13例青少年起病的男性垂体催乳素瘤临床分析

目的探讨男性青少年催乳素瘤的临床特点、治疗与预后。方法回顾性分析13例青少年男性催乳素瘤患者临床表现及疗效。结果（1）男性青少年催乳素瘤以大腺瘤为主。头痛和第二性征发育障碍常见,但较少引起生长停滞。（2）溴隐亭治疗安全有效,与手术相比,可以保护垂体前叶功能,改善第二性征发育。结论男性青少年催乳素瘤采用溴隐亭治疗较手术更为可取,必要时,联合治疗有助于缓解病情。     

The risks of medical treatment of prolactinoma

First-line treatment of prolactinoma is usually medical, based on dopamine agonists receptors, mainly cabergoline. The classical side-effects of cabergoline (low blood pressure and nausea) have been well known since it was first introduced. Other side-effects, however, are more controversial or simply less frequent, but need to be considered during monitoring. This review will focus on these side-effects: cardiac valvular fibrosis, pleural, pericardial and retroperitoneal fibrosis, addictive/compulsive behaviors, and risks secondary to significantly decreased tumor volume. We will also describe how such side-effects should be monitored and managed. In our opinion, the low prevalence of these side-effects should not cast doubt on the role of cabergoline in the therapeutic algorithm of prolactinoma.     

An unusual association of a sellar gangliocytoma with a prolactinoma

The simultaneous occurrence of a hypothalamic and sellar gangliocytoma with a pituitary prolactinoma is very rare. The explanation for such an association is not known. We describe the case of a woman who had a coexisting adjacent pituitary prolactinoma and gangliocytoma within the same sellar mass. The tumor cells of the gangliocytoma demonstrated expression of enkephalin, a product of proopiomelanocortin known to be a prolactin secretagogue. We postulate that in this patient there may be a link between gangliocytoma enkephalin and prolactin hypersecretion.     

Long-term cabergoline therapy is not associated with valvular heart disease in patients with prolactinomas

Ergot-derived dopamine receptor agonists, especially pergolide and cabergoline, have been associated with an increased risk of valvular heart disease in patients treated for Parkinson’s disease. Cabergoline at lower doses than those employed in Parkinson’s disease is widely used in patients with prolactinomas, because of its high efficacy and tolerability; however, its safety with regard to cardiac valve disease is unknown. In order to assess the prevalence of cardiac valve regurgitation in patients with prolactinomas treated with long-term cabergoline, we performed a prospective and multicentric study including four university centers in the province of Quebec. A transthoracic echocardiogram was performed in 70 patients with prolactinomas treated with cabergoline for at least 1 year (duration of treatment, 55 ± 22 months; cumulative dose 282 ± 271 mg, mean ± SD) and 70 control subjects matched for age and sex. Valvular regurgitation was graded according to the American Society of Echocardiography recommendations as mild, moderate, or severe. Moderate valvular regurgitation was found in four patients (5.7%) and five control subjects (7.1%) (P = 0.73). No patient had severe valvular regurgitation. There was no correlation between the presence of significant heart-valve regurgitation and cabergoline cumulative dose, duration of cabergoline treatment, prior use of bromocriptine, age, adenoma size, or prolactin levels. Our results show that low doses of cabergoline seem to be a safe treatment of hyperprolactinemic patients. However, in patients with prolonged cabergoline treatment, we suggest that echocardiographic surveillance may be warranted.     

