Endoscopic resection of hypothalamic hamartomas for refractory symptomatic epilepsy.

BACKGROUND: Hypothalamic hamartomas (HHs), rare developmental abnormalities of the inferior hypothalamus, often cause refractory, symptomatic, mixed epilepsy, including gelastic seizures. We present 37 patients with HH who underwent transcortical transventricular endoscopic resection. METHODS: Between October 2003 and April 2005, 42 consecutive patients with refractory epilepsy who underwent endoscopic resection of HH were studied prospectively. The endoscope was held by an articulated pneumatic arm and tracked with a frameless stereotactic neuronavigation system. Data collection and follow-up were performed by personal interview. Five patients were excluded. The remaining 37 patients (22 males, 15 females; median age 11.8 years; range 8 months to 55 years) had frequent and usually multiple types of seizures. RESULTS: Postoperative MRI confirmed 100% resection of the HH from the hypothalamus in 12 patients. At last follow-up (median 21 months; range 13-28 months), 18 (48.6%) patients were seizure free. Seizures were reduced more than 90% in 26 patients (70.3%) and by 50% to 90% in 8 patients (21.6%). Overall, the mean postoperative stay was shorter in the endoscopic patients compared with our previously reported patients who underwent transcallosal resection (mean 4.1 days vs 7.7 days, respectively; p = 0.0006). The main complications were permanent short-term memory loss in 3 patients and small thalamic infarcts in 11 patients (asymptomatic in 9). CONCLUSIONS: Endoscopic resection of hypothalamic hamartoma (HH) is a safe and effective treatment for seizures. Its efficacy seems to be comparable to that of transcallosal resection of HH, but postoperative recovery time is significantly shorter.

Fibroblast androgen receptors in patients with genitourinary anomalies.

The etiology of certain disorders of sexual differentiation is unclear. The authors have examined the hypothesis that hypospadias and other disorders compatible with a defect in androgen action, such as cryptorchidism, micropenis, chordee/penile torsion, and ectopic testis, might be explained by androgen receptor abnormalities. Therefore, 25 subjects were studied who were selected only because they had one of these developmental defects, together with a predominantly male phenotype, and no readily ascertainable explanation for the defect. Four of these subjects had mixed gonadal dysgenesis with multiple genito-urinary anomalies. They were included for comparative purposes, since there is no evidence for androgen resistance in this disorder. Patients with testicular regression syndrome (gross testosterone deficiency), impaired testosterone biosynthesis (relative testosterone deficiency), 5 alpha-reductase deficiency (altered T/DHT ratio), and a family history or endocrine profile suggestive of androgen resistance, were all excluded from evaluation. Androgen receptor content (R0) and binding affinity (Kd) were measured in 26 genital or pubic skin fibroblast strains cultured from 25 affected patients using a dispersed, whole cell assay at 22 C. There was no difference in the mean androgen receptor content (approximately 10,000 sites/cell) or binding affinity (approximately 1 nM) between the patients' fibroblasts and those from 26 fibroblast strains established from 26 normal males. Moreover, there were no differences in the nuclear uptake of [3H]dihydro-testosterone into dispersed, intact fibroblasts incubated at 37 C when 11 patient and seven normal male fibroblast strains were compared.(ABSTRACT TRUNCATED AT 250 WORDS)

Leydig cell hypoplasia causing male pseudohermaphroditism: diagnosis 13 years after prepubertal castration.

