The Value of ER∝ in the Prognosis of GH- and PRL-Secreting PitNETs: Clinicopathological Correlations.

Pituitary neuroendocrine tumors (PitNETs) are divided into multiple histological subtypes, which determine their clinical and biological variable behavior. Despite their benign evolution, in some cases, prolactin (PRL) and growth hormone (GH)-secreting PitNETs may have aggressive behavior. In this study, we investigated the potential predictive role of ER∝, alongside the clinicopathological classification of PitNETs (tumor diameter, tumor type, and tumor grade). A retrospective study was conducted with 32 consecutive cases of PRL- and mixed GH- and PRL-secreting PitNETs (5 patients with prolactinomas and 27 with acromegaly, among them, 7 patients with GH- and PRL- co-secretion) who underwent transsphenoidal intervention. Tumor specimens were histologically and immunohistochemical examined: anterior pituitary hormones, ki-67 labeling index, CAM 5.2, and ER∝; ER∝ expression was correlated with basal PRL levels at diagnosis (rho = 0.60, p < 0.01) and postoperative PRL levels (rho = 0.58, p < 0.001). In our study, the ER∝ intensity score was lower in female patients. Postoperative maximal tumor diameter correlated with Knosp grade (p = 0.02); CAM 5.2 pattern (densely/sparsely granulated/mixed densely and sparsely granulated) was correlated with postoperative PRL level (p = 0.002), and with ki-67 (p < 0.001). The IGF1 level at diagnosis was correlated with the postoperative GH nadir value in the oral glucose tolerance test (OGTT) (rho = 0.52, p < 0.05). Also, basal PRL level at diagnosis was correlated with postoperative tumor diameter (p = 0.63, p < 0.001). At univariate logistic regression, GH nadir in OGTT test at diagnostic, IGF1, gender, and invasion were independent predictors of remission for mixed GH- and PRL-secreting Pit-NETs; ER∝ can be used as a prognostic marker and loss of ER∝ expression should be considered a sign of lower differentiation and a likely indicator of poor prognosis. A sex-related difference can be considered in the evolution and prognosis of these tumors, but further studies are needed to confirm this hypothesis.

Pituitary Apoplexy: A Retrospective Study of 36 Cases From a Single Center.

Background and objective Pituitary apoplexy (PA) is a possible life-threatening disorder due to spontaneous hemorrhage or impaired blood supply in the pituitary gland. It may present as an acute or subclinical form, and treatment options include either surgery or a conservative approach. The purpose of this study was to retrospectively analyze the clinical, imaging, and hormonal features, as well as the therapeutic outcomes, in a relatively short period of time in a series of consecutive patients with pituitary apoplexy (PA). Results Thirty-six patients were included, 50% presenting typical symptoms of PA. The presenting symptoms were headache (44.4%), visual abnormalities (44.4%), and digestive symptoms (22.2%). At diagnosis, hormonal deficiency was observed in 22 (61.1%) patients. Of the evaluated patients, 78.2% of the 23 operated cases and all unoperated cases presented tumor remnants. Vision improved in 81.8% of the operated and 100% of conservatively managed cases. Of all cases, 69.4% remained with long-term hypopituitarism. Conclusion Complex management of PA frequently leads to visual improvement but long-standing hypopituitarism.

Beneficial effect of dose escalation and surgical debulking in patients with acromegaly treated with somatostatin analogs in a Romanian tertiary care center.

BACKGROUND: Somatostatin analogs (SSA) are now considered standard therapy for acromegaly, as primary or adjunctive treatment after pituitary surgery. OBJECTIVE: To evaluate the efficacy of SSA and the effect of dose escalation in non-operated patients with acromegaly as compared to patients treated after pituitary surgery in a Romanian tertiary care center. DESIGN: Retrospective study of 73 consecutively evaluated patients with acromegaly treated with SSA, divided into 2 groups: 11 patients (4M/7F, 21-62 years) with primary treatment and 62 patients (22M/40F, 21-68 years) treated after surgery. They received Octreotide LAR 20-30 mg i.m./28 days or Lanreotide SR 30 mg i.m./14/10/7 days. Random serum growth hormone (GH) was measured using IRMA, sensitivity 0.2-0.01 µg/L IGF-1 was measured using different assays and compared with ULN for age and sex. RESULTS: Overall, random GH ≤2.5 µg/L was attained in 39 patients (53.4%) and optimal GH ≤1 ng/mL) in 30 patients (41%), while normal IGF-1 was recorded in 22/72 patients (30.5%). The final random GH ≤2.5 µg/L was achieved in 27.2% of non-operated patients (3/11) as compared with 58% (36/62) of patients treated medically after pituitary surgery, p<0.05. Escalation of doses of SSA applied in 43 patients improved the number of controlled patients by 5 (12.1%, p=0.059) and the number of optimally controlled patients by 9.7%. Of the 8 patients who switched from Lanreotide to Octreotide, 2 patients achieved GH normalization. CONCLUSION: The rate of biochemical control via SSA treatment in patients with acromegaly could be improved by rise of the SSA dose or by debulking surgery. Occasionally, substituting one SSA for another may be of benefit.

