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ABSTRACT: Primary resistance to dopamine agonists occurs in 10–15% of prolactinomas but secondary resistance following initial biochemical
and anti-proliferative response is very rare and has only been hitherto described in four previous cases, two with bromocriptine
and two with cabergoline. We describe a case of a 57-year-old woman who presented with a large macroprolactinoma with suprasellar
extension. She was initially treated with bromocriptine therapy with a resolution of symptoms, marked reduction in prolactin
concentration and complete tumour shrinkage; a response which was subsequently maintained on cabergoline. After 8years of
dopamine agonist therapy, her prolactin concentration began to rise and there was symptomatic recurrence of her tumour despite
escalating doses of cabergoline up to 6mg weekly. Non-compliance was outruled by observed inpatient drug administration.
The patient underwent surgical debulking followed by radiotherapy with good response. This case adds to the previous two cases
of secondary resistance to cabergoline therapy in prolactinomas a marked initial response. While the mechanism of secondary
resistance remains unknown and not possible to predict, close observation of prolactinoma patients on treatment is necessary.
KeywordsSecondary resistance–Dopamine therapy–Prolactinoma
Pituitary 04/2012; 14(4):362-366. · 1.83 Impact Factor
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R K Crowley,
C Woods,
M Fleming,
B Rogers, L A Behan,
E P O'Sullivan,
T Kane,
A Agha,
D Smith,
R W Costello,
C J Thompson
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ABSTRACT: Somnolence and obesity are prevalent in craniopharyngioma patients. We hypothesized that somnolence was because of obstructive sleep apnoea in craniopharyngioma patients.
We assessed prevalence of somnolence and sleep apnoea in 28 craniopharyngioma and 23 obese controls attending a tertiary referral centre, by means of the Epworth Sleepiness Score (ESS) and polysomnography. All subjects with sleep apnoea were offered continuous positive airway pressure therapy (CPAP) or modafinil. All craniopharyngioma patients, with unexplained somnolence, were offered modafinil.
Somnolence was reported by 20/28 (71·5%) craniopharyngioma patients and 4/23 (17%) obese subjects (P < 0·001). Median ESS was 7·5 (IQR 6, 10·7) in craniopharyngioma patients and 4·0 (4,8) in controls, P < 0·01. Eleven somnolent craniopharyngioma patients had obstructive sleep apnoea, in whom treatment led to a reduction in ESS by 6·4 ± 1·4, P = 0·01. Among the remaining nine patients, five were offered modafinil therapy, of whom four had benefit, three were not compliant with hormone replacement, and one died before intervention. There was no difference in the prevalence of obstructive sleep apnoea between craniopharyngioma (n = 13, 46%) and obese subjects (n = 14, 61%, P = 0·4). Body mass index (BMI) does not correlate with apnoea hypopnoea index [apnoea - hypopnoea index (AHI), r = 0·25, P = 0·08], which suggests that obesity alone does not explain the prevalence of sleep apnoea in craniopharyngioma patients.
Somnolence is common in craniopharyngioma patients and in the majority is because of obstructive sleep apnoea. An additional group of somnolent craniopharyngioma patients benefits from modafinil.
Clinical Endocrinology 06/2011; 74(6):750-5. · 3.17 Impact Factor
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ABSTRACT: Craniopharyngioma (CP) is a benign tumour of the suprasellar region that is associated with increased morbidity and mortality in comparison with other causes of hypopituitarism. We aimed to establish the rate and causes of mortality and morbidity in patients with CP who attended our centre.
We performed a retrospective case note audit of patients with CP who were managed by our service. We established the standardized mortality ratio (SMR) for patients with CP. We compared obesity prevalence with two other hypopituitary groups who are managed by our service.
We identified 70 patients with CP, 97% of whom had undergone surgery and 42% radiotherapy. We compared the prevalence of obesity with that of 89 patients with hypopituitarism secondary to surgery for nonfunctioning pituitary adenoma and 29 patients with post-traumatic hypopituitarism (PTHP).
Standardized mortality ratio for patients with CP was 8.75 (95% CI of 5.4-13.3); SMR for women was 10.51 (95% CI 5.04-19.3) and 7.55 (95% CI 3.77-13.52) for men. The rates of growth hormone (GH), gonadotrophin, adrenocorticotrophic hormone (ACTH) and TSH deficiencies were 91%, 93.5%, 92% and 86%, respectively. The rate of diabetes insipidus (DI) was 81%; 7.1% had adipsic DI. Dyslipidaemia was present in 46.9% and diabetes mellitus in 11.5%. Obesity affected 66% of patients with CP, 47% of patients with nonfunctioning adenoma and 31% of those with PTHP (P < 0.001).
Patients with CP suffer from high rates of mortality and morbidity. The underlying causes for mortality and for obesity in this population remain poorly understood.
Clinical Endocrinology 10/2010; 73(4):516-21. · 3.17 Impact Factor
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ABSTRACT: Objective Craniopharyngioma (CP) is a benign tumour of the suprasellar region that is associated with increased morbidity and mortality in comparison with other causes of hypopituitarism. We aimed to establish the rate and causes of mortality and morbidity in patients with CP who attended our centre.Design We performed a retrospective case note audit of patients with CP who were managed by our service. We established the standardized mortality ratio (SMR) for patients with CP. We compared obesity prevalence with two other hypopituitary groups who are managed by our service.Patients We identified 70 patients with CP, 97% of whom had undergone surgery and 42% radiotherapy. We compared the prevalence of obesity with that of 89 patients with hypopituitarism secondary to surgery for nonfunctioning pituitary adenoma and 29 patients with post-traumatic hypopituitarism (PTHP).Measurements Standardized mortality ratio for patients with CP was 8·75 (95% CI of 5·4–13·3); SMR for women was 10·51 (95% CI 5·04–19·3) and 7·55 (95% CI 3·77–13·52) for men. The rates of growth hormone (GH), gonadotrophin, adrenocorticotrophic hormone (ACTH) and TSH deficiencies were 91%, 93·5%, 92% and 86%, respectively. The rate of diabetes insipidus (DI) was 81%; 7·1% had adipsic DI. Dyslipidaemia was present in 46·9% and diabetes mellitus in 11·5%. Obesity affected 66% of patients with CP, 47% of patients with nonfunctioning adenoma and 31% of those with PTHP (P < 0·001).Conclusions Patients with CP suffer from high rates of mortality and morbidity. The underlying causes for mortality and for obesity in this population remain poorly understood.
