Expression of ghrelin and ghrelin functional receptor GHSR1a in human pituitary adenomas.

INTRODUCTION    Pituitary adenomas are heterogenous lesions commonly observed in the central nervous system. Signal transduction of ghrelin, an endogenous ligand specific for growth hormone secretagogue receptor (GHSR), has been reported to be involved in the development of endocrine tumors. However, there are limited data concerning the role of ghrelin and its functional receptor in pituitary adenomas. OBJECTIVES    The aim of the study was to establish the expression pattern of GHRL and its functional receptor GHSR1a in human pituitary adenomas. PATIENTS AND METHODS    Tissue specimens, including somatotropinomas (n = 20), prolactinomas (n = 5), and nonfunctioning adenomas (n = 52) were obtained from 77 patients. Thirteen normal pituitaries served as controls. The expression pattern of GHRL and GHSR1a mRNAs was established using reverse transcription followed by quantitative polymerase chain reaction. RESULTS    Ghrelin mRNA was detected in 92.2% of the samples including controls, while GHSR1a transcripts were detected in 54.4% of the cases. Significant differences were found among subgroups in the GHSR1a expression (P <0.0001) but not in that of GHRL (P = 0.7). The relative GHSR1a expression level was significantly lower for nonfunctioning tumors than for the control group or somatotropinomas. Controls revealed a strong positive correlation between the expression of both genes (r = 0.8; P <0.0001), unlike adenomas, which showed a weak negative correlation (r = -0.3; P >0.05). The maximum tumor diameter for nonfunctioning adenomas was higher than that for somatotropinomas (mean [SD], 31.4 [76] mm vs 24.8 [10.9] mm; P = 0.01). Neither the GHRL nor GHSR1a expression showed a significant correlation with tumor size in the subgroups. CONCLUSIONS    The presence of GHRL and GHSR1a in the neural system indicates their effect on pituitary function regulation and suggests their possible role in adenoma pathogenesis.

Pituitary Microsomal Autoantibodies in Patients with Childhood-Onset Combined Pituitary Hormone Deficiency: an Antigen Identification Attempt.

The role of autoimmunization in the pathogenesis of pituitary disorders is poorly understood. The presence of pituitary autoantibodies (APA) has been detected in various pituitary disorders. Their role, however, remains elusive. Childhood-onset combined pituitary hormone deficiency (CPHD) may be caused by environmental or genetic factors. In some of patients, causes of the disease remain unclear and contributions of autoimmune processes have been postulated. The aim of this study was to identify the microsomes-derived pituitary antigens (MPA) as potential immunogenic autoantigens in patients with hypopituitarism, therefore 62 CPHD patients, 100 healthy controls and five autoimmune polyglandular syndrome type II (APS II) patients were included in the study. The clinical evaluation included hormonal tests and magnetic resonance imaging of the pituitary. The sources of MPA were pituitary glands taken from autopsies. Isolated MPA were then separated on SDS-PAGE gel and incubated with sera obtained from patients and controls. Microsomal APA were detected using Western blot and radioimmunological method. In all CPHD and APS II patients and in 9 % individuals from control group marked immunoreactivity was detected against MPA. Antibodies showed high affinity to 67, 60, 50 and 36 kDa MPAs. Since the identified autoantigens were of unknown nature, an in silico exploration of UniProt database was applied and indicated their possible relationship with chaperones, golgins and already known autoantigens like GAD67. Reactivity against MPA indicates that these proteins certainly play a role in the processes undergoing within pituitary of CPHD patients. The identification and further detailed studies on their role in the pathogenesis of CPHD should be continued.

Evaluation of survivin splice variants in pituitary tumors.

