Endocrine CCSG – Calcium/Bone Cases Matthew Lin

CCSG 3

Calcium
 
CASE #1
 
A. 60-year-old female sustains a forearm (radius) fracture after falling from a standing
height. She also reports having passed a small kidney stone 1 year ago. Physical
exam reveals a healthy appearing woman with a BMI of 23, dry oral mucosa, good
muscle mass, and normal spinal curvature. Lab tests show a calcium of 11.7 mg/dl
(normal, 8.5 - 10.4), a low serum phosphorus, serum creatinine 1.5 mg/dL (normal 0.6
– 1.4), Intact parathyroid hormone (PTH) is 190 pg/ml (normal 10 - 65), urinalysis with
calcium oxalate crystals, and an elevated alkaline phosphatase.
 
1. What disease does this patient have? What diseases are associated with a
high PTH? What are some hypercalcemic disorders that are associated
with a suppressed PTH? What hypercalcemic disorders are associated with
an "inappropriately" normal PTH? What should you think of in person with
a high PTH and a normal serum calcium?
 
This patient has high PTH, hypercalcemia, hypophosphatemia and decreased renal
function with signs of calcium oxalate formatioin and elevated alkaline phosphatase.
These signs point to primary hyperparathyroidism.
 
Among causes of hyperparathyroidism there are: 1) primary, 2) secondary, and 3)
tertiary. In primary, the problem is at the parathyroid gland where too much hormone is
produced; in secondary, the problem is due to chronic kidney disease that reduces
phosphate excretion leading to decreased free serum calcium and subsequent
elevated PTH; in tertiary, prolonged chronic kidney disease gives way to autonomous
parathyroid function and elevated PTH.
 
PTH-independent hypercalcemia such as excess calcium intake, cancer (humoral
hypercalcemia), and hypervitaminosis can cause hypercalcemia with suppressed PTH
(appropriate response).
 
Inappropriately normal PTH with hypercalcemia is seen in the setting of familial
hypocalciuric hypercalcemia where the Ca-sensing receptors on the parathyroid gland
are insensitive to free serum calcium and thus higher levels of Ca are needed to
negatively inhibit normal levels of PTH.
 
In a patient with high PTH and normal serum calcium, there is likely end-organ
resistance to PTH also known as pseudohypoparathyroidism 1a.
 
1. Based on your diagnosis, explain each of the following: fracture and elevated
alkaline phosphatase, kidney stone, low phosphorus, abnormal renal function,
and dry oral mucosa.
 
Fracture and elevated alkaline phosphatase - her age puts her at risk for osteoporosis
and her condition likely increases her likelihood of osteopenia from increased bone
Endocrine CCSG – Calcium/Bone Cases Matthew Lin
CCSG 3
resorption. PTH also stimulates osteoblast function which explains her high alkaline
phosphatase
 
Kidney stone - increased serum calcium levels lead to formation of renal stones
 
Low phosphorous is a result of increased PTH action on the renal tubules to increase
phosphate excretion and calcium resorption
 
Abnormal renal function - from kidney stones
 
Dry oral mucosa - High calcium levels associated with dehydration?
 
2. What would this patient's bone biopsy show? What is "osteoid"? Which disorders are
associated with increased osteoid?
 
Likely that there would be cystic bone spaces due to osteitis fibrosa cytica due to
increased PTH. Brown fibrous tissue can fill these spaces (brown tumors).
 
Osteoid is immature bone material composed of collagen type I that undergoes further
calcification to form mature bone.
 
Other conditions associated with increased osteoid include
 
CASE #2
 
A 53-year -old man comes to see you because of generalized achiness and pain in his
left lateral ribs. The achiness is been present for three months; the rib pain began after
he rolled over in bed (two days prior to his visit). He has been in good health although
is felt weak and cold over the last month and has noticed a greater frequency of
respiratory infections recently. He has no known medical problems. He is on no
medication. His physical exam is unremarkable except for very pale mucous
membranes and tenderness over his left lateral ribs. His lab dated show an anemia, a
low albumin of 2.5 g (normal, 3.5 – 5), normal renal function, a normal serum calcium
of 10.2 MG/DL (normal, 8.5 – 10.4), an ionized calcium of 6 MG/DL (normal, 4.5 –
5.5), a parathyroid hormone level which is suppressed below normal, a monoclonal
protein with suppression of the other globulins and a normal bone alkaline
phosphatase.
 
 
1. Why is there a difference between the ionized calcium and the
total calcium? How can you "correct" the reported total serum
calcium?
 
Total calcium consists of ionized calcium, complexed to organic and
inorganic anions, and bound to albumin.
 
Corrected = serum calcium + 0.8*(4-albumin)
 
Endocrine CCSG – Calcium/Bone Cases Matthew Lin
CCSG 3
1. What is the cause of the elevated calcium in this patient? What are some
mechanisms by which tumors can cause hypercalcemia?
 
He seems to have multiple myeloma causing bone marrow suppression and lytic bone
lesions. In addition to release of cytokines, production of PTHrp would lead to
hypercalcemia.
 
