Growth Hormone Oversecretion Research Articles

Role of IL33 in chronic inflammation and microvascular damage as a reflection of organ damage on a cohort of patients with acromegaly

AimAcromegaly is a rare chronic disease, caused by the over-secretion of growth hormone (GH), that creates a pro-inflammatory state, but the exact mechanisms by which GH or insulin-like growth factor 1 (IGF-1) act on inflammatory cells are not fully understood. Aim of the study was to evaluate Interleukin-33 (IL33) and the skin perfusion of hands in patients with acromegaly (AP) and healthy controls (HC).MethodsIL33 have been assessed in 40 AP and 40 HC. IL 33 was determined and skin perfusion of hands was assessed by laser speckle contrast analysis (LASCA) in both populations.ResultsIL33 was significantly higher in AP compared to HC [45.72 pg/ml (IQR 28.74–60.86) vs 14 pg/ml (IQR 6.5535); p < 0.05]. At LASCA, peripheral blood perfusion (PBP) was significantly lower in AP compared to HC [53.39 pU (IQR 40.94–65.44) vs 87 pU (IQR 80–98) p < 0.001]. The median values of ROI1, ROI2 and ROI3 were significantly lower in AP compared to HC [97.32 pU (IQR 50.89–121.69) vs 131 pU (IQR 108–135); p < 0.001], [58.68 pU (IQR 37.72–84.92) vs 83 pU (IQR 70–89), p < 0.05] and HC [52.16 (34.47–73.78) vs 85 (78–98), p < 0.001], respectively. The proximal–distal gradient (PDG) was observed in 18 of 40 (45%) AP.ConclusionSerum IL33 is higher in AP compared to HC; conversely a reduction of PBP of hands was present in AP compared to HC, probably due to endothelial dysfunction, strictly dependent on acromegaly and are not influenced by the choice of treatment.

In acromegalic patients the serum levels of interleukin-33 and Resolvin D1 influence skin perfusion of hands: A pilot study

Acromegaly is a rare chronic disease, caused by the over-secretion of growth hormone (GH), that creates a pro-inflammatory state, but the exact mechanisms by which GH or insulin-like growth factor 1 (IGF-I) act on inflammatory cells are not fully understood. Aim of the study was to evaluate Interleukin-33 (IL33) and D-series resolvins 1 (RvD1) and the skin perfusion of hands in patients with acromegaly (AP) and healthy controls (HC).IL33 and RvD1 have been assessed in 20 AP and 20 HC. Nailfold videocapillaroscopy (NVC) was performed and skin perfusion of hands was assessed by laser speckle contrast analysis (LASCA) in both populations.IL33 was significantly higher in AP compared to HC [73.08 pg/ml (IQR 47.11-100.80 pg/ml) vs 41.5 4 pg/ml (IQR 20.16-55.49 pg/ml), p < 0.05] and RvD1 was significantly lower in AP than HC [36.1 pg/ml (IQR 27.88-66.21 pg/ml) vs 60.01 pg/ml (IQR 46.88-74.69 pg/ml), p < 0.05]. At LASCA, peripheral blood perfusion (PBP) was significantly lower in AP compared to HC [56.66 pU (IQR 46.29-65.44 pU) vs 87 pU (IQR 80-98 pU), p < 0.001]. The median values of ROI1 and ROI3 were significantly lower in AP compared to HC [112.81 pU (IQR 83.36-121.69 pU) vs 131 pU (IQR 108-135 pU), p < 0.05] and [59.78 pU (IQR 46.84-79.75 pU) vs 85 pU (IQR 78-98 pU), p < 0.05], respectively. The proximal-distal gradient (PDG) was observed in 8 of 20 (40 %) AP.Serum IL33 is higher in AP compared to HC; conversely, RvD1 is lower in AP compared to HC. Reduction of PBP of hands was present in AP compared to HC, probably due to endothelial dysfunction.

