Endocrine Physiology: Case Studies in Calcium Metabolism

1. Endocrine Physiology: Case Studies in Calcium Metabolism C.W. Spellman PhD, DO Assoc. Prof. Medicine Assist. Dean, Dual Degree Program Head, Endocrinology & Dir. Diabetes Clinics UNTHSC

2. Normal Values Ca 8.4 - 10.6 mg/dL PO4 2.5 - 4.5 mg/dL Mg 1.5 - 2.5 mg/dl Creat 0.6 - 1.3 mg/dL BUN 8 - 12 mg/dL Alb 3.5 - 4.5 mg/dL TSH 0.3 - 5.0 mIU/ml iPTH 15 - 50 pg/ml

3. Review: Basic Metabolic Control of Calcium Metabolism • Low calcium: + PTH • High calcium: - PTH • PTH: + renal calcium resorption + renal phosphate excretion + renal 1,25 Vit D3 synthesis + calcium resorption from bone • Vit D3: + gut absorption of calcium + gut absorption of phosphate

4. Signs and Symptoms of Hypercalcemia • Hypercalcemia may present with vague Si/Sx • Si/Sx are quite variable • Ill-defined correlation's of symptoms with degree of hypercalcemia • Most common presentation: Asymptomatic • Calcium ≤12 mg/dL may present with Fatigue Depression Headache

5. Signs and Symptoms of Hypercalcemia • If calcium is > 12 mg/dl, one may see: Neurol Lethargy, confusion, coma Psych Depression, psychosis Cardiol Hypertension Nephrol DI, nephrolithiasis GI Nausea/emesis, PUD, anorexia Constipation, pancreatitis Rheum Proximal weakness, bone loss

6. Causes of Hypercalcemia • Differential diagnosis of hypercalcemia Increased PTH production Production of PTH-like hormone Production of Vit D-like factors Drugs Familial disorders Diseases affecting calcium metabolism

7. Hypercalcemia: Elevated PTH • Primary elevation of PTH: 85% parathyroid adenoma 10% parathyroid hyperplasia (3% MEN) 2% parathyroid carcinoma • Secondary elevation of PTH Renal failure

8. Hypercalcemia: Other causes • PTH-related peptide (cancers) Breast, lung, renal Thyroid Lymphoma, Leukemia, Myeloma • Vit-D3-like factors (granulomatous dz) TB Histoplasmosis Sarcoidosis

9. Hypercalcemia: Other Causes • Drugs Lithium Antacids Calcium Thiazides Vit-D intoxication

10. Hypercalcemia: Other Causes • Other diseases Hyperthyroidism Paget’s FHH syndrome Immobility

11. Signs and Symptoms of Hypocalcemia • Findings may include: Neurol Trousseau’s (carpopedal spasm) Chvostek’s (CN VII spasm) Paresthesias, tetany Lethargy, seizures Respiratory arrest Cardio Heart block, CHF Rheum Weakness, cramps Derm Dry skin, brittle hair

12. Causes of Hypocalcemia • PTH absent a. Hypoparathyroidism (hereditary) b. Acquired hypoparathyroidism Surgery (thyroid, parathyroid) Autoimmune disease Autoimmune parathyroid destruction PGA-1, PA, Hashimoto’s, T1DM Infiltrative disease Metastatic dz Alcohol ( PTH release, 20 to  Mg)

13. Causes of Hypocalcemia • PTH absent, cont. Hypomagnesemia a.  PTH release b.  PTH responsiveness • PTH ineffective Chronic renal failure a.  Vit-D 1,25 synthesis b. PO4 retention  PTH effects on bone Vit-D 1,25 synthesis

14. Causes of Hypocalcemia • PTH ineffective, cont. Dietary Vit-D deficiency Gut malabsorption of Vit-D  Sun light exposure Anti-convulsants  hepatic degradation of Vit-D Vit-D resistance Pseudohypoparathyroidism Defective PTH receptor

15. Causes of Hypocalcemia • PTH overwhelmed Severe, rapid loss of calcium from ECF a. Acute renal failure b. Tissue destruction Rhabdomyolysis Tumor lysis Pancreatitis c. “Hungry bone” syndrome s/p parathyroidectomy

16. Causes of Hypocalcemia • PTH overwhelmed: Mechanisms a. Acute renal failure, tissue destruction Decreased renal PO4 excretion Rapid cellular release of PO4  Acute hyperphosphatemia  urinary calcium loss  Hypocalcemia b. s/p resection of parathyroid tumor  Sudden decrease serum PTH  Rapid bone uptake of calcium  Hypocalcemia

17. Case 1: New Patient With Elevated Serum Calcium • 40 yr male is seen as a new patient to establish care. He has no complaints. • PMHx is negative • Baseline laboratory studies are significant for serum calcium of 11.5 mg/dL • Physical examination is normal

18. Case 1, Questions • What is the most common cause of asymptomatic hypercalcemia? • This patient’s iPTH would be a. High b. Normal c. Low • This patient’s PO4 would be a. High b. Normal c. Low

19. Case 2: Man With Lethargy, Fatigue and Weakness • 60 yr old male presents with complaints of fatigue and weakness over 1 month. • PMHx: Negative • PE: significant for memory and cognitive defects • Lab: Ca 15.0 mg/dL PO4 2.3 mg/dL

20. Case 2, Questions • Predict the iPTH values if this patient’s hypercalcemia was due to: a. Primary hyperparathyroidism b. Malignancy c. Vit D intoxication d. Granulomatous disease e. Hyperthyroidism

21. Case3: Lady With Back Pain • 75 yr old lady presents with complaints of low back pain. • PMHx: TAH-BSO @ age 35 No HRT HTN “Hypothyroid” • Meds: Verapamil, levothyroxine

22. Case 3, cont. • PE: Thin, kyphotic • Lab: Ca 9.2 mg/dL BUN/Creat 8/0.9 mg/dL TSH 2.1 mIU/ml • Imaging studies: CT: Compression fractures T and L spine DEXA: Loss of bone density

23. Case 3, Questions Which of the following is most likely to be found? a. Hypophosphatemia b. Hyperphosphatemia c. Low Vit D3 d. High Vit D3 e. Low alkaline phosphatase f. High alkaline phosphatase g. None of the above

24. Case 4: Child With Poor School Performance • 14 yr old boy is evaluated for poor school performance. • PMHx: Unremarkable • PE: Lethargic, DTR’s 3+ • Lab: Ca 5.1 mg/dL PO4 7.5 mg/dL Renal function = normal

25. Case 4, Questions • Possible causes of this patient’s hypocalcemia: Hypoparathyroidism? Low calcium intake? Pseudohypoparathyroidism? Vit D deficiency?