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Mark Sherlock and Chris J Thompson

Hyponatraemia is the commonest electrolyte abnormality, and syndrome of inappropriate antidiuretic hormone (SIADH) is the most frequent underlying pathophysiology. Hyponatraemia is associated with significant morbidity and mortality, and as such appropriate treatment is essential. Treatment options for SIADH include fluid restriction, demeclocycline, urea, frusemide and saline infusion, all of which have their limitations. The introduction of the vasopressin-2 receptor antagonists has allowed clinicians to specifically target the underlying pathophysiology of SIADH. Initial studies have shown good efficacy and safety profiles in the treatment of mild to moderate hyponatraemia. However, studies assessing the efficacy and safety of these agents in acute severe symptomatic hyponatraemia are awaited. Furthermore, the cost of these agents at present may limit their use.

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Aoife Garrahy, Mark Sherlock and Christopher J Thompson

Advances in the management of traumatic brain injury, subarachnoid haemorrhage and intracranial tumours have led to improved survival rates and an increased focus on quality of life of survivors. Endocrine sequelae of the acute brain insult and subsequent neurosurgery, peri-operative fluid administration and/or cranial irradiation are now well described. Unrecognised acute hypopituitarism, particularly ACTH/cortisol deficiency and diabetes insipidus, can be life threatening. Although hypopituitarism may be transient, up to 30% of survivors of TBI have chronic hypopituitarism, which can diminish quality of life and hamper rehabilitation. Patients who survive SAH may also develop hypopituitarism, though it is less common than after TBI. The growth hormone axis is most frequently affected. There is also accumulating evidence that survivors of intracranial malignancy, who have required cranial irradiation, may develop hypopituitarism. The time course of the development of hormone deficits is varied, and predictors of pituitary dysfunction are unreliable. Furthermore, diagnosis of GH and ACTH deficiency require dynamic testing that can be resource intensive. Thus the surveillance and management of neuroendocrine dysfunction in neurosurgical patients poses significant logistic challenges to endocrine services. However, diagnosis and management of pituitary dysfunction can be rewarding. Appropriate hormone replacement can improve quality of life, prevent complications such as muscle atrophy, infection and osteoporosis and improve engagement with physiotherapy and rehabilitation.

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Amar Agha, Mark Sherlock, Jack Phillips, William Tormey and Christopher J Thompson

Background and objectives: Posterior pituitary function remains poorly investigated after traumatic brain injury (TBI). We report the results of a study designed to prospectively define the natural history of post-traumatic diabetes insipidus (DI) and syndrome of inappropriate antidiuretic hormone secretion (SIADH) using standard reliable methodology.

Design and methods: 50 consecutive patients with severe or moderate TBI (initial Glasgow Coma Scale (GCS) score 3/15–13/15) were prospectively studied on three occasions: at the acute phase and at 6 months and at 12 months following TBI. In the acute phase, DI was diagnosed either by the presence of hypernatraemia in association with hypotonic polyuria or by the water-deprivation test (WDT) and, at 6 and 12 months by the WDT in all patients. Normative data on response to the WDT were obtained from healthy matched volunteers. Functional outcome was assessed using the Glasgow Outcome Scale (GOS).

Results: 13 patients (26%) had DI in the acute post-TBI phase, of whom nine patients recovered by 6 months and one additional patient recovered by 12 months. Of the remaining three patients with permanent DI, two had partial vasopressin deficiency. Acute-phase peak plasma osmolality correlated negatively with the initial GCS scores (r = −0.39, P = 0.005) and with the GOS scores (r = −0.45, P = 0.001). Seven patients had SIADH in the acute phase of TBI but none did at 6 or 12 months. No new cases of DI or SIADH were noted after the acute phase.

Conclusion: This prospective study shows that posterior pituitary dysfunction is common following TBI. Most cases recover completely but there is an appreciable frequency of long-term DI which can be subtle and should be recognized and managed appropriately.

