Treatment of acromegaly with bromocryptine.

Four men and 4 women with active acromegaly were treated with bromocryptine for 4 to 5 weeks. Serum growth hormone levels response to a glucose load were measured before and in the last weed of treatment. In only 1 patient was the grwotoh hormone response rendered normal by the drug. This patient, but none of the others, also showed an improvement in glucose tolerance and a reductin of the raised serum insulin levels during the glucose load. In three of the 8 patients vomiting was troublesome side effect of treatment.

Apoptosis and p53 suppressor gene protein expression in human anterior pituitary adenomas.

Human anterior pituitary adenomas proliferate and express the p53 tumour suppressor gene protein, but it is not known if apoptosis (programmed cell death) occurs. Therefore, the detection of apoptosis was undertaken in tumorous human anterior pituitary tissue and compared with p53 protein expression, tumour type and tumour size. Apoptosis (detected by the in situ end labelling technique) and p53 suppressor gene protein (detected by DO.1-antibody immunocytochemistry) were determined in formalin-fixed and paraffin-embedded tissue from 37 human pituitary adenomas (2 macroprolactinomas, 9 somatotrophinomas and 26 non-functioning adenomas). Two normal anterior pituitaries were also included in this study. Pre-operative tumour size was scored 1 to 4 from magnetic resonance imaging radiology. Apoptosis was found in 7 of 29 tumours (24%), 11% of somatotrophinomas and 33% of non-functioning adenomas, although this difference was not significant. The p53 tumour suppressor protein was found in 7 of 31 tumours (23%), 33% of somatotrophinomas and 19% of non-functioning adenomas. Apoptosis and p53 protein expression were not found in normal anterior pituitary. In conclusion, apoptosis occurs in human anterior pituitary adenomas, but no significant association was found between apoptosis and p53 protein expression, tumour type or tumour size.

A comparison of proliferation indices in human anterior pituitary adenomas using formalin-fixed tissue and in vitro cell culture.

The authors compared detection methods for cell proliferation in human anterior pituitary adenomas using histological sections and dispersed cell culture. After tumor cells had been grown for 4 days in dispersed culture, bromodeoxyuridine (BUdR), proliferating cell nuclear antigen (PCNA), and Ki-67 were compared by double immunostaining and contrasted with single staining of PCNA and Ki-67 indices in the corresponding histological sections from 12 human pituitary adenomas. In vitro, the BUdR labeling index was positive in six of 12 tumors (range < 0.1-5.1%), 10 of 12 tumors were PCNA-positive (range < 0.1-100%), and Ki-67 was positive in 10 of 12 adenomas (range < 0.1-8%). In vitro, BUdR and Ki-67 gave similar proliferative indices for 10 of 12 adenomas. In vivo, the PCNA labeling index was positive in 12 of 12 adenomas (range 0.9-95%) and Ki-67 was positive in 11 of 12 adenomas (range < 0.1-2%). Tumors with a labeling index less than 0.1% were considered to be negative for proliferation. High PCNA values were found in vitro and in vivo, whereas Ki-67 labeling indices were similar in vitro and in vivo for nine of 12 adenomas. It is concluded that Ki-67 proliferative indices in vivo reflect those found in vitro, at least after 4 days in dispersed culture, but that PCNA overestimates pituitary adenoma proliferation in histological sections as well as in dispersed culture.

Identification of proliferating human anterior pituitary adenoma cells in vitro.

A method to determine whether dispersed human anterior pituitary adenoma cells proliferate in mixed culture was developed. Fifteen pituitary adenomas were dispersed enzymatically to single cells, following which twelve were double immunostained after eight days. Proliferating cells were identified immunologically following one hour of bromo-deoxyuridine incorporation. Adenoma cells were subsequently identified with an anti-neuron-specific enolase antibody system. A time course of bromo-deoxyuridine labelling was performed on three nonfunctional adenomas over a four day period, with bromo-deoxyuridine being added to cultures at one hour, 24 hours and four days prior to immunostaining. Double immunolabelled cells were unambiguously identified by a dark brown nucleus surrounded by red cytoplasm. Eight out of 12 pituitary adenomas (two prolactinomas, three nonfunctional, three growth hormone secreting) showed an increased bromo-deoxyuridine labelling index (range 0.1%-1.4%). Bromo-deoxyuridine incorporation over four days showed an increase in bromo-deoxyuridine from 0.02%, 0.03% and 3.3% at one hour to 10.1%, 1.3% and 5.0% at four days, respectively, but evidence of mitosis was scant. This study shows that pituitary adenomas may proliferate in vitro and that this double immunostaining method may be used as an in vitro proliferation assay in a mixed cell population.

The long-term stability in whole blood of 14 commonly-requested hormone analytes.

Concentrations of 14 commonly-requested plasma hormones were measured in octuplicate in each of six subjects to determine their stability when unseparated from red cells for periods up to 1 week. Most of the analytes were stable when stored in this way and although statistically significant changes were recorded, in the great majority of cases the changes seen would have no bearing on the clinical interpretation of the result. In the light of these findings, we would confidently report results of analyses for these hormones in plasma that had remained in contact with red cells at ambient temperature for long periods of time.

