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D M Hoffman

Publications and source records attributed to D M Hoffman.

At least 19 recordsLinked to original sources
PubMed2001

Oral estrogen antagonizes the metabolic actions of growth hormone in growth hormone-deficient women.

We have determined whether oral estrogen reduces the biological effects of growth hormone (GH) in GH-deficient (GHD) women compared with transdermal estrogen treatment. In two separate studies, eight GHD women randomly received either oral or transdermal estrogen for 8 wk before crossing over to the alternate route of administration. The first study assessed the effects of incremental doses of GH (0.5, 1.0, 2.0 IU/day for 1 wk each) on insulin-like growth factor I (IGF-I) levels during each estrogen treatment phase. The second study assessed the effects of GH (2 IU/day) on lipid oxidation and on protein metabolism using the whole body leucine turnover technique. Mean IGF-I level was significantly lower during oral estrogen treatment (P < 0.05) and rose dose dependently during GH administration by a lesser magnitude (P < 0.05) compared with transdermal treatment. Postprandial lipid oxidation was significantly lower with oral estrogen treatment, both before (P < 0.05) and during (P < 0.05) GH administration, compared with transdermal treatment. Protein synthesis was lower during oral estrogen both before and during GH administration (P < 0.05). Oral estrogen antagonizes several of the metabolic actions of GH. It may aggravate body composition abnormalities already present in GHD women and attenuate the beneficial effects of GH therapy. Estrogen replacement in GHD women should be administered by a nonoral route.

Administration, Cutaneous↗
PubMed2000

Intratumoral interleukin 2 for renal-cell carcinoma by direct gene transfer of a plasmid DNA/DMRIE/DOPE lipid complex.

Metastatic renal-cell carcinoma (RCC) is not responsive to conventional cytotoxic chemotherapy, but a subset of patients achieve a durable remission with the use of interleukin-2 (IL-2). IL-2 is currently the only Food and Drug Administration (FDA)-approved treatment for metastatic RCC, and it benefits 10-20% of those who receive it. However, it is accompanied by significant, occasionally life-threatening toxicity. Attempts to maintain the efficacy of IL-2 while minimizing systemic side effects have led to the development of IL-2 gene therapies. Leuvectin is a plasmid DNA/lipid complex composed of a plasmid DNA expression vector (VCL-1102, 30) encoding human IL-2 complexed in a 5:1 mass ratio with DMRIE/DOPE lipid (1,2-dimyristyloxypropyl-3-dimethylhydroxyethyl ammonium bromide/dioleoylphosphatidyl ethanolamine), which has been developed for the treatment of malignancy. DMRIE/DOPE is a cationic lipid that has been shown to facilitate in vitro transfection of plasmid DNA. It has been demonstrated that in vitro transfection with the IL-2 plasmid DNA/DMRIE/DOPE complex results in the expression of sustained levels of biologically active IL-2. Established human tumor cell lines and primary human tumor cells obtained from biopsies are readily transfected in vitro, resulting in the expression of IL-2. Following in vitro transfection, IL-2 expression has been found to persist for up to several weeks in primary tumor cells. In preclinical efficacy studies in a murine model of renal-cell carcinoma the direct intratumoral administration of an IL-2 plasmid DNA/DMRIE/DOPE complex resulted in complete tumor regression in the majority of mice. In preclinical animal-safety studies, repeated administration of Leuvectin was safe and well tolerated. Following these promising preclinical trials, Leuvectin has been taken into clinical trial. The results of two early studies indicate that Leuvectin is safe, is free of systemic toxicity, and has biologic activity.

Aged↗
PubMed2000

Adoptive cellular therapy.

We provide a current review of adoptive cellular therapy in the management of metastatic renal cell carcinoma. A comprehensive literature review of peer-reviewed articles on the development and use of adoptive cellular immunotherapy was performed. Renal cell carcinoma is a highly immunogenic tumor that has proven resistant to standard cytotoxic chemotherapy, but has shown reproducible response to immune-based therapy. In an effort to improve responses, a variety of adoptive cellular strategies have been devised and tested in the setting of metastatic disease. Among the techniques developed, the use of lymphokine-activated killer (LAK) cells, autolymphocyte therapy (ALT), and tumor-infiltrating lymphocytes (TIL) have been the best studied. While further trials are ongoing, thus far, these approaches have not consistently shown benefit in comparison to standard immune-based treatment with biologic response modifiers, most importantly, high-dose bolus interleukin-2 (IL-2). Future approaches, including the use of dendritic cells (DC) to facilitate the development of tumor vaccines, are encouraging. Advanced renal cell carcinoma continues to inspire research of promising new cellular immunotherapeutics. The experience with LAK, ALT, and TIL has greatly increased our understanding of tumor immunobiology, and has led to the ongoing development of new technology, including DC, vaccine, and antibody therapy.

