Søren Krabbe

Bone turnover in male puberty: A longitudinal study

SummaryIn a longitudinal study of male puberty, 18 boys were examined every 3 months for at least 2 years. Serum bone Gla protein (BGP), a biochemical marker of bone formation, was determined and related to changes in serum testosterone (T), serum alkaline phosphatase (AP), serum calcitonin, and bone mineral content (BMC). The data demonstrate a steep increase in serum T during puberty (P<0.001), with an almost concomitant increase in serum BGP (P<0.001) and serum AP (P<0.001). Ten months after the maximal increase in serum T, the increase in BMC reached its maximum, whereas there was no significant change in the serum calcitonin. The data demonstrate that the steep increase in serum T during puberty, directly or indirectly, produces acute stimulation of bone formation (estimated from BGP and AP) followed by a highly significant increase in the integrated measurement of bone apposition (BMC).

Longitudinal Study of Calcium Metabolism in Male Puberty

ABSTRACT. With the purpose of studying calcium metabolism at the growth spurt phase in puberty, bone mineral content (BMC) of the forearm, and serum concentrations of total alkaline phosphatase, phosphate, and calcium were determined in 36 boys every three months for about 2 years. BMC increased 35 % throughout the study age period of 10.6 to 14.6 years, with a maximal rate between 12.8 and 13.8 years. In relation to growth velocity BMC rose steepest during the 12 months around peak height velocity (PHV) (p<0.001) and showed a progressive increase from 3 months before the first pubic hair stage (PH2) to PH4 (p<0.001). Serum alkaline phosphatase increased by a total of 55 % throughout the age period with a diminished rate of increase from 13.5 to 14 years, around the PHV, and from PH3 to PH4.

Longitudinal study of calcium metabolism in male puberty. II. Relationship between mineralization and serum testosterone.

ABSTRACT. Height velocity, bone mineral content (BMC), serum concentrations of alkaline phosphatase (AP), testosterone, dehydroepiandrosterone (DHEA) and androstenedione (A‐dione) were determined as a part of a longitudinal study of calcium metabolism in normal male puberty. The time of maximal increase (Tm) in concentrations was calculated for 20 boys from a curve‐fitting analysis program. Highly significant correlations were found between Tm testosterone and Tm BMC (r=0.73, p<0.001); Tm AP and Tm BMC (r=0.68, p<0.001). The mean difference in time between Tm testosterone and Tm BMC was 4.7 months and between Tm AP and Tm testosterone 0.7 month. Our data indicate a very close relationship between testosterone, osteoblastic activity, and mineralization in normal male puberty, whereas the adrenal androgens do not seem to have a major influence on the mineralization at the male puberty growth spurt phase.

Testosterone Regulates the Haemoglobin Concentration in Male Puberty

ABSTRACT. In a longitudinal study of male puberty 20 boys were examined every three months for at least two years. Haemoglobin concentration was determined and related to changes in serum testosterone concentrations. The data show a steep increase in serum testosterone during puberty (p<0.001) followed with a five months delay, by a significant increase in haemoglobin concentration (p<0.001). It is concluded that the steep increase in serum testosterone during puberty produces an acute stimulation of erythropoietin leading to an increase in erythrocyte production and thereby to a detectable increase in haemoglobin concentration a few months thereafter. The present study supports the idea that the selection of the relevant reference range for haemoglobin in boys should depend on the state of physical developments as expressed by serum testosterone.

TREATMENT OF GIRLS WITH EXCESSIVE HEIGHT PREDICTION: Follow‐up of Forty Girls Treated with Intramuscular Estradiol and Progesterone

