Tallnessimplies high rates of linear growth of the child, exceeding the average rates for a given chronological age and gender. Tallness- not a disease, but more often a sign of excessive physical development, however, it is one of the leading symptoms of endocrine pathology such as gigantism and acromegaly. Gigantism- a disease associated with excessive production of growth hormone by the adenohypophysis. The cause of the development of gigantism is a pathology of the hypothalamic-pituitary region, which develops as a result of tumors, neuroinfection, intoxication, and traumatic brain injury.

GigantismIt is more often observed in boys of pre- and pubertal age. Characterized by high rates of dew, fatigue, weakness, decreased performance and performance at school, headaches, dizziness, and possible visual impairment. Body proportions are preserved. Rapid development of the hands and feet and delayed sexual development are noted. In the presence of a growing pituitary adenoma, along with general cerebral symptoms, visual acuity gradually decreases and visual fields narrow.

AcromegalyIt is extremely rare in children. With acromegaly, there is varying sensitivity of peripheral tissues to growth hormone. All cerebral symptoms are expressed in to a greater extent than with gigantism. Children often complain of bone pain, muscle weakness, loss of smell. Characterized by disproportionate growth of the skeleton and soft tissues: an increase in the superciliary and zygomatic arches, the lower jaw and the spaces between the teeth, a significant thickening of all bones, an increase in the phalanges of the fingers and heel bone, the appearance of bone outgrowths - spines. The growth of soft tissues leads to characteristic disfigurement of the face due to thickening of the nose and loss of the ears. An increase in the size of the tongue causes dysarthria, thickening of the vocal cords causes a deepening of the voice. There are symptoms of hypogonadism.

TO rare genetic forms of tall stature include: Marfan syndrome is characterized by: tall stature, “spider” fingers, dolichocephaly, chest deformation, scoliosis, underweight, heart defects, ophthalmological disorders; Sotos symptoms are characterized by: acromegaly, lack of coordination, mental retardation; Pyle's symptoms are characterized by: disproportionate long lower limbs, valgus deviation of the knee joints, limited extension of the elbow joints; Homocystinuria is characterized by: osteoporosis, a tendency to fractures, optic nerve atrophy, arterial thrombosis, mental retardation, a phenotype similar to Marfan syndrome.

Hermaphroditismaccompanied by an abnormal (bisexual) structure of the external genitalia. Anomalies in the structure of the external genitalia in persons with a female genetic sex (karyotype 46 XX) are usually designated by the term “false female hermaphroditism”, anomalies in persons with a male genetic sex (karyotype 46 XY) are called “false male hermaphroditism”, with the exception of a rare form - true hermaphroditism , in which the presence of a karyotype 46 XY, 46 XX or 46 XY\46 XX is possible. The external genitalia have a bisexual structure with varying degrees of virilization. The internal genitalia usually have feminine traits: there is a uterus (often one-horned), vagina, tubes. At puberty, patients tend to have predominantly female characteristics.

Diagnosis of hermaphrodism

It is necessary to begin examining children, first of all, by determining sex chromatin and karyotype. Detection of positive sex chromatin and karyotype 46 XX most likely indicate false female hermaphroditism. An accurate diagnosis can only be made by laparotomy, macroscopic and histological examination of the gonads. In the case of negative sex chromatin, a differential diagnosis should be made between various forms of false male hermaphroditism.

The presence of the uterus, tubes and vagina with karyotype 46 XY and mosaic 46 XY\45 X0 suggests the presence of testicular dysgenesis syndrome. Much less often, gonadal bisexuality (true hermaphroditism) can be detected. With a karyotype of 46 XY and the absence of the uterus and upper third of the vagina, one should think about the syndrome of incomplete masculinization.

A significant difficulty is the differential diagnosis between the incomplete form of masculinization and the incomplete form of testicular feminization. The difference is revealed only during the puberty period, when in children with an incomplete form of testicular feminization, the mammary glands spontaneously begin to develop, the figure develops according to the female type, and with the syndrome of incomplete masculinization, all the signs of the male puberty are noted.

Treatment of hermaphrodism

In front of everyone forms of false female hermaphroditism the choice of the female gender is beyond doubt. In case of congenital dysfunction of the adrenal cortex, adequate and timely therapy with cortisol drugs avoids further villization and creates the preconditions for further physiological formation of the ovaries. With false male hermaphroditism with satisfactory development of the corpora cavernosa of the penis, the male gender is selected and masculinizing genital plastic surgery is performed. With true hermaphroditism The choice of female gender is desirable. Feminizing genital plastic surgery is performed.

