Gene expression in bovine nuclear transfer embryos in relation to donor cell efficiency in producing live offspring.

Developmental abnormalities associated with the cloning process suggest that reprogramming of donor nuclei into an embryonic state may not be fully completed in most of the cloned animals. One of the areas of interest in this regard, is the analysis of gene expression patterns in nuclear transfer (NT) embryos to dissect the processes that failed and develop means to overcome the limitations imposed by these factors. In this study, we investigated expression patterns of histone deacetylase-1, -2, -3 (HDAC-1, -2, -3), DNA methyltransferase-3a (DNMT3A), and octamer binding protein-4 gene (OCT4) in donor cells with different cloning efficiencies and NT embryos derived from these cells employing a real-time RT-PCR assay. All genes investigated followed altered expression patterns in NT embryos when compared to IVF-derived embryos. In general, expression of HDAC genes was elevated especially at the compact morula stage and comparable to in vitro fertilized (IVF) embryos at the hatched blastocyst stage. DNMT3A expression in NT embryos was lower than IVF embryos at all stages. Oct-4 transcript levels were also reduced in cloned compared to IVF embryos at the compact morula and blastocyst stages. This difference disappeared at the hatched blastocyst stage. There was a donor cell effect on the expression patterns of all genes investigated. These results demonstrate altered gene expression patterns for certain genes, in cloned cattle embryos from our donor cells of different efficiency in producing live offspring. Therefore we suggest that differences in expression of developmentally important genes during early embryo development may characterize the efficiency of donor cells in producing live offspring.

Restoration of euthyroidism does not improve cardiovascular risk factors in patients with subclinical hypothyroidism in the short term.

Subclinical hypothyroidism (SH) is being accepted as a condition that is associated with increased risk of cardiovascular disease. Restoration of euthyroidism might be involved in prevention of cardiovascular disease. Thus, we evaluated biochemical risk factors of 75 patients with SH without evidence of any other diseases before and after restoration of euthyroidism and compared to 27 healthy controls. Before and a mean of 18.2+/-4.4 weeks after restoration of euthyroidism, serum total and LDL cholesterol, lipoprotein (Lp) (a), total homocysteine (t-Hyc) and highly sensitive C-reactive protein (hsCRP) levels were analyzed. Pre-treatment levels of TSH (10.04+/-5.36 vs 1.74+/-1.1 mIU/l, p<0.05), total cholesterol (204+/-68 vs 179+/-26 mg/dl, p<0.05) and LDL cholesterol (129+/-50 vs 106+/-16 mg/dl, p<0.05) were significantly higher than controls while Lp (a), t-Hyc, and hsCRP levels were not different. None of these biochemical risk factors have improved after euthyroidism in patients with SH with average dose of 85+/-30 microg/day, when compared to pre-treatment levels. Only in a subgroup of patients (no. 30) with higher TSH levels (>10 mIU/l), did serum LDL cholesterol levels decrease significantly (139+/-38 vs 112+/-35 mg/dl, p<0.05). Lp (a), t-Hyc and hsCRP levels were not significantly different after treatment with levothyroxine therapy even in this subgroup of patients. We conclude that clinical management of SH does not contribute to prevention of cardiovascular disease in the short term, and monitoring risk factors of cardiovascular disease does not offer additional benefits for treating patients with SH.

Pluripotency of bovine embryonic cell line derived from precompacting embryos.

We report herein the establishment of three bovine pluripotent embryonic cell lines derived from 8-16-cell precompacting embryos. Two cell lines were cultured for 10 passages and underwent spontaneous differentiation. One cell line (Z2) has been cultured continuously for over 3 years and has remained undifferentiated. These cells express cell surface markers that have been used routinely to characterize embryonic stem (ES) and embryonic germ (EG) cells in other species such as stage-specific embryonic antigens SSEA-1, SSEA-3, and SSEA-4, and c-Kit receptor. In the absence of a feeder layer, these cells differentiated into a variety of cell types and formed embryoid bodies (EBs). When cultured for an extended period of time, EBs differentiated into derivatives of three EG layers - mesoderm, ectoderm, and endoderm - which were characterized by detection of specific cell surface markers. Our results indicate that the Z2 cell line is pluripotent and resembles an ES cell line. To our knowledge, this is the first bovine embryonic cell line that has remained pluripotent in culture for more than 150 passages.

Iodine and zinc, but not selenium and copper, deficiency exists in a male Turkish population with endemic goiter.

