Testis function in prepubertal boys and young men born small for gestational age.

BACKGROUND/AIMS: Some studies reported an impaired gonadal function in males born small for gestational age (SGA). We investigated Sertoli cell function by measuring serum inhibin B and antimullerian hormone (AMH) levels in prepubertal boys and young men born SGA in comparison with age-matched controls born appropriate for gestational age (AGA). METHODS: Inhibin B and AMH levels were determined in 73 prepubertal short SGA boys and in 72 age-matched AGA boys. In addition, 25 SGA boys were re-examined after 2 years of growth hormone (GH) treatment. Furthermore, inhibin B, AMH, testosterone, LH and FSH were studied in three groups of young men: 21 SGA men treated with GH, 15 SGA men with spontaneous catch-up growth and 25 young men born AGA. RESULTS: Prepubertal short SGA boys and AGA boys had similar inhibin B (87.3 and 78.2 ng/ml) and AMH levels (75.6 and 63.6 microg/l, respectively). GH treatment did not result in different inhibin B and AMH levels. In young SGA men, inhibin B, testosterone, LH and FSH levels were similar compared to young AGA men. AMH levels were higher in the young SGA men (p = 0.03). CONCLUSIONS: Being born SGA does not impair Sertoli cell function. Young men born SGA have a normal hypothalamic-pituitary-testis axis.

Clinical correlates of the biological variation of sperm DNA fragmentation in infertile men attending an andrology outpatient clinic.

Determination of sperm DNA fragmentation, as assessed by the sperm chromatin structure assay (SCSA), has become an important tool for the evaluation of semen quality. The aim of the present study was to describe the biological variation of sperm DNA fragmentation in men attending an andrology clinic and to identify clinical correlates of the biological variation of sperm DNA fragmentation. For this study, two consecutive semen samples from 100 patients attending our andrology outpatient clinic were subjected to semen analysis, performed in parallel according to WHO guidelines and by SCSA. A good agreement between pairs of samples was found for SCSA-derived variables, as indicated by a significantly lower median coefficient of variation (CV) of the DNA Fragmentation Index (DFI) and the high DNA stainability (HDS) compared with WHO semen parameters. In half of the men attending our andrology clinic, however, the individual biological variation of DFI and HDS, expressed as CV of two samples, exceeded 10%. Dysregulation of spermatogenesis, as seen as testicular insufficiency or varicocele, was not associated with increased variability of DFI or HDS. A backward multiple linear regression analysis, however, indicated that the biological variation of DFI may be more profound in men with characteristics of normal spermatogenesis. In conclusion, we confirm previous reports that sperm DNA fragmentation has a lower biological variability than classical semen parameters. We hypothesize that the sperm chromatin structure may be more influenced in patients with normal spermatogenesis, whereas in men with disturbed spermatogenesis, the chromatin structure may be already so impaired that the effect of unidentified factors leading to variability of sperm DNA fragmentation in time may not be as profound.

Clinical laboratory evaluation of male subfertility.

Male subfertility is a common problem with a complex etiology, requiring a complete andrological work-up for proper diagnosis. The male reproductive tract is controlled by a well-balanced hormonal system, in which hypothalamic (GnRH), pituitary (LH, FSH) and testicular hormones (androgens, inhibin B) participate. Any disturbance of this hormonal system may therefore lead to testicular dysfunction and interfere with the spermatogenesis process. In addition, also other components along the ductal system, such as epididymis, prostate and seminal vesicles, that improve sperm fertility by contributing their secretions to the semen, might function inadequately and thus fail to enhance the fertilizing capacity of the sperm cells. External factors (heat, chemicals, life style) and anatomical abnormalities (varicocele) were shown to have a negative influence on male fertility. In a number of patients genetic defects can be identified as the cause of their infertility. Laboratory tests are available to assess hormone concentrations, semen composition, accessory gland function and sperm cell function. Conventional semen analysis includes the determination of sperm concentration, semen volume, sperm motility (qualitative and quantitative), sperm morphology, sperm cell vitality, pH, leucocytes and antibodies. The usefulness of the determination of these parameters as predictor of fertility appears to be rather limited, however. Therefore, alternative tests, some based on more functional aspects (sperm penetration, capacitation, acrosome reaction), have been developed. Furthermore, there is an increasing attention for the assessment of DNA integrity, for instance by the flowcytometer-based Sperm Chromation Structure Assay (SCSA), as an additional or alternative parameter of sperm quality. It is likely and desirable that further assays with better predictive value are being developed in the near future.

