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- Long-term remission and recurrence rate in a cohort of Cushing's disease: the need for long-term follow-up. [JOURNAL ARTICLE]
- Pituitary 2014 Apr 19.
Transsphenoidal surgery is the procedure of choice in Cushing disease (CD), with immediate post-operative remission rates ranging between 59 and 94 % and recurrence rates between 3 and 46 %, both depending upon the definition criteria and the duration of the follow-up. Our aim was to assess the rate of remission, recurrence and persistence of the disease after the first treatment and to identify predictors of remission in the CD population of our center.Retrospective cohort study of the patients diagnosed of CD and with follow-up in our center between 1974 and 2011. We analyzed 41 patients (35 women and 6 men) with a mean age at diagnosis of 34 ± 13 years. The mean follow-up was 14 ± 10 years (range 1-37 years) and the median of follow-up period was 6.68 years.Thirty-five (85.4 %) patients underwent transsphenoidal surgery as first treatment option. Histopathological evidence of a pituitary adenoma was registered in 17 (48.5 %) patients. Thirty-two (78 %) patients achieved disease remission after the first treatment, 21 (65.6 %) of them presented disease recurrence. Persistent disease was observed in 9 (22 %) patients. Twelve (29.3 %) subjects developed post-surgical adrenal insufficiency, 7 of which (70 %) achieved stable remission. Two parameters were found to be significant predictors of remission after the first treatment: age at disease diagnosis and the development of adrenal insufficiency (cortisol <3 μg/dl) in the immediate post-operative state.We report a high recurrence rate, at least partially attributable to the long follow-up time. Early post-surgery adrenal insufficiency predicts remission. Hypopituitarism was also very prevalent, and strongly associated with radiotherapy. These results lead us to the conclusion that CD needs a life-long strict follow-up.
- Soluble TNFα-receptor 1 as a predictor of coronary calcifications in patients after long-term cure of Cushing's syndrome. [JOURNAL ARTICLE]
- Pituitary 2014 Apr 12.
Increased cardiovascular (CV) risk persists in Cushing's syndrome (CS), despite remission of hypercortisolism. The aim of this study was to evaluate prevalence of coronary artery disease in CS patients and its correlation with classical CV risk factors and inflammatory markers.Cardiac multidetector computed tomography (MDCT) was performed in 41 patients (7 men, 31 of pituitary origin, 29 cured, mean age: 48.6 ± 13 years), using 64-slice Toshiba Aquilion systems. Coronary atherosclerotic plaques were detected and coronary calcifications quantified by the Agatston score (AS). Clinical and biochemical parameters were correlated with the AS to identify possible surrogate markers of coronary disease. Normal values for clinical and biochemical parameters were obtained from a gender- and age-matched normal reference population (n = 82).CS patients with calcifications (AS > 0) (N = 13, 32 %) had higher levels of sTNF-R1, homocysteine, triglycerides, blood pressure and body mass index than patients without calcifications (AS = 0) and those of normal reference population. Both groups of CS patients (AS > 0 and AS = 0) had elevated trunk fat mass and IL-6 compared to reference values. Patients with AS > 0 had less adiponectin and higher insulin, HOMA and fibrinogen than those found in normal reference population. sTNF-R1 correlated positively with AS and remained significant after adjusting for confounding factors. The same result was observed when we considered only cured CS patients.In our cohort of CS patients sTNF-R1 was a predictor of coronary calcifications. Since MDCT is an expensive technique not readily available in daily clinical practice, increased sTNF-R1 could be a marker of CV risk even in cured CS.
- Influence of the exon 3 deletion of GH receptor and IGF-I level at diagnosis on the efficacy and safety of treatment with somatotropin in adults with GH deficiency. [JOURNAL ARTICLE]
- Pituitary 2014 Apr 8.