Tallness is understood as exceeding a child's height by more than 2.0 SDS (standard deviation coefficient) - 2.3 percentile - for a given age, gender and population.

In children, there are primary, secondary and idiopathic tall stature.

The primary ones include:

• syndromes with violation of sex chromosomes - Klinefelter (47 XXY), 47 XYY, fragile X chromosome, 47 XXX;
• dysmorphic syndromes due to metabolic or connective tissue disorders - Marfan syndrome, homocystinuria, total congenital lipodystrophy (Berardinelli syndrome);
• dysmorphic syndromes with symmetrical tall stature (Banayan - Riley - Ruvalcaba, Eleyalde, Marshall - Smith, Nevo, Simpson - Golabi - Bemel, Sotos, Wever);
• dysmorphic syndromes with partial (asymmetric) tall stature (Beckwith - Wiedemann, Klippel - Treponet - Weber, Proteus).

Secondary tallness includes:

• hyperproduction of growth hormone against the background of a mass formation of the pituitary gland;
• hyperinsulinism;
• exogenous constitutional obesity;
• familial glucocorticoid deficiency;
• conditions that cause tall stature in children and normal height or short stature in adults - precocious sexual development (PPD), exogenous influence of estrogens or androgens, thyrotoxicosis, congenital adrenal hyperplasia;
• conditions that predetermine normal growth in children and tall stature in adults - deficiency of gonadotropic hormones, aromatase, dysfunction of estrogen receptors.

Idiopathic (normal) tall stature includes genetic (familial or constitutional) and non-familial idiopathic forms.

Stages of examination

Anamnesis collection and clinical examination using instrumental and laboratory methods are provided.

Anamnestic data:

• clarification of parents’ height with calculation of genetic (target) height and determination of the child’s growth corridor; genetic (target) height for a boy = (mother's height in cm + father's height in cm)/2 plus 6.5 cm; for a girl = (mother’s height in cm + father’s height in cm)/2 minus 6.5 cm; growth corridor in boys: the somatogram (growth curve) shows the father’s height - one limit, the mother’s height plus 13 cm - the second limit; for girls: mother’s height is one limit, father’s height minus 13 cm is the second limit;
• growth of siblings, grandparents;
• gestational age, course of pregnancy and childbirth;
• height and weight of the child at birth;
• the rate of growth of the child from the first months of life until the moment of visiting a doctor;
• timing of the onset of puberty in parents;
• illnesses of the patient during life.

Clinical examination:

• measuring the patient's height and weight;
• measuring the ratio of the length of the upper body to the length of the lower, measuring the ratio of the arm span to the length of the body (body proportions);
• assessment of the presence of stigmata dysmorphogenesis (congenital developmental features);
• assessment of sexual development (Tanner stage);
• assessment of intelligence, sense of smell.

Laboratory and instrumental examination:

• general and biochemical (creatinine, urea, potassium, sodium, calcium, phosphorus, alkaline phosphatase, glucose, liver enzymes) blood test;
• X-ray of the left hand and wrist with assessment of bone age and calculation of projected height using index tables;
• predicted (final) height of the child in cm = height of the child in cm/% bone maturity x 100%;
• hormonal examination (the spectrum depends on the expected pathology) - growth hormone (GH), insulin-like growth factor-1 (IGF-1), insulin-like growth factor binding protein-3 (IGFBP-3), luteinizing hormone (LH), follicle-stimulating hormone ( FSH), testosterone, estradiol, dehydroepiandrosterone, 17-hydroxyprogesterone, insulin/C-peptide, thyroid-stimulating hormone (TSH), free thyroxine (T4 free), antibodies to thyroid peroxidase (TPO) and TSH receptors;
• oral glucose tolerance test (OGTT) with determination of GH levels every 30 minutes for 2 hours. Normally, in response to hyperglycemia, there is a decrease in GH levels down to minimally detectable levels (suppression). With gigantism, there is no decrease in GH below 1 ng/ml; in 30% of cases there is a paradoxical release of GH in response to a glucose load;
• examination by an ophthalmologist (fundus, visual fields), consultation with a neurologist;
• cytogenetic analysis;
• content and spectrum of amino acids (methionine and homocysteine ​​in urine and blood serum);
• CT (MRI) of the brain and pituitary gland with mandatory contrast;
• molecular diagnostics.

