Unilateral surgery for primary hyperparathyroidism on the basis of technetium Tc 99m sestamibi and iodine 123 subtraction scanning.

HYPOTHESIS: Parathyroid scanning, based on simultaneous recording of technetium Tc 99m sestamibi and iodine 123 images, is able to identify patients with multiple parathyroid gland disease and is a safe imaging technique for unilateral parathyroid surgery. DESIGN: Scintigraphic criteria of eligibility for unilateral surgery were prospectively tested against findings of conventional bilateral surgery. SETTING: Patients referred to an endocrine surgeon in a university hospital. PATIENTS: Seventy consecutive patients with primary hyperparathyroidism had dual-isotope scanning before conventional surgery. Forty-one patients had scan findings compatible with unilateral surgery, with a single focus of high intensity seen on the anterior and lateral views. The remaining 29 patients had 1 or more criteria of ineligibility: (1) scan findings pointing to multiple gland disease, (2) no well-identified focus, (3) contralateral thyroid nodule requiring surgical management, or (4) family history of hyperparathyroidism or multiple endocrine disease. MAIN OUTCOME MEASURES: Number of enlarged parathyroid glands at surgical inspection and calcemia follow-up. RESULTS: None of the 41 patients, with a single well-defined focus on the scan image, showed evidence of multiple parathyroid involvement. Each parathyroid adenoma was resected from the precise site predicted by the subtraction scan. Nine patients (13%) had surgical findings of multiple parathyroid gland disease. All 9 were ineligible based on preoperative image findings. CONCLUSIONS: Unilateral surgery can be safely offered to 60% of patients with primary hyperparathyroidism, on the basis of simultaneous (99m)Tc-sestamibi and (123)I scanning. This may reduce the length of the operation, anesthesia requirements, and hospital stay, and the risks of hypoparathyroidism and injury to the recurrent laryngeal nerve.

Comparison of octreotide acetate LAR and lanreotide SR in patients with acromegaly.

BACKGROUND AND OBJECTIVE: The most effective option for the medical treatment of patients with acromegaly is the use of somatostatin analogues. Long-acting depot formulations for intramuscular injection of two somatostatin analogues have recently become available: octreotide acetate LAR (Sandostatin LAR, Novartis Pharma AG) and lanreotide SR (Somatuline, Ipsen Biotech). We wished to compare efficacy of octreotide LAR and lanreotide SR in acromegalic patients. PATIENTS AND METHODS: A group of 125 patients with acromegaly (67 females; mean age, 47 years; 59 patients had previous pituitary irradiation) from 26 medical centres in France, Spain and Germany were studied. Before the study, all patients had been treated with intramuscular injections of lanreotide SR (mean duration, 26 months) at a dose of 30 mg which was injected every 10 days in 64 and every 14 days in 61 patients, respectively. All patients were switched from lanreotide SR to intramuscular injections of 20 mg of octreotide LAR once monthly for three months. In order to obtain efficacy and safety data of lanreotide SR under study conditions, it was decided to randomly assign at day 1, in a 3 : 1 ratio, the time point of the treatment switch; 27 of the patients were randomly assigned to continue the lanreotide SR treatment for the first 3 months of the study (group A); they were on octreotide LAR 20 mg from month 4-6. The other 98 patients were assigned to be switched to treatment with octreotide LAR 20 mg at day 1 (group B). In group B patients, octreotide LAR treatment was continued until month 6, with an adjustment of the dose based on GH levels obtained at month 3. RESULTS: The mean GH concentration decreased from 9.6 +/- 1.3 mU/l at the last evaluation on lanreotide SR to 6.8 +/- 1.0 mU/l after three injections of octreotide LAR (P < 0.001). The percentages of patients with mean GH values < or = 6.5 mU/l (2.5 microg/l) and < or = 2.6 mU/l (1.0 microg/l) at the last evaluation on lanreotide SR were 54% and 14%, and these values increased after 3 months treatment with octreotide LAR to 68% and 35% (P < 0.001), respectively. IGF-I levels were normal in 48% at the last evaluation on lanreotide SR and in 65% after 3 months on octreotide LAR (P < 0.001). Patients with pre-study pituitary irradiation had lower mean GH and IGF-I concentrations. But the effects of the treatment change did not differ between the irradiated and the nonirradiated patients. In general both drugs were well tolerated. CONCLUSION: Octreotide LAR 20 mg administered once monthly was more effective than lanreotide SR 30 mg administered 2 or 3 times monthly in reducing GH and IGF-I in patients with acromegaly.

