Circulating thrombopoietin levels in neonates with infection.

Thrombocytopenia is a commonly encountered hematologic complication in neonates with sepsis. Thrombopoietin (TPO) is the principal physiologic regulator of megakariocytopoiesis and platelet production. This study was carried out to determine whether variations in circulating TPO levels would occur in infected neonates and/or if they would correlate with platelet counts. In a prospective study of 36 sick neonates (gestational age 24-42 wk) admitted to a regional Neonatal Intensive Care Unit (NICU), blood was collected for TPO measurements and platelet counts on admission to the NICU, if infection was inferred, and at recovery before discharge. An additional group of 15 apparently healthy neonates was also studied (median postnatal age at the time of blood sampling for TPO assessment: 4 d, range 1-10) as control. TPO was measured on plasma samples using a commercially available enzyme-immunosorbent assay (ELISA). On admission, the majority (21/36) of the sick neonates had non-infectious diseases, 2 had early onset sepsis, and 13 had infection (defined as the presence of clinical signs of sepsis, abnormal leukocyte counts or C-reactive protein values, and positive results on local cultures, but negative blood culture results). During the hospital stay, 5 neonates developed sepsis (positive blood culture) and 6 had infection (as previously defined) or necrotizing enterocolitis (NEC). The median TPO level (1704 pg/ml, range 51-3912) was higher during sepsis (either early or late) than during infection (included NEC) (198 pg/ml, range 21-2504), or non-infectious disease (659 pg/ml, range 0-2533), while platelet counts (median value 37,000 cells/microl, range 15,000-486,000) were lower than during either infection (included NEC) (median value 238,000 cells/microl, range 49,000-655,000) or non-infectious disease (median value 110,000 cells/microl, range 45,000-549,000). When infants had recovered from these illnesses, TPO concentrations markedly dropped (median value 59 pg/ml, range 0-825). These values were similar to those found in the control neonates (median TPO level 85 pg/ml, range 43-620). In infected neonates (sepsis plus infection), TPO levels inversely correlated with platelet counts (r = -0.634, p = 0.001) as did those of infants with non-infectious disease (r = -0.574, p = 0.006), while there was no significant correlation between TPO levels and platelet counts in the samples obtained after recovery or in the control infants. We conclude that infected neonates have high circulating TPO levels in the face of low platelet counts. Whether larger TPO concentrations following exogenous administration of recombinant TPO would restore the number of circulating platelets warrants further investigation.

Thyroid and celiac disease: clinical, serological, and echographic study.

OBJECTIVE: We sought to reevaluate the prevalence of thyroid dysfunction and thyroid autoimmunity in 47 patients with celiac disease; 91 healthy subjects were studied as controls. Both patients and controls were from Sardinia, Italy. METHODS: Diagnosis of celiac disease was made on the basis of clinical history, presence of positive antigliadin IgA (AGA-A) and IgG (AGA-G) antibodies, antireticulin antibodies (ARA), antiendomysium antibodies (EMA), and was confirmed by jejunal biopsy. HLA class II typing for DQB1 and DQA1 alleles was performed in 36/47 celiac patients. Thyroid was evaluated by palpation and echography; serum free thyroid hormones (FT4, FT3), thyrotropic hormone (TSH), and antithyroid peroxidase autoantibodies (anti-TPO) were assayed by radioimmunoassays. RESULTS: The prevalence of anti-TPO was higher in celiac patients (29.7%) than in healthy controls (9.6%) (p < 0.001) and thyroid echography frequently displayed (42.5%) a hypoechogenic pattern. Five anti-TPO-positive celiac patients were hypothyroid (two overt, three subclinical). A higher but not significantly different prevalence of anti-TPO (3/7 = 42.8%) was found in celiac patients displaying the DQB1*0502 genotype, when compared with the remaining patients (8/29 = 27.6%). CONCLUSIONS: An elevated prevalence of clinical and subclinical autoimmune thyroid autoimmunity was found in Sardinian celiac patients, especially in those displaying the DQB1*0502 genotype; this finding could be related to a particular genetic background of the Sardinian population.

Lactose intolerance following antithyroid drug medications.

We recently observed 2 lactase-deficient women with Graves' disease who consistently developed severe diarrhea after ingestion of thionamide (methimazole and propylthiouracil) tablets containing lactose as carrier. The strict temporal relationship between ingestion of lactose-containing tablets and appearance of intestinal symptoms, as well as the absence of side effects following ingestion of methimazole tablets without lactose as carrier, provided the clue for the diagnosis. To our knowledge, severe diarrhea resulting from carrier lactose has not been previously reported for antithyroid drugs, and should be considered in occasional cases of patients with gastrointestinal symptoms on thionamide therapy.

[Purpura fulminans in the newborn. Report of two cases successfully treated with heparin and antithrombin III]. / La purpura fulminans nel neonato. Descrizione di due casi trattati efficacemente con eparina ed antitrombina III.

