Endocrine Abstracts

Background:Galectin-3, a beta-galactosidase binding lectin, has been reported to be preferentially expressed in thyroid malignancies by many authors. Moreover, it has been claimed that galectin-3 is a useful adjunct to fine-needle aspiration (FNA) in the diagnosis of follicular thyroid lesions, a notorious pitfall of this test. Although galectin-3 does seem to be expressed more often in malignant thyroid lesions, especially papillary carcinomas, it is fr...

We report a 61year old female who presented with severe Cushing's disease 13 years after diagnosed as non-functioning adenoma. First presented in 1992 with visual field defect. MRI showed macroadenoma, suprasellar, and lateral extension. Gonadotrophin and GH were low. At this time there was no clinical suspicion of Cushing's syndrome. Treated with transphenoidal pituitary surgery resulting in improved vision. Immunohistochemistry showed 50% cells positive for ACTH and negative...

Parathyroid hormone-related peptide (PTHrP)have been found to be expressed in a variety of human tumors including colon and it was originally identified as the causative agent of humoral hypercalcemia of malignancy (HHM), We used a human colonic cell line (LOVO) as a model to study the mechanism for the proliferative effects of PTHrP. The PTHrP constructs expressing PTHrP in sense or antisense orientation were constructed by cloning hPTHrP complementary DNA (cDNA) coding for a...

It has been postulated that ACTH might modulate its own secretion by a negative feedback loop and we have recently found that the ACTH receptor (MC2R) is present in both normal and tumorous human corticotrophs. In this study we investigated the expression of the ACTH receptor in mouse and rat pituitary tissue as well as mouse pituitary tumour (AtT20) cells and studied the effect of Synacthen (ACTH [1-24]) on ACTH secretion, cAMP release and cell proliferation in AtT20 cells. M...

A 28-year-old Asian female presented with a 2 year history of abdominal pain and bloating and irregular heavy periods. She had a normal menarche and had 3 uncomplicated pregnancies after conceiving naturally, the last 4 years before presentation. Investigations showed LH 0.7 IU/l (normal range 2-14 IU/l), FSH 8.6 IU/l (2-14 IU/l), oestradiol 2030 pmol/l (80-300 pmol/l), prolactin 346 mU/l, and normal alpha GSU (0.3mcg/l). Ultrasound scanning revealed enlarged multicystic ovari...

Epigenetic phenomena such as methylation or acetylation of DNA can result in transcriptional inactivation and gene silencing. In the thyroid such phenomena can bring about the loss of ability to accumulate iodide as a result of methylation of CpG islands in human sodium iodide symporter (NIS) and Pendrin (PDS) DNA, limiting the ability to utilise radioiodide therapy. This study examines the effects of Trichostatin A (TSA) a histone deacetylase (HDAC) inhibitor on a rat thyroid...

Mitogenic signaling by receptor tyrosine kinases that involve increased activity of phosphatidylinositol-3-kinase (PI3K) and over-activation of protein kinase B (PKB/Akt) triggers a cascade of responses that drive tumour progression in a variety of human cancers. Some of these events have been associated with diminished expression of the cell cycle inhibitor p27 through inhibition of a Forkhead transcription factor (FKHR-L1) by Akt, while some others have recently been reporte...

Annual reports have been provided to the UK Acromegaly Database on 72 patients seen in Aberdeen during the past decade (41 women, mean age at diagnosis 47 yrs, mean GH at diagnosis 59 mU/l and 60% with macroadenomas). Thirty percent had glucose intolerance and 33% hypertension. Fifty-eight percent underwent surgery, 36% external radiotherapy (XRT, either alone or as adjuvant therapy) and 17% primary medical therapy (PMT, 4 had declined surgery). Thirty-seven percent are curren...

Archipelago/hCdc4/Fbw7 is the F-box protein specific for recognising and binding phosphorylated cyclin E and targeting it for ubiquitination. Mutations in Archipelago that prevent it from binding to phoshorylated cyclin E have been described in various human cancers including breast, ovarian and endometrial tumours. Previous studies have suggested that cyclin E is over-expressed in corticotroph tumours and other pituitary adenoma subtypes, and we postulated that this may be se...

Background: Recommendations for the diagnosis of phaeochromocytoma are based on individual institutional experience but have traditionally advocated concurrent measurement of urine and plasma catecholamines. However, reports of phaeochromocytoma presenting with normal catecholamines suggest that this practice is insufficiently sensitive. In phaeochromocytoma there is an increased output of metadrenaline metabolites with a disproprtionate increase in the unconjugated form and e...

