Early Thyroid Research Articles

Thyroid abnormalities in dermatitis herpetiformis. Prevalence of clinical thyroid disease and thyroid autoantibodies.

We studied thyroid abnormalities in 50 patients with dermatitis herpetiformis. Two patients had a history of hyperthyroidism, and 5 had hypothyroidism and were on thyroid replacement therapy. Three patients had had thyroidectomies for nodules, and 5 had asymptomatic goiter. Two patients were clinically euthyroid with elevated thyrotrophin and low normal thyroxine levels, indicating early thyroid insufficiency. Thyroid microsomal antibodies were seen in 38% of patients with dermatitis herpetiformis compared to 12% of controls. The presence of clinical or serologic thyroid abnormalities in 26 of 50 patients shows a significant but unexplained association between dermatitis herpetiformis and thyroid disease.

EVALUATION OF THYROID DISEASES FOUND BY MASS SCREENING FOR THYROID DISEASE WITH SPECIAL REFERENCE TO THYROID CANCER

From September 1978 to October 1984, we carried out mass screening for thyroid disease in Tokushima prefecture. In this survey 13, 049 subjects were examined, and the following results were obtained. 1. Thyroid abnormalities necessitating further examination were found in 334 subjects, accounting for 2.6% of the total. 2. Diffuse goiter was prevalent in younger subjects and nodular goiter was prevalent in older ones. 3. Thyroid cancer was found in eight cases. The incidence of thyroid cancer in this survey was 0.06%. Five were in stage I and three in stage II. 4. Simple diffuse goiter and chronic thyroiditis showed higher incidences than other benign thyroid diseases. 5. Mass screening was useful in detecting early thyroid cancer and in surveying incidences of other benign thyroid diseases.

TSH stimulation of iodine organification in early foetal rat thyroid in vitro.

Thyroid glands from 15 day-old rat foetuses were incubated in Eagle's medium containing Na 125I and supplemented, or not, with TSH for 4 or 24 hours. Electron microscopic radioautographic study shows silver grains mainly in follicular cavities only in the thyroids submitted to TSH during 24 hr. A functional differentiation must therefore take place in thyroid cells under TSH stimulation.

Vascular changes in early TSH-induced thyroid tumours in the rat.

Vascular changes in early TSH-induced thyroid tumours in the rat.

Early ontogeny of iodocompound-processing neural systems in rat brain.

The distribution and localization of iodocompounds reaching the brain during early development were measured in rat pups nurtured on [125I]-containing milk from dams receiving daily [125I]-iodide injections. The regimen produced no measurable changes in growth and development of the offspring during the nursing period. Pup brains accumulated labeled iodocompounds at a faster rate than they grew and accumulated protein. The ratio of [125I]-iodocompounds in cerebrum relative to skeletal muscle increased progressively from day 11 through day 19. Significant differences in distribution of radioactivity in different brain regions were evident on day 1; developmental progress was associated with significantly different rates of regional accumulation of the isotope. On day 1 only 10% of the radioactivity in the postnuclear supernatant phase of brain homogenates was particle-bound; at the time of weaning, radioactivity in brain particles accounted for more than 50%. Growing nerve cell processes and myelin, known to be major targets of early thyroid hormone deficiency or excess, were also the major subcellular sites of [125I]-iodocompound localization in the developing rat brain. Overall, the ontogeny reflected progressive elaboration of iodocompound-processing neural systems resembling those recently recognized in adult brain.

Prolactin and thyrotrophin response to thyrotrophin-releasing hormone in growth hormone deficiency.

