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Biomedical subjects

A H Klein

Publications and source records attributed to A H Klein.

48 records · Page 3Linked to original sources

Effect of parturition on serum iodothyronine concentrations in fetal sheep.

T4, T3, and rT3 were determined by RIA on daily serum samples collected from five catheterized fetal sheep during the 2-week period before spontaneous vaginal delivery (PTD). Samples were also available from three newborn lambs during the first 4 h of life. T3 concentrations began to increase 4-6 days before spontaneous vaginal delivery, from a stable geometric mean concentration of 30 ng/dl to a mean concentration of 131 ng/dl on the day of delivery (day 0). T4 concentrations decreased in four of the animals and remained unchanged in one during this time interval. rT3 concentrations decreased from a stable mean of 472 to 249 ng/dl on day 0. The prenatal increase in serum T3 levels correlated temporally with increasing fetal serum cortisol concentrations. The mean T3 concentration increased further after delivery to a level of 487 ng/dl at 1 h of age without significant changes in T4 or rT3 levels. The following conclusions were reached: 1) fetal serum T3 concentrations increase while T4 and rT3 concentrations decrease during the 4-6 days preceding spontaneous labor, and 2) T3 concentrations increase further after delivery. Available evidence suggests that the prenatal increase in fetal serum T3 levels is mediated by a cortisol-induced increase in T4 to T3 conversion in fetal tissues. The mechanism(s) of the postnatal increase in serum T3 concentrations in the newborn is not clear.

Animals↗

Cord blood reverse T3 in congenital hypothyroidism.

Reverse triiodothyronine (rT3) was measured in cord serum from 5 infants with congenital hypothyroidism and compared with normal values in 70 euthyroid control infants. The mean (and SEM) value in the affected infants (135 +/- 12 ng/dl) was significantly lower than that in the control population (270 +/- 9 ng/dl). However, the large overlap in range of concentrations in affected and control infants indicates that newborn screening based on the determination of rT3 in cord blood specimens offers no advantage over present screening methods.

Congenital Hypothyroidism↗

Damped oscillations in serum thyroid hormone levels of normal newborn infants.

Exposure to the extrauterine environment is associated with marked stimulation of the hypothalamic-pituitary-thyroid system after which, pituitary-thyroid equilibrium must be reestablished. This marked endogenous perturbation offers the opportunity to study the manner in which the pituitary-thyroid axis is reequilibrated. T4, T3 and TSH concentrations have been measured by RIA in sera from 440 healthy newborn infants, whose ages ranged from birth to 236 h. Results were analyzed by nonlinear curve-fitting procedures to assess the changes in mean hormone concentrations with age (t). Equations have been derived by Danziger and Elmergreen to allow assessment of oscillatory behavior during hormone equilibration. Applying these equations to the present data, we observed the presence of an oscillatory cosine term in the equation for each hormone. This indicates significant oscillations in serum T4, T3, and TSH concentrations during the first 5 days of life. The period of the oscillations approximates 16 h. The oscillations in T4, lag 1/2 to 3/4 cycle behind TSH; T3 lags behind T4. Thus, disturbances in hypothalamic-pituitary-thyroid equilibrium seem to be followed by periodic oscillations in hormone concentrations; these oscillations decrease in amplitude as the negative feedback system establishes new equilibrium conditions.

Aging↗

Effect of intraamniotic fluid thyroxine injection on fetal serum and amniotic fluid iodothyronine concentrations.

Seven hundred micrograms of T4 were injected into the amniotic cavity 24 h before delivery of five pregnant women scheduled for elective cesarean section at term. T4, T3, and rT3 concentrations were measured by RIA in amniotic fluid obtained at the time of the injection and in amniotic fluid and cord serum samples collected at delivery. Iodothyronine concentrations also were determined on cord samples from 24 full term control infants. The geometric mean serum T4 concentration in the experimental infants was 27.2 micrograms/dl, almost 3 times that of the control population (10.3 micrograms/dl); serum rT3 concentrations were markedly elevated to a mean of 657 ng/dl, compared to 254 ng/dl in control infants. The mean serum T3 concentration was slightly but significantly increased to 61.3 ng/dl (control, 48.3 ng/dl; P less than 0.02). Amniotic fluid T4, T3, and rT3 concentrations all increased significantly. T4 injection into the amniotic fluid is an effective method of increasing fetal serum T4 concentrations. The preferential pathway of monodeiodination of the injected T4 in the human fetus is to rT3 rather than T3.

