Hypothalamic-pituitary-adrenal axis function and the cellular immune response in former preterm children.

CONTEXT: Animal data suggest that adverse early experiences may affect endocrine and immune functioning in later life. OBJECTIVE: Our objective was to assess the impact of preterm delivery on hypothalamus-pituitary-adrenal axis functioning, heart rate responses, and immune function. PARTICIPANTS: Former preterm children [aged 8-14 yr (n = 18)], sex and age-matched full-term born control children (n = 18), data on birth weight, gestational age, birth weight for gestational age (in sd units), actual body weight, height, and body mass index were assessed. DESIGN AND OUTCOME MEASURES: Subjects were exposed to a standardized laboratory stressor ("Trier Social Stress Test for Children"). Cortisol in saliva was determined in 10-min intervals before and after the stress test; heart rates were obtained continuously during the stress test. Additional assessment of saliva cortisol was performed: 1) on 3 consecutive days after awakening and at +10, +20, and +30 min (morning cortisol); and 2) at 0800, 1400, 1600, and 1900 h (short diurnal profile). Measurement of the delayed type hypersensitivity reaction to seven recall antigens [Multitest cellular mediated immunity (Multitest-Immignost, Biosyn, Fellbach, Germany)]. RESULTS: Exposure to the Trier Social Stress Test for Children yielded significantly increased cortisol levels [F (8, 232) = 19.86; P < 0.001] and heart rates [F (38, 988) = 10.46; P < 0.001], however, no difference between former preterms and full-terms could be observed. No between-group differences were found in the short diurnal cortisol profile. Former preterms showed significantly higher cortisol levels after awakening [F (3, 102) = 3.14; P < 0.05]. In addition, a significantly suppressed delayed type hypersensitivity response [reduced number of positive antigens (t = -2.64, P < 0.05); induration (t = -2.4, P < 0.05)] was found in former preterms. CONCLUSION: The data suggest that preterm delivery may be associated with altered endocrine and immune functions well into late childhood.

Delayed appearance of bilateral morgagni herniae in a child with Down's syndrome.

This case report describes the delayed presentation of bilateral Morgagni herniae in a 4 1/2-year-old boy with Down's syndrome. The authors emphasize the difficulties in establishing the diagnosis, although ultrasonography appears to be valuable. A review of the literature suggests an association between Morgagni hernias and trisomy 21.

Attenuated free cortisol response to psychosocial stress in children with atopic dermatitis.

OBJECTIVE: Atopic dermatitis (AD) is an inflammatory skin disease characterized by a hyperactivity of the humoral immune system with an onset in infancy or early childhood. Although most of the research has focused on the pathophysiological role of the immune system in AD, the impact of endocrine signals in the pathology of AD has received only little attention. However, because the endocrine system may play a regulatory role in immune functioning, it might be of major interest to study endocrine reactivity in AD patients. The present two-part study investigated the relationship between adrenocortical stress response, heart rate response, and psychological parameters in children with AD. METHOD AND RESULTS: In Study 1, a protocol for induction of psychosocial stress in children aged 8 to 14 years was evaluated. Healthy children (N = 16) were exposed to the Trier Social Stress Test for Children (TSST-C) that mainly consists of public speaking and mental arithmetic tasks in front of an audience. Salivary cortisol was measured 35, 15, and 1 minute before as well as 1, 10, 20, and 30 minutes after the stress; heart rate was monitored continuously. Results showed that the protocol induced a highly significant increase in free cortisol response (p < .001) and heart rate (p < .001). In Study 2, the TSST-C was applied to AD children (N = 15) and age- and sex-matched healthy controls (N = 15). All patients were in remission and medication-free for at least 3 weeks. Again, the stress test induced significant increases in cortisol and heart rate. However, the AD children showed a significantly blunted cortisol response to the stressor compared with the control group (p < .05). Heart rate responses were similar in both experimental groups. Neither subjective stress ratings nor personality traits were related to the blunted cortisol response. CONCLUSIONS: These findings suggest that the adrenocortical response to stress is attenuated in atopic children. A hyporesponsive hypothalamus-pituitary-adrenal (HPA) axis might explain in part the stress-induced eruptions of AD symptoms.

Clinical experience of a tricomponent acellular pertussis vaccine combined with diphtheria and tetanus toxoids for primary vaccination in 22,505 infants.

