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  • Author: M. A. B. Naafs x
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C. D. A. Stehouwer, W. F. Lems, H. R. A. Fischer, W. H. L. Hackeng and M. A. B. Naafs


Recently somatostatin analogues were successfully used to control insulin-induced hypoglycemia in patients with insulinoma. We observed a transient decrease in glucose levels and symptomatic hypoglycemia after administration of the long-acting somatostatin analogue octreotide (Sandostatin®) in two insulinoma patients. We studied the acute effects of octreotide (administered before breakfast) on blood glucose and glucoregulatory hormones in these patients. In one patient, we studied the effects of glucagon replacement and changing the time of breakfast (relative to octreotide administration) on octreotide-associated changes in blood glucose and glucoregulatory hormones. Compared with control levels, octreotide therapy reduced insulin levels. During hypoglycemia glucagon and growth hormone levels were suppressed, but cortisol levels appropriately increased. The increase in catecholamine levels was normal in one patient, but markedly attenuated in the other. A transient decrease in serum glucose after octreotide was absent after glucagon replacement, but present when breakfast was taken before administration of octreotide. We conclude that in patients with insulinoma, octreotide therapy may be associated with clinically important hypoglycemia, during which counterregulatory hormone secretion may be attenuated.

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M. A. B. Naafs, H. R. A. Fischer, P.C. van der Velden, H. Mulder, W. H. L. Hackeng, W. Schopman, G. Koorevaar and J. Silberbusch

Abstract. Ten hypercalcaemic patients with solid tumours were studied to evaluate the renal response on PTH infusion as assessed by nephrogenous cAMP excretion and maximum tubular re-absorption of phosphate. In addition, 20 normocalcaemic patients, 11 with an adenocarcinoma and 9 with a squamous cell carcinoma, were studied. All cancer patients had moderately extensive disease. Results were compared with those of 9 patients with primary hyperparathyroidism and with 10 elderly controls. All groups studied had comparable renal function, magnesium and 25-hydroxy-vitamin D levels. Comparable results were obtained in patients with an adenocarcinoma and in controls. cAMP response (Δ nephrogenous cAMP) was significantly lower in the hypercalcaemic patients with a solid tumour compared with the controls (8.13 ± 4.68 nmol/100 ml glomerular filtrate vs 29.52 ± 25.62 nmol/100 ml glomerular filtrate; P < 0.005). In the group of patients with primary hyperparathyroidism Δ nephrogenous cAMP was 13.41 ± 7.54 nmol/100 ml glomerular filtrate (P < 0.06 vs controls). The group of patients with a squamous cell cancer showed an intermediate value of 14.83 ± 10.74 nmol/100 ml glomerular filtrate (P < 0.025 vs the normocalcaemic adenocarcinoma patients, but NS vs controls). In two hypercalcaemic patients with a solid tumour in whom PTH infusion was repeated after normalization of serum calcium no influence on renal responsiveness was observed. Responses of maximum tubular re-absorption of phosphate were lowest in the group of hypercalcaemic patients with a solid tumour and in the patients with primary hyperparathyroidism compared with controls (0.11 ± 0.10 vs 0.22 ± 0.09 mmol/l and 0.09 ± vs 0.22 ± 0.09 mmol/l; P <0.025 and P <0.005, respectively). It is concluded that in hypercalcaemic patients with a solid tumour a humoral factor is present which inhibits the interaction of exogenous PTH and its renal receptors. In a subset of normocalcaemic patients with a squamous cell cancer the same circulating factor might be present.

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M. A. B. Naafs, P. C. van der Velden, H. R. A. Fischer, G. Koorevaar, S. van Duin, W. H. L. Hackeng, W. Schopman and J. Silberbusch

Abstract. Plasma cyclic AMP (PcAMP) concentration and the excretion of cyclic AMP dl GF were estimated in 11 thyrotoxic patients before and after medical treatment.

PcAMP concentrations were significantly higher during hyperthyroidism (2.30 ± 0.69 vs 1.88 ± 0.71 nmoldl; P < 0.05), and total urinary cyclic AMP (TcAMP) excretion showed no significant changes (3.24 ± 0.64 vs 3.44 ± 1.77 nmol/dl GF). Nephrogenous (NcAMP) excretion rose significantly (1.00 ±0.82 vs 1.68 ±1.31 mmol/dl GF; P < 0.025). The increase in NcAMP excretion correlated significantly with the decrease in serum T3 levels (r = -0.46; P < 0.05). Serum iPTH levels showed no significant change. Both the serum Ca, corrected for serum total protein and TmPO4 GFR declined after treatment (respectively 2.44 ± 0.13 vs 2.33 ± 0.08 mmol l; P <0.05 and 1.18 ± 0.29 vs 1.05 ±0.22 mmol/l; P < 0.05). It is concluded that the rise in NcAMP excretion corroborates the concept of increasing parathyroid activity following the treatment of hyperthyroidism.