[Granular cell tumors. Rare tumors of the neurohypophysis]. / Les tumeurs à cellules granuleuses. Des tumeurs rares de la neurohypophyse.

Granular cell tumours of neurohypophysis are rare. These tumours are more often encountered as incidental autopsy findings seen in up to 17% of unselected adult autopsy cases. There are few reports of parasellar granular cell tumours large enough to cause symptoms. We present three cases of neurohypophysis granular cell tumour and a review of the literature. In one patient, the asymptomatic granular cell tumour was incidentally discovered at surgical removal of a corticotroph microadenoma. The remaining 2 patients had a symptomatic tumour which caused neurological symptoms such as visual disturbance and headaches and endocrine disorders such as hypopituitarism or hyperprolactinaemia. In these 2 cases, computerized tomography showed a well-circumscribed, contrast-enhanced, intrasellar and suprasellar mass. Magnetic resonance imaging demonstrated an isointense gadolinium-enhanced mass in T1-weighted images. Transsphenoidal partial resection was performed and histology was interpreted as a granular cell tumour. The immunohistochemical study was positive for glial fibrillary acidic protein (GFAP) and neuron specific enolase (NSE) in 1 of the 2 tumours and positive for S100 protein and vimentin in both tumours but negative for CD68. The histogenesis of neurohypophysis granular cell tumours is still controversial but ultrastructural and immunohistochemical studies support the theory that they may arise from pituicytes, the glial cells of neurohypophysis. Management of these benign, slow-growing, tumours is based mainly on neurosurgical resection. Data from the literature do not support a beneficial effect of postoperative radiation therapy on postoperative recurrences.

Effects of a slow-release formulation of the new somatostatin analogue lanreotide in TSH-secreting pituitary adenomas.

OBJECTIVE: Somatostatin analogues have been proposed for the treatment of thyrotrophinomas. However, this treatment requires several s.c. injections a day to be effective. The present study had the following aims: (i) appraisal of the efficacy of a single dose of two somatostatin analogues (lanreotide and octreotide) to acutely inhibit TSH secretion of TSH-secreting pituitary adenomas; (ii) assessment of the efficacy of a single injection of a slow release formulation of lanreotide (SR-L) in reducing TSH and thyroid hormone secretions in the same cases; and (iii) evaluation of the effects of SR-L used for 3-6 months on hormone secretion and tumour size. PATIENTS: Four patients with hyperthyroidism linked to a TSH-secreting pituitary adenoma found on pituitary magnetic resonance imaging (MRI) and subsequently proved by immunohistochemistry were studied. METHODS: In the first step of the study the patients received in a random order, vehicle, 150 micrograms octreotide and 500 micrograms lanreotide as a single s.c. injection. Measurements of plasma TSH, free T4 (fT4), free T3 (fT3) and free alpha subunit (fAS) levels were carried out before injection and then every other hour for 8 hours. In the second part of the study, after a basal blood sample (0800 h), each patient received 30 mg lanreotide as an i.m. injection of SR-L. Blood was sampled 2 hours later and then three times a week for 3 weeks in order to measure plasma TSH, fT4, fT3 and lanreotide levels using radioimmunoassays. The patients then received one SR-L injection twice or in one case three times a month for 3-6 months. Plasma TSH, fT4 and fT3 levels were measured monthly and a pituitary MRI was performed at the end of the treatment with SR-L. RESULTS: 500 micrograms lanreotide acutely reduced plasma TSH and fAS levels to the same extent as 150 micrograms octreotide. Two hours after a single i.m. injection of SR-L plasma lanreotide levels reached 7.8 +/- 0.6 micrograms/l and then progressively decreased, being 1.8 +/- 0.2 microgram/l on day 2 and 1.1 +/- 0.3 microgram/l on day 14 after the injection. Plasma TSH level decreased from basal value (mean +/- SEM 4.4 +/- 1.2 mlU/l) within 2 hours (2.5 +/- 0.8 mlU/l) and further declined to 0.8 +/- 0.2 ml/Ul on day 2 following the injection. Depending on the patient, plasma TSH levels were reduced for a period of 6-15 days. Plasma fT4, fT3 levels were normalized on day 2 and remained in the normal range for a period of time of 9-20 days. During long-term treatment, abdominal cramps and diarrhoea appeared, leading to interruption of the treatment in one patient. The treatment was well tolerated in the other three patients. Plasma TSH and thyroid hormone levels progressively decreased during the treatment. No change in adenoma volume was observed after 3-6 months of therapy. CONCLUSIONS: This study shows that (i) lanreotide is able to inhibit acutely TSH secretion in thyrotrophinomas and that a single s.c. injection of 500 micrograms lanreotide is as effective as 150 micrograms octreotide; (ii) SR-L appears to be able to reduce plasma TSH and to normalize fT4 and fT3 levels for 9-20 days in patients with thyrotrophinomas; (iii) this effect is maintained throughout the treatment using two or three SR-L injections monthly for months. These results suggest that SR-L could be used as a treatment of thyrotrophinomas and avoids the drawbacks of the modes of administration of other somatostatin analogues used in such cases.

