Vaclav Hana

Gamma knife radiosurgery for acromegaly – long‐term experience

Objective  The Leksell gamma knife (LGK) is one of the treatment options for pituitary adenomas. We report on our long‐term experience treating acromegaly using LGK.

High prevalence of AIP gene mutations following focused screening in young patients with sporadic pituitary macroadenomas

BACKGROUND Aryl hydrocarbon receptor interacting protein (AIP) mutations (AIPmut) cause aggressive pituitary adenomas in young patients, usually in the setting of familial isolated pituitary adenomas. The prevalence of AIPmut among sporadic pituitary adenoma patients appears to be low; studies have not addressed prevalence in the most clinically relevant population. Hence, we undertook an international, multicenter, prospective genetic, and clinical analysis at 21 tertiary referral endocrine departments. METHODS We included 163 sporadic pituitary macroadenoma patients irrespective of clinical phenotype diagnosed at <30 years of age. RESULTS Overall, 19/163 (11.7%) patients had germline AIPmut; a further nine patients had sequence changes of uncertain significance or polymorphisms. AIPmut were identified in 8/39 (20.5%) pediatric patients. Ten AIPmut were identified in 11/83 (13.3%) sporadic somatotropinoma patients, in 7/61 (11.5%) prolactinoma patients, and in 1/16 non-functioning pituitary adenoma patients. Large genetic deletions were not seen using multiplex ligation-dependent probe amplification. Familial screening was possible in the relatives of seven patients with AIPmut and carriers were found in six of the seven families. In total, pituitary adenomas were diagnosed in 2/21 AIPmut-screened carriers; both had asymptomatic microadenomas. CONCLUSION Germline AIPmut occur in 11.7% of patients <30 years with sporadic pituitary macroadenomas and in 20.5% of pediatric patients. AIPmut mutation testing in this population should be considered in order to optimize clinical genetic investigation and management.

Regression of acromegalic left ventricular hypertrophy after lanreotide (a slow-release somatostatin analog)

A group of 13 acromegalic patients was treated with lanreotide for 18 months and followed-up echocardiographically; these patients showed significant correlations between the decrease of both growth hormone (GH) and insulin-like growth factor-1 and the decrease of left ventricular mass index. This documents a regression of left ventricular hypertrophy in acromegaly after lanreotide treatment, the degree of which is dependent on the magnitude of the decrease of GH and insulin-like growth factor-1 serum levels.

The effects of GH replacement in adult GH‐deficient patients: changes in body composition without concomitant changes in the adipokines and insulin resistance

background  Growth hormone deficiency (GHD) in adult life has been associated with increased central adiposity, decreased insulin sensitivity, dyslipidaemia and increased risk of cardiovascular disease. The effects of GH replacement on adiponectin and resistin, adipokines which have a role in modulating insulin sensitivity have not been previously reported.

Perturbations in adiponectin, leptin and resistin levels in acromegaly: lack of correlation with insulin resistance

background Insulin resistance, impaired glucose tolerance and type 2 diabetes are common in acromegalic subjects. The mechanism underlying this insulin resistance is unclear.

Recurrent ACTH‐independent Cushing's syndrome in multiple pregnancies and its treatment with metyrapone

A 17‐year‐old primigravid woman presented with Cushings syndrome. Typical clinical symptoms and signs developed at the beginning of pregnancy. By week 17 of gestation, plasma cortisol diurnal rhythm was absent and there was a paradoxical increase in plasma cortisol after a 1‐mg dexamethasone overnight suppression test. Basal urinary free cortisol was 10 times above the upper limit (in pregnancy) and ACTH levels were suppressed. The diagnosis of ACTH – independent Cushings syndrome was established. MRI scans revealed normal adrenal and pituitary glands. To control hypercortisolism, the patient was treated with metyrapone. At 34 weeks of gestation, the patient developed preeclampsia and underwent caesarean section. A female infant weighing 1070 g was delivered. No apparent metyrapone‐induced teratogenic effects were observed. Cushings syndrome in the patient resolved within three weeks of delivery. No corticosteroid replacement therapy either for child or mother was needed. Eight months after delivery the patient became pregnant again and rapidly developed Cushings syndrome with typical clinical symptoms and signs and laboratory results (urinary free cortisol 6464 nmol/24 h). This second pregnancy was unwanted and terminated by artificial abortion that was followed by rapid resolution of hypercortisolism. A third pregnancy, 12 months after delivery was also accompanied by the rapid development of hypercortisolism which recovered after artificial termination.

