An intelligent decision support tool for early diagnosis of functional pituitary adenomas

In this work, a web based integrated Medical Decision Support System (MDSS) tool for mainly early diagnosis of functional pituitary adenomas (i.e., somatotrophinoma, corticotrophinoma and prolactinoma) is developed. In the MDSS tool, hormone diseases are described by means of well-classified set of attributes generated from the typical sign and symptoms of disorders.The proposed tool is based on a stationary linear stochastic system model which specifically predicts the selected hormone diseases employing certain system parameters. The MDSS tool is user friendly which includes questions and answers at the opening session of the self-test. Questions and answers session will be completed by “yes” or “no” type of simple-responses. Based on our clinical results, MDSS tool yields more than 99% correct decisions on the selected hormone diseases. It is expected that effective use of the proposed MDSS tool will save substantial amount of valuable time of an expert endocrinologists and minimizes the cost of diagnosis. Furthermore, it will provide the opportunity for early diagnosis for the patient and the expert medical doctor to take the necessary preventive measures.Publisher's Versio

Evaluation of pulmonary side effects in prolactinoma patients treated with cabergoline

Introduction: Cabergoline (CAB) is the most used dopamine agonist in the treatment of prolactinomas. Studies related to the treatment of Parkinson’s disease have shown that dopamine agonists can lead to fibrotic syndromes affecting the heart and the lung. The aim of this study was to evaluate the possible pulmonary side effects of CAB in prolactinoma patients. Material and methods: Chest X-ray imaging and pulmonary function parameters like forced vital capacity (FVC), total lung capacity (TLC), and diffusion capacity for carbon monoxide (DLCO) were evaluated in 73 prolactinoma patients. The cumulative dose of CAB and the total duration of CAB use were also calculated, and all data were reviewed retrospectively. Results: The median cumulative CAB dose was 192 mg, and the median duration of CAB use was 64 months. Only 13 patients (17%) among this cohort had abnormal DLCO results that could be an indirect sign of pulmonary fibrosis. These abnormal DLCO results were found not to be associated with cumulative CAB dose in these 13 patients. Conclusions: CAB appears to be safe in terms of pulmonary functions with a median cumulative dose of 192 mg in prolactinoma patients

Significant benefits of AIP testing and clinical screening in familial isolated and young-onset pituitary tumors

Context Germline mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene are responsible for a subset of familial isolated pituitary adenoma (FIPA) cases and sporadic pituitary neuroendocrine tumors (PitNETs). Objective To compare prospectively diagnosed AIP mutation-positive (AIPmut) PitNET patients with clinically presenting patients and to compare the clinical characteristics of AIPmut and AIPneg PitNET patients. Design 12-year prospective, observational study. Participants & Setting We studied probands and family members of FIPA kindreds and sporadic patients with disease onset ≤18 years or macroadenomas with onset ≤30 years (n = 1477). This was a collaborative study conducted at referral centers for pituitary diseases. Interventions & Outcome AIP testing and clinical screening for pituitary disease. Comparison of characteristics of prospectively diagnosed (n = 22) vs clinically presenting AIPmut PitNET patients (n = 145), and AIPmut (n = 167) vs AIPneg PitNET patients (n = 1310). Results Prospectively diagnosed AIPmut PitNET patients had smaller lesions with less suprasellar extension or cavernous sinus invasion and required fewer treatments with fewer operations and no radiotherapy compared with clinically presenting cases; there were fewer cases with active disease and hypopituitarism at last follow-up. When comparing AIPmut and AIPneg cases, AIPmut patients were more often males, younger, more often had GH excess, pituitary apoplexy, suprasellar extension, and more patients required multimodal therapy, including radiotherapy. AIPmut patients (n = 136) with GH excess were taller than AIPneg counterparts (n = 650). Conclusions Prospectively diagnosed AIPmut patients show better outcomes than clinically presenting cases, demonstrating the benefits of genetic and clinical screening. AIP-related pituitary disease has a wide spectrum ranging from aggressively growing lesions to stable or indolent disease course

Hyponatremia as the presenting manifestation of Sheehan's syndrome in elderly patients