PURPOSE: Survivin is an apoptosis inhibitor, expressed in almost all types of human malignancies, but rarely in differentiated normal tissues. Recently, survivin gene splice variants with different anti-apoptotic activities have been reported. The current study was undertaken to examine the expression of survivin and its splice variants ∆Ex3 and 2ß in pituitary tumors, and to correlate the amount of particular transcripts with clinical staging in pituitary adenomas. Quantitative detection of survivin and its splice variants ∆Ex3 and 2ß transcripts in non-cancerous pituitary tissues (n = 12) and different types of pituitary tumor (n = 50). METHODS: Samples were collected from 50 pituitary tumors including 26 non-functional tumors, 21 GH-secreting tumors, 2 PRL-secreting tumors and 1 ACTH-secreting tumor. 12 normal pituitary glands received after autopsy served as a control of the study. 29 thyroid cancers tissues were used as a positive control. The RT-qPCR with TaqMan hydrolysis probes were used to determine the expression of analyzed splice variants of survivin. RESULTS: The obtained data showed that both survivin and its splice variants were expressed in different types of pituitary adenoma as well as in normal pituitary tissue. However, the level of its expression was similar in all studied cases. Patient age negatively correlated with tumor invasiveness. Moreover, our study showed a tendency for negative correlation between patient age and tumor diameter. CONCLUSIONS: No significant differences between survivin and its splice variants ∆Ex3 and 2ß expression in pituitary tumors and in normal pituitary glands as well as in invasive and in non-invasive tumors were found, suggesting that survivin does not play a significant role in pituitary tumorigenesis.

Acromegaly--a novel view of the patient. Polish proposals for diagnostic and therapeutic procedures in the light of recent reports.

is usually delayed and is often associated with the development of various complications causing premature mortality. In patients with hypertension, heart failure, diabetes, and arthropathy that is non-specific for age, attention should be paid to the occurrence of somatic signs of acromegaly. As a screening test, insulin-like growth factor-1 (IGF-1) concentration should be assessed. Further diagnostic and treatment procedures are possible in specialised centres. The first-line therapy is selective transsphenoidal adenomectomy. Patients with a good prognosis related to a surgical removal of the pituitary tumour should be referred only to centres experienced in performing this type of procedure, after pharmacological preparation. Other patients, and those who have not recovered after surgical treatment, should be subjected to long-term pharmacotherapy with long-acting somatostatin analogues. In each case, the complications of acromegaly should be followed-up long-term and actively treated. This proposed new recommendation should be helpful for the management of patients with acromegaly.

Struma ovarii maligna.

INTRODUCTION: Malignant struma ovarii is a rare ovarian neoplasm composed predominantly of mature thyroid tissue. CASE REPORT: A right ovarian tumor was discovered at ultrasound examination in a 20-year-old woman. Complete right ovariectomy was done - histopathological examination revealed papillary thyroid carcinoma arising in struma ovarii (malignant struma ovarii). Patient underwent subsequent total thyroidectomy - the thyroid was found to be without any pathological lesions. After operations the patient received ablative radioiodine treatment (200 mCi 131I). An 131I posttherapeutic whole-body radioiodine scintigraphy was performed and showed uptake in bone metastases. L-thyroxine TSH suppresive doses followed radioiodine ablation and thyroglobulin level is monitored. Next doses of radioiodine has been scheduled. DISCUSSION: Authors suggest that the management of malignant struma ovarii should be the same as differentiated thyroid cancer, so after surgical excision of ovarian neoplasm, we recommend thyroidectomy, radiotherapy with 131I and levothyroxine suppressive therapy. Long-term follow-up for the detection of metastases or tumor recurrence by serial serum thyroglobulin measurements and 131I scan may be required in patients with this rare tumor.

Patients with chronic hepatitis type C and interferon-alpha-induced hyperthyroidism in two-years clinical follow-up.

OBJECTIVES: Interferon-α (IFN-α) is a gold standard in the therapy of viral chronic hepatitis type C (CHC). However, such treatment might lead to thyroid dysfunction. Patients usually present hypothyroidism, but rarely also hyperthyroidism may develop. The aim of the study is to present two-year clinical follow-up of patients with CHC and IFN-α-induced hyperthyroidism (IIH), with special regard to the methods and efficacy of the therapy. METHODS: A group of 106 patients with CHC and IIH were analyzed. Subjects were divided into two groups according to etiology: group 1, with Graves' disease (GD) and group 2, with Hashitoxicosis (HT). The diagnosis of GD and HT was based on: clinical signs of hyperthyroidism, hormonal profile (TSH, fT4, fT3), level of thyroid autoantibodies (Tg-Abs, TPO-Abs, TSHRAbs). Treatment of hyperthyroidism was monitored by repeated clinical assessment and laboratory tests. RESULST: 28 patients (26 with GD of which 5 exhibited mild orbitopathy and 2 with HT) were treated with radioiodine [the average dose of was 17 mCi [668 MBq]. In adition 78 out of 80 patients with HT mostly ß-blocker therapy was successful (transient hyperthyroidism). At the end of the observation period, in group 1 remission was achieved in 17 (65.4%) cases, 6 (23.1%) patients showed hypothyroidism and 3 (11.5%) presented recurrence of hyperthyroidism. CONCLUSIONS: Most patients with IIH present Hashitoxicosis, while a minority of them develop Graves' disease. In a majority of patients with HT spontaneous remission of disease occurs. In patients with long-term hyperthyroidism, radioiodine therapy is an effective and well-tolerated.

