Thyroid function tests in preterm infants born to preeclamptic mothers with placental insufficiency

OBJECTIVE: Since preeclampsia causes placental insufficiency, it can be hypothesized that it decreases placental passage of thyroxine (T4) from mother to infant and thus may deepen the transient hypothyroxinemia seen in preterm infants after birth. The aim of this study was to compare thyroid function tests of preterm infants born to preeclamptic mothers with placental insufficiency with preterm infants born to mothers without placental insufficiency. METHODS: Thirty-one preterm infants born to preeclamptic mothers with placental insufficiency were included in the study (group I) and 31 preterm infants born to mothers without placental insufficiency were included as the control group (group II). Thyroid hormone levels were assayed from blood samples obtained from the women before birth and thereafter from the infants at delivery (cord) and on the 1st, 3rd, 7th, and 21st days of life. RESULTS: Cord blood triiodothyronine (T3), free T3 (FT3) and free thyroxine (FT4) levels in group I were lower than in group II, whereas thyrotropin (TSH) and thyroxine binding globulin (TBG) levels were higher. No statistical difference in hormone levels studied at postnatal 1st, 3rd, 7th, and 21st day was found between the two groups. CONCLUSION: Low levels of thyroid hormones and high level of TSH in cord blood in premature infants born to preeclamptic mothers with placental insufficiency suggest intrauterine hypothyroidism. Increase in TSH and thyroid hormone concentrations after birth reveal that the hypothalamic-pituitary-thyroid axis is intact.     

Umbilical Cord Dehydroepiandrosterone Sulfate and Cortisol Levels in Preterm Infants Born to Pre-Eclamptic Mothers

ABSTRACT. The influence of early-onset pre-eclampsia upon the umbilical cord serum levels of Cortisol and dehydroepiandrosterone sulfate was studied in fifty-one preterm infants not exposed prenatally to corticosteroids. Preterm infants born to pre-eclamptic mothers (group A) presented lower dehydroepiandrosterone sulfate levels than preterm infants born to non-pre-eclamptic mothers (group B). The umbilical cord serum levels of Cortisol were similar between both groups. It is suggested that the decrease in the cord serum levels of dehydroepiandrosterone sulfate in preterm infants of pre-eclamptic mothers plays an important role in the pathogenesis of the subnormal maternal urinary estriol excretion, and that the accelerated pulmonary and cerebral maturation of preterm infants born to pre-eclamptic mothers is not explained by an increased fetal serum Cortisol concentration.     

Umbilical cord dehydroepiandrosterone sulfate and cortisol levels in preterm infants born to pre-eclamptic mothers

The influence of early-onset pre-eclampsia upon the umbilical cord serum levels of cortisol and dehydroepiandrosterone sulfate was studied in fifty-one preterm infants not exposed prenatally to corticosteroids. Preterm infants born to pre-eclamptic mothers (group A) presented lower dehydroepiandrosterone sulfate levels than preterm infants born to non-preeclamptic mothers (group B). The umbilical cord serum levels of cortisol were similar between both groups. It is suggested that the decrease in the cord serum levels of dehydroepiandrosterone sulfate in preterm infants of pre-eclamptic mothers plays an important role in the pathogenesis of the subnormal maternal urinary estriol excretion, and that the accelerated pulmonary and cerebral maturation of preterm infants born to pre-eclamptic mothers is not explained by an increased fetal serum cortisol concentration.     

Skin conductance and behaviour during sensory stimulation of preterm and term infants

Aim: To investigate the responses to painful and tactile stimulation in preterm and term infants in terms of changes in the plantar skin conductance activity (SCA) and behavioural state. Plantar SCA reflects activity in the sympathetic nervous system. Design: The plantar SCA and behavioural state in response to nociceptive (the heel prick for blood samples, or immunization) and tactile (routine nursery handling) simulation was recorded in four different groups of infants (n=71): Preterm and term neonatal infants (defined here as up to 1 week old), and preterm and term infants in the postneonatal period. Results: The preterm infants had significant increases in all skin conductance variables during both tactile and nociceptive stimulation (p<0.02), except for wave amplitude when newborns were heel pricked. The term infants displayed a more varied picture, but both the number and amplitude of the waves increased significantly during both procedures in the newborn groups, while the postneonatal groups only showed significant increases in wave amplitude during nociceptive stimulation (p<0.05). Tactile stimulation of the preterm newborn infants produced significantly higher increases in SCA than nociceptive stimulation (p<0.01), while the behavioural state was highest during nociceptive stimulation (p<0.05). A gradual change in this relation was seen with advancing total age. Conclusion: Non-painful sensory stimulation of infants, especially the newborn and preterm ones, can produce equal or higher levels of physiological stress activation than painful stimulation. Repeated nociceptive stimulation probably sensitises the infants to pain.     

