Aplasia cutis congenita and methimazole.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to G N Burrow.
Explore the source record for details and available documents.
A 32-year-old woman with persistent postpartum galactorrhea, hyperprolactinemia and a sellar configuration compatible with pituitary adenoma underwent transsphenoidal surgery. Mild hyperthyroidism had been suspected clinically preoperatively and thyroxine plus cortisol therapy was given. Morphological features of pituitary thyrotroph hyperplasia were present as shown by light microscopy, immunoperoxidase staining and electron microscopy. The thyrotroph hyperplasia was secondary to primary hypothyroidism as demonstrated by the TSH response to TRH stimulation and subsequent suppression with thyroid hormone treatment. Although prolonged severe hypothyroidism has been reported to cause pituitary enlargement, this is the first case of thyrotroph hyperplasia with detailed morphologic study of the surgically-removed adenohypophysial tissue. The presentation of this patient calls attention to the possibility of mistaking pituitary enlargement due to primary hypothyroidism for a prolactinoma.
The effects of three putative growth factors and serum on [Me-3H]thymidine and Na125I incorporation into thyroid cell cultures have been examined. We found that serum and EGF could stimulate radioactively labelled thymidine incorporation into confluent cultures. However, both factors completely inhibited iodine uptake and organification at low concentrations. Insulin also stimulated [Me-3H]thymidine incorporation but had no adverse effect on thyroid differentiated function. TSH examined under the same conditions was not a growth factor but was essential to maintain differentiated functions. We conclude that thyroid growth and differentiation are not mutually exclusive processes. However, EGF and serum inhibit thyroid differentiated function at very low concentrations. Elucidation of the physiological role of these factors and their mechanism of action may lead to a greater understanding of thyroid hormone biosynthesis.
Explore the source record for details and available documents.
Metabolites of norepinephrine and dopamine were measured in urine from 12 women of normal body weight and from six women undergoing treatment for anorexia nervosa. The women with anorexia nervosa had 48% less body fat (14 +/- 1 versus 27 +/- 1%, p less than 0.001), 9% less fat-free mass (36 +/- 1 versus 40 +/- 1 kg, p = 0.05), and 26% higher energy intake (2217 +/- 147 versus 1750 +/- 43 kcal, p less than 0.01) on collection days compared to the normal weight women. Twenty-four-hour excretions of norepinephrine metabolites, 3-methoxy-4-hydroxyphenylethylglycol, 3,4-dihydroxyphenylethylglycol, and vanilmandelic acid were reduced (p less than 0.01) in anorexia nervosa by 44, 48, and 39%, respectively. Excretion of homovanillic acid, the dopamine metabolite, was the same for both groups. Urinary 3-methoxy-4-hydroxyphenylethylglycol content was best predicted by percentage body fat in the normals (r = 0.63, p less than 0.05) and for both groups combined (r = 0.79, p less than 0.001). Urinary vanilmandelic acid showed a strong relationship with fat-free mass in the normal group (r = 0.84, p less than 0.001) and for both groups combined (r = 0.79, p less than 0.001). In contrast, urinary 3-methoxy-4-hydroxyphenylethylglycol and vanilmandelic acid and energy intakes were only weekly associated in the normals, but unrelated in the anorexics, or when the data from both groups were combined.(ABSTRACT TRUNCATED AT 250 WORDS)
Because the exact site of thyroid hormone absorption in man is not known, we assessed the absorption of oral [125I]Na-L-T4 in patients with varying lengths of intact bowel and correlated this absorption with bowel length. Two normal subjects and five patients with surgical bowel resections, all of whom were euthyroid, were studied. Each received a tracer dose of [125I]Na-L-T4 orally, and serial samples of serum were assayed for radioactivity both with and without butanol extraction. The peak serum radioactivity in normal subjects occurred 2 h post ingestion and was 15% and 17% of the administered dose per liter serum and 11% and 13%/liter serum in butanol-extracted serum, respectively. In patients with shortened bowel, the peak radioactivity both in serum and butanol extracted serum was decreased, ranging from 2%-7% and 0%-5%/liter, respectively. There was no absorption of labeled T4 in the patient with a duodenum only. No consistent relationship was found between absorption and bowel length distal to the duodenum.
A 42-year-old woman developed goitrous hypothyroidism while receiving ethionamide for treatment of an atypical mycobacterial infection. Five weeks after discontinuation of ethionamide therapy, thyroid function had returned to normal. The goitrogenic effect was studied in vitro by incubating ethionamide in various concentrations (10(-3) to 10(-7) mol/L) with ovine thyroid cells in tissue cultures. Ethionamide inhibited the trapping of technetium and organification of iodine at concentrations seen clinically (10(-5) mol/L). Ethionamide appears to be a potential goitrogen in susceptible persons.
Explore the source record for details and available documents.