Abstract #1400950: Chiari I Malformation with Concomitant Nonfunctioning Pituitary and Adrenal Tumors

Chiari I malformation (CM1) is a rare finding with an incidence ranging from 3.3 to 8.2 per 100000. CM1 has been described with growth hormone secreting pituitary adenomas, and with EPAS1 gain-of-function mutation syndrome with multiple paragangliomas/pheochromocytomas, somatostatinoma, and polycythemia. There is only one case report in the literature describing a nonfunctional pituitary adenoma with CM1. We describe the first reported case of a patient with CM1 with concomitant nonfunctional pituitary and adrenal incidentalomas. A 45-year-old female with history of diet-controlled diabetes and HTN presented with a two-week history of bilateral upper extremity weakness and paresthesia, along with gait instability. She had reduced motor power in the upper extremities on physical exam. MRI cervical spine demonstrated a cervicothoracic syrinx, cerebellar tonsillar ectopia consistent with CM1. MRI brain showed diffuse enlargement of the pituitary gland measuring 16 x 14 x 13 mm bulging into the suprasellar cistern and minimally abutting the inferior aspect of the optic chiasm. MRI lumbar spine revealed a left adrenal gland nodule measuring 1.5 x 2.0 cm. Endocrine hormonal evaluation showed normal prolactin, follicle stimulating and luteinizing hormone, estradiol, free T3, free T4, and IGF-I levels. Aldosterone level was high in supine position with normal plasma renin activity initially with normal levels on repeat testing. Plasma free metanephrine, normetanephrine, testosterone levels were also normal. Patient was started on dexamethasone in anticipation of surgery. Patient underwent suboccipital craniectomy, C1 laminectomy, coagulation of cerebellar tonsils and expansile duraplasty for CM1. Patient did well postoperatively and dexamethasone was tapered off. Postoperative follow up after patient had been off steroids for three weeks showed normal levels of all pituitary and adrenal hormones, including normal dexamethasone suppression test. While CM1 is a rare finding, pituitary adenomas are relatively common. In cases of concomitant occurrence of CM1 and growth hormone secreting pituitary adenoma, over-secretion of growth hormone has been proposed as a mechanism to precipitate symptoms of CM1 by causing hypertrophy of connective and ligamentous tissue in the skull base and of the cranio-cervical canal. Our patient had normal IGF-1 levels with a nonfunctional pituitary adenoma raising the question whether there is some other underlying mechanism, possibly a genetic predisposition, that contributed to the concomitant occurrence of CM1 with pituitary and adrenal tumors. Whether these tumors become functional in the future remains to be seen.

Induction of endoplasmic reticulum stress markers in an acromegaly model.

Acromegaly is a growth hormone (GH) excess pathological condition in humans. Acromegaly is associated with somatic disfigurement and a wide range of systemic manifestations such as arthritis, neuropathy, carpal tunnel syndrome, reproductive disorders, metabolic disorders, and gastrointestinal complications. The influence of excess GHon the cellular level could aid in understanding the root causes of acromegaly-related health complications. Previously, we found that GH excess induces DNA damage to somatic cells and reduces the stem cells number and causes premature aging. In this study, an in-depth analysis of the acromegaly RNAseq data revealed the disruption of important biological cellular processes. Gene set enrichment analysis, heatmap, and enrichment analysis of acromegaly RNAseq data revealed induction of endoplasmic reticulum (ER) stress markers in various organs. Interestingly, the induction of ER stress was even more apparent than in aged zebrafish. Splicing of box-binding protein-1 (XBP1) mRNA is a hallmark of ER stress. Therefore, we quantified spliced XBP1 mRNA in different organs of our acromegaly model. Thus, our study emphasizes the importance of ER stress in GH oversecretion, which is important for understanding the health complications of acromegaly.

