Acromegaly from ectopic growth hormone-releasing hormone secretion by a malignant carcinoid tumor. Successful treatment with long-acting somatostatin analogue SMS 201-995

A 26-year-old man with acromegaly secondary to ectopic growth hormone-releasing hormone (GHRH) secretion by a metastatic carcinoid tumor is the subject of this study. He previously failed to respond to conventional therapeutic modalities (partial hypophysectomy, pituitary irradiation, high-dose bromocriptine and a combination of streptozotocin and 5-fluorouracil) and was treated with long-acting somatostatin analogue SMS 201-995 (Sandoz, East Hanover, NJ). Growth hormone and somatomedin C concentrations became normal, and GHRH-LI (GHRH-like immunoreactivity) was suppressed by more than 60%. The growth hormone response to exogenous GHRH 1-40 was stopped and growth hormone rise to thyrotropin-releasing hormone (TRH) was significantly attenuated. A significant shrinkage of the pituitary gland was observed. Similarly, the size of the metastatic carcinoid lesions decreased dramatically and was accompanied by a normalization of liver function. After almost 2 years of SMS 201-995 therapy, the patient was well and had no clinical signs of acromegaly. Thus, SMS 201-995 appears to be a remarkably effective agent for treatment of acromegaly secondary to ectopic GHRH secretion.     

乳腺癌垂体转移1例报告

目的通过报道1例乳腺癌垂体转移病例,结合相关文献,总结垂体转移癌的临床特点,以提高对垂体转移癌的认识和诊断水平。方法分析解放军第222医院1例确诊为乳腺癌垂体转移患者的临床资料,整理近期国内外关于垂体转移癌的相关文献。结果垂体转移癌十分罕见,多来源于乳腺癌和肺癌,缺乏特征性影像学表现,以尿崩症、视神经损害和垂体前叶功能障碍为主要临床表现,与腺瘤的主要鉴别要点是具有侵袭性。结论对于生长迅速、侵袭性强、同时影响垂体前后叶功能的鞍区肿瘤需注意和垂体转移癌相鉴别。     

Atypical thymic carcinoid and malignant somatostatinoma in type I multiple endocrine neoplasia syndrome: case report

Thymic carcinoid and malignant somatostatinoma are both rare, and their concurrent presence in multiple endocrine neoplasia type 1 (MEN-1) has never been reported in the English literature to date. We present a patient with thymic carcinoid and malignant somatostatinoma in association with MEN-1. The patient eventually died of pulmonary aspergillosis and respiratory failure. Autopsy showed a 16 x 10 x 8-cm thymic carcinoid tumor, parathyroid and adrenal gland hyperplasia, and malignant somatostatinoma of the pancreas with a metastatic tumor over the splenic hilum.     

Gastric cancer metastatic to the pituitary gland: a case report

Neoplasms from almost every tissue have been reported to metastasize to the pituitary. Gastric carcinoma is a rare cause of metastases in pituitary gland. Gastric carcinoma will be the primary tumor in less than 2% of patients with pituitary gland metastases. We report the case of a 60-years old white man with liver metastasis from gastric cancer with fair presentation symptoms of pituitary gland metastasis. Basal endocrinological work-up showed corticotroph, gonadotroph, somatotroph and thyrotroph cell insufficiency; serum PRL was elevated and no deficit of the ADH level was observed. Despite the hormonal deficits the patient did not report any specific symptom. After diagnosis the patient began thyroid and adrenal-replacement therapy and was referred to Radiotherapy Unit for treatment on the sellar and pituitary gland region.     

A case of a destructive lesion of sphenoidal sinus

This interesting case deals with the possible origin of pituitary tumor from cell rests located outside the pituitary gland. In the present case we found an elderly lady presenting with a suspected mass lesion of the sphenoidal sinus, clinically suspected to be either an infective granuloma or a chordoma which finally turned out to be an adenoma of the pituitary gland.     