From syncope episode to the diagnosis of ovarian dermoid cyst associated with a cystadenoma.

Ovarian teratoma has various presentations. We present a 28-year female diagnosed with a tumour after a fainting episode. Medical history was non-contributory except for mild intermittent pelvic pain. Cardiologic and neurological evaluation found no cause of syncope. Abdominal ultrasound revealed a right ovarian tumour that was laparoscopically removed. The menses continued to be normal. The pathological exam showed an encapsulated tumour of 8 cm with hair and small bone parts (mature teratoma with a cystadenoma). Immunohistochemistry was positive for CK34beta E12 in stratified squamous epithelium of skin glands; positive CK7 in kidney tubular parts; positive actin in smooth muscle. The endocrine profile was normal and the patient remained asymptomatic. The challenging in the pathological report was to differentiate a cystic part of a solid tumour to a teratoma associated cystadenoma. No apparent cause of syncope was found so a possible tumour related local pain and inflammation mechanism might be involved.

Vanishing testes syndrome-related osteoporosis and high cardio-metabolic risk in an adult male with long term untreated hypergonadotropic hypogonadism.

The male hypogonadism-related bone mass loss is often under diagnosed. Peak bone mass is severely affected if the hypogonadism occurs during puberty and is left untreated. We present an interesting; almost bizarre case of a male with non-functional testes early during childhood and undiagnosed and untreated hypogonadism until his fifth decade of life. Forty six year male is referred for goitre, complaining of back pain. Phenotype suggested intersexuality: gynoid proportions, micropenis, no palpable testes into the scrotum, no facial or truncal hair. His medical history had been unremarkable until the previous year when primary hypothyroidism was diagnosed and levothyroxine replacement was initiated. Later, he was diagnosed with ischemic heart disease, with inaugural unstable angina. On admission, the testosterone was 0.2 ng/mL (normal: 1.7-7.8 ng/mL), FSH markedly increased (56 mUI/mL), with normal adrenal axis, and TSH (under thyroxine replacement). High bone turnover markers, and blood cholesterol, and impaired glucose tolerance were diagnosed. The testes were not present in the scrotum. Abdominal computed tomography suggested bilateral masses of 1.6 cm diameter within the abdominal fat that were removed but no gonadal tissue was confirmed histopathologically. Vanishing testes syndrome was confirmed. The central DXA showed lumbar bone mineral density of 0.905 g/cm2, Z-score of -2.9SD. The spine profile X-Ray revealed multiple thoracic vertebral fractures. Alendronate therapy together with vitamin D and calcium supplements and trans-dermal testosterone were started. Four decades of hypogonadism associate increased cardiac risk, as well as decreased bone mass and high fracture risk.

Vanishing testes syndrome-related osteoporosis and high cardio-metabolic risk in an adult male with long term untreated hypergonadotropic hypogonadism

SUMMARY The male hypogonadism-related bone mass loss is often under diagnosed. Peak bone mass is severely affected if the hypogonadism occurs during puberty and is left untreated. We present an interesting; almost bizarre case of a male with non-functional testes early during childhood and undiagnosed and untreated hypogonadism until his fifth decade of life. Forty six year male is referred for goitre, complaining of back pain. Phenotype suggested intersexuality: gynoid proportions, micropenis, no palpable testes into the scrotum, no facial or truncal hair. His medical history had been unremarkable until the previous year when primary hypothyroidism was diagnosed and levothyroxine replacement was initiated. Later, he was diagnosed with ischemic heart disease, with inaugural unstable angina. On admission, the testosterone was 0.2 ng/mL (normal: 1.7-7.8 ng/mL), FSH markedly increased (56 mUI/mL), with normal adrenal axis, and TSH (under thyroxine replacement). High bone turnover markers, and blood cholesterol, and impaired glucose tolerance were diagnosed. The testes were not present in the scrotum. Abdominal computed tomography suggested bilateral masses of 1.6 cm diameter within the abdominal fat that were removed but no gonadal tissue was confirmed histopathologically. Vanishing testes syndrome was confirmed. The central DXA showed lumbar bone mineral density of 0.905 g/cm2, Z-score of -2.9SD. The spine profile X-Ray revealed multiple thoracic vertebral fractures. Alendronate therapy together with vitamin D and calcium supplements and trans-dermal testosterone were started. Four decades of hypogonadism associate increased cardiac risk, as well as decreased bone mass and high fracture risk.

