How does pregnancy affect the patients with pituitary adenomas: a study on 113 pregnancies from Turkey.

OBJECTIVE: Data regarding pregnancies in relation to pituitary tumors are limited. The effects of pregnancy on pituitary adenomas and the effects of adenoma itself (hormonal activity, mass effects and pituitary insufficiency) and/or treatment on the ongoing gestation and developing fetus were evaluated. METHODS: The study was a retrospective study. A questionnaire involving questions regarding medical history before index gestation, history of related pregnancy, result of index gestation and postpartum follow-up of the patients was filled by the investigator in one of the eight Referral Endocrinology Centers from Turkey. RESULTS: One hundred and thirteen (83 prolactinoma, 21 acromegaly, 8 NFPA and 1 plurihormonal pituitary adenoma) pregnancies of 87 (60 prolactinoma, 19 acromegaly, 7 NFPA and 1 plurihormonal pituitary adenoma) patients were reviewed. The clinically important pregnancy-related tumor growth of pituitary adenomas was found to be low in previously treated adenomas. Prolactinomas were more likely to increase in size during pregnancy especially if effective prior treatment was lacking. The risk of hypopituitarism is also minimal due to pituitary adenomas during pregnancy. The results of pregnancies did not differ in patients who were on medical treatment or not for prolactinomas and acromegaly during gestation. Neural tube defect and microcephaly associated with maternal cabergoline use; Down syndrome and corpus callosum agenesis associated with maternal bromocriptine use; unilateral congenital cataract, craniosynostosis and microcephaly associated with maternal acromegaly were detected for the first time. CONCLUSION: Medical treatment can be safely done stopped in patients with prolactinoma and acromegaly when pregnancy is confirmed and reinstituted when necessary. Prospective studies may help to determine the effects of medical treatment during gestation on the mother and fetus.

Comparison of the ability of short time low PEEP challenge and mini fluid challenge to predict fluid responsiveness in patients undergoing open pancreaticoduodenectomy: an observational cohort study.

OBJECTIVE: The mini-fluid challenge (MFC), which assesses the change in stroke volume index (SVI) following the administration of 100 mL of crystalloids, and the short-time low positive end-expiratory pressure (PEEP) challenge (SLPC), which evaluates the temporary reduction in SVI due to a PEEP increment, are two functional hemodynamic tests used to predict fluid responsiveness in the operating room. However, SLPC has not been assessed in patients undergoing abdominal surgery, and there is no study comparing these two methods during laparotomy. Therefore, we aimed to compare the SLPC and MFC in patients undergoing open pancreaticoduodenectomy. PATIENTS AND METHODS: All patients received a standard hemodynamic management. The study protocol evaluated the percentage change in SVI following the application of an additional 5 cmH2O PEEP (SVIΔ%-SLPC) and the infusion of 100 mL crystalloid (SVIΔ%-MFC). Challenges that resulted in an increase of more than 15% in SVI after the 500 ml of fluid loading were classified as positive challenges (PC). Areas under the receiver operating characteristics curves (ROC AUCs) were used for the comparison of the methods. RESULTS: Thirty-three patients completed the study with 94 challenges. Fifty-five (58.5%) of them were PCs. The ROC AUC of SVIΔ%-MFC was observed to be significantly higher than that of SVIΔ%-SLPC (0.97 vs. 0.64, p < 0.001). The best cut-off value for SVIΔ%-MFC was 5.6%. If we had stopped the bolus fluid administration when SVIΔ%-MFC ≤ 5% was observed (lower limit of the gray zone), we would have postponed the fluid loading in 35 (89.7%) of 39 negative challenges. The amount of fluid deferred would have corresponded to up to 40% of the total fluid given. CONCLUSIONS: SVIΔ%-MFC predicts fluid responsiveness with high diagnostic performance and is better than SVIΔ%-SLPC in patients undergoing open pancreatoduodenectomy. Additionally, the use of SVIΔ%-MFC has the potential to defer up to 40% of the total fluid given. CLINICALTRIALS: gov: NCT05419570.

