Predictive value of serum prolactin levels measured immediately after transsphenoidal surgery

OBJECT: Prolactin-secreting pituitary adenomas may be managed by surgery, medication, radiotherapy, or observation. The authors reviewed a consecutive series of patients who were followed for at least 5 years after surgery to assess the prognostic significance of preoperative factors (tumor size and prolactin level) and an immediate postoperative factor (prolactin level obtained the morning after surgery) on long-term hormonal outcome, thereby clarifying the indications for surgical removal of tumor, the definition of successful treatment outcomes, and the nature of "recurrent" tumors. METHODS: Between 1979 and 1991, 241 patients with prolactinomas underwent transsphenoidal resection. Nineteen patients were lost to follow-up review, whereas the remaining 222 patients underwent measurement of their prolactin levels on postoperative Day 1 (POD 1), at 6 and 12 weeks, and every 6 months thereafter for a minimum of 5 years. On POD 1, prolactin levels in 133 patients (Group 1) were lower than 10 ng/ml, in 43 patients (Group 2) between 10 and 20 ng/ml, and in 46 patients (Group 3) higher than 20 ng/ml. At 6 and 12 weeks, normal prolactin levels (< or = 20 ng/ml) were measured in 132 (99%) of the 133 patients in Group 1 but only in 32 (74%) of the 43 patients in Group 2. By 5 years postoperatively, normal levels of prolactin were still measured in 130 patients (98%) in Group 1 compared with only five patients (12%) in Group 2. No patient with a prolactin level lower than 3 ng/ml on POD 1 was found to have an elevated hormone level at 5 years. The likelihood of a long-term chemical cure was greater for patients with microadenomas (91% cure rate) than for those with macroadenomas (33%). Preoperative prolactin levels also correlated with hormonal outcome. CONCLUSIONS: Prolactin levels lower than 10 ng/ml on POD 1 predict a long-term chemical cure in patients with microadenomas (100% cure rate) and those with macroadenomas (93% cure rate). In contrast, a cure is not likely to be obtained in patients with normal levels ranging between 10 and 20 ng/ml on POD 1 if they harbor macroadenomas (0% cure rate). A recurrence reported several years after surgery probably represents the presence of persistent tumor that was not originally removed. If the initial operation was performed by an experienced surgeon, however, reoperation is not likely to yield a chemical cure.     

A comparative evaluation of effectiveness of medical and surgical therapy in patients with macroprolactinoma

BACKGROUND: The surgical success rate in macroprolactinomas is quite low, while medical treatment is more effective in reducing PRL levels and tumour mass. In this study the effectiveness of surgical, medical and radiant approaches on clinical symptoms, PRL levels and tumour size were compared in a large series of patients with macroprolactinomas. METHODS: One hundred and thirty-two patients (63 males and 69 females) were followed-up. Eighty-three patients were operated by trans-sphenoidal (TSS) approach: 18 underwent only TSS, 10 were operated and then irradiated; 30 patients underwent TSS and dopamine agonists, 25 were treated by TSS, radiotherapy and dopamine agonists. One hundred and four patients were treated by medical therapy: 49 patients were only administered dopamine agonists and 55 were given dopamine agonists after unsuccessful surgery and/or radiotherapy. RESULTS: In 83 patients serum PRL levels decreased from 1873+/-319.9 ng/ml to 831.6+/-297.8 ng/ml after trans-sphenoidal surgery: a significant PRL reduction was obtained in 18 cases (22%) and a full PRL normalization was found in 15 patients (18%). The pituitary adenoma was completely removed in the 15 cases, in whom serum PRL normalized. Sexual function was restored in 57 percent; of women and in 29 percent; of men. In contrast, dopaminergic drugs normalized PRL levels (from 1590.5+/-232.7 to 19.2+/-4.8 ng/ml) in 93/104 patients (89 percent;). Sexual function was restored in 74 percent; of women and in 75 percent; of men. Radiotherapy, performed after unsuccessful TSS, was ineffective in normalizing PRL levels. CONCLUSIONS: Medical therapy should be considered the first choice treatment in macroprolactinomas, while the surgical approach is recommended when neurological compressive symptoms are present and in patients resistant or intolerant to dopamine agonists. Radiotherapy may be indicated only in the patients in whom medical and surgical therapy have not been successful.     

