André Warnet

The diagnostic value of fine-needle aspiration biopsy under ultrasonography in nonfunctional thyroid nodules: A prospective study comparing cytologic and histologic findings

Fine-needle aspiration biopsy (FNAB) of thyroid nodules has been proposed as a preoperative screening method to reduce the number of patients with benign nodules referred for surgery. Only a few previously published studies have compared cytologic results with a systematic surgical control; furthermore, the role of ultrasound guidance for FNAB in obtaining representative material has been poorly evaluated. The authors tried to assess the diagnostic value of FNAB performed under ultrasonography in a series of patients with a cold nodule and a systematic surgical control. This prospective study included 132 consecutive patients, 19 men and 113 women, aged from 18 to 82 years. The rate of carcinomas was 13.8%. A very high rate of adequate material was obtained (96.2%). Sensitivity, specificity, and global accuracy were 95%, 87.7%, and 89%, respectively. These results, which are equivalent to those previously published but associated with a low level of insufficient material, emphasize the diagnostic value of thyroid FNAB.

Cardiovascular Effects of the Somatostatin Analog Octreotide in Acromegaly

OBJECTIVE To determine the cardiovascular effects of the somatostatin analog octreotide in patients with acromegaly. DESIGN Prospective nonrandomized study. SETTING Referral-based endocrinology clinic. PATIENTS Seven patients with active acromegaly, three of whom had refractory congestive heart failure. The other four patients were free of symptoms associated with heart failure. INTERVENTIONS All patients were treated with octreotide, 100 to 500 micrograms subcutaneously three times daily. The three patients with heart failure continued to receive cardiovascular therapy (angiotensin converting enzyme inhibitors, digitalis, diuretics). MEASUREMENTS AND MAIN RESULTS During octreotide therapy, patients showed a rapid decrease in growth hormone and insulin-like growth factor 1 (IGF-1): Mean levels (+/- SD) fell from 28.1 +/- 32.7 micrograms/L to 5.2 +/- 8.3 micrograms/L and 740 +/- 126 micrograms/L to 372 +/- 64 micrograms/L, respectively (P less than 0.025). Plasma volume returned to normal and heart rate decreased significantly. In the four patients without heart failure, right-heart catheterization done before and after 3 months of octreotide therapy showed an 18.3% +/- 11% reduction in stroke volume and a return to normal of the cardiac index. The three patients with congestive heart failure, evaluated before and after 40 days and up to 2 years of therapy, showed a dramatic clinical improvement that was associated with an increase in stroke volume (by 24% to 51%). In these patients, the cardiac index remained in the normal range, filling pressures were markedly decreased, and pulmonary wedge pressure returned to normal. This improvement was sustained for up to 3 years in the two patients with heart failure who were receiving long-term treatment. CONCLUSION The rapid and sustained cardiac improvement seen in our patients shows that octreotide therapy for patients with acromegaly may be highly beneficial, even in those patients with advanced cardiac failure.

A prospective multicenter trial of octreotide in 24 patients with visual defects caused by nonfunctioning and gonadotropin-secreting pituitary adenomas. French Multicenter Octreotide Study Group.