Differential diagnosis of tall stature in children

In Fig. 1 presents an algorithm for the differential diagnosis of diseases accompanied by tall stature in children, starting from the neonatal period.

According to the time of occurrence, tall stature is distinguished:

• fetal macrosomia or prenatal tall stature syndrome;
• postnatal advance in physical development leading to tall stature childhood;
• postnatal advance in physical development, leading to tall stature in adults.

Fetal macrosomia associated with hyperinsulinemia and hypoglycemia

Fetal macrosomia. It is divided into diseases associated with the presence or absence of hyperinsulinemia and hypoglycemia (Fig. 2).

Newborns from mothers with diabetes mellitus

Long-term uncompensated disorders of carbohydrate metabolism in a pregnant woman are the most common reason birth of a child with macrosomia. Prolonged hyperglycemia in a pregnant woman with undiagnosed (gestational), sub- or decompensated diabetes mellitus leads to hyperplasia of the β-cells of the fetal pancreas, causing an increase in the secretion of fetal insulin. Chronic hyperinsulinemia stimulates an increase in IGF-1 expression, which is manifested by increases in IGF-1 concentrations at birth. On the other hand, insulin, having an anabolic effect, has a growth-stimulating effect on the fetus.

In the presence of severe placental dysfunction and vascular disorders, a newborn from a mother with diabetes may experience intrauterine growth retardation and congenital malformations (heart, urinary system, eyes, caudal dysgenesis, microcephaly). A common problem is transient early postnatal hypoglycemia. Mothers with uncompensated diabetes mellitus have an increased risk of having premature babies, children with hyaline membrane disease, hypocalcemia, prolonged hyperbilirubinemia, thrombosis (renal veins), and transient cardiomyopathy.

Persistent hyperinsulinemic hypoglycemia of newborns (PHH)

This is a group of congenital diseases that are based on a defect in the development or functioning of pancreatic β-cells, causing uncontrolled insulin secretion. The latter leads to increased glucose utilization and the development of severe hypoglycemia. The incidence of PHG is 1 case per 50,000 newborns in the European population.

There are two forms of PHG in newborns: focal (isolated) and diffuse hyperplasia of pancreatic β-cells. Most familial and sporadic cases of the disease have an autosomal recessive mode of inheritance. In some familial forms of PHG, mutations are found in the KCNJ11 and ABCC8 genes (SUR1 and Kir6.2 subunits of the pancreatic KATP channel).

The classic clinical manifestation of PHG is macrosomia for a given gestational age and persistent symptomatic hypoglycemia in the first days of life.

Correction requires a high glucose supply rate - more than 10 mg/kg/minute. Laboratory criteria for hyperinsulinemic hypoglycemia include low levels of ketone bodies and free fatty acids, high levels of insulin and C-peptide.

Beckwith-Wiedemann syndrome (BWS)

A group of syndromes is described that are accompanied by neonatal macrosomia with enlargement of internal organs. They are based on excessive secretion of insulin-like growth factor 2 (IGF-2). The most common disease is Beckwith-Wiedemann syndrome (synonym: visceromegaly, omphacele and macroglossia syndrome). The incidence of BWS is 1 case per 13,700 newborns.

The cause of SBV is a change in the number of growth regulatory genes located at the end short shoulder 11th chromosome (11p15.5). The molecular abnormalities in this disease are complex and explain the variability of the phenotype. 10% of patients with BWS have chromosomal abnormalities. In the other 90% of cases, molecular defects are identified in known genes involved in the pathogenesis of the syndrome and candidate genes identified in sporadic cases.

Minimal diagnostic signs of BWS include macroglossia, umbilical cord hernia, macrosomia, earlobe notching, and hypoglycemia.

Frequent anomalies are macroglossia and omphacele (less commonly, separation of the rectus abdominis muscles). Macrosomia is noted from birth (the length of the newborn is more than 52 cm and weight is more than 4 kg) or develops postnatally. Microcephaly or hydrocephalus may be observed; protruding nape; malocclusion associated with hypoplasia of the upper jaw and relative hyperplasia of the lower jaw; exophthalmos; relative orbital hypoplasia. Hemihypertrophy and pigmented nevi often occur.

