Auxological Data Research Articles

A PREDICTION MODEL FOR THE FIRST YEAR GROWTH RESPONSE TO GROWTH HORMONE IN TURNER SYNDROME (TS) BASED ON KIGS (Kabi Pharmacia International Growth Study) DATA

In order to optimize treatment with GH, a large-scale, complex analysis on the response to GH in terms of auxological data, as well as treatment modalities is essential.1 We analyzed 175 TS patients <11 yrs. The median values were: CA=7.9 yrs; HT SDS = -2.5 SD; target HT=0.0 SD; Weight for Height index (WHI %)=97; GH dose (IU/kg/wk)=0.8; No. of GH inj/wk = 6). Out of 10 potential predictors, only the following were validated: No. of inj/wk, GH dose, CA and WHI. The corresponding regression equation is: HV (cm/yr)=9.02 + [0.36 × No. inj/wk] + [2.01 × GH dose (IU/kg/wk) ] - [0.25 × CA (yrs)] - (0.036 × WHI (%)]; r2=0.37; error SD=1.26 cm/yr). We concluded firstly that the mode of treatment rather than the auxology determines growth in TS, early treatment being possibly advantageous. Secondly, in contrast to GHD, WHI is negatively correlated to the growth response, thus pointing to a different body composition in TS. Thirdly, we found the growth response to GH in TS was less predictable with the variables used. Lastly, other predictors eg. degree of dysmorphology, may improve the prediction model.

TWO YEAR AUXOLOGICAL RESULTS OF A GROWTH HORMONE (GH) DOSE-RESPONSE STUDY IN TURNER SYNDROME (TS)

In a multicenter dose-response study, 68 girls with TS (Tanner stage B1), age 6.5 (2.3) yr (range 2.1-11.0 yr) were randomized into 3 groups according to CA and H-SDSCA: A (n=23) 4 IU hGH/m2 b.s. for 4 yr, B (n = 23) 1st yr 4 IU and 2nd-4th yr 6 IU/m2, C (n = 22) 1st yr 4 IU, 2nd yr 6 IU, 3rd and 4lh yr 8 IU/m2 (Norditropin11) daily s.c. We report auxological data [n = 67, drop out: 1×B) aftef 2 yr GH therapy, in which period B + C were evaluated as one group.METHODS: Standing height (H) was measured by the some observer (AvT). SD scores for CA were calculated using combined data of an untreated Dutch-Swedish Danish TS reference population. Bone age (BA) was determined according to TW2 RUS to assess the index of potential height (H·SDSBA) and according to G&P for final height (FH) prediction according to Bayley Pinneau. Values are expressed as mean (SD). compared wilh prrRx, p ≤0.001; ° change from preRx between groups, p≤0.02; change from yr 1 between groups, p-0.03.In the 1st and 2nd yr HV and H·SDSCA increased compared with preRx in both groups (p ≤ 0.001). 2nd yr HV and ΔH·SDSCA were higher for B + C than for A (p ≤ 0.002). PreRx BA and ΔBA in yr 1 and 2 were nor different between groups. It yr 2, a further increment of FM pred occured only in B + C (p=0.003). ΔH·SDSBA after 2 yr was different from preRx in both groups (p < 0.001), without difference between groups. Age at start of Rx was negatively correlated (p=0.01) with ΔH·SDSCA after 2 yr Rx in B + C (r = 0.31), but not with ΔBA.CONCLUSIONS: A GH dose increment after the 1st yr of Rx from 4 to 6 IU/m2 b.s./d results in a better growth response expressed as HV and ΔH·SDSCA as well as in a better FH pred alter the 2nd yr Rx. However, H·SDSBA did not improve more with the higher dose. Bone age appears not to be influenced by the dosage increment. Start of GH Rx at a younyer age might be favourable.

