Endocrine Abstracts

Aims: To determine the relationships between calcium:creatinine (CaCr) clearance ratio and fractional excretion of calcium (FECa).Design: Ten-week study of 15 patients aged 25–93 years undergoing investigations for parathyroid hormone (PTH)-related hypercalcaemia and 39 healthy volunteers aged 20–61 years.Outcome measures: CaCr clearance ratio calculated from 24-hour urine collection and FECa from 5 ml fasting urine aliqu...

Estrogen action is involved in the development and progression of breast cancer. In the present study, we studied the effects of bone morphogenetic proteins (BMPs) on breast cancer cell proliferation induced by estrogen using human breast cancer MCF-7 cells. MCF-7 cells express estrogen receptors (ER)α and β, BMP receptors, and Smad signaling molecules. Estradiol and membrane-impermeable estradiol stimulated MCF-7 cell proliferation. Estradiol also reduced mRNA level...

A 75-year-old gentleman was admitted with symptoms of lethargy, abdominal pain, severe nausea and vomiting in January 2008. He had solid transitional cell carcinoma of the bladder, diagnosed in May 2005, when he initially presented with microscopic haematuria. He had further undergone radical cystoprostatectomy and an ileal conduit. The histology showed aggressive tumour (G3pT3a) with vascular invasion but no metastasis. Follow-up CT scans done 9 months later showed a 3.5 cm l...

Background: The increased frequency and quality of abdominal imaging in recent years has led to a dramatic increase in the number of adrenal masses being discovered. This led to the setting up of an adrenal multi-disciplinary team (MDT) and the development of a pathway for managing patients with an adrenal ‘incidentaloma’. We investigated for evidence of hormonal activity in many of these patients.Method: A retrospective audit was carried out f...

Pheochromocytoma commonly presents with headaches, palpitations, sweating and hypertension. However, it can mimic common medical conditions, including septic shock-like syndrome, hyperthermia, pulmonary oedema, and myocardial infarction, making prompt diagnosis difficult.We present a case of phaeochromocytoma presenting as acute coronary syndrome.Case report: A 57-year-old woman presented with intermittent, intensifying central che...

Aims: To assess the short-term (one day) and longer-term (10–113 days) test-retest reliability of calcium:creatinine (Ca:Cr) ratio calculated from 24-hour urine collection and its surrogate fractional excretion of calcium (FECa) from urine aliquots.Methods: On the first visit, eight subjects (aged 22–55 years) collected two fasting urine aliquots (5 ml) at the start and end of their non-fasting 24-hour urine collection for FECa<...

Introduction: RAMPs (receptor activity-modifying proteins) are single-pass transmembrane accessory proteins required for appropriate signalling of the G-protein coupled receptors; CRLR (Calcitonin receptor like receptor) and CTR (Calcitonin receptor). There are three forms of human RAMPs known as, RAMP1, 2 and 3. RAMP3 heterodimerises with CRLR or CTR to form a high affinity receptor for the peptide hormones adrenomedullin and amylin, respectively. However, the exact mechanism...

Pituitary tumor transforming gene binding factor (PBF) is a relatively uncharacterized gene implicated in endocrine neoplasia. Given the presence of putative oestrogen response elements (ERE) in its promoter, we assessed PBF regulation by oestrogen. PBF mRNA expression was induced maximally at 48 h by 20 nM diethylstilbestrol in ERalpha-positive MCF-7 cells (2.1±0.1-fold, P<0.001, N=6). PBF protein expression levels were also significantly up-regulated b...

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder characterised by parathyroid, anterior pituitary and pancreatic islet tumours. Primary hyperparathyroidism is the first clinical manifestation in >85% of patients, although in some patients pancreatic and pituitary tumours may precede the occurrence of primary hyperparathyroidism. The earliest occurrence of MEN1-tumours has been reported at the age of 5 years following which the age-related penetr...

Multiple endocrine neoplasia type 1 (MEN1) is characterized by the combined occurrence of parathyroid, pancreatic islet and anterior pituitary tumours. Over 95% of MEN1 patients will have developed a manifestation of MEN1 by the age of forty years, and in >85% of patients, parathyroid tumours are the first to occur. In a previously reported Men1 knockout mouse model, parathyroid tumours occurred in less than 50% of Men1 heterozygous (Men1+/−...

A 67-year-old lady presented with hypoglycaemic coma, treated with dextrose infusion. Previously she had a 3-month history of weight gain with increasingly frequent episodes of shaking and blurred vision, particularly at night, relieved by food.A 72-hour fast was undertaken. Within 2 h, she became confused. Serum glucose was 1.1 mmol/l with serum insulin 527 pmol/l (0–60 pmol/l), proinsulin 320 pmol/l (0–7 pmol/l) and C-peptide 2991 pmol/l (174...