Clinical Endocrinology 09/2010; 73(4):516 - 521. · 3.17 Impact Factor
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ABSTRACT: Thyrotoxic periodic paralysis is a potentially fatal complication of hyperthyroidism, more common in Asian races, which is defined by a massive intracellular flux of potassium. This leads to profound hypokalaemia and muscle paralysis. Although the paralysis is temporary, it may be lethal if not diagnosed and treated rapidly, as profound hypokalaemia may induce respiratory muscle paralysis or cardiac arrest. The condition is often misdiagnosed in the west due to its comparative rarity in Caucasians; however it is now increasingly described in Caucasians and is also being seen with increasing frequency in western hospitals due to increasing immigration and population mobility. Here we describe the case of a patient with panhypopituitarism due to a craniopharyngioma, who developed thyrotoxic periodic paralysis due to excessive L-thyroxine replacement. This disorder has been described in Asian subjects but, to our knowledge, thyrotoxic periodic paralysis secondary to excessive L-thyroxine replacement has never been described in Caucasians.
Annals of Clinical Biochemistry 08/2009; 46(Pt 5):423-5. · 2.17 Impact Factor
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ABSTRACT: Hyponatraemia is a well-recognised complication of neurosurgical conditions, but the incidence and implications have not been well documented.
To define the incidence, pathophysiology and clinical implications of significant hyponatraemia in several neurosurgical conditions.
All patients admitted to the Irish National Neurosciences Centre at Beaumont Hospital, Dublin with traumatic brain injury, subarachnoid haemorrhage, intracranial neoplasm, pituitary disorders and spinal disorders who developed significant hyponatraemia (plasma sodium <130 mmol/l) from January 2002 to September 2003 were identified from computerised laboratory records. Data were collected by retrospective case note analysis.
Hyponatraemia was more common in patients with pituitary disorders (5/81, 6.25%; p = 0.004), traumatic brain injury (44/457, 9.6%; p<0.001), intracranial neoplasm (56/355, 15.8%; p<0.001) and subarachnoid haemorrhage (62/316, 19.6%; p<0.001) than in those with spinal disorders (4/489, 0.81%). The pathophysiology of hyponatraemia was: syndrome of inappropriate antidiuretic hormone secretion (SIADH) in 116 cases (62%) (31 (16.6%) drug-associated), hypovolaemic hyponatraemia in 50 cases (26.7%) (which included patients with insufficient data to assign to the cerebral salt-wasting group (CSWS)), CSWS in nine cases (4.8%), intravenous fluids in seven cases (3.7%) and mixed SIADH/CSWS in five cases (2.7%). Hyponatraemic patients with cerebral irritation had significantly lower plasma sodium concentrations (mean (SD) 124.8 (0.34) mmol/l) than asymptomatic patients (126.6 (0.29) mmol/l) (p<0.0001). Hyponatraemic patients had a significantly longer hospital stay (median 19 days (interquartile range (IQR) 12-28)) than normonatraemic patients (median 12 days (IQR 10.5-15)) (p<0.001).
Hyponatraemia is common in intracerebral disorders and is associated with a longer hospital stay. Cerebral irritation is associated with more severe hyponatraemia. SIADH is the most common cause of hyponatraemia and is often drug-associated.
Postgraduate medical journal 04/2009; 85(1002):171-5. · 1.38 Impact Factor
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ABSTRACT: Traumatic brain injury (TBI) is the most common cause of death and disability in young adults living in industrialised countries, in which 180-250 persons per 100 000 per year die or are hospitalised as a result. Neuroendocrine derangements after TBI have received increasing recognition in recent years because of their potential contribution to morbidity, and possibly mortality, after trauma. Marked changes of the hypothalamo-pituitary axis have been documented in the acute phase of TBI, with as many as 80% of patients showing evidence of gonadotropin deficiency, 18% of growth hormone deficiency, 16% of corticotrophin deficiency and 40% of patients demonstrating vasopressin abnormalities leading to diabetes insipidus or the syndrome of inappropriate anti-diuresis. Longitudinal prospective studies have shown that some of the early abnormalities are transient, whereas new endocrine dysfunctions become apparent in the post-acute phase. There remains a high frequency of hypothalamic-pituitary hormone deficiencies among long-term survivors of TBI, with approximately 25% patients showing one or more pituitary hormone deficiencies. This is a higher frequency than previously thought and suggests that most cases of post-traumatic hypopituitarism (PTHP) remain undiagnosed and untreated. PTHP has been associated with adverse outcome both in the acute and chronic phases after injury. These data underscore the need for the identification and appropriate timely management of hormone deficiencies, in order to optimise patient recovery from head trauma, improve quality of life and avoid the long-term adverse consequences of untreated hypopituitarism.
Journal of neurology, neurosurgery, and psychiatry 08/2008; 79(7):753-9. · 4.87 Impact Factor
