Stephanie Baldeweg

UK guidelines for the management of pituitary apoplexy

Classical pituitary apoplexy is a medical emergency and rapid replacement with hydrocortisone maybe life saving. It is a clinical syndrome characterized by the sudden onset of headache, vomiting, visual impairment and decreased consciousness caused by haemorrhage and/or infarction of the pituitary gland. It is associated with the sudden onset of headache accompanied or not by neurological symptoms involving the second, third, fourth and sixth cranial nerves. If diagnosed patients should be referred to a multidisciplinary team comprising, amongst others, a neurosurgeon and an endocrinologist. Apart from patients with worsening neurological symptoms in whom surgery is indicated, it is unclear currently for the majority of patients whether conservative or surgical management carries the best outcome. Post apoplexy, there needs to be careful monitoring for recurrence of tumour growth. It is suggested that further trials be carried out into the management of pituitary apoplexy to optimize treatment.

Heterogeneous Genetic Background of the Association of Pheochromocytoma/Paraganglioma and Pituitary Adenoma: Results From a Large Patient Cohort

Context: Pituitary adenomas and pheochromocytomas/paragangliomas (pheo/PGL) can occur in the same patient or in the same family. Coexistence of the two diseases could be due to either a common pathogenic mechanism or a coincidence. Objective: The objective of the investigation was to study the possible coexistence of pituitary adenoma and pheo/PGL. Design: Thirty-nine cases of sporadic or familial pheo/PGL and pituitary adenomas were investigated. Known pheo/PGL genes (SDHA-D, SDHAF2, RET, VHL, TMEM127, MAX, FH) and pituitary adenoma genes (MEN1, AIP, CDKN1B) were sequenced using next generation or Sanger sequencing. Loss of heterozygosity study and pathological studies were performed on the available tumor samples. Setting: The study was conducted at university hospitals. Patients: Thirty-nine patients with sporadic of familial pituitary adenoma and pheo/PGL participated in the study. Outcome: Outcomes included genetic screening and clinical characteristics. Results: Eleven germline mutations (five SDHB, one SDHC, one SDHD, two VHL, and two MEN1) and four variants of unknown significance (two SDHA, one SDHB, and one SDHAF2) were identified in the studied genes in our patient cohort. Tumor tissue analysis identified LOH at the SDHB locus in three pituitary adenomas and loss of heterozygosity at the MEN1 locus in two pheochromocytomas. All the pituitary adenomas of patients affected by SDHX alterations have a unique histological feature not previously described in this context. Conclusions: Mutations in the genes known to cause pheo/PGL can rarely be associated with pituitary adenomas, whereas mutation in a gene predisposing to pituitary adenomas (MEN1) can be associated with pheo/PGL. Our findings suggest that genetic testing should be considered in all patients or families with the constellation of pheo/PGL and a pituitary adenoma.

A spectrum of behaviour in silent corticotroph pituitary adenomas

Silent corticotroph adenomas (SCA) are pituitary tumours positive on immunohistochemical staining for ACTH but without clinical evidence of Cushings disease in the patient. Previous reports suggest that these tumours may behave in a more aggressive way then other pituitary adenomas. We have followed the natural history of SCA and assessed whether histopathological indices predict tumour behaviour. We identified 22 patients in whom trans-sphenoidal surgery was performed for a non-functioning adenoma (NFA) with positive immunostaining for ACTH between 1990 and 2000 and examined the history of their disease. Patients were followed up for a mean of 4.8 years. A total of 86.7% of patients had documented visual deficits at presentation. In four cases hypercortisolaemia was observed later in the course of the disease. Two patients died as a result of their SCA and 33.3% of tumours recurred. Recurrence was more frequent in patients treated with adjuvant radiotherapy. Pathological indices (increased mitotic range and Ki-67) did not predict recurrence or malignant transformation. We suggest that certain ‘silent’ corticotroph tumours may have the potential for ACTH secretion leading to hypercortisolaemia at a later stage in the disease. The possibility of transformation to a more aggressive tumour needs to be considered in all SCA.

Missed opportunities for diabetes prevention: post-pregnancy follow-up of women with gestational diabetes mellitus in England

BACKGROUND Women with gestational diabetes mellitus (GDM) should be followed-up to exclude ongoing diabetes and for prevention of type 2 diabetes. The National Institute for Health and Clinical Excellence (NICE) diabetes in pregnancy guideline recommends checking fasting plasma glucose (FPG) at 6 weeks postpartum (short term), and annually thereafter (long term). AIM To examine the reported practice regarding GDM follow-up. DESIGN AND SETTING Nationwide postal survey in England 2008-2009. METHOD Questionnaires were distributed to a consultant diabetologist and obstetrician in all maternity units, and to a random sample of general practices (approximately 1 in 5). RESULTS Response rates were: 60% (915/1532) GPs, 93% (342/368) specialists; 80% of GPs and 98% of specialists reported women with GDM had short-term follow-up. More GPs (55%) than specialists (13%) used a FPG test to exclude ongoing diabetes; 26% of GPs versus 89% of specialists thought the hospital was responsible for ordering the test. Twenty per cent of GPs had difficulty in discovering women had been diagnosed with GDM in secondary care. Seventy-three per cent of specialists recommended long-term follow-up; only 39% of GPs recalled women with GDM for this. A minority of GPs and specialists had joint follow-up protocols. CONCLUSION Follow-up of GDM in England diverged from national guidance. Despite consensus that short-term follow-up occurred, primary and secondary care doctors disagreed about the tests and responsibility for follow-up. There was lack of long-term follow-up. Agreement about the NICE guideline, its promotion and effective implementation by primary and secondary care, and the systematic recall of women with GDM for long-term follow-up is required.

