Raul Gutman

Twin pregnancy in a patient with Cushing's disease

Cushing’s syndrome (CS) is unusual in pregnant patients and difficult to diagnose because of the changes in cortisol metabolism normal in pregnancy. It is associated with increased maternal and fetal morbidity, including high rates of miscarriage or premature delivery, requiring careful endocrine and obstetric management. Since first reported, only 76 cases have been described, of which only 40% were the pituitary type (Cushing’s disease [CD]) compared with 70%‐ 80% in nonpregnant patients (1‐3). We report a case of CD in a woman bearing twins in particularly adverse circumstances.

Effect of therapy with a new glucocorticoid, deflazacort, on linear growth and growth hormone secretion after renal transplantation

Deflazacort is an oxazoline compound derived from prednisolone with similar antiinflammatory effects but fewer side effects. We studied changes in kidney function, growth velocity, weight/height ratio, and growth hormone secretion before and a year after substitution of deflazacort for methylprednisone in nine patients aged 9 to 15 years, 4 years after renal transplantation; all were in Tanner pubertal stage 1. Methylprednisone (mean +/- SEM: 0.2 +/- 0.02 mg/kg per day) was replaced by deflazacort (0.3 +/- 0.03 mg/kg per day) for a mean period of 15 months. Serum creatinine and calculated creatinine clearance did not change significantly during deflazacort treatment. Growth velocity increased from 1.5 +/- 0.3 to 3.2 +/- 0.5 cm/yr (p < 0.005) in the nine patients. Weight/height ratio decreased from 28.4% +/- 8.5% to 16% +/- 6.7% (p < 0.005). Cushingoid appearance decreased in all patients. Mean spontaneous growth hormone secretion increased from 2.5 +/- 0.4 to 4.4 +/- 1.2 ng/ml (p < 0.05). Our findings indicate that immunosuppressive treatment with deflazacort is as effective as methylprednisone and is associated with fewer side effects.

Evidence of hypothalamic-pituitary thyroid abnormalities in children with end-stage renal disease*

Patients with end-stage renal disease may have abnormalities of growth and of gonadal and thyroid hormones, so we attempted to determine the mechanisms that may be involved in the altered thyroid function. We evaluated serum thyroid hormone levels, their changes immediately after hemodialysis, the serum thyrotropin (thyroid-stimulating hormone (TSH) response to thyrotropin releasing hormone, and the circadian pattern of serum TSH in nine children with end-stage renal disease who were between 7 1/2 years and 17 years 1 month of age. Seven patients had been receiving hemodialysis for a median of 3.3 years; the other two were receiving continuous ambulatory peritoneal dialysis. Four patients had low serum total thyroxine (T4) values, and all nine had low free T4 values. Mean concentrations of total T4, free T4, and total triiodothyronine (T3), which were significantly less than normal before hemodialysis, returned to normal levels immediately after dialysis. Postdialysis thyroid hormone increases did not correlate with the decrease in weight or the increase in hematocrit observed immediately after dialysis. All but one patient had basal TSH levels within the normal range. Three patients had a deficient TSH response to thyrotropin releasing hormone, and the TSH response was prolonged in all of them. The mean (+/- SD) nocturnal TSH surge was 50 +/- 68%. Five of the eight patients studied had a nocturnal TSH surge below the normal range (95% confidence limits 47% to 300%). Serum free T4 values correlated with the TSH nocturnal surge (r, 0.73; p less than 0.05). Our findings support the hypothesis that some patients with end-stage renal disease have central hypothyroidism.

CorrespondenceTwin pregnancy in a patient with Cushing’s disease

Cushing’s syndrome (CS) is unusual in pregnant patients and difficult to diagnose because of the changes in cortisol metabolism normal in pregnancy. It is associated with increased maternal and fetal morbidity, including high rates of miscarriage or premature delivery, requiring careful endocrine and obstetric management. Since first reported, only 76 cases have been described, of which only 40% were the pituitary type (Cushing’s disease [CD]) compared with 70%‐ 80% in nonpregnant patients (1‐3). We report a case of CD in a woman bearing twins in particularly adverse circumstances.

