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- Primary Non-Necrotizing Granulomatous Hypophysitis Mimicking Pituitary Adenomas. [JOURNAL ARTICLE]
- Turk Neurosurg 2014; 24(5):688-694.
The authors review their experience in the endoscopic endonasal transsphenoidal treatment of 5 patients, finally diagnosed as primary hypophysitis but initially assumed to be pituitary adenomas. MATERIAL and METHODS: A retrospective study was undertaken to review 5 cases of primary non-necrotizing granulomatous hypophysitis (1.61%) through 310 endoscopic transsphenoidally operated cases with the diagnosis of pituitary adenoma between 2009 and 2013. All 5 cases were female without any background of autoimmunity or recent pregnancy. The initial presumptive diagnosis was pituitary adenoma for all patients. The endocrinological diagnoses of the patients were suspected Cushing's Disease, anterior pituitary deficiency with hyponatremia, hyperprolactinemia, and acromegaly. One of the patients had normal hormonal levels. All patients had macroadenomas including one invasive adenoma with skull base involvement. One of the patients (20%) had visual field defects. All patients underwent endoscopic endonasal transsphenoidal surgery (EETS).All patients had improvement of hormonal levels postoperatively except the one with anterior pituitary deficiency who required long term hormone replacement after the surgery. Mean follow-up duration was 14.8 months.Primary granulomatous hypophysitis without any known etiological factors is very rare in the literature. It can mimic pituitary adenomas in radiological and endocrinological aspects. EETS is an effective and safe treatment especially for visual and compression symptoms.
- Water Extract of Fructus Hordei Germinatus Shows Antihyperprolactinemia Activity via Dopamine D2 Receptor. [Journal Article]
- Evid Based Complement Alternat Med 2014.:579054.
Objective.Fructus Hordei Germinatus is widely used in treating hyperprolactinemia (hyperPRL) as a kind of Chinese traditional herb in China. In this study, we investigated the anti-hyperPRL activity of water extract of Fructus Hordei Germinatus (WEFHG) and mechanism of action. Methods. Effect of WEFHG on serum prolactin (PRL), estradiol (E2), progesterone (P), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and hypothalamus protein kinase A (PKA) and cyclic adenosine monophosphate (cAMP) levels of hyperPRL rats were investigated. And effect of WEFHG on PRL secretion, D2 receptors, and dopamine transporters (DAT) was studied in MMQ, GH3, and PC12 cells, respectively.
Results.WEFHG reduced the secretion of PRL in hyperPRL rats effectively. In MMQ cell, treatment with WEFHG at 1-5 mg/mL significantly suppressed PRL secretion and synthesis. Consistent with a D2-action, WEFHG did not affect PRL in rat pituitary lactotropic tumor-derived GH3 cells that lack the D2 receptor expression but significantly increased the expression of D2 receptors and DAT in PC12 cells. In addition, WEFHG reduced the cAMP and PKA levels of hypothalamus in hyperPRL rats significantly.
Conclusions.WEFHG showed anti-hyperPRL activity via dopamine D2 receptor, which was related to the second messenger cAMP and PKA.
- Pituitary stalk interruption syndrome: Case report of three cases with review of literature. [Journal Article]
- J Pediatr Neurosci 2014 May; 9(2):188-91.
Pickardt syndrome (Pickardt-Fahlbusch syndrome) is a rare congenital syndrome characterized by tertiary hypothyroidism caused by the interruption of the portal veins between hypothalamus and adenohypophysis. Typical features of this syndrome are tertiary hypothyroidism with low thyroid stimulating hormone, hyperprolactinemia and other pituitary hormone deficiencies. Pituitary stalk interruption syndrome is characterized by a triad of thin or interrupted pituitary stalk, aplasia or hypoplasia of the anterior pituitary and absent or ectopic posterior pituitary (EPP) seen on magnetic resonance imaging (MRI). It is a congenital anomaly of pituitary whose exact prevalence is unknown. In some cases, it is restricted to EPP or pituitary stalk interruption. We are presenting the case history along with MRI finding of three children's who presented with short stature and delayed puberty.
- Hyperprolactinemia and prolactinoma. [Journal Article]
- Handb Clin Neurol 2014.:185-95.
