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Abstract

A 9 1/2 year old boy had been treated for complete 21-hydroxylase deficiency from infancy. That diagnosis was excluded by HLA-typing of family members who wished to know their carrier status. Withdrawal of replacement therapy was very well tolerated. The patient showed distinct compensatory growth and for the first time was free of crises of adrenal insufficiency.

This instance demonstrates an unexpected application of HLA-typing. It also shows that an amount of hydrocortisone too small to give any clinical evidence of overdose can impede growth. Furthermore, it provides reassurance that adrenocortical function can recover completely after many years of treatment with exogenous steroids.

Abstract. We have established a relatively simple and sensitive system for measuring T₃ as well as cAMP secretion using cryopreserved human thyroid cells in culture. We defined optimal culture conditions and characterized the system. T₃ secretion from human thyrocytes (only 1 × 10⁵ cells/well) could be stimulated in a time- and dose-dependent fashion by both TSH (doses as low as 10 mU/l) and thyroid-stimulating immunoglobulin to levels 5- to 10-fold above baseline. The response to the thyroid stimulating agents was preserved for at least 3 weeks. Experiments with inhibitors of iodothyronine synthesis (propylthiouracil and methimazole) indicated that the bulk of the TSH-stimulated T₃ secretion measured apparently derives from de novo iodothyronine biosynthesis rather than preformed T₃. We utilized the system to investigate some aspects in the regulation of human thyrocyte T₃ and cAMP secretion. Maximum stimulation of the thyroid hormone was achieved at TSH doses capable of evoking a further rise in levels of cAMP. A rise in cAMP accumulation was observed as early as 15 min following exposure to TSH, whereas it took 1–4 days to detect a significant increase in T₃ secretion. Within 6 h of incubation, the bulk of TSH-stimulated intracellular cAMP was found released into the medium. l-methyl-3-isobutylxanthine (MIX) caused a dose-related decrease (beyond 0.1 mmol/l MIX) in TSH-stimulated T₃ secretion which contrasted with a concomitant expected increase in cAMP accumulation. Hence, as also observed in adrenal and testicular tissue, xanthines at high concentration seem to exhibit a dual action: potentiation of cAMP accumulation by inhibiting phosphodiesterase activity and a concomitant reduction of hormone formation.

Kraiem Z., Bowers CY, Sobel E, Laron Z. Growth hormone (GH)-releasing heptapeptide, but not GHreleasing hormone, inhibits thyrotropin-stimulated thyroid hormone secretion and cAMP formation in cultured human thyroid follicles. Eur J Endocrinol 1995;133:117–20. ISSN 0804–4643

Synthetic heptapeptide growth hormone-releasing peptide-1 (GHRP-1) potently stimulates GH release in many species, including humans. We investigated the direct in vitro effect of this peptide, compared to growth hormone-releasing hormone (GHRH), on cultured human thyroid follicles. The results indicate that whereas GHRP-1 (6–600 μg/l) or GHRH (6–600 μg/l) alone had no effect on basal triiodothyronine (T₃) secretion or cAMP formation, the heptapeptide (6–600 μg/l), but not GHRH (6–1200 μg/l), dose-dependently inhibited thyrotropin (TSH)-stimulated T₃ secretion and cAMP formation. Moreover, GHRP-1 also dose-dependently inhibited forskolin-stimulated T₃ secretion. It would seem, therefore, that the GHRP-1-induced inhibitory effect on thyroid function is located downstream of cAMP formation, without necessarily excluding an additional inhibitory action at a pre-cAMP site. These results additionally demonstrate differences in the mode of action of GHRP-1 and GHRH.

Z Kraiem, Endocrine Research Unit, Carmel Medical Center, 7 Michal Street, Haifa 34362, Israel

Abstract.

Transient neonatal hypothyroidism has been observed in three successive offspring of a mother with autoimmune thyroiditis. Thyroxine replacement therapy was initiated in a 23-year-old woman with overt clinical and laboratory findings of non-goitrous primary hypothyroidism. While on such treatment, she gave birth to three infants manifesting hypothyroidism immediately after birth. The neonates were treated with thyroxine replacement therapy which was discontinued in the three siblings at ages 2½ years, 3½ years, and 13 months. Continuous observation following cessation of therapy revealed clinical and biochemical euthyroidism in the children. Thyroid scanning during the neonatal period in the first child failed to identify functional thyroid tissue, suggesting thyroid agenesis, whereas thyroid scan performed on subsequent follow-up revealed a normal gland. Sequential serum measurements of autoantibodies directed towards the thyrotropin receptor were made in the mother and third child by a cAMP bioassay. High titres (five-six fold above normal) of blocking antibodies (tested by measuring the inhibition of TSH-stimulated cAMP production of cultured human thyroid cells by serum immunoglobulin preparations) were present in the mother and newborn 10 days after birth. The levels remained persistently high in the mother, whereas they declined and were undetectable in the child at four months. Thyroid-stimulating immunoglobulin was absent in both mother and child. The data are compatible with transient neonatal hypothyroidism caused by transplacental transfer of antibodies which block thyroid response to TSH. The half-life of the maternally-derived blocking antibody in the infant was estimated as 1-2 months. This is the first report on sequential serum measurements and estimate of half-life of the blocking antibodies performed by a cAMP bioassay (using thyroid cells of human origin). Unlike the radioreceptor assay employed so far in such cases, this assay can distinguish between stimulating and blocking TSH receptor antibodies.