Adjuvants, Immunologic↗
PubMed1998

Limitations of routine spiral computerized tomography in the evaluation of blunt renal trauma.

PURPOSE: We have observed that injury to the renal collecting system may be missed during routine abdominal spiral computerized tomography (CT) for trauma. A definitive protocol for spiral CT has been established to identify all cases of renal collecting system injury. MATERIALS AND METHODS: A retrospective review of 35 consecutive cases of blunt renal trauma evaluated with spiral CT between 1994 and 1997 at our Level I trauma center was performed. Each patient received 100 cc intravenous contrast at 2 cc per second. There was a 60-second delay after the start of contrast infusion before scanning was initiated. RESULTS: Of the 35 cases 3 (8.6%) injuries to the renal collecting system were detected on delayed scans obtained after the initial CT failed to demonstrate contrast extravasation. Therefore, at our institution we have modified the protocol for spiral CT for abdominal trauma by repeating scans of the kidneys after the initial scans are completed. CONCLUSIONS: Injury to the renal collecting system may be missed during routine spiral CT, thereby incorrectly under staging renal trauma. In all cases of suspected blunt renal trauma evaluated with spiral CT repeat scans of the kidneys should be performed.

Adolescent↗
PubMed1998

How is whole body protein turnover perturbed in growth hormone-deficient adults?

Adult patients with GH deficiency have reduced lean body mass (LBM), muscle mass, and muscle strength, suggesting an underlying abnormality of protein metabolism. As acute GH administration has previously been reported to decrease protein oxidation and increase protein synthesis in GH-deficient (GHD) adults, we investigated whether the converse might occur in untreated GH deficiency by undertaking studies of whole body protein turnover in 10 GHD and 13 normal subjects using a 3-h primed constant infusion of 1-[13C]leucine. Dual energy x-ray absorptiometry was used to quantify LBM and fat mass (FM). In normal subjects, LBM was the major, independent determinant of leucine appearance (Ra; r=0.80; P=0.0009), leucine oxidation (r=0.81; P=0.0008), and leucine incorporation into protein (r=0.75; P= 0.003). However, in an analysis of covariance, FM was also a significant independent determinant of leucine Ra (P=0.002) and leucine incorporation into protein (P=0.003). After correcting for LBM and FM, GHD patients had significantly reduced rates of leucine Ra (109.9+/-4.4 vs. 125.5+/-3.7 micromol/min, respectively; P=0.02) and leucine incorporation into protein (87.0+/-3.9 vs. 100.3+/-3.3 mmol/ min; P=0.02) compared to normal subjects. There was no significant difference in the corrected rates of leucine oxidation between the two groups (22.9+/-1.3 vs. 25.2+/-1.0, GHD vs. normal; P=0.20). In summary, GHD adults have reduced rates of protein synthesis and protein breakdown, but normal rates of irreversible oxidative loss; these findings are discordant with what was predicted from the acute changes in protein metabolism observed with GH administration. We conclude that normalization of protein oxidation may be a homeostatic mechanism that operates to constrain protein loss in GHD adults.

Adipose Tissue↗
PubMed1996

Short-term growth hormone (GH) treatment of GH-deficient adults increases body sodium and extracellular water, but not blood pressure.

