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The control of hypertension in diabetic hypertensive patients prevents micro and macroangiopathy complications. Our prospective study was designed to evaluate the level of treatment of hypertension in type II diabetic patients at the time of referral to our endocrinology unit and after a mean follow-up of 9.2 months. Five hundred and sixty four patients (sex ratio: 1.15, mean age of 56 +/- 13, mean BMI of 28 +/- 15, mean duration of diabetes of 11.3 +/- 9.9) were referred to our unit. Among these, 42% had an antihypertensive drug (58% under monotherapy, 42% under combinations) and 92% had a documented history of CHD. Glycemic and blood pressure controls were stable during follow-up. HbA1c remained unchanged (8.95% at admission, 8.8% at 9 months) BP decreased from 143/84 +/- 26/13 mmHg to 142/82 +/- 23/13 mmHg. Fifty six percent reached a BP goal of 140/90 mmHg whereas 42% achieved a BP goal of 130/85 mmHg at 9 months compared to respectively 56% and 39% at admission. A multivariate logistic regression analysis showed that initial value of SBP (p < 0.0001), age (p < 0.0001), BMI (p = 0.006), HbA1c (p = 0.018) were independent factors of non control of hypertension. In conclusion, follow-up of hypertension diabetic patients would be focussed on identified and modifiable factors.

Introduction: Medullary thyroid carcinoma is a rare disease which originates from the secretion of calcitonin by thyroid parafollicular cells. Sporadic (75%) and inherited (25%) forms of the disease are encountered. Familial forms (termed multiple endocrine neoplasia type IIa, IIb, or familial medullary thyroid carcinoma) may or may not be associated with other endocrinopathies such as pheochromocytoma and/or hyperparathyroidism., Current Knowledge and Key Points: Circulating forms of calcitonin, a marker of the disease, are heterogeneous in blood, thus explaining why assays lead to different results according to the method used., Future Prospect and Projects: Family screening is much easier, as germ line mutations of the proto-oncogene RET have recently been identified in inherited forms of the disease. Treatment includes extensive surgery. This, and prophylactic thyroidectomy in gene carriers, is discussed. Prognosis is much better nowadays, but precise follow-up has to be instituted.

This article analyses in a large overview several of the actual problems encountered by pathologist in the management of MTC whatever the diagnostic circumstances. We insist on difficulties upon C cell hyperplasia and early detected disease. Unusual MTC cases are discussed. The need for large multidisciplinary group in studying such tumors is underlined with reference to the French GETC (Groupe d'Etude des Tumeurs à Calcitonine).

Study: 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., Material and Methods: 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., Results: 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, p < 0.01) and age at thyroidectomy (20.4 +/- 10.5 vs 11.6 +/- 7.6 years, p < 0.01 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 always < 10 pg/ml., In Conclusion: 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.

Although rare (10% of thyroid cancers), medullary thyroid cancer is remarkable by the presence of a specific biological marker; elevation of blood calcitonin. It allows its preoperative diagnosis and this extensive surgery which is the only efficient treatment. The possibility of hereditary form (30%) must always be kept in mind; they can now be detected by genetic screening since specific mutations on Ret gene have been recently discovered. Follow up and early treatment of at risk subjects in a family is therefore possible and permits definitive surgical cure.

Objective: Medullary thyroid carcinoma (MTC) is characterized by different clinical forms and a possible prolonged survival, despite presence of metastases. In the present study, we have studied the clinical and biological characteristics of 119 decreased MTC patients., Methods: Our data were retrieved retrospectively from the French medullary thyroid cancer study group (GETC)., Results: Our results showed that the cause of death was basically MTC (87%) but not exclusively, depending on the clinical forms and the age. Patients with type IIb multiple endocrine meoplasia (MEN) died earlier from their carcinoma. Patients with type IIa MEN died of causes other than MTC, especially pheochromocytoma. Two-thirds of the patients with sporadic forms of MTC, died with advanced metastases, usually from MTC., Conclusion: A significant number of deaths in patients with medullary thyroid carcinoma result from non-cancerous causes. This study established the clinical and biological characteristics of patients at risk of death.

