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Multiple endocrine neoplasia type 2 (MEN2) is an hereditary disease with a prevalence of 1/5000. Three phenotypic variants have been identified: MEN2A associates medullary thyroid carcinoma (MTC) to pheochromocytoma in about 20-50% of cases and to primary hyperparathyroidism in 5-20% of cases; MEN2B associates MTC to pheochromocytoma in 50% of cases, to marphanoid habitus and to mucosal and digestive ganglioneuromatosis whereas in familial isolated medullary thyroid carcinoma (FMTC), the other components of the disease are absent. In MEN2, natural history of the disease and a common embryologic origin (neural crest) may explain the phenotypes observed in the organ involved, beginning from the stage of hyperplasia to adenoma and cancer. MEN2 is an inherited autosomal dominant disease with a complete penetrance, related to germline mutation in the proto-oncogene RET. MTC represent the most frequent circumstance of diagnosis. Pheochromocytoma and HPT may reveal the disease unfrequently and are systematically associated to undiagnosed MTC which is present yet. Analysis of the RET gene allows to confirm the diagnosis of MEN2 by identifying the causal germline mutation. Management of MEN2 patients include thyroidectomy associated to cervical central and bilateral lymph nodes dissection for MTC, unilateral adrenalectomy for unilateral pheochromocytoma or bilateral adrenalectomy when both glands are involved, and selective resection of pathologic parathyroid glands for HPT. Familial genetic screening detects at risk subjects who will develop the disease and allows to manage them at the earliest stage of the disease by perform early or prophylactic thyroidectomy such giving them the best chance of cure. Prognosis of MEN2 is mainly related to the stage-dependant prognosis of MTC, thus pointing the necessity of a complete thyroid surgery for index cases with MTC and the earliest thyroidectomy for screened at risk subjects.

Medullary thyroid carcinoma (MTC) is developed from thyroid C cells that secrete calcitonin (CT). MTC represents 5-10% of thyroid cancers with a 1-2% incidence in nodular thyroid diseases. Diagnosis is usually made by a solitary nodule often associated to nodal metastasis and confirmed by a high basal CT level which represents its biological marker. MTC may present as a sporadic form and in about 30% of case as a familial form as a part of multiple endocrine neoplasia syndrome, an hereditary dominant inherited disease related to germline mutation of the proto-oncogene RET. Both biological (CT) and genetic (RET) markers allows the optimal diagnosis and treatment of MTC; the former allows screening and early diagnosis of MTC by routinely CT measurements in nodular thyroid diseases that make the adequate and complete surgery required to be performed. The former leads to diagnose familial MTC and to identify at risk subjects in whom early or prophylactic surgery may be performed. Treatment of MTC is based on the complete surgical resection: total thyroidectomy associated to central and laterocervical nodal dissection. For locally advanced or metastatic MTC, complete cervical surgery is required and needs to be associated to other systemic treatments: as chemotherapy is not very efficient, radioimmunotherapy and RET target gene therapy (mainly tyrosine kinase inhibitors) appears as possible valuable therapeutic options for the future. Prognosis of MTC is mainly related to both the stage of the disease and the extend of the initial surgery. Ten-year survival is about 80% when the patients are not surgically cured and reaches 95% when the biological marker CT is normalized after surgery.

FROM A CLINICAL POINT OF VIEW: Multiple endocrine neoplasia type 2 (MEN2) is an autosomal dominant, inherited multiglandular disease with familial and individual age-related penetration and variable expression. A medullary thyroid carcinoma (MTC) is always concomitant to MEN2 and associated in varying proportion with pheochromocytoma (50%) and hyperparathyroidism (5 to 20%). PROGNOSTIC DATA: The prognosis of MEN2 is related to the carcinological evolution of MTC, which depends mainly on the stage of discovery and the quality of the first surgical treatment, emphasizing the need for early diagnosis. THE IMPORTANCE OF THE ERT GENE: The identification of mutations in proto-oncogene RET, responsible for the various forms of the disease allows subjects at risk in a family circle to be identified and early screening of various endocrine damage, notably MTC, should be performed. Biological explorations in all persons carrying this mutation would permit diagnosis and surgical treatment of the endocrine lesions, before their clinical manifestation.

