[Show abstract][Hide abstract] ABSTRACT: The purpose of the present clinical case is to remind clinicians that craniopharyngiomas, which are benign neoplasms with a high incidence of local recurrences, may also present ectopic recurrences which may at first go unsuspected. These tumors most commonly arise in the suprasellar region and despite their benign histology, they may infiltrate the surrounding neurovascular structures making total removal challenging. Ectopic recurrences of craniopharyngiomas are very rare. We describe an adult patient with ectopic recurrence of craniopharyngioma, emphasizing unique features of the case presentation and its physiopathological aspects. A 49-year-old male presented with headache and visual field defect and was diagnosed with a suprasellar tumor. He was submitted to neurosurgery and histological examination revealed an adamantinomatous craniopharyngioma. Postoperative magnetic resonance imaging (MRI) showed complete tumor resection. The patient remained asymptomatic with no imaging signs of local recurrence during follow up. Five years after surgery, the patient noticed a rapidly growing lump at the surgical incision site. He reported a mild to moderate local trauma 4 months before. A MRI showed a subgaleal cystic tumor arising in the pathway of the craniotomy. Surgical resection of that cystic lesion was performed and histological examination revealed an adamantinomatous craniopharyngioma. One year later no recurrences have been detected. The case reported has two particular features: the local trauma as a potential trigger for tumor progression and the rapidly growing pattern of the ectopic recurrent tumor. We emphasize that although ectopic recurrences of craniopharyngiomas are rare, they may occur away from the primary tumor and quite late in the follow up of the patient.
[Show abstract][Hide abstract] ABSTRACT: The syndrome of dyskinesia associated with hyperglycemia and basal ganglia hyperintensity on T1 - weighted MR images is rare and most often affects elderly patients with type 2 diabetes. We report a case of a 79 year-old female patient who presented to the ED with a 12 h history of a left sided hemichoreoathetosis. Laboratory results revealed pronounced nonketotic hyperglycemia [27 mmol/L (486 mg/dL); HbA1c 140 mmol/mol (15 %)] and brain MRI showed bilateral T1 hyperintensity in the basal ganglia, more noticeable on the right side. One week before she had been admitted with a diagnosis of transient ischemic attack consisting in left hemiparesthesia, also with nonketotic hyperglycemia [38.9 mmol/L (700 mg/dL)] and was discharged home with partial correction of her metabolic disturbance. The movement disorder did not improve with adequate glycemic control so haloperidol was started. Six weeks later she was seen on an outpatient basis. She still had minimal residual involuntary movements of the left arm and leg. Laboratory exams revealed a well controlled diabetes mellitus [glycemia 6.0 mmol/L (109 mg/dL), HbA1c 57 mmol/mol (7.4 %)]. In conclusion, the syndrome of dyskinesia associated to hyperglycemia and hyperintensity in the basal ganglia on T1 - weighted MR images is a rare, intriguing and yet incompletely understood complication of diabetes mellitus. The increasing number of reported cases may help to better understand its peculiarities such as the existence of a clear clinical radiological dissociation and to unveil pathophysiological aspects. We suggest the possibility that the metabolic disturbances unmask a previous established asymptomatic striatum vasculopathy.
[Show abstract][Hide abstract] ABSTRACT: It has been reported in some series that gsp+ somatotropinomas are more sensitive to somatostatin analogues (SA) and dopamine's actions which may be related to their somatostatin receptor (SSTR) and dopamine receptor (DR) profile. No previous studies have been undertaken to evaluate the SSTR and DR profile related with the gsp status in somatotropinomas.
To determine if (1) gsp status is correlated with response to octreotide LAR (LAR) and tumor expression patterns of SSTR1-5 and DR1-5 and (2) cAMP level can directly modulate SSTR and DR mRNA levels.
Response to SA was evaluated by GH and IGF-I percent reduction after 3 and 6 months of treatment with LAR. Conventional PCR and sequencing were used to identify gsp+ tumors. Quantitative real-time PCR was used to determine SSTR and DR tumor expression. Primary pituitary cell cultures of primates were used to study whether SSTR and DR expression is regulated by forskolin.
