Endocrine disorders: diabetes mellitus, congenital hypothyroidism, and congenital adrenal hyperplasia.
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Adolescent↗
Biomedical subjects
D B Grant
Publications and source records attributed to D B Grant.
Gonadal function after testicular radiation for acute lymphoblastic leukaemia.
Pubertal maturation, growth, and gonadal function were assessed in 13 boys with acute lymphoblastic leukaemia who had received direct testicular irradiation three to nine years earlier as treatment for testicular relapse or prophylaxis against this complication. Six boys had reached Tanner stage III-V puberty, five of whom had normal growth velocities and bone ages equivalent to chronological age. One boy exhibited maturational arrest on entering stage IV. The remaining seven children (54%) showed evidence of complete pubertal delay or arrested development in stage II, with absence of the pubertal growth spurt and often with delayed bone age. Basal gonadotrophins were abnormally high in all 13 boys, and those with delayed puberty had prepubertal concentrations of testosterone. Testicular irradiation given before puberty causes permanent Leydig cell damage in a high proportion of subjects, necessitating testosterone supplementation. The extent of damage may be related to the age at which radiation is delivered.
Adolescent↗
Diabetes insipidus and occult intracranial tumours.
We describe four patients with intracranial tumours who presented with diabetes insipidus and subsequently developed an evolving anterior pituitary endocrinopathy. The delay in imaging the tumours varied between 2.1 and 11.2 years (mean 5.4 years).
Brain Neoplasms↗
Deletion of the steroid 21-hydroxylase and complement C4 genes in congenital adrenal hyperplasia.
DNA was analysed from 20 patients with congenital adrenal hyperplasia due to cytochrome P-450 steroid 21-hydroxylase deficiency. Using probes recognising sequences in both the 21-hydroxylase gene and the adjacent fourth component of complement (C4), one patient was found to have a homozygous deletion of DNA which encompassed the C4B and 21-hydroxylase B genes. Evidence is presented for this deletion arising by recombination between homologous regions of 21-hydroxylase A and B. Seven patients appeared to be heterozygous for the same deletion, but no detectable alteration in the 21-hydroxylase gene could be demonstrated in others.
Adrenal Hyperplasia, Congenital↗
Long-term treatment with diazoxide in childhood hyperinsulinism.
This paper reviews the outcome in 12 children with hyperinsulinaemic hypoglycaemia who first developed symptoms between the ages of 2 and 8 months and who were treated with diazoxide (5-20 mg/kg/day) for 2-13 years. Two cases required subtotal pancreatectomy at the ages of 5 and 10 years because of recurrent hypoglycaemia and one girl with severe retardation died at the age of 6 years while still on diazoxide therapy. Two patients aged 3.5 and 9 years are still on treatment and in 7 cases diazoxide was discontinued between the ages of 2.5 and 14 years, indicating that spontaneous remission can be expected in a high proportion of children with post-neonatal hyperinsulinaemic hypoglycaemia. Of the 9 children who started diazoxide within 3 months of the onset of symptoms, 5 are of normal intelligence and 4 are moderately retarded (IQs 63-71). In 3 children diazoxide was started 8 months to 3 years after the onset of symptoms; two are retarded (IQs 60-70) and the third was severely retarded and died aged 6 years.
Diazoxide↗
Virilizing adrenocortical tumors in childhood.
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Adenoma↗
Lack of thirst, osmoreceptor dysfunction, early puberty and abnormally aggressive behaviour in two boys.
Two unrelated boys (C.C. 13 years; J.W. 18 years) presenting with early puberty and episodes of aggressive behaviour were found to have hypernatraemia and hypodipsia. Plasma vasopressin (AVP) levels were inappropriately low in relation to plasma osmolality, but the patients did not have diabetes insipidus since 24 h urinary volumes were less than 1 litre and the maximal urinary osmolality was 1232 in C.C. and 950 in J.W. Plasma renin activity was elevated (greater than 2000 mg AI/1/h) although aldosterone concentrations were normal. Excretion of a water load (20 ml/kg) was delayed, but plasma renin and aldosterone fell with increased naturesis. An infusion of 0.85 mol/l saline produced a rise in AVP in C.C. but not in J.W. Insulin and hypotension resulted in the release of AVP in both boys suggesting a selective defect of osmoreceptor function. Hyperprolactinaemia and an exaggerated PRL response to TRH were also noted but no intracranial lesion was demonstrable on CT scan. These boys appear to have a hypothalamic syndrome with early puberty, hyperprolactinaemia, hypodipsia and osmoreceptor dysfunction which may be associated with aggressive behaviour.