OBJECTIVE The somatostatin analog octreotide has been demonstrated to improve optic tract compression caused by pituitary macroadenomas within hours of its administration and/or reduce tumor size in some patients. We report the results of a prospective multicenter study of the effects of octreotide on visual function and tumor size in patients with nonfunctioning pituitary adenomas or gonadotropin-secreting adenomas. METHODS Twenty-four patients with visual defects caused by histologically confirmed macroadenomas were administered octreotide via continuous subcutaneous infusion, as follows: 100 micrograms the 1st day and, if necessary, 200 micrograms the 2nd and then 100 or 200 micrograms three times daily if visual function improved. Vision was assessed after 4 days, 1 month, and 2 months, including tumor size evaluation. Visual improvement was defined by a net gain of at least 2/10 in acuity and/or of more than 20% of the surface of one isopter (a reduction in tumor volume of > or = 20% of the initial measurement); opposite changes were defined as deterioration. RESULTS Visual improvement was noted in 13 of 24 patients, 10 of 23 patients and 9 of 22 patients, and was not noted in 11 of 24 patients, 14 of 23 patients, and 13 of 22 patients after 4 days, 1 month, and 2 months, respectively. After 2 months, three adenomas had shrunk, three had not changed in size, and one had increased; visual function improved in the seven patients with these adenomas. Octreotide was discontinued in 13 patients for lack of efficacy. CONCLUSION The incidence of visual improvement and tumor shrinkage noted in this study was higher than previously reported. Our data suggest that early onset of visual improvement might help in deciding which patients profit from octreotide. However, concomitant gain in visual acuity with deterioration in visual fields or visual improvement with an increase (moderate) in tumor size can occur.

Somatostatin receptor imaging in somatotroph and non-functioning pituitary adenomas: correlation with hormonal and visual responses to octreotide.

A multicentre study was undertaken to determine the value of somatostatin receptor (sst) scintigraphy in predicting hormonal and visual responses to octreotide treatment in GH‐secreting and non‐functioning pituitary adenomas.

Enhanced susceptibility of low-density lipoprotein to in vitro oxidation in type 1 and type 2 diabetic patients

Macrovascular disease represents a major cause of morbidity and mortality in patients with diabetes mellitus. Low-density lipoprotein (LDL) is involved in the pathogenesis of atherosclerotic lesions, through modifying processes such as oxidation. We examined the in vitro susceptibility to oxidation and the oxidizability of LDL isolated from the plasma of Type 1 and Type 2 diabetic patients. Two groups of diabetic patients (20 Type 1, 20 Type 2) were compared with sex- and age-matched non-diabetic control groups. In vitro oxidation of the purified LDL preparations was assessed by determination of the kinetics for the formation of conjugated dienes (lag phase duration, maximal rate and maximal dienes concentration) and by measurement of thiobarbituric acid-reacting substances (TBARS) in the presence of copper ions. LDL from both Type 1 and Type 2 diabetic patients exhibited a shorter lag phase duration for conjugated dienes formation (94 +/- 14 vs. 108 +/- 20 and 97 +/- 26 vs. 112 +/- 18 min for Type 1 and Type 2 diabetic groups vs. respective control groups, P < 0.05). We also observed an increase in maximal rate of conjugated dienes formation (2.21 +/- 0.55 vs. 1.52 +/- 0.31 and 2.02 +/- 0.55 vs. 1.52 +/- 0.31 nmol/mg LDL/min, P < 0.01) and of maximal production of TBARS (77.9 +/- 11.8 vs. 65.5 +/- 10.4 and 76.7 +/- 9.9 vs. 65.3 +/- 9.4 nmol/mg LDL protein, P < 0.05) in diabetic groups. Our results demonstrate both a higher susceptibility to oxidation and a higher oxidizability of LDL from diabetic patients, as much for Type 1 as Type 2 diabetic subjects with or without pre-existent vascular complications. This enhanced propensity of LDL oxidation in patients with diabetes mellitus could at least partly be attributable to quantitative and qualitative alterations in the chemical composition of LDL and to the glycoxidation process occurring on these lipoproteins.

Glycaemic control and development of retinopathy in type 2 diabetes mellitus : A longitudinal study