Von Hippel-Lindau (VHL) disease is an autosomal dominant disorder, predisposing to the development of central nervous system (CNS) and retinal hemangioblastomas, endolymphatic sac tumors, renal cell carcinoma and/or renal cysts, pheochromocytomas, pancreatic cysts and/or tumors. Incidence of the disease is 1/36,000. CNS hemangioblastomas and renal cell carcinoma are the main causes of death. The VHL gene, located on 3p25-26, is a tumor-suppressor gene which plays a major role in regulation of VEGF expression. Germline mutations of the VHL gene are identified in about 70-99% of the patients. Mutations associated with VHL type 2 (with pheochromocytoma) are mainly missense mutations with hot-spot at codon 167. Somatic mutations of the VHL gene are found in both sporadic central nervous system hemangioblastomas and sporadic renal cell carcinoma. For endocrinologists search for VHL disease (as for MEN) should be imperative in presence of a patient with pheochromocytoma and neuroendocrine pancreatic tumor.

Sporadic medullary cancer of the thyroid is often diagnosed late beyond the surgically curable stage. The aim of this work was to assess the capacity of routine calcitonin assay as an early diagnosis test for medullary cancer in patients with a thyroid lesion.Calcitonin was assayed (normal10 pg/ml) as a routine test from 1993-1995 in a series of 2975 patients seen for thyroid exploration. When baseline level was above 10 pg/ml, a pentagastrine test was performed (normal30 pg/ml). All patients with a calcitonin peakor = 100 pg/ml after pentagastrin underwent surgery for suspected medullary cancer. Surgery for suspected malignancy, hyperthyroidism or locoregional functional disorders was also performed in 1494 of the included patients, independent of calcitonin level. Patients with personal or familial history of multiple endocrine disease were excluded. Fine needle aspiration was done in all patients with an unique or predominant thyroid nodule.Medullary cancer of the thyroid was demonstrated in 14 patients (0.47%). Among 8 patients with clinically patent tumor, the diagnosis was established in 3 on the basis of cytology results and elevated calcitonin level; in the 5 other cases, initial cytology was incorrect (anaplastic, papillary, thyroiditis) but correct diagnosis was established on the basis of high calcitonin levels. Diagnosis was suspected preoperatively in the 6 others solely because of high calcitonin; these patients had microlesions measuring 1.2-9 mm. None of the 7 patients with a medullary cancer measuring10 mm had node extension at surgery and all 7 attained biological cure. Among the 7 other patients with a lesion10 mm, calcitonin level returned to normal level in 3 and remained high in 2; the 2 others died with distant metastasis.Routine assay of calcitonin in all patients with a thyroid nodule can improve preoperative diagnosis of medullary cancer of the thyroid and allows early diagnosis of latent infraclinical tumors.

Serum calcitonin (CT) assays are the most useful tumoral marker for the diagnosis and follow up of medullary thyroid carcinoma (MTC). Since 1988 the sensitivity and specificity of CT assays have been considerably improved. Normal basal and pentagastrin (Pg) stimulated CT ranges remain to be established and it appears necessary to determine the pathological circumstances which may be responsible for hypercalcitoninemia in addition to MCT. By reviewing literature and data from the "Groupe d'Etude des Tumeurs à Calcitonine": a/we compared basal and Pg stimulated CT values obtained with two commercially available immunometric CT assays and we observed that CT values measured by the CT-EASIA MEDGE-NIX kit were three fold the values obtained by suing the hGH ELSA CIS BIOINDUSTRIE Kit; b/we determined that hypercalcitoninemia may be observed in isolated C Cell Hyperplasia (HCC) surrounding either lymphocytic thyroiditis or follicular thyroid carcinoma loci, in chronic renal failure on maintenance hemodialysis, and in various neuroendocrine tumors. Surprisingly, the hypercalcitoninemia related to HCC has been found in genetically unaffected members (without any identified gene RET mutation) of both a Multiple Endocrine Neoplasia type 2A and isolated familial hereditary MTC.

A case of thyrocalcitonin-secreting endocrine tumour of the pancreas is reported. Endocrine pancreatic tumours are neoplasias evolving over a long period; most of them are multisecreting, usually with a predominant secretion responsible for clinical symptoms. In this particular case the retrospective diagnosis of a thyrocalcitonin-secreting tumour of the pancreas was made by immunocytochemical study of the pancreatectomy specimen. One year after pancreatectomy, the persistence of clinical signs and a plasma thyrocalcitonin level higher than 25,000 pg/ml led to the discovery of a liver metastasis. An immunocytochemical study of the segmental hepatectomy specimen showed a single population of thyrocalcitonin-secreting cells identical with those found in the pancreatic tumour. In this context, radioimmunological assays of peptides and immunocytochemistry seem to be the best diagnostic methods.