Effect of perinatal asphyxia on thyroid-stimulating hormone and thyroid hormone levels

AIM: To compare serum concentrations of thyroid hormones--T4, T3, free T4 (FT4) and reverse T3 (rT3)--and thyroid-stimulating hormone (TSH) found in the umbilical cord blood of term newborns with and without asphyxia and those found in their arterial blood collected between 18 and 24 h after birth. A further aim of the study was to assess the association between severity of hypoxic-ischemic encephalopathy and altered thyroid hormone and TSH levels, and between mortality and FT4 levels in the arterial blood of newborns between 18 and 24 h of life. METHODS: A case-control study was carried out. The case group comprised 17 term newborns (Apgar score < or = 3 and < or = 5 at the first and fifth minutes; umbilical cord blood pH < or = 7.15) who required bag and mask ventilation for at least one minute immediately after birth. The control group consisted of 17 normal, term newborns (Apgar score > or = 8 and > or = 9 at the first and fifth minutes; umbilical cord blood pH > or = 7.2). Cord blood and arterial blood samples were collected immediately after birth and 18 to 24 h after birth, respectively, and were used in the blood gas analysis and to determine serum concentrations of T4, T3, FT4, rT3 and TSH by radioimmunoassay. All newborns were followed-up until hospital discharge or death. RESULTS: Gestational age, birthweight, sex, size for gestational age, mode of delivery and skin color (white and non-white) were similar for both groups. No differences were found in mean levels of cord blood TSH, T4, T3 and FT4 between the groups. In the samples collected 18 to 24 h after birth, mean levels of TSH, T4, T3 and FT4 were significantly lower in the asphyxiated group than in the control group. Mean concentrations of arterial TSH, T4 and T3 between 18 and 24 h of life were lower than concentrations found in the cord blood analysis in asphyxiated newborns, but not in controls. In addition, asphyxiated newborns with moderate/severe hypoxic-ischemic encephalopathy presented significantly lower mean levels of TSH, T4, T3 and FT4 than those of controls. None of the asphyxiated newborns with FT4 > or = 2.0 ng/dl died; 6 out of the 11 asphyxiated newborns with FT4 < 2.0 ng/dl died. CONCLUSIONS: Serum concentrations of TSH, T4, T3 and FT4 are lower in asphyxiated newborns than in normal newborns between 18 and 24 h of life; this suggests central hypothyroidism secondary to asphyxia. Asphyxiated newborns with moderate/severe hypoxic-ischemic encephalopathy present a greater involvement of the thyroid function and consequently a greater risk of death.     

Relationship between free T4 levels and postnatal steroid therapy in preterm infants

Background: Transient hypothyroxinemia is the most common thyroid dysfunction in preterm infants. Hypothalamic–pituitary–thyroid immaturity and non‐thyroidal illness contribute to its etiology. The aim of the present study was therefore to determine the relationship between thyroid hormone status and early postnatal steroid therapy in preterm infants. Methods: A prospective study of premature infants born at <28 weeks of gestation between July 2001 and June 2007 was conducted. Selective postnatal steroid (dexamethasone) therapy was used in lung disease treatment if the infants needed high mean airway pressure‐assisted ventilation and supplemental oxygen at 2 weeks of age. Free T4 (FT4) and thyroid‐stimulating hormone (TSH) levels were assessed at 2 weeks after birth. Blood samples in eight infants were available after starting steroid therapy. Infants receiving steroids (steroid (+); n= 8) were compared to those not receiving steroids (steroid (?); n= 73). Results: The demographic data were not significantly different between the two groups. The neonatal illnesses and drug use were also not significantly different between the groups. The steroid (+) group had significantly lower FT4 and TSH levels at 2 weeks after birth than the steroid (?) group. The increase in FT4 levels after steroid withdrawal was greater than that during the same period in the steroid (?) patients. Conclusion: Even if it cannot be excluded that reduced FT4 and TSH concentrations are caused by non‐thyroidal illness, the present study suggests that postnatal steroid treatment reduces the FT4 and TSH levels in premature infants born at <28 weeks of gestation.     