Giant prolactinomas presenting as skull base tumors

BACKGROUND: Prolactinomas invading the skull base are rare, and could easily be confused with skull base tumors of nonpituitary origin. CASE DESCRIPTION: We report a series of 4 cases of giant prolactinomas invading the skull base and presenting with atypical symptoms. Case 1 presented with a short history of headache and nasal obstruction. Case 2 presented with progressive hypoacusia, dizziness, and ophthalmoplegia. In Case 3, the patient developed rapid progressive visual failure and psychiatric symptoms. Case 4 presented with a 1-year history of headache and retrorbital pain. The diagnosis of prolactinoma was made on the basis of tumor immunohistochemistry and/or high plasma prolactin levels (range from 650-6,500 ng/mL). Medical treatment with the dopamine agonist cabergoline was given; it was effective in normalizing prolactin levels and inducing tumor shrinkage. CONCLUSION: Prolactin levels should be measured in all large skull base tumors involving the pituitary region before any surgery or inappropriate radiotherapy is performed.     

Giant prolactinomas: clinical management and long-term follow up

OBJECT: Giant prolactinomas are rare tumors whose treatment and outcome has only been addressed in isolated case reports. The authors document the long-term follow-up findings and clinical outcome in a group of patients with giant prolactinomas. METHODS: This study is a retrospective chart and clinical review of more than 2000 cases of pituitary tumors treated at the authors' institution, of which 10 met the criteria for inclusion (prolactin level > 1000 ng/ml, diameter > 4 cm on neuroimaging studies, and clinical signs of hyperprolactinemia/mass effect). The average follow-up duration was 6.7 years after initial treatment with either bromocriptine or transsphenoidal resection. In more than 90% of the patients in this series the disease was controlled by medical treatment with bromocriptine alone; the other 10% required early surgery via transsphenoidal resection. All patients had improvement in visual symptoms. All tumors had extrasellar components, five of which exhibited frank invasion of the cavernous sinus. Tumor volume on magnetic resonance imaging was decreased on average by 69%; this occurred at a faster rate and in larger amounts when treated with bromocriptine than has been reported in the literature for macroprolactinomas. CONCLUSIONS: According to long-term follow-up findings, giant prolactinomas are exquisitely responsive to dopamine agonist therapy. In giant prolactinomas the prolactin level does not correlate with size. The main indication for early surgery is intratumoral hematoma, whereas our main indications for late surgery are cerebrospinal fluid leakage caused by medical treatment, or an increasing prolactin level despite medical therapy. Checking prolactin levels in suspicious sellar and/or suprasellar lesions may be diagnostic and prevent unnecessary surgery.     

Prolactin-secreting adenomas: the preoperative response to bromocriptine treatment and surgical outcome

Controversy exists regarding the effects of bromocriptine on the success of transsphenoidal surgery for patients with prolactinomas. Various studies on this drug have reported adverse effects, improvement, and no effect upon the subsequent surgical outcome. The authors have retrospectively reviewed the case histories of 55 patients with immunocytochemically confirmed prolactin-secreting pituitary adenomas operated on by a transsphenoidal approach between 1981 and 1985. All patients had received bromocriptine in a variety of doses and for variable durations prior to surgery. Thirty-nine patients were women and 16 were men, with an age range of 8 to 72 years. Basal prolactin levels prior to bromocriptine treatment ranged from 38 to 100 ng/ml in 11 patients, from 101 to 200 ng/ml in 12, and greater than 200 ng/ml in 29. The "cure" rates were 54%, 58%, and 38%, respectively. Thirty-one patients had microadenomas, with a postoperative cure rate of 68%; 12 had diffuse expansive adenomas, with a 17% cure rate; and 12 had grossly invasive tumors, with a 17% cure rate. A response to preoperative bromocriptine therapy was defined as a return of the basal prolactin level to normal: 18 patients were responders and 29 were hyporesponders; in eight the data were not available. The postoperative cure rate was 50% for the responders and 31% for the hyporesponders. Taking into account the distribution of tumor type, there was no actual difference in outcome between the responder and the hyporesponder groups. The total bromocriptine dose received preoperatively was nearly identical for all groups. No significant differences in the frequency or extent of fibrosis, calcification, or prolactin immunoreactivity were observed in the 55 patients when compared with 26 control prolactinomas not treated with bromocriptine. It is concluded that short-term bromocriptine treatment does not adversely affect surgical outcome in any of the prolactin-secreting adenoma groups, nor does response or lack of response to bromocriptine predict surgical outcome.     