GPR101 drives growth hormone hypersecretion and gigantism in mice via constitutive activation of G s and G q/11

Growth hormone (GH) is a key modulator of growth and GH over-secretion can lead to gigantism. One form is X-linked acrogigantism (X-LAG), in which infants develop GH secreting pituitary tumors over-expressing the orphan G-protein coupled receptor, GPR101. The role of GPR101 in GH secretion remains obscure. We studied GPR101 signaling pathways and their effects in HEK293 and rat pituitary GH3 cell lines, human tumors and in transgenic mice with elevated somatotrope Gpr101 expression driven by the rat Ghrhr promoter (GhrhrGpr101). We report that Gpr101 causes elevated GH/prolactin secretion in transgenic GhrhrGpr101mice. We also show that GPR101 promotes GH secretion through the activation of not only Gs, but also Gq/11, in a PKA and PKC-dependent manner, respectively. Interestingly, in stark contrast with other Gs-coupled receptors, GPR101 activation did not lead to the proliferation of somatotrope cells. These signatures of GPR101 signaling, notably PKC activation, are also present in human X-LAG pituitary tumors with high GPR101 expression. These results underline a role for GPR101 in the regulation of somatotrope axis function.

Ageing genetic signature of hypersomatotropism.

Acromegaly is a pathological condition that is caused by over-secretion of growth hormone (GH) and develops primarily from a pituitary adenoma. Excess GH exposure over a prolonged period of time leads to a wide range of systemic manifestations and comorbidities. Studying the effect of excess GH on the cellular level could help to understand the underlying causes of acromegaly health complications and comorbidities. In our previous publications, we have shown that excess GH reduces body side population (SP) stem cells and induces signs of premature ageing in an acromegaly zebrafish model. Here, we study acromegaly ageing in greater depth at the level of gene expression. We investigated whether acromegaly induces an ageing genetic signature in different organs. Using the GenAge database, our acromegaly model showed a significant enrichment of ageing genetic datasets in the muscle but not in other organs. Likewise, the hierarchical clustering of wild type (WT), acromegaly and aged RNA data from various organs revealed the similarity of gene expression profiles between the acromegaly and the aged muscles. We therefore identified overlapping differentially expressed genes (DEGs) in different organs between acromegaly and aged zebrafish. Importantly, about half of the muscle, liver and brain acromegaly DEGs overlapped with aged zebrafish DEGs. Interestingly, overlapping was observed in the same way; acromegaly-up DEGs overlapped with aged zebrafish up DEGs, not down DEGs, and vice versa. We then identified the biological functions of overlapping DEGs. Enrichment database analysis and gene ontology showed that most overlapping muscle genes were involved in ageing metabolism, while overlapping liver DEGs were involved in metabolic pathways, response to hypoxia and endoplasmic reticulum stress. Thus, this study provides a full ageing genetic signature of acromegaly at the gene expression level.

GPR101 drives growth hormone hypersecretion and gigantism in mice via constitutive activation of Gs and Gq/11

Growth hormone (GH) is a key modulator of growth and GH over-secretion can lead to gigantism. One form is X-linked acrogigantism (X-LAG), in which infants develop GH-secreting pituitary tumors over-expressing the orphan G-protein coupled receptor, GPR101. The role of GPR101 in GH secretion remains obscure. We studied GPR101 signaling pathways and their effects in HEK293 and rat pituitary GH3 cell lines, human tumors and in transgenic mice with elevated somatotrope Gpr101 expression driven by the rat Ghrhr promoter (GhrhrGpr101). Here, we report that Gpr101 causes elevated GH/prolactin secretion in transgenic GhrhrGpr101 mice but without hyperplasia/tumorigenesis. We show that GPR101 constitutively activates not only Gs, but also Gq/11 and G12/13, which leads to GH secretion but not proliferation. These signatures of GPR101 signaling, notably PKC activation, are also present in human pituitary tumors with high GPR101 expression. These results underline a role for GPR101 in the regulation of somatotrope axis function.