The response to LAR did not significantly differ between patients with gsp+ and gsp- tumors; however, gsp+ tumors expressed higher levels of SSTR1, SSTR2, DR2 and a lower level of SSTR3. Forskolin increased SSTR1, SSTR2, DR1 and DR2 expression in cell cultures.
Elevated SSTR1, SSTR2, and DR2 tumor expression may help improve responsiveness to SA and DA therapy; however, this study may not have been appropriately powered to observe significant effects in the clinical response. Elevated cAMP levels could be directly responsible for the upregulation in SSTR1, SSTR2 and DR2 mRNA levels observed in gsp+ patients.
[Show abstract][Hide abstract] ABSTRACT: A woman with a previous history of hyperthyroidism and low thyroid radioiodine uptake was admitted. Abdominal computed tomography revealed an 11 × 8.2-cm mass, located in the right iliac bone. Surgical biopsy revealed a well-differentiated follicular carcinoma of the thyroid. Whole-body I131 scan revealed intense fixation of radioactive material in the lesion. The patient was treated with radioactive iodine. Functioning metastasis of differentiated carcinoma of the thyroid should be considered in patients with hyperthyroidism and low thyroid radioiodine uptake.
The Endocrinologist 02/2010; 20(2):50-51. DOI:10.1097/TEN.0b013e3181d4ab16 · 0.12 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Insulin signalling pathways were investigated in a 33 year-old woman with immunologic insulin resistance. Her past medical history was remarkable for intermittent use of insulin and allergic reactions to several drugs, and measure of plasma anti-insulin antibodies level corroborated the clinical suspicion of immune mediated insulin resistance (8074 nU/ml - RIA - Ref value: <60). Treatment with several immunosuppressive regimens was tried, however the results were disappointing. Possible subcellular mechanisms of insulin resistance were investigated by performing analysis of insulin receptor and post receptor signaling in skeletal muscle biopsy. The expression of insulin receptor (IR), insulin receptor substrate 1 (IRS-1) and glucose transporter 4 (GLUT-4) was evaluated in total extract from muscle tissue by Western blotting. Basal IR, IRS-1 and GLUT-4 expression was detected, however receptor autophosphorylation was not observed. A study of translocation of GLUT-4 to plasma membrane showed that tissue presented low levels of membrane-associated GLUT-4. When in vitro stimulation was undertaken, tissue was capable to be responsive to insulin. Our results suggest that even though IR expression was normally occurring, IR beta-subunit tyrosine kinase activity in muscle was down-regulated leading to alterations in insulin post receptor signaling. Consistent with normal insulin receptor and post receptor signaling, our results were compatible with decreased insulin binding to IR probably due to neutralization by anti-insulin antibodies. In conclusion, this patient has immunologic insulin resistance and treatment should be based on immunosuppressive drugs as tolerated.
[Show abstract][Hide abstract] ABSTRACT: The purpose of the present study is to evaluate the prevalence of the gsp oncogene in Brazilian patients harboring somatotropinomas and non-functioning pituitary adenomas (NFPA). Patients and methods Deoxyribonucleic acid was extracted from 54 somatotropinomas and 14 NFPA. Exons 8 and 9 (including codons 201 and 227, respectively) of the GNAS gene were amplified by polymerase chain reaction (PCR). The PCR products were then purified and sequenced using the same primers. Results The gsp oncogene was found in nine tumors (eight somatotropinomas). The prevalence among somatotropinomas was 15% and among NFPA was 7%. The mutation was found in codon 201 in eight tumors and in codon 227 in one tumor (a somatotropinoma). No differences were found in age, sex, GH, and IGF-I levels or tumor volume at diagnosis between gsp+ and gsp- patients. Conclusion We found a lower than expected prevalence of gsp mutations in somatotropinomas and a similar prevalence in NFPA compared to previous studies from other countries.