Radioiodine ablation of differentiated thyroid cancers and their metastases utilises the ability of the thyroid to accumulate iodide. However, most differentiated thyroid tumours exhibit reduced iodide uptake, with the mechanisms underlying this remaining poorly understood. Pituitary tumor transforming gene (PTTG) binding factor (PBF) is a proto-oncogene over-expressed in thyroid tumours, which we have shown to repress sodium iodide symporter (NIS) mRNA expression and inhibit ...

Background: NF1 and MEN2 are rare conditions known to associate with bilateral phaeochromochtomas. We describe, with relevant associated radiology, a NF1 patient developing a series of neuroendocrine tumours including bilateral phaeochromocytomas.Clinical case: A 39-year-old lady presented with long standing episodic abdominal pain, diarrhoea, palpitation and sweating. Past history includes first arch syndrome and NF1 at teens and total thyroidectomy for...

Neuroendocrine tumors (NETs) of GI tract are a heterogeneous group of neoplasms that secrete peptides and amines. Small bowel NETs originate from enterochromaffin (EC) cells and secrete chromogranin A (CgA) and serotonin (5-HT). NETs are highly vascular, a reflection of increased tumour related angiogenesis. Adenosine, the major regulator of angiogenesis, is released by enhanced degradation of ATP, during cellular stress, damage and hypoxia.Aims: Aims of...

Neuroendocrine tumours are slow growing and could be mistaken for other more malignant tumours with poorer prognosis. Their secretory profile may alter with time. The importance of awareness of these tumours and their clinical behaviour is illustrated by the case of a 78-year-old woman who presented with recurrent fasting hypoglycaemia.The patient had been diagnosed with metastatic pancreatic adenocarcinoma a year previously on the basis of radiographic ...

Objective: The aim of this article is to acknowledge coexistence of primary hyperparathyroidism, Cushing’s syndrome in a patient with previous history thyrotoxicosis treated with radioiodine. The presentation may be another variant of multiple endocrinal neoplasias.Is there a role of previous radioiodine therapy?Case report: A 67-year-old lady with past history of thyrotoxicosis treated with radioiodine. Now hypothyroid on thy...

Objective: We present a case of primary hyperparathyroidism awaiting surgery that has probable spontaneous resolution lasting only 4 months, supposedly because of asymptomatic infarction or haemorrhage. Her PTH has risen again though her Ca is still normal. Two such cases have been described in the literature.Case report: A 74-year-old ex-smoker, hypertensive female was admitted with two days history of confusion, lethargy and feeling unwell.<p class...

Abiraterone acetate is a potent, selective inhibitor of CYP17, a key enzyme that catalyses the conversion of pregnenolone to dehydroepiandrosterone (DHEA) and progesterone to androstenedione. Inhibition of this enzyme causes suppression of the synthesis of both androgens and oestrogens. Hence treatment with abiraterone acetate could impact on the development and progression of hormone-dependent breast and prostate cancers.In a phase I/II1,2 st...

Case: We are describing a case of 57-year-old gentleman who initially presented to gastroenterology clinic with iron deficiency anaemia (Hb – 11, Ferritin – 5) and 2 stone weight loss. An OGD was performed which demonstrated a polypoidal tumor in the distal body of stomach. Histology proved it to be carcinoid tumor. Staging CT thorax/abdomen showed marked gastric rugal thickening involving the fundus and body of the stomach with no extra mural spread, nodal disease o...

A 72-year-old man known to have Churg-Strauss syndrome, Type 2 diabetes mellitus, hypertension and asthma presented with history of polyuria, night sweats, weight loss of 6 kg over 8 weeks and poor mobility. Pulse rate was 88/min and blood pressure 131/74 mmHg. He had generalised muscle wasting with significant proximal myopathy and grade 4/5 power in all four limbs. There was no evidence of vasculitis, arthropathy or other neurological deficit. Blood tests showed urea 10.6 mm...

The fertility is commonly impaired in acromegalic patients; therefore, pregnancy in acromegaly is relatively a rare event. Little is known about management of pregnant acromegalic patients and the out come of their pregnancies. This is a report of a rather unusual case of a 37-year-old acromegalic lady diagnosed in 2001. Transphenoidal surgery 2002 continued having GH IGF1A so who had two successful pregnancies in spite her active disease. She was diagnosed in 2002 after a cli...

