Showing papers by "Niki Karavitaki published in 2016"

Hormonal replacement in hypopituitarism in adults: An endocrine society clinical practice guideline

Abstract: Objective: To formulate clinical practice guidelines for hormonal replacement in hypopituitarism in adults. Participants: The participants include an Endocrine Society-appointed Task Force of six experts, a methodologist, and a medical writer. The American Association for Clinical Chemistry, the Pituitary Society, and the European Society of Endocrinology co-sponsored this guideline. Evidence: The Task Force developed this evidence-based guideline using the Grading of Recommendations, Assessment, Development, and Evaluation system to describe the strength of recommendations and the quality of evidence. The Task Force commissioned two systematic reviews and used the best available evidence from other published systematic reviews and individual studies. Consensus Process: One group meeting, several conference calls, and e-mail communications enabled consensus. Committees and members of the Endocrine Society, the American Association for Clinical Chemistry, the Pituitary Society, and the European Society of ...

THERAPY OF ENDOCRINE DISEASE: Surgery in microprolactinomas: effectiveness and risks based on contemporary literature

Abstract: Microprolactinomas are the most common pituitary adenomas. In symptomatic patients, dopamine agonists are the first-line treatment of choice; when cabergoline is used, biochemical control rates between 85 and 93% have been reported. Long-term treatment is needed in most of the cases with compliance, patient convenience, and potential adverse effects representing areas requiring attention. Based on the literature published in the past 15 years, transsphenoidal surgery can lead to normal prolactin in the postoperative period in usually 71-100% of the cases with very low postoperative complication rates. Surgical expertise is the major determinant of the outcomes, and it may be a cost-effective option in young patients with life expectancy greater than 10 years (provided it is performed by experienced surgeons at high volume centers with confirmed optimal outcomes). Larger series of patients with adequate follow-up could further validate the place of transsphenoidal surgery (particularly through the endoscopic approach for which long-term results are currently limited) in the management algorithm of patients with microprolactinoma.

Patient-reported outcomes of parenteral somatostatin analogue injections in 195 patients with acromegaly

Abstract: Background: Long-acting somatostatin analogues delivered parenterally are the most widely used medical treatment in acromegaly. This patient-reported outcomes survey was designed to assess the impact of chronic injections on subjects with acromegaly. Methods: The survey was conducted in nine pituitary centres in Germany, UK and The Netherlands. The questionnaire was developed by endocrinologists and covered aspects of acromegaly symptoms, injection-related manifestations, emotional and daily life impact, treatment satisfaction and unmet medical needs. Results: In total, 195 patients participated, of which 112 (57%) were on octreotide (Sandostatin LAR) and 83 (43%) on lanreotide (Somatuline Depot). The majority (>70%) of patients reported acromegaly symptoms despite treatment. A total of 52% of patients reported that their symptoms worsen towards the end of the dosing interval. Administration site pain lasting up to a week following injection was the most frequently reported injection-related symptom (70% of patients). Other injection site reactions included nodules (38%), swelling (28%), bruising (16%), scar tissue (8%) and inflammation (7%). Injection burden was similar between octreotide and lanreotide. Only a minority of patients received injections at home (17%) and 5% were self-injecting. Over a third of patients indicated a feeling of loss of independence due to the injections, and 16% reported repeated work loss days. Despite the physical, emotional and daily life impact of injections, patients were satisfied with their treatment, yet reported that modifications that would offer major improvement over current care would be 'avoiding injections' and 'better symptom control'. Conclusion: Lifelong injections of long-acting somatostatin analogues have significant burden on the functioning, well-being and daily lives of patients with acromegaly.

Treating prolactinomas with dopamine agonists: always worth the gamble?

Abstract: Dopamine agonists are the treatment of choice for all patients with prolactinomas They are generally safe, effective, and well-tolerated However, a link between their use and the development of impulse control disorders has been well recognized in the field of neurology for some time, and evidence for a similar effect in endocrine patients is emerging This has mainly been revealed through clinical case reports, plus a small number of comparative studies of varying robustness We review the current available literature and discuss the implications for clinical practice, in particular emphasizing the need for clinicians to be alert to these uncommon but serious adverse effects

A Follow-Up Study of the Prevalence of Valvular Heart Abnormalities in Hyperprolactinemic Patients Treated With Cabergoline

Abstract: CONTEXT Uncertainty exists whether the long-term use of ergot-derived dopamine agonist (DA) drugs for the treatment of hyperprolactinemia may be associated with clinically significant valvular heart disease; and whether current regulatory authority guidelines for echocardiographic screening are clinically appropriate. OBJECTIVE: To provide follow-up echocardiographic data on a previously described cohort of patients treated with DA for lactotrope pituitary tumors; and to explore possible associations between structural and functional valve abnormalities with the cumulative dose of drug used. DESIGN: Follow-up echocardiographic data were collected from a proportion of our previously reported cohort of patients; all had received continuous DA therapy for at least 2 years in the intervening period. Studies were performed according to British Society of Echocardiography minimum standards for adult transthoracic echocardiography. Generalised estimating equations with backward selection were used to determine odds ratios of valvular heart abnormalities according to tertiles of cumulative cabergoline dose, using the lowest tertile as the reference group. SETTING: Thirteen centers of secondary/tertiary endocrine care across the United Kingdom. RESULTS: There were 192 patients (81 males; median age, 51 years; interquartile range [IQR], 42–62). Median (IQR) cumulative cabergoline doses at the first and second echocardiograms were 97mg (20–377) and 232mg (91–551) respectively. Median (IQR) duration of uninterrupted cabergoline therapy between echocardiograms was 34 months (24–42). No associations were observed between cumulative doses of dopamine agonist used and the age-corrected prevalence of any valvular abnormality. CONCLUSION: This large UK follow-up study does not support a clinically significant association between the use of DA for the treatment of hyperprolactinemia and cardiac valvulopathy - See more at: http://press.endocrine.org/doi/10.1210/jc.2016-2224#sthash.amhpCAmP.dpuf