Pituitary macroadenoma with persisting dense lymphocytic infiltration in a young male patient.

CONTEXT: Lymphocytic anterior hypophysitis in association with a pituitary adenoma was reported previously. In rare instance, inflammatory infiltration was confined to adenoma tissue itself, excluding anterior pituitary. CASE: The patient - a 27-year-old male - presented with visual field defect. Further examination revealed a pituitary mass with suprasellar extension. Hormonal evaluation indicated mild hyperprolactinemia (42 ng/ml, normal < 19). After transsphenoidal resection, a pituitary adenoma showing cytoplasmic immunoreactivity to prolactin was identified. Dense and diffuse lymphocytic infiltration was seen within the tumor. At 15th month, a second transsphenoidal operation was necessary because of rapid development of visual compromise and headache. Excised surgical specimen consistent with previously resected adenoma showed diffuse lymphocytic infiltration composed of B and T cells within the adenoma tissue again. CONCLUSION: Presence of dense, hypophysitis-like lymphocytic infiltration within pituitary adenoma tissue obtained by two consecutive operations may reflect an host-mediated immune reaction to tumor. This rare finding could be challenging in terms of differential diagnosis and follow-up course.

Investigation of early atherosclerotic changes in acromegalic patients.

BACKGROUND: Functional and morphological changes of endothelium were risk factors for mortality attributed to atherosclerosis. Studies investigating early atherosclerotic alterations and the effect of the treatment of acromegaly on these alterations gave conflicting results. OBJECTIVE: Surrogate markers of early atherosclerotic changes, i.e. brachial artery flow-mediated dilation (FMD) and carotid artery intima-media-thickness (IMT) in active and inactive acromegalic patients were compared with control subjects matched to patients for age, sex and cardiovascular risk factors to find out the direct effects of growth hormone (GH)/insulin-like growth factor-1 excess. METHODS: In 14 active acromegalics and their 14 matched controls, 14 inactive acromegalics and their 14 matched controls, carotid artery IMT and FMD of brachial artery were measured. Inactive acromegalics were in remission for at least 1 year. RESULTS: Active acromegalics had higher IMT than matched controls and inactive acromegalics (0.85 +/- 0.20 mm, 0.64 +/- 1.77 mm, 0.66 +/- 0.20 mm respectively; p < 0.005, p < 0.05) and IMT of inactive acromegalics was not different from their matched controls (0.61 +/- 0.12 mm). FMD was significantly lower in active acromegalics than in matched controls and inactive acromegalics (2.910 +/- 2.00 mm, 6.5 +/- 2.81 mm, 5.68 +/- 2.9 mm respectively; p < 0.005, p < 0.05). FMD of inactive acromegalics was not significantly different from their matched controls (7.96 +/- 3.12 mm). A significant inverse relationship was found between GH and FMD in active acromegalics (r = -0.659, p = 0.010). CONCLUSION: In active acromegalics, early atherosclerotic changes are not only attributed to the high prevalence of risk factors, but also to the abnormal GH secretion itself.

Malignant phaeochromocytoma with cavoatrial extension: transcaval removal of tumor without cardiopulmonary bypass A case report.

Adrenal carcinoma is a rare tumor and with metastasis usually in lungs, lymph nodes, liver, and bones. However, intracaval invasion extending into the right atrium is very rare. The surgical approach to adrenal tumor extending into the vena cava is challenging. The optimal surgical approach of tumor with inferior vena cava extension depends on the level of vena cava involvement. This article reports a case of malignant pheochromocytoma extending into the cavoatrial junction in a young man.

Endothelial function and endothelial nitric oxide synthase intron 4a/b polymorphism in primary hyperparathyroidism.