An antiserum (PC-81-1) was obtained from a man who developed antibodies against hCG during treatment for hypogonadism. The antiserum was unique in that its affinity for hCG was high (greater than 10(-10) M(-1] and its cross-reaction with hLH and the hCG-subunits was only 1-12.5% and 0.01%, respectively, of intact hCG. We propose that this human antiserum be used as a laboratory standard by investigators who are developing vaccines directed against hCG. The use of this standard in the proposed protocol will permit comparison of titers between laboratories. Lyophilized samples of antiserum PC-81-1 are available on request from the Population Council.
Posttranslational processing of thyroglobulin may influence its role as the prothyroid hormone. We have examined the role of glycosylation in the subsequent export and iodination of thyroglobulin. We find that glycosylation is necessary both for the movement of thyroglobulin through the cell and for iodination. During posttranslational processing, thyroglobulin is also phosphorylated and carboxymethylated. The implications of these postsynthetic modifications are discussed.
Pregnant Rhesus monkeys treated with 131I at midgestation become hypothyroid and produce fetuses without demonstrable thyroid tissue. In an effort to prevent both maternal and fetal hypothyroidism, we treated 131I-treated pregnant monkeys with 3,5-dimethyl-3'-isopropyl-L-thyronine (DIMIT), a thyroid hormone analog with structural changes which facilitate placental transfer. Five pregnant monkeys were treated with 131I (mCi/kg) at 83-87 days of gestation. One week later, three monkeys were started on treatment with DIMIT (10 micrograms kg-1 day-1, im) and two on im L-T4 (2 micrograms kg-1 day-1). Treatment was continued until delivery by Caesarian section at 152-157 days of gestation. None of the DIMIT-treated mothers became clinically hypothyroid, nor did they have elevated serum TSH concentrations despite low serum levels of T3 and T4. T4-treated mothers were also maintained clinically and biochemically euthyroid. At delivery, infants of DIMIT-treated mothers had normal respiratory function and skeletal maturation. Basal and TRH-stimulated TSH concentrations were suppressed in two of the three infants. By contrast, both T4-treated infants resembled untreated cretinous newborns and died soon after delivery from respiratory failure. Serum TSH concentrations were elevated and skeletal maturation was markedly delayed in these animals. We conclude that DIMIT administration to 131I-treated monkeys prevents clinical and biochemical hypothyroidism in the mother and prevents the major clinical manifestations of cretinism in the fetus.
Tunicamycin, an inhibitor of glycosylation, was incubated with ovine thyroid cells in culture to determine the role of glycosylation in the subsequent processing of thyroglobulin to form thyroid hormone. After a 6-h preincubation with tunicamycin (1 microgram/ml), mannose incorporation into glycoproteins in the cell layer was inhibited effectively (greater than 90%), whereas leucine incorporation into proteins was inhibited by less than 30%. Conversely, the quantity of radioactively labeled proteins secreted into the medium by the thyroid cells was markedly inhibited. Thyroglobulin secretion into the medium and iodination were negligible. A low mol wt fragment of thyroglobulin was found after tunicamycin treatment, indicating increased susceptibility to or contact with proteases. These data suggest that glycosylation is obligatory for the processing of thyroglobulin, including iodination and subsequent thyroid hormone production.
Placental transfer of iodothyronines is minimal in most species. The nonhalogenated thyroid hormone analog 3,5-dimethyl-3'-isopropyl-L-thyronine (DIMIT) was administered to pregnant ewes to determine if this compound could prevent cretinism in the thyroidectomized fetal lamb. Pharmacokinetic studies comparing [125I]T3 and [3H]DIMIT resulted in fetal-maternal ratios for [3H]DIMIT which were 5- to 10-fold higher than the ratios for [125I]T3, suggestive of preferential transport of DIMIT across the placenta. Subsequently, DIMIT was administered to three pregnant ewes after hysterotomy and fetal thyroidectomy at 95-98 days gestation. Intramuscular DIMIT (1200-2000 micrograms/day) caused suppression of maternal T4 concentrations from a mean of 4.9 micrograms/dl before hysterotomy to less than 1 micrograms/dl within 1-2 weeks. All three thyroidectomized lambs had clinical signs of cretinism at birth and died. Skeletal and lung maturation were delayed in these animals, all of whom had undetectable serum T4 concentrations. In contrast to DIMIT's proven thyromimetic activity in other fetal animal models, this thyroid hormone analog failed to prevent cretinism in thyroidectomized fetal lambs even when administered to the ewe at a dose that suppressed maternal thyroid function.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
This study compared a group of 24 applicants who were interviewed and accepted at the Yale University School of Medicine but went to other medical schools (AYEs) with a group of 27 applicants who attended the same schools but had been rejected at Yale following an interview and committee deliberation (NAYs). Measures of performance during medical school included scores on Parts I and II of the examinations of the National Board of Medical Examiners and evaluations from the dean's office at each student's medical school. No relationship was found between admission decisions and performance during medical school when AYEs and NAYs attending the same medical schools were compared.