Background: The availability of genetic testing has major implications for family management in MEN syndromes. In order to offer systematic genetic and endocrine screening for type 1 and type 2 MEN we invited patients with possible MEN syndromes to a dedicated clinic.Outcomes: In the first year 16 subjects (from 12 families) were seen, with a total of 28 previous or current tumours (12 hyperparathyroidism, 10 pituitary and 6 foregut tumours). Eight subje...

Debate surrounds the optimal biochemical assessment in the follow-up of patients withacromegaly, particularly with the introduction of GH receptor antagonists to the treatment algorithm. Consensus statements suggest target values for GH of < 1microgram per litre with normal age and sex matched IGF-1 values. A number of groups have reported on the correlation between IGF-1 and GH levels in small cohorts of acromegalic patients. We retrospectively<p...

Virilization in post-menopausal women is usually the result of androgen production by ovarian or adrenal tumours. Androgen secreting tumours account for less than 1 % of all ovarian tumours and include granulosa cell tumours, thecomas, lipoid cell tumours and luteomas. We present a case of an occult virilizing ovarian luteoma diagnosed by selective ovarian venous sampling.A 68 year old nulliparous woman presented with a 15 month history of hirsutism and ...

This study is designed to test the hypothesis that the gonadotrophinresponses to GnRH are heterogeneous and that, in pituitary/parapituitary lesion patients, the test is of no value as a diagnostic discriminator.We carried out a 5-year retrospective review of GnRH results from a cohort of 104 male (46) and female (premenopausal 49, post-menopausal 9) patients with pituitary/parapituitary lesions. Serum LH and FSH levels were measur...

As non-invasive imaging techniques, such as sonography, become more and more available, there is a growing incidence of diagnosing of non-fuctioning adrenal tumors. They are usually called adrenal incidentalomas due to absence of any evident clinical manifestations. Adrenal incidentalomas are found in 2-8% population. Although generally non-funtioning, those tumors may secrete abundant quantities of steroid hormones and thus evoke glucose intolerance, lipid disorders, thromboe...

A Short Synacthen Test (SST) cannot be used to assess the pituitary-adrenal axis immediately post transphenoidal adenectomy (TSA). A 9am cortisol must be used to achieve a balance between avoiding hypoadrenalism and over treating with replacement steroids. In this study we have determined the cut-off levels at which an averaged cortisol is most accurate and at which patients can be safely discharged with/without regular steroids or an emergency pack.62 patients (M:F 34:28) wit...

Background: Current available data demonstrate the ability of somatostatin analogues (Ssan) to reduce tumoral size in GH-secreting pituitary adenomas. Somatostatin receptors are present on both tumour cells and vascular endothelium; therefore, potential mechanisms for tumour shrinkage with Ssan include inhibition of cell proliferation, increased cell loss, and inhibition of angiogenesis.Objective: To assess the mechanisms for tumour shrinkage in GH-secre...

Background: Standard trans-peritoneal adrenalectomy has disadvantages, which are minimised by a less invasive procedure, but laparoscopic adrenalectomy is time consuming and unsuitable for large or malignant tumours.Aims: To evaluate our experience of all laparoscopically assisted mini-adrenalectomy using a subcostal incision 10 cm or less, since July 1999.Methods: Data were collected on wound size, operative time, blood loss (fall...

IntroductionSomatostatin has antiproliferative, anti-angiogenic and pro-apoptotic actions through 5 G-protein receptors (Sstr). In view of the anti-angiogenic effects of Sstrs their relationship to the distribution of vascular endothelial growth factor (VEGF) was undertaken in non-malignant Reinke's Oedema of the larynx and squamous cell carcinoma of the larynx.MethodsSix Reinke's oedema (non malignant) and 1...

Background: Serum IGF-I and IGFBP-3 levels respectively have a positive and negative association with subsequent risk of breast cancer. The anti-oestrogen tamoxifen is widely used as adjunctive therapy after resection of primary breast tumours. Tamoxifen has been reported to influence serum IGF-I, although its effects on BP-3 are unknown. The effects of tumour resection itself on IGF-I and BP-3 levels are unclear.Aims: To determine the effects of surgery...

In this study 32 acromegalic patients were retrospectively evaluated with respect to the results of different primary treatment procedures. Study group was composed of 32 acromegalic patients admitted to our department between the years 1979-2002 (20 females, 12 males; mean age 45.2 plus/minus 14.3 years, mean follow-up: 80.7 plus/minus 62.9 months). Patients were grouped according to the primary treatment approach: 1) Patients underwent pituitary surgery (n: 28; 21 macroadeno...

