Zvi Dickerman

Paternity in Klinefelter's Syndrome—A Case Report

A boy diagnosed to have Klinefelters syndrome (KS) with a karyotype of 47XXY, at the age of 12 years underwent normal puberty and at age 17 years had a testicular volume of 10 ml. At age 22 he married and fathered a normal child. His paternity was proven by HLA typing of the parents and child. It is suggested that testosterone therapy in KS be given only when testicular failure has been definitely established.

Encephalopathy in compensated hashimoto thyroiditis: A clinical expression of autoimmune cerebral vasculitis

A young girl with compensated Hashimoto thyroiditis suffered from progressive encephalopathy while euthyroid. Seizures and mental abnormalities responded excellently to corticosteroids only, supporting the view that encephalopathy could be the clinical manifestation of autoimmune cerebral vasculitis.

Puberty in 24 patients with Klinefelter syndrome.

Twenty four boys with Klinefelter syndrome, 18 of whom were diagnosed prepubertally, were observed until adulthood. Onset of puberty, as judged from testicular enlargement and pubic hair development, occurred between 11 to 14 years in the above 18 patients. By the age of 17 pubic hair, penile length and height had reached the adult stage in all patients, but arrest of testicular growth was noted at midpuberty, 13 years, with maximal mean (±SD) volume attained being 3.5±1.5 ml. The first conscious ejaculation was reported to have occurred between 13 to 16 years in 10 patients and in the remaining 4 between 17 to 18 years of age. Sperm counts obtained after the age of 18 revealed azospermia or severe oligospermia in all patients except one, who had a sperm count of 30×106/ml. The hypothalamic-pituitary-gonadal axis, assessed by LH-RH and hCG stimulation tests, was found to be normal in prepuberty and during early pubertal stages. From mid-puberty the basal levels of plasma FSH and the response to LH-RH showed a gradual increase above the normal. Towards late puberty (>15 years) basal and peak levels of LH were above normal with a concomitant decrease in the basal level of testosterone and its response to hCG.These findings indicate that during childhood and early puberty function of the hypothalamic-pituitary-gonadal axis is normal in Klinefelter syndrome, allowing the onset of pubertal signs at the appropriate age, and that until late puberty there is a relative preservation of function in the testicular Leydig cells, permitting the normal sequential development of the androgen-dependent pubertal signs. The measurement of testicular testosterone reserve by means of hCG stimulation constitutes a useful aid in determining when and if testosterone replacement therapy should be instituted.

Prepubertal and pubertal growth, timing and duration of puberty and attained adult height in patients with congenital hypothyroidism (CH) detected by the neonatal screening programme for CH — a longitudinal study

We have evaluated parameters of growth, the pubertal process and attained adult height in patients with congenital hypothyroidism (CH) of various aetiologies, diagnosed by the neonatal screening programme, and followed up longitudinally. To the best of our knowledge, no such data are available in the published literature. Our aim was to define the most important factors affecting these parameters.

Diurnal rhythm of plasma beta endorphin, cortisol and growth hormone in schizophrenics as compared to control subjects

The diurnal variation of plasma beta endorphin was studied in ten schizophrenics, and in age/sex matched control subjects. In the controls beta endorphin was high in the morning (21.0±3.5 pmol/l) and decreased towards evening. In the schizophrenic group the beta endorphin fluctuated randomly, ranging within 9–40 pmol/l throughout the day. Plasma cortisol showed a normal diurnal pattern in both groups. The mean plasma cortisol levels in the schizophrenics were significantly higher than in the controls throughout the day. The pattern of plasma human growth hormone (hGH) level was similar in both groups at the time tested. It is hypothesized that the instability of beta endorphin secretion may contribute to the pathogenesis of schizophrenia.

Use of GnRH agonist and human chorionic gonadotrophin tests for differentiating constitutional delayed puberty from gonadotrophin deficiency in boys.

objectives The differentiation of constitutional delayed puberty (CDP) from gonadotrophin deficiency (GD) in boys at referral poses a difficult challenge. The effectiveness of the GnRH agonist (GnRH‐a) test in distinguishing between the two conditions was evaluated and compared with findings of the GnRH and hCG stimulation tests.

Follow-up of boys with unilateral compensatory testicular hypertrophy.