Initiation of GH treatment in adults is frequently complicated by the development of symptomatic fluid retention. To investigate the mechanism and extent of fluid retention that occurs with dosages of GH used in the treatment of GH-deficient adults, we conducted a double blind study in which seven GH-deficient patients (aged 24-74 yr) each received in random order daily sc injections of placebo, a physiological dose of GH (0.04 U/kg, low dose), and a supraphysiological dose of GH (0.08 U/kg, high dose) for 7 days, separated by 21-day washout periods. On the seventh day, measurements were made of serum insulin-like growth factor I, body weight, exchangeable sodium, plasma volume, angiotensinogen, PRA, aldosterone, atrial natriuretic peptide (ANP), and mean 24-h ambulatory heart rate and blood pressure. GH significantly increased mean insulin-like growth factor I levels from 105 +/- 11 to 304 +/- 45 micrograms/L during low dose treatment (P = 0.006) and 400 +/- 76 micrograms/L during high dose treatment (P = 0.004). High dose GH caused a 1.2 +/- 0.3 kg increase in body weight (P = 0.01) and a 193 +/- 65 mmol increase in exchangeable sodium (P = 0.008). Low dose GH had a lesser effect, with no significant increase in body weight, but an increase in exchangeable sodium of 113 +/- 37 mmol (P = 0.02). Plasma volume was not significantly affected by GH treatment. Mean supine angiotensinogen levels were significantly higher during both GH treatments compared to placebo (low dose, P = 0.017; high dose, P = 0.028) as were mean supine PRA levels (low dose, P = 0.0002; high dose, P = 0.0025). Supine angiotensin II, aldosterone, and ANP levels were not significantly affected by GH treatment. There was no significant change from placebo in any of the sodium-regulating hormones in the erect posture. The mean 24-h heart rate was significantly higher during low dose (82 +/- 2 beats/min; P = 0.0001) and high dose (88 +/- 3 beats/min; P = 0.0001) GH treatment than during placebo (67 +/- 3 beats/min). However, no significant change in mean 24-h systolic or diastolic blood pressure was observed. In summary, acute GH administration using doses currently employed in treating adults causes a dose-related increase in body weight and body sodium, but no associated increase in blood pressure. We conclude that 1) sodium retention is a physiological effect of GH, but does not cause an acute rise in blood pressure; and 2) the mechanism of sodium and fluid retention is not primarily due to enhanced aldosterone secretion or inhibition of ANP release, but more likely to a direct renal tubular effect.

Adult↗
PubMed1996

A highly sensitive growth hormone (GH) enzyme-linked immunosorbent assay uncovers increased contribution of a tonic mode of GH secretion in adults with organic GH deficiency.

The limited sensitivity of conventional GH assays has impeded a better understanding of the pathophysiology of GH secretion. In normal subjects, interpulse GH levels often fall below assay sensitivity, making it unclear whether secretion stops or is maintained at a tonic level below assay detectability. In patients with severe organic GH deficiency (GHD), GH levels are mostly undetectable. Using an ultrasensitive GH enzyme-linked immunosorbent assay to measure 24-h integrated GH concentrations, we recently provided evidence that these patients secrete low, but measurable, amounts of GH. In this report, we apply the same assay to characterize and compare 24-h GH profiles obtained by 20-min sampling in 10 subjects with organic GHD and 10 normal subjects matched for age, sex, and body mass index. With deconvolution analysis, which provides estimates of GH secretion and half-life, our aim was to determine 1) whether normal GH secretion is exclusively pulsatile, 2) how GH is secreted in subjects with organic GHD, and 3) the attributes of GH secretion that determine circulating insulin-like growth factor I (IGF-I) levels. All samples, including nadirs, from GHD subjects were well within the assay detection limit (1 ng/L). Peak 24-h GH levels in GHD subjects were lower and did not overlap those in the normal subjects. Nadir GH concentrations were significantly lower in GHD subjects (14 +/- 5 vs. 43 +/- 9 ng/L; P = 0.008), but the range overlapped that of normal subjects. Endogenous GH half-life did not differ significantly between the two groups. Normal subjects secreted GH in a mixed pulsatile and tonic mode, with pulsatile secretion accounting for 93 +/- 2% of the total production. Total daily GH production in GHD was approximately 5% of the production in matched normal subjects. This difference resulted from a greater reduction in the pulsatile (by 96%) than in the tonic (by 47%) component, so that the fractional daily contribution by tonic GH release in GHD subjects was markedly greater. There was a significant relationship between pulsatile GH secretion and serum IGF-I levels for the two groups combined. In summary, 1) peak, but not nadir, GH levels were completely segregated between GHD and normal subjects; and 2) although normal subjects secrete GH in a tonic and pulsatile mode, both modes are reduced in organic GHD, with a proportionately greater reduction in pulsatile secretion. We conclude that 1) nadir GH levels are not sufficiently discriminatory to be useful for the diagnosis of GH deficiency; 2) normal GH profiles arise from a mixed pattern of tonic and pulsatile secretion, whereas reduced GH secretion in organic GHD arises primarily from a marked diminution in the amount of pulsatile GH release; and 3) pulsatile GH release is a significant regulator of the IGF-I level in normal and GHD subjects.