[Show abstract][Hide abstract] ABSTRACT: Dopamine receptor (DR) and somatostatin receptor subtype expression in pituitary adenomas may predict the response to postsurgical therapies.
Our objectives were to assess and compare the mRNA levels of DR1-5 and somatostatin receptors 1-5 in normal pituitaries (NPs), nonfunctioning pituitary adenomas (NFPAs), and somatotropinomas. In addition, we determined whether the level of DR expression correlates with the in vivo response to octreotide-LAR in acromegalic patients.
Eight NPs, 30 NFPAs, and 39 somatotropinomas were analyzed for receptor mRNA levels by real-time RT-PCR. The DR2 short variant was estimated as the DR2 long/DR2 total (DR2T). The relationship between DR expression and the postsurgical response to octreotide-LAR was assessed in 19 of the acromegalic patients.
DR3 was not detected. The relationship between expression levels of DR subtypes in NPs and somatotropinomas was DR2T>DR4>DR5>DR1, whereas in NFPAs, DR2T>DR4>DR1>DR5. The DR2 short variant was the predominant DR2 variant in the majority of samples. In acromegalics treated with octreotide-LAR, DR1 was negatively correlated with percent GH reduction (3 months: r = -0.67, P = 0.002; and 6 months: r = -0.58, P = 0.009), and DR5 was positively correlated with percent IGF-I reduction (3 months: r = 0.55, P = 0.01; and 6 months: r = 0.47, P = 0.04).
DR2 is the predominant DR subtype in NPs, NFPAs, and somatotropinomas. The fact that DR1, DR4, and DR5 are also expressed in many adenomas tested suggests that these receptors might also play a role in the therapeutic impact of postsurgical medical therapies in patients with NFPA and acromegaly. This was supported by the finding that the in vivo response to octreotide-LAR was negatively associated with DR1 and positively associated with DR5.
The Journal of Clinical Endocrinology and Metabolism 03/2009; 94(6):1931-7. DOI:10.1210/jc.2008-1826 · 6.21 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Germ cell tumors (GCT) are a heterogeneous group of lesions whose origin is not well established. Several cases of primary intrasellar germinomas have been reported, however non-germinomatous GCT have rarely been described. We report the case of a young adult male patient with a mixed GCT that presented with a sellar tumor with suprasellar extension. The patient seeked medical attention because of seizures and magnetic resonance imaging evidenced a tumor of the sellar region. Hyperprolactinemia was also present and dopamine agonist therapy was started. As there was a rapid tumor growth and the patient had concomitant central diabetes insipidus and elevated testosterone levels, a GCT was suspected and confirmed by elevated serum concentration of β-human chorionic gonadotrophin. Patient underwent surgical resection of the tumor and histopathological examination confirmed the diagnosis of a mixed GCT. Chemotherapy was initiated, followed by conventional radiotherapy. In conclusion, although pituitary adenomas respond for the vast majority of sellar tumors, concomitant symptoms such as central diabetes insipidus and rapid tumor growth should raise the suspicion of a diverse diagnosis. The present report intend not only to show a rare case of sellar and suprasellar mixed GCT but also to remind clinicians that if laboratory findings do not fit into patient's diagnosis (such as high testosterone levels in our patient), then the diagnosis should be reviewed.
