1 / 39

a. Humoral Hypercalcaemia of Malignancy 1

irmahansen
Download Presentation

a. Humoral Hypercalcaemia of Malignancy 1

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Pakistan Society of Chemical PathologistsDistance Learning Programme in Chemical PathologyLesson No 3CALCIUM DisordersByBrig Aamir IjazMCPS, FCPS, FRCP (Edin)Professor of Pathology / Consultant Chemical PathologistBahria University Medical & Dental College / PNS SHIFA KarachiandMajor Sikandar Hayat KhanFCPS (Chem Path)Consultant Chemical PathologistCMH Jehlum

  2. Q 1: A 49 years male has cough with haemoptysis. Some of his Biochemical tests were as following:• Serum Calcium: 3.72 mmol/L (2.10-2.65)• Serum Phosphorus: 1.34 mmol/L (1.75-1.9) • Blood PTH: <1 pmol/L (15-62)What is the most probable diagnosis?a. HumoralHypercalcaemia of Malignancyb. Hypervitaminosis D c. Hypoparathyroidismd. Primary Hyperparathyroidisme. Secondary Hyperparathyroidism a. HumoralHypercalcaemia of Malignancy1

  3. Causes of Hypercalcaemia Two commonest causes of Hypercalcaemia: • Malignancy: in hospitalized patients • Priamry Hyperparathyroidism: in ambulatory patients

  4. Hypercalcaemia of Malignancy Hypercalcaemia of Malignancy is of THREEtypes : • HumoralHypercalcaemia of Malignancy (HHM): Tumor secretion of parathyroid hormone-related protein (PTHrP) • Localized OsteolyticHypercalcaemia(LOH): metastases with local release of cytokines. • Tumor production of 1,25-dihydroxyvitamin D.

  5. Q 2:Hyperparathyroidism with normal calcium levels is d. Secondary Hyperparathyroidism1 • Parathyroid adenoma • Parathyroid hyperplasia • Primary Hyperparathyroidism • Secondary Hyperparathyroidism • Tertiary Hyperparathyroidism

  6. Hyperparathyroidism • Primary Hyperparathyroidism is due to adenoma or hyperplasia of parathyroid • Secondary Hyperparathyroidism is a physiological response of parathyroid gland to Hypocalcaemia. • So in this condition serum calcium is usually normal • Tertiary hyperparathyroidism is due to autonomous stage of parathyroidism • In Primary and Tertiary Hypercalcaemia calcium is very high.

  7. Q 3:A 32 years female complains of attacks of numbness and spasm of the lower limbs off and on. She has following bone profile: • Serum Calcium: 1.72 mmol/L (2.10-2.65)• Serum Urea: 7.5 mmol/L (3.6-6.6)• Serum Phosphorus: 2.34 mmol/L (1.75-1.9) • Blood PTH: 36 pmol/L (15-62)What is the most probable diagnosis?a. Hypoparathyroidismb. Psudo- Psudohypoparathyroidismc. Psudohypoparathyroidismd. Renal impairmente. Vitamin D Deficiency a. Hypoparathyroidism1

  8. Hypoparathyroidism • In Hypoparathyroidism, Ca is decreased while P is increased. • Vitamin D is required for absorption of both calcium and phosphorus, so both decrease in Vitamin D deficiency.

  9. Thyroid Surgery • It is the most common cause of Hypoparathyroidism. • During thyroidectomy parathyroid gland may be removed by planning or accidentally • Any surgery in neck area can cause Hypoparathyroidism

  10. Q 4:A 46 years female complains of backache and generalized weakness. Her biochemical profile was as following : Calcium: 1.98 mmol/L (2.1-2.55 mmol/L) Phosphorous: 1.45 mmol/L (1.75-1.9 mmol/L) Urea : 6.9 mmol/L (3.3-6.8 mmol/L) e. Vitamin D Deficiency1 Congenital Hyperphosphaturia Hypoparathyroidism Renal impairment Renal Tubular acidosis Vitamin D Deficiency

  11. Vitamin D Deficiency • In Hypoparathyroidism, Ca is decreased while P is increased. • Vitamin D is required for absorption of both calcium and phosphorus, so both decrease in Vitamin D deficiency.

  12. Q 5:The term Vitamin D3is used for: d. Vitamin D of animal origin2 • 1,25 Dihydroxy Vitamin D • 25 Hydroxy D Vitamin D • Active form of any vitamin D • Vitamin D of animal origin • Vitamin D of plant origin

  13. Q 6:The metabolite of Vitamin D commonly tested in the lab for the assessment of vitamin D statusis :. c. 25 HydroxyVitamin D3 • 1,25 Dihydroxy D • 1-alpha hydroxylase • 25 Hydroxy Vitamin D • Cholecalceferol • Ergosterol

  14. Vitamin D Story

  15. Two types of Vitamin D • Cholecalciferol (D3) is of animal origin derived from parent molecule, 7-dehydrocholesterol. • Ergocalciferol (D2) is derived from plant origin precursor ergosterol.