Amnion↗

Adaptation of TSH filter paper method for regionalized screening for congenital hypothyroidism.

A sensitive, specific, rapid radioimmunoassay is described for the determination of thyrotropin (TSH) in eluates from two 3 mm discs punched from dried blood filter-paper specimens. This method is sufficiently sensitive to easily discriminate between normal infants and infants with primary hypothyroidism. The use of two 3 mm discs enables screening laboratories to easily incorporate this methodology into the currently available, fully automated systems to screen for several metabolic disorders. Since mental retardation occurs in untreated infants with primary hypothyroidism, our TSH method as the primary screening test alone, or in association with a thyroxine (T4) screening test, should detect all infants with primary hypothyroidism with a very acceptable low false-positive recall rate.

Congenital Hypothyroidism↗

Neonatal thyroid function in congenital hypothyroidism.

In the cord blood of seven infants with congenital hypothyroidism detected in our newborn screening programs, thyroxine values ranged from 2.5 to 6.7 mug/dl and thyrotropin, from 105 to 975 muU/ml; triiodothyronine values were normal. On follow-up, T3 levels increased to normal in five infants, there was a significant negative correlation between the T3 value and the severity of thyroprevia as reflected in the TSH levels and the number of clinical features present. This increase in T3 may explain in part why the diagnosis of this disease is difficult during the first few months of life and why early treatment is effective. This observation provides further rationale for the widespread institution of newborn screening programs for congenital hypothyroidism.

Congenital Hypothyroidism↗

Iodothyronine kinetic studies in the newborn lamb.

Metabolic clearance rates and production rates for thyroxine (T4), triiodothyronine (T3) and reverse T3 (rT3) were determined by pulse injection kinetic techniques in newborn sheep between 7 and 14 days of age. The mean metabolic clearance rate for T3 (39.6 +/- 4.5 l/m2 per day) was significantly greater than that for T4 (7.25 l/m2 per day, P < 0.001). The mean value for rT3 (27.5 +/- 2.8 l/m2 per day) also exceeded that for T4 (P < 0.001) but did not differ from that for T3. The mean production rate for T3 (95.6 +/- 5.8 micrograms/m2 per day) was significantly less than that for T4 (511.4 +/- 71.7 micrograms/m2 per day, P < 0.01). The mean value for rT3 (28.6 +/- 1.7 micrograms/m2 per day) was significantly less than respective values for T4 (P < 0.01) and T3 (P < 0.001). Calculated thyroid gland secretion accounted for 42.3 micrograms/m2 per day of T3 production and 4.7 micrograms/m2 per day of rT3 production. Calculated peripheral conversion from T4 accounted for 53.3 micrograms/m2 per day (56%) of the production of T3 and 23.9 micrograms/m2 per day (84%) of that of rT3. The metabolic clearance rate for T4 and the production rate for T4 and T3 in the newborn were greater than those measured earlier (Chopra, Sack & Fisher, 1975) in the fetus or adult ewe. The metabolic clearance rate of T3 in the newborn was less that the fetal value but similar to that measured in adult animals. The newborn value for rT3 was greater than that in the fetus and similar to that in the adult ewe. The production rate of rT3 was lower than that previously measured in the fetus but similar to that in adult ewes. Our results suggest that the transient chemical thyrotoxic state characteristic of the newborn is accountable on the basis of increased thyroid gland secretion of T4 and T3 as well as increased T3 production from T4 via peripheral monodeiodination.

Animals↗