Hypopituitarism Following External Radiotherapy for Pituitary Tumours in Adults

SUMMARY The development of anterior pituitary hormone deficiencies hasbeen studied in a group of 165 patients who underwent externalradiotherapy for tumours of the pituitary or closely relatedanatomical sites, and who have been observed for up to 10 years.One hundred and forty had undergone pituitary surgery beforeradiotherapy. All patients received external radiotherapy bya three-field technique, giving 3750–4250 cGy in 15 or16 fractions over 20–22 days. A combined test of anteriorpituitary function using insulin hypoglycaemia or glucagon stimulationin conjunction with thyrotrophin and gonadotrophin releasinghormone tests and basal estimations of prolactin, thyroid hormonesand testosterone or oestradiol was performed before radiotherapy.This was repeated six and 12 months later and subsequently annually.Before radiotherapy, 18 per cent of patients had normal growthhormone secretion, 21 per cent had normal gonadotrophin secretion,57 per cent had normal corticotrophin reserve and 80 per centhad normal thyrotrophin secretion. Life table analysis demonstratedincreasing incidences of all anterior pituitary hormone deficiencieswith time: by five years all patients were growth hormone deficient,91 per cent were gonadotrophin deficient, 77 per cent were corticotrophindeficient and 42 per cent were thyrotrophin deficient. At eightyears, respective incidences of deficiencies were 100, 96, 84and 49 per cent. Radiation-induced hyperprolactinaemia was seenin 73 patients; mean serum prolactin concentration rose from227±11 mU/1 to a peak of 369±60 mU/1 at two yearsand subsequently declined towards the basal value. The primarydiagnosis, patient age, sex, irradiated tissue volume and previoussurgery were examined as variables that might influence therate of development of anterior pituitary hormone deficiencies,but none of these factors had a significant effect. The radiationinduced hyperprolactinaemia was however more marked in femalepatients. Although anterior pituitary hormone deficiencies mostcommonly developed in the order growth hormone, gonadotrophin,corticotrophin, thyrotrophin (61 per cent of patients), othersequences were evident. Most notably corticotrophin deficiencyoccurred before gonadotrophin deficiency. There is a high incidence of anterior pituitary hormone deficienciesin patients treated surgically for pituitary tumours and theincidence increases after external radiotherapy. Deficienciesmay occur in an unpredictable sequence and endocrine testingis recommended on an annual basis.     

The effect of external pituitary irradiation on elevated serum prolactin levels in patients with pituitary macroadenomas.

The response of serum prolactin to external radiotherapy was studied in 58 patients (32 women) with pituitary tumours, aged between 16 and 75 years. Forty-four patients underwent pituitary surgery before radiotherapy. Six patients were irradiated with a regimen of 20 Gy in eight fractions over 10-11 days and the remainder received 35-42.5 Gy in 15 fractions over 20-22 days. Following radiotherapy, 44 patients received additional treatment with dopaminergic agonists. Prolactin levels ranged from 1078 to 491,000 mU/l (median 11,750 mU/l) before radiotherapy and all but three patients showed a fall in serum prolactin (measured 4 weeks after stopping bromocriptine in those on dopamine agonist therapy) during observation over periods of up to 154 months. All patients had evidence of pituitary fossa erosion or expansion at presentation and large tumours (Hardy-Vezina Grade 3-4) were more common in male patients (chi 2 = 10.08, p less than 0.01). The rate of fall of serum prolactin levels was greater in patients with true prolactin-secreting tumours when compared with those who had stalk or hypothalamic damage (p less than 0.005). The rate of decline of serum prolactin was also significantly related to the pre-radiotherapy value (rho = 0.519, p less than 0.01). A serum prolactin level less than 500 mU/l was achieved in 31 out of 44 patients treated with radiotherapy and dopaminergic agonist but only nine remained normoprolactinaemic when medication was discontinued for 4 weeks or more. The serum prolactin level fell permanently to less than 500 mU/l in two of 14 patients treated with radiotherapy only. Actuarial analysis of data from all patients indicated a 50 per cent probability that prolactin would be reduced to less than 500 mU/l by 10 years; this increased to 58 per cent for patients with smaller tumours (Hardy-Vezina grade 2).(ABSTRACT TRUNCATED AT 250 WORDS)     

