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- Clinical outcome and evidence of high rate post-surgical anterior hypopituitarism in a cohort of TSH-secreting adenoma patients: Might somatostatin analogs have a role as first-line therapy? [JOURNAL ARTICLE]
- Pituitary 2014 Oct 19.
Thyrotropin-secreting pituitary adenomas (TSHomas) represent a rare subtype of pituitary tumors. Neurosurgery (NCH) is still considered the first-line therapy. In this study we aimed to investigate the outcome of different treatment modalities, including first line somatostatin analogs (SSA) treatment, with a specific focus on neurosurgery-related complications.We retrospectively evaluated thirteen patients diagnosed for TSHomas (9 M; age range 27-61). Ten patients had a magnetic resonance evidence of macroadenoma, three with slight visual field impairment. In the majority of patients, thyroid ultrasonography showed the presence of goiter and/or increased gland vascularization. Median TSH value at diagnosis was 3.29 mU/L (normal ranges 0.2-4.2 mIU/L), with median fT4 2.52 ng/dL (0.9-1.7 ng/dL).Three patients (two microadenoma) were primarily treated with NCH and achieved disease remission, whereas ten patients (nine macroadenomas) were initially treated with SSA. Despite the optimal biochemical response observed during medical treatment in most patients (mean TSH decrease -72 %), only two stayed on medical therapy alone, achieving stable biochemical control at the end of the follow-up. The remaining patients (n = 7) underwent NCH later on during their clinical history, followed by radiotherapy or adjuvant SSA treatment in two cases. Noteworthy, five of them developed hypopituitarism. All patients reached a biochemical control, after a multimodal therapeutic approach.Neurosurgery ultimately led to complete disease remission or to biochemical control in majority of patients, whereas resulting in a considerable percentage of post-operative complications (mainly hypopituitarism, 50 %). In the light of the optimal results unanimously reported for medical treatment with SSA, our experience suggests that a careful evaluation of risk/benefit ratio should be taken into consideration when directing the treatment approach in patients with TSHoma.
- Frequent development of combined pituitary hormone deficiency in patients initially diagnosed as isolated growth hormone deficiency: a long term follow-up of patients from a single center. [JOURNAL ARTICLE]
- Pituitary 2014 Oct 15.
Children initially diagnosed with isolated GH deficiency (IGHD) have a variable rate to progress to combined pituitary hormone deficiency (CPHD) during follow-up.To evaluate the development of CPHD in a group of childhood-onset IGHD followed at a single tertiary center over a long period of time.We retrospectively analyzed data from 83 patients initially diagnosed as IGHD with a mean follow-up of 15.2 years. The Kaplan-Meier method and Cox regression analysis was used to estimate the temporal progression and to identify risk factors to development of CPHD over time.From 83 patients initially with IGHD, 37 (45 %) developed CPHD after a median time of follow up of 5.4 years (range from 1.2 to 21 years). LH and FSH deficiencies were the most common pituitary hormone (38 %) deficiencies developed followed by TSH (31 %), ACTH (12 %) and ADH deficiency (5 %). ADH deficiency (3.1 ± 1 years from GHD diagnosis) presented earlier and ACTH deficiency (9.3 ± 3.5 years) presented later during follow up compared to LH/FSH (8.3 ± 4 years) and TSH (7.5 ± 5.6 years) deficiencies. In a Cox regression model, pituitary stalk abnormalities was the strongest risk factor for the development of CPHD (hazard ratio of 3.28; p = 0.002).Our study indicated a high frequency of development of CPHD in patients initially diagnosed as IGHD at childhood. Half of our patients with IGHD developed the second hormone deficiency after 5 years of diagnosis, reinforcing the need for lifelong monitoring of pituitary function in these patients.
- Pituitary image: pituicytoma. [JOURNAL ARTICLE]
- Pituitary 2014 Oct 14.
