N. Álvarez Gila y L. Expository Alonsob
a Pediatric Endocrinology.
Pediatrics Department.
Torrejón Hospital.
Torrejón de Ardoz, Madrid.
Spain. b Pediatrics Department.
Torrejón Hospital.
Torrejón de Ardoz, Madrid.
Spain.
1.
We report the case of a five-year-old girl referred from her health center by height and weight in lower percentiles.
As a personal history, the patient was a preterm newborn (at 35+2 weeks of gestation) with intrauterine growth retardation (weight: 1805 g [P6; -1.62 SD], length: 41 cm (SD< 13 cm).
Growth velocity from birth has been low, with no recovery of percentiles of height and weight at two years, with persistence of these values at five years.
You have not had serious intercurrent infectious episodes.
At 3 years of age, due to thyroid stimulating hormone (TSH) with normal thyroid ultrasound, levothyroxine was started, with adequate control of thyroid function and without improvement of the thyroid height curve.
The medication was withdrawn one month before the child's endocrinology consultation, maintaining normal TSH and thyroxine levels.
Eat a varied but small diet.
School performance is adequate.
In the family there is no history of prematurity, growth hormone deficiency or other endocrine pathology.
Somatometry
Weight: 13.600 kg (P4; -1.85 SD); height: 96 cm (<P1; -3.22 SD); BMI: 14.76 (P30; -0.54 SD).
Assessment of adult height
Father's stem: 172 cm (P20; -0.85 SD); mother's height: 156 cm (P9; -1.36 SD).
Target size: 157.5±5 cm (P14; -1.11 SD).
Establishment
The patient presented blood pressure of 90/50 mmHg.
She's well nourished and hydrated.
With normal phenotype, harmonic.
Eupneic.
There are no rashes or petechiae.
No goiter or palpable thyroid was observed.
There were no changes in cardiopulmonary auscultation or abdominal examination.
Sexual development corresponds to Tanner stage I.
Complementary tests
Laboratory tests showed normal thyroid profile (TSH 2.9; TSH 1.24 ng/dl).
A normal blood count.
Biochemistry with glucose in 92 mg/dl; HbA1c of 4.9%; insulin in 1.3 mg/dl; total ferritin 234 mg bilirubindl; GOT 33 IU/L; GPT 36 alkaline creatinine 223 mg/dl; iron saturation 7.5 IU/dl;
Lipid profile: cholesterol 178 mg/dl; HDL 61 mg/dl; LDL 113 mg/dl; triglycerides 25 mg/dl.
Sample for growth factors that are normal for their age and sex (IGF1 112.9 ng/ml; IGFBP3 3.78 ng/ml) was extracted.
Celiac disease and immunodeficiencies were ruled out.
X-ray of the left wrist showed a bone age of four years and two months, fixed for chronological age of five years.
Initial diagnosis
CIR without catch-up.
Treatment and evolution
As it meets the criteria accepted by the Growth Hormone Advisory Committee of the Ministry of Health, Social Services and Equality, a request is made to initiate treatment with public funding.
One month later, subcutaneous administration of recombinant somatotropin (0.5 mg/kg/day) was initiated at a dose of 0.5 mg/day, with adequate compliance and no secondary effects.
It has a favorable evolution after one year of treatment, with an increase of percentiles of height and growth rate of 9.8 cm/year equivalent to a P99 (+4.39 SD).
Remarks
a) Perinatal period
In CIRs, during the prenatal period, changes occur in adaptive body composition, secondary to a state of malnutrition, resulting in brain development due to the presence of other organs such as liver, adipose tissue and muscle.
There is a decrease in lean mass, a lower protein and nitrogen intake, less amount of glycogen and a state of multiple hormonal resistance, highlighting the resistance in the somatotropic axes: insulin/IGF1 and prenatal GH/IGF1.
On the other hand, they have lower amounts of fat mass and bone mineral density.
Hypoxia generates an increase in erythropoietin, with a higher volume of plasma and red blood cells, which generates a higher viscosity of the blood and increases the effects of hypoxia.