Endocrine Function, Psychiatric and Clinical Consequences in Patients With Macroprolactinomas After Long-term Treatment With the New Non-ergot Dopamine Agonist CV205-502

Although bromocriptine is the mainstay of treatment of macroprolactinomas,its therapeutic usefulness may be limited by poor tolerance,lack of consistent reduction in serum prolactin levels and tumoursize, and the necessity for multiple dosing. Consequently newdopamine agonists have been developed, including the long actingnon-ergot agonist CV205–502 which has been shown to dateto be consistently effective in reducing serum PRL levels andcausing tumour shrinkage. Twelve patients were treated for periods of up to 24 monthswith CV205–502 in doses ranging from 0.075 mg to 1.65mg once daily. Clinical and psychiatric assessments, biochemicalparameters, tumour size determination, and anterior pituitaryfunction tests were performed regularly. Tumour shrinkage wasnoted in all patients, and varied from 11 per cent reductionto complete disappearance of tumour. Prolactin levels becamenormal in seven patients and were reduced by more than 90 percent in the remaining five. Normal menstruation resumed in sixof the eight women, one of whom conceived after one year oftherapy; libido returned in all patients. Psychiatric complicationsoccurred in three patients necessitating withdrawal of therapyin one. Significant weight loss was noted in 11 of 12 patients. Triglyceride concentrations fell from 1.5±0.1 to 1.0±0.1mmol/l at 12 months (p=0.006), and cholesterol fell from 6.3±0.4to 5.3±0.3 mmol/l (p=0.04). The mean TSH response 20min following TRH injection fell from 14.3±2.9 to 8.7±1.3mU/l at 2 months (p=0.027). There was a significant increasein the peak growth hormone response to the insulin stress testfrom basal median (25th–75th centiles) values of 15 (4.4–25.5)mU/l to 24.5 (9–37) mU/l at 2 months (p<0.01) and 31(19.3–63.5) at 12 months (p<0.005). CV205–502 is highly effective in the medical managementof patients with macroprolactinomas, reducing prolactin levelsand tumour size and restoring normal anterior pituitary function.It is, however, associated with the important side effects ofweight loss and pychiatric complications which should be drawnto the attention of clinicians.     

Giant Invasive Prolactinoma: A Case Report and Review of Nine Further Cases

Very large prolactinomas are rare and may be difficult to treat.We present the report of a patient with an exceptionally aggressivetumour which extended outside the skull and emerged within theinternal jugular vein. Bromocriptine induced only transientsuppression of serum prolactin. In vitro studies of tissue fromthis prolactinoma showed that although prolactin secretion wasreduced by both bromocriptine and dopamine, neither agent affectedcytoplasmic levels of prolactin mRNA, suggesting relative autonomyof prolactin synthesis. We reviewed the progress of nine other patients with very largeprolactinomas and serum prolactin levels <<100,000 mU/l.In three cases, treatment with bromocriptine rapidly reducedtumour size and serum prolactin levels became normal, but inthe other cases responses were slower and less marked. Substantialamounts of residual pituitary tumour were seen in all caseswhere serum prolactin remaii above 1000 mU/l, but also in onecase where serum prolactin returned to normal, showing thatserum prolactin levels are not reliable indicators of tumoursize. Two patients died: one developed a CSF leak, and one pneumococcalmeningitis in the absence of recognized CSF leakage. This emphasizesthe significant morbidity associated with very large prolactinomas.The ideal long-term treatment of these tumours remains uncertain,but bromocriptine therapy alone is often inadequate. Cases ofapparent bromocriptine resistance may reflect abnormal regulationof prolactin gene expression.     

Amenorrhoea and hyperprolactinaemia (author's transl)

Prolactin was determined by radioimmunoassay in the serum of 112 patients with primary or secondary amenorrhoea. 21 cases showed hyperprolactinaemia with levels above 25 ng/ml (18.7%). 10 patients with levels between 25 and 50 ng/ml showed heterogeneous clinical features. In nine women (8%) the prolactin level was above 100 ng/ml; they all had severe amenorrhoea. As a result of treatment with bromocriptine menstrual bleeding occurred in 4 out of 7 cases and 2 of these patients became pregnant. In 3 cases prolactin did not return to normal levels and in 2 out of these patients microadenomas of the pituitary gland were diagnosed by special methods. They were removed surgically by the transsphenoidal approach.     