BACKGROUND AND AIM: Patients with symptomatic primary hyperparathyroidism (pHT) have increased cardiovascular morbidity and mortality. Endothelial nitric oxide synthase (eNOS) intron 4a/b polymorphism is associated with coronary artery disease and hypertension in various populations. Our aim is to evaluate endothelial function in patients with pHT during pre-operative hypercalcemic and post-operative normocalcemic periods and to determine whether intron 4a/b polymorphism of eNOS gene influences endothelial function. SUBJECTS AND METHODS: Forty patients with pHT (age 48.48+/-11.64 yr) were examined pre-operatively and reexamined 5.8+/-1.9 months after parathyroidectomy. Forty-three healthy subjects (age 47.13+/-8.14 yr) were served as control group. Endothelial function was determined by flow-mediated dilation of brachial artery (FMD). eNOS4a/b polymorphism was detected by polymerase chain reaction. RESULTS: FMD was significantly lower in patients pre-operatively compared with controls (8.48+/-1.78% vs 19.49+/-2.34%, p<0.001). FMD improved significantly after parathyroidectomy (16.19+/-2.16%, p<0.001 compared with pre-operative measurements), but was still significantly lower than controls (p<0.001). The distribution of eNOS4a/b genotype frequencies was not significantly different between patients and controls. Logistic regression analysis showed that increased serum calcium (>2.47 mmol/l) and PTH concentrations (>7.75 pmol/l) were significant independent predictors of lower FMD (<16.7%). ENOS4a/b polymorphism did not enter in this model. CONCLUSION: Impaired endothelial function in patients with pHT improves after successful parathyroid surgery. No compelling data are evident to suggest that eNOS4a/b polymorphism modifies the endothelial function in patients with pHT.

Prognostic factors in patients with papillary thyroid carcinoma.

BACKGROUND: Papillary thyroid carcinomas are associated with metastases and decreased survival in a small group of patients. AIM: The aim of this study is to determine the factors associated with recurrences/metastases in papillary thyroid carcinoma patients. SUBJECTS AND METHODS: One hundred and thirty-one patients with papillary thyroid carcinoma were evaluated retrospectively. The diagnosis was papillary microcarcinoma (PMC) in 48 patients. All patients had undergone near-total/total thyroidectomy. Radioactive iodine was given to 103 patients. Age at diagnosis, gender, previous history of thyroid disease, tumor stage, histopathological characteristics of tumor and initial treatment strategies were evaluated. RESULTS: Recurrences/metastases developed in 17 patients during follow-up. Recurrences developed at a significantly higher percentage in patients with a tumor stage >T1 and patients with lymph node metastasis at presentation. No significant difference was observed in recurrence ratio between patients with PMC and patients with a tumor diameter > or =1cm. In the Cox-regression analysis only the advanced tumor stage (>T1) and presence of lymph node metastases were found to be significant predictors for recurrence (univariate analysis, odds ratio =4.02 and 3.15, respectively). However, multivariate analysis did not reveal any significant independent predictors. According to the Kaplan- Meier survival analysis, lymph node metastases at presentation were associated with a decrease in recurrence-free survival at statistical significance (p=0.05). No mortality was observed during follow-up. CONCLUSION: Papillary thyroid carcinoma leads to recurrences/metastases in a small group of patients. Initial characteristics of the patients--i.e. presence of lymph node metastases--may predict recurrences/metastases in these patients.

Effects of thyroxine replacement on lipid profile and endothelial function after thyroidectomy.

BACKGROUND: Hypothyroidism is a risk factor for atherosclerotic cardiovascular disease. This study investigated the effects of L-thyroxine replacement therapy on lipid profile and endothelial function after thyroidectomy in patients with overt transient non-autoimmune hypothyroidism. METHODS: Twenty-two patients with non-toxic multinodular goitre treated by total or near-total thyroidectomy and 22 healthy individuals matched for age, sex and body mass index were studied. Lipid profile and endothelial function were determined in each patient at the euthyroid phase before thyroidectomy (stage 1), the hypothyroid phase 3 weeks after surgery (stage 2), and the euthyroid phase 3 months (stage 3) and 6 months (stage 4) after the start of thyroxine treatment. RESULTS: The lipid profile and endothelial function deteriorated between stage 1 and stages 2 and 3. Findings at stage 4 were similar to those at stage 1. There was a positive correlation between serum thyroid-stimulating hormone (TSH) and total cholesterol (r(s) = 0.588, P < 0.001), and a negative correlation between serum TSH and flow-mediated arterial dilatation (r(s) = 0.506, P < 0.001). Total cholesterol and TSH were independent determinants of endothelial function. CONCLUSION: A 3-week hypothyroid period after thyroidectomy led to a more atherogenic lipid profile and impaired endothelial function that persisted for at least 3 months.

