Hypoparathyrodism

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  • Hypoparathyrodism

    1. 1.  24 years female  from - solan  Admitted-21/02/2013  Discharged on 02/03/2013
    2. 2.  episode of abnormal body movements X 1 days
    3. 3.  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 incontinence .  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 ..
    4. 4.  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
    5. 5.  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  Tem-98.8.  no neck rigidity no kernig sign
    6. 6.  During B.P monitoring it was noted that there was flexion at the MP joints  extension of the IP joints  adduction thumbs/fingers
    7. 7. I. S1 and S2 normal. no mumur . RESPIRATORY SYSTEM. Trachea central. both sides moving equally with respiration. Bilatral vesicular breath sounds . No added sounds
    8. 8.  HMF, cranial nerves, speech –normal motor system, sensory system- normal no kernig sign, no neck rigidity .
    9. 9.  CHG  Hb : 11.2gm%  ESR : 40 mm in 1st hr  TLC : 4800/mm3  DLC : P80 L15 M1 E₁  PLT : 2.7 Lac/mm3  MCV : 79.7fl MCH : 30.1pg P/S-normocytic normochromic  Urine:  Alb : absent  Sugar : absent
    10. 10. Parameter Value Urea (mg%) 27mg % Creatinine (mg%) 1.0 mg % Sodium(mEq/L) 139 mg % Potassium(mEq/L) 4.1 mg % Chloride (mEq/L) 105 mg % Total protein (gm%) 7.1 gm % Albumin (gm%) 4.0gm % Total Bilirubin(mg%) 0.6 mg % Conjugated(mg%) NIL SGOT (IU) 39 IU/L SGPT(IU) 77 IU/L ALP(IU) 78 IU/L
    11. 11. Serum calcium(8.80- 10.60)mg/dl 4.10 Serum phosphorous(2.40- 4.40)mg/dl 5.22 Corrected calcium 4.10 Ionized calcium(1.16-1.32)mmol/l 0.63 Serum magnesium(1.90- 2.50)mg/dl 1.94 i PTH(15-68)pg/dl 62.40 Vitamin D ng/ml 29.10
    12. 12. ALP (30-120)U/L 127 CSF N NCCT HEAD NORMAL XRAY CHEST NORMAL T.F.T NORMAL HIV NEGATIVE ECG QTc prolongation(.62sec)
    13. 13.  24 year female presented with GTCS followed by post ictal confusion .  carpo pedal spasm.  hypocalcemia hyperphosphotemia  normal PTH
    14. 14.  Generalized tonic clonic seizure  Cause-Hypocalcemia etio.hypoparathyroidism
    15. 15. 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
    16. 16.  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 supplements.
    17. 17.  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
    18. 18.  Promote absorption of Ca++  Effect is primarily mediated through increased levels of 1,25- dihydroxycholecalciferol
    19. 19.  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.
    20. 20.  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 concentration.  ionized calcium increases by 0.2mg/dl for each 0.1 decrease in PH
    21. 21.  PTH is 84 amino acid single chain peptide with amino and carboxyl terminal.  Amino terminal PTH(1-34) is highly conserved biologic action  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 carboxyl fragments
    22. 22.  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).
    23. 23.  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.
    24. 24. FUNCTIONAL CLASSIFICATION OF HYPOCALCEMIA(excluding neonatal conditions)
    25. 25. PTH ABSENT 1) Hereditary hypoparathyrodism 2)Acquired hypoparathyrodism 3)Hypomagnesemia
    26. 26. Chronic renal failure Active vitamin D lacking decreased intake or sunlight exposure Defective metabolism Anticonvulsive therapy Vitamin D dependent rickets type 1 Pseudohypoparathyrodism Vitamin dependent rickets type 2 Intestinal malabsorption
    27. 27. Severe acute hyperphosphatemia Tumour lysis Acute renal failure rhabdomyolysis
    28. 28. Low parathyroid hormone High parathyroid hormone (secondary hyperparathyrodism  Para thyroid agenesis- isolated, digeorge syndrome parathyroid destruction- surgical , infilteration, autoimmune. Reduced parathyroid funtion – hypomagnesemia , Casr mutations  vitamin d deficiency , impaired production or resistance parathyroid hormone resistance drugs-calcium chelators phenytoin ketoconazole bisphosphonates plicamycin miscellanous-acute pancreatitis rhabdomyolysis osteoblastic mets (prostate cancer)
    29. 29.  severe sepsis,  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 calcium.  Alkalosis increases calcium binding to proteins in this setting ionized calcium should be measured  medications protamine glucagon heparin causes transient hypocalcemia.