Hypopituitarism following external radiotherapy for pituitary tumours in adults

The development of anterior pituitary hormone deficiencies has been studied in a group of 165 patients who underwent external radiotherapy for tumours of the pituitary or closely related anatomical sites, and who have been observed for up to 10 years. One hundred and forty had undergone pituitary surgery before radiotherapy. All patients received external radiotherapy by a three-field technique, giving 3750-4250 cGy in 15 or 16 fractions over 20-22 days. A combined test of anterior pituitary function using insulin hypoglycaemia or glucagon stimulation in conjunction with thyrotrophin and gonadotrophin releasing hormone tests and basal estimations of prolactin, thyroid hormones and testosterone or oestradiol was performed before radiotherapy. This was repeated six and 12 months later and subsequently annually. Before radiotherapy, 18 per cent of patients had normal growth hormone secretion, 21 per cent had normal gonadotrophin secretion, 57 per cent had normal corticotrophin reserve and 80 per cent had normal thyrotrophin secretion. Life table analysis demonstrated increasing incidences of all anterior pituitary hormone deficiencies with time: by five years all patients were growth hormone deficient, 91 per cent were gonadotrophin deficient, 77 per cent were corticotrophin deficient and 42 per cent were thyrotrophin deficient. At eight years, respective incidences of deficiencies were 100, 96, 84 and 49 per cent. Radiation-induced hyperprolactinaemia was seen in 73 patients; mean serum prolactin concentration rose from 227 +/- 11 mU/l to a peak of 369 +/- 60 mU/l at two years and subsequently declined towards the basal value. The primary diagnosis, patient age, sex, irradiated tissue volume and previous surgery were examined as variables that might influence the rate of development of anterior pituitary hormone deficiencies, but none of these factors had a significant effect. The radiation induced hyperprolactinaemia was however more marked in female patients. Although anterior pituitary hormone deficiencies most commonly developed in the order growth hormone, gonadotrophin, corticotrophin, thyrotrophin (61 per cent of patients), other sequences were evident. Most notably corticotrophin deficiency occurred before gonadotrophin deficiency. There is a high incidence of anterior pituitary hormone deficiencies in patients treated surgically for pituitary tumours and the incidence increases after external radiotherapy. Deficiencies may occur in an unpredictable sequence and endocrine testing is recommended on an annual basis.     

Endocrine Abnormalities in Idiopathic Haemochromatosis

Anterior pituitary functions and sex steroid levels were measuredin 12 patients with idiopathic haemochromatosis (eight males,four postmenopausal females) and age-matched controls, 12 withdiabetes mellitus and five with hepatic cirrhosis. In idiopathichaemochromatosis gonadotrophin deficiency was present in sevenof 12 patients including six of seven patients who had clinicalevidence of hypogonadism. Basal prolactin levels were significantlylower in the patients with idiopathic haemochromatosis comparedwith either of the control groups (p < 0.02). Nine patientswith idiopathic haemochromatosis exhibited subnormal prolactinresponses to thyrotrophin releasing hormone. Thyroid and adrenocor-ticalfunctions were normal in all patients with idiopathic haemochromatosis.Testosterone values were subnormal in five of eight males withidiopathic haemochromatosis; females with idiopathic haemochromatosishad significantly lower testosterone values compared with thediabetic females (p < 0.05). Oestradiol values in both sexesand sex hormone binding globulin values in the males were notsignificantly different in patients with idiopathic haemochromatosiscompared with the controls. Sex hormone binding globulin levelswere significantly higher in females with idiopathic haemochromatosiscompared with either diabetic or cirrhotic females (p < 0.05). Impairment of anterior pituitary function occurs in idiopathichaemochromatosis but is selective; gonadotrophin and prolactindeficiencies are common. Clinical hypogonadism is usually hypogonadotrophicin origin.     

