Hypophosphatemia Workup

Updated: Feb 02, 2022
  • Author: Eleanor Lederer, MD, FASN; Chief Editor: Vecihi Batuman, MD, FASN  more...
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Laboratory Studies

Serum phosphate, calcium, and magnesium

In addition to serum phosphate studies, serum calcium and magnesium studies can be helpful. High calcium levels coupled with low phosphate levels suggest primary hyperparathyroidism, while low calcium levels suggest vitamin D deficiency or malabsorption. Because of the many factors that regulate calcium independently of phosphate, serum calcium concentrations may be within reference ranges in either of these circumstances and thus cannot be used for a definitive diagnosis.

Low magnesium levels are also suggestive of poor nutrition. Serum potassium derangements, especially hypokalemia, may occur with certain hypophosphatemic conditions, such as diabetic ketoacidosis and alcoholism.

Serum albumin

Because almost half of serum albumin is bound to serum calcium, changes in serum albumin levels affect the total calcium concentration. Thus, in hypoalbuminemia, a decrease in albumin of 1 g/dL causes a fall in total calcium of approximately 0.8 mg/dL.

Intact parathyroid hormone and vitamin D levels

Primary hyperparathyroidism is very common, especially in elderly persons. Vitamin D deficiency is also very common, especially in geriatric or chronically ill persons. The excellent assays available for evaluation of parathyroid hormone (PTH) and vitamin D levels have simplified confirmation of the diagnosis of PTH and vitamin D disorders.

A high PTH level in the presence of high calcium and low phosphate levels is very suggestive of primary hyperparathyroidism. If the PTH level is high and the calcium and phosphate levels are low, secondary hyperparathyroidism is probable, perhaps due to intestinal malabsorption. The intestinal malabsorption could be due to isolated vitamin D deficiency or to a primary gastrointestinal disorder.

Other studies

An arterial blood gas study should be ordered if respiratory alkalosis is under consideration as a cause of hypophosphatemia.

Serum lactate, complete blood cell count th differential, and serum ammonia level, may be useful in selected patients to investigate some of the common causes of hypophosphatemia, such as sepsis and hepatic encephalopathy, which can cause respiratory alkalosis with subsequent hypophosphatemia.wi

At the current time, FGF23 levels are available only as a non-FDA-approved test and are in limited use. Levels of Klotho, Phex, or other mediators of phosphate wasting are not clinically available.

Tests for phosphate wasting

A 24-hour urine collection for phosphate can be performed if the question of phosphate wasting is unresolved. A fractional excretion of phosphate of greater than 15% in the presence of hypophosphatemia confirms the presence of renal phosphate wasting.

Phosphate wasting and subsequent hypophosphatemia can be due to proximal tubule disorders, such as Fanconi syndrome. To determine if the patient has a generalized proximal renal tubule disorder, urinalysis should be performed and serum bicarbonate, serum glucose, and serum uric acid levels should be measured.

Full-blown Fanconi syndrome consists of renal glycosuria, aminoaciduria, type II renal tubular acidosis, hypouricemia due to hyperuricosuria, and hypophosphatemia due to phosphate wasting. When Fanconi syndrome is present, the urinalysis demonstrates the presence of amino acids (proteinuria) and glucose. If the urine dipstick is positive for glucose at a time when the serum glucose concentration is less than 180 mg/dL, then renal glycosuria or renal glucose wasting is also present. Uric acid levels are also low, often less than 2 mg/dL. Evidence of mild nonanion gap metabolic acidosis is observed on the renal profile.


Imaging Studies

If a phosphate-wasting syndrome is suggested, then bone films to evaluate for osteopenia, osteomalacia, or hyperparathyroidism are indicated. Although plain bone films cannot yield histologic data, looser zones are very suggestive of osteomalacia. Erosions of the distal phalanges and clavicles and circular punched-out lesions in the long bones are highly typical of primary hyperparathyroidism.

Ultrasonographic images of the neck can help, at times, identify a parathyroid adenoma. A technetium Tc 99m sestamibi scan may be more useful. Uptake of the radioactive tracer has the advantage of being able to pick up ectopic parathyroid tissue.

Bone densitometry is also useful for assessing the chronicity and the severity of phosphate wasting. Chronic phosphate deficiencies result in significant decreases in bone density, while mild transient hypophosphatemia does not.

Mesenchymal tumors that can cause oncogenic osteomalacia have been discovered with the use of indium-111 octreotide scanning, computed tomography, or magnetic resonance imaging.


Histologic Findings

Most parathyroid lesions are adenomas. Occasionally, a carcinoma is found. Most of the tumors causing oncogenic osteomalacia are benign (eg, hemangiopericytoma).


Bone Biopsy

Bone biopsy is the only method for defining bone pathology. Hyperparathyroidism and osteomalacia may both have classic radiologic findings, but when the radiograph shows only osteopenia, bone biopsy findings help distinguish between these pathologies. The finding of osteomalacia directs the diagnostic studies toward vitamin D deficiency, malabsorption, or oncogenic osteomalacia. On the other hand, classic findings of hyperparathyroidism prompt the search for parathyroid disease.