Transsphenoidal microsurgery for pituitary tumors associated with hyperprolactinemia.

The results of transsphenoidal microsurgery in treating 37 patients (30 women and seven men) with pituitary tumors associated with hyperprolactinemia are presented. Immediate (10-day) postoperative fasting prolactin levels were normal (less than 25 ng/ml) in 19 of 26 patients whose preoperative prolactin level was less than 200 ng/ml, and in only three of 11 patients in whom preoperative prolactin was greater than 200 ng/ml. Twelve of 13 patients with normal preoperative pituitary-target organ function maintained normal axes postoperatively. Thirteen other patients had preoperative deficiencies in one or more pituitary-target organ axes. Postoperatively, in these latter 13 patients, a pituitary-target organ axis that was deficient preoperatively returned to normal in six cases; there was no change in five, and there was impairment in another axis in four instances. Although gross total tumor removal was believed to be complete in 35 of 37 patients, serial postoperative prolactin determinations in four of these 35 patients indicate tumor regrowth. The authors conclude that transsphenoidal microsurgery is currently the operative procedure of choice for the majority of pituitary tumors associated with hyperprolactinemia.     

侵袭性垂体泌乳素腺瘤的治疗策略

目的 探讨侵袭性垂体泌乳素腺瘤的治疗策略.方法 纳入侵袭性垂体泌乳素腺瘤的标准是:(1)Knosp分级Ⅲ或Ⅳ级,即肿瘤侵袭海绵窦;(2)血浆泌乳素(PRL)9.1 nmol/L;(3)高PRL分泌症状或占位效应.符合上述标准者80例,其中单纯药物(溴隐亭)治疗21例,首选药物治疗结合手术和(或)放疗组21例,首选手术治疗结合药物和(或)放疗组(首选手术治疗组)38例.残留海绵窦肿瘤行伽玛刀治疗11例.结果 平均随访62个月,MRI检查肿瘤消失57例(71%),其中单纯药物治疗组12例,首选药物治疗结合手术和放疗组16例,首选手术治疗组29例.其余23例残留肿瘤均在鞍旁海绵窦内.PRL水平正常者52例(65%),其中首选手术治疗组31例,单纯药物治疗组10例.PRL9.1 nmol/L者7例.视力改善者33例,与治疗前一致者40例,恶化7例.垂体功能低下者9例.结论 对侵袭性泌乳素腺瘤,提倡以多巴胺受体激动剂为首选治疗的个体化治疗方案.手术后仍要服用溴隐亭并进行密切随访观察.海绵窦残留肿瘤可以行伽玛刀治疗.     

