Ectopic hyperprolactinaemia due to a malignant Uterine Tumor Resembling Ovarian Sex Cord Tumors (UTROCST)

Purpose Moderate hyperprolactinaemia (2–5 times upper limit of normal) occurring in a patient with a normal pituitary MRI is generally considered to be due to a lesion below the level of detection of the MRI scanner assuming macroprolactin and stress have been excluded. Most patients with mild-to-moderate hyperprolactinaemia and a normal MRI respond to dopamine agonist therapy. We present the rare case of a patient who had prolactin elevation typical of a prolactin-secreting pituitary macroadenoma,with a normal cranial MRI, and in whom the prolactin rose further with dopamine agonist treatment. Subsequent investigations revealed ectopic hyperprolactinaemia to a uterine tumor resembling ovarian sex cord tumor (UTROSCT) which resolved following tumor resection. Although mostly considered to be benign, the UTROSCT recurred with recurrent hyperprolactinaemia and intraabdominal metastases. Methods We have systematically and critically reviewed existing literature relating to ectopic hyperprolactinaemia in general and UTROCST specifically. Results Fewer than 80 cases of UTROSCTs have been reported globally of which about 23% have shown malignant behaviour. There are fewer than 10 cases of paraneoplastic hyperprolactinaemia originating from uterine neoplasms including one other case of ectopic hyperprolactinaemia to a UTROSCT. Conclusions Our case demonstrates the importance of screening for extracranial hyperprolactinaemia in the context of: (1) substantially raised prolactin (10× ULN) and (2) normal cranial MRI assuming macroprolactin has been excluded. The majority of extracranial ectopic prolactin-secreting tumors occur in the reproductive organs.Methods: We have systematically and critically reviewed existing literature relating to ectopic hyperprolactinaemia in general and UTROCST specifically. Results: Fewer than 80 cases of UTROSCTs have been reported globally of which about 23% have shown malignant behaviour. There are fewer than 10 cases of paraneoplastic hyperprolactinaemia originating from uterine neoplasms including one other case of ectopic hyperprolactinaemia to a UTROSCT. Conclusions: Our case demonstrates the importance of screening for extracranial hyperprolactinaemia in the context of: (1) substantially raised prolactin (10xULN) and (2) normal cranial MRI assuming macroprolactin has been excluded. The majority of extracranial ectopic prolactin-secreting tumors occur in the reproductive organs

Quantitative historical analysis uncovers a single dimension of complexity that structures global variation in human social organization.

Do human societies from around the world exhibit similarities in the way that they are structured, and show commonalities in the ways that they have evolved? These are long-standing questions that have proven difficult to answer. To test between competing hypotheses, we constructed a massive repository of historical and archaeological information known as "Seshat: Global History Databank." We systematically coded data on 414 societies from 30 regions around the world spanning the last 10,000 years. We were able to capture information on 51 variables reflecting nine characteristics of human societies, such as social scale, economy, features of governance, and information systems. Our analyses revealed that these different characteristics show strong relationships with each other and that a single principal component captures around three-quarters of the observed variation. Furthermore, we found that different characteristics of social complexity are highly predictable across different world regions. These results suggest that key aspects of social organization are functionally related and do indeed coevolve in predictable ways. Our findings highlight the power of the sciences and humanities working together to rigorously test hypotheses about general rules that may have shaped human history

Quantitative Historical Analysis Uncovers a Single Dimension of Complexity that Structures Global Variation in Human Social Organization

Do human societies from around the world exhibit similarities in the way that they are structured, and show commonalities in the ways that they have evolved? These are long-standing questions that have proven difficult to answer. To test between competing hypotheses, we constructed a massive repository of historical and archaeological information known as “Seshat: Global History Databank.” We systematically coded data on 414 societies from 30 regions around the world spanning the last 10,000 years. We were able to capture information on 51 variables reflecting nine characteristics of human societies, such as social scale, economy, features of governance, and information systems. Our analyses revealed that these different characteristics show strong relationships with each other and that a single principal component captures around three-quarters of the observed variation. Furthermore, we found that different characteristics of social complexity are highly predictable across different world regions. These results suggest that key aspects of social organization are functionally related and do indeed coevolve in predictable ways. Our findings highlight the power of the sciences and humanities working together to rigorously test hypotheses about general rules that may have shaped human history

Quantitative historical analysis uncovers a single dimension of complexity that structures global variation in human social organization

Do human societies from around the world exhibit similarities in the way that they are structured, and show commonalities in the ways that they have evolved? These are long-standing questions that have proven difficult to answer. To test between competing hypotheses, we constructed a massive repository of historical and archaeological information known as “Seshat: Global History Databank.” We systematically coded data on 414 societies from 30 regions around the world spanning the last 10,000 years. We were able to capture information on 51 variables reflecting nine characteristics of human societies, such as social scale, economy, features of governance, and information systems. Our analyses revealed that these different characteristics show strong relationships with each other and that a single principal component captures around three-quarters of the observed variation. Furthermore, we found that different characteristics of social complexity are highly predictable across different world regions. These results suggest that key aspects of social organization are functionally related and do indeed coevolve in predictable ways. Our findings highlight the power of the sciences and humanities working together to rigorously test hypotheses about general rules that may have shaped human history.This work was supported by a John Templeton Foundation Grant (to the Evolution Institute) entitled “Axial-Age Religions and the Z-Curve of Human Egalitarianism,” a Tricoastal Foundation Grant (to the Evolution Institute) entitled “The Deep Roots of the Modern World: The Cultural Evolution of Economic Growth and Political Stability,” Economic and Social Research Council Large Grant REF RES-060-25-0085 entitled “Ritual, Community, and Conflict,” an Advanced Grant from the European Research Council under the European Union’s Horizon 2020 Research and Innovation Programme Grant 694986, and Grant 644055 from the European Union’s Horizon 2020 Research and Innovation Programme (ALIGNED; www.aligned-project.eu). T.E.C. is supported by funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (Grant Agreement 716212).Peer Reviewe