Raman spectroscopic analysis identifies testicular microlithiasis as intratubular hydroxyapatite.

PURPOSE: As diagnosed by ultrasonography, testicular microlithiasis is associated with various benign and malignant conditions. The molecular constitution of these microliths is largely unknown. Raman spectroscopy provides detailed in situ information about the molecular composition of tissues and to our knowledge it has not been applied to gonadal microliths. We analyzed the molecular composition of gonadal microlithiasis and its surrounding region using Raman spectroscopy in malignant and benign conditions. MATERIALS AND METHODS: Multiple microliths from 6 independent samples diagnosed with gonadal microlithiasis by ultrasound and histologically confirmed were investigated by Raman spectroscopy. The samples included 4 testicular parenchyma samples adjacent to a germ cell tumor (4 seminomas), a gonadoblastoma of a dysgenetic gonad and testicular biopsy of a subfertile male without malignancy. RESULTS: Raman spectroscopic mapping demonstrated that testicular microliths were located within the seminiferous tubule. Glycogen surrounded all microliths in the samples associated with germ cell neoplasm but not in the benign case. The molecular composition of the 26 microliths in all 6 conditions was pure hydroxyapatite. CONCLUSIONS: Microliths in the testis are located in the seminiferous tubules and composed of hydroxyapatite. In cases of germ cell neoplasm they co-localize with glycogen deposits.

Bilateral testicular microlithiasis predicts the presence of the precursor of testicular germ cell tumors in subfertile men.

PURPOSE: A high prevalence of testicular microlithiasis has been described in adolescent and adult clinical cases of invasive testicular germ cell tumor (TGCT), that is seminomas and nonseminomas. However, to our knowledge it remains to be established whether testicular microlithiasis also indicates the presence of the pre-invasive lesion of this cancer, known as carcinoma in situ (CIS). We determined the predictive value of unilateral and bilateral testicular microlithiasis for CIS in subfertile men, a known risk population for TGCTs (approximately 1%). MATERIALS AND METHODS: In a retrospective cross-sectional study the association between testicular microlithiasis and CIS was studied in a group of 263 men referred for subfertility. Testicular microlithiasis and CIS were diagnosed in all men by scrotal ultrasound and in testicular histology specimens as part of the routine evaluation of all patients. RESULTS: Of the 263 subfertile men 53 (20%) had testicular microlithiasis. No CIS or TGCT was identified in the 23 men with unilateral testicular microlithiasis. In contrast, 6 of the 30 men (20%) with bilateral testicular microlithiasis were diagnosed with CIS. Therefore, the prevalence of CIS in subfertile men with bilateral testicular microlithiasis is significantly higher than in patients without testicular microlithiasis (1 of 210, 0.5%) and with unilateral testicular microlithiasis (0 of 23, 0%) (p <0.0001). CONCLUSIONS: Bilateral testicular microlithiasis is indicative for CIS in subfertile men. Since these men are at particular risk for invasive TGCT, an assessment of testicular microlithiasis is a valuable tool for the early diagnosis of this disease.

Androgens and male fertility.

Androgens play a crucial role in the development of male reproductive organs such as the epididymis, vas deferens, seminal vesicle, prostate and the penis. Furthermore, androgens are needed for puberty, male fertility and male sexual function. High levels of intratesticular testosterone, secreted by the leydig cells, are necessary for spermatogenesis. Intratesticular testosterone is mainly bound to androgen binding protein and secreted into the seminiferous tubules. Inside the sertoli cells, testosterone is selectively bound to the androgen receptor and activation of the receptor will result in initiation and maintenance of the spermatogenic process and inhibition of germ cell apoptosis. The androgen receptor is found in all male reproductive organs and can be stimulated by either testosterone or its more potential metabolite dihydrotestosterone. Severe defects of the androgen receptor may result in abnormal male sexual development. More subtle modulations can be a potential cause of male infertility. Treatment of an infertile man with testosterone does improve spermatogenesis, since exogenous administrated testosterone and its metabolite estrogen will suppress both GnRH production by the hypothalamus and Luteinising hormone production by the pituitary gland and subsequently suppress testicular testosterone production. Also, high levels of testosterone are needed inside the testis and this can never be accomplished by oral or parenteral administration of androgens. Suppression of testosterone production by the leydig cells will result in a deficient spermatogenesis, as can be seen in men taking anabolic-androgenic steroids. Suppression of spermatogenesis by testosterone administration is also the basis for the development of a male contraceptive. During cytotoxic treatment or irradiation suppression of intratesticular testosterone production cells may prevent irreversible damage to the spermotogonial stem cells.