Thallium-201, technetium-99m-tetrofosmin and iodine-131 in detecting differentiated thyroid carcinoma metastases.

UNLABELLED: The purpose of this study was to asses the detectability of differentiated thyroid carcinoma (DTC) metastases by 99mTc-tetrofosmin and to compare the results of 99mTc-tetrofosmin with 131I and 201Tl. The reliability of 201Tl and 99mTc-tetrofosmin scanning during suppression therapy also has been studied. METHODS: A prospective study was performed on 41 patients (30 females, 11 males) with DTC (30 papillary, 11 follicular) who had undergone total thyroidectomy and received an average dose of 117 mCi (4329 MBq) of radioiodine for ablation of postsurgical residual thyroid tissue. All patients (n = 41) had 201Tl, 99mTc-tetrofosmin or 131I whole-body imaging after discontinuation of thyroid hormone replacement (thyroxine-off group). Eight of 14 patients with distant metastases also were imaged when they were on thyroxine therapy both with 201Tl and 99mTc-tetrofosmin (thyroxine on-and-off group). Radiologic studies (chest radiography, CT and MRI), serum thyroglobulin assays and histopathologic examinations were performed to clarify the presence of metastases with positive uptake on any of three radionuclide studies. RESULTS: In 26 of 41 patients all three scans were negative. These patients also clinically didn't show any evidence of metastases. Fourteen patients were considered to have distant metastases on the basis of clinical, radiologic and histopathologic findings. The sensitivities of 201Tl, 99mTc-tetrofosmin and 131I in diagnosing distant metastases were comparable (0.85, 0.85 and 0.78, respectively). Iodine-131 was much more sensitive than 201Tl and 99mTc-tetrofosmin for demonstrating residual thyroid tissue after surgery (1.00, 0.33 and 0.33, respectively). The only false-positive case involved radioiodine uptake in a tuberculoma. Thyroxine-on images of 8 patients with distant metastases showed no difference from their thyroxine-off images regarding the site, number and uptake of metastases. CONCLUSION: Technetium-99m-tetrofosmin and 201Tl imaging are highly sensitive for detecting differentiated thyroid carcinoma metastases and do not require prior withdrawal of thyroid hormone suppressive therapy.

A rare complication of adjustable gastric banding: Wernicke's encephalopathy.

BACKGROUND: Wernicke's encephalopathy is an uncommon complication seen after morbid obesity surgery. Neurological and cardiac symptoms can occur. Early and adequate replacement of thiamin is crucial. METHODS: A patient, who was operated by adjustable silicone gastric banding had severe vomiting 1 week after the operation. Physical examination showed no abnormalities except neurological signs consisting of ataxia, disorientation and diplopia. All radiological and biochemical parameters were in the normal range. RESULT: After replacement of vitamin B1 (thiamin) intravenously 20 mg twice daily, all the neurological signs regressed day by day. Oral thiamin pills have been continued. CONCLUSION: Wernicke's encephalopathy which occurs as a result of thiamin deficiency is a rare complication that has serious morbidity with rapidly progressing neurologic symptoms, and must be treated immediately. Surgeons who treat morbidly obese patients must follow the metabolic and nutritional status of the patient.

A young female patient with an androgen-secreting tumor: a rare malignant disease.

