THE EFFECT OF o,p''-DDD ON ADRENAL STEROID REPLACEMENT THERAPY REQUIREMENTS

Two patients with adrenal carcinoma treated with 2,2-bis (2-chlorophenyl-4-chlorophenyl)-1,1-dichloroethane (o,p'-DDD) as adjuvant therapy were studied. Both patients developed hypoadrenalism while on o,p'-DDD and apparently adequate dexamethasone replacement therapy. The hypoadrenalism was overcome by increasing steroid replacement therapy. Dexamethasone levels were measured in the serum by radioimmunoassay and shown to be lowered by o,p'-DDD therapy. A study of the absorption and disappearance of dexamethasone from the circulation in response to a (1 mg oral dose indicated that the steroid was absorbed normally but was cleared more rapidly from the circulation of these two patients than from normal controls. This may be due to a change in the type of metabolites excreted. It is suggested that many of the reported side-effects of o,p'-DDD may be due to hypoadrenalism and may be controlled by greatly increasing the steroid replacement dose. The adequacy of corticosteroid replacement therapy may best be assessed by monitoring the levels of ACTH.     

HEPATIC MICROSOMAL ENZYME INDUCTION AND ADRENAL CRISIS DUE TO o,p''DDD THERAPY FOR METASTATIC ADRENOCORTICAL CARCINOMA

Two cases are described in which metastatic adrenocortical carcinoma associated with Cushing's syndrome was treated with mitotane (o,p'DDD). The first patient had initially been treated by bilateral adrenalectomy and, whilst responding to mitotane biochemically and by remission of metastases, experienced repeated episodes of adrenal crisis requiring a substantial increase in steroid therapy. The second patient failed to respond to the drug, but evidence of hepatic enzyme induction was noted during its administration. It is suggested that hepatic microsomal enzyme induction can occur in association with treatment with mitotane and that this can lead to an increased destruction of exogenous steroid with clinical consequences.     

ADRENOCORTICAL FUNCTION IN CHILDREN WITH PRECOCIOUS SEXUAL DEVELOPMENT DURING TREATMENT WITH CYPROTERONE ACETATE

Adrenal function was studied in thirty-two children with precocious sexual development who were being treated with cyproterone acetate (CPA) at doses ranging from 68 to 175 mg. m2. day for periods lasting from 2 to 79 months. In eighteen children the adrenocortical function evaluation was made before and during CPA treatment. In these eighteen patients, the mean basal plasma cortisol level during the morning hours was 11.2 +/- 4.6 micrograms/dl (m +/- SD) before treatment and fell significantly to 7.2 +/- 4.1 micrograms/dl (P less than 0.02) during therapy. In fifteen patients tested during insulin hypoglycaemia the cortisol peak fell from 21.6 +/- 5.5 micrograms/dl before treatment to 16.7 +/- 6.8 micrograms/dl (P less than 0.05) during CPA therapy. There was a significant inverse correlation between this peak and the dose of CPA but no correlation was found between the cortisol response and duration of treatment. In eight of twenty patients tested, urinary free cortisol levels were undetectable during treatment. No change in basal plasma ACTH levels were demonstrated using standard radioimmunoassay techniques. In the patient receiving the highest dose of CPA and showing complete suppression of the adrenal axis, prolonged stimulation with ACTH-Depot demonstrated a responsive adrenal gland. Addition of a replacement dose of cortisol to the CPA treatment led to the rapid development of the typical signs of Cushing's syndrome. It was concluded that despite the evidence of adrenal suppression by CPA, cortisol supplementation is not necessary and may not even be contraindicated.     

GARDNER'S SYNDROME WITH ADRENAL CARCINOMA

A young woman with familial polyposis of the colon, multiple sebaceous cysts and osteomata (Gardner's syndrome) presented with Cushing's disease associated with carcinoma of the adrenal gland. This appears to be the first recorded case of Gardner's syndrome with adrenal carcinoma, and the first case wherein a metastasizing tumour other than carcinoma of the colon has been fully documented.     

