A new prognostic clinicopathological classification of pituitary adenomas: a multicentric case-control study of 410 patients with 8 years post-operative follow-up.

Pituitary adenomas are currently classified by histological, immunocytochemical and numerous ultrastructural characteristics lacking unequivocal prognostic correlations. We investigated the prognostic value of a new clinicopathological classification with grades based on invasion and proliferation. This retrospective multicentric case-control study comprised 410 patients who had surgery for a pituitary tumour with long-term follow-up. Using pituitary magnetic resonance imaging for diagnosis of cavernous or sphenoid sinus invasion, immunocytochemistry, markers of the cell cycle (Ki-67, mitoses) and p53, tumours were classified according to size (micro, macro and giant), type (PRL, GH, FSH/LH, ACTH and TSH) and grade (grade 1a: non-invasive, 1b: non-invasive and proliferative, 2a: invasive, 2b: invasive and proliferative, and 3: metastatic). The association between patient status at 8-year follow-up and age, sex, and classification was evaluated by two multivariate analyses assessing disease- or recurrence/progression-free status. At 8 years after surgery, 195 patients were disease-free (controls) and 215 patients were not (cases). In 125 of the cases the tumours had recurred or progressed. Analyses of disease-free and recurrence/progression-free status revealed the significant prognostic value (p < 0.001; p < 0.05) of age, tumour type, and grade across all tumour types and for each tumour type. Invasive and proliferative tumours (grade 2b) had a poor prognosis with an increased probability of tumour persistence or progression of 25- or 12-fold, respectively, as compared to non-invasive tumours (grade 1a). This new, easy to use clinicopathological classification of pituitary endocrine tumours has demonstrated its prognostic worth by strongly predicting the probability of post-operative complete remission or tumour progression and so could help clinicians choose the best post-operative therapy.

[Long-term outcome of the adult onset craniopharyngiomas]. / Devenir à long-terme des craniopharyngiomes de l'adulte.

There is few published series dealing on the long-term outcome of the adult-onset craniopharyngiomas. We report the long term clinical, tomodensitometric and MRI data outcome of 35 (23 woman and 12 men) consecutive adult-onset cured for craniopharyngiomas between 1983 and 2002, and followed-up in Rennes University Hospital. The operation was performed via frontopterional approach in 59% and transphenoïdal approach in 41% of cases. Their age at the time of diagnosis was 44.7+/-15.1 years (21-74). The average postoperation follow-up was 7.4+/-7.0 years (0.1-19.1). Recurrence of tumour occurred in 8 patients (25.8%) and a tumor progression in 1 case. The delay of recurrence after initial surgery was 4.1+/-1.3 years (1.4-6.3). Two patients had 5 and 6 years treatment by growth hormone (GH), without tumor recurrence. The observed increase of weight after the surgical cure of craniopharyngiomas concerned 22 patients (63%). The average weight gain was 17.5+/-14.7 kg (1.5-58). In 7 cases (20%) neuropsychological disorders were noted, of which 2 with lost of professional activity. Three patients died. In conclusion the craniopharyngiomas recurrence is frequent and can appear in very prolonged deadlines after the initial surgery.

Technical risks with subcutaneous insulin infusion.

The popularity of continuous subcutaneous insulin infusion (CSII), as a way for achieving long term strict glycaemic control in diabetic patients, has increased over the last ten years. Most reports on technical faults, often leading to metabolic emergencies, mainly ketoacidosis, have been published in the 1980s. Obstruction of infusion set and infection of infusion site are the most frequent events. Insulin precipitation or aggregation is thought to be one of the precipitating factors. Few data are available about failures of the pump itself. We report our experience of pump malfunctions recorded between 2001 and 2004 in 376 pumps used by patients treated with CSII therapy in Brittany. Recent studies indicate a decrease of metabolic complication frequency during CSII. This suggests technical improvements and/or a greater experience of physicians in selecting and educating patients. We report instructions for monitoring insulin pump therapy that should be included in a formal educational program for pump users. Clinical studies using newly available devices should reassess technical risks associated with CSII.

Serum insulin-like growth factor-I measurement in the follow-up of treated acromegaly: comparison of four immunoassays.