[Show abstract][Hide abstract] ABSTRACT: We present two acromegalic patients in which clinical and molecular data are discussed in regard to their ability to predict long term octreotide LAR therapy response. Case reports: Patient 1: female, 36 years old at diagnosis. Basal GH and IGF-I at diagnosis were 133 ng/mL and 181% above the upper limit of reference values (ULRV), respectively. Growth hormone during acute test with subcutaneous octreotide decreased from 133 to 13 ng/mL. Patient started on primary octreotide LAR therapy (20mg q28 days) and achieved biochemical parameters of disease control after 6 months. Molecular analysis of tumor fragments: gsp +; quantitative analysis of SSTR (somatostatin receptor) and DR (dopamine receptor) mRNA - SSTR2 23954; SSTR5 2407; DR2 total 17016 copies. Patient 2: male, 38 years old at diagnosis. Basal GH and IGF-I at diagnosis were 120 ng/mL and 114% ULRV, respectively. Patient underwent non-curative trans-sphenoidal surgery. Post-operative GH and IGF-I were 112 ng/mL and 137% ULRV, respectively. Growth hormone during acute test with subcutaneous octreotide decreased from 112 to 7 ng/mL. Octreotide LAR therapy (20 mg q28 days) was then initiated. After 6 months of treatment, patient did not attain biochemical control of disease and displayed increased tumor volume. Molecular analysis of tumor fragments: gsp not done; quantitative analysis of SSTR and DR mRNA - SSTR2 416; SSTR5 3767; DR2 total 3439 copies. In conclusion, these two cases illustrate how laboratory data can be conflicting as predictors of octreotide LAR responsiveness and how molecular analysis of tumor fragments can help explain different behaviors in clinically similar patients.
Arquivos brasileiros de endocrinologia e metabologia 12/2008; 52(8):1288-95. DOI:10.1590/S0004-27302008000800014 · 0.84 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Acromegalic patients are considered "discordant" if their insulin-like growth factor type I (IGF-I) levels are increased for their age with "safe" growth hormone (GH) levels or if their IGF-I levels are normal for their age with "unsafe" GH levels. The prevalence of discordance in acromegalics has been described to vary from 9.4% to 39%, and it may be observed at diagnosis or during the follow up.
To evaluate the prevalence of discordant levels of IGF-I and GH in our acromegalic population.
Hormonal evaluation was made with an oral glucose tolerance test (OGTT) with the IGF-I being assessed in the basal sample at diagnosis and after 3 months of the adenomectomy. During treatment with octreotide LAR, a GH curve (for the calculation of mean GH) and IGF-I assessment were made every 3 months.
Among the 51 patients evaluated at diagnosis, the prevalence of discordance was 13.7% (7/51). Among the 58 patients evaluated after the surgical procedure, eight (13.8%) had discordant GH and IGF-I levels. Among the 42 patients evaluated during treatment with octreotide LAR, the prevalence of discordant GH and IGF-I levels was 33.3% (14/42). Using 1 microg/L as a cut off level for "safe" GH, the prevalence of discordance was 3.9%, 8.6% and 28.6% at diagnosis, after surgery and during treatment with octreotide LAR, respectively. No difference of sex, age or treatment modality was observed among discordant and concordant patients with any GH cut off level.
We observed a prevalence of discordance similar to that previously described in the literature. We believe that studies evaluating morbidity and mortality in discordant patients are also necessary and will enlighten the true impact of this condition in the follow up of acromegaly.
[Show abstract][Hide abstract] ABSTRACT: Ectopically ACTH producing tumors may be difficult to localize by conventional radiology and functional imaging may be helpful. Case 1: 31-year-old man was diagnosed with ectopic ACTH-dependent Cushing's syndrome (ECS). Thorax CT revealed a 1.3 cm nodular opacity in upper left lobe, suggestive of residual lesion. [(18)F] fluoro-2-deoxy-D: -glucose ([(18)F] FDG) positron emission tomography ([(18)F] FDG PET) scan revealed mild glycolytic metabolic activity. Pathological examination confirmed an ACTH-positive carcinoid tumor. Case 2: 53-year-old woman presented with very rapid onset ECS. Pituitary MRI was normal. Thorax CT revealed no tumoral lesion. Abdominal and pelvic MRI showed images suggestive of hepatic and iliac, femoral and lumbar secondary implants. [(18)F] FDG PET scan revealed intense uptake in uterus, especially cervix, suggesting this to be the primary tumor site. These cases illustrate the role of [(18)F] FDG PET in the investigation of an ECS where conventional imaging studies were not elucidative in the search for a responsible tumor.