Body mass index development during the first 6 months of life in infants born to human immunodeficiency virus-seropositive mothers

The development of body mass index (BMI) was measured during the first 6 months of life in three groups of infants [human immunodeficiency virus (HIV) -uninfected, n = 92; later symptomatic HIV-infected, n = 18; early symptomatic HIV-infected, n = 9] born to HIV-positive mothers and compared with a reference group (n = 65) born to healthy mothers. A trend towards lower values in the two groups of HIV-infected infants was already evident at birth. Among the four groups, HIV-uninfected infants showed the highest BMI values while the early-infected infants showed the lowest BMI values at all measurements. The later-infected group had a value close to the reference at 1 month, and then increased at slower rates than the uninfected and the reference groups. Infants born to HIV-positive mothers may have higher energy and nutrient requirements after birth, either to sustain an increased BMI development (when uninfected) or to meet catabolic mechanisms (when infected).     

Reverse triiodothyronine, thyroid hormone, and thyrotrophin concentrations in placental cord blood.

Reverse triiodothyronine (rT3), triiodothyronine (T3), thyroxine (T4), thyroxine binding globulin (TBG), and thyrotrophin (TSH) were measured in sera from placental cord blood in an unselected series of 272 deliveries. In this series the concentrations of rT3 (mean 3.33 nmol/l, 95% confidence limits 1.6--7.0 nmol/l), were log normally distributed and did not overlap the adult normal range (0.11--0.44 nmol/l). There were no correlations between the cord blood concentrations of rT3, T3, T4, and TSH. The cord serum rT3 concentration was not influenced by maturity, birth-weight, or neonatal risk factors, whereas these factors did affect the concentrations of T3, T4, AND TBG. There is no arteriovenous rT3 concentration difference across the placenta, therefore the cord rT3 reflects the systemic rT3 concentration in the baby at birth. As rT3 in the neonate largely, if not entirely, derives from thyroxine from the fetal thyroid, measurement of the cord rT3 concentration may be a good immediate screening test for neonatal hypothyroidism.     

Cord blood thyroxine and thyroid stimulating hormone screening for congenital hypothyroidism: how useful are they?

AIM: To determine and compare the usefulness of cord blood screening for free thyroxine (FT4) and thyroid stimulating hormone (TSH). BACKGROUND: There is a vast amount of literature on capillary heel prick screening tests, but relatively little on cord blood testing particularly FT4. For a decade all infants born at Tawam Hospital had cord blood FT4 and at Oasis Hospital cord TSH measured through the hospital-based screening programme. On January 1st 1998, the national screening programme (NSP) for congenital hypothyroidism (CH) in the United Arab Emirates (UAE) started using capillary TSH measurement (Delfia method). Since then newborns in both hospitals have been screened both ways, i.e. cord blood and capillary blood screening. METHODS: We reviewed retrospectively all infants born from January 1998 until the end of June 2004 with CH who had double screening: cord FT4 or TSH and 4th-5th day TSH screening. RESULTS: Thirteen infants (one in 1,778) had CH in Tawam Hospital. In six of these the cord blood FT4 was low (<9.1 pm/l) (0.73 ng/dl) and in seven the cord blood FT4 was normal, i.e., over half were missed. Eight infants (one in 1,198) had CH in the Oasis Hospital. Cord blood TSH was high in six of them (>13 IU/l) and two were normal. Cord FT4 detected the most severe cases, but missed most others. Cord TSH detected six out of eight cases, but there was a recall rate of one in 23. CONCLUSIONS AND RECOMMENDATIONS: Cord FT4 identifies only infants with severe CH. Cord TSH is more sensitive than cord FT4 screening. Capillary TSH dried blood spot testing on the 3rd-5th day is the most sensitive method.     

Elevated serum creatinine levels in infants with congenital hypothyroidism: reflection of decreased renal function?