Basal and thyroid-releasing hormone-stimulated (200 micrograms/m2) prolactin and thyroid-stimulating hormone (TSH) levels were measured in 31 patients with hypopituitarism (13 isolated growth-hormone deficiencies and 18 multiple pituitary hormone deficiencies). The results were compared with the prolactin response in 76 healthy prepubertal children. Normal prolactin concentrations were found in 13 patients whereas 11 had increased levels. TSH levels were either normal or increased in patients who were considered to have hypothalamic disorders. Decreased prolactin response was present in 7 children, 6 of whom had multiple pituitary deficiencies. Their TSH response was decreased as well, indicating pituitary failure. There was good overall correlation of peak prolactin with peak, TSH concentrations. Some patients with 'isolated' growth hormone deficiency had an abnormal prolactin response indicating an additional hormonal deficiency. All patients with low levels of serum thyroxine had abnormal prolactin or TSH levels, high in some, low in others. Two euthyroid patients with increased prolactin stimulation became hypothyroid during treatment with growth hormones, thus questioning whether prolactin is a more sensitive indicator of early thyroid insufficiency than thyroxine or TSH levels.

Contractile properties and fibre composition of rat skeletal muscle: effect of mild hyperthyroidism.

The effect of a chronic mild elevation of plasma triiodothyronine levels upon the contractile properties and fibre distribution of skeletal muscle was studied. The isometric twitch characteristics and passive tension-length relationship were studied in the soleus and extensor digitorum longus muscles of anaesthetized rats injected for increasing periods with triiodothyronine. This treatment results in a progressive speeding in the rates of isometric contraction and relaxation of the soleus and in a concomitant decrease in the elasticity of the muscle. There was also a conversion of slow to fast fibre types in the soleus, demonstrated histochemically. It is concluded, in view of differences in the magnitudes and time courses of the various changes, that triiodothyronine increases the rates of contraction and relaxation of existing slow fibres and contraction in the soleus muscle as a whole before any change occurs which is attributable to slow-fast fibre interconversion. The possible mechanisms of the early thyroid hormone effects on muscle are discussed.

Structural remodelling of bat thyroid parafollicular (C) cells during development.

The development of bat parafollicular (C) cells was evaluated by electron microscopy from the time of early thyroid formation, through the neonatal period, to young adulthood. Parafollicular cells were relatively few in number (3%) at the earliest developmental stage examined, but increased with subsequent fetal stages, reaching a relatively stable level of 28% of parenchymal cell volume just prior to birth. Fetal parafollicular cells were packed with calcitonin granules. Following birth, however, parafollicular cells were totally or almost totally depleted of calcitonin granules. Moreover, another cell type that resembled the parafollicular cell was also found. This cell contained tiny granules which often contained two dense cores. Parafollicular cells of maturing, juvenile bats were characterized by the massive accumulation of secretory materal within the cisternae of the rough surfaced endoplasmic reticulum and a great deal of autophagy. Remarkably, none of these changes were found in young, adult bat parafollicular cells. In conclusion, this study provides morphological evidence to support the view that parafollicular cells play a role in developing mammals.

Ultrasound in early thyroid orbitopathy.

Fourteen patients with unilateral exophthalmos were found on A-scan ultrasound examination to have enlarged extraocular muscles. Thyroid dysfunction later was documented in 12 patients (86%) by laboratory tests and subsequent clinical examination. The suspicion of endocrine orbitopathy was based on the presence of enlarged extraocular muscles in both orbits and on the difference in thickness between corresponding muscles. A-scan orbital examination including specific muscle measurements is a simple and apparently reliable method of diagnosing early thyroid orbitopathy.

99mTc pertechnetate for detection of ectopic dysgenesis of the thyroid in childhood hypothyroidism.

99mTc pertechnetate for detection of ectopic dysgenesis of the thyroid in childhood hypothyroidism. 99mTc pertechnetate scans of the neck and pharyngeal region were performed on 29 hypothyroid children. Eleven were found to have lingual or sublingual thyroid tissue. No child with persisting ectopic thyroid tissue was intellectually impaired, but 5 of 14 athyreotic children were of subnormal intelligence. Early thyroid scanning of hypothyroid infants can be of prognostic value. In addition, all children who had become hypothyroid between the ages of 6. and 11 years were found to have ectopic glands.

A new gamma camera method for the measurement of thyroid uptake of technetium 99m pertechnetate.