PITUITARY—ADRENOCORTICAL FUNCTION IN PATIENTS DURING TREATMENT WITH THE ANGIOTENSIN-CONVERTING ENZYME INHIBITOR CAPTOPRIL

To study effects on pituitary-adrenocortical activity of a sustained block of angiotensin II formation, six 'drug-resistant' patients with essential hypertension were studied before and during treatment with an inhibitor of the angiotensin-converting enzyme (Captopril, SQ 14,225). The drug was given in increasing doses (100-400 mg/day) for 2 weeks whilst patients received a moderately restricted sodium intake (60-80 mmol/day). Immunoreactive ACTH, cortisol, aldosterone, plasma renin activity (PRA) and the activity of the angiotensin-converting enzyme (ACE) were measured in blood samples drawn at 0800-0900 h. Urinary excretion of cortisol and aldosterone were measured in 24-h urine collections. Further information on pituitary-adreno-cortical function was obtained by measuring serial plasma corticosteroid levels after submaximal stimulation with a synthetic ACTH preparation. ACTH and cortisol did not change an observation which does not support the hypothesis that glucocorticoid activity is influenced by a decrease in plasma angiotensin II concentrations.     

LONG-TERM RESULTS OF ADRENAL SURGERY IN PATIENTS WITH CUSHING''S SYNDROME DUE TO ADRENOCORTICAL ADENOMA

Fourteen of 16 patients with Cushing's syndrome due to adrenal adenoma who had undergone adrenal surgery in the period 1967-1981 participated in a follow-up study 1 to 15 (mean 4.5) years after the operation. There were 14 unilateral and two bilateral adenomas. Two patients have died: one from postoperative complications, the other by suicide 10 years after surgery. None of the patients relapsed and none showed clinical features of Cushing's syndrome. However, five patients remained obese and four hypertensive. Furthermore, in the female patients the bone mineral density was lower than in age-matched controls. The function of the pituitary-adrenal axis recovered slowly. Postoperative replacement therapy was withdrawn 3 to 28 (mean 11.8) months after surgery in all but one patient. The function of the remaining adrenal gland was completely normal in 10 patients. In two patients the plasma cortisol response to ACTH-stimulation was still blunted and associated with elevated plasma ACTH-levels. The plasma ACTH-level was low in the only patient having persistent hypocortisolism. In conclusion, the results show that most patients with Cushing's syndrome due to adrenal adenoma recover fully after surgery. In some patients, however, the suppressed pituitary and/or adrenal fail to resume normal function.     

EFFECT OF CYPROTERONE ACETATE-ETHINYL OESTRADIOL TREATMENT ON ADRENAL FUNCTION IN HIRSUTE WOMEN

Pituitary adrenal suppression has been assessed in twenty-two patients receiving cyproterone acetate (100 mg) and ethinyl oestradiol (30 micrograms) for the treatment of hirsutism. Cortisol responsiveness to ACTH and to insulin induced hypoglycaemia, and diurnal variations of plasma cortisol levels were measured before and after 6 months of treatment. There was no evidence that adrenal suppression is a significant problem in this group of patients.     

INAPPROPRIATE ACTH CONCENTRATIONS IN TWO PATIENTS WITH FUNCTIONING ADRENOCORTICAL CARCINOMA

Two female patients with functioning adrenocortical carcinomas had plasma ACTH detectable by RIA at presentation. In both patients there was evidence for biological activity of ACTH. There was no evidence for an ectopic source of ACTH, nor for a pituitary tumour. Urinary steroid analysis showed patterns of multiple hormone secretion characteristic of adrenocortical carcinomas. The finding of detectable ACTH concentrations in a patient with Cushing's syndrome does not exclude the presence of an adrenocortical tumour.     

