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.     

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 tumour size, and the necessity for multiple dosing. Consequently new dopamine agonists have been developed, including the long acting non-ergot agonist CV205-502 which has been shown to date to be consistently effective in reducing serum PRL levels and causing tumour shrinkage. Twelve patients were treated for periods of up to 24 months with CV205-502 in doses ranging from 0.075 mg to 1.65 mg once daily. Clinical and psychiatric assessments, biochemical parameters, tumour size determination, and anterior pituitary function tests were performed regularly. Tumour shrinkage was noted in all patients, and varied from 11 per cent reduction to complete disappearance of tumour. Prolactin levels became normal in seven patients and were reduced by more than 90 per cent in the remaining five. Normal menstruation resumed in six of the eight women, one of whom conceived after one year of therapy; libido returned in all patients. Psychiatric complications occurred in three patients necessitating withdrawal of therapy in one. Significant weight loss was noted in 11 of 12 patients. Triglyceride concentrations fell from 1.5 +/- 0.1 to 1.0 +/- 0.1 mmol/l at 12 months (p = 0.006), and cholesterol fell from 6.3 +/- 0.4 to 5.3 +/- 0.3 mmol/l (p = 0.04). The mean TSH response 20 min following TRH injection fell from 14.3 +/- 2.9 to 8.7 +/- 1.3 mU/l at 2 months (p = 0.027). There was a significant increase in the peak growth hormone response to the insulin stress test from 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 less than 0.01) and 31 (19.3-63.5) at 12 months (p less than 0.005). CV205-502 is highly effective in the medical management of patients with macroprolactinomas, reducing prolactin levels and tumour size and restoring normal anterior pituitary function. It is, however, associated with the important side effects of weight loss and psychiatric complications which should be drawn to the attention of clinicians.     

Prolactin response to thyrotropin-releasing hormone in children with gynecomastia, premature thelarche and idiopathic precocious puberty

Plasma prolactin (PRL) response to synthetic thyrotropin-releasing hormone (TRH) was studied in six patients with pubertal gynecomastia, five patients with premature thelarche and nine female patients with idiopathic precocious puberty. The basal concentration of plasma PRL was higher (p less than 0.01) in pubertal gynecomastia as compared to control, while baseline plasma PRL levels in premature thelarche and idiopathic precocious puberty were similar to those in controls. Plasma PRL level after TRH in patients with pubertal gynecomastia was higher (p less than 0.01) than that in control, while plasma PRL responses to TRH in idiopathic precocious puberty and premature thelarche were comparable to those controls. The TRH-induced PRL release was more enhanced during treatment with cyproterone acetate (CA) than before CA therapy in four of five patients with idiopathic precocious puberty. These data suggest that the enhanced release of PRL may, at least in part, contribute to breast enlargement in pubertal gynecomastia and that seen in idiopathic precocious puberty and premature thelarche may not depend on the PRL secretion. The prolonged administration of CA enhances the PRL responsiveness to TRH.     

Laboratory assessment of prolactin status.

The laboratory assessment of prolactin status was evaluated by detailed study of 921 subjects (587 normal subjects and 334 patients with pathological conditions). The effect on serum prolactin levels of age, sex, circadian rhythm, pulsatility of secretion, stress, drug ingestion, and pregnancy was defined in normal subjects. The normal prolactin responses to stimulation (TRH metoclopramide) and suppression (L-dopa, bromocriptine) were also determined. Basal prolactin levels were measured in patients with defined pathological conditions including prolactinoma, idiopathic hyperprolactinaemia, acromegaly, Cushing's disease, chronic renal failure, primary hypothyroidism, pituitary ablation, Kallman's syndrome, Nelson's syndrome, growth hormone deficiency, gonadotrophin deficiency, craniopharyngioma, panhypopituitarism, and chronic progressive arthropathy. Based on these data, a strategy for the routine laboratory assessment of prolactin status is outlined.     