Bromocriptine treatment of invasive giant prolactinomas involving the cavernous sinus: results of a long-term follow up

OBJECT: The aim of this study was to observe long-term clinical outcomes in a group of patients treated with bromocriptine for invasive giant prolactinomas involving the cavernous sinus. METHODS: Data from 20 patients with invasive giant prolactinomas at the authors' institutions between July 1997 and June 2004 were retrospectively reviewed. The criteria to qualify for study participation included: (1) tumor diameter greater than 4 cm, invading the cavernous sinus to an extent corresponding to Grade III or IV in the classification scheme of Knosp and colleagues; (2) serum prolactin (PRL) level greater than 200 ng/ml; and (3) clinical signs of hyperprolactinemia and mass effect. Among the 20 patients who met the criteria, six had undergone unsuccessful transcranial or transsphenoidal microsurgery prior to bromocriptine treatment and 14 patients received bromocriptine as the primary treatment. Eleven of the 20 patients underwent adjuvant radiotherapy. After a mean follow-up period of 37.3 months, the clinical symptoms in all patients improved by different degrees. Tumor volume on magnetic resonance images was decreased by a mean of 93.3%. In 11 patients, the tumor had almost completely disappeared; in the other nine patients, residual tumor invaded the cavernous sinus. Visual symptoms improved in 13 of the patients who had presented with visual loss. Eight patients had normal PRL levels. The postoperative PRL level was more than 200 ng/ml in seven patients. During the course of drug administration, cerebrospinal fluid leakage occurred in one patient, who subsequently underwent transsphenoidal surgery. No case of apoplexy occurred during bromocriptine treatment. CONCLUSIONS: Dopamine agonist medications are effective as a first-line therapy for invasive giant prolactinomas, because they can significantly shrink tumor volume and control the PRL level. Tumor mass vanishes in some patients after bromocriptine treatment; in other patients with localized residual tumor, stereotactic radiosurgery is a viable option so that unnecessary surgery can be avoided. The application of radiotherapy does not reliably shrink tumor volume.     

Chromogranin A,a Marker of the Therapeutic Success of Resection of Neuroendocrine Liver Metastases: Preliminary Report

Recent publications indicate that life may be prolonged by surgical debulking of neuroendocrine tumors. A minimum 90% reduction of liver metastases has been suggested to alleviate symptoms of the carcinoid. We have used the tumor marker chromogranin A (CgA) to assess hepatic resection in patients with neuroendocrine metastatic tumor disease. Since 1998, seven patients (3 men) of median age 73 years (range 64–84 years) with carcinoid primary tumors in the ileum who had solitary (n = 2) or multiple (n = 5) liver metastases underwent hepatic resections. Two patients had synchronous small intestinal and liver resections; the rest had deferred hepatic resections after intestinal resection. Hormonal manifestations in the form of loose stools or diarrhea or flushing were observed in five patients, and five had abdominal symptoms from partial obstruction of the small bowel. The resection was deemed radical in five patients. Two patients with non-radical resection needed postoperative octreotide treatment, and symptoms were alleviated or improved in the others. All seven patients are alive with an observation period from 6 to 64 months (median 36 months). Median CgA (normal < 30 ng/ml) was 292 ng/ml (range 79-14,000 ng/ml) before liver surgery. Postoperatively, CgA became normal in three of the radically resected patients, whereas in two others, it decreased to a lowest median level of 79 ng/ml (range 52–105 ng/ml). In two palliatively resected patients, one had a near normalization to 65 ng/ml, and the last patient had a reduction from 14,000 to 2400 ng/ml following debulking surgery. A similar postoperative reduction was noted for 24 hr urinary 5-HIAA excretion. Postoperative octreotide scintigraphy suggested residual hepatic or extrahepatic tumors in three of the patients thought radically resected, whereas two had no clear sign of disease corresponding to a normal CgA value. The CgA values, however, reflected the extent of positive scintigraphy findings. Serum CgA levels monitored the extent and short-term course of the disease and corresponded well with scintigraphy findings and 5-HIAA excretion, but prolonged follow-up in more patients may be necessary before decisive conclusions are allowed to be drawn.     