An 11-yr-old patient with male pseudohermaphroditism who was castrated at nine days of age and raised thereafter as a female was evaluated to determine the cause of abnormal sexual differentiation. Stimulation with ACTH for 8 h revealed no abnormality in the biosynthesis of cortisol or adrenal androgens. The administration of fluoxymesterone (10 mg, orally, daily) for 5 weeks at age 13 yr led to significant decrements in serum levels of sex steroid-binding globulin and T4-binding globulin to a degree similar to that found in 2 normal men, but no change in the basally elevated levels of FSH and LH. LH bioactivity was normal in the rat Leydig cell bioassay. Skin fibroblasts cultured from a labial skin biopsy revealed normal 5 alpha-reductase activity and normal androgen receptors. Reexamination of the original testis specimens by light microscopy failed to reveal Leydig cells. Furthermore, when immunoperoxidase staining for testosterone was performed on the tissue sections, only 30-35 positive cells/10 high power fields were seen. In contrast, examination of testis sections from 4 male infants who died of other causes revealed 94-836 cells/10 high power fields that stained positively for testosterone. Although hCG stimulation testing to confirm Leydig cell hypoplasia could not be done in this patient because of previous castration, this patient demonstrates that the diagnosis can be made without it by the use of immunohistochemical stains and in vivo and in vitro tests to exclude other disorders of androgen biosynthesis or androgen action.

Spermiogenesis and testicular spermatozoa of the olive baboon (Papio anubis).

The ultrastructure of spermiogenesis and of testicular spermatozoa of the olive baboon (Papio anubis) has been studied. The four main (Golgi, cap, acrosome and maturation) phases of spermiogenesis are described, and these phases have been further subdivided into a total of ten phases. Spermiogenesis was found to be basically similar to that of other mammalian species, in particular to that of man. A lower number of morphologically deviating cells was found in the baboon, but in other respects most differences between human and baboon spermiogenesis and spermatozoa refer to dimensions. Aspects of the morphogenesis of certain structures of the tail are discussed in more detail.

Euthyroid familial hyperthyroxinemia due to abnormal thyroid hormone-binding protein.

A family is described in which three members had an elevated total serum thyroxine level and free thyroxine index. Each affected subject was clinically euthyroid and had a normal pulse wave arrival time (QKd), serum triiodothyronine and free thyroxine levels, and a normal serum thyroxine-binding globulin (TBG) concentration. Electrophoresis of their serum with 125I-labeled thyroxine revealed increased thyroxine binding in the albumin region. In addition, this abnormal protein, like thyroxine-binding globulin, bound 125I-labeled triiodothyronine and 125I-labeled reverse triiodothyronine. However, electrophoresis of serum treated by sialidase (neuraminidase) digestion suggested that this abnormal protein is not an anomalous form of thyroxine-binding globulin "buried" in the albumin area. These cases of euthyroid familial hyperthyroxinemia due to an abnormal thyroid hormone-binding protein show that an elevated serum thyroxine level or free thyroxine index is not always sufficient to confirm the presence of thyrotoxicosis.

Daily rhythm of plasma melatonin in normal and precocious puberty.

A previous study of normal humans has shown a decrease in plasma melatonin at the onset of puberty, suggesting that melatonin may act to restrain pubertal onset. We have measured plasma melatonin throughout a 24-h period in normal and constitutionally short males at different pubertal stages and in patients with idiopathic true precocious puberty and familial male isosexual precocity. The 24-h profile of plasma melatonin was similar for the prepubertal, pubertal, and adult males studied, with all subjects having low levels (20-50 pg/ml) during the day and high levels (80-100 pg/ml) at night between 0100-0500 h. The 24-h profiles of the patients with isosexual precocity were similar to the profiles observed throughout normal puberty. These data do not support a role for melatonin in the initiation of normal or precocious puberty in man.

The response of prolactin to chlorpromazine stimulation in men with hypogonadotrophic hypogonadism and early pubertal boys: relationship to sex steroid exposure.