A macroprolactinoma becoming resistant to cabergoline and developing atypical pathology

Abstract: Pituitary adenomas are a common intracranial neoplasm, usually demonstrating a benign phenotype. They can be classified according to pathological, radiological or clinical behaviour as typical, atypical or carcinomas, invasive or noninvasive, and aggressive or nonaggressive. Prolactinomas account for 40–60% of all pituitary adenomas, with dopamine agonists representing the first-line treatment and surgery/radiotherapy reserved for drug intolerance/resistance or in neuro-ophthalmological emergencies. We present the case of a 62-year-old man with an apparently indolent prolactin-secreting macroadenoma managed with partial resection and initially showing a biochemical response to cabergoline. Five years later, the tumour became resistant to cabergoline, despite a substantial increase in dosage, showing rapid growth and causing worsening of vision. The patient then underwent two further transsphenoidal operations and continued on high-dose cabergoline; despite these interventions, the tumour continued enlarging and prolactin increased to 107 269 U/L. Histology of the third surgical specimen demonstrated features of aggressive behaviour (atypical adenoma with a high cell proliferation index) not present in the tumour removed at the first operation. Subsequently, he was referred for radiotherapy aiming to control tumour growth. Learning points: The development of secondary resistance to dopamine agonists (DAs) is a serious sign as it may be associated with de-differentiation of the prolactinoma and thus of aggressive or malignant transformation. Significant de-differentiation of the adenoma documented on consecutive histologies suggests a possible transition to malignancy. A combination of histological ‘alarm’ features associated with persistent growth and escape from DAs treatment in recurrent adenomas should alert clinicians and demands close follow-up. A multidisciplinary approach by pathologists, endocrinologists and neurosurgeons is essential. Background Pituitary tumours are a relatively common intracranial neoplasm. Approximately 10–20% of the normal population may harbour these lesions according to autopsy and/or pituitary magnetic resonance imaging (MRI) series: most of these tumours are clinically insignificant with less than 5 mm in diameter and grow slowly over many years without local invasion or remain static. Prolactinomas account for 40–60% of all pituitary adenomas and up to 80% are present as microadenomas (1). Pituitary adenomas can be classified according to pathological, radiological or clinical behaviour as typical, atypical and carcinomas, invasive or noninvasive, and aggressive or nonaggressive: using the WHO 2004 classification (currently under revision), the majority are typical adenomas. They are slow-growing, well-demarcated, noninvasive adenomas, showing no major cellular and nuclear pleomorphism, few mitotic figures and a Ki-67 nuclear index 3%, elevated mitotic activity and excessive p53 immunoreactivity (2). Pituitary carcinomas can only be diagnosed if cerebrospinal and/or systemic metastases are documented. First-line therapy for prolactinomas are dopamine agonists (DAs): these agents are effective in controlling clinical symptoms, normalising serum prolactin (PRL) and reducing tumour volume, while being well tolerated. Surgery and radiotherapy are reserved for drug-resistant tumours or intolerance to DAs or neuro-ophthalmological emergencies. We present a patient with a macroprolactinoma who showed an unexpected and severe escape from cabergoline treatment. The tumour was originally a typical adenoma sensitive to DAs therapy, but later it became resistant to the DA and transformed into an atypical adenoma with aggressive features.

Craniopharyngiomas: Natural History and Clinical Presentation

Abstract: Craniopharyngiomas are rare epithelial tumours arising along the path of the craniopharyngeal duct and account for 2–5 % of all the primary intracranial neoplasms and for up to 15 % of the intracranial tumours in children. The majority (94–95 %) has a suprasellar component. The potential proximity to and the subsequent pressure effects of craniopharyngiomas on vital structures of the brain (visual pathways, brain parenchyma, ventricular system, major blood vessels and hypothalamo-pituitary system) predispose the patients to multiple clinical manifestations, the severity of which depends on the location, the size and the growth potential of the tumour. Headaches, nausea/vomiting, visual disturbances, growth failure (in children) and hypogonadism (in adults) are the most frequently reported. The hypothalamo-pituitary function at presentation may be severely affected and based on various series, GH deficiency is present in 35–100 % of the evaluated patients, FSH/LH deficiency in 38–91 %, ACTH deficiency in 21–68 %, TSH deficiency in 20–42 % and diabetes insipidus in 6–38 %. Early diagnosis is of major importance.