BIRTH DATA OF PATIENTS WITH CROW HORMONE DCEICICNCY

The pathogenesis of idiopathic GH deficiency (CHD) is not clear and it was presumed that GH is not essential for prenatal growth. We have therefore analysed in the clinical and auxological data of patients with CHD. History of pregnancy, birth history and birth data as well as postpartal data were evalutated. 48 unselected patients (boys:girls=2.1) with complete CHD had isolated (IGHD, n=24) or multiple pituitary hormone deficiencies (MPHD, n=24). 25% of the patients were born prematurely. Complications during pregnancy (impending abortion, gestesis) were observed in 27% of patients. Abnormal birthe occured in 40% (breech and fontling presentation, assisted delivery). Birth length of boys (−1.0±1.3SDS;p<0.01) and of girls (−0.4±1.0SDS;ns) was reduced when compared to local reference data. The data for ICHD and MPHD patients (−0.9±1.3SDS vs. −0.8±1.2SDS) were not different. Birth weight was reduced in boys (−0.8±1.2SDS;p<0.05) but not in girls (+0.06±1.3SDS). No difference in birth weight was found between IGHD and MPHD (−0.4±1.5SDS and −0.6±1.5SDS), respectively. This indicates relative overweight already at birth. 50% of patients had various complications during the postpartal period (prolonged jaundice, hypoglycemia etc.). Maternal height was −0.5±1.2SDS and did not correl;ate with patients length at birth. In conclusion, we have shown that children with idiopathic GHD as a group are short at birth and have relative overweight. This may indicate the importance of GH for prenatal growth. In a high proportion of patients with idiopathic CHD perinatal complications were observed.

IDENTIFICATION OF RESPONSIVE AND UNRESPONSIVE SHORT CHILDREN TO GROWTH HORMONE THERAPY USING A MULTIVARIATE DISCRIMINANT ANALYSIS OF PRE-TREATMENT AUXOLOGICAL DATA

BACKGROUND: Growth hormone (GH) has been proved to increase height velocity (HV) in some shoit children who are not GH deficient. OBJECTIVE: Multivariate discriminant analysis was employed to identify, using pre-treatment auxological data, the children responsive to GH. DESIGN: Open prospective study. SETTING: University hospital. SUBJECTS: Fifty-five (35 males) patients that met the following criteria were studied: birth weight >2.500 Kg; no signs of dysmorphic disease; stature below the 3rd centile for chronological age (CA); height velocity below the 25th centile for bone age (BA); no signs of puberty; growth hormone response to pharmacological stimulation >10 ng/ml; no evidence of organic disease; treatment with daily subcutaneous administrations of GH at the dosage of 12-16 UI/m2/week. MAIN OUTCOME MEASURES: Eight pre-treatment auxological variables; HV increase after six months of therapy. A HV increase >2.5 cm/y was considered as a positive response.RESULTS: Thirty-tvvO (58.2%) patients were responsive. Using univariate analysis, the variables found to have predictive value (p<0.001) were: height velocily (SD for CA) and bone age (SD). These variables were employed in the multivariate discriminant analysis. The equation obtained was: Score=1.09X1 - 0.83X2 + 0.19 (X1=HV, X2=BA). Using this scoring system we obtained a sensitivity of 95.7% and a specificity of 91.0% in predicting responsiveness to GH (X2 with Yates correction=36.78, p<0.0001). No correlation was found between responsiveness and GH dosage. CONCLUSIONS: Discriminant analysis may permit the pre-treatment prediction of response to GH therapy in short children and therefore the identification of patients in which GH would be useless.

29 MALE ADOLESCENTS WITH CONSTITUTIONAL DELAY OF GROWTH AND PUBERTY. THERAPEUTICAL EFFECT OF TESTOSTERONE

Constitutional delay of grewth and puberty (CDGP) is characterized by small stature and delay of bone age (BA) and sexual development. In order to accelerate growth velocity (GV) and sexual development 23 boys with CDGP who ware worried for their poor growth and pubertal development were treated with monthly intramuscular testosterone injections (41+7.7 mg/m2) during 18 months (T). Thirteen boys with CDGP who ware not treated served as control group (C). Before treatment there were no differences between groups in chronological age (CA) T:14.65+0.9 vs C:14.31+0.8 (p=NS), SDS of height (SDS) T:−3.30+0.81 vs C:−2.85+0.62 (p=NS), SDS of height for BA (SDSBA) T:−0.24+0.9 vs −0.04+0.4 (p=NS), BA T: 11.81+1.1 vs 11.59+1.1 (p=NS), pubic hair (Tanner) (P) T:1.82+0.7 vs. 1.88+0.6 (p=NS), testicular volume (TV) T.7.0+2.6 vs 6.8+2.1 (p=NS) nor GV T:4.01+1.3 vs 4.9+1.4 (p=NS). Patients were clinically evaluate approximately every 3.5 months. In response to treatment we obtained the following auxological data: After 18 m of treatment there ware no differences in predicted adult height by Bayley-Pinneau (PFH)T:170.5±4.7 C.172.0±4.7. In sumary administration of low dose testosterone could be an adequate therapy in boys with CDGP to produce a significant acceleration of growth, advance virilization without the inductien of exoessive bene maturation nor detericrating predicted final height.