The effects of hypothyroid status on renal function have been poorly studied in children. We assessed the renal function of hypothyroid infants detected during neonatal mass screening for congenital hypothyroidism (CH). Eighty hypothyroid infants and 20 age-matched normal infants for controls were enrolled. The 80 patients, aged 1 mo, were divided into two groups based on the initial thyroid stimulating hormone (TSH) and free thyroxine (FT4) values: a mild-moderately hypothyroid (MHT) group (n = 64, 31M and 33F) and a severely hypothyroid (SHT) group (n     

Increased leptin concentration in preterm infants of pre-eclamptic mothers

AIM: To study the effect of maternal pre-eclampsia on cord plasma leptin concentrations in preterm infants. METHODS: Leptin concentration was analysed in cord plasma of 74 preterm infants, gestational age 24 to 32 weeks. Of these, 14 were born to pre-eclamptic mothers, in 10 intrauterine growth retardation (IUGR) was present, and 59 had been exposed antenatally to corticosteroids. RESULTS: The mean (SD) concentration of cord plasma leptin was 1.31 (0.88) microg/l. A significant correlation was found between leptin concentration and gestational age (r = 0.336; p = 0.0037). Leptin levels were higher in infants of pre-eclamptic mothers (p = 0.0007), in those with IUGR (p = 0.0005), and in infants exposed antenatally to corticosteroids (p = 0.02). In multiple regression analysis, leptin was associated with gestational age and maternal pre-eclampsia (both p < 0.05), but not with antenatal corticosteroids. CONCLUSIONS: Increased fetal leptin in maternal pre-eclampsia may reflect a physiological adaptation to fetal stress such as hypoxia.     

Investigation of the relationship between low Apgar scores and early neonatal thyroid function

BACKGROUND: The aim of the present study was to assess the effects of low Apgar scores on perinatal thyroid function. METHODS: Forty full-term infants delivered by the normal spontaneous vaginal route were enrolled into the study. All babies had 1 and 5 min Apgar scores below 4. The control group consisted of 26 full-term healthy neonates. Cord blood and serum tri-iodothyronine (T3), thyroxine (T4), reverse tri-iodothyronine (rT3), free thyroxine (FT4), thyroid-stimulating hormone (TSH) and thyroid-binding globulin (TBG) determinations were performed by an enzyme immunoassay method. RESULTS: The mean values of FT4 and T4 observed in the cord blood of the study group were significantly lower compared with matched controls, whereas the mean TSH values were significantly higher. There were no differences in concentrations of T3, rT3 and TBG between the two groups. CONCLUSIONS: These results demonstrate the existence of transient hypothyroidism at birth in babies with Apgar scores below 4 delivered by the spontaneous vaginal route.     

Short-term hyperthyroidism followed by transient pituitary hypothyroidism in a very low birth weight infant born to a mother with uncontrolled Graves' disease

Transient hypothyroxinemia in infants born to mothers with poorly controlled Graves' disease was first reported in 1988. We report that short-term hyperthyroidism followed by hypothyroidism with low basal thyroid-stimulating hormone (TSH) levels developed in a very low birth weight infant born at 27 weeks of gestation to a noncompliant mother with thyrotoxicosis attributable to Graves' disease. We performed serial thyrotropin-releasing hormone (TRH) tests in this infant and demonstrated that TSH unresponsiveness to TRH disappeared at 6.5 months of age. The maternal thyroid function was free triiodothyronine (FT(3)), 21.1 pg/mL; free thyroxine (FT(4)), 8.1 ng/dL; TSH, <0.03 microU/mL; thyroid-stimulating hormone receptor antibody, 52% (normal: <15%); thyroid-stimulating antibody, 294% (normal: <180%); and thyroid-stimulation blocking antibody, 9% (normal: <25%) on the day of delivery. A nonstress test revealed fetal tachycardia >200 beats per minute, and a male infant weighing 1152 g was born by emergency cesarean section. Thyroid-stimulating hormone receptor antibody was 16% and thyroid-stimulating antibody was 370% in the cord blood. We administered 10 mg/kg per day of oral propylthiouracil from day 1. Tachycardia along with elevated FT(4) and FT(3) levels in the infant decreased from 200/minute to 170/minute, 4.7 ng/dL to 2.9 ng/dL, 7.0 pg/mL to 4.8 pg/mL, respectively, in the first 33 hours. At 5 days, FT(4) and FT(3) were 1.1 ng/dL and 2.9 pg/mL, respectively, and we stopped propylthiouracil administration. Although FT(4) decreased to 0.4 ng/dL, TSH was quite low and did not respond to intravenous TRH by 14 days of age. We began daily levothyroxine 5-micro/kg supplementation. The responsiveness of TSH to TRH did not become significant until 4 months old and normalized at 6.5 months old. At this time, levothyroxine was stopped. We conclude that placental transfer of thyroid hormones may cause hyperthyroidism in the fetal and early neonatal periods and lead to transient pituitary hypothyroidism in an infant born to a mother with uncontrolled Graves' disease.     