Prolactinomas

Hyperprolactinemia, defined by a level of serum prolactin above the standard upper limit of normal range, is a common finding in clinical practice and prolactinomas are the main pathological cause. Prolactinomas lead to signs and symptoms of hormone oversecretion, such as galactorrhea and hypogonadism, as well as symptoms of mass effect, including visual impairment, headaches and intracranial hypertension. Diagnosis involves prolactin measurement and sellar imaging, but several pitfalls are involved in this evaluation, which may difficult the proper management. Treatment is medical in the majority of cases, consisting of dopamine agonists, which present high response rates, with a very favorable safety profile. Major adverse effects that should be monitored consist of cardiac valvulopathy and impulse control disorders. Other treatment options include surgery and radiotherapy. Temozolomide may be used for aggressive or malignant carcinomas. Finally, pregnancy outcomes are similar to general population even when dopamine agonist treatment is maintained.     

Hormones in seminal plasma

Testosterone and prolactin play an important but unclear role in the process of spermatogenesis. Peripheral levels of these hormones are usually normal in infertile patients even when the characteristics of the sperm are subnormal. This study was conducted to evaluate the possible relationship between sperm quality and seminal content of testosterone and prolactin in 70 men. Men with normal semen analysis had venous blood levels of testosterone and prolactin that were not different from those seen in men with abnormal semen analysis while seminal concentration of testosterone was higher in the latter group of men. Testosterone concentration in semen from the 70 men investigated was 69 +/- 4 ng/100 ml, and in venous blood 487 +/- 20 ng/100 ml. However, in blood, one-third of this steroid was bound to testosterone binding globulin (TeBG), while no TeBG bound fraction of testosterone was found in seminal fluid. There was a direct correlation between the venous and seminal levels of these two hormones.     

Hyperprolactinaemia among infertile patients and its effect on sperm functions

Summary. The effects of hyperprolactinaemia on sperm function were investigated in 264 men with oligozoo-, asthenozoo-, or teratozoospermia and who were attending a male infertility clinic. None of the patients exhibited galactorrhea or complained of impotence. There was no correlation between abnormal values in spermiogram and hyperprolactinaemia. After multiple measurements of serum prolactin concentration, 15 cases (5.7%) were diagnosed as hyperprolactinaemic (≧ 10 ng ml⁻¹). Six of these patients were taking cimetidine and six were taking anti-anxiety drugs. Serum prolactin returned to the normal level after discontinuation of these drugs; thus these 12 cases were considered as drug-induced hyperprolactinaemia. The other three patients were diagnosed as having pituitary microadenomas and received bromocriptine treatment; the serum prolactin levels normalized within 1 month. No changes in sperm concentration, motility or morphology were found after normalization of serum prolactin levels. Sperm fertilizing ability was monitored by the hamster test for 10 months in the three patients with pituitary microadenoma, and no improvement was observed. Results suggest that hyperprolactinaemia, which does not cause symptoms, has little effect on the impairment of sperm functions. Measurement of serum prolactin in infertile men could be justified, however, for early detection of pituitary adenomas.     

Enlarged adenomectomy for enclosed prolactinomas: A preliminary study of 26 cases

Summary Preliminary results obtained from 26 cases of prolactinomas less than 20 mm in diameter after treatment by enlarged adenomectomy are described.The operation consisted in removal of the adenoma, a layer of normal pituitary at the outer edge of the tumour and the pituitary capsule in contact with the sellar meninges. 24 women and 2 men were involved whose prolactin levels (PRL) were less than 200 ng/ ml. All presented abnormal PRL responses to Thyrotropin releasing hormone (TRH) and Metoclopramide (MCP) tests and an absence of a nocturnal rise in the sleep cycle study. Postoperatively, three patients developed transitory diabetes insipidus and five transitory adrenal insufficiency. Gonadotropin reserve was always found normal. All 24 women resumed normal menstrual cycles and two became pregnant within one year. From a serological viewpoint, after surgery 100% of patients were found to be normal for levels of prolactin but only 85% turned to normal dynamic tests. The results of this small series of enlarged adenomectomies seem better than those obtained using selective adenomectomy, but must be confirmed with time.     

