Spiral computed tomography angiography (SCTA) and color coded duplex ultrasound (CCDUS): two complementary diagnostic techniques for assessment of extracranial cerebral artery stenosis

Atherosclerotic lesions of the extracranial cerebral arteries account for ischemic stroke in over half of all cases. The risk of stroke associated with symptomatic carotid artery disease is related to the severity of the stenosis. Results of the two major clinical trials, North American Symptomatic Carotid Endarterectomy Trial (NASCET) and European Carotid Surgery Trial (ECST), showed that patients with symptomatic carotid artery disease may benefit from carotid endarterectomy. Therefore, detection and quantification of stenosis are essential. Discrepancies in the angiographic criteria used in both NASCET and ECST trials resulted in continued controversy about the most accurate method of measuring carotid artery stenosis. Moreover, to avoid complications related to the angiography procedure, a good evaluation of vessel wall and plaque composition need to be considered. Both SCTA and CCDUS are non invasive techniques that could overcome angiographic complications and give detailed information on stenosis grading and plaque characteristics. They have been used to evaluate carotid stenosis as a single or combined methods.     

Combination therapy for Cushing’s disease: effectiveness of two schedules of treatment. Should we start with cabergoline or ketoconazole?

Cushing’s disease (CD) is associated with increased morbidity and mortality. Until now, no medical treatment has been shown to be totally satisfactory when administrated alone. This study aimed to assess the effectiveness of cabergoline with added ketoconazole and of the same combination in reverse, using urinary free cortisol (UFC) and late night salivary cortisol (LNSC) levels as biochemical markers of the treatments’ efficacy in CD patients. A prospective analysis conducted on 14 patients (f/m = 12/2; median age 52, range 33–70 years) divided into two groups: 6 patients initially treated with cabergoline for 4–6 months (rising from 0.5–1 mg/week up to 3.0 mg/week), after which ketoconazole was added (group A); and 8 patients first took ketoconazole alone for 4–6 months (rising from 200 mg/day to 600 mg/day), then cabergoline was added (group B). Patients were compared with 14 age-matched patients in prolonged remission after effective neurosurgery for CD. The combination therapy led to UFC normalization in 79 % of patients with no differences between the groups; only one patient failed to respond at all. Neither drug succeeded in controlling the disease when taken alone. LNSC dropped when compared to baseline levels, but not to a significant degree (p = 0.06), and it remained significantly higher than in controls (p = 0.0006). Associating cabergoline with ketoconazole may represent an effective second-line treatment, achieving a satisfactory reduction in UFC levels and clinical improvement. Although the combined treatment lowered patients’ LNSC levels, they remained higher than normal, indicating a persistent subclinical hypercortisolism; the implications of this condition need to be considered. No differences emerged between the two treatment schedules.     

Long-course temozolomide in aggressive pituitary adenoma: real-life experience in two tertiary care centers and review of the literature

Pituitary - Aggressive pituitary adenomas (APAs) and pituitary carcinomas (PCs) are challenging for their invasive nature, resistance to treatment and recurrences. Temozolomide (TMZ) is...     

Second-line tests in the differential diagnosis of ACTH-dependent Cushing’s syndrome

Introduction

Diagnosing Cushing’s syndrome (CS) can be a challenge, especially in ACTH-dependent CS, when it comes to detecting the origin of ACTH secretion.

Materials and methods

Retrospective data were collected on 170 patients with ACTH-dependent CS (149 CD, 21 EAS) referring to two endocrinology units, focusing on three non-invasive tests: dexamethasone 8 mg overnight challenge (HDDST); corticotrophin-releasing hormone (CRH) assay and the desmopressin (DDAVP) test.

Results

Patients with EAS were slightly older and had higher ACTH, serum and urinary cortisol levels than patients with CD (p < 0.01). CD patients had a stronger ACTH and cortisol response after CRH injection (p < 0.0001), and a more pronounced reduction in cortisol levels after HDDST (p < 0.0001). A threshold percentage ACTH increase after CRH stimulation of 72.4 % was able to identify CD with a sensitivity (SE) of 76 % (95 % CI 68–83) and a specificity (SP) of 100 % (95 % CI 83–100). As for HDDST, a cortisol suppression >52.7 % below the basal level suggested a pituitary origin with a SE of 88 % (95 % CI 81–93) and a SP of 90 % (95 % CI 68–99). There were no cases of EAS with positive responses to both these tests. Increases in ACTH and cortisol levels after the DDAVP test were also higher in CD than in EAS (p < 0.01), though the SE and SP were lower.