Male contraception: mechanical, hormonal and non-hormonal methods.

There is a definite need for an effective and reversible form of male contraception, both for maintaining a stable population in industrial countries and for diminishing population growth in developing countries. It has been agreed upon that contraception is an essential component of reproductive health for men and women (the Weimar Manifesto on Male Contraception). The development of new, effective methods of male contraception has been identified as a high priority by the WHO Task Force on methods of regulation of male fertility. Hormonal male contraception is based on suppression of gondotrophins and substitution of testosterone in order to maintain male sexual function and bone mineralisation and to prevent muscle waist. For complete interruption of spermatogenesis, an adequate suppression of intratesticular testosterone production is needed. Various contraceptive regimens have been developed and tested, including testosterone monotherapy, androgen/progestin combinations, testosterone with GnRH analogs, and selective androgen and progestin receptor modulators. The combination of testosterone with progestogen is currently the most promising approach to hormonal male contraception. Also, several non-hormonal approaches to male contraception are promising and may offer the foundation for developing new male contraceptives.

The effect of cryptorchidism on inhibin B in a subfertile population.

OBJECTIVE: Prepubertal cryptorchidism may cause fertility problems in adulthood, due to impaired spermatogenesis. Serum inhibin B has emerged as an accurate marker of spermatogenesis. The aim of this study was to evaluate the impact of a history of cryptorchidism on serum inhibin B levels and other markers of spermatogenesis in subfertile men. PATIENTS AND MEASUREMENTS: In a retrospective study, the effect of cryptorchidism on inhibin B, FSH, LH, free testosterone, testicular volume and semen parameters was assessed in a case-control study within a population of 2613 subfertile men. Of these, 161 and 102 subjects had a history of, respectively, unilateral and bilateral cryptorchidism that was treated by orchiopexy in childhood. Hormone data were complete for 64 cryptorchid patients (32 unilateral and 32 bilateral). A group of 128 patients was randomly selected out of the remaining group of 2350 men with idiopathic subfertility. An additional control group consisted of 32 fertile men from the general population. RESULTS: In cryptorchid subfertile men, inhibin B concentrations were significantly lower than in noncryptorchid subfertile men and fertile men (103 ng/l, 143 ng/l and 148 ng/l, respectively; P < 0.01). The FSH concentration was significantly higher in cryptorchid men vs. noncryptorchid men and controls (6.1 IU/l vs. 3.3 and 2.9 IU/l, respectively; P < 0.01). Testicular volumes and sperm concentration of cryptorchid men were significantly lower than in noncryptorchid subfertile men (12 vs. 15 ml, P < 0.01 and 3.8 x 10(6) sperm/ml vs. 17.4 x 10(6) sperm/ml; P < 0.05). A significantly higher inhibin B level and sperm concentration was observed in men undergoing orchiopexy at an early age (1-4 years) compared with men treated between 5 and 9 years or later (P < 0.05). CONCLUSION: Spermatogenesis is more impaired in cryptorchid subfertile men compared to men with idiopathic subfertility, as reflected by a lower inhibin B concentration.

Subtotal obstruction of the male reproductive tract.

Bilateral obstruction of the male reproductive tract is suspected in men with azoospermia, normal testicular volume and normal FSH. A testicular biopsy is required to differentiate between an obstruction and a testicular insufficiency. Unilateral or subtotal bilateral obstructions and epididymal dysfunction may cause severe oligozoospermia in men with a normal spermatogenesis. However, information on spermatogenesis in oligozoospermic men is lacking, since testicular biopsy is not routinely performed. Men with a sperm concentration of <1 x 10(6) spermatozoa/ml were investigated for possible partial obstruction by performing a testicular biopsy under local anaesthesia. Spermatogenesis was determined by the Johnsen scoring method. A testicular biopsy was performed in 78 men with severe oligozoospermia. The medical history showed male accessory gland infection in 12.8%, previous hernia repair in 14.1% and a history of cryptorchidism in 12.8%. A normal or slightly disturbed spermatogenesis (Johnsen score >8) was present in 39/78 (50%) of the men. Hernia repair occurred more often in men with normal spermatogenesis. A varicocele was predominantly seen in men with a disturbed spermatogenesis. FSH was significantly lower ( P<0.0001) in men with normal spermatogenesis. Subtotal obstruction of the male reproductive tract is a frequent cause of severe oligozoospermia in men with a normal testicular volume and a normal FSH. In other cases, an epididymal dysfunction might explain the oligozoospermia in men with a normal testicular biopsy score.

