Growth hormone corrects acidosis-induced renal nitrogen wasting and renal phosphate depletion and attenuates renal magnesium wasting in humans.

We have shown previously that chronic hyperchloremic metabolic acidosis (CMA) induces severe negative nitrogen balance and renal phosphate depletion and decreases serum insulin-like growth factor-1 (IGF-1) in association with growth hormone (GH) insensitivity in humans. The present study investigated whether acidosis-induced renal nitrogen wasting and renal phosphate depletion are mediated by GH insensitivity/low IGF-1 and thereby responsive to GH treatment. The effects of GH on acidosis-induced changes in divalent cation metabolism and acidosis-induced hypothyroidism were also investigated. CMA (delta[HCO3], -10.5 mmol/L) was induced in six healthy male subjects ingesting 4.2 mmol NH4Cl/kg body weight [BW]/d for 7 days. Recombinant human GH (0.1 U/kg BW/12 h subcutaneously) was administered for 7 days while acid feeding was continued. GH increased serum IGF-1 from 22.1 +/- 1.4 to 87 +/- 8.4 nmol/L (control level, 36.4 +/- 2.2). GH decreased urinary nitrogen excretion, resulting in a cumulative nitrogen retention of 2,404 mmol, thereby correcting the acidosis-induced cumulative increase in nitrogen excretion (2,506 mmol) despite continued acid feeding. GH attenuated the acidosis-induced hyperphosphaturia (cumulative phosphate retention, 91 mmol) and corrected the hypophosphatemia. GH did not affect acidosis-induced ionized hypercalcemia, but further exacerbated acidosis-induced hypercalciuria (cumulative loss, 27.3 mmol). GH significantly further increased serum 1,25-dihydroxyvitamin D (1,25(OH)2D) and further decreased intact PTH (from 10 +/- 1 to 6 +/- 1 pg/mL). Acidosis also induced hypomagnesemia and hypermagnesuria (cumulative loss, 9.4 mmol, ie, renal magnesium wasting), a novel finding, which was significantly attenuated by GH (cumulative retention, 5.0 mmol). In conclusion, GH corrected acidosis-induced renal nitrogen wasting, which may be caused, at least in part, by decreased IGF-1 levels. GH further increased serum 1,25(OH)2D and the systemic calcium load, which account for the suppression of parathyroid hormone (PTH) despite renal PO4 retention and correction of hypophosphatemia. GH attenuated acidosis-induced renal magnesium wasting.

Effect of growth hormone on renal and systemic acid-base homeostasis in humans.

The effects of recombinant human growth hormone (GH, 0.1 U.kg body wt-1.12 h-1) on systemic and renal acid-base homeostasis were investigated in six normal subjects with preexisting sustained chronic metabolic acidosis, induced by NH4Cl administration (4.2 mmol.kg body wt-1.day-1). GH administration increased and maintained plasma bicarbonate concentration from 14.1 +/- 1.4 to 18.6 +/- 1.1 mmol/l (P < 0.001). The GH-induced increase in plasma bicarbonate concentration was the consequence of a significant increase in net acid excretion that was accounted for largely by an increase in renal NH+4 excretion sufficient in magnitude to override a decrease in urinary titratable acid excretion. During GH administration, urinary pH increased and correlated directly and significantly with urinary NH4+ concentration. Urinary net acid excretion rates were not different during the steady-state periods of acidosis and acidosis with GH administration. Glucocorticoid and mineralocorticoid activities increased significantly in response to acidosis and were suppressed (glucocorticoid) or decreased to control levels (mineralocorticoid) by GH. The partial correction of metabolic acidosis occurred despite GH-induced renal sodium retention (180 mmol; gain in weight of 1.8 +/- 0.2 kg, P < 0.005) and decreased glucocorticoid and mineralocorticoid activities. Thus GH (and/or insulin-like growth factor I) increased plasma bicarbonate concentration and partially corrected metabolic acidosis. This effect was generated in large part by and maintained fully by a renal mechanism (i.e., increased renal NH3 production and NH+4/net acid excretion).

[Magnetic resonance venogram of the intracranial circulation. Technique, anatomy, indications]. / Venogramma con risonanza magnetica del circolo intracranico. Tecnica, anatomia, indicazioni.

The authors standardized the MR-venography technique in 50 patients for the study of intracranial venous circulation and identified, for each vessel and district, the best acquisitions and rotations. The possible diagnostic applications of MR-angiography were also evaluated. The examinations were performed with a 1.5-T superconductive magnet (Magnetom, Siemens) and linear head coil. Fifty subjects were examined--40 healthy volunteers, 5 patients affected with multiple sclerosis (MS) and 5 patients with pathologic conditions of intracranial venous circulation. The 40 volunteers were studied with FISP 2D techniques; in 10 of them the images were acquired on the coronal plane, in 10 on the sagittal plane, in 10 on the axial plane, and in 10 on the axial plane after a 90 degrees saturation pulse to obtain saturation of the arterial signal. The FISP 3D sequence acquired on the axial plane and after i.v. gadolinium administration was used in the study of the 5 patients affected with MS. In the post-processing all the acquired images were rotated on the axial (z), sagittal (x), and coronal (y) axes, from 0 degrees to 180 degrees with a 15 degrees step. Data correlation showed that the veins of the postero-superior group were well visualized with 2D sequences on the sagittal plane and rotated, in the post-processing, on the z axis 0 degrees-180 degrees and on the coronal axis from -45 degrees to 45 degrees. The veins of the antero-inferior group were clearly demonstrated with 2D sequences acquired on the axial plane and after arterial saturation, rotated in the post-processing on the sagittal and coronal axes from -45 degrees to 45 degrees. Small veins--i.e., veins of the scalp, diploic and emissary veins, and inferior sagittal sinus--were well visualized with 2D sequences acquired on the coronal plane an rotated during post-processing on the z and x axes 0 degrees-180 degrees following i.v. injection of gadolinium. MR-venography is a new technique which can be useful to answer such specific diagnostic questions as the staging of brain neoplasm contiguous to intracranial venous vessels, the study of arteriovenous malformations and thrombosis on intracranial venous sinuses, as it has been demonstrated in 5 pathologic cases.