Isolated adrenocorticotrophic hormone (ACTH) deficiency associated with acute adrenal crisis

A 37 year old black female presented with congestive cardiac failure, 2 months postpartum. She developed spontaneous hypoglycaemia and symptoms of acute adrenal crisis (hypotension, nausea, abdominal pain and tachycardia with small thready pulse), which responded to i.v. dextrose, sodium chloride and hydrocortisone. Biochemical investigations revealed low serum cortisol and plasma adrenocorticotrophic hormone (ACTH) levels. The patient initially showed an impaired cortisol response to intramuscular aqueous tetracosactrin, but an exuberant response after priming with intramuscular tetracosactrin depot. These findings, together with the normal remaining pituitary function, led us to conclude that this patient had isolated ACTH deficiency associated with congestive cardiac failure and acute adrenal crisis.     

Application of pyridostigmine in evaluation of growth hormone reserves in children and adolescents.

There is evidence that the cholinergic system positively modulates growth hormone (GH) secretion. In the present study, we observed the effects of cholinergic enhancement by pyridostigmine (PD), a cholinesterases inhibitor, on GH release in both normal (n = 13) and GH deficient children and adolescents (n = 10). Responses of GH to insulin hypoglycemia (Ins) were also observed. In the normal subjects, PD-induced serum GH peak level was significantly higher than that induced by Ins (P less than 0.01), while the GH level in the patients with pituitary dwarfism showed no increase in both tests. This study indicates that PD test may be considered a sensitive dynamic test in evaluating pituitary function of GH secretion in children and adolescents.

     

Pituitary hormone reserve in the Laurence-Moon-Bardet-Biedl syndrome

A patient who presented with hypgonadism was found to have classical features of the Laurence-Moon-Bardet-Syndrome. He had oligospermia and low serum testosterone. Basal serum thyroid stimulating hormone (TSH), prolactin (PRL), growth hormone (GH), cortisol, luteinising hormone (LH) and follicle stimulating hormone (FSH) were normal. Stimulation with thyrotropin releasing hormone. (TRH) showed normal pituitary reserve for TSH and PRL. Adequate insulin hypoglycaemia caused a normal rise of GH and cortisol. LH and FSH showed normal peaks after luteinishing hormone releasing hormone (LHRH). These results indicate normal pituitary hormone reserve and hypogonadotrophic hypgonadism secondary to hypothalamic dysfunction.     

Growth hormone responses to hp GRF 1-44 amide, bromocriptine and stress in acromegaly are correlated

The results of testing growth hormone (GH) reserve using human pancreatic growth hormone-releasing factor 1-44 amide (hp GRF 1-44 amide) have been compared with the GH responses in a variety of other dynamic tests in seven acromegalic patients. The GH release following hp GRF 1-44 amide correlated with the GH suppression following bromocriptine, but showed an inverse correlation with the GH release following stress tests (insulin-induced hypoglycaemia/glucagon). There was no correlation between the GH responses in these three tests and any of the other tests: TRH, GnRH and glucose. A hypothesis is proposed to explain these findings on the basis of varying degrees of GH secretion from adenomatous and normal pituitary somatotrophs in acromegaly.     

PRE- AND POST-OPERATIVE HYPOTHALAMIC-PITUITARY- THYROIDAL AXIS FUNCTION IN PATIENTS WITH PROLACTINOMA, GROWTH HORMONE TUMOUR AND ACTH TUMOUR