A 23-year-old female patient presented with hirsutism and fatigue nine months after delivery. Endocrine assessment showed high testesterone, DHEA-S and androstenedione levels. Abdominal computed tomography and ultrasonography revealed the presence of a large tumor in the right renal region. Right adrenalectomy was performed resulting in a diagnosis of a functional adrenal tumor. Pathological examination showed a steroidogenically active tumor. Adjuvant chemotheraphy was administered postoperatively. At three months following surgery all endocrinological tests normalized, but liver metastases were detected by abdominal CT. Eight months after the operation the patient died of hepatic and renal failure. Androgen-secreting adrenal tumors are seen very rarely, yet the prognosis is poor due to their agressive nature.

Relationship between cardiovascular risk indicators and types of obesity in overweight and obese women.

We aimed to evaluate the relationship between different types of obesity and cardiovascular risk indicators. A total of 623 overweight (body mass index [BMI] > 25 kg/m2), and 2559 obese (BMI > 30 kg/m2) women were divided into four groups according to their BMI and waist-to-hip ratio (WHR): simple overweight (BMI 25-30 kg/m2 and WHR < 0.8, n = 371), abdominal adiposity (BMI 25-30 kg/m2 and WHR > 0.8, n = 252), peripheral (pure) obesity (BMI > 30 kg/m2 and WHR < 0.8, n = 918) and central obesity (BMI > 30 kg/m2 and WHR > 0.8, n = 1641). The levels of the risk indicators measured (clinical, anthropometric and laboratory) were significantly higher in the central obesity group. Total body fat and abdominal fat accumulation seems to result in more serious hyperinsulinaemia and insulin resistance in central obesity. Measuring BMI and WHR in obese patients may reveal their risk for coronary heart disease.

Pituitary macroadenoma in Addison's disease.

Long-standing primary failure of pituitary-dependent endocrine glands may lead to hyperplasia of the pituitary cells. These changes in the pituitary gland may be correlated with the severity and duration of target-endocrine gland insufficiency. Production of adrenocorticotrophic hormone by the pituitary tumour and modest hyperprolactinaemia may develop due to adrenocortical insufficiency, but production of prolactin by the pituitary tumour due to primary adrenal insufficiency is rare. A case study is presented, with primary adrenal insufficiency associated with hyperprolactinaemia and pituitary macroadenoma (most probably prolactinoma). Plasma levels of prolactin were found to decrease after glucocorticoid, mineralocorticoid and bromocriptine therapy.

Relationship between adrenal cortex pathology in Cushing's syndrome and its response to the dexamethasone suppression test.

Cushing's syndrome is a severely disabling condition which can cause death if left untreated. Endogenous Cushing's syndrome can be ACTH-dependent or ACTH-independent. The ACTH-dependent type is more common and is usually caused by diffuse hyperplasia on the adrenal cortex. This study investigated the response to low- and high-dose dexamethasone suppression testing of 30 adrenalectomized patients with Cushing's syndrome, average age 37.3 +/- 9.7 years. Twenty-four (79.3%) patients were female, and six (20.7%) were male. Bilateral adrenalectomy was performed in 14 (48.2%) patients and unilateral adrenalectomy (nine and seven right adrenalectomy) in 16 (51.8%). Two of the bilateral adrenalectomies were applied via endoscopic surgical approach. In the histopathological evaluation, diffuse hyperplasia was diagnosed in 13 (44.8%) patients and nodular hyperplasia in eight (26.6%), three macronodular and five micronodular hyperplasia. Adrenal cell adenoma was diagnosed in nine (28.6%) patients. Classic dexamethasone suppression testing was performed on all patients. Plasma levels of cortisol were not significantly decreased after low-dose testing, but plasma levels of cortisol were significantly decreased after high-dose testing in the diffuse hyperplasia group. In summary, due to the pathological changes of the adrenal cortex, dexamethasone suppression testing can differentiate between the two types of Cushing's syndrome.

