| Clinical disorders of GH secretion
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| GH deficiency in children is one of several causes of short stature, while GH excess in children leads to gigantism and, in adults, acromegaly
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| The absence of a plasma reference range for GH means that GH deficiency may only be diagnosed by studying the dynamics of GH secretion, either during sleep or following a stimulation test. Basal IGF-I or IGFBP-3 measurements may serve as a preliminary screening test. Treatment is by regular injection of recombinant human GH. Adults with a definite cause of GH deficiency (hypopituitarism) are also candidates for GH replacement therapy. A rare genetic cause of short stature is Laron dwarfism in which GH levels are elevated but IGF-I levels are subnormal - a GH receptor defect is responsible.
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| In most cases, GH excess is caused by a pituitary tumor
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GH excess is almost always due to a GH-secreting pituitary tumor, although GHRH-secreting tumors in the hypothalamus and ectopic GHRH production from pancreatic tumors have been described. In children, GH excess manifests itself as gigantism. In adults, the epiphyses of the long bones have closed and so further linear growth is not possible. Therefore, the adult form, acromegaly, is characterized by a thickening of tissues and overgrowth of the bones in the hands, feet and face. Enlarged lips and tongue with mandibular overgrowth give rise to a classic facial appearance. Excessive sweating and arthritis are also common symptoms. Unfortunately, the progression of acromegaly is so slow that an average of 9 years elapses between the onset of symptoms and diagnosis. Classically, the diagnosis of GH excess has relied on showing inadequate GH suppression during a standard 75 g oral glucose tolerance test and on elevated IGF-I levels. However, pubescent patients may have paradoxical responses to glucose, and IGF-I levels are normally elevated during this developmental stage. As such, MRI evidence of a pituitary tumor is critical in making the proper diagnosis. Surgery is the preferred treatment, although long-acting somatostatin is also effective.
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| GROWTH HORMONE RESISTANCE (LARON SYNDROME) - INCIDENCE ∼1 PER 1-2 MILLION |
| A 5-year-old boy was brought to his GP because his mother was concerned that he had been the smallest in his class, and of the same size as his 3-year-old brother. Both parents were of average height. He was referred to hospital. His measured height was well below the 0.3 centile. |
| He underwent an insulin tolerance tests to assess his GH reserve and high levels were found throughout (GH >30 iU/l). The endocrinologist asked for the measurement of the insulin growth factor-I (IGF-I) to be performed. The IGF-I concentration was very low. |
| Comment. The high circulating levels of GH with the corresponding failure to produce IGF-I in the liver are diagnostic of the Laron syndrome. This is a defect in the GH receptors inherited in an autosomal recessive pattern. Without treatment the final height is likely to be 120-130 cm. GH is ineffective and specific treatment with IGF-I is required. |
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