Clinical and epidemiologic characteristics of first primary tumors of the central nervous system and related organs among atomic bomb survivors in Hiroshima and Nagasaki, 1958-1995

BACKGROUND: Analysis conducted in the Life Span Study (LSS) cohort of atomic bomb survivors in Hiroshima and Nagasaki found a significant dose-related excess of tumors of the central nervous system (CNS) and the pituitary gland. The objective of the current study was to evaluate clinical and epidemiologic characteristics of first primary tumors of the CNS and the pituitary gland in this cohort and to compare them with characteristics among other populations. METHODS: CNS and pituitary gland tumors that were diagnosed between 1958 and 1995 among 80,160 LSS cohort members were ascertained through Hiroshima and Nagasaki tumor registries, autopsy reports, and other sources. Pathologists reviewed all available records and slides to verify histologic diagnoses. Poisson regression analysis was used to model background incidence rates allowing for radiation effects. RESULTS: Meningioma was the most common tumor among clinically diagnosed tumors, followed by neuroepithelial tumor, schwannoma, and pituitary tumor. The overall incidence of these tumors increased initially with age but declined among the elderly. For all age groups and for both genders, incidence increased over time. By contrast, when tumors diagnosed at autopsy were included, incidence rose continuously with age and was stable over time. CONCLUSIONS: The main characteristics of CNS and pituitary gland tumors diagnosed in the LSS cohort were consistent with the characteristics of "spontaneous" tumors observed in other population-based studies. The predominance of meningiomas over neuroepithelial tumors in the Japanese population was noteworthy and warrants further investigation. The secular rise in incidence of all clinically diagnosed CNS and pituitary gland tumors is most likely to be attributable to the increased use of new imaging techniques.     

An autopsy case of anaplastic carcinoma of the thyroid gland with primary empty sella and marked atrophy of the adrenal glands

The patient was a 67-year-old woman, she had lost her public and axillary hair upon menopause at the age of 47, and symptoms of hypothyroidism appeared with cervical tumor one year prior to her death. A diagnosis of anaplastic carcinoma was made by biopsy of the thyroid gland. Laboratory examination revealed a high titer of antithyroid antibody and dysfunction of the thyroid gland, adrenal cortices and pituitary gland. At autopsy, the pituitary gland showed a cup-shaped deformity with atrophy, and the adrenal glands were markedly atrophic. It was considered that the atrophy of the adrenal glands was secondary to dysfunction of the pituitary gland.     

Strain difference in regulation of pituitary tumor transforming gene (PTTG) in estrogen-induced pituitary tumorigenesis in rats.

Recently a novel oncogene, PTTG (pituitary tumor transforming gene) was isolated from a rat pituitary tumor cell line whose expression is apparently correlated with pituitary tumorigenesis. In the rat, estradiol (E(2)) is known to induce anterior pituitary hyperplasia. The effects of E(2), however, vary greatly among rat strains. Therefore we examined the expression of PTTG and its regulation by E(2) in F344, Wistar, Brown-Norway and Donryu rats. Four-week-old females were ovariectomized and a pellet containing 10 mg of E(2) was given s.c. Total RNA was isolated from the pituitary gland and PTTG mRNA was measured with a competitive RT-PCR technique. The F344 strain was the most susceptible to E(2) induction of pituitary tumorigenesis, followed by Wistar and Brown-Norway, while no increase in pituitary weight was noted in Donryu rats. PTTG mRNA in the gland was induced by E(2) within 48 - 72 h in F344 and Wistar, but not in Brown-Norway or Donryu strains. These data suggest that PTTG expression may at least in part be responsible for strain differences in E(2)-induced pituitary tumorigenesis.     

