Reduced longevity in untreated patients with isolated growth hormone deficiency

Increased longevity of hypopituitary dwarf mice and GH- resistant knockout mice appears to be in contrast with observations made in clinical practice. In humans, on one hand hypopituitarism and GH deficiency (GHD) are believed to constitute risk factors for cardiovascular disease and, therefore, early death. But on the other hand, patients with a PROP-1 gene mutation, presenting with a combined pituitary-derived hormonal deficiency, can survive to a very advanced age, apparently longer than normal individuals in the same population. The aim of this study was to analyze the impact of untreated GHD on life span. Hereditary dwarfism was recognized in 11 subjects. Genetic analysis revealed an underlying 6.7-kb spanning deletion of genomic DNA encompassing the GH-1 gene causing isolated GHD. These patients (five males and six females) were never treated for their hormonal deficiency and thus provide a unique opportunity to compare their life span and cause of death directly with their unaffected brothers and sisters (11 males and 14 females) as well as with the normal population (100 males and females). Although the cause of death did not vary between the two groups, median life span in the GH-deficient group was significantly shorter than that of unaffected brothers and sisters [males, 56 vs. 75 yr (P < 0.0001); females, 46 vs. 80 yr (P < 0.0001)]. Therefore, with the wealth of information regarding the beneficial effects of GH replacement and the dramatic findings of this study, GH treatment in adult patients suffering from either childhood- or adult-onset GHD is crucially important.     

IGF-I replacement therapy in children with congenital IGF-I deficiency (Laron syndrome) maintains heart dimension and function

ObjectiveUntreated patients with congenital growth hormone deficiency (GHD) and IGF-I deficiency are characterized not only by dwarfism but also by acromicria and organomicria, such as the heart. We assessed cardiac dimensions and function in very young patients with Laron syndrome (LS) undergoing IGF-I replacement therapy.DesignTwo to seven echocardiographic measurements were performed during IGF-I replacement therapy on male (n = 4) and female (n = 4) LS -atients, mean ± SD age of 7.1 ± 3.6 years (range 1.6–11.6 years), weight 16.1 ± 9.7 kg, and height 89.9 ± 18.5 cm. As aged- and gender-matched controls served 44 healthy children, age: 8.7 ± 5.5 years, weight: 36.1 ± 22.4 kg, and height: 129.7 ± 33.1 cm. Data of LS patients were normalized to body surface area and compared to the control group as well as nomograms of normal echocardiographic parameters for this age group.ResultsLeft ventricular diastolic and systolic dimensions (LVDD/ LVSD, mm) and LV mass (gr) were significantly smaller in boys and girls with IGF-I treated LS compared with controls while the shortening fraction (%) and intraventricular septum thickness (mm) were similar. When compared with standard values for this age group, all treated LS patients were within 1 standard deviation of the mean.ConclusionIGF-I therapy of young patients with Laron syndrome maintain LV dimensions and function within the normal range of aged-matched controls.     

Diabetic retinopathy in two patients with congenital IGF-I deficiency (Laron syndrome)

OBJECTIVE: Animal and clinical studies have shown that excessive amounts of growth hormone or insulin-like growth factor-I (IGF-I) promote the development of diabetes and diabetic retinopathy. Forthwith, we present two patients with congenital IGF-I deficiency who developed type II diabetes and subsequently retinopathy. METHODS: Eighteen adult patients with classical Laron syndrome (8 males, 10 females, aged 20-62 years) were followed by us since childhood or underwent fundus photography with a Nikon NF 505 instrument. Three had been treated in childhood with IGF-I, the rest were never treated, including the two patients reported. RESULTS: Two never-treated patients were diagnosed with type II diabetes (DM) at ages 39 and 41 respectively. There was no diabetes in the families. Oral treatment was followed by insulin injections. Metabolic control was not optimal and one patient developed proliferative diabetic retinopathy, necessitating laser surgery. He also has nephropathy and severe neuropathy. The other patient has background diabetic retinopathy and has developed, progressively, exudates, microaneurisms, hemorrhages and clinically significant macular edema. He also has subacute ischemic heart disease. CONCLUSIONS: Our findings show that congenital IGF-I deficiency, similar to excess, causes vascular complications of DM, denoting also that vascular endothelial growth factor can induce neovascularization in the presence of congenital IGF-I deficiency.     