Pre- and postoperative hypothalamic-pituitary-thyroid axis function was studied in 38 patients with pituitary adenomas (PRL, GH and ACTH tumours), of whom 35 were surgically confirmed and three diagnosed by clinical signs, CT scanning and hormone assessments. About ten days after operation, the same study was repeated in 10 patients with prolactinoma and 7 with growth hormone (GH) tumour. The preoperative abnormal serum TSH response to TRH was found in 8/20 patients with prolactinoma, 9/16 with GH tumour, and 2/2 with Cushing's disease due to ACTH microadenoma. The incidence of abnormal TSH response to TRH was not significantly increased in patients with larger adenoma in either PRL or GH tumour group. In 8 cases of prolactinoma, metoclopramide (MCP, 10 mg, P.O.) test was also performed and there was a significant positive correlation between TSH responses to TRH and to MCP. Serum TT3 in the GH tumour group was within normal ranges, but significantly higher than that of the normal and prolactinoma groups. After operation, TT3 was significantly decreased as compared with that before operation and there were marked changes in TSH response to TRH. In conclusion, there were some abnormalities in TSH control in patients with non-TSH pituitary tumour, and in serum TT3 control in patients with GH tumour. The surgical treatment of pituitary adenoma can lead to transient decrease in TSH reserve and serum TT3 level probably resulting from both stress and/or destruction of thyro-trophs by the operation.     

Combined use of vasopressin and synthetic hypothalamic releasing factors as a new test of anterior pituitary function

Nine normal volunteers and 15 patients with pituitary disorders were given a combined test of anterior pituitary function using four hypothalamic releasing factors and arginine vasopressin. Rapid sequential intravenous infusions of human corticotrophin releasing factor 100 micrograms, growth hormone releasing factor 100 micrograms, luteinising hormone releasing hormone 100 micrograms, and thyrotrophin releasing hormone 200 micrograms were administered. Arginine vasopressin (10 pressor units) was given intramuscularly at the same time. Plasma or serum samples were assayed for concentrations of cortisol, growth hormone, luteinising hormone, follicle stimulating hormone, prolactin, and thyroid stimulating hormone at multiple times for 120 minutes. No troublesome side effects occurred. The results of the releasing factor combined test with arginine vasopressin were compared in the same subjects with a conventional combined test using insulin together with thyrotrophin releasing hormone and luteinising hormone releasing hormone. No difference was observed in the basal and peak concentrations of luteinising hormone, follicle stimulating hormone, thyroid stimulating hormone, and prolactin. Both cortisol and growth hormone responses to the releasing factors with arginine vasopressin were much greater than those seen with insulin induced hypoglycaemia or the combined releasing factors without arginine vasopressin. Patients with pituitary hypo-function were similarly recognised in both studies. There was a rapid increase in all hormone values with a peak usually by 60 minutes. In most people adequate assessment of individual hormone reserves may be achieved using basal, 30 minute, and 60 minute samples. This new combined releasing factor test appears to be a safe, rapid, and useful test of anterior pituitary function.     

Testing the anterior pituitary: hypoglycaemia produced by continuous intravenous insulin infusion

The response of growth hormone, cortisol, and catecholamines to hypoglycaemia produced by a continuous intravenous infusion of insulin was investigated in 10 normal subjects and 15 patients with pituitary disease. The insulin infusion rate was started at 2 U/hour for adolescents, 4 U/hour for adults, and 6 U/hour for patients with acromegaly. If required the rate was increased during the test depending on changes in blood glucose, measured by a Reflomat with low reading glucose oxidase strips. Stopping the infusion when the blood glucose concentration had fallen to 2.0 mmol/l (36 mg/100 ml) resulted in a maximum further fall of 0.7 mmol/l (13 mg/100 ml) and a subsequent spontaneous rise in blood glucose concentration. The rise was identical in normal subjects and in patients with hypopituitarism, further evidence that pituitary hormones--in contrast to glucagon and catecholamines--are relatively unimportant in the recovery from hypoglycaemia. The only patient who required intravenous glucose to restore normoglycaemia was a patient with longstanding insulin dependent diabetes. A comparison with the conventional bolus injection test showed that continuous intravenous insulin infusion was more reliable in producing adequate but not excessive hypoglycaemia and the hormone responses were equivalent. The continuous intravenous insulin infusion may offer particular advantages in the investigation of growth hormone deficiency.     

