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Biomedical subjects

L Dunkel

Publications and source records attributed to L Dunkel.

At least 73 records · Page 4Linked to original sources
PubMed1986

Adrenocortical hyporesponsiveness after treatment with ACTH of infantile spasms.

The hypothalamic-pituitary-adrenocortical axis was studied in 10 infants before and during a six week period of treatment with adrenocorticotrophic hormone (ACTH) and three days and one and two weeks after its stopping. During the treatment 24 hour urinary cortisol excretion increased 20 to 350-fold (mean 100) above the basal value. Mean morning serum cortisol concentration, measured 24 hours after the preceding ACTH dose, did not increase. After the treatment mean urinary cortisol excretion was subnormal and mean morning serum cortisol concentration was below the pretreatment value. The mean serum cortisol response to a vasopressin test was reduced and shortened throughout the post-treatment observation period. The mean serum cortisol response to an intravenous ACTH test was not significantly different from the pretreatment response three days after treatment but was clearly reduced thereafter. At one and two weeks after treatment the basal concentrations of serum cortisol of one third of the patients and the post-ACTH concentrations of two thirds were subnormal. We conclude that in infants treatment with ACTH may cause adrenocortical hyporesponsiveness.

Adrenocorticotropic Hormone↗
PubMed1986

Transient increase in postnatal testicular activity is not revealed by longitudinal measurements of salivary testosterone.

Testicular steroidogenic activity in 22 boys was monitored longitudinally over the first 6 months of life using salivary T measurements. Samples were collected biweekly. The highest T levels, 130 +/- 12 pmol/liter (mean +/- SE, n = 22), were observed on days 2-10. The values then gradually declined to a mean of about 30 pmol/liter after month 4. No secondary peak in salivary T appeared, in contrast to the 1-3 month peak in serum T previously reported. The overall levels of T, reflected by the areas under the T concentration curves over the whole period, varied by a factor of three among the subjects studied. It is concluded that postnatal testicular activity may have its most marked physiologic effects immediately after birth rather than at the time of the 1-3-month peak of serum T. Furthermore, the overall exposure to androgen is individually greatly variable.

Age Factors↗
PubMed1986

Metoclopramide test in the diagnosis of isolated hypogonadotrophic hypogonadism.

The responses of serum prolactin (Prl) to metoclopramide and LH and FSH to GnRH were studied simultaneously in 9 boys with hypogonadotrophic hypogonadism (HH), 7 boys with constitutional delay of puberty (D) and 15 controls. Metoclopramide increased the Prl levels in all groups. The boys with HH had lower Prl responses than the controls, whereas the boys with D had similar responses to the controls. Of the 9 boys with HH, 8 had subnormal Prl responses, 3 subnormal LH and none subnormal FSH. A metoclopramide test is clearly more sensitive than a GnRH test in differentiating HH and D and appears to make the differentiation between these two conditions clearer.

Adolescent↗
PubMed1985

GnRH and HCG tests are both necessary in differential diagnosis of male delayed puberty.

The discriminative power of the gonadotropin releasing hormone test and the human chorionic gonadotropin (HCG) test in the diagnosis of gonadotropin deficiency was studied in 73 boys referred because of delayed pubertal development or suspicion of gonadotropin deficiency. Hypogonadotropic hypogonadism was confirmed by clinical follow-up in 21 of the boys and excluded in the others because of normal pubertal development. Those latter boys served as a reference group. The post-HCG serum testosterone level was subnormal in hypogonadotropic hypogonadism on 12 of 19 occasions (in the reference group on two of 46 occasions) and the post-gonadotropin releasing hormone serum luteinizing hormone level was subnormal on fourteen of 22 occasions (zero of 65). Four of the seven boys with hypogonadotropic hypogonadism who had normal post-HCG testosterone levels had subnormal peak luteinizing hormone levels. Of the remaining three boys, two had low basal testosterone levels. Combining the two tests therefore improved the diagnostic accuracy.

Adolescent↗
PubMed1985

Gonadotropin-releasing hormone test and human chorionic gonadotropin test in the diagnosis of gonadotropin deficiency in prepubertal boys.