Chemical pathology of growth disorders

Growth disorders are characterized by two parameters - the absolute height measurement and the height velocity. The causes of growth failure can be classified as follows : endocrine, psychological, iatrogenic, chromosomal, nutritional, intrauterine, chronic disease and skeletal. I shall concentrate on the endocrine causes of disordered growth, in particular, abnormalities in the production of growth hormone (GH). Other endocrine abnormalities causing short stature include deficiency of thyroxine, excess Cortisol and delay in the production of sex steroids at puberty. GH is released from the anterior pituitary in a pulsatile fashion, with the greatest secretion occurring about one hour after the onset of sleep. Secretion of GH is stimulated by growth hormone releasing hormone (GHRH) and inhibited by somatostatin, both these peptides being released from the hypothalamus. GH exerts its growth promoting effects principally by acting on tissues, such as cartilage and muscle, to produce insulin-like growth factor I (IGFI) which probably acts locally in a paracrine fashion to stimulate growth. The clinical features of severe GH deficiency are relatively easy to recognize, but are less apparent in the child with partial lack of GH. The approach to the diagnosis of abnormal secretion of GH must include a complete clinical assessment, with appropriate auxological data and bone age. Provocation tests, to establish either partial or complete deficiency of GH, are based on either pharmacological or physiological stimuli. Other tests, used mainly for research, include measurement of the GH pulses over 24 hours, GHRH stimulation test and urinary GH excretion. 1GF1 measurement is of limited value in GH deficiency, but useful in states of GH excess. The introduction of biosynthetic GH has resulted in a broader spectrum of patients with growth disorders receiving treatment, and there is no longer the risk of transmission of slow virus infection, as occurred with the use of GH extracted from human pituitaries.

GH assessment and three years' hGH therapy in girls with Turner syndrome.

Fifteen girls with Turner syndrome (TS) were submitted to GH secretion assessment before undergoing hGH therapy. In the first 9 months, hGH was given at a dose of 0.5 IU/kg/week s.c. daily; afterward, the dose was increased to 1 IU/kg/week s.c. daily. The girls were prepubertal, with a mean (SD) chronological age (CA) of 12.5 (2.6) years, and a mean (SD) bone age of 10.5 (1.8) years. A clonidine stimulation test, 1-29 GHRH test and GH spontaneous nocturnal secretion assessment were performed in all patients. Results showed a variable pattern of GH secretion in 10 patients, in only 2 did we find all values definitely normal, and in 3 we found a total GH deficiency. Height velocity, expressed as standard deviation scores (SDS) for CA according to Turner references, during the first year of treatment increased significantly: 0.36 (1.15) -3.30 (2.87) (p < 0.001), and the increment remained quite unchanged during both the second and third years: 3.16 (2.96) and 2.55 (3.87), respectively (n.s.). Height, expressed in SDS for CA for Turner references, increased significantly throughout the whole period of treatment and reached the highest value at the end of the third year of therapy. GH secretion parameters poorly correlated with pretreatment auxological data or response to treatment. Our long-term study confirms that in TS GH measurement is not useful in indicating hGH therapy or in predicting the response.