PRL性垂体腺瘤术后动态垂体激素观察与MRI结果的相关性分析

目的探讨垂体泌乳素腺瘤切除后血清泌乳素水平与术后MRI结果之间的相关性,以判断PRL腺瘤患者术后有无肿瘤残留及评估预后。方法对18例垂体泌乳素性腺瘤患者的术前及肿瘤切除后泌乳素水平进行动态观察,对肿瘤切除后血清激素水平与术后MRI结果之间的相关性进行统计学分析。结果肿瘤切除前、后血清泌乳素水平具有显著性差异;肿瘤切除后24小时及以后各时点血清泌乳素水平无显著性差异;激素评定方法和MRI评定结果无显著性差异,一致性好。结论垂体泌乳素腺瘤切除术后早期连续动态血清PRL监测结果对判断术后有无肿瘤残留具有重要价值。     

Abnormal conjugated dopamine levels in patients with normoprolactinaemic amenorrhoea and in insulin-dependent diabetic patients

We determined the circulating dopamine levels in 17 patients with insulin-dependent diabetes mellitus (IDDM), of whom eight had amenorrhoea (DM-AM) and nine were normally menstruating (DM). Seven non-diabetic women with normoprolactinaemic, normogonadotrophic secondary amenorrhoea (AM) and nine normally menstruating women (controls) were studied. In all subjects basal blood concentrations of free dopamine (f-DA), conjugated dopamine (c-DA), epinephrine (E), norepinephrine (NE), prolactin (PRL), luteinizing hormone (LH), thyroid-stimulating hormone (TSH) and oestradiol-17 beta were determined and all subjects, except for three AM patients, had a Metoclopramide test performed for measurements of f-DA, c-DA, PRL, LH and TSH. Plasma c-DA was significantly (p less than 0.05) increased in patients with amenorrhoea compared to the respective control groups. In diabetic patients c-DA levels were significantly (p less than 0.05) lower compared to controls. The ratio between basal f-DA and c-DA concentrations was significantly (p less than 0.01) higher in diabetic patients compared with non-diabetic patients. After Metoclopramide stimulation DM-AM patients showed a significant (p less than 0.05) rise in c-DA, whereas this was not seen in other groups. DM-AM patients had significantly (p less than 0.05) lower basal PRL and LH levels than DM patients and controls. In addition DM-AM patients had a significantly (p less than 0.05) lower PRL response to Metoclopramide compared with DM patients. There were no significant correlations between catecholamines and basal as well as Metoclopramide stimulated pituitary hormones. This study suggests that the abnormal pituitary hormone secretion in patients with amenorrhoea may in part be caused by an increased dopaminergic activity.(ABSTRACT TRUNCATED AT 250 WORDS)     

Direct effects of catecholamines, thyrotropin-releasing hormone, and somatostatin on growth hormone and prolactin secretion from adenomatous and nonadenomatous human pituitary cells in culture.

To determine the mechanism and the site of action of catecholamines as well as hormones including thyrotropin-releasing hormone (TRH)1 and somatostatin on pituitary hormone release in patients with acromegaly and in normal subjects, the effects of these substances on growth hormone (GH) and prolactin (PRL) secretion from adenomatous and nonadenomatous human pituitary cells in culture were examined. When dopamine (0.01-0.1 microM) or bromocriptine (0.01-0.1 microM) was added to the culture media, a significant inhibition of GH and PRL secretion from adenoma cells from acromegalic patients was observed. This inhibition was blocked by D2 receptor blockade with metoclopramide or sulpiride, but not by D1 receptor blockade. Similarly, dopamine suppressed GH and PRL release by nonadenomatous pituitary cells in a dose-dependent manner, which was again blocked by D2 receptor blockade. The minimum effective concentration of dopamine required for a significant inhibition of PRL secretion (0.01 microM) was lower than that for GH release (0.1 microM). Norepinephrine, likewise, caused a suppression of PRL secretion from adenomatous and nonadenomatous pituitary cells. This effect was blocked by sulpiride, phentolamine, however, was ineffective. When TRH was added to the media, both GH and PRL secretion were enhanced in adenoma cells, while only the stimulation of PRL release was observed in nonadenomatous pituitary cells. Coincubation of TRH and dopamine resulted in variable effects on GH and PRL secretion. Somatostatin consistently lowered GH and PRL secretion in both adenomatous and nonadenomatous pituitary cells and completely blocked the TRH-induced stimulation of GH and PRL secretion from adenoma cells. Opioid peptides (1 microM) failed to affect hormone release. These results suggest that no qualitative difference in GH and PRL responses to dopaminergic agonists or to somatostatin exists between adenoma cells of acromegalic patients and normal pituitary cells, and that the direct effect of catecholamines on GH and PRL secretion from human pituitary cells is mediated mainly through dopamine receptor activation.     

