Christine H. Albini

Triad of Hypopituitarism, Granulomatous Hypophysitis, and Ruptured Rathke's Cleft Cyst

A 19-year-old girl with pituitary insufficiency and a large sella turcica was found to have granulomatous hypophysitis in association with a Rathkes cleft cyst. We think that the inflammatory process represents a foreign body reaction to leakage of cyst contents, with destruction of pituitary tissue.

Quantitation of Urinary Growth Hormone in Children with Normal and Abnormal Growth

ABSTRACT. Urinary growth hormone (GH) excretion was quantitated in 12-h overnight urine collections obtained from 31 control children, ages 3 to 17 yr (group 1); 21 children, ages 5 to 19 yr with GH deficiency (group 2), and 30 subjects, ages 10 to 18 yr with idiopathic growth failure and normal GH stimulation tests (group 3). The output of urinary GH was measured in one acromegalic woman. The authenticity of urinary GH, 22 kDa, was confirmed by high-performance liquid chromatography. The elution pattern of urinary GH was identical to that of biosynthetic and pituitary-derived GH. The immunoreactive profiles characterized by monoclonal immunoradiometric GH assay and standard GH radioimmunoassay were identical. The quantity of GH (mean ± SEM per kg body weight) in group 1 (0.27 ± 0.02 ng/kg) was significantly greater than group 2 (0.08 ± 0.02 ng/kg) or group 3 (0.17 ± 0.02 ng/kg, p < 0.01). Approximately 50% of the subjects in group 3 had urinary GH measurements indistinguishable from those observed in the GH-deficient population. Twelve hypopituitary patients (group 2) excreted significantly greater amounts of urinary GH in the first 12 h after GH administration compared to the baseline period (0.41 ± 0.07 versus 0.12 ± 0.02 ng/kg, p < 0.01). Markedly elevated output of urinary GH (2.0 ng/kg) was documented in one acromegalic patient. The data suggest that measurements of urinary GH may be a useful, simple, and noninvasive screening test for identifying patients with GH deficiency or excess.

Diagnostic significance of urinary growth hormone measurements in children with growth failure: correlation between serum and urine growth hormone.

ABSTRACT: Twelve-h overnight urine and serum samples obtained simultaneously at 20-min intervals were assayed for growth hormone (GH). Ninety-one children, 5 to 16 y (Tanner stage 1 to 3) participated; group 1 were healthy children, group 2 were children with organic GH deficiency, and group 3 had idiopathic growth failure and normal GH stimulation tests. Serum pool GH concentrations in group 1 were similar to those in group 3 (3.3 ± 0.3 versus 3.4 ± 0.2 μg/L); group 2 had significantly lower GH concentrations (1.6 ± 0.2 μg/L). Plasma IGF-I levels were significantly greater in groups 1 (14.2 ± 2.6 nmol/L, p < 0.001) than in groups 2 and 3 (2.6 ± 0.5 and 5.5 ± 0.7 nmol/L, respectively). Urinary GH (mean ± SEM) standardized for body weight (μg/kg) in group 1 (0.31 ± 0.02) was significantly greater than in group 2 (0.14 ± 0.01) and group 3 (0.20 ± 0.01). However, when expressed as μg/mol creatinine, the output of GH was similar in group 1 (4.0 ± 0.3) and group 3 (3.4 ± 0.3); both groups had significantly greater output compared to group 2 (1.3 ± 0.2). Urinary IGF-I (nmol/kg) in group 1 (0.22 ± 0.02) was significantly greater than in group 2 (0.12 ± 0.01) or group 3 (0.07 ± 0.01). Urinary GH correlated with serum pool GH concentration (r = 0.64, p < 0.001). Although urinary GH output reflects endogenous GH secretion, the overlap between groups 1 and 3 precludes using urinary GH measurements as a diagnostic test for GH deficiency in children with idiopathic growth failure.