支气管肺类癌导致的异位ACTH综合征

目的通过对支气管肺类癌引起的异位ACTH综合征患者的临床资料分析,总结其临床特点,以提高对该病的认识和诊治水平。方法回顾性分析北京协和医院1984～2009年经病理证实的13例支气管肺类癌引起的异位ACTH综合征患者的临床资料。结果13例患者就诊时的平均年龄35．4岁,就诊时的病程为19．9±18．3个月（1．3～60个月）,从初诊至发现肺部占位的时间为15．6±36．1个月（1．0—132个月）。11例（84．6％）患者存在低血钾（2．60±0．61mmol／L）。4例（30．8％）患者大剂量地塞米松抑制试验不被抑制。11例（91．7％）患者初诊时进行了肺CT检查发现了肺部病变。肿瘤平均直径为2．1cm。结论支气管肺类癌是导致隐性异位ACTH综合征的常见原因,但在临床上有时与库欣病很难鉴别。因此对于ACTH依赖的库欣综合征应常规筛查肺部病变,对可疑病例进行全面检查以明确肿瘤定位。     

Studies on estrogen induced pituitary tumor in the rat with special reference to the relationship of the tuberoinfundibular dopamine neuron system

Pituitary tumors were experimentally induced in female Wistar rats by repeated injections of estradiol dipropionate. The hypothalamus and pituitary tumors were studied simultaneously by fluorescence histochemistry and immunohistochemistry. The pituitary gland became larger with a concomitant increase of serum prolactin in proportion to the dose of estrogen. Estrogen-induced pituitary tumor exhibited a proliferating prolactin cells by the peroxidase immunohistochemical method. Ultramicroscopical findings showed that these tumor cells were in an extremely hyperfunctional state. The dopamine neuronal perikarya in the hypothalamic arcuate nucleus and their terminals in the external layer of the median eminence were examined by fluorescence histochemistry in the rats bearing estrogen induced pituitary tumor and it was concluded that in our experimental conditions, estrogen effected directly on pituitary rather than on the hypothalamus and consequently dopamine synthesis in the arcuate neurons and its release into portal capillaries were accerelated simultaneously in order to inhibit prolactin secretion from tumor cells.     

Cervical metastases from small bowel carcinoid tumors

Small bowel carcinoid tumors usually metastasize to regional lymph nodes and the liver but metastases to the neck are extremely rare. Over a ten-year period 48 cases of small bowel carcinoid were diagnosed at our institution and of these, three cases (6%) were associated with neck metastases--one to the thyroid gland and two to cervical lymph nodes. The former patient and one of the latter patients had symptoms of the carcinoid syndrome. The other patient was asymptomatic and presented with a solitary neck mass. Urine levels of 5-hydroxyindolacetic acid (5-HIAA) were elevated in the two symptomatic patients but were undetectable in the asymptomatic patient. Extirpation of the involved cervical nodes and the primary small bowel lesion was performed in two patients. In addition, both patients have received chemotherapy with 5-fluorouracil. One patient remains asymptomatic four years after diagnosis but the other patient continues to have five to six bowel movements per day nine months after operation. Small bowel resection was performed in the patient with a metastasis to the thyroid. This patient died of sepsis after a second operation for an intraabdominal abscess. The histological patterns of the primary tumor and the metastatic lesions were similar and the cells of the metastases contained argentaffin-positive granules. We conclude that 1) an intraabdominal carcinoid tumor should be considered as the location of the primary tumor in patients who present with a neck mass containing metastatic carcinoid and 2) the prognosis for patients with extraabdominal metastases is similar to that for patients with intraabdominal disease only.     

Strain Difference in Regulation of Pituitary Tumor Transforming Gene (PTTG) in Estrogen–induced Pituitary Tumorigenesis in Rats

Recently a novel oncogene, PTTG (pituitary tumor transforming gene) was isolated from a rat pituitary tumor cell line whose expression is apparently correlated with pituitary tumorigenesis. In the rat, estradiol (E₂) is known to induce anterior pituitary hyperplasia. The effects of E₂, however, vary greatly among rat strains. Therefore we examined the expression of PTTG and its regulation by E₂ in F344, Wistar, Brown–Norway and Donryu rats. Four–week–old females were ovariecto–mized and a pellet containing 10 mg of E₂ was given s.c. Total RNA was isolated from the pituitary gland and PTTG mRNA was measured with a competitive RT–PCR technique. The F344 strain was the most susceptible to E₂ induction of pituitary tumorigenesis, followed by Wistar and Brown–Norway, while no increase in pituitary weight was noted in Donryu rats. PTTG mRNA in the gland was induced by E₂ within 48–72 h in F344 and Wistar, but not in Brown–Norway or Donryu strains. These data suggest that PTTG expression may at least in part be responsible for strain differences in E₂–induced pituitary tumorigenesis     