OBJECTIVES: To assess the safety and tolerability of 12 lots of SmithKline Beecham Biologicals' diphtheria-tetanus-tricomponent acellular pertussis vaccine (DTaP) in a large cohort of 22,000 vaccinees, with detailed analyses of reactivity, immunogenicity, and immune response to pertussis toxin in subsets. METHODS: In a prospective, double-blind, multicenter trial in Germany, 22,505 healthy infants received three vaccinations of DTaP at age 3, 4, and 5 months. Serious adverse events were followed for 1 month after each vaccination, and neurologic events for 1 year or longer. Serum IgG antibodies were assayed before vaccination and 1 month after vaccination. RESULTS: After 67,000 doses, 153 serious adverse events (0.23%) were reported, 8 considered possibly related, and 5 related to vaccination, including 1 hypotonic-hyporesponsive episode. Incidence rates of sudden infant death syndrome (7; 0.01%) or acute neurologic events (20; 0.030%) were no higher than expected and not considered to be related to vaccination. Redness and swelling of 20 mm or greater occurred after 44 (0.6%) and 40 (0.6%) of the 7270 doses, respectively, and high fever (> 39.5 degrees C) in 6 (0.08%) subjects within 48 hours of vaccination. In the immunogenicity analysis of 580 infants, 98% responded to pertussis toxin, 96% to filamentous hemagglutinin, and 98% to pertactin. In an additional 5712 infants, the response rate to pertussis toxin was 99%. CONCLUSIONS: In a large cohort of 22,505 infants vaccinated, SmithKline Beecham Biologicals' tricomponent DTaP vaccine was shown to be safe, well-tolerated, and immunogenic for all component antigens.

Efficacy of acellular pertussis vaccine in early childhood after household exposure.

OBJECTIVE: To evaluate the efficacy of a three-dose primary vaccination with a diphtheria-tetanus tricomponent acellular pertussis vaccine against "typical" pertussis, defined as a spasmodic cough of 21 days or longer with confirmation of Bordetella pertussis infection by culture or serology. DESIGN: Passive monitoring for suspected first household (index) cases of typical pertussis in six areas in Germany comprising 22,505 children vaccinated with study vaccine at 3, 4, and 5 months of age. Blinded, prospective follow-up of household contacts of index cases for incidence and progression of pertussis. SETTING: Six areas in Germany with a high incidence of pertussis. SUBJECTS: Four hundred fifty-three households with index cases comprising 360 evaluable contacts eligible for analysis of vaccine efficacy. MAIN OUTCOME MEASURE: Vaccine efficacy from attack rates of pertussis in household contacts classified by vaccination status. RESULTS: Of the 173 nonvaccinated household contacts, 96 developed typical pertussis, compared with seven of 112 contacts vaccinated with acellular pertussis vaccine. Vaccine efficacy was consequently calculated to be 88.7% (95% confidence interval, 76.6% to 94.6%). Protection did not wane until at least the time recommended for booster vaccination. None of the analyzed potential confounding factors--age, socioeconomic status, erythromycin treatment, household composition, center effect, and selection bias--influenced study results in favor of the vaccine. CONCLUSIONS: Under conditions of intense household exposure, primary vaccination with acellular vaccine protected against pertussis until at least the time recommended for booster vaccination. The vaccine can be expected to be equally or more effective in settings with lower infectious pressure.

[Blunt abdominal trauma caused by child abuse]. / Stumpfes Bauchtrauma verursacht durch Kindesmisshandlung.

We report about 3 boys under 4 years of age with abdominal blunt trauma following child abuse admitted to our clinic with different diagnoses. Common were fresh or older haematomas, burn wounds, for which the parents had no plausible explanation. The children had no skeletal or intracranial lesions, but they developed abdominal pain, which became worse in the absence of the parents. X-ray and the clinical course lead us to laparatomy. In all cases we found lesions of the intestines, especially near the duodenojejunal flexure, hepatoduodenal ligament, root of the mesentery, mesocolon and retroperitoneum, in one case a pancrease rupture. All these lesions were caused by child abuse. We want to point out the problem in the diagnosis of battered child syndrome, especially of the abdominal blunt trauma.

[Reduction of table salt and diuretic therapy in arterial hypertension in childhood]. / Kochsalzreduktion und diuretische Therapie bei arterieller Hypertonie im Kindesalter.