Reduced exercise capacity in untreated adults with primary growth hormone resistance (Laron syndrome)

OBJECTIVE: Primary IGF-I deficiency (Laron syndrome, LS) may decrease exercise capacity as a result of a lack of an IGF-I effect on heart, peripheral muscle or lung structure and/or function. METHODS: Eight patients (six females) who had never received treatment with IGF-I, with mean age of 36 +/- 10 (SD) years (range 21-48), weight 47 +/- 9 kg (31-61), height 126 +/- 12 cm (112-140) and body mass index of 29 +/- 4 kg/m2 (24-34), and 12 age-matched controls, underwent lung function tests and incremental cycling to the limit of tolerance (CPX, MedGraphics). Predicted values for the patients were derived from adult equations based on height. RESULTS: In LS patients, lung function was near normal; vital capacity was 84 +/- 11% of expected (66-103). Peak exercise O2-uptake and the anaerobic threshold were reduced, 57 +/- 20% of predicted and 33 +/- 9% of predicted peak (P = 0.005 vs. controls), despite normal mean exercise breathing reserve. All parameters were normal in the controls. CONCLUSION: Exercise capacity in untreated adults with LS is significantly reduced. The limitation for most patients was not ventilatory but resulted either from low cardiac output and/or from dysfunction of the peripheral muscles. However, the relative contribution of each of these elements and/or the role of poor fitness needs further study.     

Thyroid morphology and function in adults with untreated isolated growth hormone deficiency

OBJECTIVE: GH influences thyroid function and anatomy. Although goiter is frequent in acromegalic patients, the effects of GH deficiency (GHD) are difficult to assess, because hypopituitaric subjects who lack GH often also have a partial or complete deficit of TSH. STUDY DESIGN: We studied thyroid morphology and serum levels of thyroid hormones in adult members of a large Brazilian kindred with untreated isolated GHD due to a homozygous mutation in the GHRH receptor gene (GHRHR; nine men and 15 women; GHD group) and compared them to subjects heterozygous for the same mutation (eight men and 10 women; HET group) and subjects homozygous for the wild-type allele [seven men and 11 women; control (CO) group]. RESULTS: GHD subjects had a smaller thyroid volume (TV) than HET and CO. The TV of the HET group was intermediate between those of the GHD and CO groups. When TV was corrected by body surface area, it remained smaller in the GHD and HET groups than in the CO group, but the difference between GHD and HET groups disappeared. The GHD group had lower serum T3 levels than the CO group and higher free T4 levels than HET and CO groups. CONCLUSIONS: Individuals with severe untreated GHD due to a homozygous GHRHR mutation and heterozygous carriers of the same mutation have smaller TV than normal subjects, suggesting that GH has a permissive role in the growth of the thyroid gland. In addition, GHD subjects have reduced serum total T3 and increased serum free T4, suggesting a reduction in the function of the deiodinase system.     

IGF-I treatment of adult patients with Laron syndrome: preliminary results

OBJECTIVE Laron syndrome is a genetic disease due to a defect in the GH receptor or in the pod-receptor mechanism which leads to an inability to generate IGF-I. Biosynthetic IGF-I treatment given to dwarfed children with this syndrome, produced a significant acceleration of growth velocity and reduction in obesity. In view of the known metabolic disturbances in untreated adult patients, the present clinical trial was performed to define the usefulness of IGF-I treatment in LS adults. PATIENTS AND DESIGN Five patients (1 male, 4 females) aged 28-40 years were treated during 9 months by daily administration of IGF-I (120 μg/kg), and followed for 6 months after its discontinuation. METHODS At each visit, a complete physical examination was performed and blood was drawn for biochemical and hormone determinations. Twenty-four-hour urinary samples were collected at various Intervals during treatment. Bone densitometry was performed before and after 6-9 months of therapy. RESULTS The main findings were a reduction in subscapular skinfold thickness (from 27·5 ± 1·4 (mean ± SEM) to 19·5 ± 1·0 mm; P < 0·002), a decrease in total cholesterol (from 6·78 ± 0·28 (mean ± SEM) to 5·80 ± 0·36 mmol/l) and in LDL cholesterol (from 4·86 ± 0·23 to 3·76 ± 0·35 mmol/l), an increase in creatlnlne clearance (from 71·2 ± 8·4 to 86·8 ± 4·3 ml/min/l·73m², P < 0·04), an increase in phosphate reabsorption (from 0·89 ± 0·06 to 1·14 ± 0·06 mmol%; P < 0·02) leading to an increase in serum phosphate (from 1·08 ± 0·06 to 1·27 ± 0·03 mmol/l; P < 0·03), a rise in alkaline phosphatase (from 80·8 ± 5·0 to 100·7 ± 7·0 U/I) and in procollagen I-PICP (from 44·2 ± 4·0 to 171·0 ± 19·2 μg/l; P < 0·0001) and in procoilagen III-PIIINP (from 2·68 ± 0·45 to 10·10 ± 1·4μg/l; P < 0.005). There was a transient retention of water, sodium and chloride. Pretreatment serum IGFBP-3 levels were low, but increased progressively during treatment. This permitted a reduction in the IGF-I dose. There were no adverse effects other than pain and slight erythema at the injection site during the first weeks of treatment. All the anthropometric and metabolic changes reversed upon discontinuation of IGF-I. CONCLUSIONS IGF-I treatment is beneficial in adults, as well as in children, with resistance to GH.     