Adult↗
PubMed1996

Metabolic actions of growth hormone in man.

GH continues to be produced after the cessation of childhood growth and is the most abundant pituitary hormone in the adult pituitary. There is strong evidence that GH continues to exert significant biological effects on body metabolism in adult humans. The actions of GH may be direct or indirectly mediated by IGF-1. The direct actions of GH impart major effects on glucose, lipid and sodium homeostasis. GH administration causes hyperinsulinaemia and impairs the ability of insulin to suppress hepatic glucose production and to stimulate glucose uptake and oxidation. GH enhances fat utilisation by stimulating lipolysis and fat oxidation. The significance of these effects is reflected in the finding of increased adiposity in GH deficiency (GHD) and reduced fat mass in acromegaly. GH causes sodium retention which occurs in part through activation of the renin-angiotensin system. Extracellular water volume is diminished in GHD and increased in relation to the extent of GH excess in acromegaly. Lean body mass is reduced in GHD and restored by GH treatment. The anabolic actions of GH are mediated by IGF-1. Studies of whole body protein metabolism show that this occurs through the stimulation of protein synthesis, reduction in protein oxidation but not inhibition of protein breakdown. GH plays an important role in the regulation of substrate metabolism and body composition in man.

Adult↗
PubMed1995

Defining growth hormone deficiency in adults.

The absence of a distinct clinical syndrome calls for a strategy to reliably identify patients with hyposomatotropism. However, there is no consensus as to the most appropriate method of defining growth hormone (GH) deficiency in adults. Since GH secretion falls with senescence and is also reduced by obesity, both of these factors must be controlled for in such an evaluation. We have investigated the relative diagnostic merits of measuring (1) peak GH response to insulin-induced hypoglycemia (ITT), (2) mean 24-hour GH concentration derived from 20-minute sampling (IGHC), (3) serum IGF-I levels, and (4) serum insulin-like growth factor (IGF)-binding protein-3 (IGFBP-3) levels. These tests were undertaken in 23 patients considered GH-deficient from extensive organic pituitary disease and in 35-sex-matched normal subjects of similar age and body mass index. The ITT was the only test capable of distinguishing patients with organic GH deficiency from matched normal subjects. The sensitivity of the GH radioimmunoassay (0.2 ng/mL) limited the utility of IGHC measurements, since many subjects from both groups had undetectable values. Using a GH assay with a 100-fold greater sensitivity, we found a better but still incomplete separation of values between the two groups. There was a significant overlap of IGF-I and IGFBP-3 values, with only a third of GH-deficient subjects having low IGF-I values. The limitation of IGF-I has been confirmed by others, although its sensitivity as a diagnostic test is greater in young adults. We conclude that organic GH deficiency in adults can be reliably diagnosed by the ITT.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Adults with growth hormone deficiency have abnormal body composition but normal energy metabolism.

We compared body composition and energy metabolism in a cross-sectional study involving 21 GH-deficient (GHD) and 29 normal adults. Fifteen subjects from each group were pair-matched for age, sex, height, and weight. Comparison of body composition by dual energy x-ray absorptiometry in the 15 pairs showed that GHD subjects had a significantly greater fat mass (23.9 +/- 1.8 vs. 19.8 +/- 2.6 kg; P = 0.02), lower bone mineral content (2.6 +/- 0.1 vs. 2.9 +/- 0.1 kg; P = 0.06), and lower fat-free soft tissue mass (FFSTM; 45.8 +/- 2.5 vs. 48.9 +/- 2.6 kg; P = 0.02). To determine which subcompartment changes were responsible for the reduced FFSTM in GH deficiency, extracellular water (ECW) was measured by 24Na dilution in 11 of the subject pairs, and body cell mass (BCM) was derived by subtracting ECW from FFSTM. The GHD subjects had lower ECW (19.4 +/- 1.0 vs. 21.0 +/- 1.0 kg; P = 0.05) and BCM (26.6 +/- 1.9 vs. 28.6 +/- 2.1 kg; P = 0.08) than their normal counterparts, with the difference approaching statistical significance. When the relationship between ECW and FFSTM was compared in the larger group of 18 GHD and 27 normal subjects, no statistically significant difference was found between the 2 regression lines, indicating that ECW and BCM were proportionately reduced in GH deficiency. Energy expenditure and fuel utilization before and after a standardized mixed meal were measured by indirect calorimetry in 12 matched pairs of GHD and normal subjects. Comparison of energy expenditure and fuel utilization showed no significant difference in fasting or postprandial energy expenditure, or carbohydrate or fat oxidation rates between the two groups. We conclude that GHD adults have an increased FM, a reduced FFSTM due to a proportionate reduction in ECW and BCM, and no detectable disturbance in energy metabolism.

