Interpretation of Calcium and Parathyroid Disorders What ...

1 Khawaja1 Interpretation of Calcium and Parathyroid DisordersWhat are the pitfalls?Raheela Khawaja, MDLearning ObjectiveAt the end of this module, you will learn the following:Hli Describe the physiology of Calium Intact PTH Differentiate between the causes of hypercalcemia based on the mechanism by which lii idHypercalcemiacalcium is increased. Hyperparathyroidism Distinguish the causes of hyperparathyroidism and how to differentiate. Differentiate between primary hyperparathyroidism and hypocalciuric hypercalcemia. Hypocalcemia Given a case of hypocalcemia, select the most likely etiology based upon 1 30 years old female establishes her care with you.

2 She has h/o HTN and needs refill on HCTZ as she ran out of it 4 weeksHCTZ as she ran out of it 4 weeks c/o mild dry cough. She denies any other PMH She takes multivitamins once a day. O/E She is thin built. Vitals are stable Restof the exam was normal Rest of the exam was normal. Her Calcium is found to be mg/dl( ) You decided to repeat Calcium with Calcium mg/dl ( ) with albumin tPTH70/l(1472) Intact PTH 70 pg/ml (14-72) 25 OH Vit D 38 ng/ml (30-100) 1,25 OH Vit D 90 pg/ml (18-78) PO 4 mg/dl ( ) Creatinine mg/dlKhawaja3 Case 1 What is the most likely diagnosis? Hypocalciuric of the above Ca PTH secretion ( WHILE Ca PTH secretion)PTH Regulation secretion) Seconds to minutes exocytosis of PTH from secretory vesicles into the extracellular fluid.

3 Minutes to one hour reduction in the intracellular degradation of PTH. Hours to days increase in PTH gene expression Days to weeks proliferation of Parathyroid cells (also stimulated by low serum calcitriolconcentrationsCCaa++++intracel lularintracellularextracelulaextracelula rrconcentrations PO4and 1,25 Vit D PTH transcription and proliferation G G protprotKhawaja4 Calcium Regulation Bone Bone Ca reabsorption Ca PO 1,25(OH) 1,25(OH)22 DDCa25 OH Vit D Ca absorption Ca absorption PO PO44absorptionabsorption1,25(OH)1,25(OH) 22DD(Gut and Bone)(Gut and Bone)Review: Basic Metabolic Control of Calcium Metabolism Key Players:- Calcium , Intact PTH, Po4 PTHCaCalcium, Intact PTH, Po4-1,25 OH Vit d ,25 OH Vit d ,-Creatinine, urine Calcium Low Calcium : + PTH High Calcium : - PTH PTH:+ renal Calcium resorption+ renal phosphate excretionCa+ renal 1,25 Vit D3 synthesis from 25 OH Vit d (by stimulating 1 alpha-hydroxylase)+ Calcium resorption from bone 1,25 Vit.)

4 D: + gut absorption of Calcium + gut absorption of phosphateKhawaja5 Labs Calcium mg/dl ( ) with albumin Intact PTH 70 pg/ml (14-72)25 OHVitD38/ l(30100) 25 OH VitD 38 ng/ml (30-100) 1,25 OH Vit D 90 pg/ml (18-78) PO4 mg/dl ( ) Creatinine mg/dl 24 hr urine Calcium 320 mg/24 hrsCase 1 What is the most likely diagnosis? of the aboveKhawaja6 PRIMARY HYPERPARATHYROIDISM Bone Bone resorptionresorption PTH Ca Ca reabsorptionreabsorption PO PO44reabsorptionreabsorption 1,25(OH) 1,25(OH)22DD Ca Ca absorption Ca absorption PO PO44absorptionabsorptionPrimary HyperparathyroidismDefinition:High Calcium , High PTH or Inappropriately elevated ggpppyPTH with high or high normal : Parathyroid gland Adenoma (80-90%) MEN1 (3 P, Hyperplasia of Parathyroid glands) MEN 2 a ( MTC, Pheochoromocytoma, Primary (yyHyperparathyoid) Parathyroid Neoplasia (mutations in HRPT2)12 Khawaja7 Case 2 A 42 -year-old male is being evaluated for Primary hyperparathyroidism.)

5 He was found to have hypercalcemia on screening laboratory. He has no history of nephrolithiasis. He has always had normal blood pressure and has no history of peptic ulcer disease He has no family history of similar Calcium On physical examination, blood pressure is 134/84 mm Hg, and heart rate is 80 beats/min. Examination is normal. Laboratory test results: Calcium = mg/dL ( ) Phosphorus =27mg/dL Phosphorus = mg/dL Creatinine = 1,25 OH Vit D = 99 pg/ml (18-78) 25-Hydroxyvitamin D = 36 ng/mL Urinary Calcium = 400 mg/24 h PTH = 110 pg/mL (14-72)Case 2 Which one of the following is the indication for surgery? indicationKhawaja8 Guidelines for Parathyroid surgery in Primary Hyperparathyroidism MeasurementMeasurement 199019902002200220082008calcium(>uppcalc ium(>upp1116mg/dl16mg/dl1 0 mg/dl1 0 mg/dl10mg/dl10mg/dlcalcium(>uppcalcium(> upper N)er N)))