Visceromegaly (hepatomegaly, splenomegaly, nephromegaly, pancreatomegaly, less often - cardiomegaly), hyperplasia of the uterus, bladder, clitoris, and thymus are noted.

In 30–50% of patients, hyperinsulinemic hypoglycemia is observed due to pancreatic β-cell hyperplasia. In most cases, it is transient in nature and is relieved by the administration of glucose and diazoxide. In some patients, partial pancreatectomy is required to normalize glycemic levels. Moderate mental retardation is usually associated with hypoglycemia.

Patients with BWS have an increased risk of developing embryonal tumors (Wilms tumor, hepatoblastoma, adrenocortical carcinoma, gonadoblastoma).

Simpson-Golabi-Bemel syndrome (GBS)

The disease is an X-linked syndrome with prenatal and postnatal tall stature. Minimal diagnostic signs are macrosomia (birth weight 4,000–5,000 g), abnormalities of the facial part of the skull, polydactyly, and nail hypoplasia.

Other phenotypic manifestations are similar to BWS. Macroglossia, visceromegaly, hyperinsulinemic hypoglycemia, and a tendency to embryonal tumors are noted. The height of men reaches 192–210 cm.

GBS syndrome is based on functional disturbances of a gene that plays a role in controlling the growth of embryonic mesodermal tissue, glypican 3 (GPC3). A potential relationship between the receptor of this gene and IGF-2 is discussed, which may explain the similar clinical signs of GBS and BWS syndromes.

Perlman syndrome

This rare genetic disease is characterized by prenatal macrosomia, renal hamartoma, predisposition to fetal tumors (Wilms tumor), hypoglycemia due to pancreatic islet cell hyperplasia, and facial dysmorphia. Most patients die in the neonatal period. The cause of the disease is currently unknown.

Fetal macrosomia with normal insulin levels

Sotos syndrome

The population incidence of Sotos syndrome (cerebral gigantism syndrome) is unknown. Most cases are sporadic. Familial forms of the syndrome have an autosomal dominant mode of inheritance. Minimal diagnostic signs include acromegaly, increased growth, mental retardation, and incoordination. At birth, an increase in body weight and height above the 90th percentile is typical. There is an acceleration of growth in the first years of life; the height of patients exceeds the 97th percentile. Growth acceleration continues up to 4–5 years. Sexual development occurs at normal times, and early puberty may occur.

The results of the levels (basal and during OGTT) of GH, IGF-1, IGFBP-3 have normal values. There are no specific laboratory or instrumental signs of the syndrome.

Macrocephaly with prominent frontal tubercles, prognathia, hypertelorism, anti-Mongoloid eye shape, protruding lower jaw, macroglossia, high palate, and strabismus are observed. Scoliosis, enlarged feet and hands, and syndactyly of the toes have been described. Increased risk of neoplasia, in particular hepatic carcinoma, Wilms tumor, ovarian, parathyroid glands. The degree of mental retardation is moderate. Convulsions and loss of coordination are noted.

Marshall-Smith syndrome

This disease is a rare genetic syndrome and is characterized by prenatal tallness, progression of bone age, and delayed mental development, facial stigmas, large sizes hands and feet, thickening of the proximal and middle phalanges of the fingers. The main cause of death for patients in early childhood is pulmonary failure. The molecular cause of the syndrome is currently unknown.

Being ahead of a child in growth can be called a condition when the child’s growth rate is significantly ahead of the average, i.e. is outside the 95th centile in the growth chart for children of this age (outside the norm).

If the child is significantly ahead in growth, first of all, it is necessary to draw the attention of the pediatrician observing the child to this condition and examine the child with specialists (endocrinologist, cardiologist, geneticist, etc.).

Tall stature in healthy children.

The increasing incidence of so-called constitutional tall stature, which has no pathological basis and is characteristic of completely healthy children, has become a relatively new pediatric problem. The excessively tall height of girls often forces parents to seek medical help. For certain indications, such children may be treated hormonal drugs, inhibiting growth and enhancing skeletal maturation. Most often, diethylstilbestrol, estrogen conjugates, and estradiol are used for these purposes. In relation to the predicted final height, such “treatment” for 1.5–2 years can result in a growth delay of 4–8 cm.

Tall healthy boys very rarely cause concern for parents and children themselves. Only in cases of Marfan disease, where aortic aneurysmization increases in parallel with intensive skeletal growth and in proportion to it, can there be indications for growth inhibition with adrenal androgens or testosterone.

