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Biomedical subjects

D B Grant

Publications and source records attributed to D B Grant.

At least 73 records · Page 4Linked to original sources
PubMed1989

Bilateral testicular tumours in congenital adrenal hyperplasia: a continuing diagnostic and therapeutic dilemma.

Bilateral testicular tumours are a rare but well described complication of congenital adrenal hyperplasia (CAH). It can be extremely difficult to distinguish histologically between Leydig cell tumours and adrenocortical rest hyperplasia which may lead in some cases to unnecessary orchidectomy in young men. A 26-year-old male in whom CAH had been diagnosed neonatally, was referred for further investigation of a craggy mass in the left testis. Six months earlier, right orchidectomy had been performed after presentation with bilateral enlarged, hard testes and azoospermia. The tumour was interpreted to be a malignant interstitial cell tumour of the testis. Our investigations revealed that his CAH was inadequately controlled and that the hormonal secretion from the remaining left testicular mass was ACTH dependent. Percutaneous venous sampling revealed high concentrations of cortisol and other adrenocortical hormones coming from the gonadal vein. Dexamethasone suppressed these adrenal hormones and reduced the size and softened the consistency of the testicular mass. Total disappearance of the mass was achieved by using dexamethasone, given in a reverse circadian rhythm regimen. Spermatogenesis returned and the patient's wife became pregnant after 6 months; she gave birth to a normal male infant. To our knowledge, this is the first time in this clinical setting that fertility has been achieved. This case highlights the need for both a functional and histological assessment of such 'tumours' in CAH prior to orchidectomy.

Adrenal Hyperplasia, Congenital↗
PubMed1989

Ectopic thyroid: residual function after withdrawal of treatment in infancy and later childhood.

Plasma thyroxine (T4) and thyrotrophin (TSH) were estimated in 34 children identified by neonatal hypothyroid screening and subsequently found to have ectopic thyroid tissue on isotope scan. Before treatment plasma T4 ranged from 8-143 nmol/l and TSH from 39-1,230 mU/l. After one week off treatment during their second year, repeat T4 in 26 of these cases showed a significant correlation with the pre-treatment values (r = 0.57). However, only 3 of the 5 children with pre-treatment T4 levels over 100 nmol/l at diagnosis had normal T4 values when retested. Similarly, when 10 children with pre-treatment T4 values over 65 nmol/l were retested off treatment at the ages of 5.8-8.2 years, only 4 had plasma T4 levels in the normal range. These results illustrate the wide range of thyroid function which can occur in children with ectopic thyroid tissue and indicate that some continue to have near-normal thyroid function for considerable periods. However, pre-treatment T4 results do not allow accurate identification of these latter cases.

Child↗
PubMed1989

Absence of Y specific DNA sequences in two siblings with 46XX hermaphroditism.

We report two siblings with 46XX hermaphroditism in whom we were unable to show the presence of Y specific DNA sequences using the DNA probes Y-190, GMGY-7, pHY2.1, pDP34, and 27a. We conclude that an autosomal or X chromosome gene mutation is the most likely mechanism of inheritance in this family with 46XX hermaphroditism.

DNA↗
PubMed1988

Survey of neonatal screening for primary hypothyroidism in England, Wales, and Northern Ireland 1982-4.

National screening for congenital hypothyroidism was established in the United Kingdom in 1982. During 1982-4, 488 infants with primary congenital hypothyroidism were detected by the 25 regional screening laboratories in England, Wales, and Northern Ireland. In addition, one infant had signs of cretinism at birth and was investigated before the screening test was done and four infants were known to have been missed by the screening programme; among these four infants the initial thyroid stimulating hormone concentrations were normal in two with inherited defects of synthesis of thyroxine, not measured in one, and false negative in one. The overall incidence of primary hypothyroidism was 1:3937 births (boys 1:6640, girls 1:2756). The incidence seemed to be reduced in infants born to black mothers (two cases only) and increased in those born to Asian mothers (61 cases). Congenital anomalies other than those of the thyroid glands were reported in 36 children (7%), and 15 (3%) died from various causes before the age of 4. Infants who were considered to show unequivocal evidence of hypothyroidism started treatment at a median age of 17 days (5th and 95th centiles 10 and 42 days) compared with a median age of 14 days (5th and 95th centiles 9 and 21 days) for infants with classic phenylketonuria also detected by national screening.

