Knud E. Petersen

Treatment of Cryptorchidism with Human Chorionic Gonadotropin or Gonadotropin Releasing Hormone

We have conducted a modified double-blind study on the effect of human chorionic gonadotropin (hCG), gonadotropin releasing hormone (GnRH) and placebo on bilateral and unilateral maldescended testes. One hundred and fifty-five boys with bilateral and 88 boys with unilateral cryptorchidism fulfilled the inclusion criteria and completed the treatment protocol. The boys were between 1 and 13 years of age. hCG was administered as intramuscular injections twice weekly for 3 weeks. GnRH and placebo were given intranasally. hCG was superior to GnRH and placebo in the treatment of bilateral maldescended testes (p = 0.0009). Both testes descended in 25% of the boys following treatment with hCG, and improvement in the position of the testes was obtained in a further 25% of the cases. hCG administration resulted in complete testicular descent in 14% of boys with unilateral cryptorchidism compared with 3 and 0% after placebo and GnRH, respectively (p = 0.07). The testis had moved to a more distal position in 46% of the boys treated with hCG. There was no significant difference between the treatment groups with regard to age or initial position of the testes. We conclude that a success rate of 25% justifies the use of hCG in the treatment of maldescended testes, whereas the study did not support a general use of GnRH administered intranasally.

Knemometry in the Assessment of Short-Term Linear Growth in a Population of Healthy School Children

Short-term lower leg length increments were monitored with weekly knemometry measurements during 3 months in 27 healthy school children aged 8-12 years. One year after the first visit the children were measured once again. The mean short term velocity of lower leg growth was 0.40 mm/week (SD 0.12 mm/week). The mean short-term and annual ratios between height velocity and lower leg growth velocity were identical (2.8). The relative variation between two observers was 0.08%. Knemometry is a suitable method for monitoring short-term linear growth in populations of children. Two trained observers may substitute for each other in group studies.

Hormonal treatment of cryptorchidism—hCG or GnRH—a multicentre study

In a modified, double‐blind controlled study, 163 prepubertal boys (aged 1.8–13.0 years) with bilateral and 94 (aged 1.5–13.1 years) with unilateral cryptorchidism were allocated to treatment with either human chorionic gonadotropin (im), gonadotrophin releasing hormone (intranasally) or placebo (intranasally). In individuals with the bilateral condition treatment with human chorionic gonadotrophin resulted in complete descent of both testes in 23% of patients. Treatment with human chorionic gonadotrophin in unilateral cryptorchidism resulted in complete descent in 19% of patients; all results were significantly better than those obtained with gonadotrophin releasing hormone or placebo. Linear and logistic regression analysis of the results obtained by treatment of bilateral disease showed that all treatments were more successful the younger the age of the boys. The data indicated that bilateral and unilateral cryptorchidism respond differently to hormonal treatment. We suggest that human chorionic gonadotrophin should be the first choice of treatment for prepubertal boys older than one year.

Gonadal Development and Growth in 46,XX and 46,XY Individuals with P450scc Deficiency (Congenital Lipoid Adrenal Hyperplasia)

We have investigated gonadal development and growth in 4 individuals (3 with 46,XY and 1 with 46,XX karyotype) with P450scc deficiency. One patient died at 2 months of age from adrenal insufficiency, while the remaining 3 individuals were healthy and developed normally (age at follow-up: 18, 10 and 8 years). In the surviving individuals, the diagnosis was established during the first 2-4 months of life by extensive endocrine studies of blood and urine. In the remaining patient, the diagnosis was made on the basis of karyotype (46,XY), anatomy of internal and external genitalia and adrenal pathology. Gonadectomy was performed in the 2 surviving 46,XY individuals at the age of 7 years, and histological examination showed normal testicular morphology but very few germ cells. Postmortem examination of the testes of the 2-month-old subject showed normal testicular histology, and quantitative analysis revealed a normal number of germ cells. Ultrasound of the 46,XX individual showed normal internal female genitalia including ovaries with follicles. The 3 surviving patients grew along the 75th (46,XY), the 90th (46,XY) and the 50th percentile (46,XX), respectively. The oldest girl experienced normal breast and pubic hair development after oral estrogen replacement and topical testosterone administration. The glucocorticoid and mineralocorticoid replacement was adjusted in accordance with repeated measurements of serum sodium and serum potassium, plasma renin concentration and blood pressure. No attempts were made to normalize serum ACTH. We conclude that prenatal testicular maturation and development of female internal genitalia may take place in the absence of normal steroid hormone production. Normal growth and development may be obtained in P450scc-deficient individuals with adequate hormone replacement.