Pain relief and pituitary function following injection of alcohol into the pituitary fossa.

Eleven patients were investigated for pituitary function after the injection of alcohol into the pituitary fossa; all had persistent pain and 8 had carcinoma of the breast. Most of the patients showed varying degrees of reduction of pituitary activity; 8 patients obtained significant pain relief and 3 patients exhibited polyuria. These 3 observations could not be completely correlated; the possible mechanisms which may lead to pain suppression by this method are discussed.

The induction of amenorrhoea.

A survey has shown that many women favour eliminating menstruation and it has been suggested that therapeutic induction of amenorrhoea might be an advantage in female personnel mobilised for war. The traditional method has been to take the oral contraceptive pill continuously. This produces weight gain and other side-effects; spotting and breakthrough bleeding can be a problem initially. The method is however cheap. The Gonadotrophin Releasing Hormone (GnRH) analogue, goserelin, is extremely effective, produces less side-effects, but it is very expensive. Two synthetic steroids, danazol and gestrinone, are moderately effective, have a variety of prominent side-effects and are also quite expensive. With all these drugs normal menstruation resumes in the cycle after they are discontinued. Although goserelin has many advantages over the continuously taken contraceptive pill, its cost precludes it from consideration as a means of eliminating menstruation.

PIP: The Royal Army Medical Corps (RAMC) of the UK is considering offering women in the Army the option of inducing amenorrhea especially those in war. Logistics problems of supplying sufficient sanitary protection makes inducing amenorrhea in these women an advantage. It is important that the Royal Army not force servicewomen ready for war to agree to chemical induction of amenorrhea, however. A survey of civilian women shows that 80% liked the notion of eliminating menstruation. continuous combined oral contraceptive (COC) therapy induces amenorrhea, but it poses some side effects including bleeding and spotting, 2 kg weight gain, breast tenderness, depression, and headaches. 12 weeks of COC therapy costs range form 2 to 6 pounds. The synthetic androgen used to treat endometriosis, danazol, may also induce amenorrhea at daily doses of 800 mg. It causes various side effects including reduced breast size, flushing, sweating, loss of libido, acne, weight gain, edema, hirsutism, and voice change. 12-week danazol therapy costs about 200 pounds. Another drug with androgenic, antigonadotrophic, antiestrogenic, and antiprogestogenic properties which is also used to treat endometriosis, gestrinone, in another possible amenorrhea inducer at 2 doses of 2.5-5 mg/week. Side effects are similar to those of danazol. In 1 study, all 20 patients developed acne and seborrhea. Its 12 week costs are considerably more than danazol and COC therapy (450 pounds). Intermittent administration of 2 gonadotropin releasing hormone (GnRH) analogues, buserelin and goserelin, suppresses production of gonadotropins. Health workers need to inject 3.6 mg goserelin every 28 days while they administer buserelin subcutaneously or intranasally. the leading side effect on both GnRH analogues is not flushes. 12-week therapy is about 375 pounds. Fertility is restored after discontinuation of all the aforementioned therapies. The GnRH analogue goserelin is the most effective therapy, but the cost factor causes the Royal Army to favor COCs.

The XY female in sport: the controversy continues.

The summer and winter Olympic Games have been accompanied by much press coverage of the controversy and confusion over sex tests for sportswomen. Much of this has centred on the eligibility of subjects with androgen insensitivity to compete in women's events. The purpose of this paper is to review the process of sex differentiation and its abnormalities, highlighting those conditions in which biologically active testosterone is secreted which might confer an advantage in women's sporting events.

The role of a single free beta-human chorionic gonadotrophin measurement in the diagnosis of early pregnancy failure and the prognosis of fetal viability.

The prospective controlled study investigated the concentrations of free beta-human chorionic gonadotrophin (HCG) subunit in 554 women with a singleton intrauterine or tubal pregnancy. They presented with vaginal bleeding and/or abdominal pain in the first 18 weeks of pregnancy. The control group comprised 156 women with musculoskeletal pain and no vaginal bleeding. Their pregnancies continued to term. The study group comprised 398 women (141 threatened-continuing pregnancies, 37 threatened-miscarriages, 185 non-continuing pregnancies and 35 tubal pregnancies). Free beta-HCG concentrations were significantly lower in the non-continuing, threatened-miscarriage and tubal pregnancy groups [mean 4.62, 6.50 and 4.27 ng/ml respectively; 95% confidence interval (CI) 3.75-5.69, 4.46-9.48 and 2.92-6.2 respectively] than in the control and threatened-continuing groups (mean 41.61 and 48.22 ng/ml respectively; 95% CI 34.53-50.13 and 42.03-55.32 respectively) (P < 0.001 in all cases). A cut-off value at 20 ng/ml was found to differentiate between the 'viable' (control and threatened-continuing) and the 'abnormal' (non-continuing, threatened-miscarriage and tubal) pregnancies, with 88.3% sensitivity and 82.6% positive predictive value. An excellent diagnostic and prognostic usability of free beta HCG was confirmed by a receiver operating characteristic curve plot. In conclusion, a single serum free beta-HCG measurement taken in early pregnancy is valuable in the immediate diagnosis of early pregnancy failure and the long-term prognosis of viability.