SUMMARY In twenty‐three thyrotoxic patients a prospective study was undertaken to assess the time until restoration of TSH secretion. For several methodological reasons we chose to study a model in which the patients were deliberately continued on full dose treatment until biochemical hypothyroidism was established. The period until reappearance of TSH secretion varied between 42 and 293 days. In this time FTI had become subnormal, while T3 and the clinical index remained in the normal range. The interval until TSH restoration was not correlated with the parameters of thyroid status from the initial evaluation with the exception of a negative correlation with log PB131I 48 h (r= 0·511; P < 0·02). The average follow up period in our patients was 115 days during which FTI decreased exponentially to 19±7 ± 20±5. The disappearance of T3 followed a biphasic course in which after 2–4 weeks T3 decline practically ceased and concentrations remained normal. Assuming that a FTI between 100 and 65 was the threshold value beneath which hypophyseal TSH synthesis and secretion could be expected, we were able to determine the interval between the corresponding date and the date of returning TSH secretion in twenty‐one patients. This latency time was 34 ± 9±7 days and proved completely independent of the total time until TSH reappearance. In contrast there was a highly significant correlation (r= 0·987; P<0·001) between the time to reach the assumed threshold level and the time to recovery of TSH secretion. The disappearance of FTI, although widely variable from patient to patient, showed a constant rate throughout the full scale from elevated to practically absent concentrations. Thus, the initial part of the disappearance curve determines the length of time until restoration of TSH secretion. This is illustrated by the tight relationship (r= 0·92; P < 0·001) between FTI after 28 days of treatment and the time when TSH started to rise. Knowledge of the FTI on day 28 allows treatment to be tailored to the needs of the individual patient.

Renal digoxin clearance was compared in patients suffering from atrial fibrillation with well preserved cardiac function (n = 9; salt intake +/- 170 mmol daily) and patients with chronic congestive heart failure (n = 10; salt intake 50 mmol daily and maintenance treatment with diuretics). There was no difference between the groups concerning digoxin dosage, creatinine clearance, diuresis or sodium excretion in the urine. Digoxin clearance in chronic heart failure proved to be significantly lower than in atrial fibrillation (48 +/- 21 vs 71 +/- 36 ml X min-1, p less than 0.05), and Cdig/Ccreat was similarly reduced at 0.73 +/- 0.15 compared to 1.09 +/- 0.27 (p less than 0.005). Steady state serum digoxin concentration was significantly higher in patients with congestive heart failure (1.44 +/- 0.47 vs 0.87 +/- 0.33 micrograms X 1(-1), p less than 0.01). Chronic congestive heart failure is a state with reduced digoxin clearance by the kidney, which could lead to digoxin intoxication not explicable by overdose, reduced renal function or the effect of interacting drugs.

To delineate more precisely the role of gestational age, weight at birth and thyroid status at birth on the postnatal changes in thyroid hormone levels, serum T4, T3, TSH and in some cases FT3I were measured at birth and at 3-4 h, 24-30 h, 6-9 days and 13-20 days. Subjects studied were healthy appropriate-for-date (AFD) and small-for-date (SFD) term neonates and healthy AFD and SFD preterm children. At birth T4 and T3 are related to both gestational age and weight with T4 and T3 showing lower values in preterm and SFD term neonates than in AFD term children. After birth T4 and T3 concentrations show a better correlation with gestational age than with weight at birth. For TSH no correlation was found at birth, a positive correlation at 24-30 h, no correlation at 6-9 days and a negative correlation at 13-20 days both with gestational age and weight at birth. In term and close-to-term infants (36 weeks) individual T4 levels at 6-7 days show a close relationship with those at birth; in the younger children (34 and 35 weeks) lower T4 values are found, despite equal cord blood values. The individual cord blood FT3I/TSH values correlate well with those at 6-7 days of age. It is concluded that after birth all children have changing T4 and T3 values, but the pattern and level are influenced by the maturity of the child and its thyroid status at birth measured by T4 and by the FT3I/TSH ratio.(ABSTRACT TRUNCATED AT 250 WORDS)

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Since no data are available concerning thyroid hormone levels in Snell dwarf mice from birth on, a cross-sectional study was performed of l-thyroxine (T4) and l-triiodothyronine (T3) levels in blood or serum as a function of age of several litters, starting at birth. In normal Snell mice T4 levels in blood and serum are changing with age. T4 increases during the first 2 weeks of age and declines thereafter, until adult levels of about 50 nmol/l are reached at 21 days of age. Serum T3 values are in the range of 2\p=n-\3nmol/l. They do not show such an age-related pattern. From birth on in each litter there was a clear separation between animals with low T4 levels in blood and the others. This separation was possible at all subsequent days until 9 days of age, when dwarfs can be recognized by eye. Above that age the low T4 values were associated with dwarfism. This suggests that dwarfs are hypothyroid already at birth. Serum T3 in dwarfs falls below the normal range only after 4 weeks of age, resulting in a lower T4/T3 ratio than normal.The half life time of exogenous T4 in serum of dwarfs is in the range of 13\p=n-\18h and not different from normal. For T3t\m=1/2\is 9.5\p=n-\11.1h. Dwarf mice become euthyroid by treatment with 0.1 \ g=m\ g T4 per day. 1 \ g=m\ gT4 was needed to reach a physiological level of T3. These data suggest that the peripheral conversion of T4 to T3 is slower in dwarfs than in normals. Treatment with hGH, prolactin, glucagon, insulin, testosterone and oestradiol had no influence on serum T4. As expected TSH was stimulatory.Similar results were obtained for serum T3, with the exception of prolactin which caused slightly increased levels of serum T3.The hypopituitary Snell dwarf mouse (Snell 1929) secretes very low amounts of growth hormone, prolactin and thyroid stimulating hormone