Prolactinomas are the most frequent pituitary adenomas. In patients with prolactinomas the primary cause of hyperprolactinemia is excessive and autonomic production of prolactin by lactotroph cells. In other conditions, except in case of macroprolactinemia, hyperprolactinemia is secondary to circumstances that stimulate secretion of prolactin by intrinsically normal lactotroph cells, or, rarely, that are the result of decreased clearance of prolactin. In general, cabergoline is the preferred treatment for micro- and macroprolactinomas, because it is more effective with respect to normalization of prolactin levels and reduction of prolactinoma size and because it has fewer side-effects compared to bromocriptine. Recently, it has been suggested that a standardized, individualized, stepwise, dose-escalating regimen of cabergoline may normalize prolactin levels and reduce prolactinoma size in patients who were otherwise considered to be dopamine agonist resistant. In general, the cardiac adverse effects of dopamine agonists reported in Parkinson's disease are not of clinical concern in the treatment of prolactinomas, which are treated with much lower doses. Nonetheless, there is uncertainty with respect to the dose and duration of cabergoline treatment, which requires echocardiographic follow-up. Although withdrawal of dopamine agonists may be considered in patients with prolactinomas well controlled by dopamine agonists, especially in postmenopausal women, recurrence of signs and symptoms may occur in a considerable portion of patients.
- Pituitary imaging findings in male patients with hypogonadotrophic hypogonadism. [JOURNAL ARTICLE]
- Pituitary 2014 Sep 23.
Data on pituitary imaging in adult male patients presenting with hypogonadotrophic hypogonadism (HH) and no known pituitary disease are scarce.To assess the usefulness of pituitary imaging in the evaluation of men presenting with HH after excluding known pituitary disorders and hyperprolactinemia.A historical prospective cohort of males with HH.Men who presented for endocrine evaluation from 2011 to 2014 with testosterone levels <10.4 nmol/L (300 ng/mL), normal LH and FSH levels and no known pituitary disease.Seventy-five men were included in the analysis. Their mean age and BMI were 53.4 ± 14.8 years and 30.7 ± 5.2 kg/m(2), respectively. Mean total testosterone, LH, and FSH were 6.2 ± 1.7 nmol/L, 3.4 ± 2 and 4.7 ± 3.1 mIU/L, respectively. Prolactin level within the normal range was obtained in all men (mean 161 ± 61, range 41-347 mIU/L). Sixty-two men had pituitary MRI and 13 performed CT. In 61 (81.3 %) men pituitary imaging was normal. Microadenoma was found in 8 (10.7 %), empty sella and thickened pituitary stalk in one patient (1.3 %) each. In other four patients (5.3 %) a small or mildly asymmetric pituitary gland was noted. No correlation was found between testosterone level and the presence of pituitary anomalies.This study suggests that the use of routine hypothalamic-pituitary imaging in the evaluation of IHH, in the absence of clinical characteristics of other hormonal loss or sellar compression symptoms, will not increase the diagnostic yield of sellar structural abnormalities over that reported in the general population.
- Sheehan's syndrome co-existing with Graves' disease. [JOURNAL ARTICLE]
- Niger J Clin Pract 2014 September-October; 17(5):662-665.
Sheehan's syndrome (SS), which is an important cause of hypopituitarism, is common in developing countries. The most common presentation is the absence of lactation and amenorrhea. Hypothyroidism rather than hyperthyroidism is the usual expected phenomenon in SS. Postpartum hyperthyroidism is also common and Graves' disease (GD) is an important cause of postpartum hyperthyroidism. Here we report a case of a 22-year-old female patient in our clinic presented symptoms of amenorrhea, lack of lactation, palpitations and sweating. Her physical examination revealed goiter, moist skin and proptosis. Her laboratory evaluation showed suppressed thyroid stimulating hormone, elevated levels of free thyroxine and free triiodothyronine. Thyroid antibodies were positive. Tec 99m thyroid scintigraphy results were gland hyperplasia and increased uptake consistent with GD. She gave birth 7 months ago; after delivery she had a history of prolonged bleeding, amenorrhea and inability to lactate. She had hypogonadotropic hypogonadism, hyperprolactinemia and growth hormone deficiency. Serum cortisol and adrenocorticotropic hormone levels were normal. Her magnetic resonance imaging was empty sella. Our diagnosis was GD co-existing with SS. GD with concomitant hypopituitarism is rare but has been described previously, but there are no reports of GD occurring with SS. In this case study, we report a patient with GD associated with SS.
