• Pseudohypoparathyroidism
• Renal failure
• Drugs

• Vitamin D deficiency
• Vitamin D deficiency
• Renal failure
• Heredetary type 1 vitamin D dependant rickets
• Vitamin D resistance
• Heredetary type 2 vitamin D dependant rickets
• Others