The discriminatory power of a gonadotropin-releasing hormone test and a human chorionic gonadotropin test in diagnosing gonadotropin deficiency was studied in 23 prepubertal boys with hypogonadotropic hypogonadism (HH). The boys were originally referred because of genital hypoplasia, delayed sexual maturation, or suspicion of HH. The diagnosis of HH was established clinically, in most cases after follow-up of several years. The results were compared with those of a reference group consisting of 44 prepubertal boys with incomplete testicular descent. Post-hCG serum testosterone level was the most sensitive discriminating variable, and was subnormal in 11 of 12 boys with HH (in one of 16 in the reference group). Post-GnRH serum LH concentration was the second most sensitive, and was subnormal in 15 of 23 boys with HH (two of the reference group). Our data indicate that post-hCG testosterone levels are of greater value than post-GnRH gonadotropin levels in the diagnosis of HH in prepubertal boys.

Adolescent↗
PubMed1985

Abnormal prolactin secretion in prepubertal boys with hypogonadotrophic hypogonadism--possible involvement in regulation of testicular steroidogenesis.

The interrelationships of prolactin (Prl), gonadotrophins and testicular steroids were studied in prepuberty in 6 boys with isolated hypogonadotrophic hypogonadism (HH) and 7 boys with incomplete testicular descent (who served as controls). The boys with HH had higher basal serum levels of Prl (P less than 0.001) and LH (P less than 0.05) than the controls, but lower Prl (P less than 0.001) and LH (P less than 0.05) responses after metoclopramide + LHRH and lower testosterone responses after hCG. The peak responses of Prl after metoclopramide + LHRH and of testosterone after hCG correlated strongly in the patients as a whole (r = 0.87, P less than 0.001). These observations indicate that, as well as in the gonadotrophins, changes occur in HH in prepuberty in the synthesis and/or release of Prl. The findings also raise the possibility that Prl may play a role in the regulation of testosterone synthesis by the prepubertal testis.

Adolescent↗
PubMed1985

Kinetics of the steroidogenic response to single versus repeated doses of human chorionic gonadotropin in boys in prepuberty and early puberty.

There is accumulating evidence that in adult men excessive amounts of gonadotropins induce testicular desensitization to further gonadotropin stimulus. We evaluated the effects of endogenous gonadotropins and of repeated doses of exogenous human chorionic gonadotropin (hCG) on steroidogenesis by studying prepubertal and pubertal boys. The boys received either two intramuscular injections of hCG 4 days apart (protocol I) or four injections at 3- to 4-day-intervals (protocol II). In protocol I, serum testosterone, 17 alpha-hydroxyprogesterone, and estradiol were measured basally and for 6 days after the second injection, and in protocol II, before each injection and 4 days after the last injection. In the prepubertal-boys, serum testosterone increased from very low basal levels to 10.3 (protocol I) and 8.3 nmol/liter (protocol II). In protocol I the increase after the first injection was 64-fold and in protocol II there was an increase after each injection to a final level 144-fold of the basal. No significant changes were seen in the estradiol levels. In the pubertal boys at genital stage G2, the serum testosterone levels increased after the first two injections, but at genital stage G3, the levels increased only after the first injection. Maximal testosterone increases were 27- and 8-fold, respectively. In pubertal boys estradiol levels increased progressively throughout the stimulation. The major testosterone response ws seen after the first dose of hCG and repeated doses, at least in the pubertal boys, increased estradiol but not testosterone levels, thus causing an estrogen-mediated 17,20-lyase block. We therefore suggest that a single-dose hCG test deserves further evaluation for diagnostic use.

17-alpha-Hydroxyprogesterone↗
PubMed1985

Single versus repeated dose human chorionic gonadotropin stimulation in the differential diagnosis of hypogonadotropic hypogonadism.