- The effect of short-term metformin treatment on plasma prolactin levels in bromocriptine-treated patients with hyperprolactinaemia and impaired glucose tolerance: a pilot study. [JOURNAL ARTICLE]
- Endocrine 2014 Sep 20.
Metformin was found to affect plasma levels of some pituitary hormones. This study was aimed at investigating whether metformin treatment has an impact on plasma prolactin levels in bromocriptine-treated patients with hyperprolactinaemia and impaired glucose tolerance. The study included 27 patients with hyperprolactinaemia, who had been treated for at least 6 months with bromocriptine. Based on prolactin levels, bromocriptine-treated patients were divided into two groups: patients with elevated (group A, n = 12) and patients with normal (group B, n = 15) prolactin levels. The control group included 16 age-, sex- and weight-matched hyperprolactinaemia-free individuals with impaired glucose tolerance (group C).The lipid profile, fasting plasma glucose levels, the homeostatic model assessment of insulin resistance ratio (HOMA-IR), glycated haemoglobin, as well as plasma levels of prolactin, thyrotropin and insulin-like growth factor-1 (IGF-1) were assessed at baseline and after 4 months of metformin treatment (2.55-3 g daily). In all treatment groups, metformin reduced HOMA-IR, plasma triglycerides and 2-h postchallenge plasma glucose. In patients with hyperprolactinaemia, but not in the other groups of patients, metformin slightly reduced plasma levels of prolactin, and this effect correlated weakly with the metabolic effects of this drug. Our study shows that metformin decreases plasma prolactin levels only in patients with elevated levels of this hormone. The obtained results suggest that metformin treatment may bring some benefits to hyperprolactinaemic patients with coexisting glucose metabolism disturbances already receiving dopamine agonist therapy.
- Clinicopathological characteristics and therapeutic outcomes in thyrotropin-secreting pituitary adenomas: a single-center study of 90 cases. [JOURNAL ARTICLE]
- J Neurosurg 2014 Sep 19.:1-12.
Object The aim of this study was to analyze clinicopathological characteristics and treatment outcomes in a large single-center clinical series of cases of thyrotropin (TSH)-secreting pituitary adenomas. Methods The authors retrospectively reviewed clinical, pathological, and treatment characteristics of 90 consecutive cases of TSH-secreting pituitary adenomas treated with transsphenoidal surgery between December 1991 and May 2013. The patient group included 47 females and 43 males (median age 42 years, range 11-74 years). Results Sixteen tumors (18%) were microadenomas and 74 (82%) were macroadenomas. Microadenomas were significantly more frequent in the more recent half of our case series (12 of 45 cases) (p = 0.0274). Cavernous sinus invasion was confirmed in 21 patients (23%). In 67 cases (74%), the tumors were firm elastic or hard in consistency. Acromegaly and hyperprolactinemia were observed, respectively, in 14 (16%) and 11 (12%) of the 90 cases. Euthyroidism was achieved in 40 (83%) of 48 patients and tumor shrinkage was found in 24 (55%) of 44 patients following preoperative somatostatin analog treatment. Conventional transsphenoidal surgery, extended transsphenoidal surgery, and a simultaneous combined supra- and infrasellar approach were performed in 85, 2, and 3 patients, respectively. Total removal with endocrinological remission was achieved in 76 (84%) of 90 patients, including all 16 (100%) patients with microadenomas, 60 (81%) of the 74 with macroadenomas, and 8 (38%) of the 21 with cavernous sinus invasion. None of these 76 patients experienced tumor recurrence during a median follow-up period of 2.8 years. Stratifying by Knosp grade, total removal with endocrinological remission was achieved in 34 of 36 patients with Knosp Grade 0 tumors, all 24 of those with Grade 1 tumors, 12 of the 14 with Grade 2 tumors, 6 of the 8 with Grade 3 tumors, and none of the 8 with Grade 4 tumors. Cavernous sinus invasion and tumor size were significant independent predictors of surgical outcome. Immunoreactivity for growth hormone, prolactin, or both hormones was present in 32, 9, and 24 patients, respectively. The Ki-67 labeling index was less than 3% in 71 (97%) of 73 tumors for which it was obtained and 3% or more in 2. Postsurgery pituitary dysfunction was found in 15 patients (17%) and delayed hyponatremia was seen in 9. Conclusions TSH-secreting adenomas, particularly those in the microadenoma stage, have increased in frequency over the past 5 years. The high surgical success rate achieved in this series is due to relatively early diagnosis and relatively small tumor size. In addition, the surgical strategies used, such as extracapsular removal of hard or solid adenomas, aggressive resction of tumors with cavernous sinus invasion, or extended transsphenoidal surgery or a simultaneous combined approach for large/giant multilobulated adenomas, also may improve remission rate with a minimal incidence of complications.
