Setting up a height surveillance programme: recommendations based on the Hackney growth initiative.
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Anthropometry↗
Biomedical subjects
A M Cotterill
Publications and source records attributed to A M Cotterill.
An international perspective on height surveillance.
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Birth Weight↗
Safety of milk from cows treated with bovine somatotropin.
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Animals↗
Safety of milk from cows treated with bovine somatotropin.
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Animals↗
Insulin-like growth factor binding protein 1 response to acute insulin induced hypoglycaemia in type 1 diabetes.
OBJECTIVES: Insulin is believed to be the prime regulator of insulin-like growth factor binding protein 1 (IGFBP-1) secretion, and in normal subjects acute insulin induced hypoglycaemia exerts a rapid effect on concentrations of IGFBP-1, and may also influence insulin-like growth factor I (IGF-I) concentrations. The rise in IGFBP-1 concentrations in normal subjects following hypoglycaemia has been suggested to be due to suppression of endogenous insulin secretion. We have examined this further by studying diabetics with no endogenous insulin secretion. DESIGN: We have compared the IGFBP-1 response to acute insulin induced hypoglycaemia in normal subjects and patients with Type 1 (insulin dependent) diabetes mellitus. METHODS: Insulin tolerance tests were performed using a bolus of insulin (0.15 U/kg), in six control subjects and six patients with Type 1 diabetes. MEASUREMENTS: Serum levels of IGFBP-1, insulin, glucose, and IGF-I were measured at regular intervals during the insulin tolerance test. RESULTS: Blood glucose fell to a nadir which coincided with the onset of the acute autonomic reaction 'R' in both groups. The basal concentration of IGF-I was significantly lower in the diabetic group at 0.4 +/- 0.1 kU/l, compared to 0.9 +/- 0.1 kU/l in the control group, but there was no significant change in IGF-I concentrations in response to hypoglycaemia in either group. Hypoglycaemia provoked a fall in IGFBP-1 in patients with Type 1 diabetes, from 38 +/- 9 micrograms/l basally to 17 +/- 3 micrograms/l at R + 120 minutes, with a return to basal values of 45 +/- 11 micrograms/l at R + 180 minutes. In the control subjects there was no fall in IGFBP-1, but a significant increase to 71 +/- 14 micrograms/l at R + 180 minutes. CONCLUSION: This difference in the IGFBP-1 response in the presence of a similar glucose response suggests that in Type 1 diabetes there may be different sensitivities to the actions of exogenous insulin on IGFBP-1 regulation.
Adult↗
Improvement of diagnostic criteria in growth hormone insensitivity syndrome: solutions and pitfalls. Pharmacia Study Group on Insulin-like Growth Factor I Treatment in Growth Hormone Insensitivity Syndromes.
A survey to identify children and adolescents with primary growth hormone insensitivity syndrome (GHIS) yielded 38 patients who were positively identified using a scoring system that included five criteria: height, basal growth hormone (GH), GH binding protein, basal insulin-like growth factor I (IGF-I) and the increase of IGF-I after 4 days of GH administration (IGF generation test). Because of an overlap of the accepted and excluded groups with respect to points scored, an attempt was made to improve the scoring system. The new criteria were: height below -3 SDS, basal GH 4 mU/l or above, GH binding below 10%, basal IGF-I and basal IGF binding protein-3 (IGFBP-3) below the 0.1 centile for age, an increase of IGF-I in the IGF generation test less than 15 micrograms/l, and the increase of IGFBP-3 less than 0.4 mg/l. With this scoring system, a clear separation between the accepted and the excluded groups was obtained. IGFBP-3 was included to give the GH-dependent parameters of the IGF system more weight and because the accuracy of IGFBP-3 in the IGF generation tests was greater than the accuracy of IGF-I, when the group of patients with GHIS was compared with a group of patients with GH deficiency. Unexpectedly, the IGF generation test was unable to segregate both cohorts completely. In the GHIS-positive group, a significant correlation was found between basal IGF-I or IGFBP-3 levels corrected for age (SDS) and height SDS (r = 0.49, p < 0.002 and r = 0.61, p < 0.0001, respectively). There was also a significant correlation between the changes of IGF-I or IGFBP-3 in the IGF generation test and height SDS. That is, the patients with a slight response to GH were those with the least growth retardation, suggesting the existence of partial GH insensitivity.