Adult↗
PubMed1995

Evaluation and application of a highly sensitive assay for serum growth hormone (GH) in the study of adult GH deficiency.

Previous work from our laboratory addressing the diagnosis of GH deficiency in adults showed that RIA measurement of the 24-h integrated GH concentration (IGHC) was unable to discriminate between hypopituitary and age-, sex-, and body mass index-matched normal subjects because of the occurrence of undetectable levels (< 200 ng/L) within both groups. In contrast, full separation was achieved using stimulation by the insulin tolerance test (ITT). The data showed no significant relationship between IGHC and insulin-like growth factor-I (IGF-I) within either group. To determine whether limited sensitivity obscured diagnostic and physiological information, we assessed and modified a commercially available enzyme-linked immunosorbent assay (Elegance GH ELISA, Bioclone Australia) to achieve a high sensitivity (1 ng/L) and applied it to the study of IGHC and the relationship to IGF-I in a study group of 30 normal and 19 subjects with severe organic hypopituitarism. Using this assay, the IGHCs from all subjects were detectable and correlated significantly with detectable values obtained by RIA (n = 24; r = 0.80; P = 0.0001). Mean IGHC in normal subjects was significantly higher than that in hypopituitary subjects (852 +/- 131 vs. 97 +/- 28 ng/L), but the IGHCs from the two groups were not completely separate. Twenty-six percent of hypopituitary subjects had IGHC values within the normal range (111-3454 ng/L). IGHC decreased with age in normal subjects. Age stratification improved the separation, but an overlap remained in the young (< 50 yr old) and old (> 50 yr old) groups. Measurement of 12-h nocturnal IGHC levels improved the separation between hypopituitary and normal subjects in the young subjects only. IGHC was significantly related to IGF-I in hypopituitary (r = 0.59; P = 0.0084) and normal subjects (r = 0.55; P = 0.0017) and in the combined groups (r = 0.64; P = 0.0001). The data show that a sensitive ELISA reliably quantifies IGHC in normal and hypopituitary subjects. IGHCs in hypopituitary patients are lower, but not clearly separated from values in normal counterparts despite their having unequivocally impaired GH responses to ITT. We conclude that 1) IGHC in normal subjects can be reliably defined by sensitive ELISAs; 2) the diagnostic utility of the IGHC does not match the reliability or simplicity of an ITT, and 3) GH is a significant regulator of IGF-I in both normal and reduced states of GH secretion.

Adolescent↗
PubMed1995

Energy metabolism and substrate oxidation in acromegaly.

Short term GH administration increases lipid breakdown and oxidation (lipidox) and reduces glucose uptake and carbohydrate oxidation (CHOox). It is not clear whether similar shifts in substrate oxidation occur in acromegaly, and our aim was to investigate this. Using indirect calorimetry, we compared energy expenditure, CHOox, and lipidox in 20 acromegalic patients and 20 normal subjects pair-matched for sex, age, height, and weight. Investigations were performed in the basal state (12-h fast) and during a 75-g oral glucose tolerance test (OGTT). Acromegalic patients had significantly higher fasting glucose levels and greater glucose and insulin responses during an OGTT than normal subjects. Fasting nonesterified free fatty acid and insulin-like growth factor (IGF)-binding protein-1 levels were similar in the two groups, and both were acutely suppressed by oral glucose to the same degree. Basal energy expenditure was significantly greater in the acromegalic patients (1682 +/- 49 vs. 1540 +/- 45 Cal/24 h; P < 0.05), who showed a trend toward higher basal CHOox. Oral glucose resulted in a significantly higher rise in energy expenditure in the normal compared to the acromegalic subjects. During the OGTT, CHOox significantly increased in both groups, but rose to a higher level in the acromegalic patients (177 +/- 10 vs. 138 +/- 9 mg/min; P = 0.004). Oral glucose significantly reduced lipidox in both groups, but lipidox was reduced to a significantly lower level in the acromegalic patients (32 +/- 4 vs. 46 +/- 3 mg/min; P = 0.004). In acromegaly, basal CHOox (r = 0.56; P = 0.01) and postglucose CHOox (r = 0.79; P = 0.0001) were both positively correlated to IGF-I, but not to insulin and/or glucose. In normal subjects, postglucose CHOox was positively correlated to IGF-I. In summary, hyperinsulinemia in acromegaly was associated with higher glucose levels and a blunted thermogenic response to glucose, and displayed no relationship to the pattern of substrate oxidation. CHOox was increased, and lipidox was reduced in acromegaly, and the extent of IGF-I elevation was related to CHOox in the basal and postglucose states. We conclude that 1) the chronic effects of GH excess on substrate oxidation differ from the short term effects of GH administration; 2) impaired insulin action in acromegaly extends to effects on energy expenditure; and 3) IGF-I may be an important regulator of substrate oxidation in acromegaly.