Growth hormone treatment of Turner syndrome patients with insufficient growth hormone response to pharmacological stimulation tests

Growth before and during treatment with biosynthetic human growth hormone (hGH) was studied in 13 patients with Turner syndrome (TS) and a growth hormone (GH) response of less than 10 micrograms/l to two standard provocative tests. During 1 year of treatment with hGH (0.15 IU/kg per day) height velocity (mean +/- SD) increased significantly (P less than 0.001) from 3.7 +/- 1.8 cm/year to 7.6 +/- 1.5 cm/year. The auxological data in these girls before and during treatment with hGH were similar to those observed in TS patients with a normal response of GH to pharmacological stimuli. It is concluded that in girls with Turner syndrome GH testing should only be performed when height velocity is below the Turner norm. In TS patients with residual growth potential a clinically significant growth acceleration can be obtained with a higher-than-replacement dose of hGH, i.e. 0.15 IU/kg per day, regardless of GH testing.

Noonan's Syndrome: Abnormalities of the Growth Hormone/IGF‐I Axis and the Response to Treatment with Human Biosynthetic Growth Hormone

Auxological and endocrine data from 6 children (3 male, 3 female) aged 8.5-12.8 years with Noonan's syndrome and the results of treatment with human biosynthetic growth hormone (hGH) are presented. All the children were short (Ht SDS -3.5 to -2.3) and height velocity SDS ranged between -1.76 and +0.03. The maximum plasma growth hormone (GH) response to standard provocation tests ranged from 17 to 52 mU/l, yet, plasma insulin-like growth factor I (IGF-I) concentrations were low or low normal. Overnight GH secretory profiles were normal in all but 2 children who had disordered pulsatility with high trough concentrations. In 5 children who have completed one year of hGH therapy mean height velocity increased from 4.8 to 7.4 cm/year and the height velocity SDS ranged from +0.2 to +3.75. This improvement was associated with an increase in plasma IGF-I in three subjects. These results suggest that a defect of the GH/IGF-I axis may be present in some children with Noonan's syndrome and hGH therapy may have a role in the management of the short stature in these children.

Growth and Pubertal Development during and after Treatment with a Slow-Release Gonadotropin-Releasing Hormone Agonist in Central Precocious Puberty

The auxological data of 25 patients (21 girls, 4 boys) with central precocious puberty (CPP), treated for 4 years with a slow-release gonadotropin-releasing hormone agonist [Decapeptyl-controlled release (D-CR) 3.75] every 4 weeks intramuscularly, and of 6 patients (3 girls, 3 boys), treated for 5 years, are presented. After 3 years of D-CR a stabilization of height velocity (HV) at about 4 cm/year was observed. Bone maturation (ratio of change in bone age to change in chronological age; delta BA/delta CA) slowed down to a mean delta BA/delta CA ratio of 0.5 +/- 0.2 (mean +/- SD) measured over 48 months. As a result, predicted adult height (PAH) improved from 156.3 +/- 7.4 to 162.2 +/- 6.8 cm in girls (p less than 0.001) and from 174.4 +/- 18.6 to 184.3 +/- 17.1 cm in boys after 4 years. In the 5th year an ongoing improvement of PAH was observed. 20 additional girls discontinued D-CR for at least 12 months after treatment with D-CR for 2 years or more. In 11 girls menses started after 10.6 +/- 3.1 months; 9 girls had no menarche after 12-16 months. HV increased in the first and second 6 months to a level of about 6.0 cm/year, decreased in the third 6 months after cessation to the level before discontinuing D-CR and decreased further afterwards. Bone maturation (delta BA/delta CA) increased progressively in the first 18 months after discontinuation, with a stabilization at about 1.3. PAH did not change in the first 12 months after discontinuation of D-CR, but showed a decrease afterwards.(ABSTRACT TRUNCATED AT 250 WORDS)

GROWTH OF MALES WITH IDIOPATHIC HYPOPITUITARISM WITHOUT GROWTH HORMONE TREATMENT

We report auxologic data on 23 males with idiopathic hypopituitarism who grew up at a time when human growth hormone (GH) was not yet available, while receiving other appropriate hormonal substitution. We had reported previously that their adult heights were not significantly less than those of similar patients who had received GH. In the absence of GH the pubertal growth period was remarkably protracted, averaging 8.7 years for 19 patients during androgen substitution. Pubertal increment in height averaged 20.4 cm during induced puberty, a figure which compares favourably with those reported for GH-treated patients. This implies that GH does not increase the height gained during pubertal growth; the increase in the rate of growth appears to be off-set by a rise in the rate of skeletal maturation. During pubertal growth acceleration of growth of the skeleton seems unavoidably associated with acceleration of its maturation. Adult heights were significantly correlated with the heights at the time of onset of pubertal growth. This is evidence in favour of attempts to stimulate prepubertal growth much more than hitherto by earlier, higher, and more frequent doses of GH. It remains to be proved, however, that before puberty the processes of growth and maturation of the skeleton can be dissociated.