The heterogeneity of serum hPRL in a patient with a giant prolactinoma

The heterogeneity of hPRL in the serum of a patient with a giant prolactinoma (hPRL 27 micrograms/ml) was studied employing gel chromatography, RIA and lymphoma cell bioassay. After gel filtration of serum sample on Sephadex G-100 (superfine) column, a few hPRL peaks were detected by RIA. Rechromatography of the second peak, which eluted between the void volume and the small third peak, revealed four hPRL peaks designated big-big hPRL, medium-big hPRL, big hPRL and little hPRL, with BA/RIA ratio 1.3 approximately 2.6, 0.8 approximately 1.2, 0.3 approximately 0.7 and 0.7 approximately 1.5, respectively. The molecular weight of medium-big hPRL was estimated as 80K approximately 90K daltons. Most of big-big, medium-big and big hPRL were converted to little hPRL after mercaptoethanol treatment. These data suggest that most of big-big, medium-big and big hPRL are aggregates of little hPRL.     

糖尿病合并男性性腺功能减退症的识别与处理

男性性腺功能减退症是指一组不仅出现性功能障碍,而且同时伴有性激素水平减少的临床综合征.男性性腺功能减退症的比例在糖尿病患者中明显高于非糖尿病患者,且与胰岛素抵抗及高血糖密切相关.临床上,需要注意观察糖尿病患者有无性腺功能减退症的临床表现,适时检测患者的性激素水平,尽早识别糖尿病合并男性性腺功能减退症,并予以性激素替代治疗,从而提高患者的生活质量.     

Rapid and dramatic glucose-lowering effect of bromocriptine in an inadequately controlled type 2 diabetes patient with prolactinoma

Dopamine receptor agonists are typically used to treat Parkinson’s disease and certain pituitary tumors, such as prolactinoma or a growth hormone-producing tumor. A 53-year-old woman with a history of prolactinoma was referred to Kumamoto University Hospital (Kumamoto, Japan) with poorly controlled type 2 diabetes. Her glycated hemoglobin and serum prolactin levels were increased (8.8% and 160.3 ng/mL, respectively). Bromocriptine, a dopamine D₂ receptor agonist, was administered to reduce her serum prolactin level. Because bromocriptine-QR (quick release) has been approved for the treatment of type 2 diabetes mellitus in the USA, a continuous glucose monitoring system, FreeStyle Libre Pro, was utilized to examine the effect of bromocriptine on glycemic control. After the initial administration of bromocriptine, glucose levels were rapidly and dramatically ameliorated, and the time in range (70–180 mg/dL) improved from <50% to >90% between 1 week before and after the initial administration of bromocriptine.     

男性垂体催乳素大腺瘤103例临床分析

目的　探讨男性催乳素大腺瘤的临床特点、治疗方法与疗效的关系以及预后因素。方法　回顾性分析103例男性催乳素大腺瘤患者临床特点、不同治疗方式对治疗效果的影响,并初步探讨影响预后因素。结果　(1)男性催乳素大腺瘤最常见的症状是性欲或性功能减退,其次是头痛和视力减退。(2)药物治疗的患者57 8% 达到完全缓解,而单纯手术治疗仅有5 7%的患者完全缓解(P<0 001)。手术治疗不能完全缓解的患者采取药物、放疗以及两者联合治疗, 3种治疗的疗效差异无统计学意义(P=0 498)。(3)肿瘤存在侵袭性的患者较无侵袭性的患者预后差(P=0 03), 疗效不同的患者在年龄、病程、肿瘤大小、治疗前血催乳素水平以及是否存在垂体卒中方面无明显差异。结论　男性催乳素大腺瘤应首选药物治疗。肿瘤存在侵袭性是其预后不良因素。     