An Acromegaly Disease Zebrafish Model Reveals Decline in Body Stem Cell Number along with Signs of Premature Aging

In our previous publication, it was shown that growth hormone (GH) excess in acromegaly affects the cell integrity of somatic cells through increased DNA damage throughout the body and impaired DNA repair pathways. Acromegaly is a hormone disorder pathological condition that develops as a result of growth hormone over-secretion from the pituitary gland. We produced a zebrafish acromegaly model to gain a better understanding of the excess GH effects at the cellular level. Here we show that the acromegaly zebrafish model progressively reduced the number of stem cells in different organs and increased oxidative stress in stem cells. Importantly, the decline in the stem cells was even more apparent than in aged fish. The controversy and debate over the use of GH as an anti-aging therapy have been going on for several years. In this study, excess GH induced aging signs such as increased senescence-associated (SA)-β-galactosidase staining of abdominal skin and similarity of the pattern of gene expression between aged and acromegaly zebrafish. Thus, this study highlights the role of excess GH in acromegaly stem cells.

Discovery and SAR Studies of Orally Active Somatostatin Receptor Subtype-2 (SSTR2) Agonists for the Treatment of Acromegaly.

Acromegaly is a disease caused by the oversecretion of growth hormone. It is currently treated by intravenous injection with cyclic peptide drugs that activate somatostatin receptor subtype 2 (SSTR2). Here, novel nonpeptidic, small-molecule, and orally active SSTR2 agonists were identified from a hit compound (13). Pharmacophore studies enabled scaffold hopping to obtain a unique 3,4,5-trisubstituted pyridine motif. Further optimization conferred potent SSTR2 agonistic activity and metabolic stability. Several compounds were evaluated and these showed good oral pharmacokinetic profiles in rats, and one representative compound (25) showed highly potent inhibition of growth hormone secretion induced by growth hormone-releasing hormone in rats. Based on these results, 25 was identified as a promising lead for further optimization. A structure-activity relationship (SAR) study and the metabolic stability data for this compound are also described.

Hypoxia and the hypoxia inducible factor 1\u03b1 activate protein kinase A by repressing RII beta subunit transcription

Overactivation of the cAMP signal transduction pathway plays a central role in the pathogenesis of endocrine tumors. Genetic aberrations leading to increased intracellular cAMP or directly affecting PKA subunit expression have been identified in inherited and sporadic endocrine tumors, but are rare indicating the presence of nongenomic pathological PKA activation. In the present study, we examined the impact of hypoxia on PKA activation using human growth hormone (GH)-secreting pituitary tumors as a model of an endocrine disease displaying PKA-CREB overactivation. We show that hypoxia activates PKA and enhances CREB transcriptional activity and subsequently GH oversecretion. This is due to a previously uncharacterized ability of HIF-1α to suppress the transcription of the PKA regulatory subunit 2B (PRKAR2B) by sequestering Sp1 from the PRKAR2B promoter. The present study reveals a novel mechanism through which the transcription factor HIF-1α transduces environmental signals directly onto PKA activity, without affecting intracellular cAMP concentrations. By identifying a point of interaction between the cellular microenvironment and intracellular enzyme activation, neoplastic, and nonneoplastic diseases involving overactivated PKA pathway may be more efficiently targeted.

Chronic adult-onset of growth hormone/IGF-I hypersecretion improves cognitive functions and LTP and promotes neuronal differentiation in adult rats.

Besides their metabolic and endocrine functions, the growth hormone (GH) and its mediated factor, the insulin-like growth factor I (IGF-I), have been implicated in different brain functions, including neurogenesis. Long-lasting elevated GH and IGF-I levels result in non-reversible somatic, endocrine and metabolic morbidities. However, the subcutaneous implantation of the GH-secreting (GH-S) GC cell line in rats leads to the controllable over-secretion of GH and elevated IGF-I levels, allowing the experimental study of their short-term effects on brain functions. Adult rats were implanted with GC cells and checked 10weeks later, when a GH/IGF-I-secreting tumour was already formed. Tumour-bearing rats acquired different operant conditioning tasks faster and better than controls and tumour-resected groups. They also presented better retentions of long-term memories in the passive avoidance test. Experimentally evoked long-term potentiation (LTP) in the hippocampus was also larger and longer lasting in the tumour bearing than in the other groups. Chronic adult-onset of GH/IGF-I hypersecretion caused an acceleration of early progenitors, facilitating a faster neural differentiation, maturation and integration in the dentate gyrus, and increased the complexity of dendritic arbours and spine density of granule neurons. Thus, adult-onset hypersecretion of GH/IGF-I improves neurocognitive functions, long-term memories, experimental LTP and neural differentiation, migration and maturation.