Adolescent↗
Management of pituitary gigantism. The role of bromocriptine and radiotherapy.
True gigantism with overproduction of growth hormone (GH) and prolactin (PRL) was diagnosed in two boys, aged 13 years (case I) and 7 1/2 years (case II). Both had shown increased growth rates since early childhood (from 4 years and 1 1/2 years, respectively), but no skeletal acromegalic features were noted. However, both showed increased sweating and both had advanced pubic hair relative to testis volume. No other pituitary dysfunction was recorded. Case I underwent transsphenoidal surgery with only incomplete and temporary suppression of GH and PRL levels. However, in both patients bromocriptine administration promptly suppressed PRL levels. Following combined irradiation and bromocriptine treatment, GH also gradually normalized over a period of 2 years. Both boys are still on treatment, and both showed an increase in plasma GH concentrations when the dose of bromocriptine was reduced or discontinued, indicating that even 3 1/2-5 years after irradiation therapy (and during continuous treatment with bromocriptine) the disease was controlled but not cured. However, in these two boys bromocriptine has proved effective in controlling the PRL/GH oversecretion.
Body Height↗
Isosexual precocious puberty in girls.
This paper reviews the clinical findings, pituitary gonadotrophin reserve and plasma oestradiol, neurological findings and pelvic ultrasound appearance in 47 girls with precocious puberty starting before the age of 7 years. Of the 39 girls who had air encephalograms or cranial CT scans, 19 showed intracranial abnormalities (hamartomas 11; hydrocephalus 5; optic glioma 2; arachnoid cyst 1). There was no significant difference in the peak serum luteinizing hormone and follicle-stimulating hormone responses to intravenous gonadotrophin stimulating hormone in girls with and without intracranial lesions. Pelvic ultrasound examination showed development of the ovaries, uterus, and vagina similar to that seen in normal puberty. Treatment with cyproterone acetate (50-100 mg/day) in 26 girls resulted in arrest of breast development and suppression of menstruation, but a definite effect on growth was not documented.
Brain Diseases↗
Clinical presentation, growth, and pubertal development in Addison's disease.
The clinical course of eight boys and six girls with Addison's disease has been reviewed. Adrenal antibodies were found in five boys and five girls, and four children showed clinical evidence of other autoimmune disease (hypoparathyroidism (three); diabetes (one)). The presentation was insidious in 12 children but acute in two. On treatment, linear growth was normal and, with the exception of one girl with theca cell antibodies, pubertal development proceeded normally in the older patients.
Addison Disease↗
Growth curve for girls with Turner syndrome.
A growth chart for girls with Turner syndrome has been prepared using data from four published series of European patients, and evaluated using retrospective data on the heights of girls with Turner syndrome seen at this hospital. The results indicate that calculation of height standard deviation score from this chart allows a reasonable prediction of adult stature in any patient with Turner syndrome. In addition, the results indicate that while oestrogen treatment causes an initial acceleration of growth, it has no significant effect on adult height.
Adolescent↗
Transient sexual precocity and ovarian cysts.
Nine girls presenting under the age of 7 years with unsustained sexual precocity are described. Large ovarian cysts were detected by ultrasound in three and laparotomy in one. In two girls the symptoms resolved after surgical removal of the cyst; the other seven had spontaneous remission of symptoms, but in two of these transient breast development and bleeding recurred: further ovarian cyst formation was found in one of these patients. Endocrine studies performed before resolution of the cysts showed raised plasma oestradiol concentrations (64 to 440 pmol/l) in three girls and no appreciable rise in plasma luteinising hormone after gonadotrophin releasing hormone stimulation in two. We conclude that ovarian cyst formation with spontaneous resolution may cause transient sexual precocity in girls, and that ultrasound examination is an effective means of diagnosing and following these patients.
