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Elevated CEA levels should lead to determination of serum CT concentrations (especially if cervical adenopathy is present), even in patients who present no thyroid abnormality, since it may be the first way of discovery of medullary thyroid carcinoma.

Diurnal fluctuations of plasma TSH were investigated in ad libitum fed rats as well as after a 3 day starvation period in order to study the relationship between the circadian pattern of TSH secretion and nutritional status. Our study showed the persistence of a circadian TSH rhythm after a 3 day starvation without any change in the amplitude of plasma TSH variations. However, the 24 h average plasma TSH levels were significantly lower. A suggestive acrophase occurred at the same period of the day in starved and fed rats. Our results suggest that the control of plasma TSH concentrations and nycthemeral rhythm are not closely related and may even possibly be independent of one another.

Les manifestations cardio-vasculaires de l'hypothyroidie ont ete etudiees chez 10 malades, et les modifications morphologiques ainsi que les parametres de fonction myocardique ont ete apprecies au moyen de l'echocardiographie au cours d'une etude longitudinale comportant un examen pretherapeutique ainsi qu'un autre au bout d'un an de traitement. Cette etude met en evidence chez tous les sujets un epanchement pericardique qui disparait sous opotherapie. Les parametres de fonction myocardique sont peu perturbes: la vitesse de raccourcissement circonferentielle des fibres (VCF) est de 1 ± 0,32 avant traitement et de 1,13 ± 0,09 apres opotherapie (N.S.); la vitesse moyenne d'epaississement corrigee (VMEC) du mur posterieur est de 1,48 ± 0,61 avant traitement et de 2 ± 1,06 apres traitement (p. Cette etude demontre le caractere fonctionnel des alterations contractiles du coeur hypothyroidien et attribue la cardiomegalie observee au cours de l'hypothyroidie a la pericardite et non pas a l'infiltration du myocarde.

SUMMARY A study of hypothalamo-pituitary function was carried out in chronic alcoholic women aged 29-66 years, with chronic pancreatitis or cirrhosis of the liver. Amenorrhoea was present in most of them (67%). The hormonal investigation included assessment of basal plasma steroids, gonadotrophin and prolactin values, followed by an anterior pituitary function test. Clomiphene stimulation and/or hCG tests were performed. The subjects were divided into four groups according to their oestrogen status on the one hand, and the baseline gonadotrophin concentration on the other. Results were compared with two control groups composed of twelve healthy post-menopausal women and ten normal women of reproductive age. Five different patterns of hypothalamo-pituitary ovarian activity could be distinguished: post-menopausal women (eight), perimenopausal women (eight), hypothalamic amenorrhoea (five), anovulation (four) and inadequate luteal phase (six). A normal peri- or post-menopausal hormonal profile was found in most (77%) chronic alcoholics of more than 45 years of age. In contrast, 84% of patients of reproductive age had functional hypothalamic disorders. These observations suggest that chronic alcoholism affects sexual function at the hypothalamo-pituitary level chiefly during the reproductive period. The pathogenesis of these endocrine changes is not clear. The relative importance of ethanol consumption, liver damage and non-specific factors such as nutritional status and chronic illness are discussed. Sexual dysfunction is a well-known complication of chronic alcoholism in men, resulting from both primary gonadal and central hypothalamo-pituitary defect (Baker et al., 1976; Green, 1977; Mowat et al., 1976; Van Thiel et al., 1974, 1978a). In women, chronic alcoholism is often associated with hypofertility, loss of libido, irregular menses or amenorrhoea (Borhanmanesh-Haghighi, 1970; Green-Rubin, 1959) but there is little and * Deceased. Correspondence: Dr Modigliani, HOpitaI Avicenne, 125 route de Stalingrad 93000 Bobigny, France. 0300-0664/80/0600-0543$02.00 0 1980 Blackwell Scientific Publications

After 3 days of starvation, refeeding with carbohydrate (CHO) leads to a rapid increase in plasma T4 and T3, suggesting increased TSH secretion. The aim of the present study was to describe the time course of plasma TSH changes during refeeding with CHO and fat. Repetitive blood samples were obtained from freely moving animals by indwelling jugular venous catheters. Refeeding was performed on the fourth day of starvation at either 1100 or 1900 h, and blood was sampled during the preceding hour and during the following 3 h. In control experiments, blood was sampled over 4 h without refeeding. Refeeding with CHO and fat induced a significant increase in plasma TSH in the first hour. This increase could be abolished by a previous injection of an anti-TRH serum, while normal rabbit serum was without effect. Plasma corticosterone, measured hourly, also showed a tendency to increase with refeeding. It is concluded that refeeding of starved rats represents a reproducible stimulus for TSH secretion.

