J. F. Connelly

Hypothalamic hypopituitarism following external radiotherapy for tumours distant from the adenohypophysis.

Three cases of panhypopituitarism and five of isolated growth hormone dificiency which occurred following previous external irradiation of tumours distant from the adenohypphysis are described. The hypothalamic pituitary region received between 2800 and 12000 rads in each case, 1‐9 years before endocrine deficiency was recognized. Evidence is presented that th esite of damage is in the region of the hypothalamus rather than the pituitary gland itself.

PLASMA C19 STEROID SULPHATE LEVELS AND INDICES OF ANDROGEN BIOAVAILABILITY IN FEMALE PATTERN ANDROGENIC ALOPECIA

Female pattern androgenic alopecia (AA) is a relatively common endocrine abnormality in premenopausal women. However, unlike hirsutism, little is known about the androgen metabolism and plasma C19 steroid sulphate profiles in this disorder. We have therefore measured the plasma levels of dehydroepiandrosterone sulphate (DHEA‐S), 5‐androstene‐3β, 17/β‐diol sulphate (5‐ADIOL‐S), 5α‐androstane‐3α, 17β‐diol sulphate (3α‐DIOL‐S), androstenedione (AD), total testosterone (T), free testosterone (FT), sex hormone binding globulin (SHBG), non‐SHBG bound T, luteinizing hormone (LH) and follicle stimulating hormone (FSH), and have calculated the free androgen index (FAI): 100 × T (nmol/1) ÷ SHBG (nmol/1), in premenopausal women with AA (n= 25‐45) and in normal premenopausal women (n= 17–73). While mean plasma concentrations of DHEA‐S and T were not significantly different from controls, mean SHBG concentrations were significantly lower (47 ± 3 vs 64±3 nmol/1) and the mean free androgen index (4.4±0.4 vs 2.4±0–2), and mean concentrations of free testosterone (45 ± 5 vs 26 ± 1.4 pmol/ 1), non‐SHBG bound T (0.9 ±0.2 vs 0.6±0.1 nmol/1) and androstenedione (4.3±0.3 vs 3.4±0.2 nmol/1) were significantly elevated in women with AA. Furthermore, mean plasma concentrations of 5‐ADIOL‐S (512±42 nmol/1) and 3a‐DIOL‐S (76±7 nmol/1) were significantly higher than levels found in normal women (272±12 nmol/1 and 52±2 nmol/1 respectively). The nature of the hyperandrogenism associated with AA may thus only be revealed by a comprehensive plasma androgen and androgen sulphate profile, which may explain apparently aberrant data for a given patient. In addition, 5‐ADIOL‐S and 3α‐DIOL‐S may serve as excellent plasma markers of both the existence of the disorder and the efficacy of its treatment.

Fasting plasma glucose in children

Fasting plasma glucose levels were measured in samples taken preoperatively in 116 patients, it was found that mean plasma glucose levels increased with age and that there was no relationship between the period of fasting and plasma glucose concentrations. Fewer children had levels below 3 mmols/l than in other reported series.

AN AETIOLOGICAL STUDY OF NEONATAL JAUNDICE IN A CHILDREN'S HOSPITAL*

Seventy‐six newborn infants with significant jaundice, caused by other than foetomaternal blood group incompatibility, have been studied by simple but systematic methods. Bacterial infection emerged as the most common cause. Blood culture and microscopy of urine proved to be the most rewarding routine tests and these are advocated in all newborn babies in whom jaundice gives rise to concern. ‘Neonatal hepatitis’ and biliary atresia were the main causes of jaundice which persisted for more than one month, and investigation of their aetiology is briefly reported.

Transient primary hypothyroidism in the newborn: Experience of the Victorian Neonatal Thyroid Screening Programme

Abstract Between May 1977 and December 1986, the Victorian Thyroid Screening Programme tested approximately 570 000 newborns for congenital hypothyroidism. One hundred and sixty‐six cases of primary hypothyroidism, confirmed by formal thyroid function tests, were identified, of which 24 were later found to be transient. In addition, there were two patients with permanent dyshormonogenesis who passed through a stage of being biochemically euthyroid and so could have been diagnosed mistakenly as transient hypothyroidism. Fourteen of the transient cases were due to excessive intake of iodine. In two, this was due to maternal ingestion of iodide during pregnancy and in 12 the babies received large amounts of topical iodine antiseptic. Two cases were caused by maternal anti‐thyroid antibodies and in eight instances the cause was unknown. The large number of cases due to the topical application of iodine antiseptic emphasizes the need for caution when using this substance in neonates.

Diagnosis of 21‐hydroxylase deficiency in newborn infants by GC‐MS of urinary steroids

Abstract In a study using gas chromatography‐mass spectrometry (GC‐MS) on urine specimens from 16 normal infants and 16 infants with congenital adrenal hyperplasia (CAH) due to 21‐hydroxylase deficiency (aged 1 day to 4 weeks), the major steroids recognized in all infants were: 16α‐hydroxy‐dehydroepiandrosterone, 16β‐hydroxy‐dehydroepiandrosterone, 16‐oxo‐androstenediol, androstenetriol, 15β, 17α‐dihydroxy‐pregnenolone and 16α‐hydroxy‐pregnenolone.