Background: Previous studies have implicated the GH/IGF-I axis in the pathogenesis of breast cancer and the development of tamoxifen resistance. IGF-I is a known proliferative and anti-apoptotic agent. In order to characterize the growth changes that occur when elements of the GH/IGF-I axis are disrupted we have used siRNA to transcriptionally silence the IGF-IR in the MCF-7 human breast cancer cell line.Methods: MCF-7 cells were cultured in phenol red-f...

A 71 year old obese lady was noticed to have acromegalic facies and bilateral carpal tunnel syndrome, increasing ring and shoe size, but no sweats or headaches. Random IGF-1 was raised (39.1nanomol per litre). Following oral glucose tolerance test (OGTT) fasting glucose was normal but impaired at 2hours (4.8 and 9.6millimol per litre respectively), growth hormone (GH) suppressed from a baseline of 3.8microunits per litre to 2.2microunits per litre. Following thyrotropin releas...

It is common practice to attempt withdrawal of dopamine agonist (DA) therapy in patients with microprolactinomas who have achieved sustained normoprolactinaemia. There is, however little evidence to indicate which patients might attain long-term remission. The aim of this prospective study was to identify clinical factors that might predict such remission.We recruited 40 patients (39 females and 1 male, age 24-60 years) with a diagnosis of microprolactin...

Angiogenesis is the rate-limiting step in tumour progression and metastatic spread. Both promoters and inhibitors of angiogenesis have been implicated in thyroid tumourigenesis. We have reported PTTG overexpression in thyroid and other cancers, and PTTG upregulation of the angiogenic factors FGF-2 and VEGF in vitro. To investigate whether PTTG also transactivates other downstream angiogenic effectors, we employed angiogenesis-specific cDNA arrays. Primary thyroid cells and PTT...

Neuroendocrine tumours (NETs) have an age-adjusted incidence of 1.2-2.1 per 100,000. We have studied 36 such patients with NETs who are being followed up in our multidisciplinary clinic. Of these 36 patients, there are 17 males (median age 71, range 55-88) and 19 females (median age 66, range 36-79). The presenting features were highly variable; only three patients (8.3 percent) presented with the carcinoid syndrome, eight patients (22.2 percent) presented with small bowel obs...

IntroductionIncreased cross talk between the IGF-I and oestrogen signalling pathways has been implicated in the development of tamoxifen resistance in breast cancers. We have previously demonstrated IGF-I mRNA to be down-regulated in primary breast cancers. However, the expression of IGF-I and IGFBP-3 in recurrent, tamoxifen-resistant tumours is unknown.MethodsTotal RNA was extracted from 38 paired samples of...

IntroductionIncreased cross talk between the IGF-I and oestrogen signalling pathways has been implicated in the development of tamoxifen resistance in breast cancers. We have previously demonstrated IGF-I mRNA to be down-regulated in primary breast cancers. However, the expression of IGF-I and IGFBP-3 in recurrent, tamoxifen-resistant tumours is unknown.MethodsTotal RNA was extracted from 38 paired samples of primary breast cancers (T) and adjacent normal (N) tissue and from 1...

Introduction: Somatostatin and its analogues (SSA) have been reported to have anti-proliferative effects. We have recently demonstrated expression of all 5 somatostatin receptor sub-types in normal and malignant colonic tissue. SOM-230 (Novartis) is a novel SSA that has a wider binding affinity to somatostatin receptors compared to octreotide (OCT). Its effects on proliferation of colonic cancer cells are unknown.Aims: To determine the effects of SOM-230...

Chromosomal instability (CIN) is a common feature of many malignancies including papillary and follicular thyroid cancer. During mitosis, there are multiple stages which, if dysregulated, may result in CIN. One critical stage is the regulation of sister-chromatid separation at the metaphase-anaphase transition. Three key protein complexes regulate this process: separase, cohesins and securin (also known as pituitary tumor transforming gene). In vivo, most tumours studied demon...

Background: The GH/IGF-I axis has been implicated in the development of breast cancer. However the regulation of local expression of the GH/IGF-I axis in breast tissue is unknown. In vitro studies have suggested an inhibitory effect of ghrelin on the proliferation of breast cancer cell lines, although the mechanisms for this action are unknown.Aims: Using a physiologically relevant culture system for breast tissue explants, to investigate the effects of ...

Microprolactinomas are considered not to cause pituitary hormone dysfunction, but there is little data available on the prevalence of hormone deficiencies. We aimed to establish the frequency of pituitary hormone dysfunction in patients with hyperprolactinaemia.We examined the casenotes of 124 consecutive patients (85 females) with documented hyperprolactinemia from our pituitary data-base. 52 patients had macroadenomas (tumour > 1cm diameter), 64 mic...