[Remission under treatment of cutaneous xanthomatosis disclosing myeloma: apropos of a case with a three-year course]. / Régression sous traitement d'une xanthomatose cutanée révélatrice d'un myélome: à propos d'un cas avec 3 ans d'évolution.

We report a case of IgG lambda multiple myeloma with inaugural cutaneous xanthomatosis. A three years follow up showed parallel evolution of xanthomatosis and monoclonal gammapathy during therapy suggesting that the association is not coincidental. A decrease in IDL catabolism could be responsible. The monoclonal gammapathy could react with IDL and disturb the recognition of apolipoprotein E by its hepatic receptor.

Acquired von Willebrand's syndrome associated with decrease of plasminogen activator and its inhibitor during hypothyroidism.

OBJECTIVES: In a prospective study we searched for von Willebrand's syndrome during hypothyroidism and investigated the effects of treatment with thyroid hormones on plasma concentrations or activities of the factors involved in von Willebrand's disease in addition to tissue plasminogen activator and plasminogen activator inhibitor 1. METHODS: Eleven patients with hypothyroidism were tested. Factor VIII coagulant activity (VIIIc), von Willebrand factor (vWf:Ag), von Willebrand factor activity (vWf:RCo), tissue plasminogen activator antigen (tPA) and plasminogen activator inhibitor activity (PAI) was monitored before and after correction of hypothyroidism by hormone supplementation. RESULTS: Five patients had laboratory evidence of type I von Willebrand's disease. The other six patients had concentrations or activities of the factors involved in von Willebrand's disease within the normal range. In all cases except one, during thyroxin treatment, von Willebrand factors returned to normal if initially low, or increased clearly if initially normal. With the correction of hypothyroidism, an increase of tPA was noted in the eleven patients, associated with a significant increase of PAI. CONCLUSION: Laboratory evidence of von Willebrand's disease is common during hypothyroidism. Study of plasminogen activator and its inhibitor suggest a decrease of von Willebrand factor synthesis during hypothyroidism.

Pharmacokinetics and efficacy of a long-acting formulation of the new somatostatin analog BIM 23014 in patients with acromegaly.

The treatment of acromegalics with somatostatin analogs requires continuous sc infusion using pumps or several sc injections daily. Long-acting formulations (BIM-LA) of BIM 23014 (BIM) using delayed microcapsules may provide a more convenient form of therapy. Fourteen acromegalics whose GH secretion had not been normalized by transphenoidal surgery followed, in 10 cases, by pituitary radiotherapy (performed at least 2 yr before the study) were studied. Eight of these patients participated in an initial study of the pharmacokinetics of BIM-LA, after which a 6-month efficacy study was undertaken. The 8 patients in the pharmacokinetic study had an initial blood sample collected for measurements of plasma GH and insulin-like growth factor-I (IGF-I) levels before the im injection of 30 mg BIM-LA, and blood samples were subsequently taken 2, 4, 6, and 8 h after injection and then twice a week for a month. Plasma IGF-I levels were measured on days 4, 14, 20, and 30 after the injection. Assays of plasma GH, IGF-I, and BIM levels were performed by RIAs. The results showed that plasma GH levels were markedly reduced from 26.0 +/- 2.0 to 2.5 +/- 0.2 micrograms/L 2 h after BIM-LA injection and remained lower than 5 micrograms/mL for the 11 following days. Plasma GH levels increased to 5.5 +/- 1.2 micrograms/L on day 14 and returned to basal values 23 days after injection. Similarly, plasma IGF-I decreased from an initial level of 656 +/- 43 to 324 +/- 23 ng/mL on day 4 and remained close to the normal range for the following 10 days. Plasma BIM levels reached a peak 2 h after the injection (7.2 +/- 2.3 ng/mL) and remained higher than or close to 1 ng/mL until the 14th day after injection. This initial study showed that a single injection of 30 mg BIM-LA effectively suppressed GH and IGF-I secretion for at least 14 days, in accordance with the kinetics of the drug in plasma. Based on the results of this initial study, 30 mg BIM-LA were injected twice monthly for 6 months in all 14 patients. All of the subjects had a basal evaluation before treatment with BIM-LA and were then subjected to assessment of clinical, pituitary, and hormonal parameters. Patients were evaluated after 3 and 6 months of treatment on the same basis as that previously used when starting the BIM-LA therapy. Plasma BIM levels were measured monthly. Clinical signs of acromegaly improved during the treatment.(ABSTRACT TRUNCATED AT 400 WORDS)

[Isolated zinc deficiency and necrolytic migratory erythema. Apropos of a case]. / Déficit isolé en zinc et érythème nécrolytique migrateur. A propos d'une observation.