Long-term IGF-I treatment of children with Laron syndrome increases adiposity.

Laron syndrome (LS) is an autosomal recessive disease caused by deletions or mutations in the GH receptor gene leading to an inability of insulin-like growth factor I (IGF-I) generation. Among the major resulting body changes are dwarfism and obesity. The only effective treatment is daily administration of biosynthetic IGF-I. Body composition determination by DEXA (dual energy X-ray absorptiometry) of three girls with LS treated by IGF-I for 1, 3 and 11 1/2 years, respectively, revealed that concomitantly with the increase in growth there was a significant increase in body adipose tissue to double or triple the normal values. Due to the underdevelopment of the muscular and skeletal systems body mass index (BMI) did not accurately reflect the degree of obesity. In conclusion, IGF-I similar to insulin, exerts an adipogenic effect.     

Absence of serum growth hormone binding protein in patients with growth hormone receptor deficiency (Laron dwarfism).

It has recently been recognized that human serum contains a protein that specifically binds human growth hormone (hGH). This protein has the same restricted specificity for hGH as the membrane-bound GH receptor. To determine whether the GH-binding protein is a derivative of, or otherwise related to, the GH receptor, we have examined the serum of three patients with Laron-type dwarfism, a condition in which GH refractoriness has been attributed to a defect in the GH receptor. The binding of 125I-labeled hGH incubated with serum has been measured after gel filtration of the serum through an Ultrogel AcA 44 minicolumn. Nonspecific binding was determined when 125I-hGH was incubated with serum in the presence of an excess of GH. Results are expressed as percent of specifically bound 125I-hGH and as specific binding relative to that of a reference serum after correction is made for endogenous GH. The mean +/- SEM of specific binding of sera from eight normal adults (26-46 years of age) was 21.6 +/- 0.45%, and the relative specific binding was 101.1 +/- 8.6%. Sera from 11 normal children had lower specific binding of 12.5 +/- 1.95% and relative specific binding of 56.6 +/- 9.1%. Sera from three children with Laron-type dwarfism lacked any demonstrable GH binding, whereas sera from 10 other children with other types of nonpituitary short stature had normal relative specific binding. We suggest that the serum GH-binding protein is a soluble derivative of the GH receptor. Measurement of the serum GH-binding protein may permit recognition of other abnormalities of the GH receptor.     

Combined treatment with growth hormone and gonadotropin-releasing hormone analogues in children with isolated growth hormone deficiency.

In subjects with an isolated GH deficiency the inhibition of puberty by GnRH-analogue administration may be attempted to delay the onset, or to prolong the duration, of pubertal maturation in order to improve final height. We report our experience on the matter in 10 subjects (6M, 4F) suffering from isolated GH deficiency with a chronological age ranging from 6.5 to 10.6 years at diagnosis. After a period of 1-5.1 years of GH treatment, GnRH-analogues (long-acting D-Trp-6-GnRH) were added to GH for 12 months, when six subjects were still prepubertal and four in early puberty. During combined therapy, a regression in pubertal development was shown in three out of four children in early puberty, while serum testosterone or estradiol decreased. Height velocity decreased (from 5.23 +/- 1.49 (mean +/- SD) to 4.12 +/- 0.67 cm/year; p < 0.02), whereas height SD scores for bone age increased (from -0.75 +/- 0.42 to -0.47 +/- 0.55; p < 0.02). During the year of combined therapy, bone age increased only 0.57 +/- 0.27 years. The values for predicted height (TW2 and Bayley-Pinneau method) after combined treatment were also higher than those after treatment with GH alone (p < 0.02 and p < 0.001, respectively). Our preliminary data showed that the addition of GnRH-analogues to GH in subjects with isolated GH deficiency reduces the effect of GH on height velocity, but determines an improvement in statural prognosis, although a proper answer will not be obtained until final height has been achieved.     