The value of combined radionuclide and magnetic resonance imaging in the diagnosis and conservative management of minimal or localized osteomyelitis of the foot in diabetic patients.

Early diagnosis of osteomyelitis is helpful for a successful conservative treatment. The value of bone scanning combined with granulocytes labeled with hexamethylpropylene amine oxime (HMPAO) granulocyte-Tc99m (GN) radionuclide imaging (combined [RI]) with magnetic resonance imaging (MRI) for the diagnosis of osteomyelitis was assessed in 24 diabetic patients with foot ulcers. Evidence of osteomyelitis was based on the presence of at least one of the following criteria: (1) clinical bone involvement, (2) radiological bone involvement, (3) both positive combined RI and MRI, and (4) evidence of clinical bone involvement during the follow-up period. Thirteen patients had osteomyelitis. Seven patients had clinical bone involvement (sensitivity, 54%), five had radiological bone involvement (sensitivity, 38%), and 10 had positive combined RI for osteomyelitis (sensitivity, 77%). MRI demonstrated a higher sensitivity (100%). The specificity for combined RI and MRI was 82%. These results lead to a new diagnostic strategy for the early detection of minimal or localized osteomyelitis to avoid amputations. MRI is most appropriate following a negative x-ray in determining whether to treat osteomyelitis, since a negative MRI result rules out osteomyelitis. Antibiotic therapy should be used in the case of a positive MRI result, but Charcot joint disease can lead to false-positive MRI results. In this case, combined RI should be performed.

Influence of diabetes on revascularisation procedures of the aorta and lower limb arteries: early results.

OBJECT: to evaluate the influence of diabetes mellitus on the therapeutic indications and the one-month results in patients with occlusive disease of the aorta and/or lower limbs arteries. MATERIAL: a retrospective study of fully computerised data of 1003 patients (753 men, 250 women) admitted consecutively to our vascular surgery unit over a 5-year period (1992-1996). Of the total, 169 were diabetics (group I) and 834 were non-diabetics (group II). Sixty-two per cent of patients in group I vs. 40% in group II presented with critical ischaemia or trophic changes (p<0.001). RESULTS: 15.4% of patients in group I vs. 4.1% in group II had primary amputation because of irreversible ischaemia or because arterial reconstruction was impossible. Of those who underwent revascularisation, 80% were infrainguinal in group I vs. 50% in group II. Forty-five per cent of patients in group I and 37% in group II had a percutaneous transluminal angioplasty (PTA) and approximately 3% in both groups had a combination of the two techniques. At one month, patients alive without major amputation numbered 64.4% in group I vs. 93.6% in group II, patients alive with major amputation numbered 26.6% in group I vs. 5.5% in group II, and mortality rates were 8.9% in group I vs. 0.8% in group II (P<0.001). CONCLUSIONS: the 5-times higher amputation and 10-times higher mortality rates for diabetics compared to non-diabetics call for better collaborative management of diabetics between general practitioners, vascular surgeons, diabetologists and cardiologists. PTA with a 90% initial success rate is indicated for short lesions even in the presence of limited gangrene.

Biologic material in needles and cartridges after insulin injection with a pen in diabetic patients.