Purpura fulminans is a rare form of disseminated intravascular coagulation characterized by rapidly progressive purpuric lesions, hypotension and, in some cases, fever. In neonates, purpura fulminans usually develops following deficiency of anticoagulant protein C or S, although acquired forms have been described. The management of disseminated intravascular coagulation is still controversial, with some studies finding a positive effect of anticoagulants and others showing no effect or even a detrimental one. Therefore, at present, management is limited to the treatment of underlying disease and replacement of clotting factors. Personal experience is reported on the efficacy of heparin in combination with antithrombin III in the treatment of purpura fulminans in two preterm neonates who did not have inherited deficiency of protein C or S and developed the disease possibly following prolonged labor (36 hours) in the first case, and maternal neoplasia, in the second. Both neonates presented with widespread cyanotic areas rapidly evolving in purpuric lesions and hemorrhagic bullae. Laboratory tests (prolonged prothrombin and partial thromboplastin time, fibrinogen and antithrombin III concentrations below normal ranges, d-dimer highly positive) were consistent with disseminated intravascular coagulation. In both cases anticoagulant treatment with heparin (50 UI/kg in bolus followed by 15 UI/kg/h) and antithrombin III was associated with resolution of disseminated intravascular coagulation and prompt amelioration of the purpuric lesions, without apparent side effects.

Circulating soluble IL-2 receptor levels are low in patients with hypothyroid autoimmune thyroiditis.

In hypothyroid patients serum soluble IL-2 receptor levels showed scattered and conflicting results. In our report we studied circulating soluble interleukin 2 receptors in 22 patients with hypothyroid autoimmune thyroiditis before L-thyroxine treatment and when the patients became euthyroid. The mean of soluble Interleukin 2 receptor levels in the hypothyroid state was 48.6 pmol/l (95% confidence interval, 45.6-51.5) statistically lower than in the controls (95% confidence interval, 86.4 pmol/l, 83.3-89.4) (p < 0.0001). When the patients became euthyroid during L-thyroxine treatment, soluble Interleukin 2 receptor levels increased, showing mean values comparable to the controls. A positive high correlation (p < 0.001) was observed between soluble Interleukin 2 receptor levels and thyroxine free levels in the hypothyroid as well as in the euthyroid state and between soluble Interleukin 2 receptors and the mean weekly L-thyroxine dose. Our study confirmed that in the hypothyroid state, the behaviour of soluble Interleukin 2 receptors is anomalous as compared to other autoimmune diseases. In fact a strict relationship exists between the levels of thyroid hormones and soluble Interleukin 2 receptors but not between the latter and antithyroid antibodies. These results agree with those supporting a role for thyroid hormones in the regulation of the immune system. They also suggest that the measurement of soluble Interleukin 2 receptors could be used as a marker of the peripheral action of thyroid hormones.

[Low levels of dehydroepiandrosterone sulfate in adult males with insulin-dependent diabetes mellitus]. / Bassi livelli di deidroepiandosterone solfato in maschi adulti affetti da diabete insulino dipendente.

UNLABELLED: Studies on animals and humans have suggested that dehydroepiandrosterone sulphate (DHEAS) has antiatherogenic effects. It has been hypothesized that insulin may have an atherogenic role and it has been reported recently that, surprisingly, DHEAS levels decreased in normal men and women during the hyperinsulinemic-euglycemic technique. Since a hyperinsulinemia frequently occurs during insulin therapy in patients with insulin dependent diabetes mellitus (IDDM), the present work was undertaken to determine whether DHEAS serum concentrations were decreased in IDDM patients as compared to controls and if so, to discover the possible causes. To this, purpose, out of 805 outpatients afferent to our Diabetes Centre from 1989 to 1992, three groups were selected on the basis of the criteria described below. Known interferences with the DHEAS serum concentrations such as gender (all males), age (aged 20-40 years) and Body Mass Index (BMI < 30) were excluded. Group A (cross-sectional study) was made up of 15 IDDM patients on insulin treatment with good metabolic control (HbA1C < 8%); group B (control study) was made of 18 healthy subjects (these patients were selected also on the basis of their normal oral glucose tolerance test) and group C (longitudinal study) was made up of 7 IDDM patients who had been examined previously and who were on insulin treatment. METHODS: In all three groups serum concentrations of DHEAS, 17 OH progesterone (17 OHP), delta 4 androstenedione (A4) and cortisol (F) were measured. In 10 patients from group A and in 9 patients from group B the ACTH test (9.25 mg IM Synacthen) was administered and the same hormonal pattern was measured after 60 min. In group C the same hormonal evaluation was performed 5 +/- 2.8 months after commencement of insulin therapy. RESULTS: DHEAS serum concentrations were significantly decreased in group A (median 2.9; range 1.1-5.2 mumol/l) with respect to group B (median 5.7; range 3.0-9.5 mumol/l) (p < 0.0012). However, the serum concentrations of 17 OHP (median 3.9 nm/l; range 2.9-6.9 nm/l and A4 (median 5.2 nm/l; range 1.8-10.2 nm/l) were also significantly reduced, while cortisol levels and the 17 OHP/A4 ratio were comparable to group B. After administration of ACTH, the delta increment in cortisol percentage showed a frank increase (55.1%) in group A with respect to group B (33.1%) (p < 0.01). The rise in DHEAS showed a lower increase in group A (10.2%) with respect to group B (65.5%) even though not statistically significant, while the other hormones showed an overlap between the two groups. In group C the serum concentrations of hormones before insulin therapy did not show any statistical differences with respect to the values in group B. A second evaluation, which was performed during insulin therapy, showed that only the 17 OHP/A4 ratio tended towards higher values with respect to pretherapy values (1.1 and 0.6 respectively; p = 0.07). In conclusion our data confirm low DHEAS levels during chronic insulin administration therapy. The underlying mechanism could be a general aspecific reduction in the activity of P 450 C 21 SCC enzymes in contrast with the specific inhibition of 17.20-lyase obtained during insulin bolus. Whether the low serum concentrations of DHEAS can determine an atherogenic effect of insulin needs further investigation, but the hormone could constitute a new parameter for the follow-up of patients affected by diabetes mellitus.