1. Why is the patient’s parathyroid hormone suppressed?
 
PTHrp is being produced by tumor and thus normal PTH is being suppressed by
hypercalcemia
 
3. Why is the bone alkaline phosphatase normal?
 
Alkaline phosph is normal because PTHrp doesn't stimulate osteoblasts
 
 
OSTEOPOROSIS AND METABOLIC BONE DISEASE SEMINAR
 
 
CASE #l
 
A 60 year old woman sees you because she is concerned about osteoporosis. Her
mother who is now 85 years old recently fractured her hip and has a Dowager's hump
(severe kyphosis). The patient is 9 years post-menopause (Last menstrual period at
age 51). She has no history of fracture. She has lost 1 cm of height.
 
 
4. What is osteoporosis? What is high turnover osteoporosis? What is low
turnover osteoporosis? Which type of bone turnover is your 52 year old patient
more likely to have?
 
Osteoporosis is increased bone turnover from loss of estrogen and thus brittle bones.
Low turnover osteoporosis is when osteoclasts are not increased in activity but rather
osteoblasts are decreased in activity. It is more likely that our patient (who is 60 not
52) has high turnover osteoporosis due post-menopause. 
 
5. How is the bone density measured? What anatomic sites are measured? What
is the T-score? What is the Z-score?
 
DEXA-scan. Hip and lumbar spine +/- forearm. T score compares BMD to young adult
normals (standard dev from mean) while Z score compares BMD to age and sex-
matched controls
 
What scores suggest "osteopenia" (low bone mass)? What scores
suggest "osteoporosis" (higher risk of fracture)?
 
Osteopenia: T score between -1.0 and -2.5
Endocrine CCSG – Calcium/Bone Cases Matthew Lin
CCSG 3
Osteoporosis: T score at or below -2.5
 
What results suggest that the patient might have a disease other than
age related / post-menopausal osteoporosis?
 
Secondary causes are endocrine disease (hypogonadism, hyperparathyroidism,
hyperthyroidism, Cushing's syndrome), intestinal malabsorption of calcium/vitamin D,
hypercalciuria, chronic disease 
 
6. What factors, other than bone density, predict whether this patient is likely to sustain
a fragility fracture (a low impact fracture from a standing height)?
 
Fracture is an independent risk factor for future fracture independent of BMD (fractures
beget fractures)
 
CASE #2
 
A 47-year-old woman sees you after breaking three of her ribs while coughing during a
week long bout of viral bronchitis.
 
Her first menstrual period was at age 12. She is still menstruating regularly. She has
had three children. She has been lean her entire life, but has never had an eating
disorder. She has a longstanding history of lactose intolerance and does not consume
any milk. She has a family history of skin cancer and avoids sunlight and wears
sunscreen.
 
She has recently felt an increase in fatigue and friends have noticed that she looks
pale. She has also experienced some abdominal bloating and intermittent diarrhea
over the last 6 months. Her mother has no history of fracture or becoming round
shouldered.
 
She has never smoked. She drinks one glass of wine a day. She drinks two cups of
coffee a day. She walks approximately one mile daily and does light weight training 2
days per week.
 
Physical examination reveals a lean woman, weight = 110 lbs, BMI =20, pale
conjunctiva, tenderness over her left ribs, good muscle tone and strength in her
extremities.
 
The patient's blood chemistries and urine testing reveal:
 
 serum calcium is 8.4 mg/dl (normal 8.5 -10)
 
 serum phosphorus is 2.3 mg/dl (normal 2.4 -4.5)
 
 24 hour urine calcium is 5 mg/24hrs (normal 50 -250)
 
 normal renal function
 
Endocrine CCSG – Calcium/Bone Cases Matthew Lin
CCSG 3
 normal albumin and normal calculated globulin level
 
 hemoglobin is 10 gms, and her MCV is 105 (anemia with large red cells). B12 and
folate levels are very low.
 
Bone density (DXA) shows:
    T-score Z-score  
  Lumbar spine -3.0 -2.0  
  Femoral neck -3.5 -2.5  
  Forearm (113 radius) -4.0 -3.0  
         

 
QUESTIONS:
 
1. What bone disorder does this patient have? Explain how you came to this
conclusion. What diseases cause this disorder? Which diagnoses are likely
in this patient?
 
Her T scores are all below -2.5 and this makes it likely she has osteoporosis. Due to
her megaloblastic macrocytic anemia (signs of malabsorption) and decreased intake of
calcium (lactose intolerance) and vitamin D production (avoids sunlight), in addition to
her still menstruating (pre-menopausal) this makes me think she has low-turnover
osteoporosis.
 
7. What is the likely result of each one of the following tests (elevated, normal or
low)? Explain the reasoning behind your answers.
a. 25-hydroxy Vitamin D - low (not absorbing enough/making enough)
 
a. 1,25-hydroxy Vitamin D - low (there isn't enough precursor)
 
b. Intact parathyroid hormone (PTH) - she has deficiency of vitamin D and
calcium not a dysfunction in calcium regulation
 
a. Bone alkaline phosphatase - low (low turnover)
 
a. N-terminal telopeptide (a measure of bone collagen breakdown) - normal (low
turnover, not age-related)
 
8. What would a bone biopsy show?
 
Low bone mass and microarchitectural deterioration
 
9. How would you treat this patient?
 
Calcium + vitamin D supplements, denosumab
Endocrine CCSG – Calcium/Bone Cases Matthew Lin
CCSG 3