Asian People↗
PubMed1988

Pancreatic exocrine and endocrine function after subtotal pancreatectomy for nesidioblastosis.

Pancreatic exocrine and endocrine function was assessed in seven patients 1 to 2 years after 95% pancreatectomy (group A) and three patients 9 to 11 years after 75% pancreatectomy (group B). In all cases surgery was undertaken for the treatment of hyperinsulinism and the histologic diagnosis was nesidioblastosis. The activities of pancreatic enzymes and bicarbonate concentrations were generally normal in group B, but were reduced in approximately half the children in group A. One child in group A had significant exocrine failure and poor weight gain. Blood glucose levels and fasting insulin levels were normal during a standard glucose tolerance test in all of the group B patients. One had a low fasting blood glucose level. In the group A patients three had low fasting glucose levels and one a frankly diabetic glucose tolerance test. C peptide and insulin levels were comparable but inappropriate insulin levels were noted in one patient, suggesting that the control of glucose-stimulated insulin release may remain abnormal. The results suggest that pancreatic function is not seriously impaired in the majority of patients 1 to 2 years after 95% pancreatectomy and that it is comparable to that noted in 75% pancreatectomy patients followed over a longer period of time.

Amylases↗
PubMed1988

Gonadotrophin, growth hormone and prolactin secretion in children with primary hypothyroidism.

We have studied eight children with primary hypothyroidism (6F, 2M) aged 6.7 to 14.2 years. The girls were prepubertal and the boys had early normal pubertal development. Overnight secretion of LH, FSH, TSH, PRL and GH, and ovarian ultrasound morphology were assessed before and up to 9 months after commencing thyroxine treatment. Serum FSH concentrations in all the girls were increased above LH levels and severe hypothyroidism was associated with reduced GH secretion. These abnormalities reversed with thyroxine treatment. The boys had less severe hypothyroidism and did not demonstrate abnormal gonadotropin or GH secretion. We conclude that primary hypothyroidism in childhood is associated with widespread disturbance of pituitary function, including increased FSH secretion often without signs of early sexual maturation.

Adolescent↗
PubMed1988

A reappraisal of the CHARGE association.

We describe 14 boys and six girls, including monozygotic twins, with the CHARGE association. All of the children had at least four of the seven major features included in the mnemonic CHARGE and all had ear anomalies or deafness or both and either coloboma or choanal atresia or both. All the boys had evidence of hypogonadism. A characteristic facial appearance (unusually shaped ears, unilateral facial palsy, square face, malar flattening, pinched nostrils) was observed in many of our cases. The aetiology remains unknown. All our cases are sporadic.

Adolescent↗
PubMed1988

Familial olivopontocerebellar atrophy with neonatal onset: a recessively inherited syndrome with systemic and biochemical abnormalities.

Clinical and pathological findings are reported in two siblings who presented in the neonatal period with failure to thrive, hypotonia, pericardial effusions, limitation of joint movement, retinal dystrophy and loss of visual function. Additional features were biochemical evidence of purine overproduction and liver dysfunction. Post mortem, the neuropathological findings in both children were typical of olivopontocerebellar atrophy. It is suggested that the cases represent a recessively inherited inborn error of metabolism.

Brain↗
PubMed1988

Precocious or early puberty and growth failure in girls treated for acute lymphoblastic leukaemia.

