Biomedical subjects

Niki Karavitaki

Publications and source records attributed to Niki Karavitaki.

10 recordsLinked to original sources

PubMed2006

Craniopharyngiomas.

Craniopharyngiomas are rare, mainly sellar/parasellar, epithelial tumors diagnosed during childhood or adult life. Histologically, two primary subtypes have been recognized (adamantinomatous and papillary) with an as yet, unclarified pathogenesis. They may present with a variety of manifestations (neurological, visual, and hypothalamo-pituitary). Despite their benign histological appearance, they often show an unpredictable growth pattern, which, combined with the lack of randomized studies, poses significant difficulties in the establishment of an optimal therapeutic protocol. This should focus on the prevention of recurrence(s), improvement of survival, reduction of the significant disease and treatment-related morbidity (endocrine, visual, hypothalamic, neurobehavioral, and cognitive), and preservation of the quality of life. Currently, surgical excision followed by external beam irradiation, in cases of residual tumor, is the main treatment option. Intracystic irradiation or bleomycin, stereotactic radiosurgery, or radiotherapy and systemic chemotherapy are alternative approaches; their place in the management plan remains to be assessed in adequately powered long-term trials. Apart from the type of treatment, the identification of clinical and imaging parameters that will predict patients with a better prognosis is difficult. The central registration of patients with these challenging tumors may provide correlates between treatments and outcomes and establish prognostic factors at the pathological or molecular level that may further guide us in the future.

Antibiotics, Antineoplastic↗

PubMed2006

GH replacement does not increase the risk of recurrence in patients with craniopharyngioma.

BACKGROUND: A significant number of patients with craniopharyngioma are GH deficient. The safety of GH replacement in these subjects has not been established. OBJECTIVE: To assess the effect of GH replacement upon recurrence in patients with craniopharyngioma. PATIENTS AND METHODS: All the patients with craniopharyngioma followed-up at the Departments of Endocrinology or Paediatrics in Oxford and treated or not with GH were studied retrospectively. These were recruited from the databases of the departments consisting of subjects diagnosed between January 1964 and July 2005. The impact of GH replacement upon recurrence was evaluated after adjusting for possible confounding factors. RESULTS: Forty-one subjects received GH replacement. Nine of them did not have follow-up imaging during GH therapy and were not included in the statistical analyses. The remaining 32 (22 males/10 females) received GH for a mean period of 6.3 +/- 4.6 years (median 5.1, range 0.8-22); 21 started during childhood (13 of them continued after the achievement of final height with an adult dose) and 11 during adult life. The mean duration of their follow-up (from surgery until last assessment) was 10.8 +/- 9.2 years (range 1.9-40). Fifty-three subjects had not received GH therapy (30 men/23 women). The mean duration of their follow-up (from surgery until last assessment) was 8.3 +/- 8.8 years (range 0.5-36). During the observation period, 4 patients treated with GH and 22 non-GH treated ones developed tumour recurrence. After adjusting for sex, age at tumour diagnosis and type of tumour therapy (gross total removal, partial removal, surgery + irradiation), GH treatment was not a significant independent predictor of recurrence (P = 0.06; hazard ratio = 0.309). Similar results were obtained when the impact of GH replacement was assessed according to its duration (P = 0.18; hazard ratio = 0.991/month of treatment). None of the nine patients with insufficient imaging data for inclusion in the statistical analyses [5 men/4 women, 3 treated with GH during childhood/6 during adult life, mean duration of GH therapy 2.9 +/- 2.4 years (median 1.8, range 0.4-7)] showed clinical features suggestive of recurrence during the period of GH replacement. CONCLUSION Based on the data of the craniopharyngiomas database in Oxford, there is no evidence that GH replacement is associated with an increased risk of tumour recurrence.

Adolescent↗

PubMed2006

Do the limits of serum prolactin in disconnection hyperprolactinaemia need re-definition? A study of 226 patients with histologically verified non-functioning pituitary macroadenoma.