Comparison of Urinary Growth Hormone and IGF-I Excretion in Small- and Appropriate-for-Gestational-Age Infants and Healthy Children

ABSTRACT: The output of urinary growth hormone (GH) and IGF-I were quantitated by RIA in 12-h urine collections obtained from infants who were preterm, small for gestational age (PT-SGA, n = 13); preterm, appropriate for gestational age (PT-AGA, n = 27); full term, small for gestational age (FT-SGA, n = 13); and full term, appropriate for gestational age (FT-AGA, n = 29); and from normal children (n = 33). The amounts of GH and IGF-I (mean ± SEM) excreted by the PT-SGA and FT-SGA infants were not significantly lower than those excreted by the PT-AGA and FT-AGA groups, respectively [GH (μg/kg): PT-SGA 13.7 ± 3.1 versus PT-AGA 14.0 ± 2.2, FT-SGA 7.8 ± 2.4 versus FT-AGA 6.6 ± 1.8; IGF-I (nmol/kg): PT-SGA 0.52 ± 0.09 versus PT-AGA 0.53 ± 0.04, FT-SGA 0.31 ± 0.05 versus FT-AGA 0.35 ± 0.04]. All infant groups exhibited significantly greater outputs of urinary GH and IGF-I compared with the children (p < 0.01). The plasma concentrations of GH in all infant groups were high, whereas the plasma IGF-I levels were low. Microalbumin and β-2 microglobulin excretion did not correlate with urinary GH and IGF-I output. Despite the higher microalbumin output in FT babies, urinary GH and IGF-I excretion was lower in these groups. The high plasma and urinary GH levels in the presence of increased urinary IGF-I output suggest that production of these peptides in early life is increased and they may reflect the hormonal mechanisms controlling the rapid somatic growth observed in early infancy. However, we cannot rule out the possibility that urinary IGF-I output is a reflection of renal IGF-I synthesis rather than generalized IGF-I production. Based on the comparison of urinary GH and IGF-I excretion in SGA and AGA infants, it appears that postnatal production of these peptides in SGA infants is not impaired.

Microalbuminuria in an Adolescent Cohort With Insulin-Dependent Diabetes Mellitus

To document the incidence of microalbuminuria in children and adolescents with longstanding insulin-dependent diabetes mellitus (IDDM) and to compare the clinical characteristics and determinant risk factors of those with and without microalbuminuria, 135 adolescent patients with IDDM for 5 years or longer were evaluated. The study population was divided on the basis of microalbumin excretion into normal (<20 μg/min), incipient (20-200 μg/min), and overt (>200 μg/min) nephropathy groups. There were 106 patients in the normal group, 24 patients in the incipient group, and five in the overt nephropathy group. Glycosylated hemoglobin, cholesterol concentration, and glomerular filtration rate (GFR) were analyzed. The incidence of incipient and overt nephropathy was 17.8% and 3.7%, respectively. Mean cholesterol concentration in the incipient and overt nephropathy groups (208 ± 39 mg/dL [5.4 ± 1.0 mmol/L] ) and 227 ± 49 mg/dL [5.9 ± 1.3 mmol/L] , respectively) was significantly higher than the normal group (186 ± 37 mg/dL [4.8 ± 0.9 mmol/L] P<0.05). Similarly, systolic and diastolic blood pressures were significantly higher in the incipient and overt nephropathy groups compared to the normal group. This study confirms the high incidence of incipient and overt nephropathy in adolescents with IDDM early in the course of the disease.