[Show abstract][Hide abstract] ABSTRACT: To determine the prevalence of sleep apnea (SA) and SA syndrome (SAS) in patients with acromegaly and correlate SA with clinical, laboratory, and cephalometric parameters.
Prospective and cross-sectional study of 24 patients with active acromegaly evaluated by clinical and laboratory (GH, IGF-I) parameters, polysomnography and magnetic resonance imaging (MRI) of the pharynx.
Out of 24 patients, 21 had SA (87.5%), of which 20 (95.3%) had the predominant obstructive type. Median age of these 21 patients was 54 years (range 23-75) and median estimated disease duration was 60 months (range 24-300). The frequency in SA patients of impaired glucose tolerance, diabetes mellitus (DM), and hypertension was 19, 33.3, and 71.4% respectively. Goiter was found in 10 patients (47.6%) and obesity in 18 (90%). Median GH level was 14 mug/l (1.4-198) and median %IGF-I (percentage above the upper limit of normal range of IGF-I) was 181% (-31.6 to 571.2). The prevalence of SAS was 52.4%. Apnea-hypopnea index (AHI) correlated significantly with age, waist circumference, body mass index, and hypopharynx area. The AHI was significantly higher in patients with hypertension and DM.
The prevalence of SA and SAS in acromegaly was similar to the one previously described in other series. Age was a significant risk factor, and hypertension and DM were significantly associated complications of SA. Obesity was also significantly related to SA, as a risk factor, a complication or both. Overall, cephalometric parameters by MRI did not correlate with SA.
European Journal of Endocrinology 05/2008; 158(4):459-65. DOI:10.1530/EJE-07-0753 · 4.07 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: The use of growth hormone (GH) in deficient adults has already been demonstrated to result in several benefits regarding metabolic parameters, body composition and quality of life. Due to the similarities between GH deficiency in adults and the aging process, the concept of somatopause has emerged. OBJECTIVES: Correlate the GH secretion profile in healthy men older than 50 years with anthropometric parameters and exercise capacity. PATIENTS AND METHODS: Twenty-nine healthy male were selected, with a mean age of 57.9+/-4.2 years (range 50-66). After hospital admission, body mass index (BMI), body composition (fat mass) and abdominal circumference, 24-h GH profile, GH peak and basal IGF-I were evaluated, and all the patients underwent a treadmill stress testing to estimate exercise capacity with the Bruce protocol, with evaluation of the maximum oxygen peak, maximum heart rate and METs. All the results are shown as mean+/-Std deviation: BMI -26.5+/-4.9kg/m2, percent fat mass -27.1+/-6.2%, abdominal circumference -92.1+/-10.1cm, 24h GH profile -0.3+/-0.2ng/dl, peak GH -2.5+/-2.0ng/dl, IGF-I -202.4+/-72.4ng/dl, maximum oxygen peak -31.9+/-6.8L, maximum heart rate - 161.4+/-7.5 bpm and METs - 9.1+/-1.9. After regression analysis using the GH secretion profile (mean GH in 24h, spontaneous peak GH and basal IGF-I) as dependent variable, no correlations were found between these and the other evaluated parameters.
[Show abstract][Hide abstract] ABSTRACT: To determine whether the somatostatin receptor subtype (SSTR) expression profile correlates with hormonal and tumor volume responses to postsurgical octreotide long acting repeatable (OCT LAR) treatment.
Quantitative real-time RT-PCR was used to evaluate the absolute mRNA copy numbers for all five SSTR subtypes in 22 somatotropinomas. Response to OCT LAR was studied by hormone levels (GH and IGF-I) and tumor volume (sella turcica magnetic resonance imaging).