BACKGROUND: The differentiation of a pituitary non-functioning macroadenoma from a macroprolactinoma is important for planning appropriate therapy. Serum PRL levels have been suggested as a useful diagnostic indicator. However, values between 2500 and 8000 mU/l are a grey area and are currently associated with diagnostic uncertainty. OBJECTIVE: We wished therefore, to investigate the serum PRL values in a large series of patients presenting with apparently non-functioning pituitary macroadenomas. PATIENTS AND METHODS: All patients presenting to the Department of Endocrinology in Oxford with clinically non-functioning pituitary macroadenomas (later histologically verified) between 1990 and 2005 were studied. Information documented in the notes on the medications and on the presence of conditions capable of affecting the serum PRL levels at the time of blood sampling was also collected. RESULTS: Two hundred and twenty-six patients were identified (median age at diagnosis 55 years, range 18-88 years; 146 males/80 females; 143 gonadotroph, 46 null cell, 25 plurihormonal and 12 silent ACTH adenomas). All tumours had suprasellar extension. At the time of blood sampling 41 subjects were taking medications capable of increasing serum PRL. Hyperprolactinaemia was found in 38.5% (87/226) of the patients. The median serum PRL values in the total group were 386 mU/l (range 16-3257) (males: median 299 mU/l, range 16-1560; females: median 572 mU/l, range 20-3257) and in those not taking drugs capable of increasing serum PRL 363 mU/l (range 16-2565) (males: median 299 mU/l, range 16-1560; females: median 572 mU/l, range 20-2565). Serum PRL < 2000 mU/l was found in 98.7% (223/226) of the total group and in 99.5% (184/185) of those not taking drugs. Among the three subjects with serum PRL > 2000 mU/l, two were taking oestrogen preparations. CONCLUSIONS: Based on a large series of histologically confirmed cases, serum PRL > 2000 mU/l is almost never encountered in nonfunctioning pituitary macroadenomas. Values above this limit in the presence of a macroadenoma should not be surrounded by diagnostic uncertainty (after acromegaly or Cushing's disease have been excluded); a prolactinoma is the most likely diagnosis and a dopamine agonist should be considered as the treatment of choice.

Adenoma↗

PubMed2005

The value of an acute octreotide suppression test in predicting long-term responses to depot somatostatin analogues in patients with active acromegaly.

BACKGROUND: The long-acting depot somatostatin analogues [octreotide LAR (LAR) and lanreotide (LAN)] are among the most effective available medical therapies for acromegaly. However, published data on a biochemical test suitable for predicting the responsiveness to these depot agents are lacking. AIM: To investigate the value of an acute octreotide suppression test (OST) in predicting the responses to treatment with long-acting somatostatin analogues in patients with active acromegaly. PATIENTS AND METHODS: Thirty patients with active acromegaly [mean GH in GH day curve (GHDC) > 5 mU/l] were subjected to an OST [hourly GH measurements for 6 h following 100 microg subcutaneous (s.c.) octreotide]. Subsequently, 14 patients were treated with LAR, 10 with LAN and 6 received both drugs at different times. The final response to treatment was evaluated when the subjects had achieved 'safe' GH levels (mean GH < 5 mU/l) or after receiving the maximal dose of each drug (maximum duration of treatment 6 months). RESULTS: The nadir GH values during the OST were 2.6 +/- 2.5 mU/l (mean +/- SD, range 0.2-8.7) with a percentage fall of 84.8 +/- 15.7% (mean +/- SD, range 26-99%) from the baseline levels (26.2 +/- 31.5 mU/l, mean +/- SD). All the patients except one showed a decrease of greater than 50%. The mean time to achieve the nadir GH value was 3.8 +/- 1.6 h (mean +/- SD, range 1-6). The nadir GH levels showed a positive correlation with both pre-treatment (i.e. before commencing LAN or LAR) GH values during the GHDC (r = 0.63, P < 0.01) and IGF-I levels (r = 0.56, P < 0.05). The nadir GH values during the OST showed a positive correlation with the achieved mean GH levels in patients treated with LAR (r = 0.66, P < 0.01) but not in the ones treated with LAN. The criterion of GH < 5.25 mU/l during the OST had sensitivity 100%, specificity 80%, positive predictive value (PPV) 94% and negative predictive value (NPV) 100% in predicting achievement of 'safe' GH levels in patients treated with LAR. A less optimal prognostic profile was obtained for subjects treated with LAN with the criterion of GH < 6.05 mU/l during the OST providing sensitivity 92%, specificity 67%, PPV 92% and NPV 67%. The above cut-off GH levels had a PPV of only 77% and 60% in predicting normalization of IGF-I on treatment with LAR or LAN, respectively. CONCLUSIONS: The OST is a reliable tool for the selection of patients with active acromegaly who will achieve 'safe' GH levels on therapy with LAR. Its prognostic profile is less optimal for patients treated with LAN. If GH values during the test fall < 5.25 mU/l (in case of LAR treatment) or < 6.05 mU/l (in case of LAN treatment), there is a 92-94% chance of subsequently achieving 'safe' GH levels after up to 6 months treatment with either of these agents.