The effect of chlorpromazine (CPZ) on prolactin (PRL) secretion was studied in fourteen sexually immature males; nine with idiopathic hypogonadotrophic hypogonadism and five who proved to be normal early pubertal boys. Initially, clinical features and basal levels of testosterone, LH and FSH in serum collected in the morning and the gonadotrophin responses to LHRH stimulation were similar in all subjects. Following CPZ the early pubertal boys increased PRL levels by at least 15 ng/ml, responses similar to those of normal men, whereas no subject with complete hypogonadotropism increased PRL by more than 5 ng/ml. Two subjects with incomplete hypogonadotropism ('fertile eunuchs') exhibited responses similar to normals. Treatment with human chorionic gonadotrophin (hCG) or testosterone enhanced the PRL response to CPZ in three of six hypogonadotrophic subjects. Ten additional hypogonadotrophic men studied while receiving long term treatment with hCG or testosterone also manifested normal responses to CPZ. These data indicate that lack of sex steroid exposure, rather than a more generalized hypothalamic disorder, explains the attenuated PRL response to CPZ found in untreated men with idiopathic hypogonadotrophic hypogonadism. Moreover, CPZ-stimulated PRL secretion may prove to be of practical value in distinguishing hypogonadotrophics from boys with delayed puberty.

Autonomous thyroid nodules in adolescents: clinical characteristics and results of TRH testing.

Seven adolescents with autonomous thyroid nodules were evaluated over a three-year period. They had hyperfunctioning nodules on radionuclide scan which failed to suppress with exogenous administration of thyroid hormone. They were clinically euthyroid and had normal T4, free T4, and basal TSH values. However, as a group they had elevated total serum T3 concentrations, blunted TSH response to TRH, and accelerated closure of cranial sutures, all of which suggested subtle hyperthyroidism. These patients have been followed for one to five years. Four have undergone partial thyroidectomy because of persistent elevation in the serum T3 concentration or enlargement of the nodule. The clinical presentation and laboratory findings in this group are similar to those found in adults with autonomous nodules.

Gonadal dysgenesis with mosaicism and a nonfluorescent Y chromosome: report of two cases with correlation of clinical, pathologic, and cytogenetic findings.

Two phenotypic girls with nonfluorescent Y chromosome mosaicism and histologic streak gonads were presented. H-Y antigen (a Y chromosome--determined antigen) was negative in both patients. Electron microscopic findings of "streak gonads" were presented for the first time. The authors recommend bilateral gonadectomy in patients with nonfluorescent Y chromosomes and correlation between the histologic findings and H-Y antigen status.

The pulse wave arrival time (QKd interval) in normal children.

The interval between the onset of QRS of the electrocardiogram and the arrival of the pulse wave at the brachial artery, as detected by the appearance of Korotkoff sounds at diastolic pressure (QKd), provides a measure of a pulse wave arrival time, i.e., the sum of the pre-ejection period and a pulse transmission time. This measurement has proven useful in the evaluation of cardiovascular disease, thyroid and catecholamine status, and several other conditions in adults. In order to standardize this measurement in children, measurements were obtained on 63 normal children ranging in age from 7 months to 18 years. Because of the dependence of pulse transmission time on the distance of propagation, the QKd interval (in msec) is related to height (H in cm) by the equation: QKd = 56.6 + 0.797H. By use of this equation one can obtain a "height corrected QKd." Correction for pulse rate is not necessary for resting subjects. These normal ranges permit use of the QKd interval for clinical studies in children. These studies also permit measurement of the mean pulse wave velocity for a group of individuals. PWV (m/sec) increases with age according to the equation: PWV = 2.44 + 0.203 A, (A in years) with a correlation coefficient of r = 0.823. This implies progressive loss of functional elasticity of the major arteries throughout childhood.

Dissociation of cortisol and adrenal androgen secretion in patients with secondary adrenal insufficiency.