  16. Control Of Vitamin D Synthesis • Hepatic synthesis of 25-hydroxycholecalciferol is only loosely regulated • In contrast, the activity of 1-alpha-hydroxylase in the kidney is tightly regulated and serves as the major control point in production of the active hormone. • The major inducer of 1-alpha-hydroxylase is PTH. • It is also induced by low blood levels of phosphate.

  17. Sources of Vitamin D

  18. Sunlight as the best source of Vitamin D3 20 minutes daily exposure of 40 per cent of body to the sun equals to 50 glasses of milk !!!

  19. Short answer questions

  20. Q 7: You are consultant in a Non-teaching 400 bedded hospital. In your Laboratory Total Calcium is estimated by an automated colorimetric method but every now and then you receive complaints from clinical colleagues about the clinical correlation of patients` results. Your Internal Quality Control and External Quality Assurance results are quite acceptable for the last 2 years.To find solution of this problem please answer following queries:a. Can you name a Calculated Index of Calcium which can improve the clinical correlation of total calcium? Please give its formula too. b. Name another modality of calcium estimation which you can employ in your department for instant reporting and which is reportedly more sensitive.c. Write THREE precautions of sample collection for the method you have selected above in sub-component b.

  21. Q7 (a):Suggested Answer3 • Albumin Corrected calcium (g/dl) = total calcium (mg/dl) +0.8(4-albumin g/dl) • Albumin Corrected calcium (mmol/L)= total calcium (mmol/L) + 0.02(40-albumin) Plz remember: • This equation is for correction of Total Ca only and not for Ionized Ca. • It is NOT an equivalent to Ionized Ca but gives an idea about Ionized Ca. • Both formulae should be learnt as the question may be asked as a scenario containing mg/dl or mmol/L values of a patient.

  22. Q7 (b):Suggested Answer3 • Ionized Ca has been shown to be a more sensitive test for the diagnosis of various calcium disorders4 . • The results are instant as test is done on ISE based systems e.g. electrolyte or ABG analysers. • Composite ABG analysers should be preferred to give simultaneous estimation of Ca++ and pH. • Reference method for Total Ca is Atomic Absorption photometry but for Ca++ an ISE based method been developed and approved by IFCC2 .

  23. Q7 (c):Suggested Answer3 • Precautions for Ca++ are same as for ABG analysis • It must be emphasized that factors like tourniquet and patient posture only minimally effect free calcium estimation. • Lyophilized Lithium Heparin Syringes or tubes should be used in anaerobic conditions and estimation should be done within 30 min (maximum 1 h). • If delayed should be stored at 40 C but then K+estimation is effected. • Lyophilized Lithium Heparin Syringes are available in Pakistan and may be used for ABGs and electrolytes.

  24. Q 8: A 46 years male has headaches, fatigue, anorexia, nausea, paresthesias, muscular weakness and pain in the extremities. His biochemical profile revealed: • Serum Calcium: 2.72 mmol/L (2.10-2.65) • Serum Urea: 6.9 mmol/L (3.6-6.6) • Blood PTH: 86 pmol/L (15-62) The treating physician wanted to be pretty sure before reaching a diagnosis and advised a repeat profile after one week which showed: • Serum Calcium: 2.56 mmol/L (2.10-2.65) • Serum Urea: 4.2 mmol/L (3.6-6.6) • Blood PTH: 80 pmol/L (15-62) Quite puzzled with these lab results, he refers the patient for your expert opinion. • What is the most probable diagnosis? • Give TWO reasons to support your opinion. • What is commonest pathological cause of this disorder?

  25. Q8: Suggested Answer4 • Primary Hyperparathyroidism • (1) Fluctuating Calcium levels are typical of Primary Hyperthyroidism. Hypercalcaemia does not follow any ascending pattern with increasing severity of the disease . (2) A higher calcium level should be accompanied by a low PTH. A high PTH with higher or upper normal Calcium levels and normal renal function points towards Primary Hyperthyroidism. • Adenoma of Parathyroid gland (85%)

  26. Q 9: An 18 years girl came to the A&E Department with tetany of the hands and feet. She was also hyperventilating severely. As a resident-on-call you carry out a brief interview with the extremely worried parents and quick examination of the patient: a. What biochemical abnormality comes in your mind which can cause her condition?b. Which simple and non-invasive procedure you will like to carry out that can immediately relieve the symptoms of the patient?C. What is the biochemical mechanism by which this procedure will help?

  27. Q.9: Suggested Answer • Hyperventilation due to hysterical condition leading to Respiratory Alkalosis and decreased ionized calcium and tetany. • Breathing in the shopper bag. • Mechanism: • Alkalosis causes decrease in ionized fraction and since Ionized Ca is the active form, it leads to hypocalcaemia • Tetany associated with hyperventilation is due to increased pH. • Release of tetany by breathing in bag increases PCO2 and relieves alkalosis and hypocalcaemia. .