The treatment of adults with GH deficiency (GHD) with human recombinant growth hormone has interindividual variability and several factors influence it. The aims of this study were : 1-to analyze the GH receptor (GHR) genotype in terms of exon 3 deletion GHR (d3-GHR) in adults with GHD; 2-to assess the effects of d3-GHR on initial IGF-I levels; 3-to evaluate whether d3-GHR and/or initial IGF-I levels were associated with adverse effects and/or treatment discontinuation.Forty-four adult patients with GHD were included. Demographic, clinical and biochemical characteristics were retrospectively evaluated at baseline and 6 months, 1 and 3 years after the initiation of treatment. d3-GHR was analyzed in 35 patients.37.1 % of patients were d3-GHR carriers (31.4 % heterozygous, 5.7 % homozygous). IGF-I at baseline was low in 64 % of patients and was not related to d3-GHR status. There was no association between the d3-GHR allele and baseline IGF-I (p = 0.14). Although adverse events were more frequent in the d3-GHR carriers (30.7 vs. 18.2 % in fl/fl) and in patients with normal IGF-I levels at diagnosis (43.7 vs. 17.8 % in patients with low IGF-I levels), this association was not statistically significant. d3-GHR status was not related to the incidence of adverse events (p = 0.4) or treatment discontinuation (p = 0.47). Baseline IGF-I levels were neither associated with adverse events (p = 0.08) nor treatment discontinuation (p = 0.75).The d3-GHR allele was not related to baseline levels of IGF-I. Neither d3-GHR nor baseline IGF-I level was related to adverse events or treatment discontinuation.
- Three-dimensional facial analysis in acromegaly: a novel tool to quantify craniofacial characteristics after long-term remission. [JOURNAL ARTICLE]
- Pituitary 2014 Apr 6.
The exact quantification of craniofacial characteristics in patients with acromegaly is important because it provides insight in the pathophysiology of the disease and offers a tool to evaluate the effects of treatment on tissue specific endpoints. However, until recently this was not feasible due to limitations of available cephalometric methods. The new technique of three-dimensional (3D) cephalometry enables the accurate quantification of facial anatomical characteristics of both soft tissue and bone. This is the first study that uses 3D cephalometry to analyze craniofacial disproportions in patients in long-term remission of acromegaly.Sixteen patients in remission of acromegaly for over 24 months (50 % male, mean age 56.0 ± 10.7 years, mean body mass index 29.3 ± 5.5 kg/m(2)) were compared to 16 matched control subjects. A 3D cone beam computed tomography scan and 3D stereophotograph of each individual were acquired and analyzed using 3D cephalometry.In addition to an accurate quantification of the classical craniofacial characteristics, 3D cephalometry, shows that many typical soft tissue deformities persist, even after long-term remission. Furthermore, we found that, compared to controls, the patients in remission of acromegaly have a wider face at the level of the zygoma and longer maxilla (p < 0.05).3D cephalometry is an attractive novel imaging modality to accurately investigate craniofacial disproportions of both soft tissue and bony parts of the face in patients with acromegaly, which makes it a promising technique for future research purposes and clinical practice.
- The clinical and cardiometabolic effects of d3-growth hormone receptor polymorphism in acromegaly. [JOURNAL ARTICLE]
- Pituitary 2014 Apr 6.
