Followup of Health Survey Detected Hypercalcemia

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In the Stockholm health survey, 27 randomly selected hypercalcemic patients underwent neck exploration, and all were found to have parathyroid adenoma.21 Another group of 23 hypercalcemic patients (mean age, 55 years) was monitored with regular checkups and compared with age-and sex-matched normocalcemic control subjects during a 10-year period.21 Their initial mean serum calcium of 2.75 mmol/L remained unchanged during the study period, and there was no notable deterioration of kidney function in routine serum analyses. A significant elevation of systolic and diastolic blood pressures in the hypercalcemic individuals compared with control subjects at initiation of the follow-up persisted throughout the 10-year study period.21,22 In the Gavle health survey, the mean age of hypercalcemic individuals was 59 years, and their mean serum calcium was 2.72 mmol/L.13 Eleven patients initially had surgery because of marked hypercalcemia (2.83 to 3.63 mmol/L), and another 21 underwent surgery between 1971 and 1983 to 1984 when a follow-up study was performed.13 The majority of the patients with hypercalcemia were neither informed about their hypercalcemia nor treated. At the follow-up study in 1983 to 1984, 57 patients had died and 7 were lost to follow-up. Scrutiny of patients' records did not indicate that any of these individuals had had severe hypercalcemia or renal insufficiency.13,23 Of the remaining 95 patients, 47 still had a serum calcium level greater than 2.60 mmol/L in 1983 to 1984, and 48 subjects with serum calcium levels slightly below this normal limit had displayed intermittent hypercalcemia in the intervening years.13 For the majority of hypercalcemic individuals, the serum calcium remained more or less constant throughout the study period, and no patient (including those who subsequently had parathyroid surgery) showed markedly progressive hypercalcemia or an abrupt rise in serum calcium levels.13 Serum creatinine levels were above normal in 15 patients at the 1983 to 1984 follow-up, but only 3 patients had a more marked elevation of serum creatinine, and these individuals had either urea nitrogen above normal at the initial screening or obvious nonparathyroid causes of renal impairment.23

Using national registration numbers and the causes of death registry, survival was compared between individuals who were hypercalcemic at the 1969 to 1971 survey and matched normocalcemic control subjects.23 Survival during the 14-year follow-up was significantly lower among the hypercalcemic individuals.23 The difference in survival steadily increased and became more marked after 5 years from the initial health survey.23 The hypercalcemic individuals also had significantly higher diastolic and systolic blood pressures as well as serum uric acid and a tendency toward higher glucose and cholesterol levels. Using multivariate analyses, higher levels of serum calcium were associated with increased mortality in patients older than 60 years, but this effect diminished in the oldest age groups. Life table analyses revealed a significant difference in survival between hypercalcemic persons and control subjects at age 70 or younger but not for those older than 70 years (Fig. 41-2).23 The increased mortality in the hypercalcemic

All subjects

Subjects s 70 years

Subjects > 70 years

, Controls

FIGURE 41-2. Survival curves for hypercalcemic subjects and matched control subjects from the Gavle County Health Survey. (From Palmar M, Adami H-O, Bergstrom R, et al. Survival and renal function in persons with untreated hypercal-caemia: A population-based cohort study with 14 years of follow-up. Lancet 1987; 1:59. © by the Lancet Ltd., 1987.)

Hypercalcemics

All subjects

Subjects s 70 years

Subjects > 70 years

, Controls

Hypercalcemics

FIGURE 41-2. Survival curves for hypercalcemic subjects and matched control subjects from the Gavle County Health Survey. (From Palmar M, Adami H-O, Bergstrom R, et al. Survival and renal function in persons with untreated hypercal-caemia: A population-based cohort study with 14 years of follow-up. Lancet 1987; 1:59. © by the Lancet Ltd., 1987.)

Time of follow up (years)

Time of follow up (years)

group was not due to any single disease group, but the number of deaths caused by cardiovascular diseases was predominant and distinctly higher than expected. No deaths were caused by hypercalcemic crisis, renal failure, or other conditions that were obviously related to the hypercalcemic state.23 When examined for symptoms, the hypercalcemic individuals exhibited similar but less significant psychiatric symptoms when compared with patients with clinically detected primary HPT14-24'25 but more symptoms than the nor-mocalcemic control patients. The hypercalcemic individuals were subsequently subjected to a 25-year follow-up, showing a tendency to lowering (or even normalization) of the hypercalcemia but continuing to have increased mortality in comparison with control subjects.26 The excess mortality was significant among individuals 70 years of age or younger and was valid for cardiovascular disease only.26

The studies indicate that the risk for progression of hypercalcemia or marked deterioration of renal function is low in borderline hypercalcemic primary HPT. The risk for subclinical renal impairment in HPT and thereby reduced levels of active vitamin D, which could contribute to the increased cardiovascular death rate (and also to lowering or normalization of the hypercalcemia), has been emphasized.27 The raised mortality has, however, not been found in all series2829 and may depend on the severity and duration of HPT.27 The psychiatric disturbance may be a notable complication in individuals with intellectual occupations and cause states of confusion in elderly people but may not always be impressive in patients with borderline hypercalcemia.25

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