EEC syndrome with diabetes insipidus and hypogonadism.
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Abnormalities, Multiple↗
Biomedical subjects
D B Grant
Publications and source records attributed to D B Grant.
Temporary inhibition of growth and adrenal suppression associated with the use of steroid nose drops.
Inhibition of growth and adrenal suppression are reported following the use of intranasal beta-methasone (0.1%) in a 9-year-old boy with cystic fibrosis and nasal polyps and in a 3-year-old girl with allergic rhinitis. On stopping treatment catch-up growth occurred and adrenal function returned to normal.
Administration, Intranasal↗
Identification of olfactory dysfunction in carriers of X-linked Kallmann's syndrome.
OBJECTIVE: The aim of the study was to test the hypothesis that clinically unaffected female carriers of X-linked Kallmann's syndrome have an olfactory defect. DESIGN: Assessment of the olfactory threshold to seven standard odorants, each at a concentration of 1-10(-8) mol/l. PATIENTS: Five families with X-linked Kallmann's syndrome (KS) were tested, containing 19 males with KS, and 9 female carriers. Related but unaffected males (n = 8) were used as a control group, and in addition seven patients with Turner's syndrome (XO) were assessed. MEASUREMENTS: The olfactory threshold was taken as the lowest concentration at which each odorant was clearly distinguished from control (liquid paraffin). The threshold for each odorant was compared between the subject groups using the non-parametric Mann-Whitney test. RESULTS: All patients with KS were anosmic to all odorants. The female carriers had hyposmia, with a significant reduction in the olfactory threshold to putrid, peppermint, floral and pungent odorants compared to control subjects, and to peppermint, floral and pungent odorants compared to subjects with Turner's syndrome. The latter had olfactory thresholds which were statistically identical with the control group. CONCLUSIONS: Obligate female carriers of X-linked Kallmann's syndrome are hyposmic compared to control subjects. The overlap between the two groups, however, makes olfactory testing unreliable as a diagnostic test.
Female↗
Gonadal function and response to human chorionic and menopausal gonadotrophin therapy in male patients with idiopathic hypogonadotrophic hypogonadism.
OBJECTIVE: This study was designed to determine the response to therapy using human chorionic gonadotrophin (hCG) and human menopausal gonadotrophin (hMG) in males with idiopathic isolated hypogonadotrophic hypogonadism (IHH), and to compare the responses in patients presenting with and without cryptorchidism. DESIGN: Analysis of male patients with IHH treated with hCG or combined hCG/hMG for a minimum of 6 months at St Bartholomew's Hospital. Clinical and endocrine assessment was performed in all patients prior to commencing therapy. PATIENTS: A total of 26 males with IHH have been treated with exogenous gonadotrophins. Thirteen patients (Group 1) had cryptorchidism (unilateral in 7, bilateral in 6) at presentation, and 13 (Group 2) did not. MEASUREMENTS: All patients had basal serum testosterone, LH and FSH determinations. An i.v. GnRH test was performed in 25 patients and an i.m. hCG stimulation test in 19. Testicular volume and serum testosterone were measured during both hCG and combined hCG/hMG therapy. Seminal analysis was performed at the start and monthly during hCG/hMG therapy. RESULTS: Eighty-five per cent of the 13 patients in Group 1 had an olfactory defect (Kallmann's syndrome), compared with 23% of Group 2. Both groups of patients showed a subnormal response to initial i.v. GnRH and i.m. hCG testing. During hCG therapy only three patients in Group 1 and six in Group 2 achieved normal adult testosterone levels. The non-cryptorchid group achieved a higher mean testicular volume on hCG therapy than the cryptorchid group (mean (SD); 4.7 (1.8) ml vs 3.0 (1.6) ml (P < 0.02)), and for all patients there was a correlation between initial and maximal testicular volume (R = 0.69, P = 0.001). Four patients in Group 1 and five patients in Group 2 were treated with combined hCG/hMG for 6-15 months to induce fertility; only one patient in Group 1 achieved spermatogenesis, compared to all patients in Group 2 (leading to three pregnancies). CONCLUSIONS: These data indicate that patients with idiopathic hypogonadotrophic hypogonadism (IHH) have a poor response to hCG therapy in terms of testicular growth and normalization of serum testosterone. Final testicular volume is dependent on initial testicular size. In addition, patients with IHH associated with cryptorchidism have a poor fertility potential to combined hCG/hMG therapy.
Adolescent↗
Unilateral renal aplasia in X-linked Kallmann's syndrome.