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Mark Sherlock, Lucy Ann Behan, Mark J Hannon, Aurora Aragon Alonso, Christopher J Thompson, Robert D Murray, Nicola Crabtree, Beverly A Hughes, Wiebke Arlt, Amar Agha, Andrew A Toogood and Paul M Stewart

Context

Patients with hypopituitarism have increased morbidity and mortality. There is ongoing debate about the optimum glucocorticoid (GC) replacement therapy.

Objective

To assess the effect of GC replacement in hypopituitarism on corticosteroid metabolism and its impact on body composition.

Design and patients

We assessed the urinary corticosteroid metabolite profile (using gas chromatography/mass spectrometry) and body composition (clinical parameters and full body DXA) of 53 patients (19 female, median age 46 years) with hypopituitarism (33 ACTH-deficient/20 ACTH-replete) (study A). The corticosteroid metabolite profile of ten patients with ACTH deficiency was then assessed prospectively in a cross over study using three hydrocortisone (HC) dosing regimens (20/10 mg, 10/10 mg and 10/5 mg) (study B) each for 6 weeks. 11 beta-hydroxysteroid dehydrogenase 1 (11β-HSD1) activity was assessed by urinary THF+5α-THF/THE.

Setting

Endocrine Centres within University Teaching Hospitals in the UK and Ireland.

Main outcome measures

Urinary corticosteroid metabolite profile and body composition assessment.

Results

In study A, when patients were divided into three groups – patients not receiving HC and patients receiving HC≤20 mg/day or HC>20 mg/day – patients in the group receiving the highest daily dose of HC had significantly higher waist-to-hip ratio (WHR) than the ACTH replete group. They also had significantly elevated THF+5α-THF/THE (P=0.0002) and total cortisol metabolites (P=0.015). In study B, patients on the highest HC dose had significantly elevated total cortisol metabolites and all patients on HC had elevated THF+5α-THF/THE ratios when compared to controls.

Conclusions

In ACTH-deficient patients daily HC doses of >20 mg/day have increased WHR, THF+5α-THF/THE ratios and total cortisol metabolites. GC metabolism and induction of 11β-HSD1 may play a pivitol role in the development of the metabolically adverse hypopituitary phenotype.

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Anne Marie Hannon, Triona O’Shea, Claire A Thompson, Mark J Hannon, Rosemary Dineen, Aftab Khattak, James Gibney, Domhnall J O’Halloran, Steven Hunter, Christopher J Thompson and Mark Sherlock

Pregnancy is rarely reported in acromegaly. Many patients are diagnosed in later life and younger patients may have subfertility due to hypopituitarism. We present a case series of 17 pregnancies in 12 women with acromegaly.

Twelve women with acromegaly who completed pregnancy were identified from centres involved in the Irish Pituitary Study. Eleven women had pituitary macroadenomas and one woman had a microadenoma. Only 5/17 pregnancies had optimal biochemical control of acromegaly preconception, as defined by IGF-1 concentration in the age-related reference level and plasma GH concentration of <2 μg/L. In 6/17 pregnancies, dopamine agonist treatment was continued during pregnancy; all other acromegaly treatments were discontinued during pregnancy.

Effect of pregnancy on acromegaly: No patient developed new visual field abnormalities, or symptoms suggestive of tumour expansion during pregnancy. In 9/12 patients, plasma IGF-1 concentrations that were elevated preconception normalised during pregnancy. There was a reduction in plasma IGF-1 concentrations, though not into the normal range, in a further two pregnancies.

Effect of acromegaly on pregnancy: 15 healthy babies were born at term; one patient underwent emergency C-section at 32 weeks for pre-eclampsia, and one twin pregnancy had an elective C-section at 35 weeks’ gestation. Blood pressure remained within normal limits in the remainder of the pregnancies. Gestational diabetes did not develop in any pregnancy.

Our data suggests that pregnancy in women with acromegaly is generally safe, from a maternal and foetal perspective. Furthermore, biochemical control tends to improve despite the withdrawal of somatostatin analogue therapy during pregnancy.