Reference Article
PRIMARY HYPERPARATHYROIDISM
"Description of the clinical profile of primary hyperparathyroidism (HP) has changed greatly over the past three decades."
Parathyroid hormone (PTH) secretion and action:
About 50% of serum calcium is ionized—the physiologically active form. Ionized Ca concentration is regulated by direct action of PTH on bone and the distal renal tubule, and by indirect action on the gut by the generation of calcitriol (vitamin D).
The rate of secretion of PTH is inversely proportional to the concentration of serum ionized Ca. Rapid changes in PTH secretion can, within minutes, affect osteoclastic bone resorption and renal reabsorption of Ca. Adjustments in gastrointestinal absorption of Ca via the PTH-vitamin axis take several days.The integrated action of PTH and vitamin D on the target tissues gives precise control of serum concentrations of Ca and phosphorus.
The primary pathophysiological hallmark of HP is a reduction in the ability of extra cellular Ca to suppress PTH secretion.

Epidemiology and pathology:
HP is now recognized as a common and often symptomless disorder—about 1 per 1000 population. "Of the endocrine disorders only diabetes mellitus and hyperthyroidism occur more frequently than HP".1 It is much more common in women than in men. The difference increases with age.
A single adenoma is the underlying pathology in more than 80% of cases. The distinction between adenoma and hyperplasia may be artificial, and explains why available histological techniques cannot distinguish between the two lesions.

Clinical features:
HP is most often diagnosed after the unexpected discovery of hypercalcemia in a symptom-free patient. When HP does cause symptoms, the skeleton and kidneys are the main organs affected. The symptoms and signs of HP are, in part, related to the degree of hypercalcemia. Subperiosteal resorption, most often present at the radial aspects of the middle phalanges, is the most sensitive radiologic sign of severe disease. (See illustration p 1235). The occurrence of nephrolithiasis has decreased greatly because more symptom-free patients are discovered. Nevertheless, nephrolithiasis is the most common complication of HP. The occurrence of HP among all patients who develop stones is about 5%. Screening for HP of all patients who develop stones, particularly women, in whom isolated nephrolithiasis is less common, is reasonable.
Hypercalciuria (24-h urine Ca > 250 mg for women and > 300 mg for men) occurs in about 40% of patients with HP.

Differential diagnosis and assessment:
Hypercalcemia is an essential diagnostic criterion. The ionized Ca may be raised in some patients who have normal total serum Ca. The serum phosphate is usually in the low or low/normal range because of depressed renal-tubular reabsorption.
The highly sensitive and specific immunometric assays for intact PTH has greatly simplified the diagnosis. Immunoassays refine the distinction between intact PTH (from the glands) and PTH-related protein (the humoral mediator of malignancy-associated hypercalcemia) . Circulating PTH is high in HP, and low of undetectable in malignancy-associated hypercalcemia. Conversely, PTH-related protein is high in most patients with malignancy-associated hypercalcemia and undetectable in HP.

Management:
Medical: There is little biochemical progression or continued loss of bone density in many patients who are followed without treatment. This suggests that the natural history of mild HP can be benign. Medical surveillance includes periodic measurements of serum calcium, urinary calcium and creatinine, and bone mineral density.
Patients should be instructed to: 1) avoid diuretics (particularly thiazides); 2) drink plenty of fluids; moderate their dietary calcium intake; and 3) avoid calcium and vitamin D supplements.
Estrogen therapy has been advocated for treatment of bone loss in postmenopausal women.2 This inhibits PTH-mediated bone resorption and produces modest decreases in calcium concentrations. PTH concentrations are generally not affected.
Surgical : Surgery, with its attendant risks, for all patients now seems unwise when many will have no features of metabolic bone or stone disease. Surgery is generally recommended if: 1) total serum Ca is more than 1 mg/dL (0.250 mmol/L) above upper limit of normal; 2) if there is evidence of overt bone disease; 3) if cortical bone mineral density is more than 2 SD below mean for age; 4) if there is reduced renal function; 5) for stone disease; 6) for hypercalciuria over 400 mg per day; or 6) if there has been an episode or acute HP (life-threatening hypercalcemia). In addition, persons under age 50, even in the absence of symptoms, should be considered for surgery because of the likelihood of a longer future duration of the disease. Although only about 20% of patients with HP have symptoms at presentation, these guidelines will identify an additional 30%-40% of symptom-free patients who are candidates for surgery. Therefore, about 50% of patients with HP will meet criteria for surgery.
Lancet April 26, 1997; 349: 1233-38 Seminar from Johns Hopkins Univ. School of Medicine Baltimore, MD

Comment:

1. What about hypothyroidism, subclinical and overt?

2. See also:
"Effect of Hormone Replacement Therapy on Bone Mineral Density in Postmenopausal Women with Mild Hyperparathyroidism"
"Our randomized controlled trial shows that hormone replacement therapy significantly increases bone mineral density and reduces urinary calcium excretion and bone turnover in postmenopausal women with mild primary hyperparathyroidism."
HRT should be considered an alternative to parathyroidectomy in the many postmenopausal women with mild hyperparathyroidism in whom osteopenia is the primary reason for intervention. ANNALS Int. Med. September 1, 1996; 125: 360-68
"Hormonal Influences on Bone Remodeling and Bone Loss: Application to the management of primary hyperparathyroidism"
"The question is not; When is hormone replacement therapy a reasonable alternative to parathyroid surgery? Rather—when is parathyroid surgery a reasonable alternative to hormone replacement therapy?" ANNALS Int. Med. September 1, 1996 125: 413-15

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