Bone density in women with prolactinoma treated with dopamine agonists

Objectives (1) to evaluate bone density in women with prolactinoma treated with dopamine agonists and healthy controls, using dual energy x-ray absorptiometry (DXA), (2) to classify the results according to the current International Society for Clinical Densitometry (ISCD) criteria, and (3) to correlate bone density with lean and fat masses, biochemical data and clinical aspects of prolactinomas. Materials and methods A cross-sectional study was performed in two University referral centers. Forty-five premenopausal women with prolactinoma were submitted to DXA and blood analysis (prolactin, estradiol, testosterone, SHBG, calcium, phosphorus, PTH, C-telopeptides of type 1 collagen, and osteocalcin) by the time of their clinical evaluation. They were compared with 25 control women of similar age and body mass index distribution. Results Women with prolactinoma had lower lumbar spine Z-score than controls. Femoral neck, trochanter, and total proximal femur Z-scores were similar in patients and controls. Twenty-two percent of the patients had Z-scores below the expected age range vs. 4% in the control group. Lumbar spine, femoral neck, and total proximal femur Z-scores were mainly correlated with the amenorrhea duration. The trochanter Z-score was associated with the gynoid lean/fat mass ratio. Conclusions Based on the current ISCD criteria, bone density evaluation in women with prolactinoma reveals bone loss, especially of trabecular type. Bone density in these patients was particularly associated with the duration of amenorrhea, which reinforces the importance of the adequate disease control in women with prolactinoma in order to avoid complications of this disease.     

Hyperostosis frontalis interna in a patient with giant cell arteritis

Hyperostosis frontalis interna (HFI) is a disorder characterized by progressive symmetric thickening of the inner table of the frontal bone of the human skull. HFI may be accompanied by headache and some neuropsychiatric diseases such as epilepsy and dementia. Giant cell arteritis (GCA), also called temporal arteritis, is a systemic inflammatory vasculitis of unknown etiology that affects medium- and large-sized arteries. It affects elderly people and may result in a wide variety of systemic, neurologic and ophthalmologic complications. As no association of HFI and GCA was encountered in the literature, we found it interesting to report a case with both of these clinical entities.     

Acute stent thrombosis in a patient with giant cell arteritis

A 70-year-old man presented with a non-ST elevation myocardial infarction attributable to a 99% occlusion of his mid-left anterior descending artery and concomitant symptoms suggestive of giant cell arteritis. He underwent bare metal stenting, with an excellent angiographic result, and was placed on dual antiplatelet therapy, as well as oral prednisone 30 mg twice daily, while awaiting confirmatory temporal artery biopsy. Unfortunately, 70 h after percutaneous coronary intervention, he developed acute stent thrombosis. Platelet aggregometry demonstrated that he was responsive to acetylsalicylic acid, but marginally responsive to clopidogrel. Over the next 30 days, he had a marked clinical improvement, with an improvement in platelet response to clopidogrel that paralleled the clinical resolution of his vasculitis. The present case reports the first incidence of acute stent thrombosis associated with giant cell arteritis, and suggests that the proinflammatory milieu of acute inflammatory arthritides may warrant prolonged, aggressive antiplatelet therapy in the setting of an acute coronary syndrome.     

Clinical profile and long term follow up of children and adolescents with prolactinomas

We report clinical presentation, response to medical treatment, and long-term follow-up of 39 children and adolescents with prolactinoma (F:M; 30:9) (30 macro and 9 microadenoma) diagnosed at the age of 9–20 years. Mean duration of follow up was 56 months. All patients were treated with bromocriptine (BC) at doses ranging from 2.5 to 20 mg/day or by cabergoline at doses ranging from 0.5 to 2 mg/week orally. Two patients received external conventional radiotherapy after surgery. In patients with macroprolactinoma (F:M; 21:9), headache and/or visual defects were the first symptoms. All females had primary or secondary amenorrhea. Growth arrest was not observed in any patient and pubertal development was appropriate for their age. Spontaneous or provocative galactorrhea was observed in 23 patients (all females) and none of male patient had gynecomastia. Mean serum prolactin (PRL) concentration at the time of diagnosis was 322.50 ng/ml in patients with microadenoma, 522.38 ng/ml in patients with macroadenoma and 2,294.86 ng/ml in patients with macroadenoma with suprasellar extension. In 25 patients, BC normalized PRL levels and caused variable, but significant, tumor shrinkage. Cabergoline normalized PRL concentrations in 14 patients. Pregnancy occurred in 6 patients while on treatment. Pregnancies were uncomplicated, and the patients delivered normal newborns at term. Impairment of other pituitary hormone secretion was documented at the time of diagnosis in only one patient. Postoperatively six patients had other pituitary hormone deficiencies. In conclusion, the medical treatment with dopaminergic compounds is effective and safe in patients with prolactinoma with onset in childhood, allowing preservation of the anterior pituitary function.     