Exon 3-deleted GH receptor variant (d3-GHR) is associated with increased responsiveness to exogenous GH. The aim of this study was to determine the effect of d3-GHR polymorphism on the GH/IGF-1 relationship, clinical parameters, and comorbidity in acromegalic patients.The study included 118 acromegalic patients (61 female and 57 male; mean age: 50.3 ± 12.2 years) and 108 healthy controls (94 female and 14 male: mean age: 41.1 ± 11.1 years). The prevalence of GHR genotypes was evaluated via PCR.In all, 71 (60.2 %) patients had the fl/fl-GHR genotype, 40 (33.9 %) were heterozygous for the fl/d3-GHR genotype, and 7 (5.9 %) were homozygous for the d3/d3-GHR genotype. The prevalence of fl/fl-GHR, fl/d3-GHR, and d3/d3-GHR genotypes in the control group was 57.4, 29.6, and 13.0 %, respectively-similar prevalences as in the patient group. Patients that were heterozygous and homozygous for the d3 allele were subgrouped (d3-GHR subgroup), and were compared to those with the fl/fl-GHR genotype (fl/fl-GHR subgroup). Anthropometric measures, features of pituitary adenoma, and baseline GH and IGF-1 levels were similar in both subgroups. The prevalence of coronary artery disease, hypertension, hyperlipidemia, type 2 diabetes mellitus, and multinodular goiter did not differ between patient subgroups. In total, 24 (20.3 %) of the patients had cancer and the prevalence of cancer was similar in the d3-GHR (14.9 %) and fl/fl-GHR (23.9 %) subgroups (P = 0.23). More of the acromegalic patients that were d3 carriers had discordant GH and IGF-1 levels at baseline and post surgery, but the difference was not significant. A significant correlation between basal GH and IGF-1 levels was observed only in the patients with the fl/fl-GHR genotype (R(2) = 0.227, P < 0.001).The d3-GHR variant genotype did not have an effect on clinical features or comorbidity in acromegalic patients, but it might play a role in GH/IGF-1 level discordance in acromegaly.
- Hypopituitarism patterns and prevalence among men with macroprolactinomas. [JOURNAL ARTICLE]
- Pituitary 2014 Apr 4.
Men with prolactin-secreting tumors usually harbor macroadenomas. The degree of pituitary dysfunction may vary among different adenoma size subgroups, as is recovery after treatment. Our study purpose was to characterize hypopituitarism and recovery after treatment in men with macroprolactinomas.A retrospective study, including a consecutive group of 81 men with pituitary macroadenomas (≥10 mm) and hyperprolactinemia (>7×ULN). Patients were divided into three categories according to adenoma size at presentation: 10-19 mm (group A), 20-39 mm (group B), and ≥40 mm (group C). We compared total testosterone, gonadotropins, cortisol, thyroid hormones and hemoglobin levels at presentation and after treatment.Eighty-one patients were included; 24, 31 and 26 patients in groups A, B and C, respectively. Pretreatment hypogonadism prevalence was 75.0, 93.5 and 90.9 % (p = 0.046; A vs B and C), central hypocortisolism - 0, 6.9 and 33.3 % (p = 0.005), and central hypothyroidism - 6.7, 17.9 and 26.1 % (NS) in groups A, B and C, respectively. Only 26.7 % of all patients presented with hypocortisolism and/or hypothyroidism (42.9 % in group C). Anemia (Hb < 13.5 g %) was detected in 31.3, 57.1 and 80.0 % in groups A, B and C, respectively (p = 0.04). Larger adenoma diameter correlated strongly with lower FT4 levels following treatment (r = -0.42, p = 0.043).Macroprolactinomas in men caused partial hypopituitarism, affecting testosterone in all adenoma size groups and cortisol more in patients with larger adenomas. However, most of the men did not have pituitary hormones affected, beside testosterone. Most patients recovered central hypocortisolism but not hypothyroidism following treatment.
- Towards a better quality of life (QoL) for patients with pituitary diseases: results from a focus group study exploring QoL. [JOURNAL ARTICLE]
- Pituitary 2014 Mar 30.
