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Featured researches published by H. Kaufman.


Acta Paediatrica | 1984

Premature Thelarche–Natural History and Sex Hormone Secretion in 68 Girls

A. Ilicki; R. Prager Lewin; R. Kauli; H. Kaufman; A. Schachter; Zvi Laron

ABSTRACT. Data obtained during long‐term follow‐up of 68 girls with premature thelarche were analysed. In 85 % onset was before the age of 2 years, in 30.8 % being present at birth. In 44.1 % there was a regression after 32/12±28/12 12years (SD). Basal levels of plasma FSH and response to LH‐RH were significantly higher than prepubertal controls (1.93± 1.56 vs. 0.8±0.1 mU/ml and peaks 12.3±5.4 vs. 7.9±1.0 mU/ml respectively; p<0.001). Twenty‐seven of 52 patients tested had increased plasma estradiol and in 27 of 40 patients tested, urocytograms or vaginal smear showed estrogenization. Basal levels of LH and response to LH‐RH were prepubertal. The girls with premature thelarche were significantly taller than normal controls of the same age (p<0.001). These results suggest that premature thelarche is an incomplete form of precocious sexual development probably due to derangement in the maturation of the hypothalamo‐pituitary‐gonadal axis which results in a higher than normal secretion of FSH, as well as a defect in the peripheral sensitivity to the sex hormones.


Fertility and Sterility | 1980

Follow-up of boys with unilateral compensatory testicular hypertrophy.

Zvi Laron; Zvi Dickerman; Irena Ritterman; H. Kaufman

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.


Clinical Endocrinology | 1984

TOTAL DEFICIENCY OF CORTICOSTEROID-BINDING GLOBULIN

A. Roitman; S. Bruchis; B. Bauman; H. Kaufman; Zvi Laron

An obese 15‐year‐old boy of Jewish Iranian origin who is the offspring of consanguineous parents was found to have very low levels of total cortisol in the plasma. Investigation of the family revealed a complete lack of cortisol‐binding‐globulin (CBG) in the proband and a sister, evidently the first cases of total CBG deficiency to be reported. The parents and a brother were found to have half the normal levels. This study indicates that CBG deficiency, a benign condition, is compatible with a codominant or recessive autosomal trait inheritance.


Clinical Endocrinology | 1977

GONADAL FUNCTION IN BLOOM'S SYNDROME

R. Kauli; Ruth Prager-Lewin; H. Kaufman; Zvi Laron

Five patients with Blooms syndrome aged from 2 8/12 to 27 years, all of whom had hypogonadism, were subjected to an i.v. LHRH test and two of them to an i.m. HCG test. There was increased responsiveness of plasma LH and FSH, indicating that the hypogonadism is primary in nature and of early development. The tubular element of the testis seems to be mainly affected, as indicated by the particularly high FSH response to LHRH stimulation, a history of sterility in the two adult patients and documented azoospermia in one of them. The Leydig cells seem to be less affected and secrete sufficient androgens to enable puberty within acceptable normal limits. Hypogonadism seems to be a major characteristic of Blooms syndrome.


Clinical Endocrinology | 1982

ADRENOCORTICAL FUNCTION IN CHILDREN WITH PRECOCIOUS SEXUAL DEVELOPMENT DURING TREATMENT WITH CYPROTERONE ACETATE

M. S. Stivel; R. Kauli; H. Kaufman; Zvi Laron

Adrenal function was studied in thirty‐two children with precocious sexual development who were being treated with cyproterone acetate (CPA) at doses ranging from 68 to 175 mg.m2. day for periods lasting from 2 to 79 months. In eighteen children the adrenocortical function evaluation was made before and during CPA treatment. In these eighteen patients, the mean basal plasma cortisol level during the morning hours was 11·2±4·6 μg/dl (m±SD) before treatment and fell significantly to 7·2±4·1 μg/dl (P < 0·02) during therapy. In fifteen patients tested during insulin hypoglycaemia the cortisol peak fell from 21·6±5·5 μg/dl before treatment to 16·7±6·8 μg/dl (P < 0·05) during CPA therapy. There was a significant inverse correlation between this peak and the dose of CPA but no correlation was found between the cortisol response and duration of treatment. In eight of twenty patients tested, urinary free cortisol levels were undetectable during treatment. No change in basal plasma ACTH levels was demonstrated using standard radioimmunoassay techniques. In the patient receiving the highest dose of CPA and showing complete suppression of the adrenal axis, prolonged stimulation with ACTH‐Depot demonstrated a responsive adrenal gland. Addition of a replacement dose of cortisol to the CPA treatment led to the rapid development of the typical signs of Cushings syndrome. It was concluded that despite the evidence of adrenal suppression by CPA, cortisol supplementation is not necessary and may even be contra‐indicated.


Acta Paediatrica | 1982

LOW ORAL DOSE OF CLONIDINE: AN EFFECTIVE SCREENING TEST FOR GROWTH HORMONE DEFICIENCY

Zvi Laron; I. Gil-Ad; E. Topper; H. Kaufman; Z. Josefsberg

We found that a marked increase in plasma hGH resulted from the oral administration of 0.15 mg/m2 of the central alpha-adrenergic stimulatory and anti-hypersensitivity agent clonidine HCl (1). Although this effect, subsequently confirmed by others as well (2), appeared to be greater than that elicited by other stimulating agents (3-7) it was accompanied by a number of undesirable effects, notably a fall in blood pressure and drowsiness. Trial tests using half of the above dose (i.e. 0.075 mg/m2) still gave occasional drowsiness (unpublished). An additional study was, therefore, undertaken to determine the activity of an even smaller dose, i.e. 0.025 mg clonidine given per 0s.