Serum vaspin and adiponectin levels in patients with prolactinoma

Background: Studies investigating serum vaspin and adiponectin levels in patients with prolactinoma are inconclusive. The aim of this study was to evaluate serum vaspin and adiponectin levels in patients with prolactinoma and healthy controls. Methods: A total of 42 prolactinoma patients (Group 1, 21 patients; Group 2, 21 patients) and 30 healthy controls were enrolled in the study. Group 1 consisted of newly diagnosed patients who were never treated or had not received a dopamine agonist (DA) within 6 months prior to screening. Group 2 consisted of prolactinoma patients who were on DA treatment for at least 6 months at the time of screening. The control group (group 3) consisted of healthy controls. Results. Patients with prolactinoma had higher homeostasis model assessment of insulin resistance and lower quantitative insulin sensitivity check index values in comparison to healthy controls (p?p?p?p?>?0.05) and 5.041 (1.191–21.339; p?Conclusion: This is the first study to demonstrate the presence of low vaspin levels in patients with prolactinomas. Further studies are needed to help establish the roles of vaspin and adiponectin in prolactinoma patients.     

Thyroid function after subtotal resection for hyper-thyroidism: a prospective study

B.KÅGEDAL¹
Abstract. Eight-seven patients treated for thyrotoxicosis by subtotal thyroidectomy were examined 6 weeks, 6 months and 12 months after surgery. Thirty-six of the patients were also examined 24 months after surgery.
The patients were divided into two groups according to serum concentration of thyrotrophin (TSH) 6 weeks after surgery. Group I contained fifty-five patients with a normal serum TSH, of whom three developed recurrent hyperthyroidism during the observation period. The remaining fifty-two patients were clinically euthyroid during the entire observation period but had rather low serum thyroxine (T4) levels and normal serum triiodothyronine (T3) levels 6 weeks after surgery. Most patients had a normal TSH response to thyro-trophin-releasing hormone (TRH). T4 levels rose significantly within 6 months after surgery and then remained almost unchanged.
Group II contained thirty-two patients with a serum TSH above 5 mU/1 6 weeks after surgery. Seven of these patients developed hypothyroidism within 1 year of surgery. The twenty-five remaining patients had low serum T4 with normal serum T3 levels at 6 weeks. TSH response to TRH was pathologically raised. Basal TSH level remained raised during the observation period but serum T4 levels approached those in group I within 12 months.
These investigations show that patients with a raised basal serum TSH are at risk of developing hypothyroidism. Normal serum concentrations of thyroid hormones are reached sooner by patients with normal TSH levels than by patients with raised TSH levels. The basal serum TSH level seems to be a better indicator of risk of hypothyroidism than the serum T4 level, which is low in most patients 6 weeks after surgery.     

GHRH and TRH tests in patients with idiopathic and secondary GH deficiency--with special reference to GH response patterns to GHRH