Androgenic Status and Sexual Function in Males with Rheumatoid Arthritis and Ankylosing Spondylitis

The pituitary-testicular axis was investigated in 31 males withrheumatoid arthritis (age range 19–60 years, median 55years) and 33 males with ankylosing spondylitis (age range 22–55years, median 37 years) and compared with a control group of95 normal male volunteers. Using analysis of covariance, patientswith rheumatoid arthritis showed significantly lower serum testosterone(p<0.05) and derived free testosterone (p<0.01) concentrationsand significantly higher serum LH and FSH concentrations (p<0.05)compared with controls. All patients had normal serum prolactinand cortisol concentrations. Serum testosterone correlated withESR, haemoglobln concentrations and rheumatoid factor titres(r<–0.448, p<0.02; r=0.440, p<0.02; r<–0.360,p<0.05 respectively) in the rheumatoid patients. Althoughthere was a significant negative correlation between ESR andhaemoglobin concentrations (p<0.005) in the patients withankylosing spondylitis, neither variable correlated with serumtestosterone concentrations. There was no association betweentesticular dysfunction and the presence of extraarticular featuresof rheumatoid arthritis. Ten patients (33 per cent) with rheumatoidarthritis and four (13 per cent) with ankylosing spondylitisadmitted to periods of impotence while 15 (50 per cent) of theformer and 12 (39 per cent) of the latter had periods of decreasedlibido. There was no evidence for increased rates of infertilityin either group.     

Elderly Patients with Suppressed Serum TSH but Normal Free Thyroid Hormone Levels Usually Have Mild Thyroid Overactivity and are at Increased Risk of Developing Overt Hyperthyroidism

The clinical and biochemical characteristics of 15 elderly patientswith low levels of thyrotrophin (TSH) (<0.1 mU/L) but normalfree tri-iodothyronine, (T3) and free thyroxine (T4) (groupS) were compared with 10 euthyroid subjects (group E) and 10hyperthyroid patients (group T). Free T3 and free T4 were significantlyhigher (p<0.05) in group S(6.3±0.5 and 18.6±1.0pmol/l, respectively) than in group E(4.6±0.3, 12.6+0.6).In common with elderly hyperthyroid patients (group T)patientsin group S had few signs or symptoms of thyrotoxocosis, butthe Wayne score (clinical index of hyperthyroidism) was higherin group S than in euthyroid subjects (p<0.05). Thyroid microsomal,thyrogolobulin or thyrotrophin receptor antibodies were commonin group T (n=9)but not in groups S(n=2) or E(n=1). This suggestsa low prevalence of Graves' disease in group S compared to groupT. Combined thyrotrophin releasing hormone (TRH; 200 µgi.v.) and gonadotrophin releasing hormone GnRH; 100 µgi.v.) tests were performed; no cases of low TSH due to hypopituitarismwere identified in group S. During a mean of 7.9 (4–12)months of observation TSH reverted to the normal range (>0.2mU/L)in 7 of 15 patients in group S; thyroid hormone concentrationsrose above the normal range in four, however, only two patientsrequired treatment for hyperthyroidism. It is unlikely thatthe suppressed TSH of patients in group S was due to mild thyroidhormone excess; although this is often a transitory phenomenon,these patients are at increased risk of developing overt hyperthyroidism.     

Clinico-pathological Correlations and Long-term Follow-up of 253 United Kingdom Patients with IgA Nephropathy. A report from the MRC Glomerulonephritis Registry

The Medical Research Council's Glomerulonephritis Registry wasused to study clinicopathological correlations and renal survivalin patients with IgA nephropathy reported between 1978 and 1985.IgA nephropathy was the histological diagnosis in 9.3 per centof all renal biopsies reported to the registry during this period,and in 18.1 per cent of those with a primary glomerulonephritis.The 10-year cumulative renal survival rate accounting for censoreddata (Kaplan-Meier) was 83.3 per cent. Univariate analysis ofsurvival curves (log-rank test) found the following parametersto be significantly correlated with poor renal survival: serumcreatinine >120 µmol/l (p<0.001), hypertension(p<0.001), serum albumin <40 g/l (p<0.005), proteinuria>1 g (p<0.025), age >30 years (p<0.025), and focalmesangial proliferation (p<0.05). There was no significantdifference in renal survival between males and females. Multivariateanalysis (Cox's proportional hazards model) revealed that onlya serum creatinine of > 120 µmol/l and a serum albuminof <40 g/l were independently predictive of outcome. These findings indicate marked similarities between the UK experienceof IgA nephropathy and the published European experience. IgAnephropathy is not a benign condition in the UK and patientswith impaired renal function and/or those with a reduced serumalbumin are significiantly more likely to progress to end-stagerenal failure within 10 years.     