Plasma cortisol, dehydroepiandrosterone (DHA), dehydroepiandrosterone sulfate (DHAS), and androstenedione (delta4-A) were measured by RIA during ACTH infusion in preadrenarchal children with constitutional short stature, normal adults, and patients with secondary adrenal insufficiency resulting from hypothalamic-pituitary disease or corticosteroid therapy. The plasma levels of all four steroids were decreased in patients with secondary adrenal insufficiency compared to normal adults, but the decrease in DHA and DHAS was considerably greater than that in cortisol and delta4-A, resulting in significant decreases in the plasma ratios of DHA to cortisol, DHAS to cortisol, DHA to delta4-A, and DHAS to delta4-A (P less than 0.00001). The decreased DHA and DHAS responses to ACTH persisted in one glucocorticoid-treated patient after glucocorticoid therapy was terminated and the cortisol response to ACTH had normalized. The data suggest that adrenal atrophy due to hypothalamic-pituitary disease or corticosteroid therapy is associated with a greater impairment in the secretion of the delta5 adrenal androgens DHA and DHAS than in the secretion of cortisol and delta4-A, and that the capacity to secrete cortisol and delta4-A recovers more rapidly than the capacity to secrete the delta5 adrenal androgens when corticosteroid therapy is withdrawn.

Plasma testosterone, luteinizing hormone and follicle-stimulating hormone one day after vasectomy.

Plasma testosterone, LH and FSH were measured in 20 healthy subjects prior to and one day after bilateral vasectomy. No significant change in these hormones was noted after surgery. These data suggest that the decrease in free testosterone index and FSH reported by others at one week post-vasectomy is probably not related to the effects of psychological stress, local anesthesia or surgical stress, either singularly or in concert. Further studies are indicated to evaluate the transient hormonal changes reported within the first few weeks following vasectomy.

PIP: In the attempt to clarify the stress effect of vasectomy, the plasma testosterone -- luteinizing hormone (LH) and follicle stimulating hormone (FSH) was measured before and 1 day following bilateral transcrotal vasectomy performed on 20 men between the ages of 24 and 53 years. Plasma testosterone -- LH and FSH -- were measured by radioimmunoassay. All measurements were performed in duplicate and samples from each individual were measured in the same assay. All values were in the normal range, and there was no signficant change after surgery (compared to basal values) in any of the parameters measured. The data suggest that the decrease in free testosterone index and FSH reported by others at 1-week post-vasectomy is probably not related to the effects of psychological stress, local anesthesia or surgical stress, either singularly or in combination.

Replacement oral ethinyloestradiol therapy for gonadal dysgenesis: growth and adrenal androgen studies.

We have studied growth and adrenal dehydroepiandrosterone (DHA) responses to iv synthetic adrenocorticotrophic hormone (ACTH, Cortrosyn) in 6 girls with gonadal dysgenesis before and during treatment with low-dose ethinyloestradiol (EOe2). In all patients there was a statisfactory induction of secondary sexual characteristics including increase in breasts and public hair and onset of withdrawal bleeding within 6 months of therapy. Height velocity increased from 2.8 +/- 0.9 cm/year pre-treatment to 5.3 +/- 1.5 cm/year (P less than 0.02) in the first year. There was deceleration to 1.9 +/- 1.1 cm/year in the second year. There was no disproportionate advancement in bone age and thus, presumably, no loss of ultimate height. We could demonstrate no change in basal or ACTH-stimulated levels of DHA, a specific adrenal androgen, to account for the increased public hair and growth in these patients.

The in vitro metabolism of progesterone, 4-androstene-3,17-dione, testosterone and 17 beta-hydroxy-5 alpha-androstan-3-one by fetal rhesus monkey testes.

Homogenates prepared from fetal rhesus monkey testes were incubated with progesterone, 4-androstene-3,17-dione, testosterone and 17 beta-hydroxy-5 alpha-androstan-3-one. The major progesterone metabolite was 17-hydroxy-4-pregnene-3,20-dione. Testosterone also accumulated in the progesterone incubations. 4-Androstene-3,17-dione was converted chiefly to testosterone. Testosterone was not actively metabolized by the fetal monkey testis. 17 beta-Hydroxy-5 alpha-androstan-3-one was actively converted primarily to 5 alpha-androstane-3 beta,17 beta-diol.