To study whether patients with idiopathic GH deficiency (IGHD) show a delayed GH response pattern to GHRH, 42 patients with IGHD, 14 patients with hypothalamic tumor (2ry GHD), and 23 normal short children (NSC) were examined as to their GH response patterns to GHRH together with their TSH and PRL response patterns to TRH. After TRH injection, the mean time of the TSH peak in IGHD (67.5 +/- 6.5 min, n = 36) and 2ry GHD patients (81.7 +/- 14.8 min, n = 9) was clearly delayed comparing to that of NSC (29.1 +/- 2.9 min, n = 16; both p less than 0.01). Similarly, the mean time of the PRL peak in IGHD (38.3 +/- 3.6 min, n = 36) and 2ry GHD patients (39.5 +/- 5.8, n = 11) was significantly delayed comparing to NSC (22.0 +/- 3.5 min, both p less than 0.01). In IGHD patients, the delayed response pattern of TSH and PRL was more remarkable in patients who had breech delivery than in those with normal delivery. In contrast, the mean time of the GH peak was similar in IGHD (62.1 +/- 4.0 min, n = 41), 2ry GHD (64.1 +/- 8.1 min, n = 11) and NSC (58.0 +/- 6.1 min, n = 23). However, the decline from peak GH (120 min GH/peak GH) was significantly smaller in IGHD (54.3 +/- 4.2%) and 2ry GHD (60.7 +/- 7.3%) than in NSC (39.0 +/- 8.1%) (both p less than 0.05). Further, in IGHD patients plasma GH response was greater in patients with normal delivery than in those with breech and asphyxia delivery. These results seem to indicate: 1) the stimulus-secretion mechanism is different between somatotrophs and thyrotrophs or lactotrophs in man, 2) IGHD patients have hypothalamic lesions as well as pituitary lesions, 3) such hypothalamo-pituitary lesions in IGHD patients are greater in patients with abnormal delivery than in those with normal delivery.     

The importance of anaemia in cerebral and uncomplicated falciparum malaria: role of complications, dyserythropoiesis and iron sequestration

Ninety-four per cent of 169 patients with cerebral malaria developed anaemia (haematocrit less than 35 per cent) and 30 per cent required blood transfusion to maintain the haematocrit at more than 21 per cent. Anaemia was at its worst on admission in 58 patients (34 per cent); in the rest the haematocrit fell further, reaching its nadir one to 17 days later (mean 2.3 days). The mean lowest haematocrit was 24.3 +/- 7.2 per cent (+/- 1 SD) and the mean maximum fall was 7.9 +/- 5.6 per cent. Anaemia was more severe in patients with bacterial infection, retinal haemorrhages, schizontaemia and in pregnancy. The lowest haematocrit correlated with admission parasitaemia (r = -0.33, p less than 0.001), total serum bilirubin (r = -0.25, p less than 0.01) and serum creatinine (r = -0.22, p less than 0.01). In 23 patients with uncomplicated falciparum malaria the mean serum iron on admission was 53 micrograms/dl (range 16-157) and the mean serum ferritin 1773 ng/ml (range 170-10 000). There was a significant (p less than 0.001) rise in serum iron 96 h after starting antimalarial treatment; the serum ferritin declined slowly over several weeks. Stainable iron was present in all marrows examined and in eight patients the characteristic pattern of the anaemia of chronic disorders was seen. Seventy-three per cent of patients had dyserythropoiesis which was moderate to gross in 36 per cent. Dyserythropoiesis and erythrophagocytosis were often present on admission but sometimes appeared after the parasitaemia had cleared and persisted for at least three weeks into convalescence. These disturbances in iron metabolism and haemopoiesis are not completely explicable by red blood cell parasitisation. They may contribute more to the anaemia than has previously been recognised.     

The Effects of Transsphenoidal Surgery on Endocrine Function and Visual Fields in Patients with Functionless Pituitary Tumours

SUMMARY Twenty-eight patients with functionless pituitary tumours havebeen treated by transsphenoidal surgery over the last 28 months.Mean age at presentation was 55 years. Tumour size was gradedaccording to the extent of suprasellar extension on CT headscanfrom above the interclinoid line: four were small, 15 mediumand nine large. Before surgery in 25 per cent of patients visual acuity andvisual fields were normal. In the immediate postoperative period,24 per cent of the patients with visual defects before surgeryhad normal vision, and in 38 per cent of the others it was improved.Six months after surgery, there had been further improvement;43 per cent had normal vision and 48 per cent showed an overallimprovement. In no patient did vision deteriorate followingsurgery. In the patients who presented with visual symptomsof one year or less, there was no correlation between the lengthof symptoms and the extent of visual recovery after surgery.Average age of the patients with full visual recovery was 47±4years (mean±SEM); average age of the patients with onlypartial visual recovery was 63±3years. Prolactin levels before surgery were elevated in 77 per centof patients and fell significantly after operation, remainingelevated in 28 per cent of patients six months later. Fiftyper cent of patients were treated with long-term hormone replacementtherapy. Transsphenoidal surgery led to improved vision in the majorityof patients, the results being comparable with those obtainedwith transfrontal surgery. Surgical complications were few,and long-term morbidity low. We suggest that the first-linetreatment for patients with functionless pituitary tumours shouldbe transsphenoidal surgery, even when large suprasellar extensionsare present     