Genetic risk factors in infertile men with severe oligozoospermia and azoospermia.

BACKGROUND: Male infertility due to severe oligozoospermia and azoospermia has been associated with a number of genetic risk factors. METHODS: In this study 150 men from couples requesting ICSI were investigated for genetic abnormalities, such as constitutive chromosome abnormalities, microdeletions of the Y chromosome (AZF region) and mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. RESULTS: Genetic analysis identified 16/150 (10.6%) abnormal karyotypes, 8/150 (5.3%) AZFc deletions and 14/150 (9.3%) CFTR gene mutations. An abnormal karyotype was found both in men with oligozoospermia and azoospermia: 9 men had a sex-chromosomal aneuploidy, 6 translocations were identified and one marker chromosome was found. Y chromosomal microdeletions were mainly associated with male infertility, due to testicular insufficiency. All deletions identified comprised the AZFc region, containing the Deleted in Azoospermia (DAZ) gene. CFTR gene mutations were commonly seen in men with congenital absence of the vas deferens, but also in 16% of men with azoospermia without any apparent abnormality of the vas deferens. CONCLUSIONS: A genetic abnormality was identified in 36/150 (24%) men with extreme oligozoospermia and azoospermia. Application of ICSI in these couples can result in offspring with an enhanced risk of unbalanced chromosome complement, male infertility due to the transmission of a Y-chromosomal microdeletion, and cystic fibrosis if both partners are CFTR gene mutation carriers. Genetic testing and counselling is clearly indicated for these couples before ICSI is considered.

Increased serum inhibin B levels after varicocele treatment.

OBJECTIVE: Inhibin B is secreted by Sertoli cells in response to FSH and is the major feedback regulator of FSH secretion in man. The serum inhibin B level has emerged as a good marker of spermatogenesis and Sertoli cell function. Varicocele has been associated with infertility and disturbed spermatogenesis. We have studied the effect of varicocele treatment on serum inhibin B levels, with the aim of investigating the effect on spermatogenesis and the involvement of the Sertoli cell in varicocele pathophysiology. DESIGN AND PATIENTS: In a pre-post test design, the effect of varicocele surgery on inhibin B levels was studied in 30 infertile men. MEASUREMENTS: Endocrinology (inhibin B, FSH, LH, SHBG and testosterone) and semen analysis (sperm concentration, motility and morphology). RESULTS: In men receiving varicocele treatment, a significant increase in serum inhibin B levels was observed from 133.9 +/- 13.4 pretreatment to 167.8 +/- 16.1 ng/l after treatment (mean +/- SEM, P < 0.0001). No significant changes were observed in serum levels of FSH, LH and testosterone. The serum SHBG level decreased from 32.9 +/- 3.5 to 28.6 +/- 3.4 nmol/l (mean +/- SEM, P = 0.04) and the free androgen index was significantly increased from 66 +/- 5.9 pretreatment to 85 +/- 6.8 after treatment (P = 0.02, mean +/- SEM). Semen analysis showed a significant improvement in sperm concentration, from 6.5 +/- 1.9 pretreatment to 19.3 +/- 4.9 x 106/ml after treatment (P = 0.003, mean +/- SEM), and in sperm motility from the baseline level of 17 +/- 3 to 32 +/- 4% after treatment (P = 0.001, mean +/- SEM). CONCLUSIONS: Varicocele treatment can increase serum inhibin B levels, indicating improvement of spermatogenesis and Sertoli cell function. This finding suggests that the pathophysiology of varicocele involves impairment of Sertoli cell function or a different distribution of germ cell stages.

The advantages of standardized evaluation of male infertility.

