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
Normal Values
Ca
PO4
Mg
Creat
BUN
Alb
TSH
iPTH
8.4 - 10.6 mg/dL
2.5 - 4.5 mg/dL
1.5 - 2.5 mg/dl
0.6 - 1.3 mg/dL
8 - 12 mg/dL
3.5 - 4.5 mg/dL
0.3 - 5.0 mIU/ml
15 - 50 pg/ml
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
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
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
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
Hypercalcemia: Elevated PTH
• Primary elevation of PTH:
85% parathyroid adenoma
10% parathyroid hyperplasia
(3% MEN)
2% parathyroid carcinoma
• Secondary elevation of PTH
Renal failure
Hypercalcemia: Other causes
• PTH-related peptide (cancers)
Breast, lung, renal
Thyroid
Lymphoma, Leukemia, Myeloma
• Vit-D3-like factors (granulomatous dz)
TB
Histoplasmosis
Sarcoidosis
Hypercalcemia: Other Causes
• Drugs
Lithium
Antacids
Calcium
Thiazides
Vit-D intoxication
Hypercalcemia: Other Causes
• Other diseases
Hyperthyroidism
Paget’s
FHH syndrome
Immobility
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
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)
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
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
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
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
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
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
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
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
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
Case 3, cont.
• PE:
• Lab:
Thin, kyphotic
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
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
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
Case 4, Questions
• Possible causes of this patient’s hypocalcemia:
Hypoparathyroidism?
Low calcium intake?
Pseudohypoparathyroidism?
Vit D deficiency?