A comparative study of the relative effects of anticonvulsant drugs and dietary folate on the red cell folate status of patients with epilepsy

In a survey of the red cell folate status of 200 patients with epilepsy, compared to 72 controls, we found that median red cell folate levels were reduced significantly in patients treated with phenytoin (p less than 0.01) or carbamazepine (p less than 0.001) alone. Patients taking more than one drug had reduced levels also (p less than 0.001), but in patients treated with sodium valproate alone there was no significant decrease in red cell folate levels compared to controls. Twenty-two per cent of patients in the group taking more than one drug had reduced levels of red cell folate compared with 17 per cent of those taking carbamazepine alone, 13 per cent of those taking phenytoin only, and 9 per cent of those taking sodium valproate only. Dietary folate intake was significantly reduced in all the patient groups compared with controls (p less than 0.001 for the carbamazepine and phenytoin groups, p less than 0.01 for the polypharmacy and sodium valproate groups); a significant correlation between red cell folate levels and dietary folate was not established. Significant negative relationships were established between carbamazepine dose (r = -0.35, p less than 0.01) or serum level (r = -0.27, p less than 0.05) and red cell folate level in patients on one drug only. The correlation between dose or serum level of phenytoin and red cell folate level was also negative but did not reach significance. Our findings show that all anticonvulsant drugs interfere with folate metabolism.(ABSTRACT TRUNCATED AT 250 WORDS)     

Defective dopaminergic regulation of prolactin secretion in patients with hyperprolactinemia

In order to evaluate the dopaminergic control of the lactotroph, we examined the plasma prolactin response to metoclopramide (a dopamine receptor blocker, 10 mg iv bolus) and to dopamine (1 microgram/Kg/min iv infusion for 120 min) in 52 hyperprolactinemic female patients and 19 healthy volunteer women. Three diagnostic categories were included: "idiopathic" hyperprolactinemia (21), microadenoma (24), and macroadenoma (7). Patients from all groups showed a marked blunting of the prolactin response to metoclopramide as compared to the prolactin rise in normal women (p less than 0.001). However, normal responses were observed in 8 patients with idiopathic hyperprolactinemia and in one patient with adenoma. The magnitude of the prolactin response to metoclopramide (percent of baseline level) correlated negatively with the level of basal prolactin in each group except for macroadenoma patients. Dopamine infusion significantly (p = 0.015) reduced the mean plasma prolactin levels in hyperprolactinemic patients and normal women. However, patients with idiopathic hyperprolactinemia were hyposensitive to dopamine (p less than 0.05). Furthermore, microadenoma patients were less responsive to dopamine suppression than were the patients with macroadenoma (p less than 0.05). The results indicate the presence of a relative resistance to dopamine in patients with idiopathic hyperprolactinemia and in patients with microadenoma. They also suggest that in these patients, the decrease in prolactin response to metoclopramide may be explained by the relative refractoriness to endogenous dopamine.     

Androgenic status and sexual function in males with rheumatoid arthritis and ankylosing spondylitis