Although endemic goiter has been shown to have a high prevalence in Turkey, little is known about the concentration of urinary iodine, plasma selenium (Se), copper (Cu), and zinc (Zn) in these patients. We studied on 140 male patient with endemic goiter (mean age: 22.2 +/- 0.19 yr) and 140 healthy male subjects (mean age: 21.8 +/- 0.28 yr). Daily urinary iodine excretion was determined by the ionometric method. Plasma Se, Zn, and Cu were determined by using atomic absorption spectrometry. Daily urinary iodine excretion was found to be significantly lower in the patient group (38.7 +/- 2.26 microg/d) than that of controls (50.73 +/- 2.56 microg/day, p = 0.001). Plasma Zn concentrations were also found to be significantly lower in the patient group (1.04 +/- 0.03 microg/mL) than that of controls (1.16 +/- 0.02 microg/mL, p = 0.001). No significant difference was determined in Se and Cu concentrations between the patient and control groups. Our study shows that a moderate iodine deficiency exists in both patients with endemic goiter and control subjects, which indicates the important role of iodine deficiency in the etiopathogenesis of endemic goiter in Turkey. Zinc deficiency may also contribute to the pathogenesis of endemic goiter. However, Se and Cu do not seem to have any role in the etiopathogenesis of endemic goiter in Turkey. A community-based iodine fortification program throughout the country may be proposed to take over the problem, which also can prevent the contributing effects of other element deficiencies that occur when iodine deficiency is the prevailing factor.

Event-related brain potentials in male hypogonadism.

Several studies based on psychometric tests have determined an impairment of cognitive functions in patients with androgen deficiency. However, little is known about event-related potentials (ERPs) alterations in male hypogonadism. We investigated alterations of ERP in male hypogonadism before and 3 months after gonadotropin treatment. ERPs were elicited in 20 untreated male patients with idiopathic hypogonadotropic hypogonadism (IHH) (mean age: 21.1+/-1.4 years) and in a group of 30 male controls with comparable mean age and educational level. ERP recordings were repeated 3 months after hCG/hMG treatment. Untreated hypogonadal patients had longer mean P300 latencies and increased P300 amplitudes when compared to those in controls (321.6+/-18.5 vs 299.3+/-20.1 msec, p=0.0002; 12.15+/-4.47 vs 9.38+/-3.02 microV, p=0.011, respectively). The mean P300 latencies did not change significantly 3 months after gonadotropin treatment, while P300 amplitudes were decreased significantly. P300 latencies did not correlate with serum testosterone and other hormone levels. We conclude that prolongation of P300 latencies and increased P300 amplitudes are associated with male hypogonadism, but P300 prolongation is not reversed 3 months after gonadotropin treatment. These findings confirm the occurrence of cognitive defects in hypogonadal patients and would support the hypothesis that perinatal androgen deficiency contributes to an insufficient cognitive development.

Plasma leptin levels in male patients with idiopathic central diabetes insipidus.

Leptin is known to regulate food intake and energy expenditure. Moreover, recent studies in rodents have shown that leptin in high doses decreases urine osmolality and increases water intake, together with renal sodium and water excretion. Since it is not clear whether leptin is involved in either the pathogenesis or in resulting metabolic abnormalities in diabetes insipidus, we measured leptin levels in 16 male patients with idiopathic central diabetes insipidus (DI) in comparison to a group of age- and BMI-matched male control subjects (no.=30). We found that plasma leptin concentration did not differ between patients with DI (4.45+/-3.24 microg/l) and healthy control group (3.69+/-2.81 microg/l; t test, p=0.41). Urine osmolality, plasma osmolality and urine volume of the patients with DI was not correlated to leptin. However, leptin was positively associated with body mass index (r=0.67; p=0.005). We conclude that leptin plasma concentrations are unchanged in diabetes insipidus. Furthermore, the lack of correlation between plasma leptin and urine osmolality, plasma osmolality or urine volume suggests that ADH deficiency does not have any impact on the plasma leptin levels.

Bovine oocyte cytoplasm supports development of embryos produced by nuclear transfer of somatic cell nuclei from various mammalian species.