Background and aims: Hyponatremia is not a disease in itself, but a manifestation of a variety of disorders and side-effects of diuretics; alternatively, it may be the only manifestation of hypopituitarism or hypothyroidism. In our experience, diagnosis of hypopituitarism in hyponatremic patients is often overlooked, especially in the elderly. Methods: We report here data from five elderly multiparous women (mean age 69 yr; range 62-78 yr) with a post history of complicated delivery, in whom initial symptoms were due to hyponatremia (serum sodium less than 128 mEq/L) who went undiagnosed and untreated for a long time (up to 42 years) after the initial event. Results: Initial hormonal levels indicated hypopituitarism, and magnetic resonance imaging led to diagnosis of empty sella in all patients, so that they were diagnosed as suffering from Sheehan's syndrome (SS). The occurrence of sodium and water disorders associated with SS depends on the degree of pituitary damage, time of onset since the initial pituitary insult, and concurrent medical conditions which also play a role in sodium and water balance. In these patients, clinical condition and hyponatremia improved rapidly after glucocorticoid substitution. L-thyroxine was appropriately substituted subsequently. Conclusions: We suggest that, especially in elderly patients, much more attention should be paid to patients' past history. Early recognition of severe hyponatremia due to hypopituitarism with adrenal insufficiency is critical, and treatment with hydrocortisone results in safe and improved quality of life

Outcomes of Patients with Macroprolactinoma Desiring Pregnancy: Follow-Up to 23 Years from a Single Center

Macroprolactinomas are rarely seen in women, and pregnancy is a risk factor for tumor growth. More studies are needed to determine appropriate management for macroprolactinoma and pregnancy. The aim of our study is to evaluate effects of treatment with dopamine agonists on macroadenoma before and during pregnancy, safety of dopamine agonists on fetus, post-pregnancy prognosis and long-term results. This is a single center retrospective study. Thirty-four pregnancies occurred in 21 patients under medical therapy. Prolactin levels, treatment results, tumor diameter changes, maternal-fetal outcomes, and disease activity were evaluated. The median tumor size at the time of diagnosis was 15 mm (10-28). Residual adenoma diameter was smaller in those receiving medical therapy longer than one year till the conception (p=0.047). Treatment was discontinued in 28 pregnancies after pregnancy confirmation, and 6 patients were exposed to bromocriptine throughout pregnancy. There was no symptomatic tumor growth during gestation. Among 27 live births, none of the fetuses developed neonatal malformation except for a case of Down syndrome. While early remission rate after pregnancy was 9.5%, this rate reached 33.3% at last follow-up visit. Lowered PRL levels at postpartum period (p=0.040), smaller tumor size at last follow-up visit (p=0.030), and total disappearance of tumor (p=0.026) were the contributor factors for remission. Use of dopamine agonist over one year may reduce the risk of symptomatic tumor growth during pregnancy in patients without invasive or large macroprolactinoma before pregnancy. Exposure to dopamine agonists seems generally safe for the fetus

Review of Clinical Recommendations on Prolactinoma and Pregnancy

Prolactinomas are the most common hormone-secreting pituitary adenomas. Prolactinomas account for nearly 30-40 percent of all the pituitary adenomas. Although it affects individuals over a wide age range, it is more common in 20-40-year-old female patients, who are in their reproductive age. Prolactinomas may cause hypogonadism, menstrual cycle dysfunction (oligomenorrhea or amenorrhea) and infertility (luteal phase abnormalities or anovulation) in premenopausal women. When pregnancy is excluded, hyperprolactinemia in approximately 10 to 20 percent of the patients results in amenorrhea. Women with untreated pro-lactinomas are generally unable to achieve pregnancy, as the hyperprolactinemia affects the pulsatility of gonadotropin-releasing hormone (GnRH) and diminishes follicle-stimulating hormone (FSH) as well as luteinizing hormone (LH) secretion. The sum of these effects induces amenorrhea, infertility, and hypogonadism, thereby posing difficulties in fertility. Therefore, in most women prolactinoma is diagnosed prior to conception. However, ovulation and fertility usually improve after proper diagnosis and treatment of prolactinoma. Therefore, during the surveillance of these patients, the onset of pregnancy is a common phenomenon. Management of these pregnancies may sometimes be challenging and require a multidisciplinary approach involving an endocrinologist, a gynecologist, a radiologist and an experienced neurosurgeon in order to achieve the best outcomes both for the patient as well the infant. In this report, the authors aim to summarize the consensus statements and the current guidelines for clinical practice