Healthcare can be improved by standardization and by evaluation of diagnostic methods and treatments. In the field of andrology, in which large patient numbers are required for the evaluation of diagnostic procedures and treatments, structured data collection and multicentre studies are especially warranted. Concomitant with routine clinical practice, a large amount of clinical data are collected that may be used to evaluate andrological care. Structuring and electronic storage of data holds promise in terms of clarity and accessibility of the data and its use for validation studies. The aim of the present work was to study the merits of routine collection of a common dataset in a computer-based patient record (CPR) for standardization, quality of data and clinical research. It was studied whether the data were of sufficient quality and accessibility for much needed studies on aetiology, interventions and diagnostics in andrology. Data collection in a structured CPR promoted complete and comprehensive data. We describe the advantages, pitfalls and solutions with this approach. Data on the uniform examination of 1549 infertile men became readily accessible. Population characteristics, basal associations and original studies were enabled and provided insight into the efficiency of clinical practice. In 66% of men, a cause for their infertility was identified, which provides a better rationale for treatment than semen parameters alone. For more than 30% of the patients, a rational andrological treatment was available, which could be deployed before assisted reproductive technologies were resorted to. However, most treatments have not been properly validated. The thorough diagnostic evaluation identifies subgroups that require an evidence base for treatment and further study on aetiology and diagnosis. Structured collection of uniform patient data through a CPR was feasible and facilitated the evaluation of diagnostic and therapeutic modalities. The reported advantages, pitfalls and solutions with this approach may help other centres to decide on how to implement a CPR. Conscientious collection of a standard data set in infertility centres facilitates pooling of data and evidence-based multicentre research.

[Male fertility. Possibly affected by occupational exposure to mercury]. / De mannelijke fertiliteit. Mogelijke gevolgen door beroepsmatig contact met kwik.

In the last decades there is circumstantial evidence for an increased incidence of cryptorchidisme and hypospadia in new-born boys and an increased incidence of testicular cancer in adults. Moreover, there are indications that sperm quality is declining. Exposure to endocrine disrupters in utero and during adulthood is a possible explanation for the impairment of male reproductive health. Exposure to mercury may lead to deposition in the pituitary gland and the testicular tissues causing impairment of testicular function, especially spermatogenesis. Evidence based research is needed.

Glucocorticoids inhibit gonadotropin-releasing hormone by acting directly at the hypothalamic level.

Glucocorticoids, the end-product of the hypothalamic-pituitary-adrenal (HPA) axis, suppress gonadotropin release by acting at the level of the pituitary gland. However, experimental evidence suggests that they may also act at the hypothalamic level to suppress gonadotropin-releasing hormone (GnRH) release. The lack of a direct demonstration of this assumption, prompted us to evaluate the effects of glucocorticoids on hypothalamic GnRH release from individually-incubated hemi-hypothalami explanted from male rats. Since testosterone (T), dihydrotestosterone (DHT), and progesterone suppress GnRH release and androgens potentiate the effects of glucocorticoids on GnRH release, we studied also the interaction of these steroids with glucocorticoids on GnRH release. Corticosterone (B), the main glucocorticoid of the rodents with greater affinity for the type I glucocorticoid receptor, and dexamethasone (DEX), a synthetic type II glucocorticoid receptor agonist, were able to suppress basal GnRH release in a concentration-dependent fashion. DEX induced a more profound suppression of GnRH release. Neither T (0.1 nM) nor DHT (0.01 nM) modulated the suppressive effects of low (10 nM) or high (100 nM) concentrations of B on GnRH release. On the other hand, progesterone counteracted the suppressive effect of low concentrations of B (10 nM) on GnRH release, but had no effect on the suppression caused by a higher concentration of B (100 nM). The ability of glucocorticoids to inhibit directly GnRH release suggests that these stress-responsive hormones act also at the hypothalamic level to suppress the reproductive function. The suppressive effect of B was not modulated by androgens, but it was neutralized by progesterone, at least when B was used at low concentrations. We speculate that this steroid "protects" the GnRH-secreting neuron only during basal, but not stress-induced, HPA axis activity when the concentrations of glucocorticoids are more elevated.

Is routine scrotal ultrasound advantageous in infertile men?

PURPOSE: We determine the value of routine scrotal ultrasonography in the evaluation of male infertility. MATERIALS AND METHODS: Scrotal color Doppler ultrasonography reports of 1,372 infertile men were reviewed to assess the prevalence of scrotal abnormalities and compared to clinical findings. RESULTS: The prevalence of scrotal abnormalities was 38%. Testicular tumor was found in 0.5%, varicocele in 29.7%, testicular cyst in 0.7%, testicular microlithiasis in 0.9%, epididymal cyst in 7.6% and hydrocele in 3.2% of the cases. Overall, 67% of sonography findings were not evident on palpation, and only 1 of 7 testicular tumors was suspected. Of the varicoceles 60% were not found on physical examination. The rate of testicular tumors (1/200) was higher than that reported for the general European population (1/20,000). CONCLUSIONS: Routine scrotal ultrasound provides valuable information in the diagnostic evaluation of infertile men and substantially more pathological conditions are detected compared to clinical palpation. The high prevalence of testicular malignancies underlines the clinical relevance of routine scrotal ultrasonography in infertile men.