Pituicytoma is a rare tumor arising from the neurohypophysis or pars intermedia of the adenohypophysis.A 36 year old male came to our observation presenting polydipsia, polyuria, polyphagia, decreased libido and altered sleep-wake rhythm. The biochemical tests showed hypotonic urine, mild hyperprolactinemia, hypogonadotropic hypogonadism, central hypothyroidism. Magnetic resonance revealed an expansive lesion of the suprasellar region (slightly isointense on T1, hyperintense on T2, impregnating contrast medium), that was partially removed by trans-cranial neurosurgical approach. The histopathological diagnosis was pituicytoma. After surgery, in addition to endocrine disorders, the patient presented severe neurological sequelae and hyperthermia, likely due to damage of the hypothalamus, followed by a progressive metabolic syndrome. The residual tumor was monitored by MRI, and, due to the early gradual increase in volume, was treated by stereotactic radiosurgery.Pituicytomas are often difficult to distinguish from other hypothalamic or pituitary lesions. However, their identification would be preferable in a pre-operative setting in order to optimize the work-up and to initiate a proactive management of the expected complications.
- Sella turcica: an anatomical, endocrinological, and historical perspective. [JOURNAL ARTICLE]
- Pituitary 2014 Oct 12.
The sphenoid bone has a superior depression called the sella turcica, Latin for "Turkish saddle," where the pituitary gland is found. The availability of modern radiological imaging techniques has replaced plain radiography of the sella turcica in the investigation of hypothalamo-pituitary abnormalities. However, the size of the sella turcica, and smaller sella turcica size in particular, may cause pituitary dysfunction because of the changes in the structure of pituitary gland or may be associated with some genetic or acquired endocrine disorders. The name "sella turcica" is one of the most commonly used terms in everyday endocrine practice.In this review, after a brief explanation of the anatomical and endocrinological features of the sella turcica had been given, a historical perspective of sella turcica nomenclature was presented for the first time.After Andreas Vesalius's description of it as a suitable cavity for the gland that receives the "phlegm of the brain" in De Humani Corporis Fabrica (1543), medical scholars began to use seat/saddle-related terms such as the ephippium, pars sellaris, sella equina, sella ossis, and sella sphenoidalis. The real designation of the sella turcica, however, was introduced to the anatomical nomenclature by the anatomist Adrianus Spigelius (1578-1625) in his famous work De Corpora Humanis Fabrica (1627).
- Discontinuation of somatostatin analogs while acromegaly is in long-term remission. [JOURNAL ARTICLE]
- Pituitary 2014 Oct 10.
We aimed to evaluate the disease activity of medically controlled patients with acromegaly after withdrawal of somatostatin receptor ligands (SRL).Sixteen patients who were on a stable dose of SRL for more than 2 years and had at least 1 year of remission were included in the study. Five patients were on 10 mg, four were on 20 mg and three were on 30 mg of octreotide; whereas for lanreotide, one was on 60 mg, two were on 90 mg, and one was on 120 mg. All patients had received SRL with 28-day intervals. Basal GH, IGF1, glucose-suppressed GH levels were measured with 3-month intervals for a total of 12 months after withdrawal. Sella MRI evaluation was obtained at 6-month intervals. If the nadir GH level after glucose suppression was >1 ng/ml or IGF1 was above the normal limits during the follow-up period, SRL was restarted.Three months after stopping SRL, 10 (63 %) had biochemical disease recurrence. After 12 months of follow-up, in total 13 (81 %) of the patients recurred. The final basal GH levels before withdrawal, basal GH at month-3, and glucose suppressed GH levels were significantly lower in patients with sustained remission (p = 0.003, p < 0.001, and p = 0.001). Basal GH and glucose suppressed GH levels at month-3 were correlated with the basal GH levels at month-0 (r = 0.6, p = 0.008 and r = 0.5, p = 0.03).The final GH levels prior to discontinuation of SRL should be taken into consideration in patients with acromegaly in long-term remission. Moreover, the first visit 3 months after withdrawal is critically important for determining the future status of remission.
- Inhibition of heat shock protein 90 decreases ACTH production and cell proliferation in AtT-20 cells. [JOURNAL ARTICLE]
- Pituitary 2014 Oct 4.
