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Biomedical subjects

L Perry

Publications and source records attributed to L Perry.

At least 37 records · Page 2Linked to original sources
PubMed1989

Anterior and posterior pituitary function in brain-stem-dead donors. A possible role for hormonal replacement therapy.

Blood samples were obtained, at the time of organ donation, from 31 consecutive brain-stem-dead (BSD) donors referred to one transplant coordinator during a 9-month period. Twenty-four cases (77%) had clinical diabetes insipidus (DI), which was poorly controlled with marked dehydration in a majority of cases (serum osmolality range 268-357; median 302 mOSM/kg). Serum triiodothyronine (T3) was subnormal in 25 (81%); all had normal or high serum reverse T3; and the serum free thyroxine (T4) index was subnormal in 9 (29%), and TSH was subnormal in 7 (23%). In no case were T4 and TSH both subnormal and results were typical of the sick euthyroid syndrome rather than TSH deficiency. Of 21 cases not receiving corticosteroids, 5 (24%) had a serum cortisol above 550 nmol/L (20 micrograms/dl), excluding ACTH deficiency, and only 1 had undetectable cortisol levels. Those with severe hypotension did not have significantly lower serum cortisol (mean 354 vs. 416; P greater than 0.5). Levels of prolactin, growth hormone, gonadotrophins, and gonadal steroids were variable, but only a minority were frankly deficient in these hormones. BSD donors frequently have DI, which is often managed poorly by nonspecialists and requires appropriate replacement therapy. In contrast most patients are not totally deficient in anterior pituitary hormones. Routine hormonal therapy with cortisol and T3 cannot, therefore, be justified on endocrinological grounds. Widespread introduction of such treatment should only follow controlled trials that clearly demonstrate clinically significant improvement in the transplanted organ function, without detriment to the donor.

Adolescent↗
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

The effect of ovine corticotrophin-releasing factor on the hormonal response to insulin-induced hypoglycaemia.

In order to investigate the role of hypothalamic corticotrophin-releasing factor (CRF41) in the mediation of the pituitary ACTH response to hypoglycaemia, eight normal adult males were studied on four occasions. Commencing at 0830 h after an overnight fast, each received, in double-blind, random order, intravenous boluses of: A, normal saline control; B, soluble insulin 0.15U/kg; C, ovine CRF41 (oCRF41) 100 micrograms; D, soluble insulin 0.15U/kg followed immediately by oCRF41 100 micrograms. Adequate hypoglycaemia (blood glucose less than 2.2 mmol/l) was achieved in each subject when insulin was given alone or with oCRF41, and there was no difference in the glucose nadir between the 2 days. Peak plasma ACTH was significantly higher after insulin plus oCRF41 than after insulin alone (P less than 0.05) or oCRF41 alone (P less than 0.01) and this enhancement of ACTH release was most marked in the first phase of the response at 30 min (P less than 0.001, b vs d). There was no difference in the peak serum cortisol response whether oCRF41 and insulin were given alone or together and although the area under the cortisol curve was greater after insulin plus oCRF41, this difference was explicable simply on the basis of the earlier onset of the cortisol response to oCRF41. There were no differences in the serum GH responses to hypoglycaemia on the 2 days.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗
PubMed1989

Workload of a new district AIDS counselling unit, April 1987 to March 1988.

The Hampstead district AIDS counselling unit in London was opened in January 1987. It is staffed by a clinical psychologist, a social worker, and an administrator. From April 1987 to March 1988, 141 new patients and their relatives were referred from a range of clinical departments and 544 counselling sessions were provided. In addition, 666 staff consultations were organised to help colleagues manage some of the psychosocial problems of patients. An increase in demand during 1988-89 and a need for additional resources are anticipated. A strong case is seen for training other members of health care teams so that they may counsel patients with AIDS without referring them to the unit.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Inhibition of binding of gonadal steroids to serum binding proteins by non-esterified fatty acids: the influence of chain length and degree of unsaturation.

The effect of non-esterified fatty acids (NEFA) on the in vitro binding of testosterone, 5-alpha dihydrotestosterone and estradiol E2 to sex hormone binding globulin (SHBG) was examined using pooled normal female serum, and SHBG and albumin fractions obtained from the partial purification of late pregnancy serum. A range of saturated and unsaturated fatty acids were examined for their effect on steroid-protein binding. In normal female serum, NEFA added at physiological concentrations disrupted steroid-protein binding. The shorter chain (C8-C12) saturated acids and the poly-unsaturated acids proved to be more effective inhibitors than the longer chain saturated or mono-unsaturated acids. The greatest inhibition was obtained with E2 whereas the binding of dihydrotestosterone was least affected. With partially purified SHBG, the same concentrations of NEFA were less effective at inhibiting the binding of dihydrotestosterone and testosterone but elicited the same effect with E2. The binding of steroids to albumin appeared to be unaffected by these concentrations of NEFA.

