Gilles Leboeuf

A twenty-year experience with thyroid carcinoma in children

During the past 20 years, 23 patients (7 males, 16 females) were operated on for thyroid carcinoma in our institution. The average age was 13.6 years (range, 22 months to 27 years). Our series includes papillary carcinoma in 11, follicular carcinoma in four, and medullary thyroid carcinoma in eight patients. Follow-up ranged from 8 months to 20.3 years, with an average of 7.5 years for well-differentiated carcinomas and 4.3 years for medullary thyroid carcinomas. All patients are presently alive with no evidence of progressive disease. Patients with papillary and follicular carcinomas underwent partial thyroidectomy; those with medullary carcinoma underwent total thyroidectomy. Serious complications included three permanent hypoparathyroidism and two tracheostomies, all after secondary neck explorations. The overall results observed in our series of patients seem to support the current conservative approach to well-differentiated thyroid carcinoma, reserving total thyroidectomy for medullary cancer of the thyroid. A more aggressive search for familial medullary carcinoma through use of pentagastrin stimulation leads to early detection and more effective therapy.

Immunologic and thyroid function studies in euthyroid children with goiter

Summary Thirty-one clinically euthyroid children with goiters were studied by immunologic and other laboratory procedures. The results of these studies indicate that most of the goiters were associated with an autoimmune process directed against the thyroid gland. The diagnosis of thyroiditis was confirmed by open biopsy in 3 patients. In 2 patients with thyroid antibodies in the serum, the biopsy revealed follicular hyperplasia without inflammatory changes, emphasizing the diagnostic limitations of the available immunologic tests. However, high titers of antibodies in euthyroid children with goiters, when associated with abnormalities of thyroid function tests, abnormal serumprotein patterns, and regression of the goiter in response to treatment with desiccated thyroid, are strongly suggestive of the presence of a form of chronic thyroiditis.

ENDOCRINE EFFECTS OF CHRONIC ADMINISTRATION OF |[Delta]|9-TETRAHYDROCANNABINOL |[lpar]||[delta]|9-THC|[rpar]| TO PREPUBERAL MALE RATS

Although some reports have appeared which seem to indicate that Δ9-THC, the active principle derived from marijuana, can influence some endocrine functions, no systematic study has yet been published on the endocrine effects of its chronic administration to animals. Groups of 21-day old male Sprague-Bawley rats were injected intraperitoneally 3 times a week for a month with either 1.0 or 10.0 mg;/kg of Δ9-THC or with the vehicle. At the end of the experimental period, the animals were sacrificed by decapitation, endocrine organ weights were recorded; plasma and pituitary levels of GH, LH and FSH were measured by radioimmunoassay. Endocrine organ weights of rats treated with 1.0 mg/kg of Δ9-THC were not significantly different from those of controls, but plasma levels of FSH were higher and pituitary levels lower than in controls (Mean ± S.E. Plasma FSH: Δ9-THC: 512 ± 27, controls: 382 ± 41 ng/ml, p < 0.02; pituitary FSH: Δ9-THC : 23.1 ± 0.8, controls: 30.3 ± 4.5 ug/mg, p < 0.05). Rats treated with 10.0 mg/kg of Δ9-THC had lower ventral prostate weights (Δ9-THC : 153 ± 7, controls: 184 ± 9 mg, p < 0.02) and lower plasma LH levels (Δ9-THC: 4.0 ± 1.4, controls: 25.1 + 5.0 ng/ml, p < 0.001). These results indicate that the active principle of marijuana can influence the development of the reproductive system.