However, regardless of the reasons for tall stature, it is necessary to monitor the child’s health, since active growth of the skeleton entails active growth of internal tissues and organs, which can negatively affect their functioning. This is especially true of the heart. Parents need to be especially careful during periods of active skeletal growth (5-7 years and 12-16 years). If active growth is accompanied by internal pain or disturbances in the functioning of internal organs, you should consult a doctor.

Possible reasons for a child being ahead in growth are tall stature.

Pathological tall stature is much less common than short stature. It is necessary to distinguish between transient forms of tallness and tallness that persists until the end of the extension period.

Transient forms include greater length and body weight in the intrauterine fetus of a woman suffering from diabetes. Sometimes, already in postnatal development, accelerated growth of children with hyperfunction of the thyroid gland or increased production of adrenal androgens is temporarily observed.

Persistent forms of tall stature can be of a chromosomal nature, in particular, they are characteristic of carriers of an additional Y chromosome - sets 47 XYY or 48 XXYY. Congenital syndromes, the component of which is tallness, or gigantism, are extremely rare. These include Wiedemann-Beckwitt syndrome, Berardinelli lipodystrophy, Marfan disease and one form of amino acid metabolism disorder - homocystinuria.

The congenital form of cerebral gigantism is characterized not only by tall stature, but also by its combination with profound mental retardation and anomalies of the craniofacial region.

Gigantism in children, which occurs during postnatal development, may also be of a pituitary nature, i.e. determined by hyperproduction of somatotropic hormone of the pituitary gland. In the vast majority of cases, the cause of such hyperproduction is a tumor of the adenohypophysis.

Diagnosis of the causes of tall stature

To clarify the diagnosis, parents should be interviewed and determine whether there is a hereditary-constitutional form that does not require any treatment. In some cases, if a genetic chromosomal pathology is suspected, consultation with a geneticist and genetic analysis may be required. In addition, an analysis should be carried out to determine the level of growth hormones - growth hormone and IGF-1, amino acids, glucose in the blood, as well as examinations for the content of thyroid hormones. In some cases, an MRI, tissue biopsy (if the adrenal glands are affected), radiography, ultrasound, and so on may be required.

When collecting anamnesis, attention should be paid to height and birth weight. Thus, with Marfan, Beckwith-Wiedemann, Simpson-Golabi-Bemel, Banayan-Riley-Ruvalcaba syndromes and constitutional tallness, high values ​​of body length at birth are noted.

Treatment of tall stature

If the cause of tall stature is concomitant diseases, they should be treated. For example, in case of adrenal tumors, they are removed followed by replacement therapy. Otherwise, according to indications, hormonal therapy can be carried out to slow growth to a socially acceptable level.

General provisions. There is no generally accepted definition of the concepts of “excess growth” and “giant growth”. The data cited by some authors does not take into account the height of the parents, which in some cases is of decisive importance in clarifying the question of the presence of a pathological process. If the child's height is 1.5-2 standard deviations greater than the expected average height (taking into account the age of the child and the height of the parents), further examination is indicated to exclude a pathological process. The influence of acceleration, which parents often consider the first reason for the increased growth of their child (“the child is growing by leaps and bounds”), is overestimated.

Constitutional tall height. In families where children are constitutionally tall, in addition to the fact that the parents themselves are above average height, there are other tall relatives. Body length is determined by numerous genes, so it is not surprising that, thanks to the accumulation of genetic factors that favorably influence height, children of tall parents grow even larger.

The concept of "selection" is reluctantly applied to people. However, it is believed that tall women determine the selection of partners.

Children's body length at birth is above average and approximately parallel to the 97th percentile. Standard deviations from the average values ​​do not change significantly. The differentiation of the skeleton is within the limits of normal fluctuations, and since the growth rate is greater, an increase in body length occurs to a certain extent, which worries parents, especially during the pubertal period of accelerated growth. The children are healthy. No endocrine disorders could be detected. Posture disorders are more common, and in girls - motor disharmony, aggravated by stiffness of movement. During the maximum pubertal growth acceleration (at approximately 12 years of age), orthostatic dysregulation becomes more frequent. Due to excessive growth, the well-being of many girls is significantly impaired, which is primarily due to the attitude of others. Boys of the same age, since the pubertal growth spurt, often differ even more from their peers, and from the point of view of growth physiology, they are 2 years younger. Thus, in mixed school classes There are unusual differences in growth rates among 12- and 13-year-old students. Dressing these teenagers is becoming increasingly difficult because sizes are trendy. clothes are aimed at average performance. Sometimes it should be questioned whether the psychological difficulties of excessively tall girls are as great as their mothers indicate, since the latter often project onto the behavior of their daughters the difficulties that they once had in adolescence.