The transfer of nuclei from one cell to another provides a powerful tool for studying the interactions between the cytoplasm of one cell and the nucleus of another. This study was designed to examine the ability of the bovine metaphase oocyte cytoplasm to support mitotic cell cycles under the direction of differentiated somatic cell nuclei of various mammalian species. Skin fibroblast cells from cows, sheep, pigs, monkeys, and rats were used as sources of donor nuclei. Nuclear transfer units produced by fusion of enucleated bovine oocytes and individual fibroblasts from all species examined underwent transition to interphase accompanied by nuclear swelling, further progression through the cell cycle, and completion of the first mitosis. Regardless of the species of donor fibroblasts used, some cleaving units progressed further and developed to advanced stages, as evidenced by continuation of cell proliferation and formation of a blastocoele cavity at the time appropriate for the donor fibroblast species. Although no pregnancies have been carried to term after transfer of embryos into surrogate animals, these observations suggest that mechanisms regulating early embryonic development may be conserved among mammalian species and that bovine oocyte cytoplasm can support the introduced differentiated nucleus regardless of chromosome number, species, or age of the donor fibroblast.

Sexual dimorphism in IVM-IVF bovine embryos produced from X and Y chromosome-bearing spermatozoa sorted by high speed flow cytometry.

The objective of this study was to examine preimplantation development and sperm aster characteristics of bovine male and female embryos produced by using spermatozoa sorted for the X or Y chromosome. In vitro matured oocytes were inseminated at 24 h of maturation with sorted X or Y chromosome-bearing spermatozoa, using either fresh or frozen-thawed semen. Samples were taken from each sperm group 12 h post insemination (hpi), fixed, and immunostained for the microtubule cytoskeleton. Confocal microscopy enabled visualization of sperm aster formation and microtubule characteristics of each zygote during early fertilization. Cultured embryos were checked for cleavage at 30, 35, 40 and 45 hpi, embryo development was examined daily until Day 8 of culture. Blastocyst cell numbers were determined at the end of the experiments. Reanalysis of the sorted sperm cells for DNA content showed purity rates of 90.1 and 92.1% for X and Y chromosome-bearing spermatozoa, respectively. Reduced fertilization and development rates were observed when sorted spermatozoa were used compared with fresh and frozen-thawed spermatozoa. Penetration rates at 12 hpi were 39.5, 44.7, 55.9 and 79.0%, while blastocyst formation rates at Day 8 were 26.7, 26.5, 31.7 and 40.7% for X and Y chromosome-bearing spermatozoa, using fresh and frozen-thawed semen groups, respectively. Sperm aster size was larger in males than females, while the size of pronuclei and subjective grade of sperm aster quality showed no differences between sexes. In this study, a greater cleavage rate and sperm aster size in male embryos indicated a dimorphic pattern of development in male and female embryos during fertilization and first cleavage.

Effects of gonadotropin and testosterone treatments on plasma leptin levels in male patients with idiopathic hypogonadotropic hypogonadism and Klinefelter's syndrome.

Since little is known about the effects of gonadotropin and testosterone treatment on leptin levels in male hypogonadism, we determined fasting plasma leptin levels before and 3 months after treatment in 21 patients with idiopathic hypogonadotropic hypogonadism (IHH), 16 patients with Klinefelter's syndrome and 20 male controls. Patients with IHH were treated with hCG/human menopausal gonadotropin, whereas patients with Klinefelter's syndrome received T treatment. Plasma leptin levels were measured by an RIA with a sensitivity of 0.5 microg/L. Mean leptin levels in patients with IHH before treatment (9.23+/-4.09 microg/L) were not significantly different from those in patients with Klinefelter's syndrome (7.29+/-5.05 microg/L; z=-1.41; P=0.15). Leptin levels in both IHH and Klinefelter's syndrome groups were, however, significantly higher than in the normal men (3.91+/-1.67 microg/L) (P<0.001 and P<0.01, respectively). Mean leptin levels did not change significantly 3 months after the initiation of gonadotropin (11.6+/-6.44 microg/L) or T (8.32+/-5.17 microg/L) treatment in either IHH or Klinefelter's syndrome. Our study demonstrated that mean plasma leptin levels are not influenced by short-term gonadotropin or T treatment in male hypogonadism.

The effects of thyroid status on serum apolipoprotein A-I-containing lipoprotein particles.

