Short-Term Effect on Growth of Two Doses of GRF 1-44 in Children with Growth Hormone Deficiency: Comparison with Growth Induced by Methionyl-GH Administration

Wit, Jan M.; Otten, B. J.; Waelkens, J. J. J.; Oostdijk, Wilma; Krabbe, Johannes G.; Rochefort, J. G.; Brande, J. L. Van den

doi:10.1159/000180817

“…Several other investigators also used weekly measurements of the lower leg length for studying growth promotion during treatments with growth hormone [85, 86, 87], and growth hormone-releasing hormone 1–44 [88]. But most of these studies lacked adequate statistical treatment of the weekly measurement series.…”

Section: Clinical Implications Of Short-term Growth Measurementsmentioning

confidence: 99%

The Analysis of Short-Term Growth

Hermanussen¹

1998

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The analysis of short-term growth needs repetitive measurements of body stature or of segments of the body. When body stature is measured at monthly intervals, an irregular incremental pattern becomes obvious with a number of large-scale components such as series of prepubertal and pubertal growth spurts, seasonal influences on height gain, and influences of the psychosocial and economic background. When measurement intervals decrease, incremental patterns appear even more irregular, and a number of short-scale components become apparent that are distinct from measurement error. The review summarizes the analysis of short-term growth, and presents the current findings supporting different views on how growth progresses at short term. In particular, observations are presented that suggest growth being a pulsatile, a periodic, a saltatory, and a chaotic event. Some recent animal studies and studies in human newborns are added in detail as they illustrate short-term growth on the basis of accurate 24-hour measurements of the lower leg. The latter investigations support the idea of short-term growth being characterized by chaotic series of ‘mini growth spurts’ that occur at intervals of approximately 4–5 days, not only in human neonates, but also in rats. The amplitude of mini growth spurts ranges between 2 and some 10 mm, and growth velocity of each spurt also varies considerably so that one spurt needs between less than 1 and up to several days for completion.

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“…The majority of short, growth hormone-insufficient children appear to have a hypothalamic defect in GH secretion, as they produce a G H response to a bolus injection of growth hormone-releasing hormone, GHRH (Grossman et al., 1984). This has led to the investigation of the use of GHRH as a therapeutic agent in this group of children, administered subcutaneously (s.c.) as pulses, or once or twice daily (Thorner et al, , 1988Smith et al, 1986;Ross et al, 1987a;Wit et al, 1987;Low et al, 1988). However, some children with severe GH insufficiency fail to show a significant growth response to GHRH therapy and the frequency of injection makes it, at present, an impractical therapeutic alternative to biosynthetic human growth hormone (hGH).…”

mentioning

confidence: 99%

Pyridostigmine fails to increase either spontaneous or GHRH‐stimulated GH secretion during day or night in growth hormone‐insufficient children

Kirk

¹

,

Ross

²

,

Trainer

³

et al. 1991

Clinical Endocrinology

0

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OBJECTIVE The aim of the study was to investigate whether pyridostigmine, a cholinesterase inhibitor which is thought to act at the hypothalamus to inhibit somatostatin secretion, would augment spontaneous or GHRH-stimulated serum GH levels in patients with GH-insufficiency. DESIGN Oral pyridostigmine 60 mg or placebo was administered at the start of a 9-h subcutaneous infusion of either GHRH (1-29)NH2 10 micrograms/kg/h or saline control. Studies were performed during the daytime (0900-1800 h) in five patients, and the night-time (2100-0600 h) in a further five. PATIENTS Ten short, pre-pubertal children (aged 6-11 years; eight boys) with growth hormone insufficiency were studied. MEASURES Blood for serum GH was sampled every 20 min, and analysed using the PULSAR program. RESULTS The subcutaneous infusion of GHRH 10 micrograms/kg/h increased mean serum GH levels (+/- SEM): by day 17.7(+/- 6.8) vs placebo 2.2(+/- 0.4) mU/l (P less than 0.01), and by night 26.9(+/- 3.3) vs 5.5(+/- 1.3) mU/l (P less than 0.05). There was a significant rise in mean 'baseline' GH concentration: by day 5.5(+/- 1.7) vs 1.0(+/- 0.0) mU/l (P less than 0.05); and night 8.2(+/- 2.7) vs 1.3(+/- 0.3) mU/l (P less than 0.05). Pyridostigmine failed to produce a significant overall increase in either spontaneous or GHRH-stimulated GH secretion by day or night, although there was a significant rise in mean GH levels during the 3 h following pyridostigmine administration in the morning: 4.4(+/- 1.1) vs 2.4(+/- 0.5) mU/l (P less than 0.001). GHRH or pyridostigmine given singly or in combination had no significant effect on the number of pulses. Side-effects attributable to pyridostigmine occurred in seven children. CONCLUSIONS Pyridostigmine, either on its own or as an adjuvant therapy in combination with GHRH, acts for only a brief time and does not offer any potential benefit in the management of children with short stature.

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The Growth Hormone Secretory Pattern and Statural Growth

Robinson¹,

Hindmarsh

²

1999

Comprehensive Physiology

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The sections in this article are: How is the Growth Hormone Secretory Pattern Analyzed? General Considerations in Pulse Analysis of Growth Hormone Secretion Construction of Data Arrays or Hormone Profiles Sampling Interval and Aliasing Duration of Sampling Discrete or Integrated Samples Assays and Noise Basic Evaluation Stationarization Analysis of Profiles Time Series Analysis Deconvolution Analysis Baseline Occupancy Chaos Neural Networks Characterization of Growth Hormone Secretory Patterns Ontogeny of Episodic Growth Hormone Secretion Growth Hormone Secretory Patterns in the Prepubertal Period Puberty and Effects of Gonadal Steroids on the Growth Hormone Secretory Pattern Growth Hormone Secretory Patterns in Adulthood Other Endocrine Inputs Affecting Growth Hormone Secretory Patterns Extrinsic Factors Affecting Growth Hormone Pulsatility How Does the Growth Hormone Secretory Pattern Reflect the Episodic Nature of Hypothalamic Control Mechanisms? Growth Hormone–Releasing Hormone and Somatostatin Interactions Generate Growth Hormone Pulsatility Other Growth Hormone Secretogogues Growth Hormone Feedback Effects on Endogenous Growth Hormone Pulsatility How is The Growth Hormone Secretory Signal Modified in its Passage from the Pituitary to the Peripheral Target Tissues? How Are Growth Hormone Patterns Modified by Interactions with Growth Hormone Binding Proteins? How are the Temporal Elements of the Growth Hormone Signal Detected and Interpreted by the Target Tissues? Pattern‐Dependent Growth Hormone Responses Growth Hormone Patterns and Insulin‐Like Growth Factor I Generation What is the Significance of the Growth Hormone Secretory Pattern for Statural Growth? Animal Studies Human Studies Indirect Manipulation of Growth Hormone Secretory Pattern Summary

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Short-Term Effect on Growth of Two Doses of GRF 1-44 in Children with Growth Hormone Deficiency: Comparison with Growth Induced by Methionyl-GH Administration

Cited by 14 publications

References 17 publications

The Analysis of Short-Term Growth

The Analysis of Short-Term Growth

Pyridostigmine fails to increase either spontaneous or GHRH‐stimulated GH secretion during day or night in growth hormone‐insufficient children

The Growth Hormone Secretory Pattern and Statural Growth

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