"Constitutional acceleration of development", or early normal puberty. While the manifestation of constitutional developmental delay (see p. 186) is now well known, it is rarely suspected that almost as often early development, occurring within the framework of physiological fluctuations, with acceleration of skeletal differentiation and growth already in childhood, may occur. In this case, puberty begins earlier and growth ends earlier (about differentiation with premature puberty). These somewhat taller, early-maturing children are not paid attention to and are almost never shown to the doctor, turning to him only in case of simultaneous familial tall stature, which is reminiscent of the fact of treatment in case of more frequently observed familial short stature. The prognosis for bone age is relatively good.

Endocrine diseases and gigantism. 1. Pituitary gigantism, or infantile acromegaly. This extremely rare disease in childhood is associated with autonomous or excessive production of somatotropin-releasing factor (GH-RH), as well as secondary (or primary) eosinophilic adenoma of the anterior pituitary gland. In most cases, high growth is combined with symptoms of acromegaly. Due to the rarity of this disease, it should be taken into account in the differential diagnosis only in cases where there is no family history of tall stature or obvious symptoms of acromegaly are present. It has not been established whether diabetes mellitus develops more often in young patients with acromegaly. Plasma GH levels are elevated and do not decrease (as normal) in response to glucose infusion.

2. Hyperthyroidism. Hyperfunction of the thyroid gland may be accompanied by excessive growth and accelerated differentiation of the skeleton; other symptoms are decisive in the differential diagnosis.

3. Pubertas praecox, pseudopubertas praecox. Characteristic and decisive in the differential diagnosis are a pronounced advance in bone age with a not so strong acceleration in length growth, premature appearance of sexual characteristics and closure of the epiphyseal zones, ultimately leading to short stature.

Chromosomal aberrations. Klinefelter syndrome. Tallness becomes noticeable only during the slow course of puberty. During the examination, attention is drawn, as in no other case, to the small and often dense testicles.

2. Other sex chromosome abnormalities are not noticeable at first because of increased body length, but later the height of adult patients increases in most cases.

Clinical syndromes characteristic of gigantism:

Marfan syndrome. This is a pathology of connective tissue (mesoderm) of unknown etiology to date.

Genetics. Autosomal dominant inheritance; 15% of new mutations are noted.

Symptoms 1. Tallness: Patients with Marfan syndrome tend to be unusually disproportionately tall. The tallest patient recorded was 7 feet (213 cm).

2. A more important sign than high growth are characteristic skeletal changes:

A) shift in body proportions - the ratio of the length of the upper body segment to the lower one is shifted towards the latter, i.e. the ratio is reduced;

B) the ratio of length to width of tubular bones, shifted towards length, increasing the so-called metacarpal index. It is determined as follows: using an x-ray of the hand, the ratio of the length to the minimum width of the II, III, IV and V metacarpal bones is determined, the average value of these 4 numbers is calculated, which normally ranges from 7 to 8; if the index is greater than 8.5, there is a reasonable suspicion of the presence of Marfan syndrome;

B) arachnodactyly, which manifests itself, in particular, when covering the distal part of the forearm. If the patient can put it down thumb near the terminal phalanx of the small, there is a suspicion of Marfan syndrome;

D) scoliosis, funnel chest, chicken breast;

D) insufficiency of the supporting apparatus of the lens, its trembling, subluxation or spherical lens with severe myopia; high risk of retinal detachment;

E) other mesenchymal symptoms: hyperextension of joints, aortic insufficiency. A dissecting aortic aneurysm is possible. Emphysema and spontaneous pneumothorax additionally indicate the presence of Marfan syndrome.

Differential diagnosis. Homocystinuria may resemble Marfan syndrome primarily in ophthalmological symptoms, but here we cannot talk about phenotypically completely similar diseases. The detection of increased urinary excretion of homocysteine ​​is of important differential diagnostic significance.

Treatment. For exceptionally high expected growth or changes in the spine, treatment with estrogen is indicated, and in boys, testosterone.