Adolescent↗
The insulin-like growth factor I generation test in the investigation of short stature.
Genotypic and phenotypic heterogeneity in patients with growth hormone (GH) insensitivity syndrome suggests that partial defects exist in the GH receptor. The insulin-like growth factor I (IGF-I) generation test was assessed as a means of identifying partial GH receptor defects in a heterogeneous group of 22 prepubertal children with short stature. In a subgroup of nine patients with peak GH levels of 63.7 +/- 3.7 mU/l during a glucagon tolerance test, the response to the IGF-I generation test was no different from that for the group as a whole (peak GH, 43.3 +/- 4.5 mU/l), despite the fact that this subgroup exhibited a negative relationship between height SDS and peak GH and a positive relationship between height SDS and IGF binding protein-3. This preliminary study therefore suggests that the IGF-I generation test in its present form will not be useful as a primary screening test for partial GH insensitivity. Despite this, the IGF-I generation test has been extremely useful in the confirmation of the diagnosis of GHIS and may therefore also prove useful in the confirmation of partial defects in the GH receptor. A subgroup of short children with peak GH levels above 40 mU/l had some characteristics of partial GH receptor deficiency. These children, to whom GH therapy would not normally be given, may respond better to recombinant human IGF-I.
Body Height↗
Effects of recombinant insulin-like growth factor I on craniofacial morphology in growth hormone insensitivity.
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Adolescent↗
The effect of recombinant human insulin-like growth factor-I treatment on growth hormone secretion in two subjects with growth hormone insensitivity (Laron syndrome).
OBJECTIVE: Growth hormone (GH) secretion is increased in conditions of GH insensitivity such as Laron syndrome, with elevation of both basal and peak levels. We have studied the effect of recombinant IGF-I therapy on the pattern of GH secretion in two subjects with GH insensitivity. SUBJECTS: Two pubertal subjects with GH insensitivity (female, 16.4 years, breast stage 3; male 13.6 years, genital stage 2) were investigated after 6 months of IGF-I therapy (120 micrograms/kg twice daily s.c. at 0800 and 1900 h). GH profiles taken before the start of IGF-I therapy, when both subjects were prepubertal (aged 14.0 and 11.5 years respectively), were used for comparison. METHODS: GH profiles were performed with blood samples taken every 20 minutes between 2000 and 0800 h from an indwelling cannula. MEASUREMENTS: Serum samples were assayed for GH by immunoradiometric assay and IGF-I, IGFBP-1 and insulin by radioimmunoassay. RESULTS: Before IGF-I therapy, GH profile studies demonstrated pulsatile GH secretion. Basal GH was elevated with no value falling below the limit of detection of the assay and an increase in peak levels (maximum 203 and 206 mU/l at 0000 h and 0020 h respectively). After 6 months IGF-I therapy, the GH profiles were significantly different. With the onset of puberty a further increase in GH secretion would have been expected; nevertheless, following administration of IGF-I at 1900 h, GH secretion decreased with a reduction in mean overnight GH levels from 65 to 33 mU/l and 53 to 11 mU/l respectively. GH pulsatility was also suppressed in the two subjects, for the first 3.5 and 6 hours overnight respectively. Pulsatile GH secretion then returned with peak levels reaching 130 and 63 mU/l respectively. Prior to therapy IGF-I levels were at the lower limit of assay detection. On IGF-I therapy serum IGF-I levels reached a peak within 3 hours (298 and 438 micrograms/l) coinciding with the suppression of GH secretion. IGF-I levels fell rapidly overnight to 92 and 101 micrograms/l at 0800 h prior to the next injection. The fall in serum IGF-I coincided with the return of GH secretion. IGFBP-1 levels increased overnight both before and during IGF-I therapy, rising from 24 to 83 and 22 to 110 micrograms/l before therapy and 13 to 60 and 13 to 71 micrograms/l during therapy. This rise in IGFBP-1 appeared to be inversely related to the fall in serum insulin levels overnight and appeared not to be affected by IGF-I therapy. CONCLUSION: GH secretion is suppressed by exogenous IGF-I therapy in GH insensitive subjects. The failure to maintain high serum IGF-I levels overnight, presumably due to a persisting defect in serum IGFBP-3 levels, was associated with an early return of GH secretion. These findings may have implications for the dose and regimen of IGF-I therapy in subjects with growth hormone insensitivity.