Acromegaly↗

PubMed2005

Treatment of pituitary tumors: history.

Over the past century our understanding of the pituitary disease has undergone an amazing evolution, accompanied by impressive advances in the therapeutic approaches to pituitary tumors. This historical review aims to provide insights into the contributions of key medical and scientific pioneers, their occasionally serendipitous discoveries, and the lively global debates, which have ultimately improved the therapeutic targets and the long-term outcome of these patients. The development of the three main modalities is discussed (surgery, irradiation, pharmacotherapy). More recent experimental data, which may provide a path to a stronger therapeutic armamentarium for these undoubtedly challenging tumors, are also briefly reported.

History, 19th Century↗

PubMed2005

The impact of chronic in vivo glucocorticoid excess on the functional characteristics of human skin fibroblasts obtained from patients with endogenous Cushing's syndrome.

OBJECTIVE: Chronic exposure to elevated glucocorticoid (GC) concentrations induces detrimental effects in several tissues. In the skin, GCs provoke intense alterations on various parameters of the physiology of fibroblasts, cumulatively leading to skin atrophy and impaired wound healing. As there are concerns that GCs may generate permanent adverse functional changes, we have investigated whether chronic in vivo exposure to GC excess results in persisting defects in skin fibroblasts. DESIGN AND METHODS: We have studied in vitro primary skin fibroblast cultures obtained from patients suffering from endogenous Cushing's syndrome (CF), as well as from sex- and age-matched normal donors (NF). The following functional parameters were investigated: cell proliferation, secretion of collagen, matrix metalloproteinases (MMPs) and their inhibitors (tissue inhibitors of metalloproteinases; TIMPs) and contractile capacity. RESULTS: CFs, grown under standard culture conditions in the absence of a hypercortisolemic milieu, exhibited an increased proliferative capacity and a higher final cell culture density compared with NFs. Collagen synthesis, in the absence or presence of transforming growth factor-beta, was equal to that of NFs. However, CFs secreted comparatively lower levels of MMP-1, MMP-2 and TIMP-1, and nearly equal levels of TIMP-2. CFs also exhibited an increased ability to contract gels of polymerized collagen. CONCLUSIONS: Collectively, these functional characteristics of CFs are in contrast to the known catabolic effects of GCs, and suggest that prior exposure to GC excess is not associated with a persisting adverse outcome in the functional phenotype of the fibroblasts.

Adult↗

PubMed2004

Assessment of GH reserve before and after successful treatment of adult patients with Cushing's syndrome.

OBJECTIVE: Several studies have demonstrated impaired GH secretion in patients with active Cushing's syndrome (CS). It has been suggested that persistence of GH deficiency, despite treatment of cortisol excess, may delay the recovery of these patients and therefore temporary treatment with GH may have some benefit. However, the time course of restoration of GH secretion after successful treatment of CS has only been investigated in a limited number of mostly paediatric reports. The aim of the present study was the evaluation of GH reserve in adult patients with CS before and after correction of cortisol excess. DESIGN AND PATIENTS: Sixteen patients (12 females, four males) with CS aged 44.7 +/- 5.05 years were recruited. These included seven patients with Cushing's disease, four patients with ectopic ACTH secretion and five patients with adrenal adenoma. All patients were evaluated before any therapeutic intervention. Twelve patients were successfully treated following appropriate surgery and these were further studied. The combined pyridostigmine/GHRH test was used to assess GH reserve in these patients. In a proportion of cases an insulin tolerance test (ITT) was also used. RESULTS: Before any therapeutic intervention, an impaired GH response to PD/GHRH was noted in all patients. Restoration of GH response at 6 months was observed in six patients (50%); at 12 months in two; at 18 months in one patient. Two of the patients with no restoration of GH response at 12 months did not accept further investigation. Only one patient did not achieve an adequate GH response even when tested 30 months following cure of CS. Restoration of GH reserve was more commonly observed in those patients in whom there was recovery of the HPA axis. There was a good correlation between peak GH levels to PD + GHRH and ITT. No statistically significant difference was revealed in IGF-I levels between pre- and post-treatment evaluation. CONCLUSIONS: Adult patients with active Cushing's syndrome demonstrate a profound suppression of stimulated GH secretion. In the majority of these patients the disruption of GH secretion is normalized within a year after successful treatment of endogenous cortisol excess.

