Effects of cinacalcet on gastrointestinal hormone release in patients with secondary hyperparathyroidism undergoing dialysis.

UNLABELLED: Objective. Our aim has been evaluating the influence of an acute dose of cinacalcet on the gastrointestinal hormonal responses to a test meal in uraemic patients with secondary hyperparathyroidism undergoing peritoneal dialysis (PD) or haemodialysis (HD). METHODS: Twenty patients (11 PD, 9 HD) on cinacalcet treatment (30-120 mg/day) were studied. Twelve patients (1 PD, 11 HD) who never received cinacalcet were studied as control group. Each patient received a test meal with blood samples at 0, 2 and 4 h. At 0 time, patients in the cinacalcet group received their usual oral dose of this calcimimetic. Plasma concentrations of intact parathyroid hormone (PTH), vasoactive intestinal peptide (VIP), ghrelin, substance P, serotonin, cholecystokinin (CCK) and gastrin were quantified at 0, 2 and 4 h. RESULTS: No significant differences in baseline concentrations of serum VIP, ghrelin, substance P, serotonine, CCK and gastrin were found between controls and cinacalcet-treated patients. In comparison with the control group, cinacalcet administration was followed by a significant decrease in VIP concentration at 4 h and a significant increase in substance P at 4 h. However, the areas under the curves of all studied gut hormones were similar in both groups. CONCLUSION: An acute dose of cinacalcet exerts minimal influence on gut hormone responses to a mixed meal in dialysis patients on chronic therapy with this drug. The small but significant differences between control subjects and patients on cinacalcet in VIP and substance P levels at 4 h should be investigated in symptomatic patients.

Refractory hepatic encephalopathy in a patient with hypothyroidism: Another element in ammonia metabolism.

Hepatic encephalopathy (HE) remains a diagnosis of exclusion due to the lack of specific signs and symptoms. Refractory HE is an uncommon but serious condition that requires the search of hidden precipitating events (i.e., portosystemic shunt) and alternative diagnosis. Hypothyroidism shares clinical manifestations with HE and is usually considered within the differential diagnosis of HE. Here, we describe a patient with refractory HE who presented a large portosystemic shunt and post-ablative hypothyroidism. Her cognitive impairment, hyperammonaemia, electroencephalograph alterations, impaired neuropsychological performance, and magnetic resonance imaging and spectroscopy disturbances were highly suggestive of HE, paralleled the course of hypothyroidism and normalized after thyroid hormone replacement. There was no need for intervention over the portosystemic shunt. The case findings support that hypothyroidism may precipitate HE in cirrhotic patients by inducing hyperammonaemia and/or enhancing ammonia brain toxicity. This case led us to consider hypothyroidism not only in the differential diagnosis but also as a precipitating factor of HE.

Growth hormone and insulin-like growth factor binding protein-1 responses to oral glucose in patients with primary hyperparathyroidism.

BACKGROUND: GH and IGFBP-1 both play a role in glucose homeostasis. OBJECTIVE: To assess the GH and IGFBP-1 responses to an oral glucose load and their relationship with glucose homeostasis in patients with primary hyperparathyroidism. DESIGN: A cross-sectional study with a control group followed by a longitudinal study after parathyroidectomy. PATIENTS AND METHODS: We studied 15 patients with primary hyperparathyroidism (eight women, aged 59.6 +/- 2.2 years) and nine healthy normocalcaemic controls. All subjects were ambulatory and were studied as outpatients. Glucose, insulin, GH and IGFBP-1 were measured during an oral glucose (75 g) tolerance test (OGTT). RESULTS: Patients with hyperparathyroidism showed similar glucose responses to OGTT to those found in controls. Insulin responses were higher in patients (peak insulin 96.33 +/- 9.71 mU/l) in relation to values found in controls (58.11 +/- 9.03 mU/l; P < 0.01). Suppression of GH levels after OGTT was more marked in patients [nadir 0.03 (0.02-0.05) microg/l] than in normocalcaemic subjects [nadir GH 0.12 (0.08-0.42) microg/l; P = 0.002]. However, baseline IGFBP-1 concentration and its decrease after glucose load were similar in patients and controls. Normalization of calcium levels after parathyroidectomy was not followed by any significant changes in glucose, insulin and GH responses to OGTT. The minimum concentration of IGFBP-1 and the area under the curve (AUC) of IGFBP-1 after OGTT were higher after parathyroidectomy (3.34 +/- 0.69 microg/l and 8.94 +/- 1.72 microg x h/l, respectively) than at diagnosis (2.19 +/- 0.42 microg/l and 6.74 +/- 1.28 microg x h/l, respectively; P < 0.05). No correlation was found between PTH, calcium and phosphorus concentrations and GH and IGFBP-1 values in patients before or after normalization of calcium metabolism. CONCLUSION: GH and IGFBP-1 do not seem to be directly involved in the hyperparathyroidism-associated changes in carbohydrate metabolism. The postoperative changes in the depression of IGFBP-1 after OGTT remain to be elucidated.