Relationships between glycaemic control, hypertension, and development of microangiopathy have been well documented in Type 1 (insulin‐dependent) but not in Type 2 (non‐insulin‐dependent) diabetes mellitus. Therefore, we have investigated these relationships in a cohort of 64 Type 2 patients free of retinopathy (by angiofluorography), who were regularly followed until development of retinopathy or for at least 7 years as outpatients. Glycaemic control was assessed by 1 to 4 HbA1 determinations per year. Retinal status was monitored by annual angiofluorography. Nonproliferative retinopathy developed in 14 patients (cumulative incidence at 13 years: 29.8 %) after a mean diabetes duration of 14.3 ± 8.9 years (range 2–27). In multivariate analysis (Cox model), mean HbA1 during follow‐up (p < 0.001), and hypertension at first examination (p = 0.09) were associated with the development of retinopathy, but age, sex, BMI, diabetes duration, smoking, and fasting blood glucose were not. The relative risk for developing retinopathy (RR) was 7.2 (IC 95 %: 1.61–32.4) in patients with a mean HbA1 during follow‐up above the median value of the cohort (8.3 %) compared with patients with HbA1 during follow‐up below this value. RR was 2.5 (IC 0.8–8) in patients with HbA1 at first examination above compared to below the median value (8.4 %). RR was 3.0 (IC 0.9–10) in patients treated for hypertension at baseline compared to those without treatment. A sixfold increase in retinopathy prevalence was observed between patients with mean HbA1 in the highest or lowest quartile of mean HbA1 distribution during follow‐up. This longitudinal study indicates a strong association between long‐term glycaemic control and the development of diabetic retinopathy in Type 2 diabetes.

Glycoprotein hormone α-subunit secretion in prolactinomas and in non-functioning adenomas: relation with the tumour size

OBJECTIVE Free giycoproteln hormone α‐subunit plasma levels have been reported to be Increased In glycoprotein hormone‐secreting adenomas and In acromegaly, but rarely In prolactinomas and In only two cases of Cushings disease. The prevalence of elevated plasma α‐subunit levels. In patients with non‐functioning adenomas is still unclear. In addition, no previous work has described plasma a‐subunit levels. In a comprehensive series of adenomas characterized by In‐vivo secretion and/or Immunocytochemistry.

Inhibin and follicle-stimulating hormone levels in gonadotroph adenomas : evidence of a positive correlation with tumour volume in men

OBJECTIVE Gonadotroph adenomas are generally revealed by symptoms of mass effect at the stage of macroadenoma. Most of them hypersecrete FSH and/or gonadotrophin subunits. Rarely they hypersecrete LH, which could induce endocrinological symptoms. As the glycoprotein inhibin is secreted by the gonads under FSH control, we have evaluated whether high immunoreactive inhibin (IINH) levels correlated with FSH hypersecretion and whether IINH and FSH levels were related to tumour volume in subjects with gonadotroph adenomas.

The GnRH receptor gene is preferentially expressed in functioning gonadotroph adenomas and displays a Mae III polymorphism site

Given the central role of the GnRH receptor (GnRHR) in the regulation of the gonadotrophin secretion, it might be implicated directly or indirectly in the pathogenesis of gonadotroph tumours.

Pituitary granuloma and pyoderma gangrenosum

Pyoderma gangrenosum is a rare chronic and recurrent skin disease characterized by progressing lesions from papulopustules to large necrotic sterile ulcers. Its definite etiology remains unknown. In a 40-year-old woman with typical pyoderma gangrenosum an intrasellar mass with suprasellar extension was diagnosed and removed by transsphenoidal surgery. Histo-pathological features of the lesion were those of a nonspecific granulomatous hypophysitis. Five months postoperatively the patient experienced visual defects and hypopituitarism demonstrated by endocrine evaluation. Computerized tomography showed the recurrence of the intrasellar expanding mass. Extensive and repeated evaluation failed to find any evidence of sarcoidosis, tuberculosis or histiocytosis. Corticosteroid therapy was preferred to surgery and 80 mg daily prednisone produced a dramatic shrinkage of the pituitary pseudotumor. Long-term follow-up studies did not disclose any recurrence of the pituitary granulomatous process nor objective evidence of underlying disease even after steroid dosage has been tapered. The hypothesis of a pituitary localization of pyoderma gangrenosum is suggested by the similarity between the histopathologic findings of the two conditions and the excellent response to steroid therapy.