  28. Q 10: A 62 years male known patient of Chronic Renal Failure has extreme bone pains and findings typical of Renal Osteodystrophies. He has following Biochemical Profile: • Serum Calcium: 3.23 mmol/L (2.10-2.65)• Serum Urea: 29.7 mmol/L (3.6-6.6)• Serum Phosphorus: 2.52 mmol/L (1.75-1.9) • Blood PTH: 231 pmol/L (15-62) What is the most probable biochemical diagnosis? Write TWO steps of the natural course of this illness.

  29. Q10: Suggested Answer1 • Tertiary Hyperparathyroidism • Natural course of this illness: • Initially there is secondary hyperparathyroidism due to hyperphosphataemia and hypocalcaemia because of renal failure • Continuous stimulation leads to hypertrophy of the chief cells of the parathyroid and Tertiary Hyperparathyroidism ensues . When parathyroid hyperplasia becomes so severe that removal of the underlying cause does not eliminate the stimulus for PTH secretion hypertrophic chief cells become autonomous.

  30. Hyperparathyroidism (Summary) • Primary hyperparathyroidism: most cases (85%) of hyperparathyroidism are the result of a single parathyroid gland malfunctioning and developing into an adenoma. In 15% of cases, multiple adenomas or hyperplasia are involved. • Secondary hyperparathyroidism: vitamin D deficiency and chronic kidney disease are the most common causes. Not a parathyroid disease. • Tertiary hyperparathyroidism: autonomous production of parathyroid hormone, usually the result of longstanding secondary hyperparathyroidism

  31. Q 10: A professional body of Chemical Pathologists has invited you to give a talk on “Vitamin D: Beyond Bones”. The theme of your talk is that Vitamin D is important not only for bone health but its deficiency causes many other health problems. While preparing this talk please keep following points in your mind:a. What is estimated prevalence of Vitamin D deficiency reported in the world and in Pakistan?b. Based on Laboratory Results of Vitamin D, how do you stratify vitamin D abnormalities?c. Which molecular discovery is the most important fact in implicating Hypovitaminosis D in various extra osseous diseases?

  32. Q11(a):Suggested Answer5-7 • Vitamin D deficiency (VDD) is a world-wide epidemic with recent estimates indicating more than 50% of the population at risk. • This pandemic of inadequate vitamin D (VDD, vitamin D insufficiency VDI) has been found in all age group even those who are otherwise healthy and are not prone to deficiency. • In Pakistan prevalence of VDD has been reported upto 92% (70% - 97% in AKU Karachi and 81%-92% in Lahore) ambulatory patients in various situations5.

  33. Q11(b):Suggested Answer8 • Vitamin D Deficiency: Serum 25 (OH) D <20 ng/ml • Vitamin D Insufficiency: Serum 25 (OH) D 21-29 ng/ml • Desirable level : Serum 25 (OH) D 30-150 ng/ml • Vitamin D intoxication: Serum 25(OH) D >150 ng/ml These values are now widely accepted and used by many labs for reporting Vit D results6.

  34. Q11(c):Suggested Answer9 • The discovery of vitamin D receptor (VDR) and 25 (OH) D1 alpha hydroxylase have been found in almost all tissue. • It has led to the identification of role of vitamin D in many organ systems of the body, instead of merely associated with bone disorders7. • Although called a vitamin, in fact it is a hormone which synthesize in skin or taken in diet but act on almost every tissue of body.  

  35. Q11(d):Suggested Answer9,10 • Vitamin D has been postulated to play role in glucose homeostasis e.g. pancreatic beta cell function, insulin sensitivity and up regulation of transcription of insulin receptor gene. • Hypovitaminosis D is also implicated in many Autoimmune disorders and Cancers

  36. References • UpToDate. (online) Cited on 22 Mar 2013. Available at: https://www.uptodate.com • Holick MF. High Prevalence of Vitamin D Inadequacy and Implications for Health. Mayo Clin Proc. 2006;81(3):353-373. • Enders D, Rude RK. Mineral and Bone Metabolism. In Burtis CA, Ashwoods ER and Bruns DE, (edi) Teitz Textbook oF Clinical Chemistry. 4th ed. W. B. Saunders Company; 2006;pp 1891-1963. • "The 10 Parathyroid Rules of Norman“. [online]. Cited on 30 Jan 2013. Available from: www.parathyroid.com/10_parathyroid_rules.htm. • Prentice A. Vitamin D deficiency: a global perspective: Nutrition Reviews 2008; 66:(2):S153-154. • ZuberiLM, Habib A, Haque N, Jabbar A. Vitamin D Deficiency in Ambulatory patients. J Pak Med Assoc 2008;58(9):482-484. • Iqbal R, Khan AH. Possible causes of vitamin D deficiency in Pakistani population residing in Pakistan: J Pak Med Assoc 2010;60(1):1-2. • Holick MF. Vitamin D Deficiency. N Engl J Med 2007; 357:266-268. • DanescuLG, Levy S, Levy J. Vitamin D and diabetes mellitus: Endocr 2009; 35(1):11–17. • Mathieu C, Gysemans C, Giulietti A, Bouillon R. Vitamin D and diabetes. Diabetologia 2005;48:1247–1257.

  37. Thank You

More Related