The influence of radioiodine therapy on ocular changes and their relation to urine cotinine level in patients with Graves' Ophthalmopathy.

OBJECTIVES: Radioiodine therapy (RIT) is frequently used as the definitive treatment in patients with Graves' hyperthyroidism when remission is not achieved with anti-thyroid drugs (ATDs). In this observational study, we intended to examine whether the use of high doses of radioiodine (RAI) [22 mCi (814 MBq)] with prophylaxis of oral glucocorticoids (oGCS) does not exacerbate Graves ophthalmopathy (GO) in smokers and non-smokers, especially regards to the urine level cotinine and ocular changes before and after RIT. PATIENTS AND METHODS: The studied group consisted of 26 smokers, aged 28-61 years and 25 non-smoker patients, aged 21-54 years, respectively. The patients were enrolled to RAI after one-year of ineffective ATDs treatment. Criterion for inclusion in the study were patients with mild GO with hyperthyroidism at diagnosis based on the severity (NOSPECTS) and activity (CAS) scale. All the patients were subjected to RIT with oGCS prophylaxis and evaluated prospectively during a one-year follow-up. The ophthalmological examination was performed at various stages of RIT: initial pre-radioiodine administration, at the time of treatment 6, and 12 months after RAI. The present study is unique, because the urine cotinine measurement was employed to detect nicotine exposure, also in regard to smoking intensity. RESULTS: In smokers, the values of serum TPO-Abs were statistically significant in the second and six month (p<0.05) and in the second and after one year (p<0.005). The TSHR-Abs concentration was significantly higher in smokers (p<0.05), rising from 22.9±1.2 IU/L before therapy to 29.6±5.3 IU/L - 2 months, 32.6±8.6 IU/L - 6 months, and slightly decreased 28.9±10.6 IU/L - 12 months. These observed changes were statistically different between groups at baseline (p<0.05) and after one-year of follow-up (p<0.005). Mean urine cotinine were considerably higher in smokers comparing to non smokers in each point of observation [903.4±770.0 and 5.2±1.7 ng/mL at baseline (p<0.001), 412.8±277.3 and 3.0±0.6 ng/mL after 2 months (p<0.001), 452.0±245 and 6.6±3.6 after 6 months (p<0.001), 379.4±236.8 and 1.0±1.2 after one year (p<0.001)]. The CAS values in the smoking group before RIT increased statistically from 2.8±0.2 points at baseline to 4.3±0.3 after 6 months, and 4.0±0.5 (12 months), while in the non-smoking patients it was 1.4±0.2, 2.8±0.3 and 2.2±0.2, respectively. The level of urine cotinine correlated positively with CAS and TSHR-Ab in the smoking group (r=0.41; p<0.05) at baseline and during follow-up (2 months: r=0.46; p<0.001, 6 months: r=0.47, p<0.005; 12 months: r=0.46; p<0.005). In the NOSPECS classification, the symptoms changed from mild to moderate, mostly in smoking patients. CONCLUSIONS: 1) ablative RIT dose with prophylactic oral prednisone is a safe treatment in both smokers and non-smokers with mild GO; 2) The post hoc analysis showed that urinary level of cotinine can be very helpful in the assessment of exacerbation of ophthalmological clinical symptoms before and after RIT particularly in smokers.

Differences in the psychological and hormonal presentation of lean and obese patients with polycystic ovary syndrome.