Measurement of the early thyroid uptake of 99Tcm pertechnetate complements biochemical thyroid function tests by providing an index of thyroid “trapping”. This is not affected by commonly used antithyroid drugs so the technetium uptake performed during antithyroid drug therapy is used to follow progress of the underlying thyrotoxicosis. In addition, discordance between the thyroid technetium uptake and serum thyroxine level identifies cases of thyroiditis or organification defects (Marion et al., 1974). We describe a method of measuring thyroid technetium uptake with a gamma camera and region-of-interest modification, which gives reliable results.

The Pathogenetic Significance of Low Iodine Intake in Non-Endemic Goiter — Absolute Iodine Uptake

SummaryThe blood inorganic iodine concentration (BII), the radioiodide clearance and the absolute iodine uptake (AIU) were determined in 27 patients with simple goiter and in 21 controls. The purpose was to evaluate the pathogenetic significance of low iodine intake for the formation of sporadic goiter. An early thyroid radioiodide clearance was measured by 132 I (5–30 min post injection), and the BII values were bases on the specific activity of I in saliva.The median BII levels of patients and controls were 1.1 and 1.5 μg/l respectively, and the urinary iodine excretion 67 and 79 M-g/day respectively, the difference was not significant. The radioiodide clearance was above the normal range in 13 out of 27 patients, and 16 of 27 patients had elevated or high normal AIU values. These patients included 7 out of 9 patients with diffuse, shortlasting goiter; the AIU of those with nodular goiter ranged from slightly subnormal to elevated. Only one exhibited a typical iodine deficiency pattern of very low BII, high radioiodide clearance and normal AIU.It is concluded that a simple causal relationship between low iodine intake and goiter formation could not be demonstrated.

Efficiency of Organic Binding of Trapped Iodide in Sporadic Goiter, Evaluated by the Decrease of Radioiodide Clearance

SummaryThe decrease of early thyroid radioiodide clearance was determined in 33 patients with sporadic simple goiter, in 21 normal controls, in 38 hyperthyroid, and 9 hypothyroid patients. The clearance was measured between 5 and 30 min after injection of the tracer, 132I or 123 I, using a single detector system or a gamma camera, respectively. The decrease of clearance was given as the difference between the thyroid radioiodide clearance (ml blood/min) from 5–10 min and 25–30 min post injection.The relative decrease of clearance was similar in controls and in patients with simple goiter, indicating a normal binding efficiency of trapped iodide in the patients. The median 5–10 min clearance of controls was 85 ml blood/min, and of the patients 125 ml/min, the median decrease of clearance was 26 and 36 ml/min, respectively, i. e. about 30% in both groups; the higher early clearance values correlated significantly with the higher decreases. In the hyperthyroid patients the relative decrease was less pronounced, indicating that the increased iodide trapping in these patients was accompanied by a proportionately greater binding efficiency. In patients with primary hypothyroidism and elevated serum TSH levels the fractional binding of trapped iodide did not differ from normal.It was concluded that minor degrees of organic binding defects could not be demonstrated in patients with sporadic simple goiter.

The postnatal development of rat dentate gyrus and the effect of early thyroid hormone treatment.

The postnatal development of the dentate gyrus and the effect of 5 microgram/day triiodothyronine treatment was examined by means of tritiated thymidine autoradiography. The polymorph layer of the dentate gyrus is a secondary germinal layer and forms cells for the granular layer. The cell formation in the dentate gyrus was found to be nearly completed on the 21st day, but development ended only in adulthood. Thyroid-hormone treatment did not affect significantly the postnatal cell formation of the dentate gyrus, but resulted in the appearance of a great number of pycnotic cells in the granular layer.