Low-dose Cyclopenthiazide in the Treatment of Hypertension: A One-year Community-based Study

After an 8-week placebo period, 73 patients whose diastolicblood pressures were between 90 and 110 mmHg were randomly assignedto receive 125 µg (low dose) or 500 µg of cyclopenthiazide(standard dose) for a period of one year. Blood pressure wasmeasured in the patient's home by the same observer at two-weeklyintervals during an 8-week placebo run-in period, every 4 weeksfor a further 12 weeks and at 24, 36 and 52 weeks thereafter.Serum potassium, urate, glucose, glycosylated haemoglobin, totaland HDL cholesterol, and apolipoproteins were measured at theend of the placebo period and at 4, 8, 24 and 52 weeks of activetreatment. Twelve of the 73 patients had an inadequate antihypertensiveresponse—five on the higher dose and seven on the lowerdose. One patient receiving 500 µg was withdrawn becauseof adverse effects. In the remaining 60 patients, systolic anddiastolic blood pressures were significantly reduced when comparedwith pretreatment values in both treatment groups throughoutthe one year period. The decreases in blood pressure were notsignificantly different from each other (p>0.65). Three patientson 500 µg required potassium supplements. Maximum decreasesin the serum potassium of 0.52 mmol/l(500 µg dose) and0.14 mmol/l(125 µg dose) were observed at 24 weeks oftreatment in the remaining 57 patients. The differences betweenthe two doses at this time were statistically significant (p< 0·05), as were the increases in serum urate observedat 4, 8 and 24 weeks (p<0.05). Five hundred micrograms ofcyclopenthiazide increased total serum cholesterol at eightand 24 weeks (0.35, 0.36 mmol/l respectively) when comparedwith pretreatment values (p<0.01) and almost achieved statisticalsignificance when compared with the corresponding low dose value(p = 0.066). This study confirms that 125 µg of cyclopenthiazideis a useful antihypertensive agent with a favourable metabolicprofile which is maintained in the long term.     

Nephrotic Range Proteinuria - A Good Predictive Index of Disease in IgA Nephropathy?

A combined retrospective and prospective study of 86 patientswith IgA nephropathy was conducted to determine whether thelevel of proteinuria was a good predictive index of progressivedisease. The patients fell into three groups: Group A, 31 patientswith proteinuria of less than 1g/day, Group B, 31 patients withproteinuria of 1 to 3.5g/day; and Group C, 24 patients withproteinuria of more than 3.5 g/day. The groups are comparablein age of presentation, sex ratio, and duration of study andshowed no difference in serum creatinine levels, creatinineclearance, incidence of hypertension or incidence of impairedrenal function. Compared with the patients in the other groups,those in Group C did not have increased incidence of progressivedisease. Nevertheless, they have a higher incidence of nephroticsyndrome (p<0.001), a lower incidence of macroscopic haematuria(p<0.05), lower serum albumin (p<0.05) and heavier proteinuria(p<0.01). Severity of proteinuria had no significant correlationwith the severity of renal histopathologic changes. Clinicalobservations divided the 24 patients with nephrotic range proteinuriainto three well-defined groups with different prognoses. Sixpatients had progressive disease with decreasing proteinuria.Five of these remained hypertensive and their initial renalbiopsy showed advanced pathologic changes. Thirteen patientshad persistent proteinuria although the renal function remainedunchanged. Three of these were treated with steroid but failedto respond, and their renal histopathologic changes were usuallymoderate. The remaining five patients showed good response tosteroid treatment although two became steroid-dependent. Theirrenal histopathology showed mild alteration. Our findings suggestthat severe proteinuria in IgA nephropathy does not inevitablyindicate a poor prognosis.     