Occupationally related exposures and reduced semen quality: a case-control study.

OBJECTIVE: To determine whether there is an association between abnormal semen parameters and occupational exposures to organic solvents, metals, and pesticides. DESIGN: Case-control study using three case groups based on different cutoff values for semen parameters and one standard reference group. SETTING: University Hospital Utrecht and University Hospital Rotterdam, the Netherlands. PATIENT(S): Male partners of couples having their first consultation at the two infertility clinics (n = 899). INTERVENTION(S): Men provided at least one semen sample. Occupational exposure was assessed with use of job-specific questionnaires, a job exposure matrix, and measurements of metals and metabolites of solvents in urine. MAIN OUTCOME MEASURE(S): Standard clinical semen analyses were used to define case groups and controls. RESULT(S): An association between aromatic solvents and reduced semen quality was demonstrated, irrespective of the exposure assessment method used. The associations were stronger if the case definition was based on stricter cutoff values for semen parameters. Risk estimates were higher if the analysis was restricted to primary infertile men. Exposure to other pollutants at the workplace was not associated with impaired semen quality. CONCLUSION(S): The findings indicated an association between aromatic solvent exposure and impaired semen parameters.

The complex relationships between cystic fibrosis and congenital bilateral absence of the vas deferens: clinical, electrophysiological and genetic data.

Congenital bilateral absence of the vas deferens (CBAVD) is found in 1-2% of infertile males and in most male cystic fibrosis (CF) patients. CF and some of the CBAVD cases were found to share the same genetic background. In this study, 21 males with CBAVD had extensive physical and laboratory testing for symptoms of CF. Possible defective cellular chloride transport was measured by interstitial current measurement of rectal suction biopsies. Cystic fibrosis transmembrane conductance regulator (CFTR) gene mutation analysis was performed for 10 common CFTR mutations. CF-related symptoms were found in six men. On laboratory testing slightly abnormal liver and pancreatic function was found in seven patients. The sweat test was found to be abnormal in four patients; interstitial current measurement showed defective chloride excretion in 11 patients. CFTR gene mutations were found in 66% of the patients: eight were compound heterozygotes; in six, only one common mutation could be detected. The 5T allele in one copy of intron 8 was found in four men. CBAVD appears to be a heterogeneous clinical and genetic condition. A CFTR gene mutation was found in both copies of the allele or interstitial current measurement showed defective chloride excretion in 14/21 cases. Genetic counselling is clearly indicated for couples seeking pregnancy through epididymal or testicular sperm aspiration and intracytoplasmic sperm injection.

Beta-cell function of the pancreas after necrotizing pancreatitis.

AIM: To investigate the late sequellae of necrotizing pancreatitis on the endocrine function of the pancreas. PATIENTS AND METHODS: Twenty patients, 15 men (mean +/- SEM age 52.2+/-2.6 years and BMI 26.8+/-0.8 kg/m2) and 5 women (age 51.0+/-7.6 years and BMI 26.7+/-0.8 kg/m2) were submitted to a glucagon stimulation test 63 (range 8-136) months after an attack of pancreatitis. All nondiabetic patients (n = 15) were also submitted to an oral glucose tolerance test. For comparison, 16 healthy volunteers, 8 men (age 56.0+/-0.9 years and BMI 26.3+/-0.4 kg/m2) and 8 women (age 50.5+/-1.0 years and BMI 28.2+/-0.6 kg/m2), were also studied. RESULTS: Five patients (25%) had diabetes mellitus and needed insulin treatment, 6 patients (30%) had an impaired glucose tolerance (IGT). Nondiabetic patients (IGT included) had a significantly higher basal insulin level (15.8+/-1.9 vs. 10.9 +/-2.2 mU/l, p < 0.05) and a lower glucose/insulin ratio (p < 0.05) compared with controls. The serum concentrations of insulin and C peptide, after stimulation with glucagon, calculated as peak value, maximal increment and as area under the curve were not significantly different in the nondiabetic patients compared to controls. The subgroup of IGT patients had a significantly higher basal C peptide (p < 0.05) and a reduced maximal increment (p < 0.05). CONCLUSIONS: After nonresectional therapy for necrotizing pancreatitis, there is a high prevalence of disturbances in glucose metabolism. Patients with IGT have signs of both loss of beta-cell function and insulin resistance.