Unilateral renal agenesis is an uncommon association with Kallmann's syndrome (KS) (hypogonadotrophic hypogonadism and olfactory defect). We have investigated affected individuals from six pedigrees: five with X-linked KS, and one with X-linked KS and X-linked ichthyosis (XLI). Seventeen affected individuals have had renal imaging performed, and six scans demonstrated only one kidney. In addition, two pedigrees had males who died in the neonatal period with bilateral renal agenesis. Only two of the four affected individuals in the family with X-linked KS and X-linked ichthyosis (Pedigree 6) showed unilateral renal agenesis, despite all four patients demonstrating an interstitial deletion within the short arm of the X-chromosome. These data indicate that unilateral renal agenesis is much commoner than previously suspected in patients with X-linked Kallmann's syndrome, but that it may have incomplete penetrance within a family.
Genetic Linkage↗
Impaired growth in children with asthma during treatment with conventional doses of inhaled corticosteroids.
We describe 6 (4F, 2M) prepubertal children with moderate asthma diagnosed at a mean age of 2.8 years. All patients were treated with inhaled corticosteroids in a dose of between 300 and 800 mcg of beclomethasone dipropionate (becotide) daily, given either as an aerosol or rotahaler. Mean height velocity SDS decreased from -0.8 (range +0.5 to -2.0) to -3.2 (range -1.3 to -4.8) when the dose was increased. Alternatively, when the dose was reduced or stopped, mean height velocity SDS increased from -3.2 (range -2.0 to -4.8) to +0.8 (range -1.2 to +2.7). Careful assessment of height velocity is indicated in all children receiving treatment with inhaled corticosteroids.
Administration, Inhalation↗
Diabetes insipidus with impaired osmotic regulation in septo-optic dysplasia and agenesis of the corpus callosum.
The clinical and endocrinological findings in 24 children with septo-optic dysplasia and/or agenesis of the corpus callosum are described with particular reference to posterior pituitary function. Nine had diabetes insipidus. The prevalence of diabetes insipidus was similar in children with complete and incomplete forms of septo-optic dysplasia. Maintenance of normal osmotic balance was very difficult in six of these children, even after the introduction of treatment with vasopressin, either as desmopressin, or lysine vasopressin spray in one of the early cases.
Abnormalities, Multiple↗
Growth in early treated congenital hypothyroidism.
The growth of 361 children with congenital hypothyroidism diagnosed by screening was assessed by estimating mean values for height, weight, body mass index (BMI), and head circumference on each birthday up to the age of 4 years. In the group of children with severe congenital hypothyroidism (pretreatment plasma thyroxine < or = 30 nmol/l), the mean heights at 1 and 2 years were less than standards for healthy children, but this may be due to technical factors related to difficulties in measuring young infants and the method used to estimate height on each birthday. By the age of 3-4 years the values for mean height in the children with either severe or less severe congenital hypothyroidism were equal to or greater than those for healthy children. At all ages mean head circumference in boys and girls with severe congenital hypothyroidism was greater than standards for healthy children, but this only reached statistical significance in girls at 1 year. With the exception of the results for boys at 1 year, mean values for BMI were slightly greater in the children with severe congenital hypothyroidism. The mean BMI results for children with either severe or less severe congenital hypothyroidism were significantly greater than those for healthy French children at all ages, but they showed the same trends with increasing age. It is concluded that by the age of 3-4 years stature is essentially normal in children with early treated congenital hypothyroidism but that the increased head size reported before screening may still be evident in early infancy.
Birth Weight↗
Intellectual development at 10 years in early treated congenital hypothyroidism.
Fifty nine children born between 1978 and 1981 with congenital hypothyroidism detected by neonatal screening were assessed at 10 years using the Wechsler intelligence scale for children, together with 59 matched classroom controls. Thirty one children with severe hypothyroidism who had pretreatment plasma thyroxine concentrations of 40 nmol/l or less had a mean (SD) full scale IQ score of 104.7 (15.1), compared with a mean (SD) score of 114.6 (16.3) for the 28 less severely affected children who had pretreatment thyroxine levels greater than 40 nmol/l, and mean (SD) scores of 114.5 (12.8) and 114.8 (13.8) respectively for the 31 and 28 control children. In the hypothyroid children the IQ scores at 10 years were closely related to the IQ scores at 5 years and at 3 years. It is concluded that the deficit in IQ score found at 3 and 5 years in children with severe hypothyroidism is still evident at the age of 10 years.