VA Thornton-Jones, JAH Wass and HE Turner, OBJECTIVE: Despite a recommended injection frequency of 4 weekly(4w), prolonged duration of GH suppression has been observed in some patients following treatment with long-acting somatostatin analogues. The aim of our study was to perform a prospective systematic study to determine whether extending the interval between doses of Octreotide LAR (LAR) allows maintenance of 'safe' GH in selected patients with acromegaly.<p class="abs...

Patients with histology confirmed acromegaly who have undergone trans-sphenoidal surgery and radiotherapy often have active acromegaly despite no evidence of adenoma on MRI. Currently 111In Octreotide, a radioactive tracer, is used in the assessment of neuroendocrine tumours, with 70-90 percent sensitivity for detection. Studies to date however have not looked at 111In Octreotide as an alternative measure to assess patients who present with biochemically active acromegaly desp...

A 35 year-old lady presented with classical acromegaly. Headache was a significant feature of her presentation. An oral glucose tolerance test (OGTT) confirmed acromegaly, with growth hormone (GH) levels of 21.6, 21.5, 27.0, 25.0 and 24.7 mU/l at 0, 30, 60, 90 and 120 minutes respectively. A large pituitary tumour invading the left cavernous sinus was found. Trans-sphenoidal hypophysectomy lowered GH levels but did not provide biochemical cure (10.2, 7.2, 8.1, 9.6, 9.3 mU/l). ...

BackgroundIn addition to inhibiting pituitary GH secretion, somatostatin (SS) and its analogues have been shown to exert anti-proliferative effects on a variety of different cell types. The presence of receptors for SS have been demonstrated in a number of tissues but quantification of mRNA expression of the 5 subtypes of SSTR in the colon is unknown.MethodsTotal RNA was extracted from 9 paired samples of adj...

A 65 year old lady presented to her GP in 1997 with an extensive rash. She was referred to a dermatologist but the rash which failed to settle with topical treatments. A plasma glucagon level was elevated at 275 pmol/l (NR 0-50). CTscan revealed a mass in the pancreatic tail and hepatic metastases consistent with malignant glucagonoma. She was commenced on octreotide and the rash resolved. She underwent a distal pancreatectomy, partial left hepatic lobectomy and intraoperative...

Background:Long acting somatostatin analogues are an effective treatment for acromegaly but require administration by nurses.To improve patient convenience we have taken care into the community with endocrine specialist nurse education of practice nurses in administration of injections.Methods:After an initial pilot study, a questionnaire was administered to patients receiving, and practice nurses administering, Somatuline Autogel(SA) n=10 and Sandostati...

Microprolactinomas are the commonest pituitary tumour and respond well to dopamine agonist (DA) therapy with resolution of symptoms and tumour shrinkage occurring in the vast majority of cases. Reports also suggest that up to 20% of cases may achieve long-term normoprolactinaemic remission following withdrawal of chronic dopamine agonist therapy yet interruption of therapy is not universally practised nor is there consensus on the duration of therapy. In this retrospective stu...

Surgery and radiotherapy are used in the treatment of pituitary tumours. Treatment regimens for pituitary tumours vary depending upon perceived risks of radiotherapy.The aim of the study was to determine whether pituitary disease itself, surgery or radiotherapy, affect cognitive function. This was a controlled prospective design. Two groups were studied, transphenoidal adenomectomy (TSA) pituitary patients (active), and functional endoscopic sinus surger...

Introduction: Faslodex (Fulvestrant) is a novel antiestrogen, which has been demonstrated to have clinical efficacy in metastatic breast cancer. It is thought to mediate it's effects by downregulating ER expression. ER-alpha and ER-beta function as transcription factors to modulate genes relevant to breast cancer progression. Both interact with nuclear regulatory proteins to enhance or inhibit transcription. We hypothesized that Faslodex may modulate the recruitment and intera...

Patients who have Sr. Prolactin level >3000 mU/l (n=24) were selected from the Biochemistry laboratory record & patients with confirmed diagnosis of prolactinoma (n=33) identified and / followed up at Endocrine Clinic between December 1999 and October 2001 were studied. The mean age of the patients were 45.03+ 14.09 years and 72% were women. Of the patients diagnosed to have prolactinoma, 16 had microprolactinoma. 16 had macroprolactinoma and 1 had stalk disconnection. ...