Hyperprolactinaemia resistant to dopamine agonist due to an ectopic source of prolactin arising from a Uterine Tumour Resembling Ovarian Sex Cord Tumours (UTROCST)

Introduction: Moderate hyperprolactinaemia occurring in a patient with a normal pituitary MRI, assuming macroprolactin and stress are excluded, is generally considered to be due to a lesion below the level of detection of the MRI scanner. Most patients with mild-moderate hyperprolactinaemia and a normal MRI respond to dopamine agonist therapy. We describe a patient who had prolactin elevation typical of a prolactin-secreting macroadenoma, but with a normal MRI, and in whom the prolactin rose further with dopamine agonist treatment. Case: A 46 year-old female presented with 12 months history of secondary amenorrhoea without galactorrhoea. Prolactin was 4746 mIU/l without macroprolactin complexes, LH & FSH were low and oestradiol was undetectable. She had normal visual fields and no other clinical or biochemical features of pituitary dysfunction. She was not on regular medication. Pituitary MRI was normal with no focal lesion. She was started on cabergoline 250 mcg twice weekly which was subsequently increased to 500 mcg twice weekly. Repeat serum prolactin 5 months and 8 months later showed a progressive rise to 6649 mIU/l and 9653 mIU/l respectively, and rose to 11,611 mIU/l. Compliance with medication was confirmed. Repeat pituitary MRI scan was normal. An alternative source of prolactin was considered and further clinical assessment revealed a palpable pelvic mass. Pelvic CT showed an 11 cm uterine mass which raised the possibility of an ectopic prolactin source. She underwent surgical resection. Histological examination showed a benign Uterine Tumour Resembling Ovarian Sex Cord Tumours (UTROSCT). Immunohistochemistry was negative for prolactin, however, serum prolactin postoperatively was 59 mIU/L and her menstrual cycle returned to normal. Discussion: The notable features of this case were (1) the high prolactin suggestive of a macroadenoma with a normal MRI scan (2) a paradoxical rise in the serum prolactin after initiation of dopamine agonist therapy. Out of eight previous reports of ectopic extra-cranial prolactin secretion in the published literature, there are three ovarian germ cell tumours (two teratomas, one dermoid) which had microscopic pituitary elements. UTROSCTs are very rare uterine neoplasms with the most literature review citing 77 cases. UTROSCTs have not been associated with hyperprolactinaemia prior to this report. However, two other cases have been reported with uterine tumours (one “fibroid” and one “mesenchymal tumour”) which share characteristics with this case. Hyperprolactinaemia due to extra-cranial ectopic prolactin production is very rare. Where suspected, the majority of ectopic prolactin-secreting tumours have been located in the ovaries and uterus

Implementing the UK Medical Research Council (MRC) RT01 trial (ISRCTN 47772397): methods and practicalities of a randomised controlled trial of conformal radiotherapy in men with localised prostate cancer

BACKGROUND AND PURPOSE: Radiotherapy is the most frequently used treatment for men with localised prostate cancer. Conformal radiotherapy (CFRT) is a relatively new development. MRC RT01 was set-up to explore optimum CFRT dose. PATIENTS AND METHODS: RT01 was an international multi-centre randomised controlled trial for men with T1b-T3a, N0, M0 prostate cancer that evolved from a single-centre pilot trial of similar design. All men received at least 3 months of pre-radiotherapy hormone treatment, before randomisation to standard (64 Gy) or high dose (74 Gy) radical CFRT. Accrual was completed in December 2001 with 843 men randomised from 25 centres in less than 4 years. RT01 has been a catalyst for implementing CFRT across UK. In addition to the Trial Management Group, independent Data Monitoring and Ethics Committee and independent Trial Steering Committee, a Quality of Life and Health Economics (QL/HE) group, a radiotherapy Quality Assurance (QA) Group and a Radiography Trial Implementation Group were set up. The QL/HE group ensured implementation, compliance, analysis and interpretation of the QL and HE data in the trial. The inauguration of QA and Radiography groups facilitated inter-centre collaboration. The QA Group ensured procedures were in place before and during trial participation, and monitored quality and consistency with systems including a physics questionnaire, a clinical examples exercise, a standard operating procedure document, designing and building a phantom, and convening a complications modelling subgroup. The Radiography group agreed and implemented technique improvements. RESULTS: More centres participated than initially predicted, enabling recruitment better than scheduled. The trial expedited the implementation of CFRT in many UK radiotherapy centres. Additionally, the QA and Radiography groups helped ensure smooth initiation and established consistency in planning, dosimetry and delivery of prostate CFRT services at participating UK centres. Considerable data has been collected; a series of papers will be produced, although mature clinical trial results are not anticipated until 2006-2008