Of a total of 148 boys with unilateral compensatory testiculary hypertrophy (CTH) diagnosed at our clinic, 30 were followed for many years throughout puberty. These boys underwent the pubertal stages fo pubic hair development in a normal manner, including penile growth. The basal plasma levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) of the boys with CTH showed a wider range than those of normal boys. Even in prepuberty the mean basal plasma FSH levels were significantly higher than those of normal boys, as was the peak FSH response to intravenous LH-releasing hormone. In puberty stage 4 the mean plasma LH levels were also higher than normal. Plasma testosterone levels were within the normal range in pubertal stages 1 to 4, but in stage 5 the mean basal level and response to stimulation with human chorionic gonadotropin were significantly lower than normal. Among seven spermatograms performed, five showed oligospermia and two showed azoospermia. It is concluded that compensatory hypertrophy of one testis does not seem able to prevent testicular insufficiency in adulthood.

The Pattern of Growth in Children with Constitutional Tall Stature from Birth to Age 9 Years.: A Longitudinal Study

A study was made of the longitudinal growth pattern of 29 girls and 36 boys with constitutional tall stature (CTS) from birth to age 9 years. In these children, all of whom had a normal birth length, there was very rapid growth during the first 4 years of life, following which growth velocity dropped to normal and remained parallel to the 50th percentile. In the 49 subjects for whom actual final height was also obtained there was a very good agreement between this and the final height as predicted by Tanners method from the height at ages 4 and 8 years. Significant differences were found between the mean maternal, paternal and mid‐parental height and the tall stature of their offspring, but there was a very good correlation between the individual patients final height and their parental heights. The findings of this study stress the importance of periodical measurements of length and height in all children during the first few years of life so as to have appropriate data on which to base future considerations of possible therapy.

CHANGES IN ENDOGENOUS INSULIN SECRETION DURING CHILDHOOD AS EXPRESSED BY PLASMA AND URINARY C-PEPTIDE

Basal fasting values of plasma C‐peptide (CP), plasma insulin and 24 h urine CP were determined in 224 normal non‐obese subjects of both sexes ranging in age from 1 to 20 years. Analysis of the results by age, pubertal rating, sex and bone age (BA) during childhood showed that mean±SD plasma CP levels in both sexes rose from 0.07 ± 0.08 pmol/ml at the age of 1–2 years to 0.21 ±0.11 pmol/ ml at 8–10 years. Mean ± SD plasma insulin levels in both sexes rose from 3.2 ± 4.3 μU/rnl at the age of 1–2 years to 5.9±4.5 μU/ml at 8–10 years. Mean ± SD urine CP levels rose from 6.5 ± 2.8 pmol/mg creatinine per 24 h at the age of 2.8 years to 7.7 ± 3.5 pmol/mg creatinine per 24 h at 8.11 years in both sexes. During puberty, plasma and urine CP and plasma insulin levels rose further to peak at pubertal stage P3, the values in females being higher (CP = 0.32 ± 0.06 pmol/ml) than those in males (CP = 0.22 ± 0.06 pmol/ml) (P < 0.005). Plasma insulin levels in females were 13.2 ± 6.9 μU/ml and 6.4 ± 3.1 μU/ml in males (P<0.05). Urine CP levels were 14.5 ± 5.7 pmol/mg creatinine per 24 h and 10.8 ± 5.4 pmol/mg creatinine per 24 h in females and males respectively (P<0.05). With the rise in age, CP and insulin levels declined and towards adulthood were 0.23 ± 009 pmol/ml for plasma CP, 5.1 ± 4.2 μU/ml for plasma insulin and 8.7 ± 4.1 pmol/mg creatinine per 24 h for both sexes. There was a correlation between plasma CP and plasma insulin (P=0.32, P< 0.001, n = 89) and in pubertal males and females plasma CP correlated with BA (r = 0.32, P<0.02). It is concluded that endogenous insulin secretion during childhood varies with age, pubertal stage and sex. The index of choice for the most accurate and discriminative estimation of insulin secretion would appear to be CP rather than insulin itself, due to the differences in metabolism of these substances.

Endocrinological Parameters and Cell-Mediated Immunity Postoperation for Cryptorchidism

Andrological and endocrinological parameters and cell-mediated immunity (CMI) were assessed in 25 postpubertal males who had undergone repair of unilateral or bilateral cryptorchidism in childhood or early adolescence. Among 20 patients with unilateral cryptorchidism, approximately 30% had decreased sperm density, whereas among 5 bilaterally affected, 1 was azoospermic and 2 oligozoospermic. In most patients the motility and viability values were normal, although the percentage of morphologically pathological sperm was higher than normal. Levels of testosterone, dihydrotestosterone, LH, and prolactin were within normal ranges in all the patients. Levels of FSH were slightly elevated. These findings may suggest a better fertility prognosis of postcryptorchid oligozoospermic patients than in patients with oligozoospermia of other etiology. CMI toward autologous semen revealed a positive reaction in 80% of the bilateral group and in 45% of the unilateral group. This response might be due to the damage of seminiferous tubules of undescended testis causing unmasking and exposure of antigenic determinants.