A 16-year-old boy presented in September 2007 with headaches and droopy eye lid due to pituitary mass. His initial prolactin level was 320 832 mu/l which confirmed the diagnosis of macroprolactinoma.His glucagon test revealed him to be growth hormone deficient with normal thyroid function test and testosterone on the lower end of normal. He was then treated with cabergoline 0.5 mg once a week and growth hormone injection 0.8 mg once a day. In June 2008, his prolactin levels we...

Background: Klotho was first identified as a gene involved in aging. A recent publication identified klotho as a possible tumour suppressor in breast cancer. We have previously reported decreased expression of klotho in tumours of primary hyperparathyroidism, here we have investigated whether klotho expression is silenced by CpG methylation of the promoter region.Materials and methods: Methylation status of klotho was determined by MSP in 40 parathyroid ...

Background: Extracellular signal-regulated kinase (ERK) cascades are key signaling pathways involved in regulation of normal cell proliferation, survival and differentiation. Abberrant regulation of the ERK pathway contributes to tumourigenesis. The ERK signalling cascade partially controls transcription of the cell cycle regulator cyclin D1 and also expression and protein stability of the c-Myc proto-oncogene.Methods: Western Blotting was used to invest...

A 37-year-old Asian lady was diagnosed with T3 N1b Papillary carcinoma of the thyroid and operated in 1999. Post operatively she developed hypoparathyroidism and has been on regular calcium and thyroid hormone replacement.She was on her 5th pregnancy this year. She had 2 previous Caesarian sections and 1 normal vaginal delivery. She was referred to Good Hope Hospital for obstetric care & local tertiary centre for investigation of hypocalcaemia having...

Primary hyperparathyroidism (PHP) can be isolated or a part of MEN especially in the younger patient. We report a 20-year lady presenting in early July-08 with vomiting, abdominal pain and general ill-health. On admission she was pale and dehydrated, with Hb 10.1 g/dl, urea 9.1 mmol/l, creatinine 105 μmol/l, alkaline phosphatase 1568 μ/l (30–130 μ/l) and adjusted calcium 3.92 mmol/l. Her sister reportedly has been investigated in a different hospital for PH...

Medullary thyroid cancer (MTC) is rare and mainly sporadic. About ≤25% of cases are inherited from a Ret protooncogene (RET) mutation. >90% of positive mutations develop MTC, either as familial (FMTC), or as part of MEN2. Early detection and treatment of MTC with total thyroidectomy improves prognosis.In 2006, as part of a project to deliver genetics into mainstream medicine, a multidisciplinary clinic (MDC) comprising a specialist thyroid surg...

Several recent studies have identified Npr2 gene mutations (encoding the guanylyl cyclase B (GC-B) receptor) as causing dwarfism and achondroplasia. Npr2 null mice have a similar bone phenotype, pituitary growth hormone deficiency and female infertility. As the endogenous ligand for GC-B, C-type natriuretic peptide (CNP) is expressed at high levels in the anterior pituitary of rats and mice, we examined whether components of the natriuretic peptide system were al...

Pituitary apoplexy in patients with Nelson’s syndrome has rarely been described. We report the case of a 33-year-old woman with a history of bilateral adrenalectomy for Cushing’s disease three years previously. Following adrenalectomy, despite adequate replacement therapy with prednisone and fludrocortisone, she became hyperpigmented, morning serum ACTH level rose from 185 to over 1250 pg/ml (normal range 10–60) and the pituitary tumour increased from 0.8/0.3 to...

At least 90% of human ovarian cancers may originate in the OSE. Most studies indicate that EOC is oestrogen responsive. Paradoxically, ovarian cancer generally occurs after the menopause, so the question arises if oestrogen is involved, where does it come from? We hypothesise that the high circulating concentrations of conjugated (inactive) oestrogens in post-menopausal women are substrates for formation of active oestrogen in the OSE through the hydrolytic enzyme activity of ...

In 1976, aged twenty, Mr A J was diagnosed with a cerebral haemangioblastoma, which was successfully removed. His father died from renal cell carcinoma and a Pheochromocytoma, raising the possibility of VHL syndrome. Genetic screening was positive but no follow-up was provided.In 2004, aged 48, he presented with a two year history of persistent diarrhoea. A CT scan revealed a left sided 1.7 cm adrenal adenoma. Serial 24 h urine metadrenaline ranged betwe...

The transient receptor potential canonical channels (TRPC) are a new family of Ca2+-permeable cationic channels controlling the Ca2+ influx response to the activation of the G-protein coupled receptor or the depletion of the internal Ca2+ store, which is related to the cellular signalling mechanisms of many hormones or growth factors. The role of TRPC channels in cancer development is still unclear. Therefore, we aimed to investigate the expres...