Child↗
Functional characterization of the cloned human ACTH receptor: impaired responsiveness of a mutant receptor in familial glucocorticoid deficiency.
The putative ACTH receptor gene has been identified on the basis of its tissue specific expression, structure, and limited expression data. We have expressed this gene in COS-7 cells and measured cAMP production in response to ACTH. An EC50 of 5.5 x 10(-9) M for ACTH (1-24) was determined. The S74I mutant ACTH receptor gene that associates with the syndrome of familial glucocorticoid deficiency had an EC50 of 67 x 10(-9) M. This discrepancy is consistent with the clinical data, and supports the hypothesis that this point mutation could account for the syndrome.
Adrenocorticotropic Hormone↗
Complete and partial XY sex reversal associated with terminal deletion of 10q: report of 2 cases and literature review.
We describe 2 karyotypically male infants with terminal deletion of 10q and mental retardation, multiple phenotypic anomalies and abnormal genitalia. One [karyotype 46,XY, del(10)(q26.1)] had female external genitalia; the other [karyotype 46,XY,-10,+der(10)t (10;16)(q26.2;q21)] had an intersex phenotype. Of 8 males previously reported with terminal 10q deletion as the major or only cytogenetic abnormality, 2 had an intersex phenotype, and the others all had combinations of cryptorchidism, micropenis, and hypospadias. Terminal 10q deletions appear to be strongly associated with abnormal male genital development, and should be specifically searched for in the cytogenetic workup of such cases.
Chromosome Deletion↗
Neurological and adrenal dysfunction in the adrenal insufficiency/alacrima/achalasia (3A) syndrome.
Review of 20 patients with glucocorticoid deficiency (three cases also with salt loss) associated with absent tear secretion (19 cases) and achalasia of the cardia (15 cases) revealed neurological abnormalities in 17 including hyper-reflexia, muscle weakness, dysarthria, and ataxia together with impaired intelligence and abnormal autonomic function, particularly postural hypotension. These findings indicate that significant neurological problems are common in this multisystem disorder.
Addison Disease↗
Increased plasma thyroid stimulating hormone in treated congenital hypothyroidism: relation to severity of hypothyroidism, plasma thyroid hormone status, and daily dose of thyroxine.
Plasma thyroid stimulating hormone (TSH) concentrations obtained during the first four years of treatment in 418 children with congenital hypothyroidism, identified by neonatal screening, were examined in relation to paired measurements of plasma thyroxine (n = 1945), free thyroxine (n = 836), triiodothyronine (n = 480), and free triiodothyronine (n = 231), and estimated daily dose of thyroxine at the time of blood sampling. Overall, plasma TSH was above 7 mU/l in 1280 out of 2960 samples (43%); the percentage was not related to severity of hypothyroidism at diagnosis. Mean values for thyroxine and free thyroxine, and to a lesser extent free triiodothyronine, were consistently lower in samples with TSH concentrations over 7 mU/l and this was the case in patients with either severe or less severe hypothyroidism. Raised TSH concentrations were also associated with lower mean doses of thyroxine (micrograms/kg/day) but here the mean doses of thyroxine in children with severe hypothyroidism were higher than in the children with less severe hypothyroidism. The mean dose of thyroxine associated with low/normal TSH values was highest in the first 6 months and fell progressively. Thyroxine dose was significantly related to thyroxine and free thyroxine concentrations but not to triiodothyronine and free triiodothyronine and the latter appeared to be of limited value as measures of plasma thyroid hormone status during treatment.
Child, Preschool↗
The usefulness of serum thyroglobulin in the follow-up of differentiated thyroid carcinoma in children.
Serum thyroglobulin has been measured serially in ten children aged 5-17 years presenting with differentiated thyroid carcinoma. At presentation 4 had intra-thyroidal disease, 3 had lymph node metastases, and 3 had lung metastases. During follow-up for a median of 37.0 months (range 21-108) 3 patients have been disease-free, 4 have had a local relapse, and 3 have had persistent disease. Seventy-seven separate serum thyroglobulin measurements have been performed; 36 on and 41 off thyroid replacement therapy. A level of thyroglobulin of less than 5 ng/ml was taken as indicative of absence of disease, and compared against combined clinical examination and 131I scanning. Overall sensitivity of thyroglobulin measurement was 36/37 (97%), and although specificity was 30/40 (75%), this rose to 30/32 (94%) if raised thyroglobulin levels noted within 3 months of 131I therapy in otherwise asymptomatic patients (n = 4) or in subjects with intact thyroid tissue (n = 4) were excluded. Concordance with clinical status was 30/31 (97%) in measurements taken on, and 31/32 (94%) in those taken off, thyroid replacement. These data indicate that thyroglobulin measurement is a sensitive and specific means of detecting residual, recurrent, and metastatic thyroid carcinoma in children.