SSTR5 was present at the highest level followed by SSTR2, SSTR3, SSTR1, and SSTR4 (2327 (1046-5555), 2098 (194-23 954), 97 (0-460), 14 (0-29 480), and 0 (0-652) copies respectively). Positive correlations were found between SSTR2 levels and the percentage decrease of GH and IGF-I after 3 (r=0.49, P<0.027 and r=0.49, P<0.029 respectively) and 6 (r=0.59, P<0.006 and r=0.58, P<0.008 respectively) months of OCT LAR. A negative correlation was found between SSTR5 mRNA levels and the percentage decrease of GH after 3 months of OCT LAR (r=-0.52, P=0.016, n=21). A higher SSTR2/SSTR5 ratio was observed among patients who obtained hormonal control with OCT LAR, when compared with those uncontrolled (2.4 (0.7-10) vs 0.3 (0.1-7.7), P=0.001). A ROC curve analysis showed a SSTR2/SSTR5 ratio of 1.3 as the best predictor of disease control, with a sensitivity of 88% and a specificity of 92% - area under curve, 0.9. A positive correlation was also found between SSTR2 mRNA levels and the percentage decrease in tumor volume after 6 months of OCT LAR (r=0.79, P=0.002, n=12).
Somatostatin receptor subtype 2 mRNA expression levels in somatotropinomas correlate positively with in vivo hormonal and tumor volume responses to OCT LAR.
European Journal of Endocrinology 03/2008; 158(3):295-303. DOI:10.1530/EJE-07-0562 · 4.07 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To evaluate the glucose metabolism in acromegalic patients before and after treatment with octreotide LAR.
This was a prospective and longitudinal study involving 30 patients from the acromegaly research outpatient clinic of the Endocrinology unit of the HUCFF/UFRJ. They underwent clinical and laboratorial evaluations, with measurements of growth hormone (GH), insulin-like growth factor type I (IGF-I), insulin, proinsulin, C peptide, glycosylated hemoglobin (HbA1c), IGF binding protein type 1 (IGFBP-1) and glucose, during oral glucose tolerance test (OGTT), before and after six months of treatment with octreotide LAR. The Wilcoxon signed-rank test was used and values of 5% were considered statistically significant.
We found 16 (54%) patients with normal glucose tolerance, 7 (23%) with impaired glucose tolerance and 7 (23%) diabetics. Twelve patients completed the six-month treatment, out of which three showed worsening of glucose tolerance and two (diabetics) had worse blood glucose control. Whereas there was an increase in waist circumference (p=0.03), there was a decrease in GH (p=0.04), with %IGF-I above the upper limit of reference values (% ULRV) [p=0.001], insulin (p=0.019), C peptide levels (p=0.002) and homeostatic model assessment (HOMA-IR) [p=0.039].
In this series, treatment with octreotide LAR led to a worsening of glucose tolerance in three non-diabetic patients and worsened glycemic control in two diabetics, in spite of reducing insulin resistance.
[Show abstract][Hide abstract] ABSTRACT: GH secretion, in acromegaly, is characterized by increased basal levels, as well as by increased frequency and amplitude of pulses. Evaluation of disease activity during follow-up of treated patients is frequently done with mean GH levels, although there is no established protocol for sample collection.
Determine mean GH value of 5 blood samples collected 30 min apart for 2 consecutive hours in the follow-up of acromegalic patients treated with octreotide LAR.
Ninety-one GH curves of 44 patients (25 women) were evaluated as were the respective IGF-I values (basal). Normal IGF-I for age and sex was considered standard for control of disease activity. Correlations between basal and mean GH were studied as were correlations between both values and %IGF-I above the upper limit of reference values (%ULRV).
Median age of the group was 45.5 years (range 28-73). Twenty-five patients (56.8%) had previous surgery and 7 (15.9%) had both surgery and radiotherapy. A positive correlation was found between mean and basal GH (r=0.953; p<0.001). Both basal and mean GH were correlated to %ULRV (r=0.645 and 0.661; p<0.001 for both). In only 3 of the 91 curves (3.3%) there were discordances between basal GH and IGF-I, however the latter was concordant with mean GH. In 3 other curves there was concordance between basal GH and IGF-I although the latter was discordant with mean GH.
There was no benefit to perform GH curves with the present protocol. It may be due to our established outpatient follow up protocol. The use of more complex protocols and the cost of multiple GH assays should be acknowledged, and probably reserved for patients with basal GH levels between 1 and 5 microg/L with discordant GH and IGF-I.
