Rudolph's Pediatrics, 22nd Ed.

CHAPTER 524. Tall Stature

Edward O. Reiter

Most tall children are normal, and their stature is linked to genetic background and an optimal environment for growth. Tall stature is concerning only if a child’s tallness is inappropriate for parental height or when linear growth velocity accelerates inappropriately. A number of endocrine and nonendocrine disorders cause excessive linear growth during childhood and adolescence (Table 524-1). Endocrine causes of accelerated growth include growth hormone (GH) excess or acromegaly; thyrotoxicosis; excess androgenic hormones, as in congenital adrenal hyperplasia and virilizing tumors; and sexual precocity. The latter disorders are readily apparent on physical examination because of accompanying signs of androgen excess or sexual maturation. Adolescents with hypogonadotropic hypogonadism can also be tall and have a eunuchoid habitus. Other clinical entities that can cause an increase in absolute height or accelerated height velocity include obesity, Marfan syndrome, homocystinuria, total lipodystrophy, neurofibromatosis, and chromosomal abnormalities such as Klinefelter syndrome, and 48XXYY and 47XYY syndromes.

CONSTITUTIONAL TALL STATURE

When the prediction of adult height for a girl exceeds 183 cm (6 feet), height is considered excessive by some families. Concern about the final adult height of boys is rarely about overgrowth. In general, tall children have tall parents, their body proportions are normal, their height has been greater than the 97th percentile since early childhood, and height velocity is within the normal range.

Treatment of excessively tall girls is a therapeutic dilemma for pediatricians and endocrinologists. Considerable data suggest that high-dose estrogen therapy markedly restricts final height to less than predicted. The vagaries of height prediction and the ever-present risk of dangerous long-term side effects of hormonal therapy dictate careful consideration of each patient’s clinical state, self-image, and desire for treatment. The use of high-dose estrogen in otherwise normal children must be weighed against the known (and unknown) toxicity of such therapy,3-9 including nausea, weight gain, edema, and hypertension. Other potential problems, such as thromboembolism, cystic hyperplasia of the breast, endometrial hyper-plasia, and cancer, have not been definitively related to estrogen therapy in children, but must be discussed. Height restriction is a cosmetic alteration, so the final decision must be made by well-informed parents and the child, in consultation with the physician.

Societal acceptance of tall women has markedly lowered the unease previously felt by tall women. Therapy, if and when necessary, is aimed at the acceleration of puberty prior to menarche in order to cause premature epiphyseal fusion.3,4 In the rare instances where treatment is desired, the optimal time for treatment is prior to the onset of puberty, but many girls are not referred until early puberty. A conjugated estrogen preparation such as Premarin is given cyclically: 10 mg/d for 21 days, followed by no treatment for 8 to 10 days. A progestational agent (5 mg) can be added for the last 5 to 10 days of the treatment period. Hormonal treatment is continued until growth ceases, usually when the bone age is 15 to 16 years.5 The average diminution of final adult height as a result of high-dose estrogen administration appears to be about 4 cm (range 0–9 cm). The benefits of postmenarchal treatment with exogenous estrogen therapy are limited because maximum growth after menarche is not more than 5 to 10 cm.

EXCESS OF PITUITARY GROWTH HORMONE

Excess of pituitary growth hormone (GH)10 is a rare condition among children. Gigantism is the predominant feature of extremely rare GH excess among children whose bony epiphyses have not yet fused. Many affected children have features found among adults with acromegaly.11-13 These include overgrowth of the mandible, enlargement of the hands and feet, thickening of the skin, and excessive sweating. Pituitary tumors that cause GH excess can occur spontaneously or possibly as a consequence of prolonged stimulation by hypothalamic growth hormone-releasing hormone (GHRH). Extra-hypothalamic tumors that secrete GHRH and stimulate the pituitary gland to produce excessive GH also can cause gigantism.

Screening for GH excess can be accomplished by means of measuring the concentration of insulin-like growth factor I (IGF-I) in the plasma. Levels of this GH-dependent peptide are consistently elevated among patients with active acromegaly and provide a better index of disease severity than does the level of GH itself. The diagnosis is confirmed by means of administering an oral glucose load and determining whether the serum level of GH is suppressed. Demonstration of increased GH-insulin-like growth factor (IGF) secretion should lead to radiologic evaluation of the hypothalamus and pituitary by MRI. Treatment consists of removal of a tumor if present, usually by the transsphenoidal route. Efforts are made to preserve normal pituitary tissue. If surgery is unsuccessful, irradiation of the pituitary gland may be appropriate, whereas the use of somatostatin analogs, dopamine agonists, and GH-receptor antagonists are important components of treatment programs for GH excess.10

Table 524-1. Differential Diagnosis of Statural Overgrowth

Fetal overgrowth

Maternal diabetes mellitus

Cerebral gigantism (Sotos syndrome)

Weaver syndrome

Beckwith-Wiedemann syndrome

Other IGF-II excess syndromes

Postnatal overgrowth leading to childhood tall stature

Familial (constitutional) tall stature

Cerebral gigantism

Beckwith-Wiedemann syndrome

Exogenous obesity

Excess GH secretion (pituitary gigantism)

McCune-Albright syndrome or MEN associated with excess GH secretion

Precocious puberty

Marfan syndrome

Klinefelter syndrome (XXY)

Weaver syndrome

Fragile X syndrome

Homocystinuria

XYY syndrome

Hyperthyroidism

Postnatal overgrowth leading to adult tall stature

Familial (constitutional) tall stature

Androgen or estrogen deficiency/estrogen resistance (in males)

Testicular feminization

Excess GH secretion

Marfan syndrome

Klinefelter syndrome (XXY)

XYY syndrome

IGF-II, insulin-like growth factor II; GH, growth hormone; MEN, multiple endocrine neoplasia.

OTHER OVERGROWTH DISORDERS

Several disorders are considered in the differential diagnosis of tall stature. Cerebral gigantism (Sotos syndrome) is associated with large size at birth, macrocrania, large ears, prominent mandible, subnormal intelligence, and poor coordination.15 Growth velocity is increased during the first years of life, but it later decelerates and follows a channel above but parallel to the 97th percentile. No endocrine abnormalities have yet been uncovered among these children. Beck-with-Wiedemann syndrome manifests among newborns as macrosomia, macroglossia, omphalocele, and hypoglycemia.16-20 The mechanism of overgrowth is not certain in this disorder, but evidence of abnormal insulin-like growth factor II (IGF-II) gene regulation has been found among some affected children, suggesting that IGF-II stimulates overgrowth in this syndrome.