Mutations in GPR101 as a potential cause of X-linked acrogigantism and acromegaly.

X-linked acrogigantism (XLAG) is a recently described early-onset gigantism due to GPR101 duplication that induces growth hormone (GH) oversecretion. GPR101, which belongs to Family A rhodopsin-like family of G protein-coupled receptors, is predominantly expressed in hypothalamus and pituitary, suggesting that GPR101 might be important in regulating diverse functions such as energy balance and reproduction. Most mammalian GPR101s have extremely long third intracellular loops (ICL3); however, zebrafish GPR101 has a much shorter ICL3, but a longer C-terminus. GnRH-(1-5), a GnRH metabolite, can modulate the hypothalamus-pituitary-gonad axis and cancer cell migration via activating GPR101. GPR101 couples to both Gαs and Gαi proteins. GPR101 duplication has a causative role in XLAG, while GPR101 variants, especially c.924G>C (E308D), located at ICL3, are attributed to acromegaly. Some GPR101 mutations that are associated with a small proportion of pituitary tumors without GH oversecretion have also been identified recently. This chapter will summarize studies on GPR101, including its molecular cloning and tissue distribution, physiology, pharmacology, and pathophysiology.

Early Results of Microsurgical Treatment of Acromegaly

Abstract Purpose Acromegaly is an unusual disorder caused by abnormal oversecretion of growth hormone by pituitary adenomas. Transsphenoidal surgery is frequently the first management option. The objective of this article is to establish the effectiveness of a transnasal transsphenoidal approach in the treatment of GH-producing adenomas, and to identify risk factors for disease persistence. Methods We conducted a retrospective review of 81 patients treated for acromegaly with transsphenoidal microsurgery between 2006 and 2010. Results Macroadenomas accounted for 66.7% of the cases, contrast-enhanced MRI revealing cavernous sinus invasion in 28.4% of the patients (23 subjects). Cure was achieved in 72.8% (59 of 82). All microadenomas (27 cases) were managed effectively with surgery whereas cure rates stood at 66.7% for macroadenomas. Monovariate analysis showed that disease persistence was statistically associated with three variables. Odds ratio for remission stood at 1.68 for microadenomas and 0.033 for cavernous sinus invasion (p&lt;0.001). Preoperative GH values were statistically associated with cure during follow up (p&lt;0.05). Multivariate logistic regression analysis showed that only cavernous sinus invasion continued to be significantly associated with disease persistence (OR 3.52, p&lt;0.05). Conclusion The transnasal approach proves effective in the treatment and cure of acromegaly. Cavernous sinus invasion is a major predictor of disease persistence.

Prevalence of neoplasms in patients with acromegaly - the need for a national registry.

Acromegaly is an endocrine disorder caused predominantly by pituitary adenoma leading to autonomic oversecretion of growth hormone and secondary elevation of insulin-like growth factor 1 (IGF-1). Consequently, there are both theoretical and experimental grounds for establishing a correlation between this disorder and the higher incidence of neoplasms. The aim of the study is to evaluate the incidence and types of neoplasms among patients with acromegaly. The study included 67 patients with acromegaly, aged between 24 and 75±18.8 years, 46 women (68.7%) and 21 men (31.3%), BMI: 30.7±5.7 kg/m2, age at diagnosis 49.1±12.5 years, with the medians of GH and IGF-1 levels at diagnosis of 11.3 ng/ml and 663.8 ng/ml, respectively. A retrospective analysis of medical records with particular regard to physical examination, medical history, laboratory and imaging tests was performed. Fifty-one patients (76.1%) suffered from at least one neoplasm, among whom 48 patients (71.6%) had benign proliferations, whereas malignant neoplasms (larynx, endometrial and colon cancers) were found in only three patients (4.5%). Benign neoplasms were found in majority of patients with acromegaly (71.6%) most notably: nodular goiter and colon polyps; malignant lesions were rare (4.5%). Only every fifth patient suffered from no neoplastic proliferations. No correlations between the studied parameters and the incidence of neoplasms were found, most likely due to the small number of patients. This is the reason for proposing the creating of the first national register of incidences of neoplasms among acromegalic patients.