BACKGROUND: Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders found in women of reproductive age. Differences in hormonal and metabolic profiles are observed in groups of patients with normal and elevated BMI. Cause of disturbances observed in the two groups of patients with PCOS is analyzed. The aim of the study is to assess whether psychological parameters of lean and obese patients with PCOS are comparably significantly different and whether there is a correlation between these characteristics and the concentration of various hormones. PARTICIPANTS AND PROCEDURES: The study consisted of 20 patients with diagnosed polycystic ovary syndrome and 20 healthy women of similar age. Both groups were stratified according to BMI. Specific psychological parameters and hormones were estimated in all patients. RESULTS: In our study, we found that patients with BMI <25 represented personality traits associated with lower resistance to stress. We also observed significantly higher ACTH levels in the same group as compared to patients with BMI >25. A correlation between plasma ghrelin and the severity of anxiety experienced by test subjects was also observed. CONCLUSION: The type of personality and emotional disorders in lean PCOS patients may lead to the activation of the hypothalamic-pituitary-adrenal (HPA) axis and disturbences in hypothalamic-pituitary-ovary (HPO) axis. The results suggest participation of primary hypothalamic dysfunction in the pathogenesis of PCOS in patients with specific fenotype. Ghrelin is a hormone that may affect the symptoms of PCOS in lean patients. Psychological therapy should be considered as a permanent element in the therapeutic plan provided to PCOS patients.

Assessment of real-world usage of lanreotide AUTOGEL 120 in Polish acromegalic patients - results from the prospective 12-month phase of Lanro-Study.

AIM OF THE STUDY: To assess resource utilization and costs of treatment with lanreotide AUTOGEL 120 mg (ATG120) administered as part of routine acromegaly care in Poland. MATERIAL AND METHODS: A multicentre, non-interventional, observational study on resource utilization in Polish acromegalic patients treated with ATG120 at 4 weeks or extended (> 4 weeks) dosing interval. The study recruited adult acromegalic patients treated medically for ≥ 1 year including at least 3 injections of ATG120. Data on dosing interval, aspects of administration, and resource utilization were collected prospectively during 12 months. Costs were calculated in PLN from the public health-care payer perspective for the year 2013. RESULTS: 139 patients were included in the analysis. Changes in dosing regimen were reported in 14 (9.4%) patients. Combined treatment was used in 11 (8%) patients. Seventy patients (50%) received ATG120 at an extended dosing interval; the mean number of days between injections was 35.56 (SD 8.4). ATG120 was predominantly administered in an out-patient setting (77%), by health-care professionals (94%). Mean time needed for preparation and administration was 4.33 and 1.58 min, respectively, mean product wastage - 0.13 mg. Patients were predominantly treated in an out-patient setting with 7.06 physician visits/patient/year. The most common control examinations were magnetic resonance imaging of brain and brain stem (1.36/patient/year), ultrasound of the neck (1.35/patient/year), GH (1.69/patient/year), glycaemia (1.12/patient/year), IGF-1 (0.84/patient/year), pituitary-thyroid axis hormone levels assessment (TSH-0.58/patient/year, T4-0.78/patient/year). There were 0.43 hospitalizations/patient/year. For direct medical costs estimated at PLN 50 692/patient/year the main item was the costs of ATG120 (PLN 4103.87/patient/month; 97%). The mean medical cost, excluding pharmacotherapy, was PLN 1445/patient/year (out-patient care - 49%, hospitalization - 23%, diagnostics/laboratory tests - 28%). CONCLUSIONS: These results represent the current use of ATG120 in the population of Polish acromegalic patients in a realistic clinical setting. Findings that 50% of patients could be treated with dose intervals of longer than 28 days support the potential of ATG120 to reduce the treatment burden.

Amiodarone-induced thyrotoxicosis in a case of Eisenmenger's syndrome.

Eisenmenger's syndrome is a condition due to any congenital heart defect with an intracardiac left-to-right communication that leads to pulmonary hypertension with reversed right-to-left blood flow and secondary cyanosis. The main complications of Eisenmenger's syndrome are heart failure and arrhythmias. Amiodarone, the drug of choice for arrhythmia treatment in such patients, can cause a number of complications, including amiodarone induced thyrotoxicosis (AIT). Hereby, we present a 41-year-old patient with Eisenmenger's syndrome who developed AIT and was successfully treated with radioactive iodine therapy. The patient had an accompanying heart failure and had been treated with amiodarone due to chronic atrial fibrillation. Twenty months later he developed an AIT for which was treated with 814 MBq (22 mCi) radioactive iodine. Since 7 weeks later only a slight decline in thyroid hormones was observed, the patient was received a transient treatment with methimazole, which had to be withdrawn soon due to severe leucopenia. Because of the need to maintain amiodarone, a second ablative radioactive iodine dose was administered leading to complete clinical remission. In conclusion, this case demonstrates that even though amiodarone reduces iodine uptake to a very low level, the therapy with radioactive iodine can be still effective if it is given in a repeated dose to patients who require continuation of amiodarone.