Assessment of Growth Hormone Secretion: What Are We Looking for Practically?

GH is a dominant factor in determining growth during childhood. Hence, the assessment of GH secretion is of major importance in the diagnosis of growth disorders. Since GH is secreted in a pulsatile fashion, a truly accurate production rate can only be calculated by using very frequent or continuous blood sampling over a 24-hour period. Several standard provocative tests have been established to evaluate GH secretory status. They remain the cornerstone in the assessment. Recent data have shown the existence of a wide spectrum of GH secretory disturbances ranging from severe GH deficiency to partial insufficiency and neurosecretory dysfunction. There is no well-defined cut-off point at which a particular child can be regarded as GH insufficient or sufficient for optimal growth. In clinical practice, the assessment of GH secretion starts with the careful analysis of the growth chart and height velocity. Careful clinical examination of the patient is essential for the proper diagnosis, and to exclude diseases influencing GH secretion. Additional biochemical tests may be required for the differential diagnosis. Thus, assessment of GH secretion in children requires auxological, clinical and biochemical data. GH insufficiency is documented by additional testing of pituitary secretory capacity either by standard provocative tests, by studying 24-hour GH profile or by measuring 24-hour production rate. The main goal is to detect those children who will benefit from treatment with hGH. The final assessment might consist in the response of growth velocity to exogenous hGH.

Noonan syndrome: growth and clinical manifestations in 144 cases.

We have analysed growth and the major clinical manifestations of 144 patients (89 males, 55 females) with Noonan syndrome from two West German centres. Size at birth was normal in both sexes. In both males and females, the mean height followed along the 3rd per centile until puberty, but decreased transiently due to an approximately 2 year delay in onset of puberty. Final height approaches the lower limits of normal at the end of the 2nd decade of life. The mean adult height was found to be (n = 20) 162.5 cm in males and (n = 13) 152.7 cm in females, respectively. Smoothed means and standard deviations for height were derived. These data may be used for the statistical evaluation of height of Noonan syndrome patients. Except for mental retardation and microcephaly, which are more frequent in males, the relative frequencies of minor anomalies and malformations were found to be similar in both sexes. The characteristic non-cyanotic heart defects in the Noonan syndrome do not appear to have a major influence on growth. The auxological data were compared with those in the Ullrich-Turner syndrome.

136 TREATMENT OF PRECOCIOUS PUBERTY BY INIRANASAL D-SER (TBU)6 LHRHI – 9EA10(BUSERELIN

GnRH analogues afford effective, selective, reversible inhibition of pituitary gonadotropin secretion. We administered Buserelin (300 ug × 6/die) to 18 girls affected by precocious puberty, for 6-24 months (onset of first symptoms before 8 years of age). We evaluated Buserelin's effects on pituitary-gonadal, pituitary-thyroid, pituitary-adrenal Function, ultrasonographic pelvic organs and thermographic mammary patterns, clinical and auxological features. Results: significant decreases (paired t test) were observed in: both LH and FSH reserves (LHRH test) and basal FSH since the First month (m) of treatment, E2 (3rd m), Progesterone (6th m); also TSH reserve (TRH test) since the 6th m, T3 (12th m) and fT3 (6th m) decreased significantly, though remaining in control range. 14, fT4, PRL, ACTH and adrenal hormones did not change significantly. Ultrasonography of the pelvis showed significant decreases of uterine (6th m) and ovarian (12th m) volume; the ovarian structure did not progress and follicle diameter uas always 9 mm. Clinical/thermographic evaluation oF the breast showed a generalized arrest or regression of its maturational patterns. Auxological data (slower bone maturation and growth velocity, lower SD scores For chronological and bone age, adult height prediction tending to improve) suggested a good prognosis. We conclude that these results of intranasal Buserelin administration and the absence of serious side effects make it advisable in the treatment of girls with true precocious puberty.