[Show abstract][Hide abstract] ABSTRACT: Ectopic growth hormone-releasing hormone (GHRH)-secreting tumors are rare and cause acromegaly with somatotroph hyperplasia. We report a case of acromegaly secondary to GHRH secretion by an incidentally discovered pheochromocytoma in a normotensive patient. A 23-year-old man presented with signs and symptoms of acromegaly. Laboratory evaluation confirmed the diagnosis and magnetic resonance imaging (MRI) revealed a sellar mass which was thought to be a macroadenoma and surgically resected. The patient was not cured and medical treatment was indicated. An abdominal ultrasound performed before initiation of medical treatment showed a solid/cystic lesion superiorly to the right kidney. An abdominal MRI confirmed an adrenal tumor. Hormonal workup of the adrenal incidentaloma revealed elevated urinary catecholamine and total metanephrines findings strongly suggestive of a pheochromocytoma. Acromegaly was then suspected to be due to ectopic secretion of GHRH by the tumor. Patient underwent surgical resection and histopathologic examination confirmed a pheochromocytoma which stained positively for GHRH. Also, review of the pituitary specimen confirmed somatotrophic hyperplasia. Genetic analysis of the ret proto-oncogene showed no mutation. Pituitary MRI was repeated 10 months after pheochromocytoma resection and revealed a slightly enlarged pituitary and partial empty sella. The diagnosis of acromegaly caused by ectopic production of GHRH is a challenging task. A careful histopathological examination of the surgically excised pituitary tissue has a key role to arouse the suspicion and guide the investigation of a secondary cause of acromegaly.
[Show abstract][Hide abstract] ABSTRACT: It is believed that the variable effectiveness of somatostatin analogs in post-surgical management of somatotropinomas and non-functioning pituitary adenomas (NFPA) may be due in part to variable expression of somatostatin receptor isoforms (SSTR1-5), within and between pituitary tumor types.
Quantitative real-time RT-PCR was used to compare absolute mRNA copy numbers for all five SSTR isoforms in 23 somatotropinomas and 19 NFPA.
Somatostatin receptor subtype 5 mRNA was present at the highest level in somatotropinomas, followed by SSTR2>SSTR3>SSTR1>SSTR4. In contrast, SSTR3 mRNA was present at the highest level in NFPA, followed by SSTR2, while SSTR1, SSTR4, and SSTR5 transcripts were only detectable in select tumors. Among somatotropinomas, a positive correlation was found between SSTR2 mRNA levels and the percent decrease of GH (%GH) after 3 and 6 months of therapy with octreotide long acting repeatable (LAR) (r=0.51 and r=0.66; P=0.05 and P=0.008). Also the percent decrease of IGF-I (%IGF-I) after 3 months of octreotide LAR was negatively correlated with SSTR5 and %IGF-I after 6 months of octreotide LAR was positively correlated with SSTR2.
The present report is a large series examining SSTR mRNA levels in somatotropinomas and NFPA. These initial findings suggest that detailed knowledge of the SSTR mRNA expression profile in somatotropinomas can help to predict the hormonal response to therapy with LAR. Also, it appears that SSTR3 in NFPA may be a potential target for SSTR3 preferential or universal ligands such as pasireotide.
European Journal of Endocrinology 01/2007; 156(1):65-74. DOI:10.1530/eje.1.02313 · 4.07 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Acromegaly is a systemic disease with various etiologies. It can occur as a sporadic or, more rarely, as a familial disease. Numerous complications such as endocrine, cardiovascular, respiratory, metabolic, osteoarticular and neoplastic disturbances occur and must be taken into account when establishing a therapeutic strategy. For this reason, the decision as to a treatment modality of acromegaly must be followed by a thorough evaluation of the patient and once the diagnosis of complications is settled, adequate treatment should be instituted. Follow up of the patients requires periodical re-assessment of complications status.