Dihydrotestosterone↗
PubMed1988

CRF in the differential diagnosis of Cushing's syndrome: a comparison with the dexamethasone suppression test.

Accurate differential diagnosis of the precise cause of Cushing's syndrome can be difficult, and conventional tests such as those based on the use of dexamethasone may be misleading. We have therefore studied the cortisol and ACTH responses to ovine corticotrophin-releasing factor (CRF-41) in 28 consecutive patients with Cushing's syndrome, and compared the diagnostic value of this test with that of the high-dose dexamethasone suppression test (8 mg/day for 48 h). Of 20 patients with confirmed Cushing's disease (pituitary-dependent Cushing's syndrome), only 16 (80%) showed the expected 50% or more suppression of serum cortisol following high-dose dexamethasone administration. Four patients each with adrenal adenomas and three patients with the ectopic ACTH syndrome failed to suppress, while a child with probable Cushing's disease showed a variable response depending on the dose used. Following CRF stimulation, 15 out of the 20 patients (75%) with Cushing's disease showed an excessive rise in serum cortisol, outside the normal range, while in five the response to CRF-41 was normal on at least one occasion. None of the patients with adrenal adenomas or the ectopic ACTH syndrome showed a cortisol response to CRF. Thus, either test on its own may be misleading in differentiating Cushing's disease from other causes of the syndrome. Every patient with Cushing's disease, however, showed either suppression in response to high-dose dexamethasone or an excessive cortisol response to CRF testing. It appears, therefore, that the combination of the high-dose dexamethasone and the CRF test, with measurement of serum cortisol, is superior to either test alone in the differential diagnosis of Cushing's syndrome.

ACTH Syndrome, Ectopic↗
PubMed1988

Immunoreactive human chorionic gonadotrophin from the cyst fluid and CSF of patients with craniopharyngioma.

A specific radioimmunoassay for the beta-chain of human chorionic gonadotrophin irHCG beta has demonstrated HCG-like material to be present in craniopharyngioma cyst fluid in nine consecutive patients with craniopharyngioma. There was no detectable LH/HCG bioactivity as assessed using testosterone production from isolated Leydig cells from rat testis in seven samples tested. One patient was also found to have measurable irHCG beta in the cerebrospinal fluid (CSF), which fell to undetectable levels following surgery; in this patient, there was clinical evidence that the cyst fluid had leaked into the CSF pre-operatively. Immunocytochemical staining for HCG beta and intact HCG was positive in five of the tumours. irHCG beta was not measurable in the serum of any of the patients.

Biological Assay↗
PubMed1988

Opioid peptides do not modulate atrial natriuretic peptide or aldosterone release under basal conditions in man.

The effect of two analogues of [Met]-enkephalin, [D-Ala2,N-Phe4,Met(0)-ol5]-enkephalin and its guanyl derivative, on plasma concentrations of atrial natriuretic peptide (ANP) and serum aldosterone in six normal subjects was investigated. All subjects were given a 1 litre water load to inhibit vasopressin release. Both analogues, when injected i.v. at a dose of 100 micrograms, stimulated release of prolactin and GH and inhibited serum cortisol; there was no significant change in blood pressure, pulse rate or urine output. Neither plasma concentrations of ANP nor serum aldosterone levels changed significantly after injection of either analogue at a low or high dose. Naloxone, given i.v. as an 8 mg bolus, also failed to alter concentrations of either ANP or aldosterone, while it significantly stimulated the release of serum LH and cortisol. It was concluded that under basal conditions opiate receptors are unable to modulate plasma ANP or serum aldosterone concentrations.

Adult↗
PubMed1987

The effect of alpha adrenergic manipulation on the 24 hour pattern of cortisol secretion in man.

We have studied the role of central alpha-1 adrenoceptor mechanisms which stimulate cortisol secretion throughout the 24 h period in man. Six normal subjects were given 24 h i.v. infusions of the alpha-1 adrenoceptor agonist methoxamine, the alpha-1 antagonist thymoxamine, and saline under double-blind conditions. The only cardiovascular effects of these adrenergic manipulations was a slight bradycardia accompanying the methoxamine infusion. The methoxamine infusion was accompanied by higher concentrations of cortisol than the saline infusion during waking hours and the food related secretory surges were exaggerated, while the converse held with thymoxamine. In contrast, the nocturnal surge of cortisol secretion was unaffected by these adrenergic manipulations. These findings suggest that an alpha-1 adrenoceptor mechanism contributes to the maintenance of cortisol secretion during waking hours, but not at night.

Adult↗
PubMed1987

Alpha-adrenergic stimulation of corticotropin secretion by a specific central mechanism in man.