Use of the Leksell gamma knife in the treatment of prolactinoma patients

Objective  Pharmacological treatment with dopaminergic agonists (DA) is the treatment of choice for prolactinomas. Surgical and radiation treatment is also indicated in certain situations. We describe our 12‐year experience in treating prolactinomas with the Leksell gamma knife (LGK).

Adipokine levels in Cushing's syndrome; elevated resistin levels in female patients with Cushing's syndrome

background  Cushings syndrome (CS) is associated with central adiposity, insulin resistance and impaired glucose homeostasis. Adipose tissue is thought to regulates glucose homeostasis via circulating adipokines, such as resistin, leptin and adiponectin, although their role in the insulin resistance associated with CS has not been established.

The effects of three-month intravenous ibandronate on bone mineral density and bone remodeling in Klinefelter's syndrome: the influence of vitamin D deficiency and hormonal status

The aim of this study was to evaluate the effects of a 2-year treatment with intravenous ibandronate (2 mg every 3 months) and calcium (1000 mg daily) on bone mineral density (BMD) and bone markers in 14 patients with Klinefelters syndrome who served as their own controls. During the follow-up of 5.9 years before the treatment was started, the mean rates of bone loss per year were 1.3, 0.9, and 0.6% in the lumbar spine, femoral neck, and total body, respectively. The rate of bone loss from the spine was significantly inversely related to both serum estradiol and testosterone. At the onset of treatment, the average age of the patients was 55.2 years (48-64 years), and T score, mean +/- SD, at the lumbar spine was -2.6 +/- 1.0. After 6 months, the mean serum CTX and PINP decreased by 39 and 55% below the pretreatment concentrations, respectively (P < 0.05). After 12 months of treatment, the patients gained mean +/- SD, 7.8 +/- 2.3% of BMD in the lumbar spine, 3.8 +/- 4.0% in the femoral neck, and 4.7 +/- 2.2% in the total body (P < 0.05). During the second year of treatment, all patients also received 700 IU of vitamin D daily. After 24 months of treatment, the patients gained 10.1 +/- 4.3% of BMD in the lumbar spine, 6.7 +/- 5.5% in the femoral neck, and 5.5 +/- 2.5% in the total body. The increase in BMD in the second year of ibandronate treatment was not significant. The rate of gain of BMD in the femoral neck was positively related to serum concentrations of testosterone and inversely related to 25-hydroxyvitamin D (P < 0.005). After the discontinuation of treatment, serum CTX and PINP increased to the pretreatment levels, and the lumbar spine and femur neck BMD decreased (P < 0.05). In conclusion, ibandronate was effective in increasing BMD at all sites, but the effects were adversely influenced by vitamin D insufficiency or deficiency. The overall changes in biochemical markers of bone remodeling were consistent with the antiresorptive effect of the drug.

The effects of growth hormone status on circulating levels of vascular growth factors

Background  Vascular growth factors are important not only in angiogenesis but also for the maintenance of normal endothelial integrity and function. Elevated levels of vascular endothelial growth factor (VEGF), angiopoietin‐2, hepatocyte growth factor (HGF), endostatin and angiogenin have been associated with endothelial dysfunction and atherosclerosis. Both acromegaly and growth hormone deficiency (GHD) are associated with endothelial dysfunction and changes in blood vessel morphology.