The pituitary-testicular axis was investigated in 31 males with rheumatoid arthritis (age range 19-60 years, median 55 years) and 33 males with ankylosing spondylitis (age range 22-55 years, median 37 years) and compared with a control group of 95 normal male volunteers. Using analysis of covariance, patients with rheumatoid arthritis showed significantly lower serum testosterone (p less than 0.05) and derived free testosterone (p less than 0.01) concentrations and significantly higher serum LH and FSH concentrations (p less than 0.05) compared with controls. All patients had normal serum prolactin and cortisol concentrations. Serum testosterone correlated with ESR, haemoglobin concentrations and rheumatoid factor titres (r = -0.448, p less than 0.02; r = 0.440, p less than 0.02; r = -0.360, p less than 0.05 respectively) in the rheumatoid patients. Although there was a significant negative correlation between ESR and haemoglobin concentrations (p less than 0.005) in the patients with ankylosing spondylitis, neither variable correlated with serum testosterone concentrations. There was no association between testicular dysfunction and the presence of extra-articular features of rheumatoid arthritis. Ten patients (33 per cent) with rheumatoid arthritis and four (13 per cent) with ankylosing spondylitis admitted to periods of impotence while 15 (50 per cent) of the former and 12 (39 per cent) of the latter had periods of decreased libido. There was no evidence for increased rates of infertility in either group.     

Osteocalcin and urinary hydroxyproline/creatinine ratio in the differential diagnosis of primary hyperparathyroidism and hypercalcaemia of malignancy

Osteocalcin (serum bone-Gla protein, sBGP), serum alkaline phosphatase (sAP) and urinary hydroxyproline/creatinine ratio (uOH-Prol/creatinine) have been measured in 21 patients with primary hyperparathyroidism (PHPT) and in nine patients with hypercalcaemia of malignancy (HM). A positive linear correlation between sBGP and uOH-Prol/creatinine ratio (y = 0.023 + 0.0025x; r = 0.705; p less than 0.01) and between sBGP and sAP (y = 35.6 + 2.14x; r = 0.430, p less than 0.05), have been observed in the PHPT patients. No correlation was found in the HM patients. PHPT patients have been grouped according to their uOH-Prol/creatinine ratio (group A: uOH-Prol/creatinine greater than 0.034; group B: uOH-Prol/creatinine less than or equal to 0.034). Group A presented sBGP higher than the control group (11.06 +/- 5.7 vs. 4.2 +/- 1.2 ng/ml; p less than 0.001) (mean +/- SD). Group B presented sBGP similar to the control group (4.4 +/- 1.96 ng/ml) (mean +/- SD). Group A presented serum calcium (sCa) higher than group B (3.11 +/- 0.28 vs. 2.78 +/- 0.09 mmol/l; p less than 0.01) (mean +/- SD). In HM patients uOH-Prol/creatinine ratio was elevated as compared with the control group (0.074 +/- 0.036 vs. 0.024 +/- 0.004; p less than 0.001) (mean +/- SD), but sBGP was normal or low (range: indetectable-5.1 ng/ml). The simultaneous estimations of sBGP and uOH-Prol/creatinine ratio improve the differential diagnosis between these two forms of hypercalcaemia: high uOH-Prol/creatinine ratio with concomitant high sBGP point to the presence of PHPT. Elevated uOH-Prol/creatinine ratio with normal or low sBGP suggest the existence of HM.(ABSTRACT TRUNCATED AT 250 WORDS)     

The effects of transsphenoidal surgery on endocrine function and visual fields in patients with functionless pituitary tumours

Twenty-eight patients with functionless pituitary tumours have been treated by transsphenoidal surgery over the last 28 months. Mean age at presentation was 55 years. Tumor size was graded according to the extent of suprasellar extension on CT headscan from above the interclinoid line: four were small, 15 medium and nine large. Before surgery in 25 per cent of patients visual acuity and visual fields were normal. In the immediate postoperative period, 24 per cent of the patients with visual defects before surgery had normal vision, and in 38 per cent of the others it was improved. Six months after surgery, there had been further improvement; 43 per cent had normal vision and 48 per cent showed an overall improvement. In no patient did vision deteriorate following surgery. In the patients who presented with visual symptoms of one year or less, there was no correlation between the length of symptoms and the extent of visual recovery after surgery. Average age of the patients with full visual recovery was 47 +/- 4 years (mean +/- SEM); average age of the patients with only partial visual recovery was 63 +/- 3 years. Prolactin levels before surgery were elevated in 77 per cent of patients and fell significantly after operation, remaining elevated in 28 per cent of patients six months later. Fifty per cent of patients were treated with long-term hormone replacement therapy. Transsphenoidal surgery led to improved vision in the majority of patients, the results being comparable with those obtained with transfrontal surgery. Surgical complications were few, and long-term morbidity low. We suggest that the first-line treatment for patients with functionless pituitary tumours should be transsphenoidal surgery, even when large suprasellar extensions are present.     