Breast↗
Neonatal screening with emphasis on congenital hypothyroidism. Sir William Power memorial lecture.
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Congenital Hypothyroidism↗
Steroid biochemistry of virilising adrenal tumours in childhood.
Steroid excretion in urine of 12 infants with virilising adrenal tumours has been determined using gas chromatography. In six children, (Group A, five female, one male) aged 2.8-5.3 years, very high urinary excretions of 17 oxosteroids (greater than 40 mumol/24 h) were largely accounted for by dehydroepiandrosterone (DHA). In one of the girls, the pattern of steroids excreted in urine was similar to that of newborn infants, with high excretions of 16-oxygenated derivatives of DHA. The histology of this tumour suggested a neoplasia of fetal-type adrenocortical cells. Very large tumours were found in three of the infants, two of whom have died and one has multiple metastases. From the other three children, small, well-encapsulated adenomas were successfully removed. Six children (Group B), had moderately elevated 17-oxosteroid excretions (8-17 mumol/24 h). In five of these cases (four female, one male) aged 0.8-5 years, 11 beta-hydroxyandrosterone was a consistently prominent urinary steroid. In one boy, aged 7.7 years, 17-oxosteroid excretion was 15 mumol/24 h and the major steroids in urine were metabolites of pregnenolone. These six children have survived with no clinical evidence of recurrent tumour. The in vivo functional activities of the tumours can be deduced from the different profiles of steroids in urine. These have revealed heterogeneous patterns of steroid biosynthesis.
17-Ketosteroids↗
Neonatal hyperparathyroidism.
We describe a girl with congenital hyperparathyroidism who presented soon after birth with respiratory distress, hypotonia, feeding difficulties, and bone deformities. Hypercalcaemia, hypophosphataemia, and raised alkaline phosphatase were present and plasma parathyroid hormone levels measured by radioassay and bioassay were raised. X-rays showed gross demineralisation with metaphyseal fractures, erosions, and sub-periostal reaction along the bones. Following surgical removal of four hyperplastic parathyroid glands and subsequent maintainance therapy with 1-alpha-hydroxycholecalciferol there has been virtually complete reversal of her bone abnormalities.
Female↗
Familial hypocalciuric hypercalcaemia: association with neonatal primary hyperparathyroidism, and possible linkage with HLA haplotype.
A kindred is described, six members of which fulfilled criteria for the syndrome of familial hypocalciuric hypercalcaemia (FHH). The majority of these individuals were asymptomatic: their hypercalcaemia was revealed by biochemical screening after parathyroid surgery had failed to diminish the elevated serum calcium concentration of the index case. In contrast to those members of the family diagnosed as adults, the daughter subsequently born to the index case included in her expression of FHH clinical features of severe neonatal primary hyperparathyroidism. Four hyperplastic parathyroid glands were excised, and following surgical intervention the baby improved clinically and accelerated the healing of her skeletal lesions. Her case suggests that an association does exist between FHH and neonatal primary hyperparathyroidism. Of the ten individuals at risk, inheritance of hypocalciuric hypercalcaemia was paralleled in eight cases by inheritance of the HLA haplotype All BW55 CW3 DR4. Such possible linkage has not previously been reported.
Adult↗
Body proportions in precocious puberty.
Sitting height (SH) and sub-ischial leg length (SLL) were measured in 10 boys and 16 girls with precocious puberty; the patients were aged from 1.5 to 13.4 years at the time. Standard deviation scores (SDS) calculated for chronological age and bone age showed higher scores for SH than for SLL in all but two patients, both girls: the differences between the SDS for SH and SLL were more marked in the boys. The findings indicate that growth of the trunk is usually greater than growth of the legs in precocious puberty, particularly in boys.
Age Determination by Skeleton↗
Precocious puberty: a follow up study.
Follow up of women previously seen between 1951 and 1971 with precocious puberty showed that most had normal menstrual cycles and that fertility was generally normal in those with 'constitutional' precocious puberty. Three patients, however, with the McCune-Albright syndrome had not yet proved to be fertile.
Adolescent↗