Transitional cell tumor of the pituitary gland developing from a Rathke's cleft cyst

A tumor of the pituitary gland is reported which developed from the wall of a Rathke's cleft cyst. This was an incidental autopsy finding in a 79-year-old diabetic woman. The cyst wall was lined by ciliated, mucus producing columnar epithelium with areas of squamous metaplasia, the solid portion of the tumor was composed of cells with light and electron microscopic characteristics of squamous cells, mucus producing cells and anterior lobe cells of the pituitary: they displayed intercellular bridges, intracellular mucus droplets and on electron microscopy varying numbers of intracytoplasmic secretory granules in the 220-450 millimicron range. The cells thus correspond to an early developmental stage of the pituitary anterior lobe, when the still squamous and columnar Rathke's cleft cells begin to develop their endocrine granulation. For this reason it was felt that "transitional cell tumor of the pituitary" would best characterize this hitherto undescribed neoplasm.     

Ectopic insulin production by a primary ovarian carcinoid

An insulin-containing ovarian carcinoid was found at the autopsy of a 63-year-old woman with a 12-year history of episodic hyperinsulinemic hypoglycemia. In terms of histology, the carcinoid displayed both insular and trabecular patterns and contained a small focus of mucinous cystadenoma. Beta secretory granules were demonstrated by electron microscopy, and immunoreactivity for insulin was demonstrated in tumor cell cytoplasm by immunohistochemistry. Additional autopsy findings included a solitary parathyroid adenoma and a microscopic focus of pituitary hyperplasia. This is the first recorded case of insulin production by a primary ovarian neoplasm. The patient's constellation of endocrine findings may represent a variant of the syndrome of type I multiple endocrine neoplasia.     

Clinical usefulness of 99mTc-EDDA/HYNIC-TOC scintigraphy in oncological diagnostics: a pilot study

The clinical usefulness of a new 99mTc-labeled somatostatin analogue has been studied from the standpoint of oncological diagnostics. The group of patients studied included 40 individuals with diagnosed malignant neoplasms (32 primary and 8 metastatic). Among the primary tumors were 7 pituitary adenomas (5 hormonally active and 2 inactive), 1 liposarcoma, 2 carcinoids, 1 breast carcinoma, and 21 cases of lung cancer (2 small cell and 19 non-small cell) were represented. The metastatic tumors consisted of: 3 malignant melanomas, 1 pheochromocytoma, 1 prostatic cancer, 1 leiomyosarcoma, 1 pancreatic carcinoma ectopically secreting ACTH, and 1 carcinoid of the thymus. The radiopharmaceutical, 99mTc-EDDA/HYNIC-octreotide, was i.v. administered at the activity of 740-925 MBq. The imaging was comprized of a whole-body scan and single photon emission computed tomography. Positive scintigrams were obtained in 4 of 5 hormonally active pituitary adenomas, in 1 of 2 cases of carcinoid, in liposarcoma, breast cancer, and all cases of small cell (SCLC) and non-small cell lung cancer (NSCLC). The neoplastic metastases were visualized in 2 of 3 cases of melanoma and in patients with pheochromocytoma, pancreatic carcinoma secreting ACTH, and thymic carcinoid. Scintigrams were negative in both hormonally inactive pituitary adenomas, in one case of metastatic malignant melanoma, leiomyosarcoma, and in cases of metastasis from the prostatic carcinomas. The results of this pilot study indicated that 99mTc-EDDA/HYNIC-TOC is a potentially useful radiopharmaceutical for the imaging of a wide range of primary and metastatic tumors. More detailed indications for the clinical usefulness of the new tracer for the imaging of selected tumor types require studies on much larger groups of patients. Special attention should be paid to the successful imaging of all cases of NSCLC.     