OBJECTIVE: To evaluate the frequency of non-inert material, including cells, in needles and cartridges after insulin injection with pen-like devices in diabetic patients. RESEARCH DESIGN AND METHODS: A prospective study was conducted in 120 insulin-treated diabetic patients who used pen-like devices. The patients, 46 women and 74 men, were 20-77 years old; 60% had type 1 diabetes, and 38% were overweight. Duration of diabetes ranged from 1 month to 40 years, and insulin therapy ranged from 1 month to 30 years. Insulin injection was performed by a trained nurse, using the patient's usual pen and cartridge. A cytopathological examination was performed on the material obtained from the needle and found in the cartridge after centrifugation. All slides were read by a single investigator. RESULTS: In 62% of the patients, non-inert material was found, including squamous (32%) and epithelial (58%) cells. Biologic material was found in 30% of the needles and 58% of the cartridges, and in both needle and cartridge in 25% of the population. Biologic material was found more frequently in patients who had a longer duration of diabetes, who were treated with insulin for a longer time, and who performed injection in the thighs or upper arms (P < 0.05). In multivariate analysis, the presence of biologic material was associated with the duration of diabetes (R2 = 0.09; P < 0.01). CONCLUSIONS: Our data suggest that biologic material can be trapped in the delivery system, including the cartridge, after an insulin injection with a pen-like device. Our results emphasize the strict need for individual use of insulin delivery systems, including cartridges and nonrefillable pens, especially in clinics and hospitals.

Parathyroid imaging using simultaneous double-window recording of technetium-99m-sestamibi and iodine-123.

UNLABELLED: Technetium-99m-sestamibi represents an important advance in the scintigraphic location of parathyroid neoplasms. However, the optimal procedure for 99mTc-sestamibi parathyroid scanning has not been defined. The first objective of this work was to optimize the technical aspects of subtraction scanning, using simultaneous double-window recording of 99mTc-sestamibi and 1231 instead of successive image recording. The second objective was to compare two protocols for detecting abnormal parathyroid glands: subtraction scanning and single-tracer double-phase scanning. METHODS: Thirty patients referred for first surgery of primary hyperparathyroidism had both subtraction scanning and double-phase scanning in the same imaging session. Images of 99mTc-sestamibi and 123I were recorded simultaneously in nonoverlapping windows and then subtracted. For double-phase scanning, images of 99mTc-sestamibi, acquired 15 min and 120 min after tracer injection, were visually compared. Surgery disclosed a solitary adenoma in 27 patients, bilateral adenomata in 2 patients and 3 hyperplastic glands in the last patient. No patient had persistent hypercalcemia. RESULTS: Preoperative 99mTc-sestamibi/123I subtraction scanning located 25 of 27 solitary adenomas, the bilateral adenomata and 3 of 3 hyperplastic glands. The overall sensitivity for enlarged parathyroids was 94%, and the false-positive image rate was 3%. The 99mTc-sestamibi single-tracer technique located 22 of 27 solitary adenomas, the bilateral adenomata and 1 of 3 hyperplastic glands. Overall sensitivity was 79% and the false-positive image rate was 10%. The gamma camera imaging time was 30 min for the subtraction technique and 50 min for the single-tracer double-phase study. An ectopic adenoma in the sheath of the right carotid artery was detected by both techniques. CONCLUSION: These results, together with other data in the literature, indicate that 99mTc-sestamibi/123I subtraction imaging is accurate in locating enlarged parathyroids. Classical difficulties of this technique (motion artifacts and prolonged immobilization) were avoided by using simultaneous recording of the two isotopes. In this series subtraction imaging was more rapid and more sensitive (p < 0.04) than the single-tracer technique.

Mutations at the lipoprotein lipase gene locus in subjects with diabetes mellitus, obesity and lipaemia.