Iron Overload, but not Treatment with Desferrioxamine Favours the Development of Septicemia in Patients on Maintenance Hemodialysis

During a 19-month period we determined the incidence of bacterialinfection among 39 patients treated with desferrioxamine whohad end-stage renal disease and were undergoing maintenancehemodialysis. Twenty-three received desferrioxamine becauseof aluminium-related bone disease, and 16 because of iron overload.A control group of 193 patients on maintenance hemodialysisbut without desferrioxamine was used. No difference was foundin the incidence of septicemia or of all bacterial infectionsbetween the patients with aluminium-related bone disease treatedwith desferrioxamine and the control patients (0.12 vs. 0.12septicemia per patient-therapy-year, p>0.05; 0.23 vs. 0.26bacterial infections per patient-therapy-year, p>0.05). Theincidence of septicemia in patients treated with desferrioxaminefor iron overload, however, was almost three times that in thecontrol patients (0.36 vs. 0.12 septicemia per patient-therapy-year,p<0.01). To assess the effect of iron overload itself, wedetermined the frequency of bacterial infection in patientson regular hemodialysis who have never received desferrioxamine.These were subdivided into three groups according to serum ferritinlevel which indicated normal or low iron stores (Group I: serumferritin 10-330 µg1/1, n=125), moderate (Group II: serumferritin 331-1000 µg/1, n=49) or more advanced iron overload(Group III: serum ferritin 1001-2000 µg/1, n=10). Comparedto patients with normal or low serum ferritin levels (GroupI), we found a significantly higher rate of bacterial infectionamong patients in Group II compared with Group I (0.18 vs. 0.34infections per patient-therapy-year, p<0.05) and Group IIIcompared with Group I (0.18 vs. 0.58 infections per patient-therapy-year,p<0.01). These results suggest that treatment with desferrioxaminedoes not favour the development of septicemia or bacterial infectionindependently of iron overload and that iron overload itselfmay predispose patients on regular hemodialysis to bacterialinfection.     

Prolactin Dynamics and Tumour Size in the Prediction of Surgical Outcome for Prolactinoma

Each of 62 females were studied for a period of between twoand 72 months ( mean 36 months) following the removal of a prolactinomaby transsphenoidal pituitary surgery. Our aims were to definethe relationships between pre- and post-operative features,the operative findings and the functional outcome. Pre-operativeserum prolactin (PRL) concentrations correlated with tumourdiameter (r = 0.55, p < 0.001). Following surgery two groupsof patients were identified: Group 1, 46 spontaneously and regularlymenstruating patients and Group 2, 16 patients with persistentamenorrhoea. The patients in Group 1 had significantly lowerpre-operative and postoperative serum (PRL) concentrations (p< 0.02 and p < 0.001 respectively) and significantly greaterPRL responses to thyrotrophin releasing hormone (TRH) and metoclopramidestimulation after surgery (p < 0.001). There was not a significantdifference in tumour size between the groups. Forty-four (96per cent) of the patients in Group 1 had normal post-operativeserum PRL concentrations within one week of surgery. By comparison(p < 0.001) only 42 and 20 per cent respectively of Group1 patients who were tested had normal TRH and metoclopramideevoked PRL secretion following surgery. Return of regular menstruationwas associated with cessation of galactorrhoea in 44 patients(96 per cent) and ovulation occurred in 37 of 38 menstruatingpatients for whom data are available. All patients with normalTRH and metoclopramide stimulation tests menstruated spontaneously.Nevertheless most patients who menstruated did so in spite ofretaining suppressed PRL responses. Of 46 patients followedto date whose serum PRL was normal one week after surgery, sevenlater were found to have an elevation of serum PRL outside thenormal range but in only two has this been persistent. We suggestthat a single measurement of serum PRL one week following transsphenoidalpituitary surgery for prolactinoma provides a good basis fordeciding about the future management of patients who desiremenstruation and pregnancy.     