Cardiac systolic time intervals and thyroid hormone levels during treatment of hypothyroidism.

This study was undertaken to compare results of modern serum thyroid hormone assays with cardiac systolic time intervals (STI) during thyroxine treatment in hypothyroid patients. The patients were assessed clinically (Billewicz index) and the STI and serum thyrotropin (TSH), total and free thyroxine (T4) and total and free triiodothyronine (T3) were determined in 16 hypothyroid women (Group I) treated with 50 micrograms increments of thyroxine, and in 13 women who had a history of thyroid carcinoma and high-dose thyroxine replacement therapy and had elevated thyroid hormone concentrations (Group II). The STI of 24 matched healthy female controls were used for reference of STI. The pre-ejection period (PEP) index and the PEP/LVET ratio (left ventricular ejection period) were greater in untreated overtly and mildly hypothyroid patients (p less than 0.05) than in the controls. During stable thyroxine therapy [mean daily dosage for Group I 137.5 (7.3) micrograms and for Group II 220 (61) micrograms] the PEP correlated with serum free T4 (FT4), as measured by a two-step method (SpectriaR) (r = -0.55, p less than 0.01, n = 29) and total T4 (r = -0.51, p less than 0.05, n = 29), but not with TSH, T3, FT3 or FT4 measured by an analogue method Amerlex-M(R). The TRH test was not valuable in follow-up because of the strong correlation between basal TSH and stimulated TSH values (r = 0.95). In conclusion, STI are useful for assessment of the thyroid state in untreated hypothyroid patients. Serum TSH becomes normal in the same time as STI and is the best for follow-up. If serum TSH is low and the patient is on stable thyroxine therapy, we recommend serum FT4 for monitoring thyroxine replacement. Two-step FT4 assays had the best correlation with STI, which has significance in patients with non-thyroidal illness.     

Carbonyl iron for short-term supplementation in female blood donors

A randomized, double-blind trial of iron replacement after repeated blood donation was conducted in 75 menstruating women; 51 completed the study. Volunteers were assigned randomly to one of three treatment groups: 1) carbonyl iron (nontoxic elemental iron powder), 600 mg; 2) ferrous sulfate, 300 mg (60 mg Fe++); or 3) placebo, each given three times daily for 1 week immediately after blood donation. Blood samples obtained initially and 56 days later were tested for hemoglobin, mean corpuscular volume (MCV), free erythrocyte protoporphyrin, serum ferritin, serum iron, total iron binding capacity (TIBC), and percent saturation of TIBC. The prevalence of gastrointestinal side effects was similar in both groups taking iron. At the end of the study there was no laboratory evidence of change in iron status in women who received carbonyl iron (n = 15). In those treated with ferrous sulfate (n = 17) the mean TIBC increased (p less than 0.001), and in the placebo group (n = 19) there were decreases in mean MCV (p less than 0.01), serum ferritin (p less than 0.001), and percent saturation (p = 0.027) with an increase in mean TIBC (p = 0.004). Carbonyl iron seems to be effective for short-term iron replacement in repeat blood donors and may have the advantage of decreased or absent risk of poisoning if accidentally ingested by children.     

Factors determining the long-term outcome of surgery for acromegaly

Seventy-nine patients with acromegaly were investigated beforeand after transsphenoidal adenomec-tomy, to determine the immediateand late outcome, the pre-operative features associated witha good result, and the accuracy of post-operative testing inpredicting outcome. Pre-operative evaluation included basalgrowth hormone (GH), GH response to oral glucose tolerance test(OGTT), GH response to thyrotrophin-releasing hormone (TRH),tests of pituitary reserve, and pituitary scanning to assesstumour size. A few weeks after surgery, these tests were repeated.The patients were recalled for late assessment 1-13 years (median86 months) after the operation. At the immediate postoperativetesting, minimum GH after oral glucose was