1. The common association of obesity, diabetes mellitus and hyperlipidaemia may have a primary aetiological basis. Insulin resistance has been postulated as a possible cause, but defects in the plasma transport of triacylglycerol or fatty acids could also be primary determinants. 2. We have therefore studied 18 patients with diabetes mellitus, obesity and severe hypertriglyceridaemia for defects of a key protein involved in the clearance of plasma triacylglycerols, lipoprotein lipase. 3. DNA was prepared from leucocytes of 18 patients with the above syndrome, and exons encoding lipoprotein lipase were amplified by PCR. The products were sequenced using the dideoxy chain-termination method. 4. Eight of the subjects were found to possess genetic variants at the lipoprotein lipase gene locus. These were: (a) G579-->A, V108V; (b) G818-->A, G188E; (c) C829-->T, R192; (d) A1127-->G, N291S; (e) C1308-->G, F351L; (f) C1338-->A, T361T; and (g) C1595-->G, S447. Three of these, (c), (e) and (f), have not hitherto been described. Variant (f), appears to be a population polymorphism whose allele frequency in normolipidaemic diabetics was found to be 0.12 (162 chromosomes studied). The others are all rare at frequencies of < 0.01 and may contribute to the phenotype by impairing clearance of plasma triacylglycerols. 5. We conclude that genetic variants at the lipoprotein lipase locus occur commonly in subjects with this syndrome (four out of 18 subjects with probably functional mutants) and may affect the individual's response to obesity and diabetes mellitus for the development of lipaemia.

Primary hyperparathyroidism: higher success rate of first surgery after preoperative Tc-99m sestamibi-I-123 subtraction scanning.

PURPOSE: To evaluate the usefulness and cost-effectiveness of routine preoperative technetium-99m sestamibi-iodine-123 subtraction scanning in patients with parathyroid gland disease. MATERIALS AND METHODS: Tc-99m sestamibi-I-123 subtraction scanning was performed in 65 patients with primary hyperparathyroidism who were referred for evaluation before first surgery. RESULTS: Focal tracer uptake was detected in the mediastinum in two patients who then underwent primary sternotomy; a parathyroid adenoma, anterior to the ascending aorta, was resected in each case. In a third patient, imaging showed tracer uptake above the thyroid gland; this patient underwent resection of an undescended parathyroid adenoma located in the sheath of the right carotid artery. Initial surgery was curative in all patients. Preoperative subtraction scans depicted 56 of 59 (95%) solitary adenomas. Four patients had hyperplasia; two had double adenoma. Imaging findings indicated multiple parathyroid involvement in five of these patients and facilitated location of 12 of 15 (80%) enlarged glands. Four adenomas and two hyperplastic glands that weighed less than 100 mg were detected. The positive predictive value for any suspected location was 96%. Average surgery time was reduced from 120 to 90 minutes. CONCLUSION: Preoperative subtraction scanning is useful in planning parathyroid surgery and appears to be cost-effective.

Evidence of non-inert material in needles and cartridges following a single insulin injection with a pen.

Preliminary results of an observational study are described in 50 unselected diabetic patients treated with insulin pens. The study was conducted to detect the presence of unexpected material in needles and cartridges after a single insulin injection. The injection was done by a trained nurse with the patient's usual pen and insulin cartridge. Cytopathological examination was performed on the material obtained from the needles and found in cartridges after centrifugation. Non-inert material was found in 28% of needles and 58% of cartridges, including squama (18 and 50% respectively) and epithelial cells (20 and 42% respectively). These data, which suggest a non-passive capture of biological material into the delivery system after injection, emphasise the rule of strictly individual use of insulin delivery systems, including cartridges. The precise impact of self-injection of this non-inert material on individuals during repeated pen injections remains uncertain.

[Leptin: a genetic solution to obesity?]. / Leptine: une solution génétique de l'obésité?