Calcitonin gene-related peptide (CGRP), a 37 amino acid peptide resulting from the specific maturation processes of calcitonin gene products, was discovered in 1982. Its messenger RNA was isolated from a calcitonin cancer in rats similar to the human thyroid medullary carcinoma. CGRP is closely related to calcitonin and amylin, and to a lesser extent, to the region coding for the alpha chains of relaxins, insulin and insulin growth factors. In thyroid C cells, calcitonin itself is the major gene product, but CGRP is predominant in the central and peripheral nervous system. CGRP is found in most all tissues and is considered to be a neuromediator of particular importance in the cardiovascular system. CGRP is a powerful endogenous vasodilator in man; plasma concentrations of 56 pmol/l (slightly above physiological levels) provoke flush, hypotension and secondary catecholamine release and subsequent tachycardia. Intravenous injections lead to systemic vasodilatation and redistribution of blood flow to the skin, the brain, and probably the splanchnic territory. It has been suggested that CGRP plays a role in blood pressure modulation in certain pathological conditions. CGRP level is decreased in hypertension and increased in septic shock. In patients with terminal renal failure, CGRP is correlated with excess volaemia. It could affect blood pressure by redistributing blood flow, interacting with the renin-angiotensin system or by inhibiting aldosterone secretion. CGRP may also play a role in modulating cutaneous vascular constriction in Raynaud's syndrome and cerebral vascularization in patients with migraine or meningeal hemorrhage subsequent to rupture of cerebral aneurisms. CGRP increases arterial flow in the cavernous body. Coronarian vascular tone and cardiac performance (positive chronotrope and inotrope effects) are improved. CGRP has also been studied in connection with glucose metabolism and may have other endocrine effects. Finally, CGRP increases electrolyte and water flow in the colon and its bronchoconstrictor effect could be implicated in asthma. The clinical significance of plasma CGRP is not yet known although it may be a marker of poor prognosis in thyroid medullary cancer. Recent studies suggest that CGRP could be a useful therapeutic agent in severe Raynaud syndrome, impotency, ischaemic neurological lesions due to ruptured aneurisms and in severe heart failure.

There is still a consensus about systematic surgery for solitary isolate nodules in case of suspicious nodules larger than 4 cm. In view of the increasingly frequent possibility of recurrence, this policy may now be made more flexible by the results of cytological puncture, leading to the removal of malignant or suspicious nodules and of those with follicular cytology. Better knowledge of the populations at cancer risks (subjects younger than 30 or older than 60, male subjects, history of cervical radiation therapy), allows setting up follow-up for women from 30 to 50 years of age.

Multiple endocrine neoplasia type 2 (MEN 2) is transmitted as an autosomal dominant trait, with 3 different forms. MEN 2a consists of medullary thyroid carcinoma, phaeochromocytoma(s) and hyperparathyroidism. In MEN 2b, parathyroid hyperplasia is absent, but a Marfan-like syndrome and neuromas of the mucosae are present. In some families, the only manifestation of MEN 2 is a medullary thyroid carcinoma. These 3 forms seem to related to one or several gene(s) located in the pericentromeric region of chromosome 10. The histological lesions of MEN 2a are multifocal, bilateral and associated with hyperplasia (which affects C-cells in the thyroid gland). Screening for familial medullary thyroid carcinoma is based upon plasma calcitonin levels measured before and after a pentagastrin stimulation test. The demonstration of DNA markers near the gene(s) of the disease in chromosome 10 pericentromeric region makes it possible to identify, with good probability, the subjects at risk for the disease. It is only by determining the responsible gene(s) that subjects carrying the hereditary anomaly will be identified directly, without marker assays.

The rhythmic pattern of TSH secretion is now well-established and is characterized by a circadian (24 h) periodicity with a pre-sleep acrophase which is modulated by endogenous oscillators and environmental synchronisers. Among external synchronisers, the sleep-waking cycle has been extensively studied and sleep onset appears to have a negative influence on the nycthemeral TSH peak. Nutritional status may affect the TSH rhythmicity since a short term starvation induces a shift in the acrophase time. Major neurotransmitter involved in the TSH rhythms are serotonine which could be responsible for the TSH nadir. By contrast dopamine is not directly implicated in the circadian pattern of TSH secretion. TRH, the main neuropeptide controlling the thyrotrope cell, certainly has a major role in the mediation of the TSH rhythmicity. The involvement of somatostatine is less clear but as assumed for dopamine, its negative influence on TSH secretion would be stronger at the time of TSH peak than at the time of nadir. The major inhibitory effect of thyroid hormones on TSH secretion and release is evident on mean serum TSH levels but does not seem responsible for serum circadian variations. Likewise, the TSH rhythm is present in both sex and influence of estrogens and androgens would only be to modulate the mean serum TSH level. Finally the physiological influence of glucocorticoids on TSH secretion has not been clearly demonstrated.

The case reported here consisted of an association of a Wolff-Parkinson-White syndrome (WPW) with thyrotoxicosis, with simultaneous recovery by thyroidectomy; this lead the authors to review 13 previous cases in the literature. The physiopathologic discussion emphasized several points: 1) the specific action of thyroid hormones, 2) the hypothesis of the possible existence of inapparent pathways of pre-exitation in most subjects and 3) a simple practical attitude to adopt in all Wolff-Parkinson-White cases especially when rapid.