    30. 30.  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.
    31. 31.  1) DiGeorge syndrome-  Heterozygous Deletion Of chromosome 22q11.2  may include conotruncal cardiac defects,  parathyroid thymic hypoplasia,  neurocognitive problems,  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
    32. 32.  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
    33. 33.  Inheritance-Autosomal dominant  Mutation in GATA 3 which is required for kidney otic vesicle parathyroid development
    34. 34.  Kearns–Sayre syndrome Progressive external ophthalmoplegia, pigmentary retinopathy, heart block or cardiomyopathy, diabetes, and hypoparathyroidism).  MELAS with diabetes and hypoparathyroidism
    35. 35.  Kenny–Caffey syndrome  short stature, osteosclerosis, cortical bone thickening, calcification of basal ganglia, ocular abnormalities, and hypoparathyroidism that is probably due to agenesis of the glands.  Sanjad–Sakati syndrome  parathyroid aplasia, growth failure, ocular malformations, microencephaly
    36. 36.  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 hypoparathyrodism
    37. 37.  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;
    38. 38.  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
    39. 39.  Severe hypomagnesemia <0.8meq/l associated with hypocalcemia by two mechanism of action.  1) Impaired PTH secretion  2) reduced responsiveness of PTH  CAUSES  Malabsorption  diarrhea,  chronic alcohlism,  drugs (aminoglycoside, cisplatin, diuretics, cyclosporine, cisplatin,  renal disorders :RTA, Post obstructive nephropathy
    40. 40.  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 decreased.  Intact PTH is often undetectable or inappropriately low. phosphate levels are not elevated as in case of idiopathic hypoparathyrodism.
    41. 41.  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 ineffective 3) chronic renal failure
    42. 42.  PTH binds to PTH receptor which acts through G protein pathway.  PHP results from some form of disruption in this patway.  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 autosomic dominant
    43. 43. PTH PHP
    44. 44.  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.
    45. 45. Type Hypocalcemi a, Hyperphopha temia Respone of Urinary cAMP to PTH Serum PTH Gs Subunit Deficiency AHO Resistance to Hormones in Addition to PTH 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
    46. 46.  ALBRIGHT’S HEREDITARY OSTEODYSTROPHY  short, stocky build,round face  low, flat nasal bridge,  short neck,  ectopic ossification,  Brachymetaphalangism-short 4th and 5th metacarpal and metatarsal  developmental delay, with or without endocrine abnormalities.
    47. 47.  Cutaneous calcification  Intracranial calcification (commonly involving the basal ganglia )  MENTAL RETARDATION :  Seizures, usually grand mal, occur in AHO and may be independent of hypocalcaema  Sensorineural hearing loss and impaired olfaction has been identifed in some patients  Cataracts and lenticular opacities are common in these patients.  ENDOCRINE ABNORMALITIES  THYROID: Hypothyroidism secondary to TSH resistance is common.  GONADAL : Gonadal dysfunction, particularly menstrual irregularity is seen
    48. 48. Albright’s  Short stature & limbs  Obesity  Round, flat face  Short 4/5 metacarpals  Brachydactyly  Eye problems  IQ problems  Basal ganglia calcifications
    49. 49.  -vitamin D deficiency impaired cutaneous production dietary absence malabsorption  accelerated loss of vitamin d increased metabolism(phenytoin rifampicin ) impaired enterohepatic circulation nephrotic syndrome  impaired 25 hydroxylation liver disease isoniazid
    50. 50.  Hypoparathyrodism renal failure ketoconazole 1@ hydroxylase mutations target organ resistance-vitamin D resistance mutation
    51. 51. Vitamin D dependent rickets type 1 Vitamin D dependent rickets type 2  Also called psedovitamin D resistant rickets.autosomal recessive.caused by mutations 25(OH)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 abolite 1,25(OH)2D.partial or total alopecia.requires nocturnal calcium infusions
    52. 52.  Delayed closure of fontanels  Bossing  Craniotabes  Delayed eruption of teeth  Rickety rosary  Pectus carinatum  Harrison sulcii  Splaying of distal ends of  long bones bones  Hypotonia  Weakness  Growth retarded  Recurrent chest infections CLINICAL FEATURES OF vitamin D deficiency
    53. 53.  Bone pain and pathologic fractures. proximal myopathy is striking feature severe vitamin D deficiency both in childrens and adults  Decreased bone density osteopenia  Hypophosphatemia, increase in alkaline phosphatase and serum PTH levels  Late hypocalcemia Mild hypocalcemia ,secondry hyperparathyrodism , severe hypophosphatemia.