2型糖尿病患者肾上腺皮质功能及储备功能研究

目的探讨2型糖尿病患者肾上腺皮质功能及储备功能改变。方法选取2型糖尿病患者40例为观察组,40例健康志愿者为对照组;比较2组受试者血清糖化血红蛋白(HbAlc)、游离甲状腺素(FT4)、游离三碘甲状腺原氨酸(FT3)及促甲状腺激素(TSH)水平;比较2组受试者促肾上腺皮质激素(ACTH)兴奋试验前后血浆及尿皮质醇水平。结果 2组受试者血清FT3、FT4、TSH水平比较差异均无统计学意义(P>0.05)。观察组患者空腹血糖和血清HbAlc水平显著高于对照组,差异均有统计学意义(P<0.01)。2组受试者血浆皮质醇基础值及ACTH兴奋试验后15、30 min时血浆皮质醇水平比较差异均无统计学意义(P>0.05)。观察组患者ACTH兴奋试验后60、120 min时血浆皮质醇水平显著低于对照组,差异均有统计学意义(P<0.01);观察组患者血浆皮质醇峰值、峰值/基础值均显著低于对照组,差异均有统计学意义(P<0.05,P<0.01)。ACTH兴奋试验前2组受试者24 h尿皮质醇水平比较差异无统计学意义(P>0.05);ACTH兴奋试验后当日,观察组24 h尿皮质醇水平显著低于对照组,差异有统计学意义(P<0.01)。结论 2型糖尿病患者基础皮质醇水平可维持正常,但肾上腺皮质储备功能降低,对ACTH的反应性降低。     

Ⅰ型糖尿病患者酮症时胰岛素拮抗激素的变化

本文研究了10例男性I型糖尿病患者在酮症状态下和酮症纠正后血糖、血浆胰高糖素(GG)、ACTH、血清皮质醇(F)、生长激素(GH)、泌乳素(PRL)、促甲状腺激素(TSH)、T_3、T_4、尿儿茶酚胺(CA)和尿VMA的变化。结果显示在酮症状态时,血GG、ACTH、F和尿CA明显升高(P<0.05,P<0.01),酮症消失后均恢复正常,其余激素水平变化不大。提示胰岛素缺乏,GG、ACTH、F、CA升高与酮症的发生有密切关系。     

低生长激素性巨人症

报告 1例低生长激素水平且垂体大小正常的巨人症。患者 ,女 ,11岁 ,因生长过速 6年入院。查体 :身高 181cm,体重 77kg,指间距 187cm。骨龄 11.1岁 ,血清基础生长激素水平小于 1ng/ml,血清 T3 、T4、FT3 、FT4、TSH、E2 、L H、FSH、PRL、PTC及血浆 ACTH水平正常。胰岛素低血糖刺激试验、精氨酸刺激试验显示生长激素无反应。双手及头颅 X片显示尺、桡骨、掌指骨粗大 ,双手指骨骨皮质变薄 ,指骨增长 ,颅骨增大 ,颅板增厚 ,枕骨粗隆呈倒钩状。心三位片显示左、右心室轻度增大。头颅 MRI显示垂体大小正常 ,无异常信号。对于该例患者 ,非脉冲式的 GH分泌和组织对 GH敏感性增加也许导致 IGF- 1过度分泌 ,以及未分类的促生长因子和具生物活性的抗生长激素受体抗体的存在可能是导致临床上出现巨人症的原因     

Criteria for distinguishing normal from subnormal adrenocortical function using the Synacthen test

The Synacthen test consists of the measurement of plasma corticosteroid concentrations by a fluorimetric method before (basal) and 30 min after a single intramuscular administration of 250 μg of tetracosactrin (Synacthen), a synthetic polypeptide with ACTH activity equivalent to that of natural corticotrophin.     

小剂量吸入激素与β受体激动剂对哮喘的治疗作用

目的:研究β受体激动剂合并小剂量皮质类固醇对哮喘患者的疗效及对下丘脑-垂体-肾上腺轴的影响.方法:43例轻、中度的哮喘患者随机分成两组.β受体激动剂组(A组)21例,给予沙丁胺醇(1～2喷/次),加二丙酸倍氯米松(BDP)每天300 μg吸入;单纯激素组(B组)22例,仅给予BDP每天600 μg吸入及每晚吸入安慰剂,...     