The prognosis depends critically on cardiovascular symptoms.

Literature. If Marfan syndrome is suspected, it is recommended to review the extensive information provided by McCushick. It is simply impossible to do without his monograph if there is an assumption about the presence of erased forms of the disease.

Sotos syndrome. Tall stature with general manifestations of non-progressive cerebral symptoms and craniofascial signs. Accelerated growth in length, enlargement of the head, and often skeletal differentiation begin at birth.

Genetics and pathogenesis are unknown.

The frequency is low, but due to the lack of accurate data on the geographical pattern of the disease, it may be higher than expected.

Symptoms Tall, macrocephaly with partially acromegaloid features, often intellectual underdevelopment. Mild hydrocephalus and, accordingly, expansion of the ventricles of the brain (not caused by pressure). Sometimes there are cerebral seizures. A typical change in the facial skeleton, along with mild acromegaloid symptoms (without increased GH production), is characterized by an antimongoloid position of the eyes, as well as hypertelorism. In most cases, skeletal maturation is clearly accelerated. The final height is at the upper limit of normal. As for the neurological status, the most precise movements are impaired.

Differential diagnosis. It is possible to distinguish Sotos syndrome from early maturation observed with hydrocephalus of the third ventricle, when only accelerated skeletal differentiation occurs without premature appearance of sexual characteristics, only on the basis of determining the level of gonadotropins or sex steroid hormones in the plasma. However, often the changes in the facial skeleton are so distinct that the diagnosis can only be made using physiognomy.

Treatment. As a rule, the cerebrospinal fluid pressure is not increased. Due to the fact that the final height does not exceed the upper limit of normal, there is no need for hormonal therapy.

Forecast. Relatively further development No patient information available. The general consensus is that cerebral changes do not progress.

Treatment of constitutional gigantism in girls. Mechanism of action. In 1962 and 1963 Whitelaw et al reported successful treatment of tall stature with estrogens. This method was initially introduced only for the treatment of pre-pubescent girls. Meanwhile, it has been shown that it can be successfully used even after the onset of puberty. The effect of estrogens on growth cannot be explained from any one point of view. There are two didactic positions.

In addition to the reduction in expected final height in adrenogenital syndrome or pubertal syndrome, estrogen-induced premature onset of the pubertal growth spurt means earlier closure of the epiphyseal zones. If this happens 2 years earlier, then the theoretically predicted growth is reduced by the increase in body length that would have occurred over these 2 years, since the factors influencing growth act 2 years less.

Estrogens influence skeletal maturation while having relatively little effect on length growth. However, with later treatment after the maximum pubertal growth acceleration, estrogens also negatively affect length growth. Based on the latest research, it becomes obvious that along with the acceleration of skeletal maturation, and therefore the earlier closure of the epiphyseal growth zones, the introduction of estrogens also has a negative effect on the growth process itself. When treated with high doses of estrogen, the level of somatomedin in plasma is significantly reduced. At present, it can be assumed that in this case we are talking specifically about the suppression of the secretion of this humoral growth factor by high concentrations of estrogens.

According to the first hypothesis, a decrease in final height is achieved by an earlier course of sexual development. The second hypothesis indicates inhibition of the growth process due to a decrease in the effect of somatomedin while simultaneous estrogen-induced acceleration of the closure of the epiphyseal zones.

It has long been controversial whether the magnitude of final height can be influenced after the onset of puberty, when the chance to accelerate the onset of maturation has been lost. Prader, Birich and our group were able to unequivocally confirm this possibility. The discrepancy between Whitelaw's observations and more recent data may be explained by the different dosages of estrogens used. Whitelaw often used high doses of estrogen - 30-60 mg of estradiol per month, although this is a very weak estrogen, which roughly corresponds in effect to estrogen conjugates. Consequently, Whitelaw used estrogens in doses that corresponded to 1.5 mg of commonly commercially available estrogen conjugates per day. Biric, who managed to obtain good results also when starting treatment already during puberty, used five times daily doses. The doses used by Biric correspond approximately to equivalent doses used with success by other authors after the onset of puberty.

The possibility of treatment with relatively small doses of estrogens before the onset of puberty has been clearly established, but the responsibility for possible psychological complications associated with artificially induced premature onset of puberty should be recognized. After the onset of the physiological course of puberty, in accordance with the treatment methods currently used in most cases, approximately a fivefold dose is required. One can hardly expect psychological problems.