Sulfonylureas act as hypoglycemic agents by stimulating insulin secretion and improving insulin sensibility by a post-receptor mechanism. Their long term results mainly depend on extra-pancreatic mechanisms. Moreover they indirectly decrease triglyceridemia. Glipizide and gliclazide enhance fibrinolysis. Gliclazide also inhibits platelet aggregation and adhesion. The best indication of sulfonylureas is non insulin dependent diabetes with normal weight.

Thyrotoxicosis may be held responsible for osteoporosis. The question is whether a very slight subclinical hyperthyroidism, as is desirable in the post-operative treatment of differentiated thyroid carcinoma, can in the long run be detrimental to bone tissue. In a series of 37 patients, aged 50.9 +/- 11.1 years, presenting with the features of subclinical hyperthyroidism of 8.0 +/- 4.8 years duration, the authors have been unable to find any change in paraclinical parameters of bone and calcium-phosphate metabolism. Thirty-six of these 37 patients showed no abnormal decrease of vertebral bone density measured by dual photon absorptiometry.

Plasma DHA, DHAS and cortisol levels were measured by R.I.A. before and after intravenous and intramuscular injection of beta 1-24 ACTH. In 7 normal adult women, plasma cortisol and DHA levels rose sharply in response to beta 1-24 ACTH (0,25 mg) i. v injection; in opposition, plasma DHAS levels did not change significantly 30 and 120 minutes after the injection. In 9 normal adults women, the i. m injection of Zn beta 1-24 ACTH (1 mg) caused a significant increase in both plasma cortisol, DHA and DHAS levels 8 and 24 hours after the injection.

A peptide with 41-residue having CRF activity both in vivo and in vitro has recently been isolated from ovine hypothalami (41-CRF). Passive immunization of Sprague-Dawley Rats with an antiserum against this peptide is followed by a significant decrease in plasma ACTH and cortisosterone levels under basal conditions as well as after ether-stress and adrenalectomy. These data demonstrate that 41-CRF plays a major role in the physiological regulation of ACTH secretion.

Dopamine exerts an inhibitory or stimulant action on some of the hormones produced by the anterior pituitary gland. The dopamine content of the hypothalamus is considerably reduced in patients with Parkinson's disease. We have tested the anterior pituitary endocrine function in such patients to evaluate the repercussions on this function of the dopaminergic deficiency: the secretion of pituitary stimulins was found to be unaltered both at baseline level and after pharmacological stimulation.

A 58-yr-old man presented a Cushing's syndrome gradually developed for two years, and a cervical tumor. Urinary free cortisol and 17-hydroxy-corticosteroids were elevated and non suppressible under high dose dexamethasone (8 mg a day X 2 days). Plasma calcitonin (7,200 pg/ml), CEA (803 ng/l), beta LPH (624 pg/ml), and CRF (29 pg/ml) were elevated. Total thyroidectomy revealed a medullary carcinoma of the thyroid. Postoperatively the Cushing's syndrome disappeared and plasma CRF became undetectable although plasma calcitonin remained elevated. One out of 3 CRF antisera tested for immunocytology was positive in 10 to 30% of the cells. In tumor extract, CRF (RIA) concentration was 4.75 ng/g. There was no detectable ACTH in the tumor by biochemical as well as immunocytochemical method. In the present report, the next evidences are--for the first time--simultaneously present to demonstrate an ectopic secretion of CRF by a medullary thyroid carcinoma: presence of CRF in systemic blood being undetectable after surgery; cure of the clinical and biological features of Cushing's syndrome after thyroidectomy; characterization of CRF immunoreactivity in tumor. Taken together, the radioimmunological and the immunocytochemical data suggest the production of several molecular forms of CRF.

The hypothalamic regulation of ACTH secretion has been reviewed. Recent biochemical investigations on corticotropin-releasing factor (CRF) suggest that CRF is present in the hypothalamus under two or more different molecular weight forms, their structure being not elucidated yet. Vasopressin has a CRF-like activity. However, contradictory results have been reported on the role of AVP as a physiological CRF. The synthesis of CRF appears to occur in a large hypothalamic area outside the median eminence. CRF-carrying fibers are thought to pass through the lateral retrochiasmatic area and project on the hypophysial portal vessels at the junction between the pituitary stalk and the median eminence. Conflicting data have been published on the influence of monoamines on ACTH secretion. In the dog, ACTH release is inhibited by the alpha-adrenergic receptors, this effect being not as clearly demonstrated in other species. The stimulation of nicotinic and muscarinic receptors followed by increased ACTH secretion. Glucocorticoids appear to lower ACTH secretion through an action at both the hypothalamic and pituitary levels.