Experimental, epidemiological and clinical evidence indicates that salt plays a major role in the pathogenesis of arterial hypertension. Endocrine and membrane ion transport studies suggest a genetic disposition with regard to salt susceptibility. In the industrialized countries sodium intake in children probably exceeds the physiological needs. However, a reduction of salt consumption in the general paediatric population cannot be recommended as the longterm risk benefit ratio is currently unknown. In children with manifest arterial hypertension sodium intake should be reduced below 2 mval/kg/day. Diuretic therapy is an important part of antihypertensive treatment. Thiazides and in renal insufficiency furosemide are the drugs of choice. The side effects of diuretic therapy, such as hypokalemia, hyperuricemia, and hyperlipidemia, in children require further investigation.

[Nocturnal hypoglycemias and cortisol excretion in overnight urine]. / Nächtliche Hypoglykämien und die Cortisolausscheidung im Nachturin.

In 20 juvenile diabetic inpatients the relationship between nocturnal hypoglycemia and overnight urinary cortisol excretion was studied. Cortisol was expressed as absolute quantity per kg body weight because the cortisol/creatinine ratio does not always yield reliable results in diabetic patients. Comparison between different patients yielded no significant difference between posthypoglycemic and non-posthypoglycemic cortisol values. Testing the difference between urinary cortisol excretion in posthypoglycemic and non-posthypoglycemic urine samples for every one of the patients intraindividually, however, a significant posthypoglycemic elevation was found. Posthypoglycemic cortisol response was irregular and variable not only in different patients, but also within the same patient. If a high excretion of cortisol is found in an overnight urine sample, it is very likely to be caused by nocturnal hypoglycemia. On the other hand it is impossible to exclude nocturnal hypoglycemia by normal urinary cortisol findings. Reactive hyperglycemia as described by Somogyi was seen only rarely in this study. It is concluded that even if a distortion by falsely high creatinine measurements in diabetics is ruled out, cortisol measurement in overnight urine samples cannot be used as easy routine method for the detection of nocturnal hypoglycemia.

Determinants of plasma arginine-vasopressin in children.

Plasma concentration of arginine-vasopressin (AVP) was measured in 145 healthy subjects aged one day to 18 years of age. AVP decreased with age immediately after birth. Above one year of age values of children did not significantly differ from those in adults. AVP significantly correlated with plasma and urine osmolality after water deprivation during 16 h. Plasma AVP rose during exercise and fell after volume expansion. Nausea and vomiting are potent nonosmotic determinants of AVP release in children. Nonosmotic factors of AVP release should be controlled when sampling blood for measuring AVP in children for diagnostic and investigational purposes.

[Endocrine and neurogenic hypertension in childhood]. / Der endokrine und der neurogene Hochdruck im Kindesalter.

Endocrine and neurological diseases are rare causes of arterial hypertension in childhood. They represent less than 5% of all cases of secondary hypertension. Inflammatory, traumatic, and tumorous disorders of the central nervous system rarely result in chronic hypertension but may frequently be associated with acute hypertensive crisis. The most important hypertensinogenic endocrine diseases are the catecholamine producing tumors pheochromocytoma and neuroblastoma and disorders of the adrenal cortex such as Cushing's syndrome, hyperaldosteronism, 11-hydroxylase deficiency and other mineralocorticoid excess syndromes. Renin producing tumors, hyperthyroidism and hyperparathyroidism are rare causes of hypertension in children. Neurogenic and endocrine forms of hypertension have contributed considerably to a better understanding of the pathophysiology of blood pressure regulation. They are of particular interest to the pediatrician since specific therapy may be available.

Hypothalamo-pituitary-gonadal axis in children with chronic renal failure.

Delayed puberty in children with chronic renal failure (CRF) may be due to gonadal dysfunction, increased plasma binding of gonadal hormones, or changes of the hypothalamo-pituitary axis. Plasma androgens were studied in 17 prepubertal boys with preterminal CRF. In addition, the response of luteinizing and follicle-stimulating hormones (LH, FSH) to luteinizing-releasing hormone (LHRH) was followed in the plasma of these boys and of 12 prepubertal girls with CRF. Plasma testosterone (T) was significantly lower in the CRF boys than it was in the controls (mean, 9 vs. 22 ng/ml) and concerned also the free T fraction (2.5% in both groups). Dihydro-T was similarly reduced in CRF, resulting in a normal T/DHT ratio. Basal plasma LH levels were significantly elevated in boys (1.0 vs. 0.5 ng/ml) and in girls with CRF (1.4 vs. 0.4 ng/ml), whereas mean basal FSH values were similar to controls. After LHRH administration, peak levels of LH and FSH were not different in CRF and control children; however, the absolute differences from basal to peak values were lower in CRF. These findings may indicate that Leydig cell dysfunction in CRF already occurs before the onset of puberty. The blunted LH and FSH responses to LHRH suggest an additional disturbance at the hypothalamo-pituitary level.

