The gold standard of diagnosis is the PTH
immunoassay. Once an elevated PTH has been confirmed, the goal of diagnosis is to determine the type of hyperparathyroidism (primary, secondary, or tertiary hyperparathyroidism) by obtaining a serum
calcium, phosphate, and PTH levels. Primary hyperparathyroidism has high
calcium,
vitamin D, and
PTH levels and a low
phosphate level. Additionally a
CT scan without contrast or
renal ultrasound can be done to assess for
nephrolithiasis and/or
nephrocalcinosis if there is concern for it. Additionally,
familial benign hypocalciuric hypercalcamia can present with similar lab changes.
Calcium levels In cases of primary hyperparathyroidism or tertiary hyperparathyroidism, heightened PTH leads to increased serum calcium (hypercalcemia) due to: • increased bone resorption, allowing the flow of calcium from bone to blood • reduced kidney clearance of calcium • increased intestinal calcium absorption
Serum phosphate In primary hyperparathyroidism, serum phosphate levels are abnormally low as a result of decreased reabsorption of phosphate in the kidney tubules. However, this is only present in about 50% of cases. This contrasts with
secondary hyperparathyroidism and tertiary hyperparathyroidism, in which serum phosphate levels are generally elevated because of kidney disease.
Alkaline phosphatase Alkaline phosphatase levels are usually high in hyperparathyroidism due to high bone turn over. In primary hyperparathyroidism, levels may remain within the normal range, but this is inappropriately normal given the increased levels of plasma calcium.
Nuclear medicine Nuclear medicine imaging methods are used by surgeons to locate which parathyroid gland is responsible for hyperparathyroidism or to find
ectopic parathyroid adenomas, most commonly found in the anterior
mediastinum. Historically,
technetium sestamibi scintigraphy was the main method used or this indication. Recently 18F-fluorocholine
PET/CT tend to be more and more performed due to excellent diagnostic performance.
Classification Primary .
Primary hyperparathyroidism results from a
hyperfunction of the
parathyroid glands themselves. The oversecretion of PTH is due to a
parathyroid adenoma,
parathyroid hyperplasia, or rarely, a
parathyroid carcinoma. This disease is often characterized by the quartet
stones, bones, groans, and psychiatric overtones referring to the presence of
kidney stones, hypercalcemia, constipation, and
peptic ulcers, as well as
depression, respectively. In a minority of cases, this occurs as part of a
multiple endocrine neoplasia (MEN) syndrome, either
type 1 (caused by a mutation in the gene
MEN1) or
type 2a (caused by a mutation in the gene
RET), which is also associated with the adrenal tumor
pheochromocytoma. Other mutations that have been linked to parathyroid neoplasia include mutations in the genes
HRPT2 and
CASR. Patients with
bipolar disorder who are receiving long-term
lithium treatment are at increased risk for hyperparathyroidism. Elevated calcium levels are found in 15% to 20% of patients who have been taking lithium long-term. However, only a few of these patients have significantly elevated levels of parathyroid hormone and clinical symptoms of hyperparathyroidism. Lithium-associated hyperparathyroidism leads to
hypercalcemia in about 4% of lithium-treated patients.
Calcium levels should be checked for patients undergoing long-term lithium treatment. (caused by lack of sunlight, diet or malabsorption) and
chronic kidney failure. Vitamin D deficiency can result from malabsorption or decreased vitamin D intake such as with
gastric bypass, small bowel disease,
pancreatic disease, and
dietary causes. Other causes include decreased skin synthesis of vitamin D such as decreased exposure to sunlight and skin disorders. Insufficient vitamin D synthesis such as defective 25-hydroxylation,
1-alpha hydroxylase, and 1-alpha 25-hydroxylation can also contribute to vitamin D deficiency. Lack of vitamin D leads to reduced calcium absorption by the intestine leading to hypocalcemia and increased parathyroid hormone secretion. This increases bone resorption. In chronic kidney failure the problem is more specifically failure to convert vitamin D to its active form in the kidney. The bone disease in secondary hyperparathyroidism caused by kidney failure is termed
renal osteodystrophy.
Tertiary Tertiary hyperparathyroidism is seen in those with long-term secondary hyperparathyroidism, which eventually leads to hyperplasia of the parathyroid glands and a loss of response to serum calcium levels. This disorder is most often seen in patients with end-stage kidney disease and is an autonomous activity. Patients with late-stage kidney disease have an increased likelihood of developing tertiary hyperparathyroidism if not promptly corrected. ==Treatment==