Short-term administration of the H2-antagonist cimetidine (400 mg three times/day for 5 days) was performed in eight healthy male volunteers and its effects on both thyroid hormone levels and on hypophyseal hormone release induced by acute hypoglycaemia and TRH were tested. Absolute values of basal and post-TRH serum T3 were decreased by treatment, while basal and stimulated serum rT3 and T4 levels were not altered significantly. Cimetidine administration did not change the hormone release induced by acute hypoglycaemia but significantly enhanced the prolactin and TSH responses to TRH. Our results suggest that cimetidine administration can modify the peripheral metabolism rather than the secretion of thyroid hormones.

The reduction of hypophyseal hormone secretion during starvation is not completely understood. A previous study showed that the concomitant reduction of plasma TSH and T3 may be related to an increased sensitivity of the thyrotrope cell to T3. This suggests that regulation of hypophyseal secretion by peripheral hormones may be altered in starved rats. As GH and PRL secretion are under the control of thyroid and steroid hormones, the aim of the present study was to investigate the modification of feed-back control by T3 or E2 on hypophyseal secretion during starvation. For this purpose, pituitary GH, PRL and TSH contents and their plasma responses to TRH injection were measured in euthyroid, thyroidectomized (Tx), T3-supplemented Tx and E2-treated male Wistar rats before and after a 3-day starvation. TRH (0.25 μg/100 g) was injected iv through a chronically-implanted catheter. Our results show that GH content and GH plasma response to TRH are dramatically increased in T3-treated Tx starved rats, suggesting that starvation also increases the effectiveness of T3 influence on somatotrope cell secretion. By contrast, effects of T3 on PRL secretion remain unchanged during starvation. Furthermore, starvation in E2-treated rats is associated with a marked rise in the PRL and GH responsiveness to TRH without any significant change of hormonal pituitary content. This suggests that, in starved rats, E2 increases the effects of TRH on lactotrope and somatotrope secretion. No significant effect on TSH secretion could be demonstrated. Thus, starvation seems to act differentially on the feed-back mechanisms controlling the hormonal secretion of the three adenohypophyseal target cells to TRH.

The aim of our study was to study therapeutic results after thyroidectomy in patients positive for predictive genetic analysis and with preoperative calcitonin (CT) response to pentagastlin (Pg)150 pg/ml.36 patients (13 F, 23 M) were selected: 13 F-MTC from 8 families, 22 MEN 2A from 15 families and 1 MEN 2B. They were positive for direct RET mutation analysis. CT was assayed by immunoradiometric method before and after Pg. Pg test results before and after thyroidectomy, age at operation and histologic results were analysed.Mean preoperative peak CT was 82.5 +/- 34.0 pg/ml (22-133): among these 36 patients preoperative basal and peak CT were normal in 16 and 2 patients respectively. F-MTC and MEN 2A patients were different according to their preoperative peak CT levels (58.1 +/- 24.0 vs 97.6 +/- 31.3) pg/ml, p0.01) and age at thyroidectomy (20.4 +/- 10.5 vs 11.6 +/- 7.6 years, p0.01 by Mann-Whitney test). Total thyroidectomy was performed in all patients at a mean age of 14.8 +/- 9.8 years (2.5-41.7) and was associated with lymph node dissection in 30 cases. The 2 F-MTC patients with normal preoperative peak CT levels had bilateral C-cell hyperplasia (CCH) associated with uni or bilateral micro-MTC. Other patients had uni or bilateral micro MTC except 4 who had isolated CCH without carcinoma. The age of two MEN-2A and 1 MEN 2B patients with micro-MTC ranged from 2.5 to 4.7 yr. Micro MTC was present in 100% of MEN-2A cases after the age of 10 yr. There were no lymph nodes metastases. During postoperative survey, the last PG tests (n = 33) were performed 27.5 months (1-92) after thyroidectomy: peak CT values were always10 pg/ml.Thyroidectomy should be performed at a very young age in RET mutation carriers, regardless of the plasma CT values. This choice is justified in NEM-2A and NEM-2B patients but must be discussed in F-MTC families with less aggressive forms of the disease.