Acta Paediatrica | 1981

ADDISON'S DISEASE ASSOCIATED WITH PRECOCIOUS SEXUAL DEVELOPMENT IN A BOY

R. Marilus; Zvi Dickerman; H. Kaufman; I. Varsano; Zvi Laron

ABSTRACT. Marilus, R., Dickerman, Z., Kaufman, H., Varsano, I. and Laron, Z. (Institute of Pediatric and Adolescent Endocrinology, Steroid Laboratory and Pediatric Department B, Beilinson Medical Center, Petah Tikva, Sackler School of Medicine, Tel Aviv University, Israel). Addisons disease associated with precocious sexual development in a boy. Acta Paediatr Scand, 70:587,.–An eleven‐year‐old boy was diagnosed to have Addisons disease with an ACTH level of over 4 500 pg/ml after a short episode of fever and dehydration. From the age of 6 years his skin and buccal mucosa had been hyperpigmented but there were no other subjective complaints. The clinical examination also revealed signs of advanced puberty for his age (3rd‐4th stage according to Tanners criteria), with advanced bone age (13 years). The elevated levels of plasma testosterone and gonadotropins and their response to LH‐RH stimulation were appropriate for his clinical stage of puberty and supported the diagnosis of true precocious puberty. It is proposed that the concomitant appearance of Addisons disease and precocious puberty is due to a “drift” phenomenon of LH‐RH and/or gonadotropins following the prolonged elevation of ACTH secretion.


Hormone Research in Paediatrics | 1980

Evaluation of the renin-aldosterone system during hypo- and hyperglycemia in children and adolescents.

Z. Hochberg; Zvi Dickerman; H. Kaufman; Zvi Laron

The effect of hypo- and hyperglycemia on the renin-aldosterone system was studied in 10 endocrinologically normal children. Insulin-induced hypoglycemia caused an elevation of plasma renin activity (PRA) up to 371 +/- 23% (mean +/- SEM) over the basal level (p less than 0.001) and of the plasma aldosterone level up to 243 +/- 7% (mean +/- SEM) over the basal values (p less than 0.001). Hyperglycemia caused an elevation of PRA up to 135 +/- 40% (mean +/- SEM) over the basal values (p less than 0.05) and a reduction in the plasma aldosterone level to 53 +/- 12% (mean +/- SEM, p less than 0.01). It is suggested that the widely used diagnostic procedures, the insulin tolerance and oral glucose tolerance tests, be also applied for the investigation of the renin-aldosterone system.


Clinical Endocrinology | 1978

UNILATERAL ADRENALECTOMY AND PITUITARY IRRADIATION IN THE TREATMENT OF ACTH‐DEPENDENT CUSHING'S DISEASE IN CHILDREN AND ADOLESCENTS

B. Landau; S. Leiba; H. Kaufman; C. Servadio; B. Wainrach

In four juvenile patients with Cushings disease, the therapeutic approach used was unilateral adrenalectomy followed by irradiation of the pituitary. The follow‐up time of these patients has ranged from 1.5 to 10 years. All four are clinically well. Concentrations of adrenal steroids are within normal limits and they require no additional medication. It is felt that this method gives young patients the chance for normal growth and pubertal development as well as a normal social life, so important in the stressful adolescent years, thus avoiding the handicap incurred by bilateral adrenalectomy and the consequent requirement for continuous substitution therapy.


Annals of the New York Academy of Sciences | 1985

HLA Associations in Late-Onset 21-Hydroxylase Deficiency in Israel

Zvi Laron; A. Roitman; A. Pertzelan; H. Kaufman; R. Zamir

In the mid-1960’s and early ~ O ’ S , we observed in our clinic a considerable number of pubertal females who had normal genitalia a t birth, but, with the onset of puberty, developed marked acne and hirsutism accompanied by irregular menstruation, with advanced bone age in the younger patients. In many, there was also obesity, and, in some, clitoromegaly.The only definite pathological laboratory finding was an elevated urinary excretion of pregnanetriol (3-4 mg/24 hr) often accompanied by elevated 17-ketosteroids. In contrast to the large number of females with this disorder, there were only two such males showing precocious adrenarche and having high urinary pregnanetriol levels. These subjects were all diagnosed as having “postpubertal” congenital adrenal hyperplasia (CAH),’ i.e., 21-hydroxylase deficiency (21-OH deficiency), and some were treated with glucocorticoids for various lengths of time. At that time, it was not clear whether this metabolic derangement was of hereditary or acquired nature. Other investigators described in adults a nontypical form of 21-OH deficiency of late-onsetz4 characteristically found in female patients with normal genitalia and a normal onset of puberty, followed by the appearance of mild to severe hirsutism, irregular menstruation, and infertility. After Dupont et al.’ observed that CAH due to 21-OH deficiency behaved as an autosomal genetic trait in close linkage with HLA, we decided to investigate the linkage between HLA and the late-onset form of 21-OH deficiency. A collaborative study (carried out by teams from Petah Tikva and New York) of five Jewish Ashkenazic families in Israel, in which the index case had been diagnosed as having late-onset 2 1 -OH deficiency, revealed a relationship between the biochemical abnormality in this syndrome and the HLA haplotype of B14, DR1, BfS.6 This association was also reported for a number of Caucasian adults who were probably of non-Jewish Subsequently, we were able to investigate additional families of probands diagnosed to have this syndrome either prepubertally or during puberty Forthwith, we present a review of all the patients in Israel known by us to have late-onset 21 -OH deficiency, including all our published6s10 and unpublished cases, a patient reported from a nearby hospital,” and eight cases brought to our attention by colleagues in Haifa,” with particular emphasis on the HLA haplotypes and 21-OH deficiency in various ethnic groups.

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