Impact of elective resection on plasma TIMP-1 levels in patients with colon cancer

OBJECTIVE: Pre- and post-operative plasma tissue inhibitor of metalloproteinases-1 (TIMP-1) levels have a prognostic impact on patients with colorectal cancer. However, the surgical trauma may play an essential role in regulation of plasma TIMP-1 levels, which in turn may influence subsequent TIMP-1 measurements. PATIENTS AND METHODS: Consecutively, 48 patients with colon cancer (CC) and 12 patients with nonmalignant colonic disease were randomised to undergo elective laparoscopically assisted or open resection followed by fast track recovery. Plasma samples were collected just before and 1, 2 and 6 h after skin incision, and 1, 2, 8 and 30 days after surgery. TIMP-1 was determined concurrently in all samples by a validated ELISA method. RESULTS: Geometric mean preoperative TIMP-1 level was 142 ng/ml (range 54-559 ng/ml) among CC patients compared with 106 ng/ml (range 64-167 ng/ml) among patients with nonmalignant diseases (P<0.0001). TIMP-1 levels were decreased significantly 2 h after skin incision compared to the preoperative levels returning to preoperative levels at 6 h. A highly significant (P<0.0001) maximum level was observed 1 day after surgery and was decreasing to preoperative levels 30 days after surgery. Patients undergoing laparoscopically assisted or open resection had similar TIMP-1 levels at each time point. CONCLUSIONS: Major surgery has considerable impact on plasma TIMP-1 levels. Intra- and post-operative changes of plasma TIMP-1 levels are independent of the surgical approach, and resection for CC does not lead to a significant decrease of plasma TIMP-1 levels within 30 days postoperatively.     

Endocrine profiles and gonadotropin response to Gn-RH of men with testicular cancer

PURPOSE: To investigate the function of the hypothalamic-pituitary-testicular axis in testicular germ cell tumors, we evaluated gonadotropin responses to gonadotropin-releasing hormone (Gn-RH), semen quality, and serum levels of sex steroid hormones in patients with testicular cancer. PATIENTS AND METHODS: Basal serum levels of luteinizing hormone (LH), follicle stimulating hormone (FSH), and human chorionic gonadotropin-beta (hCG-beta) were measured before and after high orchiectomy in 20 patients with germ cell tumors of the testicle (9 with seminoma and 11 with nonseminomatous tumor). Semen quality and basal serum levels of testosterone, free testosterone, and estradiol were measured before orchiectomy. The Gn-RH test was performed before orchiectomy in all patients and after orchiectomy in patients without detectable gonadotropin levels in pre-operative serum samples. Gonadotropin levels were measured at 0, 30, 60, 90, and 120 minutes after intravenous injection of 100 micrograms of luteinizing hormone-releasing hormone (LH-RH). RESULTS: Serum gonadotropin concentrations were not detectable in 6 of 8 (75%) men with hCG positive tumors or in 4 of 12 (33.3%) men with hCG negative tumors before orchiectomy. Before surgery, 10 men without detectable gonadotropin levels showed complete suppression of the LH and FSH responses to LH-RH and 10 men with detectable gonadotropin levels showed significant increases in the LH and FSH responses (p < 0.01) at 30 minutes. After surgery, the Gn-RH test was performed in 9 men without detectable gonadotropin levels prior to surgery. Seven of these 9 men exhibited significant increases in the LH and FSH responses (p < 0.01) at 30 minutes while no response to LH-RH before or after surgery was seen in 2 men with detectable serum hCG-beta. We observed a significantly lower sperm density (median 7.5 x 10(6)/ml, range 0.4 to 17.8) in men with hCG positive tumors than in men with hCG negative tumors (median 33 x 10(6)/ml, range 0 to 103) (p < 0.002). Although testosterone levels did not differ significantly in men with hCG positive tumors and men with hCG negative tumors, free testosterone levels were significantly higher in men with hCG positive tumors (median 28.4 ng/ml, range 8.5 to 39.8) compared with men with hCG negative tumors (median 18.7 ng/ml, range 4.9 to 24.1) (p < 0.002). Estradiol levels were significantly increased in men with hCG positive tumors (median 44 pg/ml, range 26 to 110) compared with men with hCG negative tumors (median 33.5 pg/ml, range 10 to 87) (p = 0.002). CONCLUSION: The present findings indicate that serum hCG producing testicular cancers are associated with a complete suppression of the gonadotropin response to Gn-RH at the pituitary level, resulting in an inhibition of LH and FSH secretion, and also that serum hCG secreted by testicular cancers may suppresses spermatogenesis and may stimulate androgen and estradiol production by the testes. Since suppressed serum gonadotoropin levels are found in men with hCG non-producing testicular cancers, other factors derived from the tumor may cause downregulation of the gonadotropin response to Gn-RH.     