We have studied 41 children with early or precocious puberty who have been treated for acute lymphoblastic leukaemia with prophylactic cranial irradiation (1,800-2,400 cGy) accompanied by intrathecal methotrexate and systemic chemotherapy. Mean age at radiotherapy was 3.9 years (range 1.7-7.7) in the girls and 4.8 years (range 2.6-7.8) in the boys. Mean age at the onset of puberty was 8.6 years (range 6.7-9.7) in the girls and 9.3 years (range 7.8-10.3) in the boys. Of the 41 children with early puberty (greater than 1.4 SD from the mean) 36 were females and 5 were males. 21 of the 36 girls had an absent or inadequate growth acceleration of puberty. 7 of 12 girls who had a pharmacological test of growth hormone (GH) secretion had GH insufficiency (peak level less than 20 mU/l). Early or precocious puberty combined with GH insufficiency may produce severe growth failure and we have used a treatment regimen of a gonadotrophin-releasing hormone analogue, in order to reduce the rate of epiphyseal maturation, combined with biosynthetic GH to increase or sustain growth rate. We have treated 4 girls in this manner. During a mean treatment period of 0.86 years, height SDS for bone age rose from a mean of -1.06 to -0.59. Longer treatment periods will be required to assess the effect on final height.

Child↗
PubMed1988

A short water deprivation test incorporating urinary arginine vasopressin estimations for the investigation of posterior pituitary function in children.

The value of a 7-h water deprivation test incorporating urinary osmolality and urinary arginine vasopressin (AVP) measurements was investigated in 20 children with suspected anterior or posterior pituitary dysfunction (group A) and 11 presenting with polyuria and polydipsia (group B). A control group of 16 healthy children was also studied. Urinary osmolalities in the control subjects after 7 h of water deprivation were 827-1136 mosmol/kg and urinary AVP 114-320 pmol/l. Of the group A patients, 5 had symptomatic diabetes insipidus with urinary osmolalities less than 300 mosmol/kg, and urinary AVP concentrations of less than 10 pmol/l, and 5 had normal urinary concentrating ability. The other 10 patients had varying degrees of partial diabetes insipidus (urinary AVP 6-53 pmol/l) although in 3 urinary concentrating ability was well maintained (osmolality 650-747 mosmol/kg). In group B, a diagnosis of compulsive water drinking was made in 9 patients, 1 had nephrogenic diabetes insipidus (urinary osmolality 68 mosmol/kg, AVP 782 pmol/l), and the final patient had transient diabetes insipidus. The test described was easy to perform and well tolerated even in young children. Using this test alone, it was possible to identify patients with partial defects of posterior pituitary function even when urinary concentrating ability was maintained, as well as those with complete cranial diabetes insipidus, nephrogenic diabetes insipidus, and compulsive water drinking.

Adolescent↗
PubMed1988

New concepts of the growth spurt of puberty.

The timing of the growth spurt of normal children does not affect their final height attainment. Growth rate during the growth acceleration of puberty correlates with changes in GH, and not sex steroid, secretion. GH secretion during puberty is pulse amplitude, and not frequency, modulated. In both central precocious puberty and normal puberty suppressed with a GnRH analogue, the rate of epiphyseal maturation is decreased as are GH pulse amplitude and growth, but with no influence on final height.

Adolescent↗
PubMed1988

Somatomedin-C/IGF-I measured by radioimmunoassay and somatomedin bioactivity in adolescents with insulin dependent diabetes compared with puberty matched controls.

Plasma concentrations of insulin like growth factor-I in the adolescent diabetic remain controversial. IGF-I levels were determined by radioimmunoassay in 81 insulin dependent adolescent diabetics (49 boys and 32 girls) and compared with 75 puberty stage matched normal controls. Plasma somatomedin bioactivity was determined by cartilage bioassay in a smaller group of 10 normal and 25 diabetic subjects. IGF-I concentrations increased in the normals during puberty and there were no observed differences between the sexes. (P1, 0.77 +/- 0.08; P2, 1.33 +/- 0.2; P3, 1.59 +/- 0.16; P4, 1.76 +/- 0.16; P5, 2.24 +/- 0.09). IGF-I also increased in the diabetics reaching a peak level at stage three in both girls and boys. Combining the data from both sexes the diabetics had significantly lower levels of IGF-I compared to controls at stages; (P1, 0.67 +/- 0.05, ns. P2, 0.92 +/- 0.1, p less than 0.05; P3, 1.16 +/- 0.09, p less than 0.01; P4, 0.73 +/- 0.11, p less than 0.001; P5, 1.13 +/- 0.11, p less than 0.001). Plasma somatomedin bioactivity was elevated in the normals but inhibitory responses were observed in all but two of the diabetic subjects, highlighting the presence of inhibitory factors in diabetic plasma. HbA1C levels rose in the diabetics during puberty, however using covariance analysis there was no relationship between IGF-I and HbA1C when changes relating to puberty were excluded. The importance of controlling for pubertal stage as opposed to age is noted when assessing IGF-I status in the diabetic adolescent.