X-LINKED CONGENITAL ADRENAL HYPOPLASIA A Study of Five Generations of a Greenlandic Family

ABSTRACT. In a Greenlandic family comprising 171 descendants in 5 generations, 11 boys had died with a clinical picture of adrenocortical insufficiency within three weeks of birth. Three treated male patients, who survived, were closely studied. The adrenal glands could not be identified by computed tomography. The clinical picture and biochemical studies were consistent with congenital adrenal hypoplasia. The pedigree indicates X‐linked recessive inheritance. The pubertal development was delayed in two patients aged 14 years. LHRH stimulation yielded a significant rise in LH and FSH in at least one of the patients, adrenal androgen values were very low. A family instruction programme has been set up.

Mode of action and relative value of imipramine and similar drugs in the treatment of nocturnal enuresis

SummaryThe present study was partly a clinical pharmacological analysis of the action of imipramine in nocturnal enuresis and partly an attempt to select children who would benefit most from this treatment. 61 fairly severe cases of nocturnal enuresis were studied as out-patients, divided by the criteria primary/secondary enuresis and with/without associated behavioural disturbances. The patients received imipramine, imipramine-N-oxide, emepronium, and a placebo in random sequence in a double-blind cross-over trial. There was no difference in effect between placebo and emepronium; after imipramine the frequency of enuresis fell to 58% of the figure during placebo treatment, i.e. 31% of the children became dry; imipramine-N-oxide reduced the number of wet nights only to 78% of the number on placebo, 18% of the children became dry. When the patients were classified into groups imipramine and imipramine-N-oxide were found to have had the greatest effect in cases of presumed psychogenic aetiology, a 65% reduction of the frequency of wet nights whilst taking the placebo. The most favourable results were in children with combined nocturnal and diurnal enuresis and in those with urinary frequency and imperative urgency. The effect was maintained during treatment for 3 months with the most suitable drug. The dose was 50 mg regardless of the body weight of the patient. There were no serious side effects. It was concluded that the psychopharmacological actions of imipramine and imipramine-N-oxide appear to be important in their effects on enuresis. Imipramine might have been the best drug because success may require the combination of antidepressant and anticholinergic activity. It was not possible to assess in detail its presumed effect on the level of sleep. Thus many children can be treated successfully and the final cure of enuresis may be hastened by breaking a vicious circle of psychological phenomena.

COMBINED TEST OF HYPOTHALAMIC‐PITUITARY FUNCTION IN GROWTH RETARDED CHILDREN TREATED WITH GROWTH HORMONE I. Secretion of Growth Hormone and Somatomedin before and after Treatment