ACTH Syndrome, Ectopic↗

PubMed2002

Recurrent and/or metastatic thyroid cancer: therapeutic options.

Thyroid cancer is relatively rare, accounting for 0.5 - 10 cases per 100,000 individuals per year. Despite their generally favourable prognosis, patients with differentiated thyroid cancer are at risk of tumour recurrence for decades after diagnosis. The optimal management remains controversial even in the low-risk patients because of the high cure rates, long natural history and rarity of these tumours. Therapeutic interventions in recurrent and metastatic differentiated thyroid cancer depend on the type of initial treatment, the site and the extent of disease. Surgical excision of the amenable-to-surgery lesions and radioiodine administration remain the first approach. External radiotherapy may be given to patients with inoperable lesions or those not concentrating radioiodine. Chemotherapy has not provided consistently successful results. Various therapeutic approaches for anaplastic carcinoma give poor results, making the development of novel treatments necessary. Innovative strategies, including recombinant human thyroid stimulating hormone, retinoic acid redifferentiation therapy and gene therapy, may lead to further improvement in the management of thyroid cancer arising from follicular cells.

Adenocarcinoma, Follicular↗

PubMedDate not supplied

Pegvisomant: a new treatment modality for acromegaly.

Acromegaly, a multisystemic disease resulting from excessive growth hormone (GH) and insulin-like growth factor-I (IGF-I) levels in adults, is associated with a two-to-threefold increase in mortality. The available treatment options (surgery, radiotherapy and medical treatment with somatostatin analogues or dopamine agonists) fail to achieve the currently accepted goals of therapy in a substantial number of patients. Pegvisomant, a newly developed GH receptor antagonist, represents a novel treatment modality for this disease. It binds with the GH receptor and induces internalization, but blocks receptor signaling events, thereby reducing IGF-I production. The two main published studies suggest that it is the most potent medical therapy with greater specificity, without being dependent on the tumour characteristics. However, apart from its high cost and the dilemmas raised concerning the appropriateness of using serum IGF-I concentrations as a marker of disease activity, it may also occasionally be associated with elevations in liver enzyme levels. Further studies are required to confirm its high success rates as well as to investigate the possibility of inducing an increase in the pituitary tumour size. Currently, pegvisomant is a second line treatment for acromegaly with an adjuvant role and possibly of greater value in cases of resistance to other therapeutic options.

Journal Article↗

PubMedDate not supplied

Molecular staging using qualitative RT-PCR analysis detecting thyreoglobulin mRNA in the peripheral blood of patients with differentiated thyroid cancer after therapy.

BACKGROUND: The prognostic significance of molecular staging using thyroglobulin (Tg)-based RT-PCR analysis in the peripheral blood of patients with differentiated thyroid cancer (DTC) was investigated. Herein, the specificity of molecular staging in DTC patients after thyroidectomy and 131I ablation therapy was analysed, using different specific cDNA primers in qualitative nested and classical RT-PCR protocols. PATIENTS AND METHODS: Ninty-five patients receiving TSH suppressive therapy were included, of whom 51 were disease-free and 44 presented residual/recurrent or metastatic disease as evidenced by biochemical and/or 131I whole-body scan. RESULTS: Our analysis detected RT-PCR products suggestive of the presence of Tg mRNA in all the blood samples tested, including healthy controls. A splice variant (350 bp) of Tg transcript (missing exon 3) was detected by nested RT-PCR in 34% of blood samples, however, without correlation to disease status. CONCLUSION: Qualitative Tg-based molecular staging in the peripheral blood of patients with DTC shows poor specificity in assessing DTC disease status.

Cell Differentiation↗