Conclusions

Patients with CD showed a stronger response to HDDST and CRH, and the adopted cut-offs showed a good SE and SP in discriminating them from patients with EAS. Concordant tests indicated CD when positive, whereas no response to either test was highly suggestive of EAS. The DDAVP test was of limited utility in the diagnostic phase. In conclusion, the choice of tests may play an important part in the differential diagnosis of ACTH-dependent CS.

     

Traumatic brain injury and subarachnoid haemorrhage are conditions at high risk for hypopituitarism: screening study at 3 months after the brain injury

OBJECTIVE: Acquired hypopituitarism in adults is obviously suspected in patients with primary hypothalamic-pituitary diseases, particularly after neurosurgery and/or radiotherapy. That brain injuries (BI) can cause hypopituitarism is commonly stated and has been recently emphasized but the management of BI patients does not routinely include neuroendocrine evaluations. AIM: To clarify the occurrence of hypopituitarism in patients after traumatic brain injury (TBI) or subarachnoid haemorrhage (SAH) 3 months after the BI. SUBJECTS AND METHODS: The occurrence of hypopituitarism in conscious patients after traumatic brain injury [TBI, n = 100, 31 women, 69 men; age 37.1 +/- 1.8 years; body mass index (BMI) 23.7 +/- 0.4 kg/m(2); Glasgow Coma Scale (GCS) 3-15] or subarachnoid haemorrhage [SAH, n = 40, 14 men, 26 wpmen, 51.0 +/- 2.0 years; 25.0 +/- 0.6 kg/m(2); Fisher's scale 1-4] was studied in a multicentre study 3 months after the BI. All patients underwent wide basal hormonal evaluation; the GH/IGF-I axis was evaluated by GHRH + arginine test and IGF-I measurement. RESULTS: In TBI patients, some degree of hypopituitarism was shown in 35%. Total, multiple and isolated deficits were present in 4, 6 and 25%, respectively. Diabetes insipidus was present in 4%. Secondary adrenal, thyroid and gonadal deficit was present in 8, 5 and 17%, respectively. Severe GH deficiency (GHD) was the most frequent pituitary defect (25%). In SAH patients, some degree of hypopituitarism was shown in 37.5%. Despite no total hypopituitarism, multiple and isolated deficits were present in 10 and 27.5%, respectively. Diabetes insipidus was present in 7.5%. Secondary adrenal, thyroid and gonadal deficit was present in 2.5, 7.5 and 12.5%, respectively. Severe GHD was the most frequent defect (25%). CONCLUSIONS: TBI and SAH are conditions associated with high risk of acquired hypopituitarism. The pituitary defect is often multiple and severe GHD is the most frequent defect. Thus neuroendocrine evaluations are always mandatory in patients after brain injuries.     

High prevalence of thyroid ultrasonographic abnormalities in primary aldosteronism

The study was performed to evaluate the prevalence of thyroid abnormalities detected by ultrasonography and, in particular, of multinodular nontoxic goiter in primary aldosteronism. We analyzed 80 consecutive of patients with primary hyperaldosteronism (40 with unilateral adenoma and 40 with idiopathic hyperaldosteronism) and 80 normotensive healthy controls, comparable for age, sex, iodine intake, and geographical area. Blood pressure, thyroid palpation, thyroid function, and ultrasonography were evaluated. The prevalence of ultrasonographic thyroid abnormalities was 60% in primary aldosteronism and 27% in controls (p<0.0001). There was a statistically significant difference in prevalence of these abnormalities in unilateral adenoma and idiopathic hyperaldosteronism with respect to controls (p<0.05 and p<0.0001, respectively). The prevalence of multinodular nontoxic goiter in idiopathic hyperaldosteronism was higher than in controls (p<0.001) and, in particular, in female patients. From these data it seems to be worth considering the existence of primary hyperaldosteronism in patients with multinodular goiter and hypertension.     