垂体非生长激素瘤病人术后生长激素储备功能观察

目的了解垂体非生长激素瘤病人术后生长激素(GH)储备功能状况。方法对23例垂体非生长激素瘤术后6个月以上病人行胰岛素耐量试验(ITT),在试验前30 min及试验后0、30、45、60、90、120 min分别采血测葡萄糖(GLU)和GH,试验前30 min的血标本加测胰岛素样生长因子-1(IGF-Ⅰ)和胰岛素样生长因子结合蛋白-3(IGFBP-3)。结果垂体非生长激素瘤病人术后IGF-Ⅰ的浓度平均为(0.32±0.14)g/L,与年龄呈负相关关系(r=-0.555,P<0.05)。IGFBP-3的平均浓度为(5.92±1.15)g/L,与年龄无相关关系(r=0.036,P>0.05)。GH峰值平均为(3.92±4.71)μg/L,仅有4例病人GH峰值>5.0μg/L,其余19例病人GH峰值均<5.0μg/L,其中15例GH峰值<3.0μg/L。GH峰值<5.0μg/L的病人中有8例IGF-Ⅰ与IGFBP-3水平在正常值范围。GH峰值高度与GLU水平最低值不相关(r=-0.352,P>0.05)。结论多数垂体非生长激素瘤病人术后会发生GH缺乏或严重缺乏,对于垂体瘤术后垂体前叶功能低下者应注意评估GH储备功能。在常规补充糖皮质激素、甲状腺激素的同时,对GH缺乏或严重缺乏者应重视GH的长期替代治疗。     

Clinical and biochemical characteristics of growth hormone-secreting pituitary tumors

It has been confirmed that gsp oncogene is oneof the main cause of growth- hormone secreting pitu-itary tumor in native acromegaly patients[1] ,but dif-ference in clinical and biochemical characteristics be-tween gsp- positive and gsp- negative patients re-mained unknown. We selected 1 8cases of growthhormone( GH) - secreting pituitary tumors to studytheir clinical and biochemical characteristics.All pa-tients also underwent pituitary function combinativestimulating testto evaluate the pituita…     

DAT和D2R在垂体腺瘤组织中的表达及其意义

目的探讨垂体腺瘤组织中多巴胺转运体（DAT）和多巴胺D2受体（D2R）的表达变化及其意义。方法选取179 例手术治疗的垂体腺瘤患者,根据术前内分泌激素检查和术后病理学检查结果,将患者分为泌乳腺瘤（PRL）45 例、生长激素腺瘤（GH）43 例、促肾上腺皮质激素腺瘤（ACTH）32 例及无功能垂体腺瘤（NFPA）59例,免疫组织化学法检测垂体腺瘤组织和瘤旁正常组织中DAT、D2R的表达,分析D2R、DAT 在垂体腺瘤组织中表达的相关性。结果PRL、GH及ACTH组织中D2R、DAT 表达高于NFPA 和瘤旁正常组织,PRL 和GH 组织中D2R、DAT 表达高于ACTH 组织（p <0.05）;D2R、DAT 在垂体腺瘤组织中的表达与性别、年龄、肿瘤直径、肿瘤质地、KNOSP 分级、是否侵袭及是否复发无关（p >0.05）;Spearman 相关分析显示,D2R 在垂体腺瘤组织中的表达与DAT 呈正相关（r =0.571,p =0.000）。结论D2R、DAT 在PRL 和GH腺瘤组织中呈高表达,而在ACTH 和NFPA 腺瘤中组织呈低表达,提示多巴胺代谢紊乱可能参与不同病理学类型垂体腺瘤的发生。     

EFFECTS OF AMINOGLUTETHJMIDE ON HYPOTHALAMIC- PITUITARY-ADRENAL FUNCTIONS

This study was performed on four groups of subjects, including 10 patients with Cushing's disease, 10 patients with simple obesity, 8 patients with hypopituitarism and 13 normal subjects. The study was conducted by measuring the sequential changes of plasma ACTH, serum cortisol, 24-h UFC, 24-h 17 KS and 24-h 17 KGS following aminoglutethimide (AG) administration. The results suggest that normal subjects showed sequential changes of hypothalamic-pituitary-adrenal hormone concentrations with normal feedback regulation of the axis following AG administration. Patients with Cushing's disease had obvious autonomy in the production of ACTH from the pituitary. Patients with simple obesity might display abnormality to some degree in the production from the pituitary. Patients with hypopituitarism lost the capacity of ACTH production in various degrees because of pituitary lesions.     