LEPTINE: Produced by adipose tissue, leptine is a regulatory hormone controlling body fat mass. GENETICS: The human gene coding for leptine was first cloned in 1984. Its receptor, a member of the class 1 cytokine receptor family, has also been identified. VARIABLE SERUM LEVELS: Plasma levels of leptine in normal-weight subjects are in the 5ng/ml range and reach 50 ng/ml in obese subjects. Weight gain leads to higher blood levels and weight loss to lower levels. The effect of leptine is to approach a weight equilibrium. Leptine level is correlated with energy balance. MODE OF ACTION: Leptine acts on hypothalamic centers controlling satiety. One of the essential mediators is neuropeptide Y. Resistance to leptine has been evidenced in human obesity. Resistance can occur as several levels and would be one of the explanations for massive obesity involving genetic factors. Leptine may also play a role in certain types of infertility.

[Primary hyperparathyroidism. Optimization of surgical results with systematic preoperative 99mTc-Sestamibi scintigraphy]. / Hyperparathyroïdie primaire. Optimisation des résultats chirurgicaux par la scintigraphie au 99mTc-Sestamibi pré-opératoire systématique.

OBJECTIVE: The importance of preoperative 99mTc Sestamibi (MIBI) scintigraphy in case of reoperation for persistent hyperparathyroidism is well recognized, but it use as a systematic exploration technique remains a question of debate. We conducted this study to determine whether preoperative MIBI scans performed in all cases before surgery have any real impact. METHOD: Two successive series of 65 operated patients were included in the study. In the first group, the MIBI scan was not performed prior to surgery while in the second group the MIBI scan was part of the systematic work-up. RESULTS: The sensitivity and positive predictive value of MIBI were 92% and 96% respectively. Sensitivity for unique adenomas was 95% and 80% for multiple forms. In the first group without systematic scans, there were two unproductive procedures. In the second group, all procedures were productive and no reoperations were required. Two mediastinal adenomas were removed at the first cervicotomy in this group. The rate of complications was similar for both groups. Mean operation time was 2 hours in the first group and 1 hour 30 minutes for the second. CONCLUSION: Our series shows that there are three main advantages of using MIBI scintigraphy systematically prior to surgery for hyperparathyroidism: the procedure is easier in patients with cervical adenomas, particularly in case of ectopic localizations; the mean duration of the operation is shortened by 30 minutes; mediastinal ectopic localizations can be removed by sternotomy at the first operation. These advantages appear to be great enough to propose systematic use of MIBI scan prior to surgery. When MIBI scan shows a single gland, the risk of missing a multiple localization is less than 2% in our experience. It appears possible to operate under local anesthesia via a single-sided approach in elderly patients or high-risk patients.

[Primary hyperparathyroidism. Relationships of symptoms to age, sex, calcemia, anatomical lesions and weight of the glands]. / Hyperparathyroïdies primaires. Relations des symptômes avec l'âge, le sexe, la calcémie, les lésions anatomiques et le poids des glandes.

OBJECTIVES: Primary hyperparathyroidism is a polymorphic disease. We evaluated the effect of different factors on clinical expression. METHODS: Clinical expression in 259 patients who underwent surgery for primary hyperparathyroidism were analyzed as a function of patient age, sex, calcium level, anatomic lesions and weight of the diseased glands. RESULTS: Behaviour disorders and bone images were more frequent in women and urinary lithasis and gastric ulcers were more frequent in men. Behaviour disorders, bone images, chondrocalcinosis, renal failure and acute episodes were more frequent in elderly patients. Inversely, urinary lithiasis was more frequent in young subjects. The prevalence of asymptomatic forms was not related to the level of calcaemia, even for very high levels. Calcium levels above 3.5 mmol/l led to a significantly higher rate of behaviour disorders and acute episodes. Moderately elevated calcium levels were associated most frequently with urinary lithiasis. There was no evidence that anatomic lesions were related to symptomatology, particularly cancer which was not related with more frequent or more severe forms. Finally, nephrocalcinosis, renal failure and acute episodes were particularly frequent when the weight of the parathyroid tissue was greatest. CONCLUSION: The main therapeutic conclusion concerned primary hyperparathyroidism with moderately elevated calcium levels: since there is no difference between the clinical expression of primary hyperparathyroidism with moderately elevated calcaemia, the same surgical approach is recommended.