Abstract. Kastrup, K. W., Andersen, H., Eskildsen, P. C., Jacobsen, B. B., Krabbe, S. and Petersen, K. E. (Childrens Hospital, Fuglebakken and Herlev Hospital, Copenhagen, Denmark). Combined test of hypothalamic—pituitary function in growth retarded children treated with growth hormone. Acta Paediatr Scand, Suppl 277: 9, 1979.—In 23 growth retarded children two consecutive insulin tolerance tests (ITT) were performed to establish a diagnosis of growth hormone (GH) deficiency. Nine children did not respond (GH peak value less than 8 mU/l), whereas 14 were classified as having partial GH deficiency (GH peak value less than 20 mU/l). All were treated for an average period of 40 months with human growth hormone (HGH). In a combined stimulation test at the end of the treatment period 9 children demonstrated a persistent GH deficiency, whereas a normal response was found in 14 of the previous partial GH deficient children. During treatment the monthly growth rate rose from 0.21 cm to 0.58 cm in the GH deficient children and from 0.31 cm to 0.70 cm in the partial deficient children, in most of whom spontaneous pubertal development occurred during treatment. Somatomedin (SM) values were decreased in the GH deficient children before and after treatment but increased to normal levels during treatment. Growth velocity in these children during treatment was correlated to SM values before treatment. In the partial GH deficient children SM values were subnormal before but normal after treatment. This supports the assumption that in some children with constitutional delay in puberty a reversible functional hypopituitarism exists, which is normalized after the onset of puberty, due to androgens sensitizing growth hormone releasing mechanisms. Treatment with HGH may induce increased growth velocity in some of these patients.

ENURESIS: An Attempt at Classification by Genesis

ABSTRACT. Andersen, O. Ortved and Petersen, K. E. (Childrens Hospital Fuglebakken, Copenhagen, Denmark). Enuresis. An attempt at classification hy genesis. Acta Paediatr Scand. 63: 512, 1974.—A series of 133 enuretic children aged 4–15 years is reported. Age variation. sex ratio. and distrihution of anamnestic data substantiate that the sign enuresis comprises an extremely heterogeneous group. The disease is therefore probably due to several causes. In an effort to elucidate in greater detail the causal relationship, int. al. with a view to its therapeutic significance. the material was divided into 4 groups: (A) Children with primary enuresis without behavioural disturbances. (R) Children with primary enuresis and behavioural disturbances

COMBINED TEST OF HYPOTHALAMIC-PITUITARY FUNCTION IN GROWTH-RETARDED CHILDREN TREATED WITH GROWTH HORMONE: II. Secretion of LH, FSH, TSH, Prolactin and ACTH

Abstract. P. C. Eskildsen, B. B. Jacobsen, K. W. Kastrup, S. Krabbe, P. E. Lebech and K. E. Petersen (The Childrens Hospital Fuglebakken, Herlev Hospital and Frederiksberg Hospital, Copenhagen, Denmark). Combined test of hypothalamic‐pituitary function in growth‐retarded children treated with growth hormone. Acta Paediatr Scand, Suppl. 277: 14, 1979.—A total number of 23 patients treated with human growth hormone were retested by use of a combined pituitary stimulation test. Plasma concentrations of GH, FSH, LH, TSH, T4, T3, prolactin (PRL), ACTH and cortisol were measured before and after stimulation with hypoglycemia, TRH and LHRH. The test was performed in patients with persistent GH deficiency (group A) and patients with transitory GH deficiency (group B). In group A a normal pubertal development was found in three patients, whereas in prepubertal subjects the FSH/LH responses were smaller than those of prepubertal patients in group B. Also plasma ACTH increase was less pronounced in group A patients than in group B. In contrast, the plasma TSH and PRL responses were more sustained in group A than in group B. The secretory pattern of TSH and PRL was comparable in the two groups of patients. Thus, in patients with persistent GH deficiency additional multiple disturbances of the hypothalamic‐pituitary function often appeared whereas in most patients with transitory GH deficiency the combined pituitary test was normal at the reinvestigation.

68. THE MODE OF ACTION OF IMPRAMINE AND RELATED DRUGS AND THEIR VALUE IN THE TREATMENT OF DIFFERENT CATEGORIES OF ENURESIS NOCTURNA

osteomyelitis. In this connection it should perhaps be emphasised that repeated roentgen examination is necessary, also of the lumbar spine if the patient has symptoms referable :o the hips and knees. If osteomyelitis is clearly suspected, treatment should not be suspended until a firm diagnosis has been obtained, but started immediately. We have obtained good results with conservative treatment, but occasionally biopsy should be done, especially to exclude malignant disease.