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ENDOCRINE CAUSES OF SHORT STATURE

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Several pituitary hormones are involved in growth and development. Pituitary hormones contribute to growth by regulating hormone secretion by peripheral glands, which act on tissues to increase growth and modulate the secretion of the pituitary itself. Growth hormone (GH) from the pituitary, thyroid hormone, and sex steroids all act synergistically at the growth plates of long bones to increase height during childhood and adolescence. Through long feedback loops, these peripheral hormones regulate the hypothalamic pituitary signals that stimulate their own release but also modulate other hypothalamic pituitary signals such as the effect of thyroid hormone on thyrotropin-releasing hormone (TRH) and thyroid-stimulating hormone (TSH) secretion as well as its effect on GH secretion.

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The deficiency of GH, thyroid hormone, or sex steroids generally leads to suboptimal growth and eventually to short final height. These deficiencies can result from peripheral gland disease, in which case it is categorized as a primary deficiency. Examples of primary deficiencies include primary hypothyroidism due to autoimmune thyroid disease (Hashimoto thyroiditis) or primary ovarian failure (whether autoimmune, idiopathic, or secondary to Turner syndrome). Primary deficiencies are characterized by inadequate secretion of hormone by a peripheral gland and a reflex increase in pituitary and hypothalamic signals. Because the hypothalamic-pituitary unit is exquisitely sensitive to minor fluctuations of peripheral hormones, the hypothalamic-pituitary hormone secretion increases in response to a minute reduction in the concentration of the peripheral hormone, which may still fall within the normal range. As a result, for example, primary hypothyroidism is characterized by a normal or low thyroid hormone concentration and elevated TRH and TSH concentrations.

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Secondary deficiencies refer to a decline in peripheral hormone secretion caused by a decrease in the pituitary secretion of its trophic hormones. A case in point is secondary hypothyroidism where both TSH and T4 concentrations are low. Tertiary deficiencies refer to an abnormal release of hypothalamic factors leading to decreased stimulation of the pituitary, which eventually decreases peripheral hormone concentrations.

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Although short stature can be the result of GH deficiency (isolated or due to panhypopituitarism), thyroid hormone deficiency (whether primary or secondary/tertiary), or sex steroid deficiency or a combination of all 3, this chapter will only focus on GH deficiency. Another cause of short stature is the concentration of steroid, whether endogenous or more commonly exogenous, which will be discussed in a separate chapter.

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GROWTH HORMONE DEFICIENCY

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EPIDEMIOLOGY

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It is hard to estimate the true incidence and prevalence of growth hormone deficiency (GHD) because GHD lies on a spectrum from mild (in which cases may be missed) to severe, with genetic and biochemical confirmation. In addition, the definition of GHD varies from one geographic region to another and sometimes from one center to another based on how the diagnosing physician interprets the clinical auxologic and biochemical data. In addition, there is variability in terms of whether provocative ...

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