Randomized study of nasal continuous positive airway pressure in the preterm infant with respiratory distress syndrome

Aim: To evaluate whether very preterm babies can be extubated successfully to nasal continuous positive airway pressure (nCPAP) within one hour of birth after receiving one dose of surfactant in the treatment of respiratory distress syndrome (RDS). Methods: Forty-two infants of 25 to 28[Formula: See Text] wk of gestation were intubated at birth and given one dose of surfactant. They were then randomized within one hour of birth to either continue with conventional ventilation or to be extubated to nCPAP. Results: Eight out of 21 (38%) babies randomized to nCPAP did not require subsequent reventilation. (Ventilation rates of 62% vs 100%, p = 0.0034). The smallest baby successfully extubated weighed 745 g. There were also significantly fewer infants intubated in the nCPAP group at 72 h of age (47% vs 81%, p = 0.025). There was no significant difference between the two groups in the number of babies that died, developed chronic lung disease or severe intraventricular haemorrhage.

Conclusion: A significant number of very preterm babies with RDS can be extubated to nCPAP after receiving one dose of surfactant. nCPAP is a potentially useful modality of respiratory support even in very premature infants.     

Lung maturation in small for gestational age fetuses from pregnancies complicated by placental insufficiency or maternal hypertension

BACKGROUND: Clinical studies suggest that respiratory outcome of infants born preterm may be influenced by placental insufficiency and hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome. If so, one could expect to see differences in lung maturation indices (lecithin/sphingomyelin (L/S) ratio and lamellar body count (LBC)) in the amniotic fluid. The present study investigates lung maturation indices of preterm small for gestational age (SGA) fetuses with or without abnormal Doppler ultrasound examination and with or without maternal hypertension/HELLP syndrome. STUDY DESIGN: Retrospective cohort study of 76 neonates born in our center between 1997 and 2003 with gestational age (GA) <34 weeks, birth weight 相似文献   

The effect of maternal, umbilical cord and placental malaria parasitaemia on the birthweight of newborns from South-western Cameroon

Aim: The impact of maternal, umbilical cord and placental malaria parasitaemia on the incidence of low birthweight was investigated in pregnant women reporting for delivery at the Mutengene Maternity Centre, Fako Division, South West Province, Cameroon. Methods: The malaria parasitaemia status of 770 umbilical cords, parturient women and placental impression smears were determined by light microscopy using blood samples collected between June 1999 and September 2001. The birthweights (BW) of the newborns were recorded soon after delivery. Results: The results show that malaria parasites were present in the blood samples of 57 out of 730 (7.8%), 233/711 (32.8%) and 248/735 (33.7%) cord, maternal and placental biopsies respectively. Low birthweight (LBW) was recorded in 72 (9.6%) newborns, and the incidence was higher in primiparae. Newborns of mothers who had malaria parasites in their peripheral blood (12.4%) had a higher incidence (p=0.014) of LBW when compared with malaria parasite-free mothers (6.8%). Similarly, neonates born from malaria-positive placentas (13.5%) had a significantly higher incidence of LBW (p=0.006) than those from parasite-negative placentas (6.8%). Furthermore, newborns of malaria parasite-positive mothers, umbilical cords, placentas and primiparae had lower mean birthweight than malaria-negative mothers, placentas, umbilical cords and multiparae.

Conclusion: We suggest that parity and maternal and placental malaria parasitaemia at delivery have an important negative impact on birthweight, especially in first pregnancies. This observation emphasizes the need for appropriate aggressive intervention strategies such as the use of insecticide-treated bed nets or intermittent preventive treatment to control malaria in pregnancy in the study area.     