Adolescent↗
PubMed1987

The effect of cyproterone acetate on the growth of children with central precocious puberty.

We have examined the growth and skeletal maturation of 19 children (6 male, 13 female) with central precocious puberty. The aetiology in nine patients (5 male, 4 female) was secondary to a hypothalamic hamartoma. Six children (2 male, 4 female) received no treatment whereas 13 children (4 male, 9 female) were treated with cyproterone acetate in a mean dose of 68 mg/m2 per day (range, 34-260) for a mean duration of 4.5 years (range, 0.8-7.9). There was no significant difference between height SDS for bone age at the beginning and end of observation in either treated or untreated groups. No significant relationship between the mean dose of cyproterone acetate used and change in height SDS for bone age could be determined. We conclude that cyproterone acetate has no beneficial effect on the growth prognosis of children with central precocious puberty.

Body Height↗
PubMed1987

Two cases of Winchester syndrome: with increased urinary oligosaccharide excretion.

We present our findings in two unrelated patients with the characteristic clinical and radiological features of the Winchester syndrome. The histological findings in gum and skin biopsies taken from one of the subjects, indicated excessive collagen turnover (active phagocytosis, an active endoplasmic reticulum, and an abundance of fibrillogranular material of probable collagen origin). An abnormal oligosaccharide was detected in urine from both patients which was identified as a trisaccharide containing one fucose and two galactose residues. The finding of this oligosaccharide may prove a useful marker in other cases of this rare syndrome and may help elucidate the underlying biochemical defect.

Child↗
PubMed1987

The effect of total body irradiation and bone marrow transplantation during childhood and adolescence on growth and endocrine function.

Seventeen children (11 M, 6 F) with acute leukaemia and myeloproliferative disorders were investigated for growth and endocrine dysfunction. All had undergone bone marrow transplantation prepared with cyclophosphamide and single fraction total body irradiation (900-1000 cGy) between 1.5 and 3.8 (mean 2.2) years previously. The majority of children exhibited growth failure, which was of multiple aetiology. Ten patients, of whom eight had had previous prophylactic cranial irradiation, had evidence of growth hormone deficiency based on the reduced growth hormone response to insulin induced hypoglycaemia. Three patients had evidence of hypothalamic damage as shown by their growth hormone response to 200 micrograms GHRH (1-29) NH2 intravenously. Gonadal failure was common, assessed clinically, and biochemically by basal gonadotrophin and sex steroid concentrations. All four girls of adolescent age (10.6-14.1 years) had ovarian failure requiring sex steroid replacement. Of the eight boys of adolescent age (12.3-18.3 years), two had testicular failure requiring sex steroid supplements. Both of these had had previous testicular irradiation. Five others had compensated gonadal failure, and one had normal Leydig cell function. Abnormalities of the TSH response to TRH occurred in 10 patients but only three had overt hypothyroidism. Unlike growth hormone deficiency, gonadal and thyroid dysfunction showed no correlation with previous cranial radiotherapy.

Adolescent↗
PubMed1987

Muscle strength in girls with congenital adrenal hyperplasia.

To assess whether exposure to excessive adrenal androgens increases muscle strength in girls with congenital adrenal hyperplasia, eighteen girls with 21 hydroxylase type congenital adrenal hyperplasia (CAH), aged 4.3-12.1 years were studied and compared with 78 healthy control girls aged 4-16 years. Maximum voluntary isometric strength was measured using a muscle testing chair, and the highest value from at least three attempts with each leg was recorded. Height and weight were also measured in the patients and controls. When compared with normal girls of similar age, some of the girls with CAH seemed unusually strong, but this difference was less marked when the CAH girls were compared with controls of similar weights. However, our data suggest that girls diagnosed later in childhood may have unusual muscle strength.

Adolescent↗