急性颅脑创伤后垂体前叶激素变化及其相关因素

目的探讨颅脑损伤后患者的垂体前叶激素水平变化规律和颅脑损伤轻重分级的相关性,并探讨其对颅脑损伤预后的影响。方法回顾性分析67例颅脑损伤患者外伤后测得的垂体前叶激素水平,按照GCS积分分成轻型、中型、重型颅脑损伤组,并对所有患者随访半年。结果中、重型颅脑损伤急性期血清PRL、FT4含量显著升高,而LH、FSH、FT3含量显著降低;部分患者受伤72h后及3月后复测,上述指标逐渐恢复正常。颅脑损伤病情稳定期垂体前叶激素的LH／FSH、GH、ACTH、TSH缺乏的发生率分别为25．0％、26．0％、7．8％和4．2％。结论颅脑损伤患者急性期内分泌功能有异常变化,垂体前叶激素水平与损伤轻重程度相关,与患者预后相关。     

Do acute diseases transiently impair anterior pituitary function in patients over the age of 75? A longitudinal study of the TRH test and basal gonadotrophin levels.

Several studies have shown that anterior pituitary function is affected by the ageing process. Little is known, however, about the effect acute diseases have on the anterior pituitary. Should they be associated with a disturbance of anterior pituitary hormone production, they might make anterior pituitary function tests difficult to interpret when they are most needed. To test this hypothesis, we studied the thyrotrophin (TSH) releasing hormone (TRH) test and basal plasma gonadotrophins, taken as indicators of anterior pituitary function and reserve, in 74 consecutive patients (49 women) mean age 82 +/- 5.1 suffering from acute diseases soon after admission to hospital. A total of 44 (30 women) were followed up and retested after 3 disease-free months following recovery and discharge home. Seventy-one age- and sex-matched healthy controls (47 women), mean age 82 +/- 5.0 living in the community were also studied. The mean peak TSH increment after TRH (mean delta max TSH) increased from 5.7 soon after admission, to 7.7 U/l at follow-up (P = 0.01). The mean plasma LH increased from 25 to 35 U/l in women (P = 0.0004) and from 9.7 to 14 U/l in men (P = 0.03). The mean plasma FSH increased from 21 to 25 U/l in women (P = 0.04) and from 7.5 to 9.4 U/l in men (P = 0.01). Controls had greater TSH responses to TRH and higher plasma gonadotrophins levels when compared with acute patients (LH women P = 0.17, for all other tests P < 0.05). We conclude that a transient reduction of anterior pituitary function is a common occurrence in patients over the age of 75 suffering from acute diseases. This has diagnostic relevance and therapeutic implications.     