Acromegaly↗
PubMed1995

Do androgens regulate growth hormone-binding protein in adult man?

To determine whether adult serum GH-binding protein (GHBP) is regulated by androgen, serum GHBP concentrations were compared between 20 normal and 18 hypogonadal men matched for age and body mass index, and the effect of im testosterone treatment (250 mg testosterone enanthate) on GHBP levels in the 18 hypogonadal men was studied. Nine of the hypogonadal subjects had coexistent GH deficiency. Serum GHBP concentration was measured by a ligand immunofunctional assay. The mean serum GHBP level in untreated hypogonadal men was not significantly different from that of normal men (0.98 +/- 0.15 vs. 1.17 +/- 0.16 nmol/L). The mean serum insulin-like growth factor I (IGF-I) level was significantly lower in the hypogonadal men (132 +/- 22 vs. 206 +/- 17 ng/mL; P < 0.01). Basal testosterone (3.7 +/- 0.7 nmol/L) in hypogonadal men increased during treatment to a mean level of 29.1 +/- 2.8 nmol/L, which was not significantly higher than that in normal men (22.6 +/- 1.9 nmol/L). The mean serum GHBP level in hypogonadal men fell significantly during treatment to 0.60 +/- 0.11 nmol/L (P = 0.0003), whereas the serum IGF-I level rose significantly to 151 +/- 26 ng/mL (P < 0.04). The decrease in GHBP level was significant in both the GH-sufficient and GH-deficient subjects (P < 0.02 in both instances), whereas the increase in IGF-I level was significant in the GH-sufficient group (199 +/- 22 to 235 +/- 29 ng/mL; P < 0.04) but not in the GH-deficient group (53 +/- 7 to 55 +/- 5 ng/mL; P > 0.8). Thus, serum GHBP is normal in hypogonadal men but is reduced by testosterone treatment irrespective of endogenous GH-secretory status. It was concluded that the effect of testosterone on GHBP is pharmacological and occurs independent of GH mediation.

Adolescent↗
PubMed1994

Diagnosis of growth-hormone deficiency in adults.

There is no consensus as to the most appropriate method of diagnosing growth-hormone (GH) deficiency in adults. We have evaluated the relative diagnostic merits of measuring peak GH response to insulin-induced hypoglycaemia (insulin tolerance test), mean 24 h GH concentration derived from 20 min sampling, serum insulin-like growth factor I (IGF-I) concentrations, and serum IGF binding protein 3 (IGFBP-3) concentrations. These tests were undertaken in 23 patients considered GH deficient from extensive organic pituitary disease, and in 35 sex-matched normal subjects of similar age and body-mass index. Hypopituitary subjects had significantly lower stimulated peak GH, mean 24 h GH, IGF-I, and IGFBP-3 concentrations than normal subjects. The ranges of stimulated peak GH responses were clearly separated between the hypopituitary (< 0.2-3.1 ng/mL) and normal (5.3-42.5 ng/mL) groups, but mean 24 h GH, IGF-I, and IGFBP-3 concentrations overlapped. Mean 24 h GH concentrations were below assay sensitivity in 80% of hypopituitary subjects and 16% of normal subjects. 70% and 72%, respectively, of the IGF-I and IGFBP-3 values in hypopituitary subjects were within the range for normal subjects. We conclude that GH deficiency in adults is most reliably identified by stimulatory testing, and that IGF-I and IGFBP-3 are poor diagnostic tests of adult GH deficiency.

Adolescent↗