An audit of outcome of treatment in acromegaly

In order to determine whether acromegaly is still associatedwith increased mortality, a hospital case note review of allpatients with acromegaly followed up in Stoke-on-Trent since1967 was carried out Of 79 subjects identified, 51 are aliveand being monitored and 28 have died. Mortality was comparedto the general population by life table analysis. Secretionof growth hormone was assessed and compared in dead and alivepatients. The effect of diabetes, hypertension, and growth hormonesecretion on long-term outcome was assessed. Acromegaly is stillassociated with increased mortality, with an overall ratio ofobserved to expected deaths equal to 2.68 (95% C.I. 1.8–3.9;p<0.001), but the survival of 31 (39%) patients whose growthhormone level had been reduced to below 5 mU/l was equal tothat of the general population (O/E = 1.42; 95% C.I. 0.46–3.31:p<0.05). The dead patients had had significantly higher growthhormone levels than those still alive, but mortality did notappear to be influenced by diabetes or hypertension. The causeof death was vascular in 57% of cases. Growth hormone hypersecretionis still associated with excess mortality in acromegaly. Thepresent study suggests that the therapeutic objective shouldbe to lower average daytime growth hormone levels to less than5 mU/l. There is need for a large study to compare differentmodes of treatment in terms of their effect on growth hormonesecretion and on long-term outcome.     

Study of Lupus Nephritis in Males

Clinical and pathological findings were studied in 23 male patientswith lupus nephritis who were followed up for a period of 41±36months after renal biopsy. Age at renal biopsy was 31±14years and 19 patients (83 per cent) were between 15 and 50 yearsold. C3 and C4 levels were below normal in 23 (100 per cent)and 16 (70 per cent) respectively, CH₅₀ was <25 u/ml in 67per cent, and antinuclear and anti-DNA antibodies were foundin 87 per cent and 82 per cent respectively. Serum albumin levelincreased from 2.9±0.8 g/dl to 3.7±0.8 g/dl duringthe follow up period (p<0.01), while urinary protein decreasedfrom 2.0±2.3 g/day to 1.4±2.5 g/day. There wasa significant improvement in the degree of haematurai (p <0.01),but serum creatinine levels showed no change (mean 1.5 mg/ml).Active proliferative lupus nephritis of, moderate or severedegree was observed in 65 per cent of patients at the initialbiospsy. A trend to regression in this activity was seen inmost serial biopsies, but the chronicity index showed a slightincrease. These data demonstrate that systemic lupus erythematosusin males, in comparison to our previous report of the diseasein female patients, is accompanied by more active nephritis,but that is follows a benign course with therapy.     

Male Hypogonadism -- A Non-specific. Consequence of Illness

Depressed thyroid hormone levels are commonly found in sickpatients. Low serum testosterone concentrations have also beendescribed in men suffering from a number of illnesses. To investigatewhether this might be a non-specific marker of illness, variousendocrine parameters were measured in 30 male patients in ageneral medical ward. Patients were suffering from a wide spectrumof medical disorders and were not receiving drugs known to affectendocrine function. Results were compared with a healthy age-matchedcontrol group. Serum testosterone concentrations (mean±SE)were low in the patient group (8.9±1.1 vs. 18.2±1.4nmo 1/1, p<0.001), correlated significantly with serum T3levels but were not related to prognosis. Half the patientshad testosterone levels below the normal control range. Changesin testosterone concentrations could not be explained on thebasis of binding protein changes, hyperprolactinaemia or depressedpituitary secretion of gonadotrophins. Depression of serum testosteroneconcentrations is a non-specific marker of illness.     

A prospective study of serum lipoproteins after coronary artery bypass surgery

We examined the acute and long-term effects of coronary arterybypass (CABG) surgery on serum lipid, lipoprotein and apolipoproteinlevels. One series of 34 patients having CABG surgery was studiedpre-operatively and for six weeks afterwards, and another 22patients were investigated before and two years after CABG surgery.None of the patients studied received any lipid-lowering drugtherapy or specific dietary advice. In both groups, pre-operativeserum lipoprotein (a) (Lp(a)) and serum triglyceride concentrationswere raised and serum high-density lipoprotein (HDL) cholesteroland apolipoprotein Al (apo Al) were low compared to healthypeople. Acutely, there were profound decreases of 40–60%in the serum levels of cholesterol (p<0.001), low-densitylipoprotein cholesterol (p<0.05), triglycerides (p<0.01),Lp(a) (p<0.05) and apolipoprotein B (apo B) (p<0.05).There was a small decrease in serum apo A1 (p<0.05), andserum HDL cholesterol showed no change. All these variablesregained their pre-operative values within six weeks. Two yearspostoperatively, serum Lpa was 40% less than its pre-operativeconcentration (p < 0.001) and HDL cholesterol had increased(p< 0.001 ). Triglyceride levels decreased (p<0.02) whenß-blockade was withdrawn. The long-term decrease inLp(a) following surgery is unlikely to be due either to stoppingbeta-blockers or to life-style changes. Myocardial ischaemiarelieved by the operation may have been partially responsiblefor its previously raised concentration.     