Survivin--prognostic tumor biomarker in human neoplasms--review.

Accurate diagnosis and proper monitoring of cancer patients remain important obstacles for successful cancer treatment. The search for cancer biomarkers is carried out in order to quickly identify tumor cells and predict treatment response, ultimately leading to a favorable therapeutic outcome. One such prognostic marker seems to be survivin. Many studies have shown that survivin is strongly expressed in a vast majority of cancers. Its overexpression was demonstrated in breast and lung cancer prostate, gastric, colon, bladder and esophageal carcinomas, osteosarcomas, and lymphomas. In many of those tumors, high activity of the surviving gene was associated with a poor prognosis and worse survival rates. Moreover survivin expression was correlated with resistance to chemotherapy and radiotherapy-induced apoptosis. Since survivin may be identified as an independent prognostic factor and inhibitor of apoptosis, it may prove to be a useful therapeutic target in cancer therapy

A rare case of Interferon-alpha-Induced Hyperthyroidism in patients with a chronic hepatitis C with granulocytopenia and transaminasemia treated successfully with radioiodine.

BACKGROUND: Conventional management of Interferon-α-Induced Hyperthyroidism (IIH) with radioactive iodine (RAI) may be used when treatment with beta blockers or antithyroid drugs (ATD), proves ineffective or is contraindicated. CASE PRESENTATION: We present a 38-year-old woman who has been treated with combined pegylated interferon alpha (INF-α) and Ribavirin for chronic hepatitis C. Destructive thyrotoxicosis appeared after four months of continuous IFN-α therapy and a beta blocker was prescribed. Initially, the patient presented normal TSH 2.4 µIU/mL, however during therapy with INF-α, TSH diminished to 0.05 and thyroid hormones were elevated: fT4 23.1 pmol/L, fT3 7.2 pmol/L. Ultrasound examination showed completely irregular and greatly decreased echogenicity of the thyroid gland. The radioiodine uptake (RAIU) was deeply decreased to 2 and 3% at 5 h and 24 h, respectively. The thyroid scintiscan showed lack of isotope accumulation. Hypothyroidism developed and L-thyroxine was prescribed. The following year, hyperthyroidism reoccurred with TSH 0.08 µIU/mL, fT4 26.4 pmol/L, fT3 8.2 pmol/L, positive TSHR-Abs 6.2 (normal <2 IU/L) and mild Graves' Ophthalmopathy (GO). RAIU values were 23% at 5 h and 46% at 24 h. Thyroid scintiscan showed diffuse goiter. At this point beta blocker was introduced and ATD was started. After three months of therapy an increased level of aminotransferases and granulocytopaenia were observed. Hence, the patient received RAI and glucocorticosteroid, while INF-α therapy was continued. After approximately 4 months, hypothyroidism reappeared with insignificantly raised TSH level. One year later the patient was euthyroid and required no further treatment. CONCLUSIONS: Our report suggests that: 1. Radioiodine therapy might be an effective and safe method of treatment in cases of IIH with mild GO. 2. IFN-α therapy need not be discontinued in patients with IIH.

Combined octreotide and peptide receptor radionuclide therapy ((90)Y-DOTA-TATE) in case of malignant insulinoma.