Patients treated for pituitary adenomas generally report a reduced quality of life (QoL). At present, the patient's perspective of QoL has not been fully addressed and this, and further insight in potential determinants of QoL in pituitary diseases is required to design strategies to improve QoL. We aimed to define patients' perceived QoL and to identify potential factors they perceive to contribute to QoL.We conducted four independent focus groups of six patients each, per specific pituitary disease (Cushing's disease, Non-functioning pituitary macroadenoma, acromegaly, prolactinoma). In two sessions these focus groups discussed aspects of QoL. Verbatim transcripts were analyzed using a grounded theory approach.The issues raised by the patient groups were compatible with statements and items of available QoL questionnaires. In addition, other QoL aspects emerged, such as visual limitations (physical problems); issues with a desire to have children/family planning, fear of collapsing, fear of recurrence, panic, persisting thoughts, problems with an altered personality, anger, jealousy, sadness, frustration (psychological problems); and difficulties communicating about the disease, lack of sympathy and understanding by others, and a reduced social network (social problems). Next, this study uncovered factors which might contribute to a decreased QoL (e.g. less effective coping strategies, negative illness perceptions, negative beliefs about medicines, unmet needs regarding care).This focus group study demonstrated that important disease-specific aspects of QoL are neglected in current pituitary disease-specific questionnaires and elucidated potential factors that contribute to a decreased QoL. Information provided in this study can (and will) be used for developing additional items for disease-specific QoL questionnaires and for the development of a self-management intervention aiming to improve QoL in patients treated for pituitary diseases.
- Combined high-field intraoperative magnetic resonance imaging and endoscopy increase extent of resection and progression-free survival for pituitary adenomas. [JOURNAL ARTICLE]
- Pituitary 2014 Mar 6.
The clinical benefit of combined intraoperative magnetic resonance imaging (iMRI) and endoscopy for transsphenoidal pituitary adenoma resection has not been completely characterized. This study assessed the impact of microscopy, endoscopy, and/or iMRI on progression-free survival, extent of resection status (gross-, near-, and sub-total resection), and operative complications.Retrospective analyses were performed on 446 transsphenoidal pituitary adenoma surgeries at a single institution between 1998 and 2012. Multivariate analyses were used to control for baseline characteristics, differences during extent of resection status, and progression-free survival analysis.Additional surgery was performed after iMRI in 56/156 cases (35.9 %), which led to increased extent of resection status in 15/156 cases (9.6 %). Multivariate ordinal logistic regression revealed no increase in extent of resection status following iMRI or endoscopy alone; however, combining these modalities increased extent of resection status (odds ratio 2.05, 95 % CI 1.21-3.46) compared to conventional transsphenoidal microsurgery. Multivariate Cox regression revealed that reduced extent of resection status shortened progression-free survival for near- versus gross-total resection [hazard ratio (HR) 2.87, 95 % CI 1.24-6.65] and sub- versus near-total resection (HR 2.10; 95 % CI 1.00-4.40). Complication comparisons between microscopy, endoscopy, and iMRI revealed increased perioperative deaths for endoscopy versus microscopy (4/209 and 0/237, respectively), but this difference was non-significant considering multiple post hoc comparisons (Fisher exact, p = 0.24).Combined use of endoscopy and iMRI increased pituitary adenoma extent of resection status compared to conventional transsphenoidal microsurgery, and increased extent of resection status was associated with longer progression-free survival. Treatment modality combination did not significantly impact complication rate.
- Angiolipoma of the sellar region. [JOURNAL ARTICLE]
- Pituitary 2014 Feb 22.
- Central hypothyroidism in adults: better understanding for better care. [JOURNAL ARTICLE]
- Pituitary 2014 Feb 20.
Central hypothyroidism (CH) is a rare cause of hypothyroidism generally related to a hypothalamic-pituitary disorder or arising as an iatrogenic complication. In adults, CH may be secondary to quantitative and/or qualitative alterations in thyroid-stimulating hormone (TSH) secretion. The disease is difficult to diagnose clinically because it lacks specific clinical signs and these may be masked by other anterior pituitary hormone secretion deficiencies. In patients with long-standing and marked CH, a diagnosis may be made based on low free T4 levels and normal, low or moderately increased TSH levels. In patients with early-stage or moderate CH, exploration of the circadian TSH cycle, determination of TSH response after a TRH test or recombinant TSH injection, estimation of TSH index, or evaluation of peripheral indexes of thyroid hormone metabolism may be required to establish a diagnosis. Regarding treatment, patients should receive levothyroxine replacement therapy, but hormone objectives during follow-up need to be precisely determined in order to reduce cardiovascular risks and to improve the quality of life of patients.