Age and Other Determinants of Survival After In-hospital Cardiopulmonary Resuscitation

A retrospective review of 274 patients who received in-hospitalcardiopulmonary resuscitation was performed to determine whetherage is independently associated with survival to discharge.Eighty-two (29.9 per cent) of the 274 patients were resuscitatedinitially, but only 25 (9.1 per cent) were discharged alive.Survival to discharge was significantly poorer in patients aged70 years (6/175; 3.4 per cent) than in patients <70 yearsold (19/99; 19.2 per cent) (p<0.001). Severity of illness,assessed by the number of diagnoses and a multifactorial morbidityindex, did not differ between the two age groups. The best resultswere obtained with witnessed arrests, ventricular arrythmiasand resuscitation lasting less than 5 minutes; however, elderlypatients were less likely to be resuscitated in all circumstances.Age (r=–0.31, p<0.001) and the morbidity index r=–0.18,p<0.05) were independently associated with survival by multivariateanalysis. These results indicate that advanced age is an important independentdeterminant of survival after resuscitation. This should betaken into consideration when making in-hospital resuscitationdecisions.     

A Three-Year Survey of Viral Hepatitis in West London

During a total population survey of viral hepatitis in the LondonBoroughs of Hounslow, Richmond and Ealing, 784 patients wereseen in three years from 1 March 1972 to 28 February 1975. Adiagnosis of viral hepatitis was accepted in 489. The annualincidence was 24 per 100 000. 455 of the patients were testedfor the hepatitis B surface antigen (HBsAg) by a radioimmunoassaytechnique and 93 (20 per cent) of these were positive. The majorityof the patients with typc B hepatitis were in their third orfourth decades. None was under the age of 16. The male to femaleratio among patients with hepatitis B was 2 to 1 in those underthe age of 30 and 5 to 1 in those aged 30 and over. The seasonal distribution of viral hepatitis showed a peak inthe spring, solely from an increased incidence of non-B hepatitis,and a second, smaller peak in the autumn. There was no appreciableclustering of patients except for one local outbreak in a housingestate during the first year affecting mainly children goingto the same primary school, and their parents. Patients with hepatitis B had a longer pre-icteric illness (p< 0·05), greater duration of jaundice (p < 0·001)and higher peak levels of serum bilirubin (p < 0·0005)and sernum alanine amino transferase (A1 T) (p < 0·03)than patients with non-B hepatitis. The finding of the surfaceantigen was also associated with a higher frequency of skinrash (p < 0·0005) and a greater duration of arthralgia(p < 0·03). Among the HBsAg negative patients theincidence of arthralgia increased with age (p < 0·0005).Abdominal pain (p < 0·005) and vomiting (p < 0·005)were more common in the young. The injection experience of patients with hepatitis B showeda high proportion of ‘nontherapeutic’' exposuresuch as drug addiction. Significantly more HBsAg positive menwere single than in the local community (p < 0·0001)or among the HBsAg negative men (p < 0·01). Therewas no significant difference between the proportions of singlewomen among the antigen positive and negative patients. Manyof the HBsAg positive single men were either known to be orstrongly suspected of being homosexual. The ad subtype of the HBsAg was found more often in males (p< 0·01), particularly over the age of 30. All eightdrug addicts tested for subtype were ay, as were two non-addictedfemale consorts. The association between addiction and ay subtypewas highly significant in the males (p < 0·001). Tbcad subtype was found in an 11 of the admitted homosexual HBsAgpositive men and in all but one of the 17 strongly suspectedof being homosexual.