Serum levels of free 1,25-dihydroxyvitamin D in vitamin D toxicity.

OBJECTIVE: To determine the serum level of free 1,25-dihydroxyvitamin D [1,25-(OH)2D] in patients with vitamin D toxicity and to assess the in vitro effect of differing concentrations of vitamin D metabolites on the free serum levels of 1,25-(OH)2D. DESIGN: 1) A case study of patients hospitalized with vitamin D toxicity after accidentally ingesting a veterinary vitamin D concentrate and 2) an in vitro experiment in which vitamin D metabolites in various concentrations were added to normal serum and their effect was noted on percentage of free 1,25-(OH)2D. PATIENTS: 11 patients (age range, 8 to 69 years) were studied 10 to 40 days after hospitalization for hypercalcemia. MEASUREMENTS: Serum total 25-hydroxyvitamin D (25-OHD) and 1,25-(OH)2D levels were measured by radioreceptor assays. The percentage of free 1,25-(OH)2D was measured by centrifugal ultrafiltration isodialysis and was used to calculate actual free 1,25-(OH)2D levels. In the in vitro studies, vitamin D metabolites [25-OHD; 24,25-(OH)2D; 25,26-(OH)2D; and 25-OHD-26,23 lactone] were added to normal serum in concentrations expected to occur with vitamin D toxicity. The percentage of free 1,25-(OH)2D was measured by isodialysis. RESULTS: All patients presented with marked hypercalcemia (mean calcium level, 3.99 +/- 0.33 mmol/L). Serum 25-OHD levels ranged from 847 to 1652 nmol/L, and total 1,25-(OH)2D levels (mean, 106 +/- 86 pmol/L) were elevated in only three patients. The percentage of free 1,25-(OH)2D (mean, 1.023% +/- 0.366%) was elevated in all nine patients in whom it was measured. Actual free 1,25-(OH)2D levels (mean, 856 +/- 600 fmol/L) were elevated in six of the nine patients. Total 1,25-(OH)2D levels were correlated with 25-OHD levels (r = 0.66; P = 0.03), whereas total and free 1,25-(OH)2D levels were highly correlated (r = 0.957; P < 0.001). In the in vitro studies, the percentage of free 1,25-(OH)2D increased after 25-OHD or 24,25-(OH)2D was added. CONCLUSIONS: Although the patients had normal or near-normal total 1,25-(OH)2D values, most patients had elevated free 1,25-(OH)2D levels. These findings suggest that elevated free 1,25-(OH)2D levels might play a role in the pathogenesis of hypercalcemia in vitamin D toxicity.

Coronary risk factors in newly diagnosed and previously diagnosed type 2 diabetic men with myocardial infarction.

Risk factors for coronary artery disease in 131 known non-insulin-dependent (type 2) diabetic patients is compared to that in 115 newly diagnosed type 2 diabetic subjects and in 316 non-diabetic patients. The subjects, all Indian men aged 21-60 years, represent consecutive survivors of myocardial infarction and were investigated 3-4 months after their acute episode. A group of 524 healthy Indian men aged 21-60 years were included as controls. Significant differences in parameters measured were noted when all diabetic and non-diabetic patients were compared to the control group. Diabetic patients were older than the non-diabetic patients and with significantly higher frequency of hypertension and hypertriglyceridaemia, whilst smoking and family history of coronary artery disease were elicited more frequently in the non-diabetic patients. Mean concentrations of serum total cholesterol and lipoproteins in the diabetic and non-diabetic men were similar, whereas serum triglyceride concentrations were significantly higher in the diabetic patients. Newly diagnosed and known diabetic patients did not differ with respect to the risk factors examined. Clusters of various combinations of hypertension, obesity, hypertriglyceridaemia and low HDL-cholesterol values were encountered more frequently in diabetic patients when compared to non-diabetic patients, whilst no significant differences were observed when the two groups of diabetic subjects were compared. In conclusion, this study has demonstrated that in men with myocardial infarction there are significant differences between diabetic and non-diabetic patients with respect to certain risk factors. However, newly diagnosed diabetic men have similar risk profiles to their known diabetic counterparts.

Hepatocellular carcinoma in South African Indians resident in Natal.

Hepatoma is a rare disease in Natal Indians. It occurs in male patients in the fifth decade. They have no history of alcohol intake. The main presenting feature is abdominal pain, weight loss and hepatomegaly. Blood tests reveal a raised alkaline phosphatase, hypoalbuminaemia, hypergammaglobulinaemia and markedly raised gamma glutamyl transferase. The tumour is a single large expanding mass in the right lobe. The patient usually presents in a late stage of the illness and shows a progressive downhill course. Hepatitis B virus infection is emerging as the likeliest carcinogen.

Thrombocytosis associated with tuberculous peritonitis.

A young African female is described who showed marked thrombocytosis (platelet count 1372 X 10(9)/l) in association with tuberculous peritonitis, a rare association.