BACKGROUND: Insulinomas are the most common functioning neuroendocrine tumours of the pancreas. Hypoglycemia due to excessive production of insulin is a main feature of this disease. Usually these neoplasms are benign and single with surgical excision as a treatment of choice. About 10% are malignant with tendency to form metastases especially to the liver then therapy requires various medical technics. CASE REPORT: 43 years old female with reccurent syncopies in course of hypoglycemia was admitted to the hospital to be diagnosed. Having suspected pathology within the pancreas the abdominal MRI was performed. It showed presence of numerous metastatic changes in the liver with no any other deviations in the abdomen including pancreas. Subsequent 18FDG PET-CT revealed metastases to the regional lymph nodes and the liver and suggested the presence of a primary lesion in the tail of the pancreas which was confirmed in EUS. Surgical excision of the tail of the pancreas was done. Pathological result: pancreatic neuroendocrine well differetiated cancer. Due to the recurrence of hypoglycemia patient was admitted to Department of Endocrinology where somatostatin analogue scintigraphy showed the presence of tracer accumulation foci in the liver. Combined long-acting somatostatin analogue (octreotide) and peptide radionuclide receptor ((90)Y-DOTA-TATE) therapy were introduced. Stable blood glucose levels with no tendency to hypoglycemia and partial regression (PR) of liver lesions according to RECIST citeria were observed in course of the treatment.

Delayed diagnosis of primary hyperparathyroidism in a patient with osteoclastoma.

Primary hyperparathyroidism (HPTo) nowadays is most often recognized incidentally in the asymptomatic period as a result of biochemical screening or evaluation of low bone mass. Classical manifestations of the disease are present in about 15-20% of patients. We present the case of a 28-year-old male patient who had been treated for two years for osteoclastoma of the proximal tibia, first by intralesional curettage with cement filling followed by bone grafting, and finally with a reconstructive arthroplasty of the knee joint. The patient had been consulted in different medical centers by at least 14 doctors representing 9 different specialties, but the correct diagnosis of HPTo had not been made, although classic manifestations of the disease had been present for 5-6 years. This suggests that a diagnosis of HPTo is difficult nowadays. Therefore, determination of serum calcium concentration and other markers of calcium and phosphate metabolism should be obligatory in patients with bone lesions.

Transverse testicular ectopia with abnormal karyotype - a case report.

OBJECTIVES: Growth disturbances and developmental malformations of external genitalia, such as hypospadias, bifid scrotum and micropenis, coexisting with non-palpable testes, may develop as a result of primary endocrinological dysfunctions as well as an effect secondary to chromosomal aberrations. Therefore, patients with these symptoms require specific diagnostic and therapeutic approaches. DESIGN AND METHODS: We present an example of TTE as a presentation of karyotype abnormalities. Clinical presentation - 9.5 year old boy presented with hypospadias, bilateral cryptorchidism and right inguinal hernia and short stature. RESULTS: Endocrine test showed low testosterone levels with adequate gonadal response. Laparoscopy was performed and revealed the presence of TTE. CONCLUSIONS: The presence of mosaic karyotype with abnormal Y chromosome does not exclude a possibility of testis migration disorders, including TTE, caused by other (possibly genetic) factors. Laparoscopy is a technique of choice for diagnosis and treatment in cases of cryptorchidism.

Pregnancy in a patient with adrenocortical carcinoma during treatment with Mitotane - a case report.

We present the case of a female patient with virilising adrenocortical carcinoma treated surgically who conceived during adjuvant treatment with mitotane. We discuss the frequently erroneous routine treatment with oral hormonal contraception without thorough differential diagnosis in female patients with oligo-/amenorrhea and subsequent delay in the proper diagnosis of adrenocortical carcinoma.

Pituitary abscess: a case report.

OBJECTIVES: Pituitary abscess is rare disease and the correct diagnosis is difficult because there are non-specific symptoms and it is often radiologically indistinguishable from other pituitary lesions. CASE PRESENTATION: We present one case of pituitary abscess that constitute 0.15% of all pituitary adenomas operated in our department in the 20 years. A 49-year-old woman presented with a history of 10 months bifrontal headache. The MRI showed cystic intra and suprasellar mass with ring enhancement after contrast injection. During transsphenoidal surgery, copious yellowish pus was found. Antibiotic therapy was performed. Histological study of the cyst wall confirmed the diagnosis of pituitary abscess. CONCLUSION: Pituitary abscess should be considered in the differential diagnosis of all other cyst mass in patients with diabetes insipidus.

Difficulties in diagnosis and treatment of acromegaly in a patient with a McCune-Albright syndrome. A case report and a review of literature.