The effects of radiotherapy, one of the main options currently available for cancer therapy, depend on various factors, including the dose and the radiosensitivity of tumour cells. Radiotherapy is known to induce apoptosis in breast cancer cells, but the effects of irradiation on components of the intracellular pathways involved in apoptosis and survival are largely unknown. BAD, which is a pro-apoptotic member of the Bcl-2 family plays a central role in the interaction betwee...

Background: Management of ACTH-dependent Cushing's syndrome (ACTH-CS) remains a challenge. In the past 2 decades open bilateral adrenalectomy, associated high morbidity and long post-operative in-patient stay, has usually been reserved for cases of failed transsphenoidal surgery (TpS) and radiotherapy (RT), or where the source of ACTH is not found. Laparoscopic adrenalectomy is a significant advance with low morbidity and mortality.Aim: To assess the eff...

Somatostatin (SST) modulates exocrine and endocrine secretion, proliferation and apoptosis, via 5 transmembrane receptors (SSTRs 1 to 5), which predominantly signal through inhibitory G proteins. Stable analogs such as Lanreotide and Octreotide have been developed for use in clinical practice. Both have high affinity for SSTR 2, and moderate affinity for SSTR 5. Octreotide has been shown to inhibit endothelial proliferation, probably via SSTR 2, which is expressed by prolifera...

The short-term results of transsphenoidal surgery as initial treatment for acromegaly were analyzed according to consensus defining the criteria for cure of acromegaly.Thirty nine newly diagnosed patients with acromegaly (20 females and 19 males, mean age 46.9 plus/minus 1.4 years, range 29-66 yrs), underwent transsphenoidal pituitary adenomectomy by the same neursurgeon. Patients have been assessed postoperatively at 8 weeks (GH after 75 g oral glucose ...

ObjectiveTo assess the results of bilateral adrenalectomy and further assess the relevance of Nelson's syndrome as a complication of bilateral adrenalectomy.Patients33 patients treated by bilateral adrenalectomy at the Hammersmith Hospital were identified (earliest operation performed in 1958). Although all bilateral adrenalectomies in recent years were included, it was not possible to confirm that all bilate...

Pre-operative localization of parathyroid adenoma using parathyroid imaging remains a controversial issue. However, with the advent of minimally invasive parathyroid surgery and the use of more sensitive radionuclide (Technetium Seastamibi and recently Technetium tetrofosmin); the belief in the usefulness of parathyroid imaging is increasing.Our objectives were a) to compare the sensitivities of three parathyroid imaging modalities (Thallium Substraction, Low Dose and High Dos...

In many centres a test dose (TD) of octreotide is administered prior to commencing LAR. The value of the TD as a predictor of subsequent response to therapy remains uncertain. We have studied the relationship of the GH response to a TD to the subsequent response to LAR in 26 patients (median age 59 years, range 20- 84). After baseline GH sampling, 50mcg subcutaneous octreotide was administered and sampling continued for six hours. Results of the TD were compared to the lowest ...

The UK Acromegaly Register was established in 1997 and holds data on patients with acromegaly from 17 centres in the UK. Of 1466 records, 431 (29%) were diagnosed pre-1984, 580 (40%) between 1984 and 1993 and 455 (31%) between 1994 and 2003.Surgery was and remains the most frequently applied primary treatment for acromegaly: 46% of cases pre-1984, 53% 1994-2003. The proportion treated by surgery alone has risen from 16% to 28% in 1994 to 2003 (P<1x10-...

We have previously reported comparisons of ACROQOL, a disease-specific questionnaire for QOL in patients with acromegaly, with the non-disease-specific generic tools Psychological General Well-Being Schedule (PGWBS) and EUROQOL and disease-specific signs and symptoms score (SSS). ACROQOL comprises 22 questions (subdivided into physical and psychological classes, total score out of 110 quoted as percentage, higher scores = better QOL). SSS rates 5 features of acromegaly each ra...

Cardiovascular outcomes are better predicted by 24 hour ambulatory BP monitoring than random clinic BP (mmHg). In acromegaly, hypertension is common and cardiovascular disease is the principal cause of death. We investigated prevalence and characteristics of hypertension in 44 patients (26 male, mean age 53.1 ± 14.2), 17 of whom were receiving treatment for hypertension. A random clinic BP (normal <140/90) and IGF-I were measured prior to 24 hr ABPM assessment (Astra...

Introduction Some published studies suggest acromegalic patients have an increased risk of colonic tumours or pre-malignant dysplastic polyps. We assessed the prevalence of colonic polyps in Oxford acromegalic patients.Methods Patient database identified all 80 acromegalic patients who had had a colonoscopy.Control Patients Our data and published data on two autopsy and eight colonoscopic screening studies in asymptomatic non-acrom...