Comparison of T4, T3, rT3 and TSH concentrations in cord blood and serum of infants up to 3 months of age

T4, T3, TSH and rT3 concentrations were measured by radioimmunoassay in cord and postnatal (8--94 days of age) serum samples from randomly selected normal newborn infants (Group I). T4 and TSH levels also were determined in cord and postnatal sera from an additional group of apparently healthy infants 8--260 days of age, whose cord serum T4 levels were in the upper or lower 10% of the normal range of values (Group II). Postnatal T4, T3 and TSH concentrations were stable over this age range; there were no significant differences between male and female infant samples. However, there was a significant decrease in serum rT3 concentrations from 8 to 50 days of age. For the Group I infants, there were significant positive correlations between cord serum T4 and postnatal serum T4 levels, cord serum TSH and postnatal serum TSH levels, and cord serum rT3 and postnatal serum rT3 concentrations. For Group II infants, a significant positive correlation was found for cord T4--postnatal T4 serum concentrations.     

Transepidermal water loss in infants born at 24 and 25 weeks of gestation

The rate of evaporation of water from the skin of 13 infants born at 24 (n = 3) and 25 (n     

Higher urinary excretion of essential amino acids in preterm infants fed protein hydrolysates

Aim: Protein hydrolysates have been introduced in preterm formulae, but it is not clear whether they are needed for the feeding of preterm infants. We designed a randomized, controlled trial to test the effects of a preterm formula with hydrolysed cow's milk proteins on short-term growth and urinary and plasma amino acids levels. Methods: Infants with a birthweight ≤1750 g and gestational age ≤34 wk fed a conventional preterm infant formula (formula B) or a hydrolysed formula (formula A). Weight was measured daily; length, head circumference, mid-arm circumference and total skinfold thickness were measured weekly. Blood and urine were analysed for amino acid concentrations at start, 14 and 28 d. Results: Twenty-one infants met the criteria for randomization. The daily feeding volumes were: formula A 172.8±5.6 vs formula B 170.1±2.8 ml/kg/d. Infants fed with formula A showed slower weight gain (17.4±3.4 vs 20.5±3.3 g/kg/d; p=0.045) and lower mean change in Z-scores for weight (-0.18±0.16 vs 0.00±0.09; p=0.009) and for head circumference (-0.06±0.13 vs 0.06±0.13; p=0.049). After 14 d, infants receiving formula A had statistically significant higher urinary levels of essential amino acids compared to infants receiving formula B.

Conclusion: Our results support the hypothesis of less nutritional value of hydrolysed versus conventional preterm formulae. Higher renal excretion of essential amino acids may be one of the mechanisms involved. These findings must be confirmed by further studies with larger sample sizes and protein hydrolysates with different degrees of hydrolysis.     

Plasma thyroid hormones and prolactin in premature infants and their mothers after prenatal treatment with thyrotropin-releasing hormone.

We assayed TSH, triiodothyronine, free thyroxine, and prolactin (PRL) in plasma of women and infants participating in a trial of prenatal thyrotropin-releasing hormone (TRH) treatment for prevention of newborn lung disease. Women in labor at 26-34 wk of gestation received 400 micrograms of TRH i.v. every 8 h (one to four doses) plus 12 mg betamethasone (one or two doses); controls received saline plus betamethasone. Mean cord concentrations in control infants were TSH 9.7 mU/L, triiodothyronine 0.6 nmol/L (40.2 ng/dL), free thyroxine 14.4 pmol/L (1.13 ng/dL), and PRL 67.6 micrograms/L. TRH increased maternal plasma TSH by 100% at 2-4 h after treatment and decreased levels by 28-34% at 5-36 h. In cord blood of treated infants delivered at 2-6 h, TSH, triiodothyronine, and PRL were all increased about 2-fold versus control, and free thyroxine was increased 19%; the response was similar after one, two, three, or four doses of TRH. In treated infants delivered at 13-36 h, cord TSH and triiodothyronine levels were decreased 62 and 54%, respectively, and all thyroid hormones were lower after birth at 2 h of age versus control. We conclude that prenatal TRH administration increases thyroid hormones and PRL in preterm fetuses to levels similar to those normally occurring at term. Pituitary-thyroid function is transiently suppressed after treatment to a greater extent in fetus than mother, and infants born during the early phase of suppression do not have the normal postnatal surge in thyroid hormones.