Assessment of adrenal functions in patients with autosomal dominant polycystic kidney disease.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disease and extrarenal manifestations may be observed in many organ systems. Hypothalamus-pituitary-adrenal axis was not evaluated extensively in patients with ADPKD. We aimed to evaluate this axis in these patients. METHODS: Twenty two patients with ADPKD and 27 healthy subjects were enrolled. Basal dehydroepiandrosterone sulfate (DHEAS) levels and cortisol and DHEA responses to low dose short adrenocorticotropin stimulation test were assessed. Correlation analyses of these parameters with glomerular filtration rates (GFR), renal volumes and pain characteristics in patients with ADPKD were performed. RESULTS: Patients with ADPKD had higher basal cortisol levels (12.1 ± 3.4 vs. 9.6 ± 4.3 µg/dL, p=0.033), and higher basal cortisol/DHEAS ratios (0.073 ± 0.05 vs. 0.045 ± 0.02, p=0.015) compared to controls. None of the subjects had inadequate response to adrenocorticotropin stimulation. Patients with ADPKD had lower delta cortisol (absolute increase between peak and basal) levels (10.3 ± 2.8 vs. 12.6 ± 4.2 µg/dL, p=0.026) compared to controls. Subgroup analysis showed that significant differences existed only between female patients and female controls. There was no significant correlation between cortisol levels and renal volumes or GFR. A significant correlation was found only between delta cortisol and pain frequency in female patients. CONCLUSIONS: Patients with ADPKD had higher basal cortisol levels, higher basal cortisol/DHEAS ratios and lower delta cortisol levels compared to controls, indicating promptly stimulated zona fasciculata function. Further studies are needed to confirm these results and to investigate possible underlying mechanisms.

Graves' disease, with and without nodules, and the risk of thyroid carcinoma.

OBJECTIVE: Thyroid nodules are frequently present in Graves' disease. The aim of this study was to evaluate the risk of thyroid carcinoma in Graves' disease patients, with and without ultrasonographically identified nodules, who subsequently underwent surgical treatment. DESIGN: The study group included 150 consecutive patients with diagnosed Graves' disease who subsequently underwent surgery. SUBJECTS: The patients were divided into two groups according to whether the pre-operative ultrasound scan showed diffuse parenchyma (group one; n = 70) or nodules (group two; n = 80). RESULTS: Of the 150 patients, 18 (12 per cent) were found to have papillary thyroid carcinoma. Papillary carcinoma was found in seven patients (10 per cent) in group one and in 11 patients (1.7 per cent) in group two. After evaluating the overall groups, the incidence of carcinoma in the parenchyma outside a nodule was 67 per cent, whereas the incidence of carcinoma in a nodule was 33 per cent. CONCLUSION: Carcinoma can occur in Graves' disease patients without nodules, and the absence of nodules on ultrasonographic examination does not reduce the risk of malignancy.

Predictive factors for recurrent non-toxic goitre in an endemic region.

AIMS: We aimed to determine the risk factors for recurrence and to assess the complication rate associated with surgery for benign, recurrent goitre. METHODS: We studied 125 consecutive patients with recurrent goitre who underwent re-operative thyroid surgery (group one). Patients in the control group were randomly selected from those undergoing their first procedure during the same period (group two). Age, initial surgery, presence of multinodular goitre, presence of carcinoma in the resected thyroid tissue, interval between initial operation and re-operation, and complications were analysed and compared for the two groups. RESULTS: The mean age (+/- standard deviation) was found to be significantly greater in group one compared with group two. The mean age at the time of primary thyroid operation was found to be significantly less in group one compared with group two. The interval between the initial and the re-operative procedures was a mean of 15.8+/-eight years. Initial surgery was conservative. Papillary thyroid carcinoma was found in 14/125 (11 per cent) of group one patients. The incidence of complications was found to be significantly higher in group one compared with group two. CONCLUSION: The incidence of recurrent goitre has been directly related to conservative thyroid surgery and to the retention of large amounts of remnant tissue. To avoid recurrent goitre and possible re-operative complications, total or near-total thyroidectomy should be performed in all patients with bilateral, multinodular goitre, especially in endemic regions.