IMPLICATIONS OF THE UNITED KINGDOM PROSPECTIVE DIABETES STUDY

The United Kingdom Prospective Diabetes Study (UKPDS) is the largest ever study to clarify the role of glycemia and blood pressure control in improving morbidity and mortality in patients with type 2 diabetes. The study examined the impact of glycemia and blood pressure control on microvascular and macrovascular risk, and if any particular therapy was advantageous for these patients. This articles discusses the background, methodology and results of the UKPDS and develops recommendations for treatment and management of patients with type 2 diabetes in the clinical setting.

An objective scoring tool in the management of patients with pituitary apoplexy

1 Bilezikian, J.P., Khan, A.A. & Potts, J.T. (2009) Guidelines for the management of asymptomatic primary hyperparathyroidism: summary statement from the third international workshop. Journal of Clinical Endocrinology and Metabolism, 94, 335–339. 2 Sakaran, S., Damble, G., Bolland, M. et al. (2010) Skeletal effects of intervention of mild primary hyperparathyroidism: a meta analysis. Journal of Clinical Endocrinology and Metabolism, 95, 1653–1662.

Increased Population Risk of AIP-related Acromegaly and Gigantism in Ireland.

The aryl hydrocarbon receptor interacting protein (AIP) founder mutation R304* (or p.R304*; NM_003977.3:c.910C>T, p.Arg304Ter) identified in Northern Ireland (NI) predisposes to acromegaly/gigantism; its population health impact remains unexplored. We measured R304* carrier frequency in 936 Mid Ulster, 1,000 Greater Belfast (both in NI) and 2,094 Republic of Ireland (ROI) volunteers and in 116 NI or ROI acromegaly/gigantism patients. Carrier frequencies were 0.0064 in Mid Ulster (95%CI = 0.0027–0.013; P = 0.0005 vs. ROI), 0.001 in Greater Belfast (0.00011–0.0047) and zero in ROI (0–0.0014). R304* prevalence was elevated in acromegaly/gigantism patients in NI (11/87, 12.6%, P < 0.05), but not in ROI (2/29, 6.8%) versus non‐Irish patients (0–2.41%). Haploblock conservation supported a common ancestor for all the 18 identified Irish pedigrees (81 carriers, 30 affected). Time to most recent common ancestor (tMRCA) was 2550 (1,275–5,000) years. tMRCA‐based simulations predicted 432 (90–5,175) current carriers, including 86 affected (18–1,035) for 20% penetrance. In conclusion, R304* is frequent in Mid Ulster, resulting in numerous acromegaly/gigantism cases. tMRCA is consistent with historical/folklore accounts of Irish giants. Forward simulations predict many undetected carriers; geographically targeted population screening improves asymptomatic carrier identification, complementing clinical testing of patients/relatives. We generated disease awareness locally, necessary for early diagnosis and improved outcomes of AIP‐related disease.

The relationship between obesity, vascular reactivity and endothelial dysfunction in subjects with non-insulin dependent diabetes mellitus.

The relationship between obesity, vascular reactivity and endothelial dysfunction in subjects with non-insulin dependent diabetes mellitus

SOCIETY FOR ENDOCRINOLOGY ENDOCRINE EMERGENCY GUIDANCE: Emergency management of pituitary apoplexy in adult patients

See Fig. 1 for an emergency management summary. Open in a separate window Figure 1 Pituitary apoplexy emergency management summary.

The screening and management of pituitary dysfunction following traumatic brain injury in adults: British Neurotrauma Group guidance

Pituitary dysfunction is a recognised, but potentially underdiagnosed complication of traumatic brain injury (TBI). Post-traumatic hypopituitarism (PTHP) can have major consequences for patients physically, psychologically, emotionally and socially, leading to reduced quality of life, depression and poor rehabilitation outcome. However, studies on the incidence of PTHP have yielded highly variable findings. The risk factors and pathophysiology of this condition are also not yet fully understood. There is currently no national consensus for the screening and detection of PTHP in patients with TBI, with practice likely varying significantly between centres. In view of this, a guidance development group consisting of expert clinicians involved in the care of patients with TBI, including neurosurgeons, neurologists, neurointensivists and endocrinologists, was convened to formulate national guidance with the aim of facilitating consistency and uniformity in the care of patients with TBI, and ensuring timely detection or exclusion of PTHP where appropriate. This article summarises the current literature on PTHP, and sets out guidance for the screening and management of pituitary dysfunction in adult patients with TBI. It is hoped that future research will lead to more definitive recommendations in the form of guidelines.