Growth Hormone-Insulin-Like Growth Factor-I (IGF-I) Axis in Prepubertal Children with Chronic Renal Failure

UNLABELLED The hypothalamic-pituitary insulin-like growth factor I (IGF-I) axis was evaluated in 12 children with chronic renal failure (CRF) aged 3.2 to 16.5 yr (mean 9.5) on chronic dialysis, and in 13 renal transplantation patients aged 7.5 to 15.0 yr (mean 11.1). Height standard deviation score (SDS) was -2.8 +/- 0.5 (mean +/- SE) and -3.0 +/- 0.3 SDS (p = NS), and growth velocity was 3.7 +/- 0.4 and 1.5 +/- 0.3 cm/year (p < 0.01), respectively. Mean nocturnal growth hormone (mean GH) and number of pulses > 5 ng/ml in CRF and transplantation children were 4.2 +/- 0.8 vs 2.4 +/- 0.3 ng/ml, p = 0.08 and 1.7 +/- 0.2 vs 1.0 +/- 0.2, p < 0.05, respectively. In transplant children there was a positive correlation between mean GH and growth velocity (p < 0.02). GH peak response and the area under the curve post GH releasing hormone test were significantly higher in CRF and transplant children treated with deflazacort (new steroid derived from prednisolone) vs transplant children treated with methylprednisone. Mean serum IGF-I levels were -0.5 +/- 0.2 SDS for chronological age (CA) in CRF patients and +0.8 +/- 0.2 SDS(CA) in transplant patients, p = NS. In the latter, serum IGF-I values were positively correlated with growth velocity (p < 0.02) and negatively correlated with methylprednisone dose (p < 0.05). CONCLUSIONS Patients with CRF and growth retardation have a higher number of GH peaks and slightly elevated mean GH levels compared to transplant patients. After renal transplantation GH secretion may be influenced by glucocorticoids as shown by the lower GH response to GHRH which improved with deflazacort and the inverse correlation between methylprednisone dose and IGF-I levels.

Thyroid Function and Serum IGF-1 in Children Before and After Liver Transplantation

We report results of serum thyroid hormone and IGF-1 concentrations in 20 children, 1.2 to 13.6 years old, with various degrees of chronic liver dysfunction (CLD), before and after successful orthotopic liver transplantation (OLT). Ten children presented with moderate chronic liver disease (CLD-M) with prothrombin time (PT) > 50% and serum albumin concentration > 3 g/dl; 7 children had severe chronic liver disease (CLD-S) with PT < 50% and serum albumin concentration < 3 g/dl; and 7 children who had received an OLT, who had normal liver function at the time of the study. Four of the latter group were also studied before OLT. Patients with CLD-M had normal mean +/- SD serum levels of total T3 (2.0 +/- 0.7 nmol/l), total T4 (125 +/- 25.9 nmol/l) and fT4 concentrations (16 +/- 2.8 pmol/l). In contrast, children with CLD-S showed a significant decrease in thyroid hormones together with normal basal TSH values (T3 0.8 +/- 0.0 nmol/l; T4 45.6 +/- 19.5 nmol/l; fT4 7.4 +/- 1.1 pmol/l; TSH 3.8 +/- 0.9 mU/l). Patients who received a successful OLT showed mean peripheral thyroid hormone concentrations significantly higher than CLD-S patients (T3 1.7 +/- 0.7 nmol/l, p < 0.005; T4 92.8 +/- 18.2 nmol/l, p < 0.001; fT4 14.5 +/- 3.1 pmol/l, p < 0.001). A significant correlation was found between thyroid hormone levels and PT or serum albumin. In the nine patients with CLD-M and CLD-S in whom serum IGF-1 concentration was measured, values found (mean +/- SD 0.08 +/- 0.05 U/ml) were below the 95% confidence limit of matched controls.

Hypothalamic-pituitary thyroid abnormalities in children after renal transplantation

Patients with a successful renal transplant may have abnormalities in thyroid function. We evaluated serum thyroid hormone levels, serum thyrotropin (TSH) response to thyrotropin-releasing hormone (TRH), and the circadian pattern of serum TSH in 18 children aged 6.6−19.4 years (median 12.6 years), 4.0±2.9 years after renal transplantation. In 14 children, immunosuppressive therapy included methylprednisone [mean (±SD) 0.17±0.05 mg/kg per day], while in 11 it included deflazacort (0.32±0.1 mg/kg per day). Seven children were studied twice, under methylprednisone and again while on deflazacort therapy. Mean total and free thyroxine (T4) values were significantly below the mean control levels (total T4 108.5±21.5 vs. 118.7±22.1 nmol/l, P<0.05 and free T4 14.4±4.0 vs 18±4.9 pmol/l, P<0.001). Morning basal TSH levels were within the normal range. The mean TSH increment after TRH was 4.4±3.5 mU/l, significantly lower than that of controls (10.8±4.26, P<0.001). Of 7 patients on methylprednisone, 4 had nocturnal TSH surges below the normal range (95% confidence limits 47%–300%); this occurred in 3 of 8 patients on deflazacort therapy. The TSH response to TRH was correlated with deflazacort dose. Patients on methylprednisone and deflazacort therapy had similar thyroid alterations. Our findings support the hypothesis that after renal transplantation some children have hypothalamic-pituitary thyroid abnormalities in which glucocorticoids may play a significant role.