Management of prolactinomas associated with very high serum prolactin levels

The authors have reviewed the results of transsphenoidal microsurgical management in 69 patients with prolactin-secreting pituitary adenomas who had preoperative serum prolactin levels over 200 ng/ml. The patients were divided into three groups based on their preoperative serum prolactin levels: over 200 to 500 ng/ml (Group A); over 500 to 1000 ng/ml (Group B); and over 1000 ng/ml (Group C). The percentage of successful treatment ("control rate") was 68%, 30%, and 14%, respectively, in these three groups of patients. Based on these results, the authors offer guidelines for the management of patients with prolactin-secreting pituitary adenomas associated with exceptionally high serum prolactin levels. The surgical control rate of 68% in Group A seems to justify surgery for these patients, while primary medical care with bromocriptine is recommended for most patients with serum prolactin levels over 500 ng/ml.     

Cardiomegaly and heart failure in a patient with prolactin-secreting pituitary tumour.

Unexplained cardiomegaly with cardiac failure was observed in a 42-year-old woman in whom a pituitary tumour had been treated by radiotherapy five years previously. She had been amenorrhoeic for 10 years. Thyroid and adrenal function was normal. Despite treatment with digitalis and diuretic, her cardiac disease progressed until she died suddenly at the age of 45. Hyperprolactinaemia was evident some weeks before death, her serum concentration of 68 ng/ml being well above both the reported normal range (2--20 ng/ml) and the concentrations in eight female controls being treated for severe cardiac failure (5--25 ng/ml). Although the association of these two disorders might merely represent coincidence, heart disease with similar features is common in acromegaly and does not correlate with plasma growth hormone concentration. Since prolactin is known to exert metabolic growth hormone-like effects in animals and in man, the possibility should be considered that prolactin hypersecretion might induce or maintain cardiac disease in some patients with pituitary tumours. A preliminary survey of 35 subjects with hyperprolactinaemia has shown five with raised blood pressure and four, two of whom were normotensive, with cardiomegaly on chest radiography.     

The value of serum prostate specific antigen determinations before and after radical prostatectomy

We evaluated serum prostate specific antigen before and after radical prostatectomy. In 100 consecutive patients who underwent radical prostatectomy, preoperative prostate specific antigen levels tended to increase with the increasing severity of pathological stage. However, even at levels of greater than 10 ng. per ml. the positive and negative predictive values (78 and 61 per cent, respectively) of prostate specific antigen to predict extracapsular disease were not sufficient to make this test useful alone for staging. In theory, after radical prostatectomy prostate specific antigen should be zero if no remaining prostatic tissue is present. Tests of precision and analytical sensitivity in our laboratory using a commercial prostate specific antigen assay revealed that a value of 0.4 ng. per ml. or more is different from zero at a greater than 95 per cent confidence level. With this guideline we evaluated the meaning of prostate specific antigen levels 3 to 6 months after radical prostatectomy in 59 men. Among men whose prostate specific antigen level was less than 0.4 ng. per ml. only 9 per cent demonstrated recurrence as evidenced by the development of positive bone scan or progressively elevated prostate specific antigen levels within 6 to 50 months. Alternatively, in men whose 3 to 6-month prostate specific antigen level was 0.4 ng per ml. or more there was evidence of recurrence in 100 per cent within 6 to 49 months (p less than 0.0001). Progressively elevated (more than 0.4 ng. per ml.) prostate specific antigen levels preceded recurrence from 12 to 43 months in all 6 patients who had positive bone scans, while increasing prostate specific antigen levels since radical prostatectomy have continued from 9 to 65 months in the 11 patients who have no radiological evidence of recurrent disease to date. Prostatic acid phosphatase serum values after radical prostatectomy were not useful to predict persistent disease. Prostate specific antigen values 3 to 6 months after radical prostatectomy are a sensitive indicator of persistent disease after radical prostatectomy and often precede other evidence of this occurrence by many years. This fact may alter concepts about surgical results, and possibly shorten and sharpen clinical studies involving adjuvant therapy after radical prostatectomy.     