Alterations of lipid profile are a well-known phenomenon in thyroid dysfunction. However, little is known about the influence of thyroid hormone on Lp A-I and LpA-I:A-II particles. We have, therefore, studied LpA-I and LpAI:A-II concentrations in a group of 20 patients with hyperthyroidism and in a group of 15 patients with hypothyroidism before and one month after attainment of euthyroidism. In hypothyroid patients, LDL-cholesterol and apo B concentrations decrease significantly after L-T4 replacement treatment (from 4.49+/-2.51 to 2.76+/-0.70 mmol/ L, P=0.036 and from 89.4+/-16.1 to 78.3+/-13.3 mg/dL, P=0.05, respectively), whereas no significant change was observed in the total cholesterol, HDL-C, LpA-I, LpA-I:A-II and apo A-I concentrations. In hyperthyroid patients, total cholesterol (from 3.58+/-0.72 to 4.74+/-1.39mmol/L, P=0.0025), HDL-C (from 1.19+/-0.23 to 1.41+/-0.27mmol/L, P=0.0084), LDL-C (from 1.83+/-0.69 to 2.96+/-1.20 mmol/l, P=0.0025), apo A-I (from 85.6+/-12.5 to 91.7+/-18.1 mg/dL, P=0.05) and apo B (from 52.7+/-8.2 to 65.6+/-16.5 mg/dL, P=0.0013) increased after restoration of euthyroidism while triglycerides, LpA-I and LpA-I: A-II concentrations were unchanged. LpA-I and LpA-I:A-II concentrations were not related to thyroid hormones in both groups. Our study suggests that LpA-I and LpA-I:A-II particles are not under the direct control of thyroid hormones.

Lymphocytic hypophysitis in a patient with Graves' disease.

A case of lymphocytic hypophysitis is described in a patients with Graves' disease and diabetes mellitus. The 62-year-old man was admitted to hospital with the complaints compatible with hyperthyroidism in April 1993. His medical history, physical examination, thyroid function tests, thyroid scintigraphy and thyroid ultrasonography revealed Graves' disease. The patient had also suffered from diabetes mellitus for three years. After this, the patient's progress was not monitored for two years. The patient presented himself again in September 1995 with complaints of hypothyroidism, hypogonadism and hypoadrenalism. Hormonal investigation showed panhypopituitarism. A magnetic resonance imaging of the pituitary gland disclosed an enlarged pituitary and a thickened infundibulum. The high intensity signal of the neurohypophysis was absent. Transsphenoidal hypophysectomy was performed which revealed a grey-white, relatively avascular pituitary mass. Histology showed diffuse infiltration of the anterior pituitary by numerous lymphocytes. The neurohypophysis also showed evidence of lymphocytic infiltration. On the basis of these findings we suggest that lymphocytic hypophysitis may be associated with Graves' disease.

Magnetic resonance imaging of posterior pituitary for evaluation of the neurohypophyseal function in idiopathic and autosomal dominant neurohypophyseal diabetes insipidus.

We investigated the role of MR imaging for evaluation of the functional status of the neurohypophyseal system in both idiopathic central diabetes insipidus (DI) and familial autosomal dominant neurohypophyseal DI. The patients and family with DI were analyzed retrospectively for the presence or absence of posterior pituitary gland hyperintense signal on MR images. A total of 19 adult patients with idiopathic central DI, 7 members of a family with autosomal dominant DI and 20 control subjects were included in the study. Diagnosis of idiopathic DI was based on the presence of central DI in the absence of any alteration that is known to be responsible for DI. The patients were studied retrospectively and the morphology and intensity of the posterior lobe by MR imaging was assessed by blinded reading. In all patients with idiopathic central DI and the affected members of the family, the posterior bright signal was absent while the stalk was normal on MR images. In contrast, normal posterior pituitary bright signal and stalk were found in unaffected members of the family and all control subjects. We conclude that MR imaging of the posterior pituitary lobe can be used to evaluate the functional status of the neurohypophyseal system in idiopathic central DI and familial autosomal dominant DI.

A case of thyrotropin-secreting pituitary microadenoma with normal thyrotropin alpha-subunit level.

We present a 32-year-old male with a thyrotropin (TSH)-secreting pituitary microadenoma with normal alpha-subunit (SU) and/or alpha-SU/TSH molar ratio. An interesting feature of this patient is that the size of the pituitary tumor remained unchanged during a 6-year follow-up without treatment. The tumor was clearly visualized with somatostatin receptor imaging, indicating that it was somatostatin receptor-positive. Subcutaneous injection of 100 microg octreotide acetate three times daily resulted in significant reduction of TSH and free thyroid hormones 6 weeks after initiation of treatment. However, tumor size was not changed 3 months after initiation of octreotide therapy and thyroid hormones, but not TSH level, eventually increased in spite of increasing the octreotide dosage up to 600 microg/day. This led to discontinuation of treatment. The patient responded only temporarily to octreotide in spite of somatostatin receptors. This case further demonstrates that a normal alpha-SU and/or alpha-SU/TSH molar ratio cannot exclude the possibility of a TSH-secreting pituitary adenoma.