We describe a female patient aged 43, who at the age of five was diagnosed with polyostotic fibrous dysplasia (FD). The patient was intermittently treated in our department since the age 33, for approximately 10 years, with intravenous bisphosphonates. At the age of 42 acromegaly was diagnosed incidentally, since clinical manifestations were poor, and, if present earlier, they had been related to FD. Only retrospectively, having biochemical confirmation of GH excess, we could relate them to acromegaly. Because of the involvement of the base of the skull there was no possibility of transphenoidal surgery. Long-acting somatostatin analogues were started, but no response was observed, with IGF-1 and GH being even higher during than before treatment. After the 37-year-history of FD, the occurrence of additional endocrine disorder enabled to make diagnosis of McCune-Albright syndrome (MAS) even in the absence of two out of three classical manifestations such as café-au-lait skin pigmentation and peripheral precocious puberty in the past medical history.

Coexpression of survivin and PCNA in pituitary tumors and normal pituitary.

OBJECTIVES: The survivin is the protein involved in regulation of basic and cycle-specific functions of cells both in normal and cancer tissue. Recent studies present survivin as a factor having the leading role in the regulation of apoptosis and mitosis as well as a target of anticancer therapy. The employing of survivin in this therapy is based on its high expression level in most human cancers, as well as its association with the disease's progression. The aim of our study was to evaluate the expression and localization of survivin's gene product on the protein level in different types of pituitary tumors and normal pituitary. The coexpression of survivin and proliferating cell nuclear antigen - PCNA in pituitary was also examined. DESIGN AND METHODS: The study was conducted on the postoperative pituitary tumors tissue taken during standard neurosurgical removal of tumor from 43 patients. The group of patients consists of 23 women and 20 men, aged from 27 to 71 years. As a control of the study three normal pituitary tissues obtained at the autopsy were used. Evaluation of survivin and PCNA expression was performed using immunohistochemical staining. RESULTS: The study demonstrated the presence of survivin in all analyzed by us pituitary tumors. Survivin was present also in normal pituitary tissue. The protein was localized mainly in cell's nuclei, however the less intense immunostaining was observed also in the cytoplasm of pituitary tumors cells. Furthermore survivin was found in normal pituitary, but the positive immunostaining was limited to a single cells. The analysis of pituitary tumor cells proliferation index based on PCNA reactivity showed that survivin is coexpressed with PCNA, especially in invasive tumors. CONCLUSIONS: The study documented the presence of survivin in different types of pituitary tumors as well as in normal pituitary. Additionally the coexpression of survivin and PCNA in tumor cells was shown. The expression of survivin in both normal and cancer pituitary cells suggests that it may play an important role in regulation of the gland's proliferation.

The occurrence of thyroid focal lesions and a need for fine needle aspiration biopsy in patients with acromegaly due to an increased risk of thyroid cancer.

OBJECTIVE: The high prevalence of goiter in acromegalic patients is well known. Several studies revealed increased frequency of thyroid carcinoma in these patients. The aim of the study was to evaluate the incidence of thyroid lesions, including thyroid cancer in acromegalic patients and to estimate possible factors influencing their occurrence, especially high IGF-1 level. MATERIALS AND METHODS: 86 consecutive patients with acromegaly were retrospectively analyzed. 45 patients had been previously treated for acromegaly and 41 were newly diagnosed. In all subjects hGH, IGF-1, TSH, FT4 levels were determined. Thyroid gland was evaluated in ultrasound examination. Fine needle aspiration biopsy (FNAB) was performed in every solid or mixed thyroid nodule. RESULTS: Thyroid morphology abnormalities were found in 75 patients (87.2%). 10 patients (11.6%) had diffuse goiter and 65 patients (75.6%) had nodular goiter. There were 5 cases of thyroid carcinoma (5.8%): 3 papillary carcinomas and two follicular variants of papillary cancer. Out of five cancers three were multifocal, one infiltrated thyroid capsule and one was diagnosed at the stage of metastases to four lymph nodes. CONCLUSIONS: Our study confirmed common co-existence of acromegaly and thyroid lesions. Furthermore, it revealed considerably high occurrence of thyroid carcinoma in these patients. In view of this correlation, the potential role of IGF-1 in pathogenesis of benign and malignant thyroid neoplasms should be considered. Due to high frequency of thyroid cancer in acromegalic patients, we suggest to perform fine needle aspiration biopsy in each case of thyroid nodule.