Cushing's disease is primarily caused by adrenocorticotropic hormone (ACTH)-producing pituitary adenomas. If excision of the tumor from the pituitary, which is the primary treatment for Cushing's disease, is unsuccessful, further medical therapy is needed to treat the resultant hypercortisolism. Some of the drugs used to treat this condition have shown potential therapeutic benefits, but a more effective treatment should be explored for the treatment of Cushing's disease. In the present study, we determined the effect of heat shock protein 90 inhibitors on ACTH production and cell proliferation of AtT-20 corticotroph tumor cells.AtT-20 pituitary corticotroph tumor cells were cultured. The expression levels of mouse proopiomelanocortin (POMC) and pituitary tumor transforming gene 1 (PTTG1) mRNA were evaluated using quantitative real-time PCR. Cellular DNA content was analyzed with fluorescence-activated cell sorting (FACS) analysis. The protein levels were determined by Western blot analysis.Both 17-allylamino-17-demethoxygeldanamycin and CCT018159 decreased POMC mRNA levels in AtT-20 cells and ACTH levels in the culture medium of these cells, suggesting that both drugs suppress ACTH synthesis and secretion in corticotroph tumor cells. Both drugs also decreased cell proliferation and induced apoptosis. FACS analyses revealed that both agents increased the percentage of AtT-20 cells in the G2/M phase. These drugs decreased cell proliferation, presumably due to the induction of cell death and arrest of the cell cycle in AtT-20 cells. Tumor weight in mice xenografted with AtT-20 cells and treated with CCT018159 was lower than in AtT-20-xenografted control mice. CCT018159 also decreased plasma ACTH levels, and POMC and PTTG1 mRNA levels in the tumor cells.CCT018159 inhibits ACTH production and corticotroph tumor cell proliferation in vitro and in vivo.
- Growth hormone deficiency after mild combat-related traumatic brain injury. [JOURNAL ARTICLE]
- Pituitary 2014 Sep 30.
Traumatic brain injury (TBI) has been recognized as a cause of growth hormone deficiency (GHD) in civilians. However, comparable data are sparse in veterans who incurred TBI during combat. Our objective was to determine the prevalence of GHD in veterans with a history of combat-related TBI, and its association with cognitive and psychosocial dysfunction.Single center prospective study.Twenty male veterans with mild TBI incurred during combat 8-72 months prior to enrollment.GHD was defined by a GH peak <3 μg/L during glucagon stimulation test. Differences in neuropsychological, emotional, and quality of life of the GHD Veterans were described using Cohen's d. Large effect sizes were considered meaningful.Mean age was 33.7 years (SD 7.8) and all subjects had normal thyroid hormone and cortisol levels. Five (25 %) exhibited a subnormal response to glucagon. Sixteen participants (80 %) provided sufficient effort for valid neuropsychological assessment (12 GH-sufficient, 4 GHD). There were large effect size differences in self-monitoring during memory testing (d = 1.46) and inhibitory control (d = 0.92), with worse performances in the GHD group. While fatigue and post-traumatic stress disorder were comparable, the GHD group reported more depression (d = 0.80) and lower quality of life (d = 0.64).Our study found a 25 % prevalence of GHD in veterans with mild TBI as shown by glucagon stimulation. The neuropsychological findings raise the possibility that GHD has adverse effects on executive abilities and mood. Further studies are needed to determine whether GH replacement is an effective treatment in these patients.
- Preoperative somatostatin analogues versus direct transsphenoidal surgery for newly-diagnosed acromegaly patients: a systematic review and meta-analysis using the GRADE system. [JOURNAL ARTICLE]
- Pituitary 2014 Sep 28.
Whether the preoperative use of somatostatin analogues (SA) improves surgical outcomes in acromegaly is still a matter of debate.We conducted a systematic review of randomized, controlled trials that compared the short-term outcomes of preoperative use of SA (Pre-SA) with direct TSS (No-SA) for the treatment of newly diagnosed acromegaly.Embase, Pubmed, Lilacs, and Central Cochrane were used as our data sources. The primary outcomes were no need for any adjuvant treatment 3 months after surgery, based on biochemical results (GH nadir after OGTT <1 μg/L and normal IGF-1 for age and gender), quality of life and mortality. The included trials were analyzed using the Grading of Recommendations Assessment, Development, and Evaluation approach.A total of 2.099 references were identified and two reviewers independently screened the titles and abstracts. From the 14 potentially eligible studies, four were included and ten were excluded due to lack of randomization or different outcomes. A pool of 261 patients was randomly assigned to Pre-SA or No-SA. Meta-analysis of IGF1 normalization showed a significant difference in favor of Pre-SA (RR 2.47; 95 % CI 1.66, 3.77). Adding a GH nadir on OGTT ≤1 μg/L, we found a RR of 2.15 (95 % CI 1.39, 3.33). Quality of evidence for no need of adjuvant postoperative treatment was moderate, but for improving quality of life was very low and for mortality was absent.Pre-SA increases the chance of biochemical control of acromegaly 3 months after TSS in patients harboring GH-secreting pituitary macroadenomas.
