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Growth Disorders: Pathophysiology and Treatment

	Abstract

Top Abstract Introduction

 
Growth Disorders: Pathophysiology and Treatment, C.J.H. Kelner, M.O. Savage, H.F. Sterling, and P. Saenger, Editors; Lippincott-Raven, Publ. (Philadelphia, PA), 1998 [or Chapman & Hall, Publ. (London, UK), 1998], 822 pgs., price $135.

	Introduction

Top Abstract Introduction

 
The development of sophisticated techniques for measuring circulating GH levels, the discovery of a plethora of growth factors, and the development of molecular biological techniques for studying the process of growth on cellular and tissue levels has enabled scientists involved in the study of human growth to move from auxology to a beginning comprehension of the complex physiological mechanisms involved in human growth and development. At the same time, the availability of an inexhaustible supply of biosynthetic human GH has raised the possibility of intervention in that very growth process. This has led to an urgent interest in identifying which child would benefit from such an intervention, an awareness of the many difficulties involved in making that identification, and a concern whether such interventions are warranted from a medical, social, and psychological point of view.

Acknowledging the multifactorial nature of physical growth and development, the editors have set out in this book to survey the large number of physiological and nonphysiological factors that affect the growth process.

An international cohort of 71 authors has contributed the 45 chapters that make up the book. The chapters are short and, therefore, depend on the ability of the authors to present data succinctly, yet comprehensibly, and to derive general and up-to-date guiding principles. Following a historical orientation to the study of human growth, the book is divided into five sections addressing the physiology of normal growth, growth assessment, general and specific endocrine disorders, and available therapies.

Part One addresses the physiology of normal linear growth. Chapters on cellular growth and bone and cartilage growth are excellent, providing useful concepts and hypotheses. There is a well written discussion of the nature of growth velocity and the fallacies inherent in short- and long-term linear measurements. A chapter on nutrition and growth is well done, providing a good overview of the multifactorial effects of protein-energy, protein, and micronutrient deficiencies on somatic growth and on the GH-insulin-like growth factor (IGF) I axis. The chapter on the central regulation of GH secretion is marred by the failure to separate clearly contradictory animal and human data. This contrasts with a very good chapter on peripheral growth factors, in which the author successfully summarizes complex material. The first section ends with well written surveys of fetal growth, and growth in the three postpartum phases of infancy, childhood, and adolescence.

Part Two, Growth Assessment, begins with a very good discussion of the clinical evaluation of abnormal growth, with excellent algorithms for the assessment of the short or tall child and of the child with growth failure and early and delayed puberty. The other chapters in this section deal with the techniques one uses to make such assessments: 1) proper methods for measuring linear length or height; 2) a detailed discussion of the pitfalls in the use of bone ages for determining skeletal maturation; 3) a good chapter on the radiological assessment of skeletal dysplasias; and 4) a chapter on the tools used to assess the psychological state of mind of the short child. The chapter on endocrine assessment of growth is disappointingly limited in scope, focusing too much on statistical problems in interpreting test results and saying little about the rationale for using one or another testing agent. The use of IGF-I and IGF-binding protein-3 levels in diagnosing GH deficiency is dealt with in a cursory manner only; a more extensive discussion is warranted in light of current recommendations that those factors be given strong consideration in the diagnosis of GH deficiency.

Part Three concerns the many chronic disorders that can impinge on the growth process. Here, much depends on the ability of the authors to address specifically how disorders in their area of specialization affect a child’s growth. In general, they succeed. There is an informative chapter on the evaluation of prenatal growth restriction and available intrauterine therapeutic interventions. In the several chapters on the effect of respiratory, gastrointestinal, renal, cardiovascular, hematologic, and calcium disorders and diabetes on growth, the authors are successful in emphasizing the mechanisms whereby such disturbances affect the growth process. A chapter on genetic and dysmorphic syndromes of short stature consists mostly of extensive lists and is of limited usefulness. The chapter on psychological disorders associated with short stature provides an excellent discussion of the many factors leading to psychological stress in children with constitutional short stature, hypopituitarism, and Turner syndrome and discusses evidence for and against the belief that GH therapy alleviates that stress. A disappointment is the chapter on the etiology and management of growth failure in tropical and developing countries, which is, in large part, a repetition of earlier chapters. A discussion of the effect of socioeconomic conditions on growth in those parts of the world where over 450 million children are stunted in height from chronic malnutrition would have provided an additional dimension to the book.

Part Four encompasses the endocrine causes of abnormal growth, including of course abnormalities of the secretion and action of GH. Thyroid, adrenal, and gonadal disorders are discussed primarily from the viewpoint of their relevance to growth.

Part Five of the book discusses treatment. There is an excellent chapter on GH deficiency with a good discussion of the molecular and biochemical effects of recombinant GH therapy, complemented by another excellent chapter on the metabolic side effects and adverse effects of GH therapy. There is a well written, reasoned overview of the use of recombinant GH in idiopathic short stature and the difficulties of predicting and judging therapeutic outcomes. The Food and Drug Administration approved use of recombinant GH therapy in Turner syndrome, and its still experimental use in Noonan syndrome and intrauterine growth retardation are covered. Therapeutic options other than GH are discussed, in particular the potential for alternate therapy offered by GHRH and the interesting development of protein and nonprotein GH secretagogues. The author of the chapter on surgical limb lengthening procedures is appropriately cautious.

Finally, the book ends with chapters that address normal and abnormal conditions resulting in tall stature, hormonal interventions in constitutional tall stature, and the treatment of precocious puberty and gigantism, including surgical limb-shortening procedures.

The editors have managed to avoid excessive overlap in the chapters, although some is inevitable. The figures and tables are, in general, good, although there are some notable lapses in providing appropriate legends. The index is adequate. There are a few pages of color plates, several of which seem irrelevant to the theme of the book; these could have been eliminated without much loss. The chapters are well referenced, although there are no citations after 1997. The editors have succeeded in their aim to address the broad spectrum of growth and growth-related disorders. The book provides a good foundation for understanding the physiology of linear growth and the spectrum of adverse influences on growth, endocrine and nonendocrine. It addresses important clinical considerations in the evaluation of growth disturbances. The book provides the context into which rapidly developing molecular insights can be fit. The book will be most useful to pediatric endocrinologists, especially those in training, and should also have a broad interest for the many professionals whose responsibilities include the observation of the growing child.

Received March 10, 2000. Accepted March 21, 2000.

Address correspondence and requests for reprints to: Jennifer J. Bell, M.D., Columbia University College of Physicians and Surgeons, Department of Pediatrics, 3959 Broadway, New York, New York 10032. E-mail: jjb4@columbia.edu.\.

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