迟发性睾丸功能减退症的睾酮补充治疗

原发性或继发性性腺功能减退的中青年男性往往需要终生睾酮补充治疗（TST）。诊断明确的迟发性睾丸功能减退症（LOH）的中老年男性,也应尝试TST。TST可使情绪紊乱,性功能障碍,肌量、骨量及体能下降等症状好转。可能与TST有关的不良反应包括前列腺疾病风险、红细胞增多症、阻塞性睡眠呼吸暂停综合征、体液潴留等,TST长期治疗的安全性及疗效仍需进一步研究观察。     

Testosterone modulates serum leptin concentrations in a male patient with hypothalamic hypogonadism

Serial measurements of body mass index (BMI), serum concentrations of testosterone (T), estradiol (E) and leptin (L) were performed before and after gonadotropin (Gn) therapy in an 18-year-old male subject (BMI 25.4 kg/m2) with idiopathic hypothalamic hypogonadism (IHH). We also measured the BMI and serum concentrations of L in 99 age-matched healthy subjects. Serum L correlated significantly with BMI in control subjects (r=0.84, p<0.0001). Baseline serum concentrations of L in our case were markedly high and both T and E were very low, but Gn therapy resulted in a gradual decrease in L and improvement in T and E, finally reaching the control levels of BMI-matched subjects. Our results demonstrate that T is a powerful negative modulator of serum L independent of BMI in conditions associated with low T levels, such as IHH.     

SIADH is only an atypical clinical feature in a patient with prolactinoma

A 50-year-old man was admitted to determine the pathogenesis of hyponatremia. He had a poor appetite and was easily fatigued. Physical findings showed that he was conscious and alert. He had neither dry skin or tongue, nor pretibial edema. Laboratory data revealed that the serum sodium level was 110 mmol/l; plasma osmolality, 238 mmol/kg; and urinary osmolality, 417 mmol/kg. Plasma arginine vasopressin was 0.5 pg/ml despite plasma osmolality of 242 mmol/kg. An acute water load showed impaired water excretion, as percent excretion of water load was 30% and minimal urinary osmolality was 642 mmol/kg. Serum prolactin was 254 ng/ml, and anterior pituitary hormones of ACTH, TSH and GH were in the normal ranges. Brain magnetic resonance imaging (MRI) showed a pituitary tumor with a size of 20 x 22 x 21 mm and it pushed a pituitary stalk upward. Immunohistochemistry revealed prolactinoma. After the adenomectomy, serum sodium level has been kept normal with free access to water intake. The present study indicates that syndrome of inappropriate secretion of antidiuretic hormone (SIADH) is manifested in association with pituitary macroadenoma of prolactinoma.     

Temozolomide in the treatment of an invasive prolactinoma resistant to dopamine agonists

Prolactinomas are common tumors of the anterior pituitary gland. While conventional therapies, including dopamine agonists, transsphenoidal surgery and radiotherapy, are usually effective in controlling tumor growth, some patients develop treatment-resistant tumors. In this report, we describe a patient with an invasive prolactinoma resistant to conventional therapy that responded to the administration of the alkylating agent, temozolomide.     