Medullary thyroid carcinoma is a rare and sometimes hereditary disease. The tumour can be diagnosed and followed up by measuring the amounts of calcitonin it secretes. The prognosis of this cancer largely depends on an early diagnosis and treatment. From the clinical and laboratory (calcitonin assays) data recorded in our department, we have endeavoured to determine the influence of a national multidisciplinary co-operative group (GETC: French medullary study group) on the diagnosis and prognosis of this malignancy. We are able to show that the number of medullary thyroid carcinomas detected (principally in their familial forms) has increased by 141 per cent after the GETC was created. Calcitonin levels at the time of diagnosis are significantly lower (P less than 0.05) in familial cases, which reflects an early detection. The same applies to post-operative calcitonin levels (P less than 0.005), so that in the long run a better prognosis can be expected. It seems therefore that together with a better knowledge of this cancer and its detection, the setting up of a national multidisciplinary co-operative group results in a better clinical and therapeutic approach of these patients, and particularly of the familial cases of medullary thyroid carcinoma.

Starting from 48 cases of gynecomastia, the authors report the following findings: -- Impairment of the testis function, as assessed by a low plasma level of testosterone, is rare. -- Basal values of gonadotropins are generally normal. -- Increased oestrogen urinary excretion and blood level are rarely found but, when present, they tend to decrease at successive evaluations. -- In six cases, plasmatic oestradiol can be suppressed by dexamethasone; although the small number of cases does not allow a definite conclusion, one might suggest a predominant adrenal source of plasmatic oestradiol.

A study of thyroid function was undertaken in 53 patients with chronic alcoholism the following tests were performed: T3 RIA, T4 RIA, T3 test and I.V. TRH-test. The patients were divided into 3 groups according to the degree of liver injury: histologically documented fibrosteatosis (group 1), cirrhosis (group 2); group 3 consisted of severe cirrhosis with coagulation defects precluding liver biopsy. 32 healthy subjects served as controls. Free thyroxine index was normal in the 3 groups of patients; on the contrary, serum T3 RIA was significantly reduced in the 2nd and the 3rd group. The decrease of T3 correlated with the degree of hepatocellular failure. TRH test was almost always normal. If patients are separated into two groups according to their circulating T3 levels, it appears that subjects with low T3 show a TRH-induced increase in TSH lower than in the other group, but not significantly different from normal subjects, suggesting an inadequate hypothalamic reactivity.

MTC is characterized by multiple humoral and hormonal manifestations. Although calcitonin is the specific marker of the disease, somatostatin, the pro-opiomelanocortin derived peptides and bombesin--among hormones produced by the tumor--can represent an exacerbation of normal C cells potentialities through genome derepression induced by the cancer. In this paper, the functional polymorphism of princeps tumoral markers and the endocrinological aspects of this neoplasia are reviewed. Molecular biology has been instrumental in discovering new tumoral peptides ("ancestral" CT forms, cryptic peptide and CGRP) and methods of CT detection; therefore, the role of CT could be better evaluated. In addition to its calciotropic role, CT acts also as a neuromodulator on some hypophyseal hormones. Conversely, CT secretion is also regulated by amines and neuropeptides, providing the basis of potential hormonal treatment.

A clinical, scintigraphic and hormonal study of the thyroid was performed in 50 patients with intrathoracic sarcoidosis. The patients were divided into two groups: T - : n = 32, no thyroid abnormality; T +, 18 cases, with thyroid disorders (9 moderate diffuse goitres, 2 thyroid nodules, 7 nodular goitres). All had normal T4, T3 and TSH levels, except one patient with Graves's disease. Scarce sarcoid granulomas were found in 3 out of 4 patients who underwent thyroidectomy. Dissemination, activity, type of sarcoid thoracic involvement were not different in the two groups. In contrast, T + group had higher seric IgG levels than T - group (p less than 0,05). The association of sarcoidosis and goitre is not fortuitous but thyroid enlargement and sarcoid diffusion do not seem interrelated. Auto-immune thyroiditis seems unlikely in our cases, according to the low frequency of thyroid auto-antibodies. We discuss the possible role of seric immunoglobulins in the constitution of thyroid hypertrophy with or without hyperthyroidism in sarcoidosis.

Muscular, articular and periarticular symptoms were reviewed in 19 patients with adrenal failure and compared with previously published data. Symptoms are variable and non-specific; muscular cramps and periarticular calcification were common. Hypercalcaemia was uncommon but its incidence was probably underestimated. Calcification of the ear cartilage was rare but characteristic.