BACKGROUND: Measurement of serum insulin-like growth factor I (IGF-I) is currently used for the diagnosis and for monitoring treated acromegaly. In this work, we have studied the performances of four IGF-1 immunoassays in the follow-up of acromegaly. METHODS: The study was carried out on 52 sera from 40 patients with treated acromegaly. Serum IGF-I was measured with radioimmunoassays from Immunotech, DiaSorin and Schering Laboratories and by the chemiluminescent automated immunoassay (Advantage) from Nichols. Normal age- and gender-matched subjects constituted the reference population for two assays. RESULTS: Deming regression and Bland-Altman analyses showed a high correlation with the four methods tested. The use of restricted number of age-adjusted controls with the Immunotech assay, the DiaSorin assay and the Schering assay induced discordance with the Nichols assay in the interpretation of results in treated acromegaly. When normal ranges of the Immunotech assay and the DiaSorin assay were defined from large number of controls, the frequency of normal IGF-I became similar as that obtained with the Nichols assay. CONCLUSION: The four immunoassays display suitable analytical performance for serum IGF-I measurement in the follow-up of acromegaly. For correct interpretation, IGF-I normal ranges should be defined in a large number of age-adjusted healthy subjects.

Clinical and statistical evaluation of self-monitoring blood glucose meters.

OBJECTIVE: Our objective was to compare statistical and clinical methods for the evaluation of five self-monitoring blood glucose (SMBG) meters. RESEARCH DESIGN AND METHODS: Two successive capillary blood glucose measurements were performed, and a simultaneous laboratory venous glucose measurement was used as the reference value. Accuracy was studied by comparing each of the two successive meter values with the reference value by 1) a Spearman's correlation test, 2) a Wilcoxon's paired test, 3) the percentage of values within the 10% interval of the reference value according to the American Diabetes Association consensus statement, and 4) the error grid analysis. RESULTS: The first two methods did not discriminate between the SMBG systems: r was >0.92 for the five meters, and a significant difference between the meter and reference values was found for all but one meter. The two other methods allowed classification of the devices into three groups according to their accuracy: good (two meters), acceptable (two meters), and unacceptable (one meter). These two methods gave consistent results and both had a good reproducibility, because the classification was similar for the two successive measurements. CONCLUSIONS: Both the Spearman's and Wilcoxon's paired tests, although commonly used, are inappropriate to evaluate SMBG systems. The percentage of SMBG values within the +/-10% interval and the error grid analysis are more accurate, because they consistently classified the five glucose meters tested in our study with a high degree of reproducibility.

[Nuclear medicine in the diagnosis of diabetic foot osteomyelitis]. / Place de la médecine nucléaire dans le diagnostic d'ostéite du pied diabétique.

The diagnosis of diabetic foot osteomyelitis is often difficult both clinically and radiologically with a delay in radiological sign occurrence and difficulties of imaging interpretation. Bone biopsy is known to be the diagnosis gold standard. However, if negative, the diagnosis of osteomyelitis cannot be excluded and this method is not harmless. An early diagnosis of osteomyelitis is necessary to start an antibiotic treatment in conjunction with conservative surgery. (99m)Tc-HMPAO labelled leucocyte scintigraphy performed in conjunction with bone scintigraphy significantly contributes to the diagnosis of osteomyelitis (sensitivity=100% and specificity > 95%). In case of osteomyelitis suspicion, after plain radiography, the (99m)Tc-MDP bone scintigraphy is the first step. If negative, osteomyelitis is unlikely. If positive, a (99m)Tc-HMPAO leucocyte scintigraphy should be performed in order to exclude or to confirm the diagnosis of bone infection.

Determination of lipoprotein(a) concentrations and apolipoprotein(a) molecular weights in diabetic patients.

Lipoprotein(a) (Lp(a)) with atherogenic and thrombotic properties has been frequently studied in diabetes, because a high cardiovascular risk has been reported both in type 1 and type 2 diabetes. Few studies have considered genetic factors, especially the isoforms of apolipoprotein(a). The aim of this work is to determine the distribution of apo(a) phenotypes in the serum of 148 diabetic patients (59 type 1, 89 type 2) with or without vascular complications. Apo(a) phenotypes are determined using 4-15% sodium dodecyl sulfate polyacrylamide gel electrophoresis followed by immunoblotting (PhastSystem - Pharmacia). An inverse relationship is observed between Lp(a) serum concentration and the apparent molecular mass of apo(a) isoforms: type 1 r=- 0.61, p<0.01; type 2 r=- 0.55, p<0.01. The frequency of apo(a) isoforms is significantly different between type 1 and type 2 diabetes mellitus. A higher prevalence of isoforms of low molecular weight was observed in the type 2 diabetic population.