Urinary Excretion of IGF-I and Growth Hormone in Children With IDDM

Objective To compare the urinary output of insulinlike growth factor I (IGF-I) and growth hormone (GH) in prepubertal and pubertal children with insulin-dependent diabetes mellitus (IDDM) versus nondiabetic subjects and to analyze the relationship between the urinary excretion of these peptides and degree of metabolic control. Research Design and Methods Group 1 included 30 IDDM patients who had had diabetes for 4.9 ± 0.7 yr and had normal renal function (mean age 11.6 ± 0.9 yr); group 2 consisted of 31 control subjects (mean age 9.2 ± 0.6 yr). Sensitive radioimmunoassays were used to measure IGF-I and GH in urine aliquots from 12-h timed overnight collections that had been dialyzed, concentrated 50-fold, and lyophilized. Results Significantly lower IGF-I and GH outputs per kilogram body weight per 12 h were observed in IDDM subjects compared with control subjects. When data were expressed per kilogram of body weight, no difference was observed between the urinary output of IGF-I and GH between prepubertal and pubertal subjects within group 1 or group 2. The prepubertal children had significantly lower HbA1 than the pubertal population; however, no correlation was found between urinary output of IGF-I or GH and HbA1. A positive correlation was observed between urinary IGF-I and GH (r = 0.85, P < .001). Conclusions Patients with long-standing IDDM excrete significantly lower urinary levels of IGF-I and GH compared with normal subjects. Serial measurements of these peptides from onset of IDDM are needed to define whether the changes observed are present at diagnosis or are secondary to duration of disease.

Diagnostic value of the growth hormone—releasing factor stimulation test

Growth hormone (GH) responses to growth hormone‐releasing factor (GRF) were evaluated in 55 children with growth failure. The study groups consisted of group 1, severe GH deficiency; group 2, partial GH deficiency; group 3, patients with prior cranial radiation for nonpituitary brain tumors; and group 4, children with idiopathic growth failure. Children in group 1 were unresponsive to GRF (mean GH peak ± SEM, 1.6 ± 0.5 ng/ml). Higher GH responses to GRF were observed in both groups 2 (17.2 ± 4.1 ng/ml) and 3 (10.4 ± 2.8 ng/ml). The highest GH responses to GRF were observed in group 4 (35.9 ± 4.3 ng/ml). ANOVA revealed a significant difference between groups (F = 12.9; df = 3; p < 0.01), and further analysis by the Scheffe and Student‐Newman‐Keuls tests revealed that group 4 was significantly higher than groups 1, 2, or 3 (p < 0.05). These data suggest that GRF unresponsiveness is a reliable predictor of severe GH deficiency. In patients with partial GH deficiency or idiopathic growth failure, the GRF gives semiquantitative information about somatotrope responsivity to exogenous stimulation.

Etanercept Treatment in Children With New-Onset Type 1 Diabetes: Pilot Randomized, Placebo-Controlled, Double-Blind Study Response to Peters

We thank Dr. Peters (1) for his thoughtful comments regarding our study (2). Dr. Peters suggests that etanercept may effect the partial remission period of type 1 diabetes by mediating declines in autoantibodies, GAD-65 in particular. Clinical data supports the concept that titer and number of autoantibodies correlates with accelerated β-cell demise and a lower likelihood of clinical remission compared with individuals who tested negative for diabetes-associated …

Urinary Growth Hormone and Insulin-like Growth Factor I Effects of Growth-Hormone Injection Schedule

Urinary growth hormone (GH) and insulin-like growth factor I (IGF-1) excretion profiles were compared in children receiving biosynthetic GH. Group 1 included 18 healthy controls. Group 2 included nine children given biosynthetic GH three times a week. Group 3 included 14 children given daily GH injections. Overnight urine samples were collected for three consecutive nights in all groups. No significant day-to-day variation in urinary GH output was observed in group 1. In group 2, urinary GH output was significantly higher on day one following injection than on days two and three. Urine GH outputs in group 2 were significantly lower on days two and three than the values observed on all days in group 3. Throughout the three-day study, subjects in group 3 excreted similar amounts of GH significantly higher than those of controls. Urinary IGF-I output (nmol/kg) was similar on all three study days in groups 1 and 3. Group 2 had significantly lower urinary IGF-I output on day three compared with day one. Urinary IGF-I output on day three was also significantly lower in group 2 than in group 3. We conclude that urinary GH and IGF-I outputs are influenced by the frequency of GH administration.

Disorders of sex development: management of gender assignment in a preterm infant with intrauterine growth restriction.

We describe how a gender specialist team managed the case of a disorder of sex development in a preterm infant where definitive diagnosis and gender assignment were delayed due to complications of prematurity, anemia, and severe intrauterine growth restriction.