In the neonatal period, they are more prone to fasting hypoglycemia, because the glycogen storage is lower, without the occurrence of glycogenosis, and due to the decrease in the use of oxidation in free lactating acids.
This has consequences because the oxidation of free fatty acids saves the use of glucose by peripheral tissues.
In addition, prenatal polycythemia would increase the risk of hypoglycemia3.
on growth
The CIR are usually smaller in size during childhood and adolescence, reaching in adulthood a height, approximately, a standard deviation lower than the mean (P15)4.5.
Accelerated catch-up or catch-up growth usually occurs mostly in the first 12 months of life and in 90% of cases is almost completed at two years, reaching a height above -6.2 SD (P3)
In the case of premature CIRs, recovering growth can occur7.
Very premature CIRs or those with greater growth restriction, especially those with low birth length, are less likely to reach normal height6.
on carbohydrate metabolism and cardiovascular risk
They usually present high levels of total cholesterol and LDL-cholesterol, as well as increased insulin resistance.
Moreover, systolic blood pressure is higher than in children born with adequate weight for gestational age.
Therefore, they have an increased risk of presenting metabolic syndrome (hyperlipidemia, type 2 diabetes mellitus), in younger ages of adult life3.
This risk is increased if there has been a rapid weight gain in the first years of life.
Establishment plan
Male CIRs have been shown to have hypersecretion of follicle-hypophysis hormone (FSH) and luteinizing hormone (LH) with lower levels of testosterone and testicular inhiferbine B, which is associated
In the case of women3 higher levels of FSH, LH, estradiol, 17-hydroxyprogesterone and dehydroepiandrosterone (DHEA) have been observed, which associates a higher number of premature anonychia and ovary
Height at the beginning of puberty is lower than in children born with adequate weight for gestational age.
Delayed maturation of bone age is observed at the beginning of puberty. It is usually rapidly evolving with a decrease in pubic stretch and therefore an adult height smaller than expected 1,8,9.
Treatment
Recombinant human growth hormone (TSH) therapy with recombinant growth hormone (GH) recovers in children with inadequate growth hormone levels10.
In Europe, since 2003, it has been approved in patients who, at four years of age, have not had catch-up or catch-up growth and have a height below -2.5 SD (P1) and/or less than -1 SD adjusted.
Before starting treatment, blood pressure should be measured and laboratory tests should include free T4, IGFI, IGFBP3, baseline glycemia and insulinemia, glycohemoglobin and lipid profile.
Severity dose varies from 0.035 mg/kg/day to 0.050 mg/kg/day.
It should be administered daily in the evening by subcutaneous injection.
The degree of response depends on the dose, age at onset of treatment (response in younger patients), and the individual height deficit corrected by target height.
Cases were reassessed one year after treatment.
In those in whom the growth rate is less than +1 SD, it should be considered to discontinue treatment.
On the other hand, systolic arterial hypertension also improves lipid profile and body composition.
The effects on the carbohydrate metabolism by the anti-insulinemic action are reversible upon discontinuation of treatment.
Follow-up and role of Primary Care Pediatricians
The primary care pediatrician plays a key role in the follow-up of children with intrauterine growth retardation.
Close monitoring of weight and height is essential, but not less important adequate education and nutritional assessment:
• Breast-feeding should be supported for at least six months11.
• Individualize the use of formulas or reinforced diets.
• Start complementary feeding at six months without excess cereals or protein excess.
• To recommend avoiding juices and following a healthy low cholesterol diet from the first year of life.
It is important that these children grow progressively, with no increase in percentiles significantly in the first 3-4 years of life.
The IUGR is “saving” during the fetal period, so that, with overnutrition, the body is not able to adapt, triggering obesity, other metabolic alterations such as diabetes or hypertension, or addict
In cases such as that of our patient, in which recovering growth is not achieved at two years of age, the administration of child Endocrinology should be ruled out, in order to rule out other pathologies that could rule out this growth pattern.
After starting treatment, it is essential that your pediatrician also reinforces the need for hormonal medication daily with adequate compliance to achieve the greatest benefit and assess possible side effects of the medication.