The association of thyroid dyshormonogenesis and deafness (Pendred syndrome): Experience of the Victorian Neonatal Thyroid Screening Programme

Abstract Between 1977 and 1989, the Victorian Neonatal Thyroid Screening Programme detected five subjects with thyroid dyshormonogenesis and sensorineural deafness. These patients have been diagnosed as having Pendred syndrome. In two of the children, thyroid function tests which were initially abnormal at birth returned to normal spontaneously without treatment. However, hypothyroidism subsequently recurred and the children required thyroxine therapy. These two children could have been mistakenly diagnosed as having transient hypothyroidism. The detection of five patients with Pendred syndrome illustrates the importance of audiological assessment in all babies with thyroid dyshormonogenesis in whom there is increased uptake of isotope on thyroid scanning. In our experience, hearing loss in patients with Pendred syndrome may be progressive over time, so that repeated audiological assessments are necessary.

Serum levels of 5-androstene-3β, 7β-DIOL sulphate, 5α-androstane-3α,17β-DIOL sulphate and glucuronide, in late onset 21-hydroxylase deficiency

Abstract Serum sulphates of 5-androstene-3β,17β-diol (5-ADIOL-S), 5α-androstane-3α,17β-diol (3α-DIOL-S) and dehydroepiandrosterone (DHEA-S), as well as 5α-androstane-3α,17β-diol glucuronide (3α-DIOL-G) and unconjugated androstenedione (AD) and testosterone (T), sex hormone binding globulin (SHBG), free androgen index (FAI) and 17α-hydroxyprogester-ne (17OHP) were measured by specific radioimmunoassays (RIA) in 14 women with late-onset 21-hydroxylase deficiency (LOCAH), and in normal women ( n = 73). The diagnosis of LOCAH was made on the finding of a (17OHP) response level greater than 30 nmol/1 following ACTH stimulation, and/or an elevation of urinary metabolites of 17OHP. Mean values for serum concentrations of all steroids measured and the free androgen index (100 × T nmol/1 ÷ SHBG nmol/1) were significantly elevated, and SHBG levels depressed in patients with LOCAH. These studies show that in LOCAH, in addition to the unconjugated steroids AD and T, the sulphoconjugated steroids DHEA-S, 5-ADIOL-S and 3α-DIOL-S are increased, as is the glucuronide conjugate 3α-DIOL-G and the index of bioavailable testosterone (FAI), and that mean SHBG levels are depressed. These data suggest that as well as AD, 5-ADIOL-S and DHEA-S may act as pro-hormones for more potent steroids (T and 5α-dihydrotestosterone) in peripheral tissues, while 3α-DIOL-S and 3α-DIOL-G may both reflect peripheral androgen metabolism in patients with LOCAH.

Serum 5-androstene-3β,17β-diol sulphate, sex hormone binding globulin and free androgen index in girls with premature adrenarche

Abstract Serum sex hormone binding globulin (SHBG), testosterone (T), DHEA sulphate (DHEA-S), androstenedione (AD) and Δ5-androstene-3β,17β-diol sulphate (5-ADIOL-S) levels were measured by specific radioimmuoassay in 16 girls presenting with premature adrenarche (PA) and in 14 normal girls. Mean levels of steroids measured were significantly elevated, and SHBG significantly depressed, in the girls with PA, with values (mean ± SE) for DHEA-S (1.73 ± 0.17 vs 0.25 ± 0.06 μmol/l), 5-ADIOL-S (104 ± 8 vs 31 ± 4nmol/l), AD (0.89 ± 0.06 vs 0.62 ± 0.04 nmol/l), and T (0.49 ± 0.03 vs 0.23 ± 0.06 nmol/l). SHBG levels were 68 ± 6 vs 108 ±5 nmol/l, and the free androgen index [100 × T (nmol/l) ÷ SHBG (nmol/l)] was 0.89 ± 0.17 vs 0.22 ± 0.01. These studies show that SHBG is depressed in girls with premature adrenarche; with the increased testosterone levels, this results in a markedly elevated free androgen index, a measure of testosterone which is bioavailable to target tissue. This may be compounded by the elevated levels of 5-ADIOL-S in girls with PA since its role may be as a prohormone for more potent androgens (testosterone, 5α-dihydrotestosterone) in target tissues such as pubic skin.

Measurement of TSH receptor blocking immunoglobulins using 3H‐adenine incorporation into FRTL‐5 and JPO9 cells: use in a child with neonatal hypothyroidism

OBJECTIVE The aim of this study was to develop an assay for the measurement of thyroid blocking antibodies (TBAb), based on the ability of patient serum to inhibit TSH stimulated 3H‐cAMP production following incubation of FRTL‐5 or JPOS cells with 3H‐adenine. The assay was then used to evaluate a child born with neonatal hypothyroidism.