Differentials
Primary hyperparathyroidism
SIGNS / SYMPTOMS
There may be a family history of hyperparathyroidism. Most patients are asymptomatic. However, symptoms include fatigue, poor sleep, anxiety, depression, memory loss, bone pain, and constipation.
Although rare, physical examination of the neck may identify a hard, dense, firm mass suggestive of parathyroid carcinoma. An eye examination may demonstrate signs such as band keratopathy (a deposition of calcium just inside the iris).
INVESTIGATIONS
Elevated serum calcium, elevated intact PTH, and a low-normal or low fasting serum phosphate level.[80]
Multiple myeloma
SIGNS / SYMPTOMS
Symptoms and signs are non-specific and commonly include bone pain and anaemia. Weight loss can also occur.
INVESTIGATIONS
Elevated serum calcium, low level of intact PTH and 1,25-dihydroxyvitamin D.
Bone x-ray shows lytic bone lesions, characteristic of multiple myeloma.
Gamma globulin assessment defines the disorder as well.
Serum creatinine and urea levels are abnormal in 50% of multiple myeloma patients.
Serum and urine protein electrophoresis is diagnostic of multiple myeloma.
Fibromyalgia
SIGNS / SYMPTOMS
A chronic pain syndrome diagnosed by the presence of widespread body pain (defined as pain in at least four of five regions) for at least 3 months.[81]
INVESTIGATIONS
Clinical diagnosis.
Normal serum 25-hydroxyvitamin D.
Myalgic encephalomyelitis (chronic fatigue syndrome)
SIGNS / SYMPTOMS
Characterised by persistent disabling fatigue, post-exertional malaise/exertional exhaustion, and other associated symptoms (e.g., musculoskeletal pain, sleep disruption, memory impairments) lasting for 6 months or longer.[82]
The fatigue is not related to other medical conditions, disease processes, or identifiable biological causes. Sleep, rest, and activity restriction do not improve symptoms.
Patients may present with a low-grade fever, tender lymph nodes, muscle pain/joint stiffness on palpation, tachycardia, hyperventilation, and/or orthostatic hypotension.
INVESTIGATIONS
Clinical diagnosis.
Normal serum 25-hydroxyvitamin D.
Paget's disease
SIGNS / SYMPTOMS
Usually asymptomatic, but may present with severe pain in long bones and, although unusual, in some facial areas.
INVESTIGATIONS
Normal serum calcium and a markedly elevated serum alkaline phosphatase (due to increased bone remodelling in the Pagetic bone). Serum calcium can be elevated in patients with prolonged bed rest.
On x-ray there is a mottled appearance and gross deformities of bone may be seen, such as enlargement of the skull and bowing of the femur or tibia.
Hypophosphatasia
SIGNS / SYMPTOMS
An autosomal-recessive disorder that radiographically resembles rickets.
It is an inborn error of metabolism in which activity of tissue-non-specific (liver/bone/kidney) alkaline phosphatase is deficient.[83]
INVESTIGATIONS
Defined by low serum alkaline phosphatase activity.
Large quantities of phosphoethanolamine are found in the urine.
Metaphyseal dysostoses
INVESTIGATIONS
Absence of abnormalities of low serum levels of calcium and phosphate, alkaline phosphatase activity, or vitamin D metabolites.
Blount's syndrome
SIGNS / SYMPTOMS
Condition that causes osteochondrosis of the tibia, resulting in bowing of the legs.[84] May be related to obesity.
INVESTIGATIONS
Absence of abnormalities of low serum levels of calcium and phosphate, alkaline phosphatase activity, or vitamin D metabolites.
Idiopathic infantile hypercalcaemia
SIGNS / SYMPTOMS
Rare genetic disorder of the 25-hydroxyvitamin D-24-hydroxylase that markedly reduces the catabolism of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D.[85][86]
Causes hypercalcaemia in infancy. Can also present in older children and adults with unexplained hypercalcaemia often associated with kidney stones.
INVESTIGATIONS
High normal or elevated levels of both 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D with a suppressed parathyroid hormone level and a normal ACE level.
The diagnosis can be made by measuring serum 24,25-dihydroxyvitamin D level or a genetic test for the 25-hydroxyvitamin D-24-hydroxylase gene. Typically 24,25-dihydroxyvitamin D levels are approximately 10% to 15% of the total 25-hydroxyvitamin D level. If the level is undetectable or <~5% the diagnosis should be suspected.
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