Allele Loss on Chromosome 11 in a Pituitary Tumor from a Patient with Multiple Endocrine Neoplasia Type 1

We have examined the allele loss of chromosome 11 in a pituitary tumor from a patient with familial multiple endocrine neoplasia type 1 (MEN 1). The extensive loss of chromosome 11, including loci of D11S149, HRAS1 and F2 , was detected by the loss of heterozygosity. All of the lost alleles of these loci were transmitted from the unaffected father and not from an affected mother. This is the first evidence of allele loss of chromosome 11 in a pituitary tumor of MEN 1 and supports the idea that similar allelic deletion of MEN1 locus on chromosome 11 is the common genetic basis for tumorigenesis in the pituitary, endocrine pancreas, and parathyroid gland in MEN 1.     

经鼻蝶窦行垂体瘤切除术后的激素变化及激素替代治疗疗效

目的:探索经鼻蝶窦行垂体瘤切除术后激素变化规律及激素替代治疗疗效,为垂体瘤患者的手术治疗及术后激素替代治疗提供依据。方法:收集我院2013年9月至2015年9月接受手术治疗的垂体瘤患者82例,分别检测患者术前1天、术后3天、术后1周、术后1个月、术后3个月、术后1年的垂体及相应靶腺分泌的激素水平,并根据术后腺体功能评估选择是否需相应药物进行替代治疗。结果:生长激素（GH）腺瘤（24例）、泌乳素（PRL）腺瘤（15例）患者术后3天GH、PRL激素水平显著下降（P＜0.05）,进一步随访发现,术后1周、1个月、3个月、1年激素水平在正常范围内有一定下降趋势。15例无功能瘤患者促甲状腺素（TSH）、游离三碘甲腺原氨酸（FT3）水平,9例无功能瘤患者皮质醇（COR）水平在术后3天至术后1周显著下降（P＜0.05）,然后分别使用左旋甲状腺素和氢化可的松进行替代治疗。所有接受左旋甲状腺素和氢化可的松进行替代治疗的患者中,分别有9例、8例患者随访的过程中停药或者减量,分别有6例（7.2%）、3例（3.6%）患者新发甲状腺功能减退及肾上腺功能减退,需要6个月以上时间的替代治疗。结论:经鼻蝶窦行垂体瘤切除后可以解除肿瘤的压迫效应并有效改善术前的高激素水平状态,远期疗效较好。但术后可能会新发较少垂体功能减退,需要进行较长时间的药物替代治疗。     

Parathyroid carcinoma in a patient with non-secretory pituitary tumor: a variant of multiple endocrine neoplasia type-I?

We report a case of pituitary adenoma in association with parathyroid carcinoma as an unusual combination of multiple endocrine neoplasia (MEN). A 48-year-old man had a trans-sphenoidal hypophysectomy and transcranial partial removal of a recurrent pituitary chromophobe adenoma followed by a course of radiotherapy in 1980. Four years later, he developed hypercalcemic crisis from a parathyroid carcinoma with invasion to the adjacent thyroid gland and skeletal muscle. A hemithyroidectomy and resection of the left lower parathyroid gland was performed. Three years later, he had local recurrence and anterior chest wall metastasis accompanied by hypercalcemia. After resection of the remnant and metastatic lesion, eucalcemia was achieved. There was no family history of endocrine tumors. This case illustrates the rare association of a malignant parathyroid tumor and a chromophobe adenoma of the pituitary as a variant of MEN syndrome.     

Allele loss on chromosome 11 in a pituitary tumor from a patient with multiple endocrine neoplasia type 1.

We have examined the allele loss of chromosome 11 in a pituitary tumor from a patient with familial multiple endocrine neoplasia type 1 (MEN 1). The extensive loss of chromosome 11, including loci of D11S149, HRAS1 and F2, was detected by the loss of heterozygosity. All of the lost alleles of these loci were transmitted from the unaffected father and not from an affected mother. This is the first evidence of allele loss of chromosome 11 in a pituitary tumor of MEN 1 and supports the idea that similar allelic deletion of MEN1 locus on chromosome 11 is the common genetic basis for tumorigenesis in the pituitary, endocrine pancreas, and parathyroid gland in MEN 1.