The case of 87-old year woman with necrolytic migratory erythematosus rash without elevated plasma enteroglucagon is discribed. Decreased serum zinc level, response to oral zinc substitution and follow up proved the zinc deficiency.

[Hypocholesterolemia: prevalence, diagnostic and prognostic value. Study in a department of internal medicine]. / Hypocholestérolémie: prévalence, intérêt diagnostique et pronostique. Etude dans un service de Médecine interne.

Serum cholesterol was measured in all patients admitted to the Department of Internal Medicine over one year. 6.2 percent had hypocholesterolaemia defined as total serum cholesterol level below 4 mmol/l. Comparison with non-hypocholesterolaemic patients showed male predominance and indirect arguments for increased morbidity: longer duration of hospital stay, greater number of rehospitalizations, greater number of associated diseases. In over a quarter of the cases, hypocholesterolaemia was associated with malignant disease. These results should entice physicians to caution when finding a low serum cholesterol level: this could be a marker of associated disease, especially malignant.

Clinical correlations and prognosis based on hyaluronic acid serum levels in patients with progressive systemic sclerosis.

The serum levels of hyaluronic acid (sHA) were measured using an affinoimmunoenzymatic assay in patients with distal (n = 16) and proximal (n = 15) progressive systemic sclerosis (PSS) and in 31 controls. The severity of PSS was evaluated using a standardized organ-involvement score. The mean sHA was significantly higher in the patients with PSS than in controls (mean +/- SD:80 +/- 43.4 micrograms/l vs. 42.3 +/- 19.1 micrograms/l, P less than 0.001). sHA was significantly higher in patients with proximal PSS than in patients with distal PSS (106.4 +/- 44.6 micrograms/l vs. 55.4 +/- 23.8 micrograms/l, P less than 0.001). A positive correlation was found between sHA and the disease score (r = 0.67, P less than 0.001). sHA was also correlated with lung diffusion capacity for carbon monoxide (r = 0.70, P less than 0.001), but only in the those patients who had abnormal lung function, and therefore presumably had lung PSS involvement. We suggest that sHA could be an indicator of the degree of systemic involvement in PSS. Its prognostic value and possible use in the follow up of patients with PSS remain to be clarified.

[Primary carcinoma of the pituitary gland with Cushing's syndrome and metastases. Apropos of a case with review of the literature]. / Carcinome primitif de l'hypophyse avec syndrome de Cushing et métastases. A propos d'un cas avec revue de la littérature.

We report the case of a 25 year old man with pituitary carcinoma with Cushing's syndrome. Though the diagnosis was initially proposed, it was only confirmed by the appearance of meningeal and lymphatic metastases. These were secretory, as confirmed by immunocytochemistry and electron microscopy. These tumours are rare, whether they secrete or not, and can be confirmed only by the existence of metastases, most often in the brain or the liver.

[Idiopathic hypereosinophilic syndrome with predominant digestive manifestations or eosinophilic gastroenteritis? Apropos of 2 cases]. / Syndrome hyperéosinophilique idiopathique à manifestations digestives prédominantes ou gastroentérite à éosinophiles? A propos de deux observations.

We report two cases of hypereosinophilic syndrome with predominant gastrointestinal signs, which could have been mistaken for eosinophilic gastroenteritis. In the first case, the patient presented with eosinophilic ascites; documentation of pulmonary involvement allowed to easily establish the diagnosis. In the second case, the patient presented with diarrhea and malabsorption; gastrointestinal and pancreatic involvement seemed isolated. Cases reported as eosinophilic gastroenteritis in the literature with polyvisceral involvement raise the possibility of hypereosinophilic syndrome. We suggest that diffuse eosinophilic gastroenteritis could in fact be an isolated manifestation of the idiopathic hypereosinophilic syndrome.

Evolution of atenolol kinetics when hypothyroidism is corrected.

A single oral dose of atenolol 100 mg was given to 7 hypothyroid patients (4 F, 3 M), before and after correction of hypothyroidism, mean delay 3.5 months (2 to 6.5 months). There was no change in the elimination parameters of atenolol, but the maximal plasma atenolol concentration was increased (1.66 to 7.37 mg.l-1) as was the AUC (14.9 to 52.1 mg.l-1.h) when the hypothyroidism had been treated. Only one patient differed: he had had a supra-selective vagotomy, and had similar curves before and after treatment of the hypothyroidism, both being similar to the plasma concentration curves found in the other patients after correction of the hypothyroidism. The results suggest an increase in the bioavailability of atenolol when hypothyroidism is corrected. The findings in the patient with vagotomy suggest that the decreased bioavailability during hypothyroidism might be related to changes in intestinal pH. Further studies are needed of the impact of hypothyroidism on gastric and pancreatic or biliary function and its consequences for drug absorption, and drug pharmacokinetics.