17 Urinary C21 Corticosteroid Sulfates in the Urine of Premature Infants Pre and Post ACTH

We have studied the urinary excretion of cortisol (F), cortisone (E), tetrahydrocortisol (THF), tetrahydrocortisone (THE), 6β-hydroxycortisol (6β-OHF) and corticosterone (B) in premature infants. Each specimen was extracted sequentially for free, β-glucuronidase and solvolysis liberated steroids; each metabolite was identified by constant isotope ratios, and quantitated by a double-isotope derivative assay. In 3 normal prematures studied within the first 48 hours of life, 6β-OHF, THF, F and B were mainly recovered as free or sulfated compounds. THE and E were mainly sulfurylated. In a 4th infant, with respiratory distress syndrome, studied similarly, 6β-OHF was mainly sulfated while THF was mostly as a glucuronoside. THE and B were equally glucuro and sulfo-conjugated while F and E were equally recovered in free or sulfated form. In a pool of 8 premature infants studied from two weeks of age, prior to ACTH, approximately 60 % of F and E were sulfo-conjugated, while a larger proportion of B was in the sulfate form. 6β-OHF and THF were predominantly excreted as sulfates, while THE was mostly unconjugated. Post ACTH, there was a considerable increase of all steroids and glucuro-conjugation seemed genererally enhanced except for F. These studies suggest that: 1. in resting state, most C21 steroids are excreted unconjugated or conjugated with sulfuric acid, in accord with limited glucuro-conjugation; 2. some limitation in reduction of Ring A of the steroid molecule exists since more unreduced metabolites are recovered than in older children and adults; 3. glucuroconjugation can be enhanced under stress or ACTH, suggesting that glucuro-conjugation is not maximal in resting state; 4. these metabolic particularities persist at least up to four weeks of age. (SPR)

481 A NEW TYPE OF LIGAND-INDEPENDENT PARTIAL ANDROGEN RESISTANCE DETECTED WITH THE AID OF THE SYNTHETIC ANDROGEN , 17α-METHYL MIBOLERONE (MB)

Mutations that cause androgen resistance by altering various properties of the androgen receptor other than its maximum binding capacity (Bmax) are termed receptor-positive (R+). We have studied intact pubic and genital skin fibroblasts (SF) from an XY infant with markedly ambiguous genitalia. Their androgen receptor activity had a Bmax of 20 fmol/mg protein (normal: 10–40), an equilibrium binding constant (Kd) of 0.7 nM (normal: ∼ 0.1), and failed to «up-regulate» in response to prolonged incubation with ∼ 3 nM MB (normal: 2- to 4-fold during 72 h). In addition, the mutant MB-receptor complexes dissociated with a half-life of 52 min at 33°C (normal: 300), and were more thermolabile than normal (<10% remained after 4 h at 42°C; normal: >50%). In contrast, the unliganded mutant receptor activity had a normal half-life (at 37°C, 10 h; at 42°C, 80 min). The aberrant properties were also demonstrable with 5α-dihydrotestosterone, or with a second synthetic ligand, methyltrienolone.Conclusions: (i) these data reveal a severely defective R+ mutant androgen receptor that is distinct from any we have described heretofore (J Clin Endocrinol Metab 59: 679, 1984); (ii) the native mutant receptor does not misbehave until it is, or has been, bound to ligand; (iii) the latter suggests that free receptor molecules derived from mutant MB-receptor complexes differ from their never-liganded counterparts.

RELATIONSHIP BETWEEN ADRENAL STEROIDS AND GONADOTROPHINS IN PUBERTAL DEVELOPMENT

The mechanisms which lead to the activation of the hypothalamopituitary gonadal axis at puberty remain speculative. It is generally accepted that a change in sensitivity of the hypothalamus to feedback effect of circulating sex hormones occurs in the early phases of sexual maturation. Last year, Ducharme et al have presented at this society suggestive evidence that some adrenal steroids may play a role in elevating the gonadostatic threshold to circulating androgens and estrogens at this period. In order to study this interrelationship further, plasma Testoesterone (T), Androstenedione (Δ), Estrone (E1), Estradiol (E2) were measured by radioimmunoassay at different stages of sexual development and correlated with plasma HIH and HFSH. In addition, the response to LH/FSH-RH was evaluated in precocious and delayed puberty. An elevation of Δ and E1, preceded any increase in gonadotrophins which in turn preceded the expected increase in T and E2. A parallel displacement in this time sequence relationship was noted in subjects with precocious or delayed puberty. The pattern of gonadotrophins response to LH/FSH-RH correlated better with plasma levels of “adrenal” than “gonadal” steroids. These studies bring additional confirmatory evidence that adrenal steroids may play an important role in the early hypothalamo-pituitary regulatory changes characteristic of puberty.