Severity and timing of early thyroid deficiency as factors in the induction of learning disorders in rats

In Experiment 1 ( N = 277 rats), more extreme deficits in maze learning than heretofore shown appeared in the adult offspring of mothers exposed for 16 pre- and 16 postnatal days to thiouracil-treated mash diets in doses up to 0.3%; the same offspring also displayed deficits in single-alternation pattern learning and a modified operant discrimination task. Surprisingly small maze learning deficits, however, were found in the offspring of mothers which received thiouracil during the 16 postnatal days only, despite previous findings indicating that the postnatal half of the total 32-day perinatal period was the more critical in determining later learning impairments. Reconciliation was provided by Experiment 2 ( N = 54), in which the manipulation of a 0.2% thiouracil diet starting at birth or 3, 6, 10, or 15 days before birth indicated a lower age boundary of the critical period for the induction of maze learning deficit by thyroid deficiency at approximately the fetal age at which thyroid tissue becomes functional-around the 18th day of gestation.

Environmental Stimulation Reduces Learning Deficits in Experimental Cretinism

Behavioral deficits in adult rats exposed perinatally to thiouracil were substantially reduced or elimated by a 5-week period of "superenriched" postweaning rearing conditions before testing. This treatment resulted in remediation of hypothyroid rats' deficits in maze learning, maze retention, and resistance to extinction of bar-pressing; the facilitative effect persisted for more than 4 months. These behavioral results were consistent with neurohistological findings from studies of early thyroid deficiency and postweaning environmental stimulation in rats.

Congenital hypothyroidism--signs and symptoms in the newborn period.

Infants with athyrotic hypothyroidism usually manifest signs and symptoms of hypothyroidism prior to or during the period in the newborn nursery. These features are variable and include: prolonged gestation with large size at birth, large posterior fontanel, respiratory distress, hypothermia, peripheral cyanosis, hypoactivity, poor feeding, lag in onset of stooling, abdominal distension with vomiting, protracted icterus, and/or edema. Retrospective assessment of newborn nursery records of three infants from the Collaborative Perinatal Project who were subsequently found to have congenital hypothyroidism disclosed that they had six, eight, and nine, respectively, of these features while in the newborn nursery. Evaluation of newborn records on 12 other infants, often less complete, who were later found to have congenital hypothyroidism disclosed that each infant had from one to seven of these signs and symptoms, with an average of 3.2 per infant. Thus the most important period for clinical consideration of athyrotic hypothyroidism is in the newborn nursery to initiate early thyroid replacement therapy in affected infants.

A new pertechnetate thyroid uptake technique

A method of measuring early thyroid uptake of pertechnetate and excluding extrathyroidal radioactivity is described. Data derived from 100 patients are statistically analysed and the clinical significance of the results obtained are discussed. 99m Tc pertechnetate uptake values obtained at 15 and 30 minutes after intravenous injection of the tracer are compared with results of standard 4 hour and 24 hour 131 I iodide uptake.

Use of 99 Tc m for the routine assessment of thyroid function.

(99)Tc(m)-pertechnetate is concentrated in the thyroid in the same way as iodide but it does not become organically bound. The uptake of (99)Tc(m) is a measure of the thyroid trap, and this measurement is satisfactory as a routine test in the diagnosis of thyrotoxicosis. The reproducibility of the method is such that suppression tests can be carried out when necessary even when uptake is within the normal range of 0.4-3%. (99)Tc(m) gives a low radiation dose to the thyroid and has certain other advantages over radioactive isotopes of iodine for early thyroid uptake measurements. It is particularly suitable when serial tests of thyroid function are required during treatment with an antithyroid drug.

Hormonal regulation of brain development. III. Effects of triiodothyronine and growth hormone on the biochemical changes in the cerebral cortex and cerebellum of neonatally thyroidectomized rats

The effects of l-triiodothyronine and bovine growth hormone, administered to neonatally thyroidectomized rats, have been studied in connection with the changes in nucleic acid content and enzymic activities of the cerebral cortex and cerebellum. When administered from the 10th day of age, both triiodothyronine and bovine growth hormone were effective in correcting the alterations produced by neonatal thyroidectomy. On the contrary, when the beginning of treatments were delayed until the 15th day of age, triiodothyronine and/or bovine growth hormone showed no restoring effect. The finding that bovine growth hormone was as effective as triiodothyronine raises the question of whether the effects of early thyroid dysfunction on cerebral development reflect a direct action of thyroid hormone on this process or whether they are indirectly mediated.