Diagnosis of osteomyelitis in the diabetic foot with a 99mTc-HMPAO leucocyte scintigraphy combined with a 99mTc-MDP bone scintigraphy.

BACKGROUND: The aim of this prospective study was to assess the role of 99mTc-HMPAO leucocyte scintigraphy combined with a 99mTc-MDP bone scintigraphy in the diagnosis of the diabetic foot infection (HMPAO-Leu/MDP). METHODS: 75 diabetic patients with suspected osteomyelitis were included. The HMPAO-Leu/MDP scan was considered to be consistent with osteomyelitis when the HMPAO-Leu uptake was concordant in all the incidences with an MDP bone uptake. A HMPAO-Leu uptake without concordant bone MDP activity was considered as a soft-tissue infection. The results of the HMPAO-Leu/MDP scan were compared to the following diagnostic criteria: bone infection was confirmed by radiological follow-up or bone biopsy; the absence of bone infection was confirmed by clinical (healing of the ulcer without antibiotherapy) and radiological follow up. RESULTS: According to these criteria, among the 83 ulcers, bone infection was observed in 41 (49.4%): the HMPAO-Leu/MDP scan was positive in 38 cases, including 14 ulcers with normal or doubtful radiographs at inclusion. In the group of 42 ulcers without proven bone infection, the HMPAO-Leu/MDP scan was negative in 41 cases, including 17 lesions with a soft-tissue infection. CONCLUSION: With a sensitivity of 92.6%, a specificity of 97.6%, the HMPAO-Leu/MDP scan is a reliable tool for the diagnosis of osteomyelitis in the diabetic foot. Neuroarthropathy did not affect the performances of the HMPAO-Leu/MDP scan. Owing to a high spatial resolution this test is very helpful to differentiate bone infection from soft-tissue infection especially in case of neuroarthropathy.

Increased prevalence of thyroid autoantibodies and subclinical thyroid failure in relatives of patients with overt endocrine disease-associated diabetes but not type 1 diabetes alone.

The purpose of this study was to determine the prevalence of thyroperoxidase (TPO) and thyroglobulin (Tg) antibodies, using a sensitive and specific radioimmunoassay method in a large cohort of 254 first-degree relatives of Type 1 diabetic patients with or without other autoimmune endocrinopathy, and to evaluate the predictive value of thyroid antibodies for impaired thyroid function in these groups. TPO and Tg antibodies were found at similar frequencies (12%) in the 254 relatives, and both antibodies were present in 23 cases (9%). Seven subjects displayed subclinical thyroid dysfunction without an abnormal free T4 level. Among first-degree relatives of probands with Type 1 diabetes alone, TPO or Tg antibodies were found in 8 subjects (6%), including 6 with both antibodies. The prevalence of TPO antibodies was significantly greater among relatives of TPO-positive than TPO-negative probands (p < 0.01). In relatives of diabetic patients with other endocrinopathy, frequencies of TPO (20%), Tg (19%) and a combination of both antibodies (15%) were significantly higher than in relatives of Type 1 diabetic patients without endocrinopathy (p < 0.001). TSH levels were abnormal in only one relative of the group without endocrinopathy but occurred in 6 relatives of the proband with overt endocrinopathy-associated diabetes (p < 0.02) in marked association with TPO antibodies (p < 10(-4). It is concluded that relatives of probands with overt endocrine autoimmune disease-associated diabetes, unlike those of probands with diabetes alone, showed increased prevalence of thyroid antibodies and thyroid dysfunction. These results argue for a different risk of thyroid autoimmunity and clinical disease in families of diabetic patients without or with overt endocrine disease. A screening of thyroid autoimmunity is highly recommended for the latter group.

Serum paraoxonase activity and paraoxonase gene polymorphism in type 2 diabetic patients with or without vascular complications.

