Knud W. Kastrup

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.

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.

METABOLIC CONTROL IN CHILDREN WITH INSULIN DEPENDENT DIABETES MELLITUS ASSESSED BY HEMOGLOBIN A1c

ABSTRACT. The glycosylated hemoglobin component, hemoglobin A1c, was estimated in 92 children with insulin dependent diabetes mellitus by an iso‐electric focusing procedure during an observation period of 18 months. A significant correlation between hemoglobin A1c and the actual metabolic control according to clinical ratings was found. A seasonal variation in the concentration of the hemoglobin A1c was observed with the lowest level in the months of June and July consistent with an improved metabolic control in the diabetic children during the summer period. A direct relationship was found between metabolic control as assessed by hemoglobin A1c and retarded linear growth expressed as standard deviation score for height. Children with poorly controlled diabetes (intial hemoglobin A1c level above 12.5%) improved their carbohydrate tolerance shown by a significantly lower glycohemoglobin level at the end of the observation period. Consequently, hemoglobin A1c is particularly useful in the routine management of insulin dependent diabetic children in poor metabolic control. Frequent determinations are necessary since in these patients the glucose profiles are prone to great variations, which may lead to changes in the hemoglobin A1c concentration of about 1% in a week.

Predicting and Monitoring of Growth in Children with Short Stature during the First Year of Growth Hormone Treatment

ABSTRACT. Fifteen prepubertal short stature children (10 girls, 5 boys), mean age 9.6 years (range 5.2–12.7 years), with normal response to growth hormone stimulation tests (group A) or partial growth hormone deficiency (GHD) of idiopathic nature (group B) were included in a controlled longitudinal study for evaluation of predictive parameters for the long‐term growth response after administration of biosynthetic human growth hormone (B‐hGH). The average knee–heel length velocity for the first 3 months was significantly correlated to total body height velocity during the following 9 months (p<0.0008). By contrast, this association could not be found for height velocity during the same period. The increase in serum values of alkaline phosphatase and insulin‐like growth factor I (IGF‐1) during the first month of treatment was not significantly correlated to height velocity during the first year. During one year of treatment with B‐hGH the mean height velocity for groups A and B increased from 4.4 cm/year (range 2.5–6.5) to 7.6 cm/year (range 4.7–10.6). Bone age advanced by 1.08 t0.60 per chronological year. The ratio between total height and knee‐heel length prior to treatment was 3.34 ± 0.10 and after one year 3.33 ± 0.10, suggesting a proportional linear growth. An inverse relationship was observed between the ratio and chronological age. In conclusion, early knee–heel measurement may be a useful non‐invasive predictor of long‐term linear growth in children during treatment with growth hormone, and the ratio of total height to lower leg length may be of importance in detecting dysproportional growth.

Oestrogen Therapy in Turner's Syndrome

Oestradiol stimulates growth and development in Turners syndrome. Previous results with low‐dose oestradiol on growth rate are reviewed. The effect of oestradiol in low concentrations on somatomedin generation, GH secretion and directly on osseous tissue, may explain the growth response. The observations presented here of 35 girls treated with 17‐β‐oestradiol demonstrated a definite increase in growth rate in the first year of therapy. Bone maturation was accelerated, but a reduction in final height was not found.

The impact of idiopathic childhood‐onset growth hormone deficiency (GHD) on bone mass in subjects without adult GHD

objective  Despite seemingly adequate growth hormone (GH) treatment during childhood, children with GH deficiency (GHD) have reduced bone mineral density (BMD) at final height. The aim was to evaluate BMD and bone mineral content (BMC) in adults treated for idiopathic childhood‐onset (CO) GHD, 18 years after stopping GH treatment.

PLASMA ADRENALINE RESPONSE IN KETOTIC HYPOGLYCEMIA. INVESTIGATIONS IN PATIENTS WITH OR WITHOUT ADRENAL CALCIFICATIONS

In some patients with ketotic hypoglycemia a reduced urinary output of catecholamines has been reported. Emplying a double isotope derivative technique (Clin.Sci.1973, 45:163) plasma adrenaline and noradrenaline were determined in six children with ketotic hypoglycemia. One of the patients had extensive bilateral adrenal calcifications. Adrenal cortical insufficiency was excluded.The plasma adrenaline values (mean value, ng/ml) before - during hypoglycemia were: (A) in patients without adrenal calcifications 0.05−0.10, (B) in one patient with adrenal calcification 0.01−0.04, (c) in healthy children (n=3) 0.22–1.33, (D) in healthy adults (n=5) 0.09−0.69. The plasma noradrenaline changed insignificantly in patients and controls.Estimated from blood glucose level during hypoglycemia the plasma adrenaline was only four per cent of the expected values.These preliminary results seem to indicate that in patients with ketotic hypoglycemia the immediate plasma adrenaline response during hypoglycemia is greatly reduced in patients with as well as without adrenal calcifications.

PLASMA ADRENALIN IN A CHILD WITH KETOTIC HYPOGLYCEMIA AND CALCIFICATIONS OF THE SUPRARENAL GLANDS

ABSTRACT: Jacobsen, B. B., Kastrup, K. W. and Christensen, N. J. (Childrens Hospital Fuglebakken, Copenhagen, and 2nd Clinic of Internal Medicine, Kommunehospitalet, Aarhus, Denmark). Plasma adrenalin in a child with ketotic hypoglycemia and calcifications of the suprarenal glands. Acta Paediatr Scand, 64:559, 1975.–Urinary excretion of adrenalin has been reported to be reduced during insulin‐induced hypoglycemia in a significant proportion of children having ketotic hypoglycemia. By employing a sensitive double‐isotope derivative technique, plasma adrenalin and plasma noradrenalin were determined in a boy 6 years 9 months old who had had ketotic hypoglycemia with intermittent hypoglycemic symptoms from the age of 10 months. Bilateral calcifications of the suprarenal glands were present. The adrenocortical function was normal. The plasma adrenalin response to hypoglycemia were practically absent, being only 4 % of the value obtained in healthy children. The results were related to previous findings of a low plasma adrenalin response in patients with ketotic hypoglycemia without adrenal calcifications and support the assumption that ketotic hypoglycemia is associated with hypoadrenalinemia.

Evaluation of the combined test of hypothalamio-pituitary function

In 47 children with disturbances in growth and/or puberty a test was performed with simultanous injection of insulin (0.1 U/kg), TRH (3-5 μg/kg) and LHRH (100 μg). The mean bone age retardation was 39 months and the mean standard deviation score - 2.8 SD. In 11 children a Growth Hormone deficiency (GHD) was demonstrated: GH peak value 3.34 mU/1 and Somatomedin 0.63 U/ml (mean) - 5 of these were patients with intracranial tumours. The other 36 children had GH peak value 20.44 mU/1 and Somatomedin 1.27 U/ml (mean). ACTH response was subnormal in 15/32. In these 15 patients 13 had GHD or subnormal GH response. In the 15 children in the highest age group (girls > 12 years, boys > 14 years) a normal response to LHRH was found, regardless of pubertal development or coexisting GHD. In the 24 children in the youngest age group was found a definite abnormal response in 4, two of which had GHD. TSH response was low in 6/45, three of which were hypothyroid and had GHD. Defect of 3 pituitary axes were found in 5 patients, 3 of these had intraoranial tumour. In conclusion: The combined test of pituitary function seems to be of limited value. The essential information is acquired by the hypoglycemia to establish GHD and ACTH deficiency (these 2 are often coexisting). Stimulation with LHRH is valuable in older children without signs of puberty and may be of prognostic value in young prepubertal children with GHD. Stimulation with TRH does not give any supplemental information.