男性2型糖尿病患者性腺功能减退相关因素分析

目的探讨男性2型糖尿病（T2DM）患者血清总睾酮（TT）水平与肥胖、胰岛素抵抗（IR）、血糖、血脂间的关系。方法对120例男性T2DM患者进行性激素、FPG、Fins、FC—P、HbA,c、血脂水平测定。根据稳态模型评估法（HOMA）评价IR程度。结果120例男性T2DM患者中1vr低下者占14％,IR占71％,BMI≥23kg／m2者占52％。TT与BMI、Fins及WHR成负相关（r=-0．335,-0．307,-0．232,P〈0．01）,与年龄、病程、血糖、FC-P、HbAtc水平等无相关性。BMI与WHR、Fins、FC-P及InHO—MA-IR成正相关（r=0．489,0．348,0．356,0．301P％0．01或P〈0．05）,年龄与黄体生成素、卵泡刺激素成正相关（r=0．310,0．442,P〈0．01）。结论肥胖是男性T2DM患者TT水平低下的主要影响因素,通过肥胖的介导,TT与IR及脂代谢紊乱相关。     

Reversal of chronic ethanol-induced testosterone suppression in peripubertal male rats by opiate blockade

Teenage drinking continues to be a significant problem in the U.S., as well as abroad. We have previously demonstrated that opiate blockade with naltrexone, a drug currently used in patients to diminish alcohol craving, prevented the fall in serum testosterone seen after acute ethanol (EtOH) exposure in young, peripubertal male rats. To follow-up on this reversal, a series of experiments was performed to determine if naltrexone would also prevent the testosterone suppression caused by chronic EtOH exposure. Peripubertal rats either 45 days old (mid-pubertal) or 55 days old (late pubertal) were fed an EtOH-containing liquid diet or pair-fed control diet for 14 days. Each animal was implanted with either a naltrexone containing or placebo pellet before starting the liquid diet. In each age group, EtOH alone significantly suppressed testosterone, whereas naltrexone prevented this fall, although it had no effect alone. Serum luteinizing hormone was also suppressed by EtOH; however, naltrexone did not abrogate this fall. In the 45-day-old animals, beta-luteinizing hormone mRNA levels rose significantly in the EtOH group, but not when naltrexone was coadministered with EtOH. There was no change in hypothalamic luteinizing hormone releasing hormone (LHRH) mRNA, pro-LHRH, or LHRH in any group at either age. Thus, naltrexone is able to partially prevent the EtOH-induced suppression of gonadal testosterone of young, adolescent male rats. This effect appears to be mediated directly at gonadal level, because hypothalamic and pituitary hormone changes were minor and nonsignificant.     

Evidence of male hypogonadism at an early age as a familial risk of type 2 diabetes

Objective

Previous investigations provide evidence of an association of hypogonadism with type 2 diabetes in men, and low testosterone levels have been regarded a risk factor for the disease. Since a strong genetic predisposition to type 2 diabetes has been demonstrated, here we investigate a possible tendency towards hypogonadism in young male offspring of diabetic parents.

Material and methods

The study compares 32 male offspring of diabetic parents with 31 male offspring of nondiabetic parents matched by age. The subjects comprised boys (9–17 years) and young adults (19–25 years). Anthropomorphic measurements were made in all subjects. Fasting blood samples were analyzed for glucose and serum concentrations of testosterone (T), sex hormone-binding globulin (SHBG), luteinizing hormone (LH), insulin and leptin were measured by ELISA. Free testosterone (FT) was calculated using T and SHBG levels.

Results

Serum T, FT and bioavailable T (BAT) levels in offspring of diabetic parents were significantly lower than those of offspring of nondiabetic parents across all age groups. Mean serum LH levels were also lower in offspring of diabetic parents compared to the controls. Although LH levels in young adults with diabetic parents, tended to be lower than those of age-matched controls but the difference was not statistically significant. Serum insulin and leptin, and insulin resistance measured by HOMA-IR were significantly raised in older offspring of diabetic parents but were within the normal range.

Conclusion

Whereas hypogonadism was the only indicator of a possible predisposition to metabolic dysfunction in peripubertal children of diabetic parents, a significant change in other metabolic markers becomes apparent at a more advanced age.