纤维支气管镜检查对肺癌的诊断价值

本文报告了经纤支镜检确诊肺癌５０２例，描述了肺癌的组织学类型与纤支镜下的独特表现。着重分析了鳞癌、腺癌、未分化癌纤支镜下表现与病理类型的关联，并对如何提高镜下取材阳性率以及纤支镜检对肺癌手术根治有何指导意义进行分析。     

RECOVERY OF LUTEAL FUNCTION AFTER INTERRUPTION OF GONADOTROPHIN SECRETION IN THE MID-LUTEAL PHASE OF THE MENSTRUAL CYCLE

Ovulation was induced by a pulsatile infusion of GnRH in a patient with hypogonadotrophic amenorrhoea. In order to investigate the effect of short-term withdrawal of gonadotrophin support in the luteal phase, the pulsatile infusion was stopped 3 d after ovulation and restarted 48 h later. After stopping the pump gonadotrophin and progesterone concentrations fell rapidly to very low levels, but when the infusion was restarted progesterone concentrations returned to normal mid-luteal values. Menstruation occurred 14 d after the LH surge. We conclude that normal progesterone secretion by the corpus luteum can be restored after temporary withdrawal of gonadotrophin support.     

EFFECTS OF LONG TERM DEXAMETHASONE TREATMENT IN ADULT PATIENTS WITH CONGENITAL ADRENAL HYPERPLASIA

We have followed nine adult patients with congenital adrenal hyperplasia (CAH) for between 7-77 months on dexamethasone (DXM) 0.5 mg mane and 0.25 mg nocte, reducing to 0.5 mg mane. Twenty-four hour profiles of ACTH, 17-hydroxyprogesterone (17OHP), and androstenedione were performed; the areas under the curves (AUC) and the heights of the morning peaks were used to assess biochemical control. Comparisons were made between treatment before DXM (pre-DXM), 0.75 mg for 2 weeks (DXM-ST), 0.75 mg for at least 3 months (DXM-LT), and 0.5 mg for at least 3 months (DXM-0.5). None of the three males suffered any significant side-effects. All women had menstrual disturbance but in three ovulation was induced. One female developed Cushing's syndrome and two developed hirsutism which resolved on stopping DXM. Overall there was no significant difference between DXM-ST and DXM-LT (mean AUCs for ACTH: DXM-ST 660, DXM-LT 383, for 17OHP: DXM-ST 1177, DXM-LT 587, for androstenedione DXM-ST 232, DXM-LT 121). Reduction of the dose from 0.75 mg to 0.5 mg led to significant deterioration in control (Mean AUC's for ACTH DXM-0.5, 1123 (P less than 0.02), for 17OHP DXM-0.5, 2068 (P less than 0.002), for androstenedione DXM-0.5, 213 (P less than 0.5). We conclude that DXM is a satisfactory regime but the dose must be adjusted for each patient.     

吡喹酮治疗血吸虫病引起四肢驰缓性瘫痪1例

患者刘某 ,男 ,5 0岁 ,在普查血吸虫病时 ,IHA1∶ 10 (++) ,于 2 0 0 0年 10月住院治疗。入院检查　体重 6 5 kg,心肺无异常 ,粪便常规检查正常、集卵孵化血吸虫阴性。乙肝 5项指标阴性 ,肝功能正常 ,B超提示血吸虫性肝纤维化。诊断为慢性血吸虫病。病原治疗　吡喹酮 (韩国产 )总剂量 6 0 m g/kg,二日疗法 ,早、中、晚 3次分服。第 1天服药后稍感恶心 ,腹部不适 ,第 2天早晨突然感觉四肢瘫痪。追问病史 ,既往无软瘫发病史。体检发现 :患者神志清晰 ,心肺正常 ,四肢肌张力降低 ,呈[作者单位 ]　江西省高安市血吸虫病防治站 (高安 330 80 0 …     

HEPATOCELLULAR CARCINOMA IN A NON-CIRRHOTIC PATIENT WITH SUSTAINED VIROLOGICAL RESPONSE AFTER HEPATITIS C TREATMENT

Chronic infection by hepatitis C virus (HCV) is one of the main risk factors for the development of liver cirrhosis and hepatocellular carcinoma. However, the emergence of hepatocellular carcinoma (HCC) in non-cirrhotic HCV patients, especially after sustained virological response (SVR) is an unusual event. Recently, it has been suggested that HCV genotype 3 may have a particular oncogenic mechanism, but the factors involved in these cases as well as the profile of these patients are still not fully understood. Thus, we present the case of a non-cirrhotic fifty-year-old male with HCV infection, genotype 3a, who developed HCC two years after treatment with pegylated-interferon and ribavirin, with SVR, in Brazil.