Vasoactive hormones in children with chronic renal failure.

Plasma renin activity (PRA), aldosterone, vasopressin and catecholamines were measured in 15 children (ages 7.3 to 16.2 years) with chronic renal failure (CRF) before and after one session of hemodialysis and in 15 control children. Basal levels of PRA and aldosterone in children with CRF did not differ significantly from control values, but showed a wider range. Uremic patients with nephronophthisis showed the highest basal PRA and aldosterone levels. In children with CRF, basal vasopressin levels were significantly higher (9.7 +/- [SEM] 2.0 ng/liter) than control values (3.2 +/- 0.8 ng/liter). Plasma noradrenalin and adrenalin concentrations were similar in children with CRF and controls. During hemodialysis, a fall in blood pressure and a rise in heart rate was observed in all children. PRA and catecholamines increased twofold to fivefold during dialysis while aldosterone and vasopressin showed a variable response. In contrast to reports in adults, there is no evidence for an insufficiency of vasoactive hormones or of the sympathetic nervous system in children on hemodialysis.

Progressive adrenal failure in polyglandular autoimmune disease.

We describe the clinical course of a boy who developed progressive adrenal failure, beginning with failure of the zona glomerulosa, as part of polyglandular autoimmune disease. Initially the patient presented with hypoparathyroidism and mucocutaneous candidiasis. ACTH tests at ages 8 and 11 yr resulted in a normal response of both mineralo- and glucocorticoids. The constellation of hyponatremia , hyperkalemia, and growth failure at age 14 yr prompted a reevaluation. A repeat ACTH test, assessing individual contributions of zone fasciculata and glomerulosa, showed normal plasma cortisol, desoxycorticosterone, and corticosterone responses and a normal urinary response of 18-hydroxydeoxycorticosterone and tetrahydrodeoxycorticosterone. Urinary 18-hydroxycorticosterone and urinary as well as plasma aldosterone were undetectable. PRA was markedly elevated. The ACTH response of adrenal androgens, presumably metabolic products of the zona reticularis, was also deficient. Antiadrenal antibodies against all three layers of the adrenal cortex were present. Mineralocorticoid therapy resulted not only in normalization of electrolytes and PRA but also in catch-up growth. Repeat testing of fasciculata function at age 19 yr now shows that the patient's cortisol response to ACTH response in abnormal. The course of this patient suggest that in addition to monitoring the electrolyte status, periodic tests for both mineralo- and glucocorticoid synthesis should be performed in children with polyglandular autoimmune disease because progressive adrenal insufficiency may go unrecognized.

Adrenal glomerulosa function in patients with dexamethasone-suppressible hyperaldosteronism.

The response of the adrenal glomerulosa to renin stimulation was determined in 10 patients with dexamethasone-suppressible hyperaldosteronism. The patients were treated continuously with 2 mg/day dexamethasone (DEX) and were studied on a regular sodium diet (87 meq/m2 . day) and on a 10 meq/day sodium diet. With DEX treatment all patients showed a prompt suppression of adrenal fasciculata function as evidenced by suppression of serum cortisol, corticosterone, desoxycorticosterone, and urinary 18-OH-desoxycorticosterone. The complete suppression of urinary pH 1 aldosterone (aldo) by DEX, unique to this disorder, was paralleled by a prompt suppression of urinary 18-OH-corticosterone. With continued DEX administration, plasma renin activity rose to the normal or supranormal range. Dietary sodium restriction resulted in a further rise in plasma renin activity and a rise in urinary pH 1 aldo and 18-OH-corticosterone. We conclude that in DEX-suppressible hyperpaldosteronism, although ACTH appears to be the primary stimulus for aldo secretion in the untreated state, when ACTH is suppressed, the adrenal glomerulosa responds normally to the stimulation of renin-angiotensin II.