Adenocarcinoma↗
Familial glucocorticoid deficiency with achalasia of the cardia associated with mixed neuropathy, long-tract degeneration and mild dementia.
This paper describes the progress of two previously reported brothers with familial glucocorticoid deficiency, achalasia of the cardia, and alacrima. In their early 'teens both boys developed polyneuropathy with sensory, motor and autonomic components, Parkinsonism, and signs of both dorsal column and pyramidal tract damage. The older boy also showed signs of dementia. Red cell folate levels were markedly reduced but plasma and CSF folate were normal. Serum B12 and erythrocyte concentrations were at or below the lower limit of normal CSF levels of homovanillic acid and 5-hydroxyindole acetic acid (the major metabolites of dopamine and serotonin in brain) were low, indicating impaired turnover of the two amines within the nervous system. Positron emission photometry scans in the older boy showed low binding of c-methyl-spiperone and reduced uptake of 18-F-L-fluorodopa in the striatum, confirming the impairment in dopamine metabolism and suggesting both reduced synthesis and reduced receptor density. Treatment with L-dopa up to 800 mg/day (along with carbidopa 200 mg/day) corrected the low CSF homovanillic acid levels and produced some improvement in the Parkinsonism but no other obvious clinical benefit. Empirical treatment with hydroxycobalamin (1000 micrograms three times a week) and folinic acid (15 mg/day) was without clinical effect. The cause of the neurological disorder, low red-cell folate concentrations, and amine disturbance remains unknown, as does the pathogenesis of the adrenocortical failure.
Adolescent↗
Rising IQ scores in British children: recent evidence.
Between 1987 and 1990 IQ scores for 333 5-year-old white school children were obtained using the Wechsler Pre-School and Primary Scale of Intelligence (WPPSI) and the results were compared with 112 children assessed in 1967. The mean full scale IQ score of 113.3 was 8 points higher than the mean of 105.1 in the 1967 study. These findings indicate that the rate of increase of IQ scores was comparable and probably higher than that reported in the U.S.A. for the period 1932-78. It is important that this large increase is taken into account for correct interpretation of IQ test results.
Child, Preschool↗
Congenital hypothyroidism detected by neonatal screening: relationship between biochemical severity and early clinical features.
The relationships between biochemical severity of hypothyroidism (as judged by plasma thyroxine) and the clinical and radiographic findings at diagnosis were evaluated in 449 infants born in 1982-4 with congenital hypothyroidism identified by neonatal screening. Details of pregnancy, delivery, and the neonatal period were also examined and compared with the findings in a normal population of 36,727 infants born in 1988. Infants with plasma thyroxine values of 30 nmol/l or less had a significantly higher incidence of prolonged jaundice, feeding difficulties, lethargy, umbilical hernia and macroglossia, showed more severe delay of bone maturation on a knee radiograph, and had a higher proportion of thyroid agenesis on isotope scan. In contrast, an ectopic or hypoplastic gland was more common in infants with plasma thyroxine values above 30 nmol/l. Prevalence of illness in pregnancy and mode of delivery was not related to severity of hypothyroidism and were similar to figures for the normal population. Induction of labour, gestation over 40 weeks, and birth weight above 3500 g were significantly more common in the hypothyroid infants. Perinatal illness and congenital malformations were more common in the infants with low plasma thyroxine values at diagnosis.
Adult↗
Surgical treatment of hyperinsulinaemic hypoglycaemia in infancy and childhood.
Despite a greater awareness of hyperinsulinaemic hypoglycaemia, one in three patients has some degree of mental retardation by the time the diagnosis is made. The diagnosis is established by demonstrating high plasma insulin concentrations during an episode of hypoglycaemia. Twenty one hyperinsulinaemic infants and children were referred for surgical treatment after failing to respond to medical management. The surgical procedure of choice is a 95% pancreatectomy. Recurrence of the hypoglycaemia may develop after less radical resections as occurred in one patient who then underwent an extended resection 72 hours postoperatively. Patients who fail to respond to optimal medical treatment should be referred for surgery early and not as a last resort if permanent neurological damage is to be avoided.
Child, Preschool↗