Expression of osteogenesis regulatory genes in the bone tissue of patients with acromegaly and endogenous hypercorticism

Excessive hormone secretion during hypercorticism and acromegaly results in significant disturbances in bone remodeling, decrease in bone quality, and bone fractures following small traumas. However, the mechanisms of the development of such changes are not clear. In the present study, we examined specimens of bone tissue from patients with endogenous hypercorticism (increased cortisol secretion) and acromegaly (increased growth hormone secretion) obtained during transnasal adenomectomy. Our main purpose was to analyze the expression of genes responsible for osteogenesis in the bone tissue specimens from patients with hypercorticism and acromegaly, targeting an assessment of pathogenetic aspects associated with bone complications. The study included 19 specimens of bone tissue from patients with pituitary tumors (samples with acromegaly, Cushing disease, and inactive pituitary adenomas; the latter served as a control group). We revealed 14 genes (ACP5, ALPL, BGLAP, BMP7, CD40, COL1A1, COL1A2, IGF1, IGFBP2, IL6, LEP, LTA, MMP2, WNT10B) which appeared to be the most important and require further detailed study. The present study confirmed the key role of the Wnt-signaling pathway in the osteogenic process. In addition, we present new data on molecular mechanisms of development of skeletal complications in the case of cortisol and growth hormone oversecretion in humans.

Thyroid lesions in patients with acromegaly - case-control study and update to the meta-analysis.

Acromegaly results from oversecretion of growth hormone and subsequently insulin growth factor-1. According to some authors, the disease can cause increased prevalence of nodular goitre and thyroid cancer (TC). However, the number of studies comparing acromegalic patients with control groups is low. We aimed to assess the prevalence of thyroid lesions in patients with acromegaly in comparison to an age- and sex-matched control group and to update the meta-analysis previously performed in our department by the same authors. We searched medical documentation of patients with acromegaly treated in our department between 2003 and 2013. The prevalence of thyroid abnormalities was compared with the group of patients with hormonally inactive adrenal incidentalomas. To perform the meta-analytic part of the paper we also searched ten databases to find relevant papers. Two hundred and five patients with acromegaly and 184 patients with incidentalomas were included. Any thyroid lesions were present in 77.6% of patients with acromegaly vs. 63.0% with incidentalomas (p = 0.002), multinodular goitre - 66.8% vs. 47.8% (p = 0.0002), and TC- 5.4% vs. 2.7% (p = 0.21) respectively. For thyroid lesions the pooled odds ratio (OR) was 3.1 (95% confidence interval [CI] 1.8-5.5), and for TCs the OR was 4.5 (95% CI 1.9-10.3). According to our results thyroid lesions were significantly more common in patients with acromegaly; in case of TC the difference was not significant. The updated meta-analysis showed significantly increased prevalence of both disorders. In conclusion, systematic thyroid examination should be an important part of follow-up in case of acromegalic patients. (Endokrynol Pol 2017; 68 (1): 2-6).

The surgical treatment of acromegaly.