6 Hr urine ca24 hr urine ca >400mg/d>400mg/d>400mg/d>400mg/dNot indicatedNot indicatedCr ClearanceCr ClearanceReduced by Reduced by 30%30%Reduced by Reduced by 30%30%Reduced to Reduced to <60ml/min<60ml/minBMDBMDZ score<Z score<2020 TTscore<score<2525 TTscore<score<2525 BMDBMDZ score<Z score< forearmforearmTT--score<score< at any siteat any siteTT--score<score< at any site or at any site or h/o fractureh/o fractureAgeAge<50<50<50<50<50<50J Clin Endo Meta Feb 2009 94(2):335-339 Familial Hypocalciuric Hypercalcemia Autosomal dominant syndrome of asymptomatic hypercalcemia Must be ruled out before sending patient to surgery for primary HPTH Inactivating mutation of CaSR(PTH less sensitive to ca) PTH and Calcium will be high or high normal Low Urine Calcium Diagnose by measuring Ca/Cr clearance ratio = [24-hour Urine Ca x serum Cr] [Serum Ca x 24-hour Urine Cr] HPTH > 01 FHH < 3 66 year old woman is seen in ER for malaise and confusion.

7 She has smoked 1 pack of cigarettes a day for the past 40 years. Physical examination reveals distant breath sounds. Chest radiograph shows a mass in the upper lobe of the right lung A bone scan indicates no evidence of focal or metastatic disease. Laboratory studies: CBC =Normal Calcium = mg/dL Phosphorus=40 Cr= Intact Parathyroid hormone = < pg/ml (14-72) 25 OH Vit D = 30 ng/dl (30-100) 1,25 OH vit D = 35 pg/ml ( 18-78 )Case 3 Which of the following is the most likely cause of the patient s hypercalcemia? hypercalcemia of disease Khawaja10 Causes of Hypercalcemia-( with PTH Interpretation )PTH Dependent (PTH high)PTH Independent (PTH appropriately suppressed)Mli(H itli d Primary hyper-PTH (Asymptomatic) Familial hypocalciurichypercalcemia Tertiary hyper-PTH Malignancy (Hospitalized pts) Sarcoidosis,Granulomayous disease Thyrotoxicosis Immobilization Adrenal Insufficiency Lithium toxicity Drugs (HCTZ) Milk Alkali Syndrome Vitamin D excessKhawaja11 High Calcium ( mg/dl)Intact PTH(14-72 pg/ml/)PTH (High or mid to high normal )Primary HTP/FHHPTH (Low<20pg/ml))

8 Non PTH mediated hyperparathyroidismMeasure 24h urine calciumMeasure PTHrp & Vit D metabolitesElevated >200mgLow<100mg/Ca/Cr<.01 PHPTHFHHHigh PTHrpHigh 1,25OH VitDNormal DNormal PTHrpHigh Vit DMalignancyLymphoma,SarcoidOther causes SPEP,TSH,Vitamin AVitamin DLab Differential Diagnosis of HypercalcemiaCaPO4 Uca25(OH)D 1,25(OH)D PTHPHPT Nl Nl Nl NlPHPT Nl Nl Nl NlHHM /Nl Nl FHH Nl NlNl NlSarcoid Nl Vit D Khawaja12 Case 4 A 60-year-old woman comes to your office after getting repeat Dexa 4 weeks. Her initial Dexa was done 6 years ago which was normal. She has never taken estrogen, but does take Calcium supplements, 600 mg daily. Current Dexa shows T score of at the spine and at the hip.

9 She has no family history of osteoporosis or fracture. She does not smoke cigarettes. She is working, has no personal history of fracture, and has never taken steroids. She is very much concerned about her bone loss. On physical examination, blood pressure is 128/84 mm Hg, and heart rate is 88 beats/min. You detect a small, diffuse goiter that is not tender Laboratory test results: Calcium = mg/dL ( ), Albumin = g/dLPhosphorus = mg/dLPTH = 114 pg/mL (14-72)Albumin = g/dL25-Hydroxyvitamin D = 9 ng/mL (30-100)Creatinine mg/dlSerum and urine protein electrophoresis, normal23 What should you do next?ASt t 50 50,000 iuVitD Fosamax 70 mg Fosamax 35 mg 50,000 iu Vit D weekly with Boniva 50,000 Iu Vit D with 35 mg Fosamax weekly24 Khawaja13 Secondary Hyperparathyroidism Secondary hyperparathyroidismrefers to the excessive secretion of (PTH) by Parathyroid gland in thliditdresponse to hypocalcemiaand associated hypertrophy of the glands.

10 This disorder is especially seen in patients with Vit D deficiency OR chronic renal failurePTH25 Calcium PTHCase 560-year-old woman with long-standing hypertension and hemodialysis-dependent renal failure due to interstitial nephritis Onphysical examination, blood pressure is 150/70 mmOn physical examination, blood pressure is 150/70 mm Hg, height is 69 inches, and weight is 155 pounds (BMI = kg/m2 Laboratory test results: Calcium = mg/dL ( ), Albumin = g/dLPTH=800pg/mL (14-72)PTH 800 pg/mL (1472)Po4 = ( )1,25 OH vit D= 16 pg/ml (18-78 )25 OH vit D 28 =ng/dl Creatinine = mg/dlKhawaja14 Case 5 What is the most likely diagnosis?)