Lipid profiles in untreated severe congenital isolated growth hormone deficiency through the lifespan

OBJECTIVE: Growth hormone deficiency (GHD) is associated with adverse changes in lipid profile. However, changes in lipids through life in a homogeneous group of GHD subjects have not been defined. PATIENTS AND MEASUREMENTS: We examined lipid levels in a group of untreated severely GHD patients with a mutation in the GHRH receptor gene from a rural community in North-east Brazil. Lipid profiles in 15 GHD subjects [eight children and adolescents (one male), age (median [range]) 13.2 (5.4-19.9) years; seven adults (one male), age 47 (33-66) years] were compared with those in 29 indigenous controls from the same extended kindred [17 children and adolescents (six male), age 10.2 (5.3-18.4) years; 12 adults (eight male), age 54.5 (33-80) years]. All GHD subjects had a peak GH response of < 0.5 ng/ml in response to an insulin tolerance test and extremely reduced IGF-1 levels (median 5.5 ng/ml). Data were compared between cohorts and with an age- and sex-matched white American reference population. RESULTS: Abnormalities were confined to plasma total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels. More GHD children had levels of plasma TC and LDL-C above the 95th percentile for our reference population (3/8 and 4/7, respectively) compared to controls (0/17 and 1/15, respectively) (P < 0.05). In the adults, median TC and LDL-C levels were higher in the GHD than controls (P < 0.05) (6.3 vs. 4.1 mmol/l; 4.4 vs. 2.7 mmol/l, respectively). Median Z-scores, calculated using values from the reference population, were not different between GHD children and adults for both TC (+0.8 vs.+0.4) and LDL-C (+1.4 vs.+0.7). CONCLUSIONS: The lipid profile in children as well as in adults with very severe GHD is adversely modified. There would appear to be no significant worsening of the lipid abnormality with duration of GHD or achievement of adulthood.     

Transitory growth hormone deficiency successfully treated with human growth hormone

This study was carried out in order to determine whether children with a transitory type of growth hormone deficiency showed an accelerated growth in height velocity on treatment with human growth hormone (HGH). Following careful diagnostic routine procedures 13 extremely short children were diagnosed as having isolated growth hormone deficiency, and were successfully treated with HGH. A true isolated growth hormone deficiency was present in 5 of the children, whereas 8 showed a normal increase in serum growth hormone on repeated growth hormone stimulation tests after their development of puberty and termination of HGH treatment.Three boys with bone ages of 5.5, 8.0 and 9.5 years showed an undisputable effect following HGH administration. They showed an initial growth at the start of treatment, and a second growth spurt during development of puberty. Two of the boys reached final statures of 14 cm taller than the predicted heights. The other patients, including the children with true isolated growth hormone deficiency showed an initial spurt of growth at the start of the HGH treatment immediately followed by a pubertal growth spurt. The mean accleration of height velocity for the children with true isolated growth hormone deficiency was from 3.4 cm during the year before treatment to 7.0 cm during the first year on treatment, as compared to 2.8 and 7.4 cm, respectively, for the children with transitory growth hormone deficiency. A girl with severe anorexia nervosa who had a transitory growth hormone deficiency, showed an accelerated high velocity from 1.1 cm to 7.6 cm during the first year following treatment with HGH.     

Body composition in untreated adult patients with Laron syndrome (primary GH insensitivity)

OBJECTIVE: To quantify body adiposity and its distribution in untreated adult patients with Laron syndrome (LS; primary GH insensitivity) caused by molecular defects of the GH receptor gene or postreceptor pathways and characterized by dwarfism, obesity, insulin resistance and hyperlipidaemia. PATIENTS: Eleven LS patients (seven females and four males) aged 28-53 years were studied. Seven healthy males and six healthy females served as controls. MEASUREMENTS: Body composition of the total body trunk, upper and lower extremities was determined using dual-energy X-ray absorptiometry (DEXA). Statistical analysis using an analysis of variance (anova) and Mann-Whitney nonparametric methods was performed separately in males and females. RESULTS: Percentage body fat in the LS patients was much higher (P < 0.01) than that in the control population and the female LS patients were significantly more obese (59% total body fat) than the male patients (39% total body fat) (P < 0.002). It was also evident that in these types of patients with markedly increased body fat and decreased muscle and bone mass, body mass index (BMI) does not accurately reflect the body composition. CONCLUSIONS: Lifelong congenital IGF-I deficiency leads to extreme adiposity.     