    54. 54.  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.
    55. 55. A. Neuromuscular ◦ 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. Clinical Features:
    56. 56. A. Neuromuscular ◦ Parathesia ◦ Tetany ◦ Hyperventilation ◦ 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 seizures. ◦ Signs of latent tetany  Chvostek sign  Trousseau sign  Extrapyramidal signs (due to basal ganglia calcification) Clinical Features:
    57. 57. Signs & Symptoms: A 2-in-1 Reference for Nurses, Copyright © 2007 Lippincott Williams & Wilkins, www.wrongdiagnosis.com/bookimages/14/4721.1.png
    58. 58. Trousseau sign: A blood pressure cuff is inflated to a pressure above the patients systolic level. Pressure is continued for 2-3 minutes. Carpopedal spasm: flexion at the wrist flexion at the MP joints extension of the IP joints adduction thumbs/fingers
    59. 59. CVS 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
    60. 60.  Hypocalcaemia leads to decreased myocardial contractility.  Although the mechanism is undefined, calcium plays a critical role in excitation-contraction coupling and is required for epinephrine-induced glycogenolysis in the heart.  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 normal
    61. 61. 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 deficiency congenital defects point to the DiGeorge syndrome
    62. 62.  The skin should be examined carefully for a neck scar (which suggests a postsurgical cause of hypocalcemia);  for candidiasis and vitiligo (which are suggestive of APS-1); and for generalized bronzing and signs of liver disease (which are suggestive of hemochromatosis).
    63. 63.  Features such as growth failure, congenital anomalies, hearing loss, or retardation point to the possibility of genetic disease.  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
    64. 64. Hypoparathyroidism is diagnosed when Hypoparathyrodism  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 us Normal or inappropi ately low low High or at high end of normal range
    65. 65. . Patients with pseudohypoparathyroidi sm have a laboratory profile that resembles that in patient with hypoparathyroidism(i.e. , low calcium and high phosphorus levels),  but they have elevated PTH levels PTH CALIUM PHOSPHO RUS
    66. 66.  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 hypocalcemia.PTH stimulates 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 PTH calciu m phosp horous 25(0H) D
    67. 67. Mild decrease(7-8)mg/dl Severe hypocalcemia  Oral therapy with calcitriol and calcium supplements  With symtoms and signs seizure bronchospasm laryngospasm intravenous therapy
    68. 68.  If ECG changes or symptoms present begin with iv replacement 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 normal 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
    69. 69.  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 elemental calcium/kg/hr 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 meals 3) add 0.25-4 ugm/day calcitriol 4) can add salt restriction and hydrochlorthiazide if hypercalciuria occurs
    70. 70. 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.
    71. 71. Calcitriol is preferred over Vitamin D2 and D3 as it has high potency rapid onset and rapid offset of action hyperphosphatemia can be addressed by decreasing patient dietary intake (eggs, milk products cola ) if needed phosphate binders can be used.
    72. 72.  Symptoms control  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
    73. 73.  CHRONIC HYPOCALCEMIA  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
    74. 74.  Calcium carbonate  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 stomach.  Calcium citrate  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)

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