Central and peripheral neural responses in acromegaly.

OBJECTIVE: To assess the function of the central and peripheral nervous systems in patients with untreated acromegaly. METHODS: We recorded the somatosensory evoked potentials (SSEPs) and brain stem auditory evoked potentials (BAEPs) in 10 patients with untreated acromegaly of brief duration and in 20 age- and sex-matched healthy control subjects to evaluate the function of the central nervous system and at least the median and tibial components of the peripheral nerves. Electrophysiologic studies were done at the time of diagnosis and before the initiation of any treatment for acromegaly. We also studied the distal motor latency, nerve conduction velocity, compound muscle action potentials, and F response in the peroneal nerve; the sensory nerve conduction velocity and sensory potential amplitude were measured in the sural nerve. RESULTS: The mean duration of acromegaly (expressed as time elapsed since patients first recognized signs or symptoms) was 2.4 years. The N(9) and N(13) latencies in median SSEPs and the N(22) latency in tibial SSEPs were significantly prolonged in patients with acromegaly in comparison with the control group; however, central nervous system components of SSEPs and all components of BAEPs were normal. We also noted abnormalities in peroneal motor and sural sensory nerves. No correlation was found between the neurophysiologic data and the basal growth hormone level, the fasting blood glucose level, or the duration of disease. CONCLUSION: Our results suggest that peripheral, but not central, nervous system involvement exists in patients with untreated acromegaly of short duration.

Event-related brain potentials in patients with hypothyroidism.

OBJECTIVE: To evaluate the cognitive function of patients with hypothyroidism, based on long-latency auditory event-related potentials (ERPs). METHODS: We investigated alterations of P300 latency in patients with hypothyroidism before treatment and after restoration of euthyroidism. ERPs were elicited in 14 untreated patients with hypothyroidism (mean age, 26.71 +/- 2.39 years) and in a group of 30 control subjects with comparable mean age, sex distribution, and educational level. ERP recordings were repeated at 1 and 6 months after attainment of euthyroidism. RESULTS: Untreated patients with hypothyroidism had longer P300 and N1 wave latencies in comparison with those in the control subjects (P = 0.003 and P = 0.018, respectively). The mean P300 latencies did not change significantly 1 month after restoration of euthyroidism. At 6 months after attainment of euthyroidism, however, the mean P300 latencies returned to normal values, similar to those in the control subjects. CONCLUSION: We conclude that P300 latencies are impaired in patients with hypothyroidism, which is indicative of cognitive dysfunction. These alterations, however, may be reversed 6 months after attainment of euthyroidism.

Effects of gonadotropin and testosterone treatments on prostate volume and serum prostate specific antigen levels in male hypogonadism.

It is known that prostate specific antigen (PSA) is strongly androgen dependent, but little is known about the effects of gonadotropin and testosterone treatments on the prostate and serum PSA levels in male hypogonadism. We have therefore determined serum PSA levels before and 3 months after treatment in 13 patients with idiopathic hypogonadotropic hypogonadism (IHH) and 14 patients with Klinefelter's syndrome. Plasma FSH, LH, testosterone, PRL, testis and prostate volumes were also determined before and 3 months after treatments. Patients with IHH were treated with hCG/hMG and patients with Klinefelter's syndrome received testosterone treatment. PSA levels were determined by a kinetic enzyme immunoassay method. In patients with Klinefelter's syndrome FSH and LH levels were significantly decreased but total and free testosterone and PSA levels were significantly increased after 3 months of treatment. Right and left testicular volumes were not significantly changed whereas prostate volumes were significantly increased after treatment. In this group PSA levels were significantly and positively correlated with the prostate volume both before (r=0.54, P=0.048) and after treatment (r=0.61, P=0.012). In the IHH group total and free testosterone and PSA levels were significantly increased after gonadotropin treatment but FSH and LH levels did not change significantly. Right and left testicular volumes and the prostate volumes were also significantly increased after 3 months of gonadotropin treatment. In this group PSA levels were correlated with prostate volume before (r=0.74, P=0.004) treatment but not after therapy (r=0.35, P=NS). Our results show that serum PSA levels increase after gonadotropin and testosterone treatment in male hypogonadism, but this could not be used as an index for the evaluation of the androgen action in the treatment of male hypogonadism, since PSA levels following treatments were correlated with the prostate volume or T levels only in patients with Klinefelter's syndrome but not in the IHH group.