In a double-blind study in normal subjects, methoxamine, a highly selective agonist at alpha-1-adrenoceptors, significantly increased circulating ACTH and cortisol. The stimulant effect of methoxamine on cortisol secretion was dose dependent in the range 3.5-7 micrograms/kg/min, was abolished by concomitant administration of the strong alpha-1-adrenergic (and weak H1) antagonist thymoxamine but unaffected by the antihistamine, chlorpheniramine. In order to test whether the action of methoxamine on ACTH secretion was exerted centrally or peripherally, the effects of norepinephrine (NE), an alpha-1-agonist that does not cross the blood-brain barrier, were studied. Doses of NE (1-12 micrograms/min) that increased systolic blood pressure by amounts similar to the changes produced by methoxamine, did not result in any rise in plasma cortisol in normal subjects. The effect of methoxamine, which is more lipid soluble than NE, on plasma ACTH and cortisol, appears to be exerted on the CNS and not at the pituitary or via nonspecific peripheral mechanisms. In addition to its water solubility, NE differs from methoxamine in its beta-1-, beta-2- and alpha-2-agonist actions. However, prenalterol (2 mg) and salbutamol (250 micrograms), respectively beta-1- and beta-2-adrenergic agonist drugs, had no effect on the secretion of ACTH or cortisol and the alpha-2-antagonist yohimbine in an effective dose did not unmask a stimulant effect of intravenous NE on plasma cortisol. At high infusion rates, NE significantly inhibited cortisol secretion. Stimulation of central alpha-1-adrenergic mechanisms results in secretion of ACTH in man, presumably by increased release of a corticotropin-releasing factor.

Adrenocorticotropic Hormone↗
PubMed1987

Effect of adrenaline on basal and ovine corticotrophin-releasing factor-stimulated ACTH secretion in man.

Six normal male subjects were given, in single blind random order on six separate occasions, i.v. bolus doses of synthetic ovine corticotrophin-releasing factor-41 (oCRF-41; 25 and 50 micrograms) with and without adrenaline (3 micrograms/min) i.v. for 150 min, the adrenaline infusions alone and saline placebo. The adrenaline infusions resulted in plasma adrenaline concentrations of 4.33 +/- 0.82 (S.E.M.) nmol/l and were associated with an increase in blood glucose, heart rate and systolic blood pressure and a reduction of diastolic blood pressure. Despite these evident biological effects at several sites, there was no stimulation of plasma ACTH or cortisol by adrenaline in comparison with the effect of saline, and no enhancement of the stimulatory effect of either dose of oCRF-41 on ACTH or cortisol secretion. The ACTH response to 50 micrograms oCRF-41 was greater than that to 25 micrograms, indicating that the 25 micrograms dose of oCRF-41 was submaximal and capable of further enhancement. As the plasma adrenaline concentrations during the adrenaline infusions reached the upper limit of the physiological range of plasma adrenaline in man, yet failed to enhance the ACTH or cortisol responses to a submaximal dose of oCRF-41, we conclude that circulating adrenaline neither exerts a direct stimulatory effect on pituitary corticotrophs nor enhances the effect of CRF under physiological circumstances. The adrenaline infusions attenuated the ACTH and cortisol responses to oCRF-41 and were associated with a transient reduction of basal concentrations of both hormones.

Adrenocorticotropic Hormone↗
PubMed1986

Diagnosis and management of ACTH-dependent Cushing's syndrome: comparison of the features in ectopic and pituitary ACTH production.

The clinical features, diagnosis and management of 16 consecutive patients with ectopic ACTH production are described and biochemical data are compared with those of 48 consecutive patients with pituitary-dependent Cushing's disease. In 10 cases the ectopic ACTH secreting tumour was completely occult to routine clinical and radiological investigation, and no basal or dynamic investigation of adrenal-pituitary function was able clearly to differentiate these patients from those with Cushing's disease. High dose dexamethasone suppression testing assessed by plasma cortisol was usually helpful but unexpected responses were seen in both diagnostic groups; the metyrapone test yielded no useful information and should now be abandoned. Hypokalaemia was seen in all patients with ectopic ACTH production but in only 10% of those with Cushing's disease who were not on diuretics at presentation. Successful diagnosis and tumour localization was most frequently achieved by a combination of CT scanning of the chest and abdomen and venous catheter sampling for ACTH. All patients in whom the ectopic ACTH-secreting tumour was obvious at presentation died of their primary tumour within 8 months, whereas seven of the 10 patients with occult tumours at presentation are alive 1.5-16.5 years later, and appear cured. Occult ectopic ACTH secretion may be impossible to distinguish from pituitary Cushing's disease. Multiple and repeated investigations are often required to make this differential diagnosis, essential for appropriate therapy.

ACTH Syndrome, Ectopic↗
PubMed1986

Maternal oestriol levels reflect placental function rather than foetal function.

We have examined the relationship between foetal levels of E3 and DHEA-SO4 and the birthweight of the child. Levels of these steroids do not relate to birthweight--although the concentration of DHEA-SO4 was marginally but not significantly higher in infants of lower birthweight. These findings suggest that the placental conversion of foetal precursors, and not the level of the precursors themselves, determines the concentration of E3 in the mother. Measurement of E3 as a clinical test reflects the function of both the foetus and the placenta.

Birth Weight↗