Adolescent↗
Suppression of endogenous insulin secretion regulates the rapid rise of insulin-like growth factor binding protein (IGFBP)-1 levels following acute hypoglycaemia.
OBJECTIVES: Recent animal studies have suggested that insulin-like growth factor binding protein (IGFBP)-1 may regulate the insulin-like actions of the circulating IGFs. In man, IGFBP-1 levels change rapidly with nutritional status and are inversely related to changes in insulin. In-vitro studies have shown that both insulin and glucose independently regulate IGFBP-1 secretion in an inverse manner. A rapid rise of serum IGFBP-1 levels following insulin-induced hypoglycaemia suggested that glucose or glucose availability, rather than insulin, may be the major regulator of IGFBP-1. DESIGN: Three separate experiments both in patients and in normal volunteers were designed to examine the possibility that in these extreme circumstances glucose rather than insulin was the predominant regulator of IGFBP-1. METHODS: Insulin tolerance tests (ITT) were performed during the routine assessment of pituitary function in seven patients, four female and three male (mean age +/- SEM 36.8 +/- 6.3 years, range 20.7-69.3 years) with pituitary disease. Hypoglycaemic glucose clamp studies (insulin 2 mU/kg/min for 180 minutes) were performed in five normal volunteers, two female and three male (mean age 33.6 +/- 2.2 years, range 23.5-42.0 years). A three-part infusion study was performed in five volunteers, three female and two male (mean age 22.9 +/- 0.9 years, range 20.8-25.0 years) who received for 45 minutes on three occasions separated by at least 7 days either octreotide (long-acting somatostatin analogue) (1 microgram/min), adrenaline (3 micrograms/min) or control. MEASUREMENTS: Serum levels of IGFBP-1, insulin, glucose, C-peptide and cortisol were measured at varying intervals during the three studies by radioimmunoassay (RIA). RESULTS: Symptomatic hypoglycaemia (1.0 +/- 0.1 mmol/l) occurred at 30 minutes in all patients during the ITT. Serum IGFBP-1 levels rose from 28 +/- 7 to 86 +/- 15 micrograms/l at 180 minutes. During the hypoglycaemic glucose clamp study plasma glucose fell from 4.8 +/- 0.3 to 2.2 +/- 0.3 mmol/l. In contrast to the response observed during ITT, IGFBP-1 levels fell from 22 +/- 6 to 10 +/- 1 microgram/l by 180 minutes. During the octreotide infusion study there was no change in plasma glucose and plasma insulin levels fell from 5.8 +/- 1.9 to < 2.0 mU/l. Serum IGFBP-1 levels rose from 21 +/- 2 to 68 +/- 5 micrograms/l by 180 minutes. There was no change in IGFBP-1 during either the adrenaline infusion or the control study. The rise in IGFBP-1 following the octreotide infusion (68 +/- 5 micrograms/l) was similar to that in the patients undergoing the ITT (86 +/- 15 micrograms/l) (P = 0.3). CONCLUSION: The rapid rise of serum IGFBP-1 levels induced by acute hypoglycaemia could be reproduced in euglycaemic conditions with octreotide when insulin secretion was suppressed, whereas IGFBP-1 levels did not rise with hypoglycaemia induced by a prolonged insulin infusion. These findings suggest that the surprising rise of IGFBP-1 levels observed during ITT is not secondary to changes in glucose. The rapid removal from the portal circulation of endogenous insulin with its inhibitory effect on IGFBP-1 secretion therefore appears to be the likely cause for the rapid rise of IGFBP-1 following an ITT. This conclusion supports the hypothesis that IGFBP-1 may inhibit the insulin-like actions of 'free' IGF when insulin secretion is low and so directly link the availability and hence actions of IGFs to acute but temporary changes in nutritional status.
