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Abstract. A Turkish family with frequent intermarriages is described, in which two siblings were born with persistent forms of congenital hypothyroidism, in the elder child concomitant with absent radioactive thyroid imaging. The mother was clinically euthyroid throughout the period of observation, but showed in addition to thyroid microsomal antibodies, high levels of immunoglobulins blocking the trophic action of TSH. These maternal growth blocking antibodies were transiently present in the youngest of the siblings (from birth to 2 months of age). She had a relatively mild form of congenital hypothyroidism (T3: 33 μg/100 ml; T4: 3.9 μg/100 ml). The older sibling, with proven non-functioning thyroid tissue (negative thyroidscan, T4: 0.4 μg/100 ml) produced the growth-blocking immunoglobulins herself and may thus represent a juvenile form of thyroid autoimmunity with a very early onset.An aunt and uncle of the children, both hypothyroid since birth, were at the age of 19 and 18 years weakly positive for growth blocking immunoglobulins.This study indicates that familial forms of congenital hypothyroidism are probably complex and may be brought about by maternal to foetal passage of thyroid reactive autoantibodies, but also by the inheritance of a trait for thyroid autoimmunity. In some cases these two mechanisms might act in conjunction.

In order to test the clinical usefulness of new commercially available kits for determination of calcitonin serum concentrations, we investigated the family (N=10) of a patient with medullary thyroid carcinoma and bilateral pheochromocytoma including his affected son, 10 athyreotic patients, totally thyroidectomized for non-medullary thyroid cancer, and 4 normal volunteers. Pentagastrin tests were performed in all subjects. Serum calcitonin levels before and after pentagastrin were determined by 4 kits. Kits A and B are immunoradiometric assays of the sandwich-type, kits C and D are radioimmunoassays, D being the one hitherto routinely used. Our results show that the new assays (kits A, B and C) have a better diagnostic accuracy in screening for medullary thyroid cancer than the RIA (kit D), hitherto used, where basal values overlapped with normals. Although basal values of normals were mostly near the detection limit of all 4 kits, kits A and B were sensitive enough to detect stimulation of calcitonin secretion by pentagastrin in all subjects with intact thyroid glands and kit C in most of them. The lack of increase in calcitonin after pentagastrin observed by kits A, B and C in athyreotic patients suggests deficiency of secretion of this hormone. Only kit D was unable to show this deficiency.

Abnormalities of thyroid and pituitary function are well recognized in patients with end-stage renal failure. We have investigated the influence of varying degrees of renal insufficiency on serum thyroid (total thyroxine, TT4; total 3,5,3′-triiodothyronine, TT3, and 3′,5′,3′-triiodothyronine, reverse T3) and pituitary (thyrotrophin, TSH; growth hormone, GH; prolactin, PRL) hormone levels before and after 200 μg thyrotrophin releasing hormone (TRH) iv administration.Patients with mild renal insufficiency (= group 1, plasma creatinine (Cr) > 1.3 mg% but < 3.0 mg%) had normal basal and TRH-stimulated hormone concentrations. In patients at a more advanced stage of the disease (= group 2; Cr > 3.0 mg % but < 7.0 mg %) basal hormone concentrations were also normal. In contrast to the normal group, where no GH reaction to TRH could be detected, GH serum concentrations increased in these patients after TRH. The TT3and PRL response to TRH remained normal. The TSH reaction to TRH was blunted in four, normal in two and exaggerated in one patient. Patients with end-stage renal failure (= group 3; Cr > 7.0 mg%) had significantly decreased basal TT3concentrations but a normal TT3response to TRH. Basal TT4, TT3and TSH concentrations were normal. The TSH reaction was blunted in four and normal in three patients. The mean basal GH was elevated, albeit not significantly different from the control mean value. The GH increase after TRH was even more pronounced than in group 2. Basal PRL concentrations were significantly increased, but maximal differences between basal and TRH-stimulated concentrations were not significantly different from control.Our data suggest that changes in the pituitary and hypothalamic control of GH are an early consequence of renal insufficiency. Alterations in thyroid function occur simultaneously on the pituitary – hypothalamic and peripheral level at a more advanced stage of the disease. PRL basal levels increase with decreasing renal function. In contrast to other studies we could not observe any significant influence of uraemia on the TRH-stimulated PRL reserve of the pituitary.