Screening for secondary endocrine hypertension in young patients.

BACKGROUND: Secondary endocrine hypertension accounts for 5-12% of hypertension's causes. In selected patients (type 2 diabetes mellitus, sleep apnea syndrome with resistant hypertension, sudden deterioration in hypertension control), prevalence could be higher. OBJECTIVES: To present etiology of endocrine secondary hypertension in a series of patients younger than 40 years at hypertension's onset. MATERIAL AND METHODS: Medical records of 80 patients (39M/41F), aged 30.1 ± 8.2 years (range: 12-40 years), with maximum systolic blood pressure=190.4 ± 29.2 mm Hg, range: 145-300 mm Hg, maximum diastolic blood pressure=107.7 ± 16.9 mm Hg, range: 80-170 mm Hg) referred by cardiologists for endocrine hypertension screening were retrospectively reviewed. Cardiac and renal causes of secondary hypertension were previously excluded. In all patients, plasma catecholamines were measured by ELISA and plasma cortisol by immunochemiluminescence. Orthostatic aldosterone (ELISA) and direct renin (chemiluminescence) were measured in 48 patients. RESULTS: Secondary endocrine hypertension was confirmed in 16 out of 80 patients (20%). Primary hyperaldosteronism was diagnosed in 7 (4M/3F) out of 48 screened patients (14.6%). i.e. 8.75% from whole group: 5 patients with adrenal tumors (3 left/2 right), 2 patients with bilateral adrenal hyperplasia; all patients were hypokalemic at diagnostic (average nadir K+ levels = 2.5 ± 0.5 mmol/L); four patients were hypokalaemic on diuretic therapy (indapamidum); other 3 patients were hypokalaemic in the absence of diuretic therapy. Cushing's syndrome was diagnosed in 6 patients (7.5%): subclinical Cushing due to 4 cm right adrenal tumour - n = 1, overt ACTH-independent Cushing's syndrome due to: macronodular adrenal hyperplasia associated with primary hyperparathyroidism - n = 1; due to adrenal carcinoma - n = 1; due to adrenal adenomas - n = 2; Cushing's disease - n = 1). Pheochromocytomas were diagnosed in 3 patients (3.75%). CONCLUSION: Primary hyperaldosteronism was the most frequent cause of secondary endocrine hypertension in our series, followed by Cushing's syndrome and pheochromocytomas. Screening of young hypertensive patients for secondary causes, especially primary hyperaldosteronism, is mandatory.

Pituitary incidentalomas--how often is too often?

INTRODUCTION: Clinical nonfunctional pituitary microadenomas, also known as incidentalomas are accidental observations made due to the application of high resolution imaging techniques as computed tomography or magnetic resonance. There are no standards regarding the follow-up of these tumors and taking into account their increased frequency among general population (during the last years they were based on the high performances of the imaging methods), we decided to study their dimensions and their evolution over time. We have also analysed their behavior with respect to their endocrine phenotype and the minimum period of time needed for the repetition of the imagistic procedure. AIM: To observe the natural evolution of tumors' dimensions in a group of patients, diagnosed with nonfunctional pituitary microadenomas based upon hormonal measurements and computed tomography scan. METHOD: There is a retrospective observational study on 149 patients hospitalized in our Clinic between 1994 and 2006. Initially, all the pituitary hormones and the computed tomography were performed. Only nonfunctional microadenomas were included (the maximum diameter 11 mm). 69 patients were examined for a long period of time--29.75 +/- 24.79 months by CT scan and secretory profile, repeated at different periods of time. RESULTS: At the end of 29.75 months, the aspect of microadenoma was still present, without any statistically significant changes of the diameter. One of the cases became macroadenoma and another proved to be a microprolactinoma. Only 5 cases of all 149 presented a double lesion. No case of pituitary apoplexy was registered. These observations lead to the conclusion that it is not necessary to repeat the computed tomography scan sooner than 2 years once the diagnosis ofincidentaloma was established.