Acute Disease↗
The regulation of insulin-like growth factor binding protein (IGFBP)-1 during prolonged fasting.
OBJECTIVE: Insulin-like growth factor binding protein (IGFBP)-1 levels increase overnight, being inversely related to changes in insulin. With prolonged fasting IGFBP-1 levels increase further. In animal studies high IGFBP-1 levels increase plasma glucose levels possibly by regulating the insulin-like actions of 'bio-available' plasma IGF. Following prolonged fasting, there is an increase in insulin requirement. A proportion of this reversible insulin resistance may be due to inhibitory effects of high IGFBP-1 levels on IGF action. This study examined the regulation of IGFBP-1 in the presence of reversible insulin resistance. SUBJECTS: Nine normal adult volunteers, seven female and two male (mean age 27.6 +/- SD 2.6 years, range 21.7-46.0 years) of normal body mass index were studied. METHODS: Subjects fasted from 2200 h day 0 to 0900 h day 3 (59 hours), the fast being completed with a 75-g glucose meal. At least one week later, an 11-hour overnight fast was performed, followed by a repeat glucose meal. Blood samples were taken at regular intervals from 0900 h day 1 and for 5 hours during both glucose meal studies via an indwelling cannula. MEASUREMENTS: Serum levels of IGFBP-1, insulin, GH, glucose, IGF-I and cortisol were measured at varying intervals during the fast and both glucose meal studies. RESULTS: Following the initial 11-hour overnight fast IGFBP-1 levels rose from (mean +/- SEM) 32 +/- 5 micrograms/l to reach a maximum of 144 +/- 24 micrograms/l after 32 hours of fasting. IGFBP-1 levels then fluctuated, falling in the morning (93 +/- 8 micrograms/l) and then rising overnight (126 +/- 9 micrograms/l), but not regaining the initial peak levels. The increase of IGFBP-1 from overnight fasting levels was associated with a fall in plasma insulin from 5.7 +/- 0.7 to 2.2 +/- 0.2 mU/l. In comparison, 30 minutes after termination of the fast with the glucose meal, IGFBP-1 levels fell from 120 +/- 11 to 24 +/- 2 micrograms/l within 4 hours. After an overnight fast IGFBP-1 levels fell from 35 +/- 5 to 13 +/- 2 micrograms/l within 3 hours. There was glucose intolerance and increased insulin levels following the glucose meal preceded by the 59-hour fast when compared with the overnight fast. The fall of IGFBP-1 levels after the glucose meal was best expressed, taking into account subject variation, by the following regression equations: Glucose meal preceded by 11-hour fast: log [IGFBP-1] = 1.64-0.255 log [1 h previous insulin] (R2 0.51); Glucose meal preceded by 59-hour fast: log [IGFBP-1] = 1.41-0.265 log [1 h previous insulin] + 0.557 log [current glucose] (R2 0.82). CONCLUSION: In man, insulin appears to regulate circulating IGFBP-1 levels in all circumstances, this regulation being unaffected by the resistance to insulin action induced by prolonged fasting. The high IGFBP-1 levels were statistically related to the higher glucose levels and may have directly contributed to the increased insulin requirement observed after prolonged fasting.
Adult↗
Clinical features and endocrine status in patients with growth hormone insensitivity (Laron syndrome).