The influence of metabolic control on peripheral neuropathy was studied in a population of adult insulin-dependent diabetic patients. Motor conduction velocity (MCV), measured on the common peroneal nerve, was used as electrophysiological index of neuropathy. Following control of hyperglycaemia, rapid and significant improvement in MCV was observed in diabetics without renal or ocular complications, but not in diabetics presenting with these complications. This would suggest that peripheral diabetic neuropathy is governed by two different mechanisms and that one of these is metabolic, as it can be reversed by reinstating glucide balance.

Ether stress-induced ACTH and corticosterone secretion is similar in 60 days adrenal medullectomized and intact Long-Evans Rats. Passive immunisation with a 41-CRF antiserum impairs corticotropic function after stress. This decrease is more pronounced in adrenal medullectomized than in intact animals. These results suggest that epinephrine plays a minor role on the stress induced ACTH secretion. This role can be demonstrated only after immunoneutralisation of endogenous 41-CRF.

Using the radioimmunoassay (R.I.A.) for neurophysins (I.R.N.) described in 1969, we demonstrated a concomitant, rapid release of both A.D.H. and I.R.N. within the first minutes (2') of the i.v. infusion of nicotine in 11 patients with normal neuropituitary function and 1 patient suffering from a Schwartz-Bartter syndrome. There is a close relationship (r : 0,82, p less than 0.001) similar to that described by other authors, between peak levels of A.D.H. and I.R.N. in all the patients. Hence, we proved that our R.I.A. system is influenced by nicotine stimulated neurophysins (N.S.N.). The negative results previously published by two of us in 5 normal men could have been due to the length of the period between the beginning of the test and the first blood sampling (30 mn).

Serum vasopressin level has been measured by radioimmunoassay in 5 healthy subjects during water loading, before and during treatment by carbamazepine. Serum vasopressin drops significantly during carbamazepine in spite of antidiuresis. This drop may be explained by an effect of carbamazepine on renal tubular cell.

Adrenal medulla has recently been shown to contain high concentrations of enkephalin immunoreactive peptides. In the present study, we report the levels of M-ENK and L-ENK in extracts from 6 cases of human pheochromocytoma. The molecular forms of M-ENK have been characterized by gel filtration chromatography and HPLC. mRNA extracted from one tumor has been proved to code for a 80,000 kilo daltons protein containing M-ENK sequence. M-ENK immunoreactive peptides are secreted in the culture medium of dispersed cultured cells of human pheochromocytoma. This secretion is stimulated when nicotine (10(5) M) is added to the medium. However, the level of plasma M-ENK in pheochromocytoma patients is not significantly different from normal patients. Data from Holaday and al. have established that naloxone (an opiate antagonist) has a beneficial role in shock. But the origin and meaning of plasma M-ENK remain to be established.

An adrenal mass without any clinical or biological symptom was accidentally discovered in thirteen patients. All patients underwent surgical exploration. After surgery, pathological studies showed lesions of corticosuprarenaloma (5 considered benign, 1 malignant and 1 uncertain) myelolipoma (2 cases), adrenal cyst, ganglioneuroma, haemangioma and lymphangioma (1 case each). Since no reliable preoperative investigations are yet available to assess the nature of adrenal masses, and since these may be due to benign or malignant endocrine tumours, their surgical removal is indicated.

Immunoreactive ACTH has been found in human pituitary and plasma under different molecular forms: Big ACTH, intermediate ACTH, ACTH 1-39 and fragments of ACTH. In the literature, there are some controversies especially regarding to the importance of Big ACTH in plasma and tissue. Big ACTH is absent or present in only low amounts in plasma and pituitary extracts from normal subjects. However, the proportion of Big ACTH is very high in tumor extracts and plasma obtained from patients with ectopic ACTH syndrome High concentrations of small ACTH fragments are also present in this syndrome.