BACKGROUND: Serum paraoxonase (PON) activity and the relevance of PON gene polymorphism in vascular complications of type 2 diabetic patients were investigated in a case-control study. METHODS: The population included 105 control subjects, 96 diabetic patients without vascular complications and 71 diabetics with vascular complications. RESULTS: Serum PON activity was significantly decreased (p<0.001) in diabetic patients without vascular complications: 207 IU (25-817) compared with the controls: 259 IU (24-950). Although serum PON activity was also decreased: 232 IU (34-797) in the population with vascular complications, the difference was not statistically significant (p=0.11). The Q192 allele frequency is significantly higher (p<0.005) in diabetics without vascular complications (77%), and with vascular complications (73%) than in the controls (63%). No significant association was found between either PON(1)55 L/M and PON(2)311 C/S gene polymorphisms and vascular complications. CONCLUSIONS: The difference in allele frequency for the PON(1) Q/R 192 gene polymorphism may be the cause of the low paraoxonase activity observed in type 2 diabetes mellitus. Further studies need to be conducted to elucidate the role of the enzyme in the development of vascular complications in diabetes.

Comparison of Tc-99m-labelled antileukocyte fragment Fab' and Tc-99m-HMPAO leukocyte scintigraphy in the diagnosis of bone and joint infections: a prospective study.

Between January and July 1998, we conducted a prospective study to compare Tc-99m-labelled antigranulocyte monoclonal antibody fragment Fab' (LEUKOSCAN) scintigraphy versus Tc-99m-hexamethylpropyleneamine oxime (Tc-99m-HMPAO)-labelled leukocyte scintigraphy (HMPAO-LS) for the diagnosis of unselected patients with bone and joint infection. Twenty-three patients (16 men and 7 women; mean age, 67 years) with suspected bone infection were explored successively with bone scintigraphy, HMPAO-LS and LEUKOSCAN scintigraphy. Thirty-two foci were studied (diabetic foot = 11, prosthetic material = 8, joint disease = 4, others = diagnosed in 18 cases, eight on the basis of bacteriological and histological examination of surgical or puncture specimens, with or without radiographic signs, and 10 on the basis of clinical course and radiographic findings. Overall sensitivity, specificity and accuracy were 86%, 72% and 78%, respectively, for LEUKOSCAN scintigraphy (12 true positives (TP), 13 true negatives (TN), 5 false positives (FP), 2 false negatives (FN)), 93%, 100% and 96%, respectively, for HMPAO-LS (13TP, 18TN, 0FP, 1FN), and 100%, 17% and 53.3%, respectively, for bone scintigraphy. In this small series, LEUKOSCAN scintigraphy was found to be less specific for the diagnosis of osteomyelitis than HMPAO-LS. In addition, the interpretation of LEUKOSCAN scintigraphy is more difficult than HMPAO-LS for the diagnosis of bone infection in the diabetic foot, and would appear to be less discriminating for differentiating soft tissue infection from osteitis in the case of plantar perforating ulcers.

Rathke's cleft cysts: surgical-MRI correlation in 16 symptomatic cases.

Rathke's cleft cysts (RCCs) are non neoplastic epithelial lesions of the sellar region that have been rarely reported as a clinical entity. We retrospectively reviewed the magnetic resonance imaging (MRI), intraoperative, and pathological findings of a series of 16 cases of RCCs operated at our institution since 1992. Concurrently, we discussed the different hypotheses about their embryological origin. The patients included 12 females and 4 males, 11 to 73 years of age. Endocrine disturbance was the most common presentation, followed by headaches and visual impairment. The location of the cyst was intrasellar in 7 cases, intrasellar and suprasellar in 6 cases, and suprasellar in 3 cases. The size of the cyst ranged from 8 to 26 mm (mean 12 mm). MRI signal intensity was quite variable on T1-weighted images. The cyst appeared hyperintense in 6 cases, hypointense in 6 cases, isointence in 3 cases, and heterogeneous in one case. On T2-weighted images (available in 13 cases), the signal intensity was more constant and appeared hyperintense in 11 cases and hypointense in 2 cases. After Gd-DTPA, we did not observe enhancement either of the cyst contents or of the cyst wall, but only of the pituitary gland in all patient. Most often, the pituitary gland was displaced inferiorly by the cyst located above showing a typical image of "an egg in a cup". Fifteen patients were operated upon via the transsphenoidal approach and one upon a frontal craniotomy. Intraoperatively, the cyst contents were gelatinous or thick, and dark colored. In 2 cases, it was cerebrospinal fluid-like corresponding to the signal observed on MRI. The position of the pituitary gland confirmed by surgery in 15 cases coincided with enhancement seen and MR imaging. In 13 cases where biopsy of the cyst wall was performed, it confirmed focally ciliated columnar or cuboid epithelium. A coexistent adenoma was found in one case. In conclusion, we consider that RCCs have varied MRI characteristics so that no pathognomonic sign may be observed. Except in few cases, there were no correlation between MRI and intraoperative findings. Therefore, even with MRI studies, differential diagnoses with others cystic lesions of the sellar region remains extremely difficult. The most interesting findings on MRI studies of RCCs were to locate the pituitary gland to help the surgeon to preserve pituitary tissue during surgery.

