PRIMARY HYPERPARATHYROIDISM

'Primary hyperparathyroidism' causes hypercalcemia (elevated blood calcium levels) through the excessive secretion of parathyroid hormone (PTH), usually by an adenoma (benign tumors) of the parathyroid glands. Its incidence is approximately 42 per 100,000 people. It is almost exactly three times as common in women as men.

Contents

Signs and Symptoms

Diagnosis

Parathyroid hormone activity

Causes

Complications

Treatment

Surgery

See also

References

Signs and Symptoms

The signs and symptoms of primary hyperparathyroidism are those of hypercalcemia. They are classically summarized by the mnemonic "stones, bones, abdominal groans and psychic moans".

★ "Stones" refers to kidney stones, nephrocalcinosis, and diabetes insipidus (polyuria and polydipsia). These can ultimately lead to renal failure.

★ "Bones" refers to bone-related complications. The classic bone disease in hyperparathyroidism is osteitis fibrosa cystica, which results in pain and sometimes pathological fractures. Other bone diseases associated with hyperparathyroidism are osteoporosis, osteomalacia, and arthritis.

★ "Abdominal groans" refers to gastrointestinal symptoms of constipation, indigestion, nausea and vomiting. Hypercalcemia can lead to peptic ulcers and acute pancreatitis.

★ "Psychic moans" refers to effects on the central nervous system. Symptoms include lethargy, fatigue, depression, memory loss, psychosis, ataxia, delirium, and coma.

★ Left ventricular hypertrophy.^[1]
Other signs include proximal muscle weakness, itching, and band keratopathy of the eyes.

Diagnosis

The diagnosis of primary hyperparathyroidism is made by blood tests. Serum calcium levels are elevated.
The serum chloride phosphate ratio is 33 or more in most patients with primary hyperparathyroidism. ^[2][3][4] However, thiazide medications have been reported to causes ratios above 33.^[5]
Urinary cAMP is occasionally measured; this is generally elevated.

Parathyroid hormone activity

Intact PTH levels are also elevated.

Causes

The most common cause of primary hyperparathyroidism is a sporadic, single parathyroid adenoma resulting from a clonal mutation (~97%). Less common are hyperplasia of all parathyroid glands (~2.5%), parathyroid carcinoma (malignant tumor), and adenomas in more than one gland (together ~0.5%). Primary hyperparathyroidism is also a feature of several familial endocrine disorders: Multiple endocrine neoplasia type 1 and type 2A (MEN type 1 and MEN type 2A), and familial hyperparathyroidism.
In all cases, the disease is idiopathic, but is thought to involve inactivation of tumor suppression genes.

Complications

The classic bone disease in hyperparathyroidism is osteitis fibrosa cystica, which results in pain and sometimes pathological fractures. Other bone diseases associated with hyperparathyroidism are osteoporosis, osteomalacia, and arthritis.

Treatment

Treatment is usually surgical removal of the gland(s) containing adenomas. Medications (such as estrogen replacement therapy in postmenopausal women and bisphosphonates) thus far have not been very effective. Future developments such as calcimemetic agents (e.g. cinacalcet) which activate the parathyroid calcium-sensing receptor may offer a good alternative to surgery.

Surgery

A consensus statement in 2002 recommended the following indications for surgery^[6]:

★ Serum calcium (above upper limit of normal): 1.0 mg/dl

★ 24-h urinary calcium >400 mg

★ Creatinine clearance reduced by 30% compared with age-matched subjects.

★ Bone mineral density t-score <-2.5 at any site

★ Age <50
More recently, three randomized controlled trials have studied the role of surgery in patients with asymptomatic hyperparathyroidism. The largest study reported that surgery showed increase in bone mass, but no improvement in quality of life after one to two years among patients with^[7]:

★ Untreated, asymptomatic primary hyperparathyroidism

★ Serum calcium between 2.60 - 2.85 mmol/liter (10.4 - 11.4 mg/dl)

★ Age between 50 and 80 yr

★ No medications interfering with Ca metabolism

★ No hyperparathyroid bone disease

★ No previous operation in the neck

★ Creatinine level < 130 µmol/liter (<1.47 mg/dl)
Two other trials reported improvements in bone density and some improvement in quality of life with surgery.^[8][9]

See also

★ Secondary hyperparathyroidism

★ Tertiary hyperparathyroidism

References

1. Cardiac abnormalities in patients with primary hyperparathyroidism: implications for follow-up, Stefenelli T, Abela C, Frank H, ''et al'', , , J. Clin. Endocrinol. Metab., 1997
2. Differential diagnosis of hypercalcemia by the chloride/phosphate ratio, Reeves CD, Palmer F, Bacchus H, Longerbeam JK, , , Am. J. Surg., 1975

This study found a ratio above 33 to have a sensitivity of 94% and a specificity of 96%.

3. The chloride-phosphate ratio in hypercalcemia, Palmer FJ, Nelson JC, Bacchus H, , , Ann. Intern. Med., 1974
4. The chloride phosphate ratio as the screening test for primary hyperparathyroidism, Broulík PD, Pacovský V, , , Horm. Metab. Res., 1979

This study found a ratio above 33 to have a sensitivity of 95% and a specificity of 100%.

5. Chloride:phosphate ratio with hypercalcemia secondary to thiazide administration, Lawler FH, Janssen HP, , , The Journal of family practice, 1983
6. Summary statement from a workshop on asymptomatic primary hyperparathyroidism: a perspective for the 21st century, Bilezikian JP, Potts JT, Fuleihan Gel-H, ''et al'', , , J. Clin. Endocrinol. Metab., 2002
7. Medical observation, compared with parathyroidectomy, for asymptomatic primary hyperparathyroidism: a prospective, randomized trial, Bollerslev J, Jansson S, Mollerup CL, ''et al'', , , J. Clin. Endocrinol. Metab., 2007
8. Surgery or surveillance for mild asymptomatic primary hyperparathyroidism: a prospective, randomized clinical trial, Ambrogini E, Cetani F, Cianferotti L, ''et al'', , , J. Clin. Endocrinol. Metab., 2007
9. Randomized controlled clinical trial of surgery versus no surgery in patients with mild asymptomatic primary hyperparathyroidism, Rao DS, Phillips ER, Divine GW, Talpos GB, , , J. Clin. Endocrinol. Metab., 2004