The responses of serum testosterone (T), 17 alpha-hydroxyprogesterone, and 17 beta-estradiol (E2) to four im injections of hCG (5000 IU/1.7 m2) given on days 0, 4, 7, and 10 were studied in 10 prepubertal and 10 pubertal boys with hypogonadotropic hypogonadism (groups O and P, respectively). Serum was obtained before each injection and on day 14. The results were compared with those of controls, 16 prepubertal boys with incomplete testicular descent and 6 pubertal boys with constitutional delay of puberty. Serum T levels increased significantly in groups O and P to 2.0 and 4.6 nmol/liter, respectively, after the first injection, then progressively to 5.8 and 11.2 nmol/liter. Basal T levels of group O did not differ from those of the controls, but were subnormal for group P (P less than 0.001). Stimulated T levels were subnormal in both groups (P less than 0.01 and P less than 0.001), but repeated doses increased the difference from the control value only in group P. A difference in E2 response between patients and controls appeared in puberty; only the pubertal control boys had substantial increases in E2 (P less than 0.001). Our results show that the optimal protocol for a diagnostic hCG test in prepubertal boys is a single dose of hCG, with determination of T levels 4 days later. In puberty, if the basal T levels are inconclusive, repeated doses of hCG should be given with determination of both T and E2. These findings also suggest that the full inhibitory effect of E2 on T synthesis results from a pubertal maturation process, possibly induced by endogenous gonadotropins, which cannot be induced by two weeks of hCG stimulation in prepubertal boys or those with hypogonadotropic hypogonadism.

17-alpha-Hydroxyprogesterone↗
PubMed1985

Decrease in serum sex hormone binding globulin during human chorionic gonadotrophin stimulation in prepubertal boys.

Temporal relationships between steroidogenic and sex hormone binding globulin (SHBG) responses to hCG were studied in 27 prepubertal boys: 19 with incomplete testicular descent and 8 with hypogonadotrophic hypogonadism (HH). Nine of the boys with incomplete testicular descent were given a single im injection of hCG and blood samples were taken daily for 5 days. Six of them showed a slight decrease in SHBG concentration by day 5. All the other 18 boys were given four im injections of hCG on days 0, 4, 7 and 10. Blood was taken before each injection and on day 14. In the boys with incomplete testicular descent SHBG concentration decreased by day 14 (P less than 0.01). All the boys with HH had an impaired testosterone response to hCG, and SHBG levels did not decrease after hCG. In only 2 of these boys SHBG concentrations were greater than 10% below the basal by day 14. These boys, however, also had the highest testosterone responses of their group. Thus it appears that if testosterone increases in prepubertal boys, SHBG decreases.

Adolescent↗
PubMed1984

Hypergonadotropic hypogonadism in newborn males with primary testicular failure.

Four infants with genital ambiguity but with apparent testes were given a gonadotropin-releasing hormone (GnRH) test and a human chorionic gonadotropin (hCG) test at age 3-12 days. The results were compared with those from 16 newborn males (aged 2 to 6 days) with minor genital anomalies; 9 with unilateral and 3 with bilateral incomplete testicular descent, 2 with surgically insignificant glandular hypospadias and 2 with penis length less than (means-2 SD) for gestational age. Treatment with testosterone resulted in clear phallus growth in all four patients. All four patients had elevated basal luteinizing hormone (LH) concentrations as well as an exaggerated LH response to GnRH; three of them also had an exaggerated follicle stimulating hormone (FSH) response. Thus in all patients the etiology of genital ambiguity was considered to be testicular. The testosterone response to hCG was normal in two of the patients but impaired in the other two. The steroidogenic response did not show any specific enzyme defect. We conclude that newborn boys with Leydig cell failure are clearly hypergonadotropic, the GnRH test is a more sensitive indicator of Leydig cell failure neonatally than the hCG test and normal testes greatly inhibit the secretion of both LH and FSH during the first week of life.

Chorionic Gonadotropin↗
PubMed1984

Responsiveness of the pituitary-testicular axis to gonadotropin-releasing hormone and chorionic gonadotropin during the first week of life.

Qualitative changes are known to occur in testicular steroidogenesis at birth as the testosterone peak is reached without significant elevation of basal luteinizing hormone in the 2nd wk of life. This study was designed to evaluate testicular activity prior to these changes. Pituitary-testicular function was studied by measuring serum gonadotropins and steroids after stimulation by gonadotropin-releasing hormone (GnRH) (one intravenous injection) and human chorionic gonadotropin (hCG) (three intramuscular injections). The subjects had minor genital anomalies; their ages ranged from 2 to 6 days. All had a strong luteinizing hormone response and a weaker follicle-stimulating hormone response to GnRH stimulation. hCG induced significant increases in serum pregnenolone, 17-hydroxyprogesterone, androstenedione, testosterone, and dihydrotestosterone. Serum estradiol and estrone did not change, and progesterone decreased. The results clearly show that the pituitary-testicular axis is functional neonatally. The responsiveness of the testis to hCG supports the assumption that the postnatal decrease of testicular steroids is due to the simultaneous disappearance of hCG from the circulation. The neonatal testis does not show any estradiol response to hCG, which is a feature typical of prepuberty.