Bone density and body composition in children with growth hormone insensitivity syndrome receiving recombinant IGF-I

OBJECTIVE: There are few reports of the metabolic action of insulin-like growth factor 1 (IGF-I) in vivo. Growth hormone insensitivity syndrome is a good model to examine the effects of IGF-I deficiency. This study was designed to assess body composition and bone density in children with growth hormone insensitivity syndrome before and after receiving treatment with recombinant IGF-I. DESIGN: A prospective longitudinal study. PATIENTS: Four prepubertal boys age 6.1-9.8 years with short stature due to growth hormone insensitivity syndrome. MEASUREMENTS: Assessment of body fat by skinfold thickness measurements and dual energy X-ray absorptiometry (DXA) was made during the first 6 months of recombinant IGF-I treatment. Assessment of lumbar spine bone density by DXA was performed prior to IGF-I treatment and during the subsequent five years. RESULTS: Each child showed a significant reduction in fat mass (0.26-1.22 kg) after 6 weeks of IGF-I treatment. Bone density prior to treatment was reduced in comparison to age-matched controls but calculated volumetric bone density was within the normal range. Volumetric bone density progressively improved over the 5-year treatment period. CONCLUSIONS: Children with growth hormone insensitivity syndrome exhibit a metabolic response to IGF-I within 6 weeks analogous to that seen in GH-deficient children receiving GH. Bone density when corrected for body size is within normal limits and demonstrates a response to IGF-I, confirming the anabolic action on bone.     

Physiological growth hormone secretion in adult growth hormone deficiency: comparison with normal controls

A comparison was made between the pulsatile pattern of growth hormone secretion in 14 growth hormone deficient adults (serum growth hormone less than 7 mU/I following insulin-stimulated hypoglycaemia) and 14 age and sex matched controls. The 24-h secretory profile was generated by 2-hourly sampling from 0800 to 2200 h, and 30-min sampling from 2200 to 0600 h. Plasma GH in each sample was measured using a double antibody radioimmunoassay. The profiles were analysed using a computer program (Pulsar). Sleep-electroencephalography was recorded in all subjects. The total amount of GH secreted in a 24-h period (area under the curve over baseline) was significantly less in the growth hormone deficient group (P less than 0.002). The pulse frequency, amplitude, height and percentage GH secreted in peaks were also significantly less in the growth hormone deficient group (P less than 0.002 respectively). We conclude that adults deficient in GH, as defined by conventional pharmacological stimuli, are in addition physiologically deficient of pulsatile GH secretion.     

A novel growth hormone receptor gene deletion mutation in a patient with primary growth hormone insensitivity syndrome (Laron syndrome).

OBJECTIVE: Growth hormone (GH) insensitivity syndrome (Laron syndrome) is known to be caused by genetic disorders of the GH-IGF-1 axis. Although many mutations in the GH receptor have been identified, there have been only a few reports of deletions of the GH receptor gene. DESIGN: A Japanese adult female patient with Laron syndrome was subjected to chromosome analysis with basic G-banding and also with a high accuracy technique. Each exon of the GH receptor gene was amplified by means of PCR. Since this patient was diagnosed with osteoporosis, the effects of alendronate on bone mineral density (BMD) were also examined. RESULTS: The chromosome analysis with the high accuracy technique demonstrated a large deletion of the short arm in one allele of chromosome 5 from p11 to p13.1 [46, XX, del (5) (p11-p13.1)]. PCR amplification of exons of the GH receptor gene showed that only exons 2 and 3 were amplified. Low-dose IGF-1 administration (30microg/kg body weight) failed to increase her BMD, whereas alendronate administration resulted in an increase associated with a decrease in urinary deoxypyridinoline (DPD) and serum osteocalcin concentrations. CONCLUSIONS: The GH receptor gene of the patient was shown to lack exons 4-10. To the best of our knowledge, this is the third case report of Laron syndrome with large GH receptor deletion. Alendronate was effective for the enhancement of BMD.     