程序性死亡蛋白-1抑制剂治疗晚期肺癌出现垂体免疫不良反应3例

程序性死亡蛋白-1(programmed cell death protein 1,PD-1)及其配体-1(PD-1 ligand 1,PD-L1)的抑制剂广泛用于肺癌治疗,但引起的免疫相关不良反应(immune related adverse events,irAEs)值得关注。垂体irAEs包括垂体炎和垂体功能减退,常见于细胞毒T淋巴细胞相关抗原-4抑制剂治疗后,而较少见于PD-1/PD-L1抑制剂治疗后。孤立性促肾上腺皮质激素(adrenocorticotropic hormone,ACTH)缺乏是垂体irAEs的一种特殊亚型,不伴垂体其他功能紊乱和垂体肿大。本研究报告3例晚期肺癌患者,PD-1抑制剂治疗后出现孤立性ACTH缺乏及其他irAEs。病例1是68岁男性患者,先确诊PD-L1高表达的肺腺癌,采用帕博利珠单抗(pembrolizumab)单药治疗,期间出现免疫性肝炎,经高剂量甲基泼尼松龙[0.5~1.0 mg/(kg·d)]治疗后缓解;间隔11个月又确诊原发性胃癌,故在帕博利珠单抗基础上增加阿帕替尼(apatinib)治疗;帕博利珠单抗治疗共17次后,患者的肺癌和胃癌均未进展,但出现严重恶心和无力,此时甲基泼尼松龙已停药10个月,血液生化检查提示重度低钠血症(121 mmol/L,参考值137~147 mmol/L,下同),8:00 a.m.皮质醇(<1 μg/dL,参考值5~25 μg/dL,下同)和ACTH(2.2 ng/L,参考值7.2~63.3 ng/L,下同)降低,但甲状腺功能、性激素和泌乳素均正常。病例2是66岁男性肺腺癌患者,参加新型PD-1抑制剂HX008联合化疗的Ⅱ期临床研究(登记号:CTR20202387)。治疗5个月(共7次用药)后,患者的肺癌达到部分缓解,但恶心和呕吐却突然加重,伴轻度呼吸困难和双下肢无力,其血液生化检查提示轻度低钠血症(135 mmol/L),8:00 a.m.皮质醇(4.3 μg/dL)和ACTH(1.5 ng/L)降低,但甲状腺功能正常;同时肺CT显示中度免疫性肺炎。病例3是63岁男性肺鳞状细胞癌患者,一线使用信迪利单抗(sintilimab)联合化疗,肺癌最佳疗效为部分缓解,仅出现轻度免疫性皮疹;治疗5周期后,肺癌进展,此后6个月未使用免疫治疗;再次免疫治疗前,常规评估发现8:00 a.m.血皮质醇降低(1.5 μg/dL),ACTH正常(8.0 ng/L),但无肾上腺皮质功能减退症状,使用替雷利珠单抗(tislelizumab)联合化疗2周期后出现肺部感染伴持续低热、中度无力和重度低钠血症(116 mmol/L),此时, 8:00 a.m.血皮质醇为3.1 μg/dL,ACTH为7.2 ng/L,甲状腺功能、性激素和泌乳素均正常。这3例患者均无头痛和视力障碍,脑磁共振成像均未见垂体肿大或垂体柄增粗,且无动态变化。患者均接受了泼尼松(2.5~5 mg/d)激素替代治疗,相关症状缓解后均恢复PD-1抑制剂治疗。病例2较特殊,其因同时伴有中度免疫性肺炎而采用高剂量泼尼松[1 mg/(kg·d)]治疗,并逐渐减量至生理替代剂量,8:00 a.m.血皮质醇和ACTH恢复并维持正常,但其他两例患者的垂体功能减退均未恢复。本组病例提示,PD-1抑制剂诱发的垂体irAEs可表现为孤立性ACTH缺乏,其发病时间跨度大,临床表现不特异,恢复模式也不同。因此,对PD-1抑制剂治疗的患者,尤其是疗效好的患者,要定期监测垂体相关内分泌激素水平,警惕垂体irAEs。     

Glucagon-initiated human growth hormone release: a comparative study

Human growth hormone (HGH) responses in 20 healthy adults to subcutaneous glucagon, arginine infusion and tolbutamide and insulin hypoglycemia were compared. HGH rose in all four tests. HGH response to glucagon was also studied in 49 patients with suspected pituitary insufficiency, of whom 25 also later received an arginine infusion; an abnormal response to glucagon was the most frequent functional abnormality and often HGH was the only anterior pituitary hormone of which a deficiency was detectable. In seven subjects (two healthy controls and five patients with suspected hypopituitarism) there was a subnormal HGH response to arginine but a normal response to glucagon. It is concluded that glucagon is a simple and effective stimulus to HGH release, equal or superior to arginine, tolbutamide and insulin, and is an important test of anterior pituitary function.