A 21-year-old female was first seen in 1974 for periodic hypersomnia. It had started at 13 years of age and was characterized by 4-6 days of drowsiness with megaphagia and some light psychic disorders. The attacks usually occurred at approximately 5-6 days after menstruation. Later, after an interval of oral contraception, they appeared during ovulation and increased in duration. During the periods of contraception, these attacks disappeared completely. At present (1980), the episodes are characterized by periodic hypersomnia, seen in a nocturnal polygraphic study; megaphagia has decreased, but the patient appears uncommunicative, sub-active and inexpressive when awaking in the course of the periods of somnolence. Several EEG recordings were made between 1974 and 1980, which showed few or no abnormalities during the attacks and which were normal with in the inter-ictal periods. Hormonal investigations failed to show any striking abnormality or correlation with continuous polygraphic studies. Similarity of this syndrome with the 'periodic hypersomnia and megaphagia in adolescent males' syndrome (Kleine-Levin) is discussed.

Alterations in the secretion of iodothyronines, cortisol, testosterone and growth hormone have previously been described in anorexia nervosa. We have studied prolactin and gonadotropins secretion in 23 cases of anorexia nervosa. Prolactin secretion was normal. Modifications in gonadotropins release were observed. However they could not be always related to weight loss since amenorrhea could either precede weight loss or still be present after return of the weight to normal. In all cases, FSH release after LHRH stimulation was normal. No increase in LH levels was observed after LHRH injection when the weight was 70% below the ideal weight. With increasing weight, LH release progressively recovered and normal LHRH-induced LH release was obtained when the weight was above 90% of the ideal weight. At normal weight, the ratio of LH/FSH was normal in patients menstruating less than 3 months after the test, while the ratio was low in non-menstruating females. In conclusion, when the weight was insufficient basal levels of FSH and LH and responses after LHRH stimulation corresponded to a prepuberal stage. An increase in the LH/FSH ratio and a normal LH/FSH ratio preceeded the recovery of menstruations. In about 1/3 of the cases, such an evolution was not observed without any satisfactory explanation. Other factors than weight may be involved, especially when the amenorrhea persists after weight recovery.

A nosological entity, calloso-genital dysplasia, is described from a case of primary amenorrhoea with coloboma and total agenesis of the corpus callosum. Deficiency of the thalamic gonadotropic hormone secretion was elicited, together with normal or moderately elevated prolactinaemia, the significance of which is discussed. Thyrotropic, somatotropic and corticotropic functions were normal. It may be that the hypogonadotropic eunuchoidism of this 24-year old woman with normal olfaction evolved towards panhypopituitarism over a number of years, but in such a malformation that had not changed since birth the thalamic hypophysiotropic dysfunction seems to be fixed and stable. Unless a most unlikely coincidence occurred, the primary amenorrhoea seems to be related to the malformation. Agenesis of the corpus callosum with panhypopituitarism is well known, but this case is original in that the pituitary deficiency is very limited. A comparison with its mirror image, olfacto-genital dysplasia or Kallman's syndrome is tempting, but it remains to be documented anatomically by other cases.

Changes in serum levels of corticotrophin (ACTH), immunoreactive beta-endorphin, antidiuretic hormone and cortisol were compared in children undergoing minor surgery under either general anaesthesia with halothane or epidural anaesthesia by the caudal route. A rapid and major increase in hormone levels was observed under general anaesthesia but not under epidural anaesthesia.

Specific binding sites for rat CRF (r-CRF) have been characterized on rat anterior pituitary membranes. The binding of the radioiodinated analog of r-CRF (125I Tyr-r-CRF) was time, temperature, pH and protein dependent. No interaction was found with other neurohormones except with Arginine Vasopressin, but at supra physiological levels. Two classes of specific binding sites (high affinity and low affinity) for r-CRF were identified. Bilateral adrenalectomy provoked, since the 24th hour and up to 7 days, in addition of an increase of ACTH plasmatic levels, an abolition of the high affinity binding site; corticosterone treatment reversed these changes. This finding suggests that circulating glucocorticoids may control the anterior pituitary binding sites for CRF, either by a direct action on the anterior pituitary, or by a modulatory effect on hypothalamic CRF secretion.

For 24 hrs. after i.v. injection of 1 ml of an undiluted immune serum raised against oCRF41, the diurnal surge of plasma ACTH dropped to a short-lived limited rise above baseline level. On the second day after injection, the ACTH level in treated rats rose to a subnormal level, although both plasma dilution of the immune serum and its binding capacity in the plasma remained unchanged throughout the experiment. Plasma corticosterone, on the contrary, displayed a normal circadian rhythm during the entire experiment. However, in animals given a second injection of 0.5 ml oCRF41 immune serum 32 hrs. after the first, both ACTH and corticosterone titers fell rapidly below their circadian minimal levels in controls. Concomitantly, the concentration of immune serum in the peripheral plasma, and its capacity to bind to oCRF, rose by 50%. The major role of CRF41 as a diurnal trigger of the circadian rhythm of ACTH is discussed, as well as the limits of passive immunization.