Optimum duration of antithyroid drug treatment determined by assay of thyroid stimulating antibody in patients with Graves' disease.

OBJECTIVE: To determine the optimal duration of antithyroid drug treatment by monitoring serum thyroid stimulating antibody values in patients with Graves' disease. DESIGN: Prospective longitudinal trial of patients with Graves' disease followed up for 24 months after withdrawal of treatment. SETTING: Tertiary referral centre. PATIENTS: A total of 64 consecutive patients with untreated Graves' disease, eight of whom were subsequently excluded. Fifty six patients completed the study. INTERVENTIONS: All patients were treated initially with carbimazole 40 mg, then with decreasing doses that maintained a euthyroid state. Treatment was scheduled to continue for 18 months but was withdrawn earlier if serum thyroid stimulating antibody became undetectable. END POINT: Serum values of thyroid stimulating antibody (assayed by stimulation of human thyroid cells in vitro) and thyroid hormones and thyroid state every three months during treatment and afterwards every six months for 24 months. MEASUREMENTS AND MAIN RESULTS: In 44 patients serum thyroid stimulating antibody became undetectable during treatment and treatment was withdrawn (median duration of treatment nine months, range 3-18 months). In 12 patients the antibody could be detected during 18 months of treatment. Among the first group of 44 patients initial values of the antibody before treatment were significantly lower than in the second group of 12 patients (median 225% (range 138-1236%) v 570% (250-1480%), p less than 0.001); the incidence of relapse was also lower (41% v 92%, p less than 0.001); and among those who did relapse the disease free interval after treatment was longer (median 12 months v 1 month, p less than 0.001). Moreover, the initial median serum values of thyroid stimulating antibodies were not related to the occurrence of relapse or remission as these did not differ between patients who did and did not have a relapse (median 267% (range 139-1480%) v 220% (range 138-1236%). CONCLUSION: Monitoring of serum thyroid stimulating antibody was a good guide to the duration of treatment as it allowed the treatment period to be considerably shortened in a large group of patients with no loss of efficiency.

[Comparison of 2 methods of measuring microalbuminuria. Immunonephelometry and radioimmunology]. / Comparaison de deux méthodes de dosage de la microalbuminurie. L'immunonéphélémétrie et la radioimmunologie.

The early detection of microalbuminuria in insulin dependent diabetes is considered as a sign of initial stage of nephropathy (possibly reversible if glycemic balance is well maintained). This detection requires very accurate methods as radioimmunoassays. Yet, they are so slow that they represent an obstacle to systematic detection. We report an appraisement of an immunonephelemetric method. Results reveal that immunonephelemetry is a sensitive and accurate method (threshold of sensitivity 0.5 mg/l; CV intra assay less than 5%; CV inter assays less than 10%; analytical recovery: 94-104%). Moreover, immunonephelemetry and radioimmunology are significantly well correlated (r = 0.977, p less than 0.001). As a conclusion, we can say that thanks to complete automation, immunonephelemetry is a choice method to test great lines of samples.

[Pseudohypoparathyroidism or hypoparathyroidism? A misleading clinical presentation]. / Pseudohypoparathyroïdie ou hypoparathyroïdie?