- Heart rate variability is reduced in acromegaly patients and improved by treatment with somatostatin analogues. [JOURNAL ARTICLE]
- Pituitary 2014 Sep 27.
Cardiovascular complications, including arrhythmias and cardiac sudden death, are the most common causes of enhanced mortality in acromegaly. However, few data are available on cardiac autonomic functions and sympathovagal balance in acromegalic patients.The aim of this study was to investigate both the time and frequency domain parameters of Heart Rate Variability (HRV), in order to characterize the cardiac autonomic functions in patients affected by acromegaly. This study correlated anthropometric, metabolic, echocardiographic parameters and blood pressure with those relating to HRV, to identify the main factors responsible for the HRV related alterations possibly present. We also aimed to analyze the effects of the treatment with somatostatin analogues (SSAs) on HRV.This study enrolled 47 acromegalic patients (23 males, age 49.1 ± 13.5 years) and 37 (13 males) age matched (52.3 ± 13.3 years) healthy subjects. All participants underwent 12-lead 24 h ECG Holter recordings and a HRV analysis of the ECG tracings was performed. The parameters obtained from the time domain analysis of HRV included pNN50, SDNN, SDNN index, SDANN and RMSSD. The power spectral analysis of HRV was obtained by summing powers of the LF (low frequency) and the HF (high frequency) band. Sympathovagal balance was estimated by calculating the LF/HF ratio during 24 h and 15 min of clinostatism. The HRV of 28 acromegalic patients was studied before and after SSAs treatment.Acromegalic patients showed significantly lower SDNN and SDANN compared to controls. Diabetic and non-diabetic acromegalic patients showed decreased SDNN and SDANN, when compared to healthy subjects. Diabetic acromegalic patients had a lower LF/HF ratio during 24 h when compared to non-diabetic acromegalic patients. Similar results were obtained analyzing patients affected by acromegaly and impaired glucose tolerance. SDNN and SDANN were lowered by hypertension in the acromegalic population, when compared to controls, and hypertensive acromegalic patients also displayed a decreased LF/HF ratio during 24 h when compared to normotensive acromegalic subjects. Patients with ventricular arrhythmias in Lown classes 3-5 showed a decreased SDANN compared to patients in Lown class 0-2. The treatment with SSAs was able to ameliorate all the time domain parameters of HRV, without altering the 24 h LF/HF ratio.Cardiac autonomic functions and sympathovagal balance are altered in patients affected by acromegaly and could be ameliorated by SSAs therapy. HRV analysis allows an estimation of the autonomic sympathovagal balance and may be a useful clinical tool for the cardiac risk stratification in acromegalic patients.
- Endoscopic endonasal transsellar approach for laterally extended pituitary adenomas: volumetric analysis of cavernous sinus invasion. [JOURNAL ARTICLE]
- Pituitary 2014 Sep 27.
The authors conducted a statistical analysis of surgical results of the endoscopic endonasal transsellar approach to provide quantitative indices for selection of the approach in the treatment of laterally extended pituitary adenomas.Surgical results of 25 patients with laterally extended pituitary adenomas of Knosp grade 3 or 4 were retrospectively analyzed. The removal rate was evaluated by the volumetric change of the lateral tumor compartment.The transsellar approach was used exclusively in all cases. Gross total removal of the lateral tumor compartment was achieved in 14 (56.0 %). Factors affecting the tumor removal through the transsellar approach were lateral tumor volume (p = 0.006), maximal distance to the cavernous sinus outer wall (p = 0.004) and history of previous surgery (p = 0.017). The cut-off values for the lateral tumor volume and maximal distance to the cavernous sinus outer wall predicting the gross total removal were 0.479 ml and 8.1 mm, respectively. The surgical complications of the transsellar approach included each case of anterior lobe function insufficiency and liquorrhea.The transsellar approach is adequate for removal of lateral tumor compartment in the majority of cases with laterally extended pituitary adenomas. The tumor compartments dorsal and ventral to the horizontal portion of the intracavernous carotid artery are amenable to the removal. But for removal of the tumor compartment lateral to the carotid siphon requires additional use of the parasellar approach.