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OBJECTIVE -To investigate the prevalence of autoimmune diseases in young patients (probands) with type 1 diabetes and their first-degree relatives, and to determine the spectrum of extrapancreatic manifestations in these subjects. RESEARCH DESIGN AND METHODS-The study population included 109 probands age 13 Ϯ 4.9 years and 412 first-degree relatives age 28.7 Ϯ 16.2 years. The prevalence rates of autoimmune thyroiditis and celiac disease were determined in all probands and in 100 of the 412 first-degree relatives. Control groups included 78 subjects age 14.9 Ϯ 10.4 years for the prevalence of autoimmune thyroiditis and 120,000 youth ages 16 -17 years for the prevalence of celiac disease. Thyroiditis and celiac disease were diagnosed by abnormally high thyroid peroxidase (TPO), thyroglobulin (TG), antigliadin, and antiendomysial antibody titers. Celiac was confirmed by biopsy. A questionnaire was used to interview probands and relatives to determine the spectrum of autoimmune manifestations.RESULTS -The prevalence of autoimmune thyroiditis determined by high TPO and/or TG titers was 27 and 25% for probands and relatives, respectively. These rates were higher than those for control subjects (P Ͻ 000.1). The prevalence of celiac disease among probands and screened relatives was 8.3 and 6%, respectively. These rates were higher than those for control subjects and the 312 family members interviewed only (0.1 and 0.3%, respectively; P Ͻ 0.0001). Interviews of participants revealed a wide range of associated autoimmune diseases. The risk of developing an autoimmune disease was higher (P Ͻ 0.001) in families with a proband who had an additional autoimmune manifestation.CONCLUSIONS -Screening for autoimmune thyroiditis and celiac disease should be performed in patients with type 1 diabetes and their first-degree relatives, especially when the probands have an additional autoimmune manifestation.

Explants of human chorion-decidual tissue obtained at delivery from normal, full-term pregnancies synthesize and secrete prolactin. This hormone is indistinguishable from pituitary prolactin by chromatographic, electrophoretic, immunologic, and receptor assay techniques. These results suggest that chorion-decidua may be the source of the large quantities of prolactin in amniotic fluid.

The aim of the present study was to examine the use of low-dose ACTH-(1-24) stimulation for assessment of adrenal function and the detection of mild adrenal insufficiency. The criteria for normal response to ACTH-(1-24) are a peak cortisol level of more than 500 nmol/L (18.1 micrograms/dL) and an increment of the cortisol level above the basal one of more than 200 nmol/L (7.2 micrograms/dL). These criteria were satisfied by 32 of 33 healthy children and adults subjected to an ACTH-(1-24) dose 500 times lower (0.5 micrograms/1.73 m2) than the dose of 250 micrograms in the standard test. At 20 min, the peak cortisol level was the same in the low-dose test [(621 +/- 28 nmol/L) (22.5 +/- 1.0 microgram/dL)] as in the standard ACTH test [(654 +/- 31 nmol/L) (23.7 +/- 1.1 microgram/dL)]. Of 46 asthmatic patients who had been treated with inhaled beclomethasone dipropionate (482 +/- 42 micrograms/m2 daily; n = 32) or budesonide (507 +/- 62 micrograms/m2 daily; n = 14) for over 6 months, 16 (35%) failed to reach a cortisol peak of more than 500 nmol/L (18.1 micrograms/dL) following stimulation with 0.5 micrograms ACTH-(1-24)/1.73 m2. Of these, 11 (24%) showed a cortisol increment of less than 200 nmol/L (7.2 micrograms/dL). These 16 patients, showing insufficient response to low-dose ACTH-(1-24), also had a significantly lower (P < 0.01) mean 24-h urinary free cortisol excretion [(71 +/- 10 nmol/m2.24 h) (25.7 +/- 3.6 micrograms/m2.24 h)] than patients who responded normally [(118 +/- 11 nmol/m2.24 h) (42.8 +/- 4.0 micrograms/m2.24 h). Nonetheless, all but one of the poor responders to a 0.5 microgram ACTH showed normal stimulation with the standard 250 micrograms ACTH test. Therefore, it appears that a low-dose ACTH test is capable of revealing mild adrenal insufficiency, which is not detected by the standard high-dose ACTH test.

Lower cortisol levels in children born with IUGR may reflect impaired function of the hypothalamic-pituitary-adrenal axis associated with this condition. The significantly lower IGF-I levels of the 'non-catch-up' subgroup may be involved in their failure to grow.

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The concentrations of ovine placental lactogen (oPL) have been determined in maternal plasma, umbilical cord plasma, and allantoic fluid by an homologous radioimmunoassay for oPL which is sensitive to 0-1 ng hormone. Ovine placental lactogen was first detected in maternal plasma at 41-50 days of gestation and reached a peak concentration of 2547 +/- 226 (S.E.M.) ng/ml at 121-130 days in ewes with singleton gestations. The oPL concentration in cord plasma was 336-4 +/- 60-3 ng/ml and in allantoic fluid was 29-6 +/- 6-4 ng/ml. After surgical removal of the placenta, oPL disappeared from maternal plasma with a half-life of 29-1 +/- 1-3 min.

Parathyroid hormone-related (PTHrP), the major mediator of humoral hypercalcemia of malignancy, may also regulate placental calcium flux, uterine contraction and fetal tissue development. In the present study, we demonstrated that the mean immunoreactive PTHrP concentrations in amniotic fluid at mid-gestation (21.2 +/- 3.7 pmol/l) and at term (19.0 +/- 2.7 pmol/l) were 13-16-fold higher than levels measured in either fetal (1.6 +/- 0.1 pmol/l) or maternal plasma (1.4 +/- 0.3 pmol/l) at term and equal to levels found in plasma of patients with humoral hypercalcemia of malignancy. In vitro studies pointed to three possible sources of PTHrP in amniotic fluid: cultured amniotic fluid cells, cells derived from the amniotic membrane overlying the placenta and placental villous core mesenchymal cells. Treatment of cultured amniotic fluid cells with human prolactin, human placental lactogen (hPL) or human growth hormone (100 micrograms/l) increased PTHrP secretion after 24 h by 43%, 109% and 90%, respectively. Insulin-like growth factors I and II (100 micrograms/l), insulin (100 micrograms/l) and epidermal growth factor (EGF) (10 micrograms/l) increased PTHrP secretion by 53%, 46%, 68% and 118%, respectively. The stimulation of PTHrP secretion by EGF or by hPL was both time- and dose-dependent. In contrast, calcitriol and dexamethasone (10 nmol/l) decreased PTHrP secretion by 32% and 75%, respectively. Estradiol, progesterone, dihydrotestosterone and human chorionic gonadotropin had no effect on PTHrP secretion. These findings support the notion that PTHrP may play a physiological role in the uteroplacental unit and demonstrate that human amniotic fluid cells could be a useful model for studying the regulation of PTHrP production and secretion by hormones and growth factors.