Myocardial failure may complicate hyperthyroidism. Some authors consider that preexisting myocardial lesions are necessary for its development. We studied a case of myocardial failure, presenting as a dilated cardiomyopathy, complicating hyperthyroidism in a 57 year old woman. She had a bio-clinical evaluation and a haemodynamic study with endomyocardial biopsy of the left ventricule. No valvular or coronary disease were noted. The light and ultra-microscopic aspects of the myocardium were within normal limits. We conclude that preexisting myocardial lesions are not essential to the development of myocardial failure complicating hyperthyroidism.

Recent studies have suggested that somatostatin could reduce calcitonin plasma levels (CT) in normal subjects and in medullary thyroid carcinoma (MTC). The aim of this study was to examine the usefulness of the somatostatin analog, sandostatine (SMS 201.995) in MTC with elevated residual CT levels post-thyroidectomy with or without metastases. 18 patients (17-64 years, 12 men and 8 women) with CT greater than 850 pg/ml (N less than 150 pg/ml) and with metastases in 12 cases, were studied. MTC was sporadic in 11 cases, familial in 4 cases and of undefined form in 3. Initial posology was 300 micrograms/d of sandostatin (3 injections/day). It was then increased by 300 micrograms/d every 9 day till a maximum of 1500 micrograms/d. Treatment duration was 37 days in 11 cases and 60 days in 7 cases. Plasma CT and carcinoembryonic antigen levels (CEA) were measured before treatment and at the end of each dosage plateau. Morphologic evaluation of metastases was done at 0, 30, 60 days. 7/18 patients were reevaluated 2 to 8 months after with drawal of sandostatine. Treatment was well tolerated. Flushes improved in 4 out of 5 cases but diarrhea in only 2 out of 9 patients. Sandostatine was without any effect on plasma CEA. Heterogenous responses were observed for plasma CT levels (CT decreases greater than 20% in 8/18 patients when 900 to 1500 micrograms/day were administered). Patients were subdivised into 3 groups according to CEA levels and presence or absence of metastases. Group A (n = 9) had elevated CEA levels (greater than 10 mg/ml) and metastases.(ABSTRACT TRUNCATED AT 250 WORDS)

Three cases of virilizing tumors of the adrenal gland are reported. Two were malignant and are briefly summarized, and the other was benign. A review of the literature concerning benign virilizing tumors of the adrenal is included.

An echocardiographic study of nine patients with graves' disease before and after treatment demonstrates changes in myocardial contractility predominantly in the posterior wall and, to a lesser extent, in the intraventricular septum. The parameters most significantly changed were: velocity of posterior wall thickening and posterior left ventricular wall relaxation rate. There was not in any of the cases neither evidence of cardiac insufficiency nor a diminution of VCF. All of the modifications regressed rapidly with the euthyroid state. These results affirm the functional character of this disease dismissing the existence of an autonome cardiomyopathy of thyroid etiology.

202 cases of Grave's disease were reviewed; among the 81 patients submitted to medical treatment, 53,1 p. 100 of patients failed to respond; 10 p. 100 relapsed and 35,9 p. 100 are euthyroid. The factors favouring a treatment failure were: age below thirty, severity of thyrotoxicosis, big enlargement of thyroid gland, duration of treatment shorter than 12 months. Relapses are more frequent after two years of medical treatment. Subtotal thyroidectomy was performed in 82 patients: 9,5 p. 100 relapsed, permanent hypothyroidism developed in 30,5 p. 100 and 50 p. 100 were euthyroid. The factors favouring post-operative hypothyroidism are estimated weight of the thyroid remnant, the moderate size of goiter and perhaps a six to twelve months preoperative medical treatment. 39 patients had I 131 therapy: among them, 24 p. 100 relapsed, 25,7 p. 100 had permanent hypothyroidism and 50,3 p. 100 are euthyroid.

The paper describes the case of a 38 year's old alcoholic patient. The investigation of his severe asthenia led to the discovery of an isolated ACTH deficiency: plasma cortisol was less than 1 microgram 100 ml reactivable by tetracosa-peptide beta 1-24. Plasma ACTH was low and remained so after LVD and metyrapone. Persistent leuconeutropenia without myelogram and agar cultures abnormalities was noted. Etiocholanolone test was negative and epinephrine induced a significant rise in blood leucocytes. The authors review the mechanisms of corticoid action on leucopoiesis. After 10 months corticoid treatment, leuconeutropenia improved but was still present suggesting an other underlying mechanism than cortisol insufficiency per se.