Adult height in sixty girls with Turner syndrome treated with growth hormone matched with an untreated group

The main clinical feature of Turner syndrome (TS) is growth failure, with a mean spontaneous adult height ranging between 136 and 147 cm, according to the specific curves of various populations. Though a classical deficiency of GH has not been generally demonstrated, GH has been administered since 1980 in trials, using replacement doses just initially, with a subsequent trend to increase it. We report the outcome of GH therapy given at the fixed dose of 0.33 mg/kg/week in 60 TS girls observed until adult height; 59 untreated TS girls, matched for auxological, karyotypical characteristics and time of observation, born within the same decade served as controls to evaluate GH efficacy. The calculation of the gain in cm over PAH was performed on specific Italian Turner curves, as well as height evaluation as SD score and growth velocity. The same calculations were made using Lyon references and Tanner standards. The mean CA at the beginning of GH treatment was 10.9 +/- 2.76 yr (range 4.5-15.9). Mean adult height of treated group was 151 +/- 6.1 cm with a gain over the PAH calculated at start of therapy (142.9 +/- 5.3 cm) of 8.2 +/- 3.9 cm. Ns change was observed between the PAH at first observation (143.6 +/- 7.0 cm) and adult height (144.3 +/- 5.6 cm) in the control group. Treatment was well tolerated, no relevant side effects were observed, glucose metabolism resulted no more affected than in untreated subjects, IGF-I levels remained within 2 SD. Our results in 60 TS girls, though the dose remained unchanged throughout the treatment, show a good response, characterized by a striking variability in each patient (mean gain in cm over PAH at adult height of 8.17 +/- 3.9, range 3-21 cm), and significant also in comparison with the control group. As the chronological age at start of therapy ranged between 4.5 to 15.9 yr, the results were further evaluated dividing the patients into two groups, according to the age, < or >11 yr. Thirty girls were <11 yr (mean 8.7 +/- 1.76 yr) and 30 were >11 yr (mean 13.2 +/- 1.4 yr). The gain in cm over the PAH in each group was, respectively, 8.1 +/- 3.4 and 8.2 +/- 4.3 cm without any significant difference between the two groups, showing no negative correlation between the CA at the beginning of GH and the response to treatment.     

HLA-DQA1等位基因与自身免疫性甲状腺病的相关性

自身免疫性甲状腺病 (ＡＩＴＤ)主要包括Ｇｒａｖｅｓ病 (ＧＤ) ,桥本甲状腺炎 (ＨＴ)及特发性粘液水肿 (ＩＭ)等。ＡＩＴＤ的发病是与遗传、环境和人体内源因素之间复杂的相互作用所致 ,其遗传易感性与ＨＬＡ Ⅱ类抗原某些等位基因密切相关 ,并存在种族差异。本研究在天津市人群自身免疫性甲状腺病流行病学调查的基础上 ,应用ＰＣＲ ＲＦＬＰ技术对ＡＩＴＤ患者进行ＨＬＡ ＤＱＡ1等位基因分型 ,研究北方汉族人群ＨＬＡ ＤＱＡ1等位基因与ＧＤ ,ＨＴ的相关性 ,从而进一步探讨ＡＩＴＤ的发病机制及分子遗传背景。一、对象和方法1.对象 :ＧＤ…     

Placental growth hormone and IGF-I in a pregnant woman with Pit-1 deficiency

The respective contributions of pituitary and placental GH to circulating IGF-I in pregnant women have not been well established. We measured the serum concentrations of placental growth hormone (PGH) and IGF-I in a woman with pit-1 deficiency before, during and after pregnancy, resulting in the birth of a healthy child (not pit-1 deficient). Both PGH and IGF-I concentrations were below the assay detection limit before and after pregnancy. During pregnancy, PGH and IGF-I levels increased steadily; the concentrations of PGH and IGF-I in late pregnancy were comparable with levels previously measured in normal pregnancies. PGH and IGF-I concentrations were strongly correlated throughout pregnancy (r = 0.90; P = 0.002). PGH was undetectable in cord serum, whilst the IGF-I concentration was within the normal range. The findings of this case study corroborate the notion that PGH is the prime regulator of maternal serum IGF-I during pregnancy.