Abstract. Andersen, H., Brock Jacobsen, B., Kastrup, K. W., Krabbe, S., Peitersen, B., Petersen, K. E., Thamdrup, E. and Wichmann, R. (Endocrine Clinic, Childrens Hospital Fuglebakken, University of Copenhagen). Treatment of girls with excessive height prediction. Follow‐up of 40 girls treated with intramuscular estradiol and progesterone. Acta Pædiatr Scand, 69:293, 1980.—In a follow‐up study of 40 tall girls treated with intramuscular estradiol and progesterone, the final height, bone age maturation, side effects and acceptance of treatment were evaluated. The mean duration of treatment was 18 months. During treatment, mean height increase was 6.5 cm (height velocity 3.7 cm/year), which is nearly 50 % reduction of normal growth rate. The mean increase in bone age was 2.7 years (bone age velocity 1.8 years/year), which approximates twice the normal maturation rate. The mean reduction in final height was 5.0 cm as evaluated by the method of Bayley‐Pinneau (BP), 2.9 cm by the method of Tanner et al. (TW) and 3.0 cm by the method of Roche et al. (RWT). The reduction was greatest when treatment was started before menarche, according to all three prediction methods. When treatment was started after menarche the calculated height reduction was greatest according to the BP method. There was good agreement between the three prediction methods in girls with a bone age below 12 years before treatment. In girls with a bone age above 12 years the height reduction by the BP method was much greater than when measured by the other methods. Side effects evaluated at follow‐up were minimal and first menstruation occurred within 3 months (mean) after cessation of treatment. The number of pregnancies was estimated to be normal for age. All but three accepted the treatment. It is concluded that this type of treatment must be restricted to girls with severe psychological problems due to excessive height prognosis and selection for treatment must be based on an individualized evaluation.

157 VITAMIN D METABOLISM IN MALE PUBERTY

The increased growth and mineralization together with higher serum levels of 1.25(OH)2D3 in puberty compared to adult levels may indicate a regulatory role of sexhormones in vitamin D metabolism. Twenty pubertal boys, aged 11.0-12.6 years, were included in a 2-year study. Local bone mineral content (BMC), serum levels of testosterone (T), 25OHD3, 1.25(OH)2D3, 24.25(OH)2D3, and 25.26(OH)2D3 have been determined at 3 months intervals. A curve fitting analysis was performed to define the time (tm) at which T and BMC displayed the maximal increase. tm for T occurred about 5 months before tm for BMC. The seasonal variation in the vitamin D metabolites was taken into account by calculating the ratios to 25OHD3. No significant changes (Students t test for paired data) in neither 1.25(OH)2D3, 24.25(OH)2D3 nor 25.26(OH)2D3 could be found within a period of 1 year before to 1 year after tm for T and BMC.The data demonstrate that the changes in testosterone secretion during puberty seem to have no significant short-term influence on vitamin D metabolism.

Myelofibrosis and T3-thyreotoxicosis in a girl with McCune-Albright Syndrome

The pathogenesis of McCune-Albright Syndrome involving bone, skin, and endocrine organs remains unknown. The syndrome might be associated with dysfunctions of the hematopoietic system. A girl with severe polyostotic fibrous dysplasia and vaginal bleedings from 3 months of age is presented. The concentration of serum T3 was increased from the age of 13 months but se-T4 was normal. A T3-thyreotoxicosis was diagnosed at the age of 3½ years (no TSH response to TRH). Aged 3½ years she developed severe anemia, thrombocytopenia and splenomegalia. Bone marrow biopsy showed myelofibrosis. Following splenectomi the hemoglobin concentration increased and the platelet count was normalized. The patient was treated with medroxyprogesterone-acetat (MPA) during the first 3 years of life and with propylthiouracil (PTU) from the age of 3½ years. The myelofibrosis developed before unset of PTU, excluding any causal relationship. Nor the myelofibrosis seems to be associated with MPA since no such side effect of MPA is known, and the only patient previously reported with McCune-Albright syndrome and myelofibrosis was not treated this way.

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.

Combined test for hypothalamic/pituitary function in growth retarded children, treated with hurian growth hormone (HGH)

Among 23 growth retarded children, 9 showed a lack of growth hormone (GH) response and 14 an intermediary response to insulin tolerance test (ITT). After HGH treatment for 42 months (mean) all were retested with a combined pituitary stimulation test(ITT + TRH + LHRH) with estimation of GH, somatomedin (SM), ACTH, TSH, prolactin (PRL), LH and FSH.The 9 formerly GH-non responders showed a permanent GH deficiency (group I), while 10 of the previously GH-intermediary responders now had a normal GH response (group II) and 4 still had intermediary response (group III).In group I SM was low, the ACTH response subnormal, the TSH and PRL response prolonged and in prepubertal children deficient LH and FSH response was found, whereas these parameters with few exceptions all were normal in group II and III.This indicates: 1) Lack of GH response is a persistent condition often accompanied by hypothalamic dysfunction with abnormal secretion of other anterior pituitary hormones. 2) Intermediary GH response may be transient and associated with normal secretion of anterior pituitary hormones.