Surgical extraction of as much tumour mass as possible is considered the first step of treatment in acromegaly in many centers. In this article the potential benefits, disadvantages and limitations of operative acromegaly treatment are reviewed. Pertinent literature was selected to provide a review covering current indications, techniques and results of operations for acromegaly. The rapid reduction of tumour volume is an asset of surgery. To date, in almost all patients, minimally invasive, transsphenoidal microscopic or endoscopic approaches are employed. Whether a curative approach is feasible or a debulking procedure is planned, can be anticipated on the basis of preoperative magnetic resonance imaging. The radicality of adenoma resection essentially depends on localization, size and invasive character of the tumour. The normalization rates of growth hormone and IGF-1 secretion, respectively, depend on tumour-related factors such as size, extension, the presence or absence of invasion and the magnitude of IGF-1 and growth hormone oversecretion. However, also surgeon-related factors such as experience and patient load of the centers have been shown to strongly affect surgical results and the rate of complications. As compared to most medical treatments, surgery is relatively cheap since the costs occur only once and not repeatedly. There are several new technical gadgets which aid in the surgical procedure: navigation and variants of intraoperative imaging. For the mentioned reasons, current algorithms of acromegaly management suggest an initial operation, unless the patients are unfit for surgery, refuse an operation or only an unsatisfactory resection is anticipated. A few suggestions are made when a re-operation could be considered.

Risk of malignant neoplasms in acromegaly: a case\u2013control study

PurposeAcromegaly is a chronic disease resulting from pathological oversecretion of growth hormone and subsequently insulin growth factor-1. Several complications of the disease have been reported, including cardiovascular diseases, respiratory disorders but also increased risk of benign and malignant neoplasms. The aim of the study was to evaluate the risk of malignant neoplasms in the patients with acromegaly in comparison with the control group.Patients and methodsMedical documentation of acromegalic patients treated in one medical center between 2005 and 2016 has been analyzed. Results were compared with sex- and age-matched group of subjects with prolactinomas and hormonally inactive pituitary lesions hospitalized in the same department.ResultsTwo hundred patients with acromegaly were included. Control group was composed of 145 patients. Any malignant neoplasm in anamnesis was present in 27 (13.5 %) patients with acromegaly and six (4.1 %) subjects from control group (p = 0.003). Thyroid cancer was present in 14 (7.0 %) patients with acromegaly and two (1.4 %) in control group (p = 0.02). Breast cancer was present in seven women (5.4 % of women) in acromegaly group but none of subjects in control group (p = 0.02). Colon cancer—4 (2.0 %) patients in acromegaly group and 0 in control group (p = 0.14).ConclusionsMalignant neoplasms are significantly more common in patients with acromegaly. Particularly, risk of thyroid cancer was increased over fivefold. Systematic screening for neoplastic diseases should be important part of follow-up in these patients. Further case–control studies are strongly indicated to evaluate which neoplasms are more common in acromegalic patients and what is the exact risk of malignancy.

Neurosurgical Treatment of Acromegaly.

Surgical removal of as much tumor mass as possible is usually considered the first step of treatment in acromegaly, unless the patients are unfit for surgery or refuse an operation. To date, in almost all cases, minimally invasive, transsphenoidal microscopic or endoscopic approaches are used. Whether a curative approach is feasible or a debulking procedure is planned, can be anticipated on the basis of preoperative magnetic resonance imaging. It mostly depends on localization, size, and the invasive character of the lesion. The surgical results depend on tumor-related factors such as size, extension, the presence or absence of invasion, and the magnitude of IGF-1 and growth hormone oversecretion, respectively. However, even surgeon-related factors such as experience and case load of the centers have been shown to strongly affect surgical results and complication rates. A reoperation can be considered at various stages in the treatment algorithm. There are several new technical gadgets which might aid in the surgical procedure: navigation, the Doppler probe, and variants of intraoperative imaging.

Acromegaly and Sleep Disordered Breathing

Acromegaly is the result of oversecretion of growth hormone and IGF-1 and the disease can affect several organ systems. Sleep Disordered Breathing (SDB) is a frequent disease in acromegaly patients. The mechanism of SDB is somewhat different in acromegaly patients than SDB in normal population. Although central apneas can be seen, obstructive apneas according to structural changes complicate the course of the disease. Treatment of SDB is as important as the treatment of acromegaly. In this review, we searched the medical literature and summarized the etiology, pathogenesis, mechanism of SDB development and treatment of SDB in acromegaly patients.