Spontaneous growth hormone and somatomedin-C/insulin-like growth factor-I secretion in obese subjects during puberty.

It has been reported that adult obese subjects present a reduced growth hormone secretion. As no data are available in the pubertal period, which is characterized in lean subjects by an increased spontaneous growth hormone secretion, the growth hormone circadian concentration was studied in a group of 18 obese male subjects in different pubertal stages, and compared to 26 age-matched control subjects. The data observed evidenced no statistically relevant differences regarding LH and FSH circadian secretion and morning testosterone concentration. On the contrary a statistically significant (p less than 0.02) difference in growth hormone 24 h integrated concentration was evident, particularly in prepubertal subjects; the sleep-related peak was evident in 28% of obese subjects and in 85% of controls. Sm-C/IGF-I concentration was similar to the concentration observed in controls in the prepubertal stage, but did not show the expected increase in the late puberty. Auxological data, performed on a sample of 80 subjects, showed both advanced height and bone age at beginning of puberty, and a trend toward a reduction of percentile for height in parallel with the pubertal maturation, suggesting that pubertal growth spurt in obese subjects is at least less pronounced than in lean subjects. It is concluded that GH and Sm-C/IGF-I secretion is impaired during puberty in obese subjects, leading to a reduced growth rate, while in the prepubertal period factors other than GH may replace or even potentiate its action.

Growth and development in simple obesity.

It is well known that fat children tend to be taller than their peers and to present a slight acceleration of skeletal and pubertal maturation. To verify this tendency and to examine some of the points that are still controversial, auxological data were studied concerning 303 subjects (141 males and 162 females, aged 6-16 years) affected by simple obesity. Subjects were seen to be taller than average by about 1 SD from 6 to 9 years of age, becoming close to or shorter than average at later ages. Height below the 10th percentile was common in 17% of males and 8% of females, due to hereditary shortness, growth delay or late puberty. Girls had early puberty and menarche; the rate of sexual maturation was variable in boys.

Blood pressure (BP) and metabolic control in IDDM

We studied BP patterns and the Renin-Angiotensin-Aldosterone axis (RAA) of 97 IDDM children (3-15 yrs old) in relation to the auxological data,the metabolic control and duration of diabetes (1-13 yrs).We analysed a total of 712 BP measurements. RESULTS. Mean systolic BP levels for age groups were at the 50th percentile of the general population,while the mean diastolic BP were at the 75th in both sexes.Systolic and diastolic BP levels were directly and significantly related to age, weight,height,Quetelet index,duration of disease and HbA1. Plasma Renin Activity (PRA) levels,all within normal limits, were related neither to age,Natruria and Kaliuria (contrary to normal children) nor to the parameters of metabolic control. CONCLUSIONS. BP levels were not grossly altered but were under the influence of metabolic control. The absence of a correlation between PRA and age or electrolytes excretion suggest an early disturbance of RAA, probably caused by concomitant metabolic alterations.

The Potential of Auxological Data for Monitoring Economic and Social Well-Being

The Potential of Auxological Data for Monitoring Economic and Social Well-Being

The Potential of Auxological Data for Monitoring Economic and Social Well-Being

Auxology, the study of physical growth (from auxein, to increase), has long been pressed into service as a measure of human welfare. In the sixteenth century Levinus Lemnius, doctor and later priest in the Low Countries, castigated “schoolmasters and others that take upon them to teach and boord young boyes (and) pinch their poore Pupils and Boorders by the belly, and allow them meate neither sufficient nor yet wholesome.” “Whereby it cometh to passe,” he continued, That in growth they seldome come to any personable stature, to the use of their full powers, to perfect strength and firmity of their members, or to any handsome feature or composition of bodily proportion: and the cause is for that in their tender and growing age, being kept under by famine and skanted of common meate and drinke, their natural moisture which requireth continuall cherishing and maintenance, was skanted and bebarred of his due nourishment and competent allowance [English translation of 1633, The Touchstone of Complexions, original 1561; see Tanner, 1981: 25].