- Does this patient have hyperparathyroidism?
- What tests to perform?
- How should patients with hyperparathyroidism be managed?
- What happens to patients with hyperparathyroidism?
- How to utilize team care?

- Does this patient have hyperparathyroidism?
- What tests to perform?
- How should patients with hyperparathyroidism be managed?
- What happens to patients with hyperparathyroidism?
- How to utilize team care?
Are there clinical practice guidelines to inform decision making?
What is the evidence?
Does this patient have hyperparathyroidism?
There are four parathyroid glands which produce parathyroid hormone (PTH). PTH is the primary regulator of calcium homeostasis and vitamin D conversion. PTH maintains the calcium concentration (ionized) in the extracellular fluid within a narrow normal range due to calcium's wide array of cellular functions. Secretion of PTH is normally stimulated by falls in the extracellular calcium concentration. To accomplish calcium homeostasis, PTH acts directly on the bone, kidney, and indirectly at the intestine via 1,25 (OH)2D to regulate calcium concentrations.
At the kidney, PTH actions stimulate renal calcium reabsorption in the cortical thick ascending limb. In the intestines it stimulates the hydroxylation of 25-hydroxyvitamin D allowing for calcium absorption. At bone, PTH acts to increase serum calcium by stimulating bone resorption via osteoclast-activating factors such as interleukin-6 from osteoblasts.
Hyperparathyroidism, the state of excess parathyroid hormone, is a common cause of hypercalcemia and the primary disorder is most commonly due to an autonomously functioning solitary adenoma (80-85%), gland hyperplasia (10-15%) or multiple adenomas (5%).
Secondary hyperparathyroidism occurs when there is partial resistance to the metabolic actions of PTH, leading to excessive production of the hormone. This is seen most commonly with renal failure. The topic of renal osteodystrophy will be discussed in subsequent sections.
Pseudohypothyroidism is an extremely rare genetic condition linked to dysfunctional G proteins (heterozygous loss of g alpha function) and is manifested by parathyroid hormone resistance. There are 3 types (1a, 1b, 2), and all present with low serum calcium, high phosphate and appropriate elevations in PTH.
Type 1a (Albright's hereditary osteodystrophy), due to a maternal allelic mutation GNAS 1 on chromosome 20, has a distinct phenotypic appearance with short fourth and fifth metacarpals described as the "knuckle, knuckle, dimple, dimple" sign, rounded faces and is associated with thyroid stimulating hormone resistance.
Type 1b and type 2 lack phenotypic abnormalities but are biochemically similar. Pseudo-pseudohyperparathyroidsm presents with a phenotypic picture similar to psuedohyperparathyroidism type 1a, but subjects are biochemically normal. This is due to a paternal defect in the GNAS1 allele.
This topic will focus on primary hyperparathyroidism.
The age adjusted incidence of primary hyperparathyroidism is estimated to 15.7 per 100,000 patient years, and this estimate has been in steady decline despite innovations in testing that have allowed for early detection. Possible explanations for the decline include the addition of calcium with vitamin D supplementation to the diet, supplemental estrogen use in post-menopausal females, and recognition of the complications of excessive radiation exposure that are implicated in causing parathyroid malignancies.
The estimated mean age at diagnosis based is between 52 - 56 years. Women account for the majority (74%) of the cases. At diagnosis the most common findings are serum calcium concentration within 1 mg/dL the upper limit of normal, and parathyroid hormone concentration 1.5 times the upper limit of normal. Hypercalciuria is seen in approximately 40% of patients and hypophosphatemia in less than 25% of patients.
Today, most patients are asymptomatic with few overt manifestations due to early detection. Hypercalcemia, an early laboratory finding in hyperparathyroidism, is often the impetus for checking parathyroid hormone (PTH) levels. The paradigm shift in clinical presentations from clinically symptomatic to asymptomatic can be attributed to the multichannel biochemical testing assay (1974) that includes serum calcium, thus allowing for early identification and treatment.
Rheumatological manifestations of primary hyperparathyroidism
Classically, effects of excess parathyroid hormone affected the kidney and musculoskeletal system giving rise to the well-known moniker for the clinical manifestations "bones, stones, and groans".
Osteitis fibrosa cystica
Also referred to as osteitis fibrosa, osteodystrophia fibrosa and Von Recklinghausen's disease of bone.
This was a term applied to the characteristic subperiosteal erosions that were initially identified in primary hyperparathyroidism. This is now an extremely rare complication in primary hyperparathyroidism in the United States (seen with severe disease, especially with parathyroid carcinoma), although in the developing world, where calcium and vitamin D nutrition is inadequate, it is still seen.
Clinically this is characterized by diffuse bone pain, bone tenderness, and skeletal 