Randomized Study of Neoadjuvant Testicular Androgen Ablation Therapy Before Radical Prostatectomy in Men with Clinically Localized Prostate Cancer

Purpose

We determined whether 12 weeks of neoadjuvant testicular androgen ablation therapy using a luteinizing hormone-releasing hormone agonist could improve pathological outcomes in men undergoing radical retropubic prostatectomy for clinically localized (stages T1C, T2A and T2B) prostatic carcinoma.

Materials and Methods

A total of 56 participants was randomized to receive either monthly injections of a luteinizing hormone-releasing hormone agonist at 4-week intervals followed by radical retropubic prostatectomy (28) or to undergo immediate radical retropubic prostatectomy alone (28). Operations were performed via a similar technique and all prostatic specimens were processed histologically in their entirety.

Results

There was no improvement in pathological outcome using a luteinizing hormone-releasing hormone agonist preoperatively compared to surgery alone. Of 28 men undergoing immediate radical retropubic prostatectomy 23 had organ-confined (17) or specimen-confined (6) disease versus 22 of 28 who received luteinizing hormone-releasing hormone neoadjuvant therapy for 12 weeks preoperatively (16 with organ-confined and 6 with specimen-confined disease, p = 1.00). In addition, when the study population was analyzed by pretreatment prostate specific antigen (PSA) levels (10 ng./ml. or less, or greater than 10 ng./ml.) there was also no difference in pathological outcome (p = 0.65 for PSA greater than 10 and p = 0.32 for PSA less than 10).

Conclusions

Neoadjuvant androgen ablation therapy for 12 weeks before radical prostatectomy in patients with clinically localized adenocarcinoma of the prostate does not result in improved pathological outcomes.     

A case of prolactinoma with galactorrhea in man

A 28-year-old man was admitted to the Kyushu University Hospital with an episode of severe headache. When driving a car, he suddenly developed severe headache and this was followed by nausea and vomiting. he had been quite well except for slightly decreased libido before this episode. On admission, he showed galactorrhea. The pubic and axillary hairs appeared normal and the development of the external genital organs seemed normal. However, the movement of the sperma was decreased. Ophthalmologic examination was negative. Endocrinological studies revealed hyperprolactinemia of 697 ng/ml, and the serum prolactin level was suppressed by bromocriptine and L-DOPA loading test. The serum testosterone level was 282 ng/dl. Growth hormone and gonadotropin levels were normal. Plain films of the skull and tomograms of the sella showed double floor and slight ballooning. CT scan showed an isodensity mass in and above the sella, and this mass was slightly enhanced with contrast media. The suprasellar extension was better demonstrated by metrizamide cisternography and CT. The diagnosis of prolactinoma was made, and a radical removal of the tumor was done through the transsphenoidal route. During surgery, dark reddish fluid was aspirated in an amount of 1.8 ml. Histologically the tumor was chromophobe adenoma, and immunohistochemical stain revealed prolactin granules in the majority of the tumor cells. Postoperative serum prolactin level decreased to 150 ng/ml and finally returned to normal by administration of 2.5 mg of bromocriptine. The serum testosterone level was slightly elevated. The movement of the sperma showed no improvement. There were no postoperative complications such as hypopituitarism and CSF rhinorrhea. The usefulness of combination therapy of operation and medication with bromocriptine was suggested.