Acute hypothyroidism leads to reversible alterations in central nervous system as revealed by somatosensory evoked potentials.

Although functional alterations in the central nervous system (CNS) and peripheral nerves are well documented in overt hypothyroidism, little is known about alterations of CNS in acute hypothyroidism. Sixteen patients with differentiated thyroid carcinoma were studied when prepared for radioiodine scanning after stopping levothyroxine (L-T4) therapy for 6 weeks to determine whether acute hypothyroidism leads to alteration in somatosensory evoked potentials (SSEPs). Repeat SSEPs were performed on the same patients at 6 months following L-T4 therapy when patients were euthyroid. Neurophysiological findings were compared with a group of 20 normal controls with no history of thyroid disease. Peripheral and central conduction in the median and tibial nerve stimulated SSEPs studied. A significant prolongation of central conduction time in SSEPs was found in patients with acute hypothyroidism when compared to those in control subjects. Abnormal latencies were not correlated with thyroid hormone levels. These neurophysiologic abnormalities were completely restored to normal at 6 months after L-T4 therapy. We conclude that acute hypothyroidism leads to reversible alterations in CNS as determined by SSEP recordings. Our results also suggest that SSEPs could be useful tests to monitor functional alteration of the CNS in acute hypothyroidism.

Effects of octreotide treatment on Graves' ophthalmopathy and circulating sICAM-1 levels.

Efficacy of octreotide treatment for Graves' ophthalmopathy (GO) and the effects of this treatment on the serum levels of the circulating intercellular adhesion molecule-1 (sICAM-1) were evaluated. Ten patients with GO were treated with octreotide three daily SC injections of 100 micrograms, for 3 months. Octreotide treatment was initiated after restoration of euthyroidism with antithyroid drugs. All patients were treated with methimazole to maintain euthyroidism during the study. Sera were collected from all patients before and 3 months after initiation of the study, and from 20 age- and sex-matched healthy subjects for sICAM-1 measurement. sICAM-1 was measured by a sandwich ELISA method. Proptosis in all patients was evaluated by orbital CT scan before and 3 months after initiation of the study. Two of 10 patients did not respond to octreotide therapy, while the remaining eight patients showed regression or improvement after therapy. Octreotide therapy was particularly successful in patients with soft tissue involvement of GO (class II or III disease). Mean proptosis and ophthalmopathy index scores were significantly decreased after 3 months of octreotide therapy. Mean sICAM-1 levels were significantly higher in patients before octreotide therapy (470.5 +/- 52.6 ng/mL, p < 0.0001) when compared to normal subjects (186.5 +/- 53.3 ng/mL). Mean sICAM-1 levels were significantly decreased 3 months after octreotide therapy (from 478.7 +/- 52.6 to 415 +/- 42.8 ng/mL, p = 0.012) in the 8 patients who responded to therapy. In contrast, sICAM-1 levels remained unchanged or increased in two patients with poor response to octreotide therapy. Our results suggest that octreotide therapy could be a treatment modality in patients with GO. The mechanism by which octreotide acts on GO is not clear. The observed decrease in sICAM-1 levels during octreotide therapy suggests that octreotide may have immunomodulatory properties. Further investigation is needed to determine the optimal dose and duration of octreotide therapy.

Central and peripheral neural responses in males with idiopathic hypogonadotropic hypogonadism.

It has previously been shown that abnormal neurophysiologic responses are associated with Kallmann's syndrome. However, little is known about neurophysiologic responses in idiopathic hypogonadotropic hypogonadism (IHH). Fifty-six untreated male patients with IHH (mean age: 20 +/- 0.7 years) were compared with a control group of 20 age-matched male subjects to determine whether IHH can lead to alterations in somatosensory evoked potentials (SSEPs) and brainstem auditory evoked potentials (BAEPs). We have also investigated the effect of gonadotropin replacement (hCG/hMG) therapy on these tests in 20 randomly selected patients. Significant cervical 7 (N13), Erb (N9) and thoracic 12 (N22) latency prolongation was observed in median and tibial nerve SSEPs in patients with IHH as compared with a matched control group. Other components of SSEPs and interpeak latencies of BAEPs yielded no significant difference between untreated patients and control group. Abnormal components of SSEPs did not correlate with basal hormone levels and did not improve with gonadotropin therapy. We conclude that IHH results abnormalities in peripheral but not central nervous system components of SSEPs and that short term gonadotropin treatment cannot correct these abnormalities.