Twenty-seven patients with GH insensitivity were identified from 44 possible cases, using a scoring system based on height standard deviation score (SDS), basal GH, insulin-like growth factor-I (IGF-I), IGF-I response to IGF-I generation test, and GH-binding protein (GH-BP) determinations. The 27 cases were from 8 European countries and Australia. Clinical features were as follows: age 2.8-22.6 yr; 12 male, 15 female, 19 prepubertal. Birth weight was median -0.72 SDS (1.75(-)-3.29) and birth length, median -1.59 SDS (0.63(-)-3.63). Hypoglycemia had been documented in 33% of the cases, and micropenis was present in 58% of the males. At assessment, height was median -6.1 SDS (-3.8(-)-10.2), weight was median -3.2 SDS (-0.1 to -5.2), and percentage weight for height, median 111.3 (72-271). Puberty was absent in 2 boys aged 15 yr and in 3 girls aged 13 yr. Bone age was delayed in 19 of the 27 patients. Endocrine investigations showed basal serum GH median 17 micrograms/L (0.5-79), IGF-I values less than 5th percentile, and all except 2, age less than 8 yr, less than 0.1 percentile for age. Percentage increment of IGF-I during IGF-I generation test (hGH 0.1 U/kg body weight daily x 4) did not exceed twice the intraassay coefficient of variation, being less than 0.1 percentile for age. IGF-II was median 135.0 micrograms/L (62-232), all values being less than 5th percentile for age. Insulin-like growth factor binding protein-3 (IGFBP-3) values were median 0.53 mg/L (0.10-1.17 mg/L), all being less than 5th percentile for age. IGFBP-3 values after hGH remained less than 5th percentile. IGFBP-1 values showed the normal fall with age, some being above the normal range; IGFBP-2 values were normal. There was a positive correlation between height SDS and IGF-II SDS (r = 0.66, P < 0.001) and IGFBP-3 (r = 0.64, P < 0.001). Specific binding of [125I]hGH to GH-BP was undetectable in 18 patients and extremely low (< or = 5.6%) in 2. GH-BP was normal (14.2-45.9% radioactivity) in 7 subjects, all female, demonstrating that normal GH-BP does not exclude GH insensitivity.
Adolescent↗
The therapeutic potential of recombinant human insulin-like growth factor-I.
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Adolescent↗
The insulin-like growth factor (IGF)-binding proteins and IGF bioactivity in Laron-type dwarfism.
Laron-type dwarfism (LTD) is caused by a variable defect in the GH receptor gene and is, therefore, an ideal model to study the physiology of the insulin-like growth factors (IGFs) and their binding proteins (IGFBPs) in the complete absence of GH action. In this study we examined the overnight variation of the IGFs, IGFBPs, and IGF bioactivity in two prepubertal subjects with LTD. Subject 1 was a 14-yr-old female, 103 cm tall (-8.3 SD), and subject 2 was a 11.5-yr-old male, 103.6 cm tall (-5.9 SD). Both had serum IGF-I levels below 0.07 U/mL and low constant serum IGF-II levels overnight (185 +/- 10 and 232 +/- 8 micrograms/L), despite high serum GH levels [mean GH, 65 (32.5 micrograms/L) and 53 mU/L (26.5 micrograms/L)]. Serum IGFBP-1 levels increased overnight (from 24 and 22 micrograms/L at 2000 h to 83 and 110 micrograms/L at 0800 h) as serum insulin levels fell [from 19 (136 pmol/L) and 17 mU/L (122 pmol/L) at 2000 h to less than 2 (less than 14 pmol/L) and 5 mU/L (36 pmol/L) at 0800 h] in subjects 1 and 2, respectively. Serum IGFBP-2 levels remained constant overnight, as assessed on Western Ligand blotting and, despite the changes in IGFBP-1, remained the most prominent IGFBP throughout. On size separation, most of the IGF-II (greater than 60%) eluted with IGFBP-2 and the other low mol wt IGFBPs. Serum IGFBP-3 levels were reduced, and IGFBP-3 was not the major IGF carrier in LTD serum, in contrast to normal serum. An IGFBP-3-specific protease that was heat sensitive and cation dependent was identified as the cause of an apparent overnight rise of serum IGFBP-3 levels. No IGFBP-3 variation and no proteolytic activity was seen in normal serum or rapidly separated LTD plasma. Serum IGF bioactivity, measured in a porcine cartilage bioassay, was 0.18 and 0.55 U/mL in subjects 1 and 2; differences in bioactivity between subjects did not relate to serum IGF-II levels, but, rather, to differences in IGFBP-3 levels. Serum IGF bioactivity was not constant overnight and varied in a similar fashion in both subjects 1 and 2, with reduction in bioactivity between 0600-0800 h by 55% and 32%, suggesting the presence of inhibitory factors in the LTD serum; this decrease coincided with the rise in serum IGFBP-1 levels.(ABSTRACT TRUNCATED AT 400 WORDS)