- Color Doppler analysis of uterine, spiral, and intraovarian artery blood flow before and after treatment with cabergoline in hyperprolactinemic patients. [JOURNAL ARTICLE]
- Gynecol Endocrinol 2014 Sep 15.:1-4.
Abstract Prolactin (PRL) may have stimulatory effects on vascular resistance. We aimed to analyze uterine, spiral, and intraovarian artery blood flow by Doppler ultrasonography in hyperprolactinemic patients prior to and after treatment with cabergoline. The study was conducted in Sisli Etfal Training and Research Hospital gynecology outpatient clinic between 1 March 2010 and 30 September 2011. Twenty-four women with symptomatic hyperprolactinemia in reproduction age were included in the study. All hyperprolactinemic patients were studied prior to and following the suppression of circulating PRL levels by cabergoline. Patients were examined by standard B-mod and color transvaginal ultrasonography. Pulsality index (PI), resistance index (RI), and systolic/diastolic ratio (S/D) were recorded. The median PRL value was 86 (62-120) ng/ml before treatment and 4.0 (2.5-6.4) ng/ml after the treatment (p < 0.001). We found a significant association among PRL, uterine, spiral, and intraovarian artery RI with linear regression analysis (p < 0.001 for all three arteries). Uterine, spiral, and intraovarian artery PI (p = 0.021, p < 0.001, and p < 0.001, respectively) and RI (p = 0.001, p < 0.001, and p < 0.001, respectively) significantly decreased after cabergoline treatment. In conclusion, this is a pilot study which shows for the first time that PRL increases the uterine, endometrial, and intraovarian vascular resistance and cabergoline reverses this effect.
- Serotonergic 5-HT2A/2C receptors are involved in prolactin secretion in hyperestrogenic rats. [JOURNAL ARTICLE]
- Neurosci Lett 2014 Sep 8.:71-74.
Serotonin (5-HT) has been shown to participate in prolactin secretion through a complex process resulting in both positive and negative effects. Estrogen has also been recognized as being involved in this serotonergic effect on prolactin release. Therefore, the aim of the present study was to assess whether estradiol modulates serotonergic involvement in prolactin secretion though 5-HT1A and/or 5-HT2A/2C receptors. Ovariectomized female Wistar rats, treated for 2 weeks with estrogen to induce a hyperprolactinemic status (hyperestrogenic rats) or with sunflower oil vehicle (hypoestrogenic rats), were injected daily with normal saline solution or 6-chloro-2-(1-piperazinyl)pyrazine (MK-212), an 5-HT2A/2C receptor agonist, for 4 days. Other groups of ovariectomized animals received 8-hydroxy-2-(di-N-propylamino)tetralin (8-OH-DPAT) or pindolol, an agonist and antagonist of the 5-HT1A receptor respectively, on the last day of treatment with estrogen or vehicle. Prolactin levels were compared among groups in each experiment under the distinct drug treatments. MK-212 was found to increase prolactin concentrations both in hyper- and hypoestrogenic females compared to controls (p<0.05). In contrast, prolactin levels remained similar to those of controls both in hyperestrogenic animals treated with 8-OH-DPAT and pindolol and in hypoestrogenic rats administered the same treatments. In conclusion, our findings indicate the involvement of 5-HT2A/2C receptors on prolactin release through serotonergic pathways in female animals, especially in hyperestrogenic states.