Chorionic Gonadotropin↗
PubMed1983

Steroidogenic response to a single injection of hCG in pre- and early pubertal cryptorchid boys.

The temporal response patterns of the concentrations of serum testosterone, oestradiol, 17-hydroxyprogesterone, pregnenolone, progesterone, androstenedione and 5 alpha-dihydrotestosterone to a single i.m. dose of hCG (5000 IU/1.7 m2) were investigated in prepubertal and early pubertal cryptorchid boys, and compared with the response patterns obtained earlier in adult men. The rapid response (at approximately 2-4 h) of serum testosterone was lacking in all boys, whereas the slow response at 2-5 days was constant. The relative response (the maximum stimulated concentration vs. the basal level) of serum testosterone was 70-fold in prepubertal boys and 6-fold at early puberty, compared with 2.4-fold in adult men. Serum oestradiol and 17-hydroxyprogesterone concentrations did not increase in the prepubertal boys, but did increase at early puberty, revealing a pattern similar to that observed in adult men. Hence, the prepubertal endocrine testis appears to be very responsive to hCG stimulation, and this responsiveness is rapidly lost with advancing puberty. The absolute increases, however, were smallest in prepubertal boys, perhaps reflecting the small potential Leydig cell mass. The responses of serum oestradiol and 17-hydroxyprogesterone to hCG appeared later during the boys' development than the response of serum testosterone. The relative testosterone response was maximal in the absence of an oestradiol response. It is suggested that testicular oestradiol production in response to LH/hCG appears in the course of puberty and results in intratesticular short-loop feed-back inhibition of androgen production. This is reflected by the appearance of a 17-hydroxyprogesterone response and by a decrease in relative testosterone response.

17-alpha-Hydroxyprogesterone↗
PubMed1983

Male pseudohermaphroditism due to deficiency of testicular 17-ketosteroid reductase.

A 12.9 year-old girl, genotypically 46, XY, and considered to have a testicular feminization syndrome, developed signs of virilization and gynaecomastia. Very high androstenedione concentrations (10-fold the mean of the reference interval in boys) in relation to low normal testosterone in peripheral serum indicated a 17-ketosteroid reductase deficiency. In addition to androstenedione, the basal peripheral levels of 17-hydroxyprogesterone and estrone were increased, being 5- and 3-fold the mean of the reference interval, respectively, whereas pregnenolone, progesterone, dehydroepiandrosterone, 5 alpha-dihydrotestosterone and estradiol concentrations were within pubertal stage-appropriate reference intervals. The total spermatic vein serum steroid concentrations were about 5-fold the mean in old men, and androstenedione, estrone and dehydroepiandrosterone were particularly elevated, whereas estradiol was normal and testosterone subnormal by a factor of 1/8. In the testis tissue, the concentration of androstenedione was extremely high, whereas that of testosterone tended to be relatively low. Our patient was obviously producing testicular steroids at her maximal rate, because no response to hCG administration was observed. This state was associated with a high-normal circulating LH concentration. The concentration of testicular LH/hCG receptors was only one-fifth of that seen in old men, which may have resulted from receptor down-regulation associated with a high degree of stimulation.

17-Hydroxysteroid Dehydrogenases↗
PubMedDate not supplied

Growth after treatment of solid tumours in childhood.

We examined 90 survivors of childhood solid tumours diagnosed in our hospital between 1960 and 1976. Their ages at the time of this study ranged from 12.2 to 41.5 years. Adult standing height was usually normal. However, final standing height was less than expected in the females, and sitting height was below the normal mean in the males. The males who had received both chemotherapy and radiation therapy to the spine had a greater decrement in sitting height, but we did not find any association between radiation therapy to the spine without chemotherapy and subsequent total growth of the spine as measured by sitting height. We conclude that these children generally do not experience any major growth disturbances.

Adolescent↗