Adolescent↗
The induction of specific proteases for insulin-like growth factor-binding proteins following major heart surgery.
Insulin-like growth factors (IGF-I and IGF-II) circulate bound to specific high-affinity binding proteins (IGFBPs). Recent evidence has shown that in pregnancy and severe illness, specific proteases modify these binding proteins, reducing their affinity for IGFs. We have studied 12 patients, undergoing elective coronary artery vein-bypass graft surgery, for the appearance of these proteases and have demonstrated the induction of two independent, heat-labile, cation-dependent proteases. Proteolytic activity directed against IGFBP-3 was detected in all patients between 24 h and 5 days after surgery; the second IGFBP-4 specific protease was active 1 h after sternotomy. The total IGF-I levels were found to decrease following surgery, with the IGF-I distribution in the plasma being radically altered from that seen prior to the operation. One day after the operation the majority of the IGF-I, instead of being bound in the relatively inert 150 kDa complex, was associated with the smaller binding proteins which are more readily accessible to the tissues. These findings are in contrast to pregnancy where, despite similar proteases, the majority of the IGF-I remains in the 150 kDa complex. The alteration seen in IGF-I distribution after surgery did not appear to be a direct result of the IGFBP-3 proteolytic activity or an effect of the addition of heparin to the circulation. The potential increase in bioavailability of IGFs caused by the alteration in carrier protein may play a pivotal role in countering the catabolic state induced by surgery.
Adult↗
Regulation of growth hormone secretion in patients with growth hormone insensitivity.
Two subjects with growth hormone (GH) insensitivity were studied using standard methods of examining GH regulation: overnight GH sampling, stimulation of GH secretion with two sequential intravenous injections of GH-releasing hormone (GHRH), and suppression with somatostatin. Subject 1 was a girl, aged 14 years (height, 103 cm; -8.3 SDS for chronological age). Subject 2 was a boy, aged 11.5 years (height, 103.6 cm; -5.9 SDS for chronological age). The overnight pattern of GH secretion was similar in both subjects and appeared pulsatile with three pulses overnight, the major peaks of 203 mU/l and 206 mU/l in subjects 1 and 2 occurring at 00.00 hours and 00.20 hours, respectively. Serum GH levels were detectable throughout and the mean overnight serum GH levels were 65 mU/l and 53 mU/l for subjects 1 and 2 respectively. The pattern of GH response to GHRH stimulation was similar in both subjects, with a large rise in GH after the first injection, to a peak of 512 mU/l and 216 mU/l in subjects 1 and 2 respectively. The response to the second GHRH injection was less than the first, with peaks of 486 mU/l and 150 mU/l. During somatostatin infusion, GH levels fell to 7 mU/l and were undetectable in the two subjects respectively, with a rebound following the cessation of infusion. High resolution computerized tomography (CT) scans of both subjects confirmed normal anatomy of the hypothalamus and pituitary with a small gland at the base of the fossa. In conclusion, GH secretion in GH insensitivity is pulsatile and the pituitary is responsive to exogenous GHRH and somatostatin.(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
The presence of cation-dependent proteases for insulin-like growth factor binding proteins does not alter the size distribution of insulin-like growth factors in pregnancy.