Carrying out treatment. It is not the intention here to fully outline the various treatment regimens. The "Pediatrics Manual" presents the technique used by Birich. Our group uses conjugated estrogens before the onset of puberty in average doses of 1.25 mg/day, but after a few months this dose increases 2-4 times. At a later start of treatment, when the endogenous production of estrogen is already obvious, treatment is carried out with ethinyl estradiol (0.5 mg / day), from the 20-25th day a gestagen is added, and from the 25-30th (or 31st) day break in treatment.

At a panel discussion on the treatment of constitutional tallness at the German Society of Pediatrics in September 1974 in Hamburg, intermittent estrogen treatment (as we do) was considered less justified. Continuous treatment is recommended, which corresponds to the technique proposed by Prader and Birich.

The discussion about estrogen treatment tactics is discussed here in detail in order to clearly show that there are no uniform recipes for the treatment of constitutional tallness. However, the treatment regimen with conjugated estrogens indicated by Birich is fully consistent with modern concepts.

Treatment success. The average reduction in actual final height compared to expected is 4-7 cm. This average is based on very heterogeneous results from individual observations. The success of treatment in each case is definitely unpredictable. However, data from the Zurich working group indicate that growth inhibition is greater the earlier treatment is started after the onset of physiological puberty. Currently, treatment is not recommended before the first signs of maturation appear.

Side effect. It is necessary to distinguish between truly constant or frequently observed symptoms accompanying treatment with theoretically expected consequences. Observed side effects include nausea or vomiting at the beginning of treatment, weight gain (4-6 kg), as well as severe pigmentation of the nipples, especially when using synthetic estrogens. After cessation of treatment, a delay in menstruation is often observed, but this amenorrhea, as observations show, has a short duration (2 - maximum 6 months). Transient lactation is occasionally observed.

No one has yet reported a tendency to thrombosis as a side effect, which should be expected theoretically based on the experience of using drugs that inhibit ovulation. Suggestions that long-term treatment may lead to partial suppression of cyclic hypothalamic functions with impaired ovulation have also not been confirmed. However, Wettenhall and Crauford report normal pregnancy in previously treated patients. Whether treated girls have the fertility seen in the normal population can only be proven on the basis of extensive statistical data.

Treatment of threatened abortion with stilbestrol can cause adenocarcinoma of the cervix or vagina in the child of a mother treated in this way with a probability of 1: 250. To date, the occurrence of tumors in connection with the treatment of tall stature with estrogens has not been observed. Stilbestrol, which has estrogenic activity but is not physiological, is not used, nor is treatment carried out in pregnant women, in whom such side effects may be feared. The associated emotions regarding estrogen treatment for constitutional tallness are unfounded. However, such observations call for caution.

Conclusion. The attitude towards the treatment of constitutional tall stature with estrogens is formed by every doctor who is interested in this based on familiarity with the literature. Participants in the aforementioned discussion were unanimous in the opinion that such treatment is at the stage of clinical trials and should only be carried out by a doctor with the necessary experience and knowledge in the field of endocrinology and growth physiology. Opinions also coincided in that treatment should initially be carried out only in centers that also guarantee follow-up of patients. Various indications for treatment are given. The Hamburg group only accepts girls with a predicted height of 185 cm or more for treatment. Knorr and Stendzik adhere to the same boundaries. Biric considers an expected height of 181 cm to be an indication for treatment. Prader points out that if certain prerequisites are present, treatment is indicated for an expected height of above 175 cm.

The exception to this rule is for us cases with the presence of juvenile scoliosis and significant obvious impairments mental development. In this case, one should take into account the emotionality of tall mothers who would like to protect the child from the problems they experienced in their time. During a discussion at the European Society of Pediatric Endocrinology in Paris, Josso said: "Don't treat the parents."

Treatment of constitutional gigantism in boys. The question of such treatment arises much less frequently than in girls. In accordance with Prader's recommendation, parenteral treatment with testosterone preparations is carried out (initially 250, then 500-1000 mg per month). This results in an acceleration of skeletal maturation and a decrease in predicted final height by an average of 5.4 cm. As Zachmann and Prader point out, there are large individual differences in the effectiveness of treatment. A manifestation of the inhibition of gonadotropin production by exogenous sex steroid hormones is a clear decrease in the size of the testicles. According to Prader, normalization occurs within 12-18 months after stopping treatment.

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