Prognostic value of the dense middle cerebral artery sign in patients with acute ischemic stroke

The presence of a dense appearance of the horizontal part of the middle cerebral artery (the “dense middle cerebral artery sign”) was looked for on CT scans taken on admission in 90 consecutive patients with ischemic stroke in the carotid artery distribution. The outcome of the 14 patients with the sign was poorer than that of 76 patients without the sign (Odds ratio 4.3). We suggest that this sign could be a useful prognostic variable in the acute phase of an ischemic stroke.

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Sommario è state ricercata retrospettivamente la presenza della immagine iperdensa del tratto orizzontale della cerebrale media (“dense middle cerebral artery sign”) negli esami TAC eseguiti in 90 pazienti consecutivi con sintomatologia riferibile ad ischemia acuta nel territorio del circolo carotideo. L'evoluzione clinica dei 14 pazienti in cui il segno della cerebrale media iperdensa è stato rilevato è stata peggiore degli altri 76 (Odds ratio 4.3). Gli autori suggeriscono che il rilievo di questo segno può rappresentare una utile indicazione prognostica precoce nei casi di ischemia cerebrale acuta.

     

Cyclic Cushing's syndrome: an overview

Cyclic Cushing's syndrome (CS) is a disorder in which glucocorticoid levels are alternately normal and high, the latter occurring in episodes that can last from a few days to several months. It is more common in children than in adults. Cyclic CS may be either of the two different forms of CS (ACTH-dependent or -independent CS). Clinically, it may present with one or many symptoms, depending on the duration of disease activity and the timing of the fluctuations. A serotoninergic influence, cyclic changes in central dopaminergic tone, spontaneous episodic hemorrhage in the tumor, and the action of inflammatory cytokines with antitumor properties are some of the mechanisms suggested to explain the physiopathology of this phenomenon but the exact mechanism remains to be clarified. The cyclic pattern of hypercortisolism can delay the final diagnosis of CS and make it difficult to interpret the results of dynamic tests. Patients may have paradoxical responses to dexamethasone that can reflect increasing or decreasing levels of endogenous activity. Hormone assessments have to be repeated periodically when a diagnosis of CS is suspected. The cyclic pattern can also interfere with medical treatment because patients may show unexpected clinical and biochemical signs of hypocortisolism when cortisol secretion cyclically returns to normal, so an accurate follow-up is mandatory in these patients.     

The Role of Unilateral Adrenalectomy in ACTH-Independent Macronodular Adrenal Hyperplasia (AIMAH)

Background ACTH-independent macronodular adrenal hyperplasia (AIMAH) is a rare cause of Cushing’s syndrome. Bilateral adrenalectomy is considered the treatment of choice, with subsequent lifetime steroid replacement, but unilateral adrenalectomy has been recently proposed to reduce the secreting tissue. This prospective study was designed to evaluate the long-term results of unilateral adrenalectomy in AIMAH concerning the main laboratory and clinical abnormalities and the patient’s quality of life. Methods Seven consecutive patients with confirmed AIMAH underwent unilateral adrenalectomy of the largest gland. ACTH and cortisol levels, arterial blood pressure (BP), glycometabolic parameters, and patient’s subjective perception of health-related quality of life (by the SF-36 questionnaire) were measured preoperatively and postoperatively. Results No surgery-related morbidity occurred. One patient with a large contralateral adrenal enlargement required a completion adrenalectomy after 7 months because of persistent hypercortisolism. At a median follow-up of 53 (range, 27–68) months, the remaining six patients were cured, because serum and urinary free cortisol levels significantly decreased and ACTH increased, thus regaining the normal range. Both systolic and diastolic BP levels significantly reduced: 50% of patients definitively became normotensive, and the remaining patients reduced the need for antihypertensive treatment; 40% of patients suffering from preoperative diabetes were cured, whereas 40% reduced the need for hypoglycemizing drug. SF-36 evaluation of the health-related quality of life confirmed a significant amelioration. Conclusions Unilateral adrenalectomy of the largest gland can be an effective and safe treatment for AIMAH in case of asymmetric involvement. It may achieve long-term remission of Cushing’s syndrome and improve BP values, glycemic control, and patient’s quality of life.