Endocrine Physiology: Case Studies in Calcium Metabolism

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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

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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

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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

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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

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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

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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

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Hypercalcemia Elevated PTH

• Primary elevation of PTH
• 85 parathyroid adenoma
• 10 parathyroid hyperplasia
• (3 MEN)
• 2 parathyroid carcinoma
• Secondary elevation of PTH
• Renal failure

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Hypercalcemia Other causes

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

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Hypercalcemia Other Causes

• Drugs
• Lithium
• Antacids
• Calcium
• Thiazides
• Vit-D intoxication

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Hypercalcemia Other Causes

• Other diseases
• Hyperthyroidism
• Pagets
• FHH syndrome
• Immobility

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Signs and Symptoms of Hypocalcemia

• Findings may include
• Neurol Trousseaus (carpopedal spasm)
• Chvosteks (CN VII spasm)
• Paresthesias, tetany
• Lethargy, seizures
• Respiratory arrest
• Cardio Heart block, CHF
• Rheum Weakness, cramps
• Derm Dry skin, brittle hair

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Causes of Hypocalcemia

• PTH absent
• a. Hypoparathyroidism (hereditary)
• b. Acquired hypoparathyroidism
• Surgery (thyroid, parathyroid)
• Autoimmune disease
• Autoimmune parathyroid destruction
• PGA-1, PA, Hashimotos, T1DM
• Infiltrative disease
• Metastatic dz
• Alcohol (? PTH release, 20 to ? Mg)

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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

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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

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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

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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

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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

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Case 1, Questions

• What is the most common cause of asymptomatic
  hypercalcemia?
• This patients iPTH would be
• a. High
• b. Normal
• c. Low
• This patients PO4 would be
• a. High
• b. Normal
• c. Low

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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

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Case 2, Questions

• Predict the iPTH values if this patients
  hypercalcemia was due to
• a. Primary hyperparathyroidism
• b. Malignancy
• c. Vit D intoxication
• d. Granulomatous disease
• e. Hyperthyroidism

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Case3 Lady With Back Pain

• 75 yr old lady presents with complaints of low
  back pain.
• PMHx TAH-BSO _at_ age 35
• No HRT
• HTN
• Hypothyroid
• Meds Verapamil, levothyroxine

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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

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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

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Case 4 Child With Poor School Performance

• 14 yr old boy is evaluated for poor school
  performance.
• PMHx Unremarkable
• PE Lethargic, DTRs 3
• Lab Ca 5.1 mg/dL
• PO4 7.5 mg/dL
• Renal function normal

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Case 4, Questions

• Possible causes of this patients hypocalcemia
• Hypoparathyroidism?
• Low calcium intake?
• Pseudohypoparathyroidism?
• Vit D deficiency?