An experimental system allowing both the incubation and rapid transfert of rat hypothalamic slices has been developed in order to approach the regulation of CRF secretion. The release of CRF has been quantified by a specific radioimmunoassay. Under basal conditions, immunoreactive CRF release reached an optimum of 96.2 +/- 10.4 pg/3 hypothalami/20 min. A depolarizing concentration of KCl (56 mM) or veratridine (50 microM) applied for 20 min. induced a 222 and 257% increase, respectively, in CRF release. The in vitro CRF values released under basal and stimulated conditions are comparable to those of other hypothalamic neuropeptides. Furthermore, in vitro CRF release from the hypothalamus is in the same order of magnitude as in vivo CRF secretion estimated by hypophysial portal blood collection or median eminence push-pull cannulation.

The search for a neurohormone specifically controlling ACTH secretion resulted in the discovery of the corticotropin-releasing factor (CRF). This factor, located mainly in a paraventricular-infundibular hypothalamic tract, stimulates ACTH synthesis and secretion through a cAMP-dependent mechanism. The corticotropin-releasing factor is the predominant component of a complex control system of adrenal cortex secretion, which also includes catecholamines and the antidiuretic hormone. Its specificity as stimulant of the corticotropic function makes it an extremely useful tool for physiological and physiopathological studies of the hypothalamus-pituitary-adrenal cortex axis regulation.

alpha-MSH secretion was significantly lowered in Rats after lesion of the mediobasal hypothalamus with microinjections of kainic acid. beta-Endorphin release after ether-stress was also reduced. In opposition, no significant change in basal and ether-stress ACTH secretion was observed.

High concentrations of Thyrotrophin-Releasing Hormone (TRH) have been found in the dorsal skin of the Frog Rana esculenta, lower levels being measured in the ventral skin. alpha-MSH and somatostatin were undetectable in these tissues. Nor was TRH detected in the blood of these animals. The concentration of somatostatin in the pancreas was similar to that of the hypothalamus and twice or one hundred times higher than in the intestine or stomach respectively.

With the aim of clarifying the effects of an excess of thyroid hormones on calcium and phosphate metabolism, a study was made of blood and urine calcium and phosphate levels and urinary hydroxyproline excretion in 35 hyperthyroid patients and 20 obese individuals receiving 150 microgram/day of l-tri-iodo-thyronine for a period of 8 days. There was a high degree of correlation (p less than 0.01) between values of hydroxyproline excretion and those of blood thyroid hormones in the hyperthyroid patients. There was no significant difference between the values of the parameters studied before and after the administration of l-tri-iodo-thyronine. A trial involving the simultaneous administration of thyrocalcitonin produced no significant result.

The authors have developed a radioimmunoassay for human plasma vasopressin (AVP) which permits the estimation of antidiuretic hormon (ADH) levels as low as 0,8 pg/ml. The average plasma level of AVP after overnight water restriction was found to be 14,3 pg/ml (sd = 4,4 pg/ml) in normal subjects. They provoked a hypersecretion of ADH by the intravenous injection of 1-2 mg of nicotine. In 11 volunteer normal subjects this stimulation by nicotine provoked ADH hypersecretion which reached a maximum between 2nd and 15th minutes after injection. In 3 cases of diabetes insipidus, nicotine injection did not induce ADH hypersecretion; in 1 case of potomania this response was weak; in 2 cases of syndrome of inappropriate ADH secretion, AVP plasma levels were elevated and the response after nicotine stimulation was exaggerated.

By means of electrical stimulation of the supraoptic nuclei, in a stereotaxic apparatus, partial or complete degranulation of the neurohypophysis is obtained, with often a continued presence of large vesicles; the number of microvesicles is always increased.

3 cases of inappropriate vasopressin secretion during one case of anaplastic carcinoma of the lung, one case of carcinoma of the prostate with bony metastases and one case of acute intermittent porphyria are presented. The plasma levels of vasopressin, measured by radioimmunoassay were high. Treatment with demeclocycline was attempted in one case. The clearance of free water was positive but the treatment was poorly tolerated by the digestive tract.