We report the case of a 27-year old woman who presented hypocalcemia and hyperphosphoremia during her first pregnancy. Her phenotype was in favor of Albright's hereditary osteodystrophy: short stature, obesity, round face, brachymetacarpy and mental retardation. However, the diagnosis of pseudohypopara thyroidism type Ia was ruled out due to low PTH level (10 pg/ml). The patient's 22q11 microdeletion was suspected and identified because of the association of severe neonatal hypocalcemia, abnormal face and renal malformation in her children. Deletion 22q11 leads to various syndromes, including Di George syndrome, also referred to as CATCH 22 syndrome (Cardiac defect (C), Abnormal face (A), Thymic hypoplasia (T), Cleft palate (C) and Hypocalcemia (H)). Retrospectively, the patient presented with symptoms suggestive of CATCH 22: abnormal face, hypernasal voice suggestive of velopharyngeal insufficiency, mental retardation, recurrent otitis in childhood. It is also noteworthy that there was an idiopathic thrombocytopenic purpura. In conclusion, while the phenotype was suggestive of Albright's hereditary osteodystrophy, the constatation of a low PTH level would cast doubt on this diagnosis. Furthermore, the 22q11 microdeletion should be searched by FISH (Fluorescence In Situ Hybridization) in all patients with hypopara thyroidism of unknown origin, even in the absence of cardiac malformations. Finally, it seems that patients with CATCH 22 would be predisposed to auto-immune disease as a result of thymic dysfunction.

[Anti-TPO antibodies and screening of thyroid dysfunction in type 1 diabetic patients]. / Intérêt du dosage des anticorps anti-TPO pour le dépistage d'une dysthyroïdie chez des patients diabétiques de type 1.

The diagnosis of thyroid dysfunction is often late in type 1 diabetic population. So, the aims of this study were 1) to evaluate the prevalences of thyroperoxydase (TPO) and thyroglobulin (Tg) autoantibodies detected by highly sensitive radioimmunological method in a cohort of 258 adult type 1 diabetic patients without evidence of clinical thyroid disease; 2) to determine whether or not measurement of TPO and/or Tg antibodies can identify subjects at risk of clinical or infraclinical thyroid dysfunction by measuring TSH in the entire group. TPO antibodies were found in 45 of the 258 diabetic patients (17%). The prevalence of TPO antibodies was not influenced by the following factors: gender, duration of disease, age at screening and at diabetes diagnosis, positivity of familial history. Tg antibodies were found in 19 patients (7%), including 13 cases with TPO antibodies. All patients without TPO antibody (n=213), including Tg-positive patients displayed TSH values in normal range. Among the 45 TPO-positive patients, 11 patients displayed infraclinical thyroid dysfunction. At the end of the 5-year follow-up, only 2/45 patients became anti-TPO negative. Thirteen of the 45 patients developed subclinical or clinical thyroid diseases (4 Graves'disease and 9 thyroiditis with hypothyroidism). By contrast, none of 45 TPO negative patients, sex and age matched with the TPO-positive patients, developed during follow-up anti-TPO positivity and/or infraclinical thyroid dysfunction. In conclusion, the determination of TPO antibodies by a highly sensitive method allows identifying diabetic patients with thyroid autoimmunity and at risk of subsequent impaired thyroid function, whatever age at diagnosis and diabetes duration. By contrast, anti-Tg determination did not give further information about subsequent thyroid dysfunction. In TPO antibody positive patients repeated thyroid clinical examination and TSH determination could be recommended to detect infraclinical thyroid dysfunction.

[Primary adrenal lymphoma with latent adrenal insufficiency: a case report and literature review]. / Lymphome primitif des surrénales avec insuffisance surrénalienne latente: à propos d'un nouveau cas et revue de la littérature.

We report a new case of primary adrenal lymphoma with latent adrenal insufficiency and long-term remission after hydrocortisone replacement therapy. We have analyzed 29 other cases described in the literature. This disease with poor prognosis can be revealed by an incidentally discovered, frequently bilateral, adrenal mass. Adrenal insufficiency may be latent and the diagnostic procedure should include both cortisol and ACTH determination with an additional ACTH stimulation test if appropriate. Early adrenal substitution can improve patient survival.

[Value of the urinary albumin/creatinine ratio in the detection of microalbuminuria]. / Intérêt et valeur du rapport albumine/créatinine urinaires dans le dépistage d'une microalbuminurie.

Microalbuminuria is currently defined as a urinary albumin excretion rate of 20 to 200 micrograms per minute, measured in the urine of 24 hours. We present an indirect approach to the urinary albumin daily excretion rate which minimizes the errors due to chronometric measurement and to the difficulty of collecting 24-hour urine. The albumin (mg/l)/creatinine (mmol/l) ratio calculated in urine collected daily indicates microalbuminuria when it is higher than 2.97 in women and 2.48 in men. The interpretation of this ratio is discussed in terms of sensitivity, specificity and predictive value.