OBJECTIVE: The aim was to investigate the sera of pregnant women for the presence of specific proteases for insulin-like growth factor binding proteins (IGFBPs) and to determine the effect of these on the distribution of IGFs in the circulation. DESIGN: The method used was the chromatographic and electrophoretic analysis of patients' serum. PATIENTS: Sera were examined from normal women during pregnancy: first trimester (n = 4), second trimester (n = 4) and third trimester (n = 10). Eight women with Type I diabetes in the third trimester were also studied along with sera from ten normal adult volunteers. MEASUREMENTS: Circulating IGF-I and IGF-II levels were measured by RIA and their distribution examined by gel filtration. The pattern and stability of the IGFBPs was investigated by Western ligand blotting. RESULTS: A marked reduction in the serum levels of IGFBP-2, IGFBP-3 and IGFBP-4 on Western ligand blotting, which was associated with the presence of three independent, cation-dependent proteases that were specific for different IGFBPs, was found in late pregnancy. Gel filtration of third trimester serum revealed most of the IGF-I to be present in a complex larger than 130 kDa, with a similar distribution to that found in serum of non-pregnant women. The enzymatic modification of the binding proteins made apparent by the decrease in binding protein bands on Western ligand blotting of preincubated samples had no effect on the distribution of IGF-I following size fractionation. CONCLUSIONS: There appear to be at least three independent enzymes that are induced or activated during pregnancy to modify IGFBP-2, IGFBP-3 and IGFBP-4 sufficiently to prevent their detection by ligand blotting. However, this enzymatic processing does not alter the distribution of IGFs, suggesting that the altered binding proteins are still able to carry IGFs but with reduced affinity. Such an alteration in the carrying mechanism of IGFs may have profound effects upon the bioavailability of the IGFs to the maternal tissues and contribute to the altered metabolic demands of pregnancy.
Blotting, Western↗
Inter-relations between growth hormone, insulin, insulin-like growth factor-I (IGF-I), IGF-binding protein-1 (IGFBP-1) and sex hormone-binding globulin in acromegaly.
Acromegaly is characterized by a hypersecretion of GH, which in turn results in an excess of IGF-I, an important mediator of its actions. IGF-I itself is intimately related to insulin both in structure and function. IGF-I circulates associated with specific binding proteins which appear to have important effects on its activity. We have examined the inter-relations between GH, prolactin, insulin, IGF-I and one of the binding proteins, IGFBP-1, in 62 patients with acromegaly of varying activity. Serum IGF-I levels were closely related to the logarithm of mean GH levels (r = 0.76; n = 62; P less than 0.001) but multiple regression analysis suggested that, after accounting for the variation due to GH, insulin accounted for some of the additional variation of IGF-I. IGF-I concentrations were independent of prolactin. Fasting insulin levels were high and unrelated to mean GH levels but correlated with those of IGF-I (r = 0.542; n = 57; P less than 0.001). This correlation coefficient was further improved by also accounting for variations in IGFBP-1 (r = 0.684; n = 57; P less than 0.001). Even in subjects whose acromegaly was well controlled or cured, as indicated by GH levels of less than 1 mU/l or IGF-I levels of less than 2 U/ml, fasting insulin levels remained significantly elevated in some individuals. The reason for this persistent abnormality is not clear. Fasting IGFBP-1 levels were low and unrelated to mean GH but were inversely related to fasting insulin levels (r = -0.593; n = 57; P less than 0.001). We propose that a cascade of events occurs in acromegaly.(ABSTRACT TRUNCATED AT 250 WORDS)
Acromegaly↗