Pituitary Region Research Articles

Space occupying processes of the sellar region with emphasis on tumor-like lesions

Most space occupying lesions of the sellar region are tumors (e.g., pituitary adenomas, craniopharyngiomas, but also meningiomas). In approximately 8% of patients with sellar mass lesions, non-neoplastic disorders (e.g., inflammations, cysts, hyperplasia) are causal. Cystic lesions of the pituitary region are classified as Rathke's cysts, colloid cysts, arachnoidal cysts and epidermoid cysts. These have to be differentiated from cystic craniopharyngeomas or cystic pituitary adenomas. Autochthonous inflammations (lymphocyctic hypophysitis, idiopathic granulomatous hypophysitis, xanthomatous and peritumorous hypophysitis) have to be distinguished from generalized diseases involving the pituitary (e.g., sarcoidosis, tuberculosis). Hyperplasia can result in a doubling of pituitary size. Lactotroph and corticotroph hyperplasia are the most common and may be of a diffuse and nodular type. The nodular form of pituitary hyperplasia may show transition into adenoma. Other hyperplasias may be found adjacent to adenomas or other tumours. Furthermore, vascular (aneurysms) and bony lesions (especially fibrous dysplasia) can appear as space occupying lesions of the sellar region.

Posterior ocular malformations in children: somatic, neuroradiological and cognitive aspects

Aim: To investigate associated neurological, endocrinological and cognitive dysfunctions in children with visual impairment caused by optic nerve hypoplasia or optic nerve/fundus coloboma and/or microphthalmus. Methods: Forty children born between 1990 and 1998 were assessed by neurological examination, re‐evaluation of neuroradiological investigations, review of medical records and examination of cognitive levels. Results: Neurological dysfunctions (epilepsy and/or motor impairment) were found in 13/28 children with optic nerve hypoplasia and in 3/12 children with coloboma/microphthalmus. The optic pathways were thin in 22/24, an abnormal posterior pituitary gland and/or thin infundibulum was found in 16/22 and absence of septum pellucidum in 14/27 children with optic nerve hypoplasia. Other types of cerebral abnormalities occurred in 9/26 children. Among children with coloboma/microphthalmus, the optic pathways were thin in 4/8 children but none had pituitary or cerebral midline abnormalities. Sixteen children with optic nerve hypoplasia were receiving hormone substitution but none of the children with coloboma/microphthalmus. Thirteen of the 16 children with optic nerve hypoplasia and with an abnormal pituitary region had endocrinological deficiencies. Mental retardation was found in 9/24 of the children with optic nerve hypoplasia and in 5/10 of the children with coloboma/microphthalmus. Conclusion: Endocrinological, neurological and neuroradiological defects seem more common in children with optic nerve hypoplasia than in children with coloboma. A pituitary region that appears abnormal in magnetic resonance imaging seems to predict endocrinological deficits in children with optic nerve hypoplasia.

Pituitary size in patients with Laron syndrome (primary GH insensitivity).

The purpose of the present study was to investigate whether lifelong secretion of high levels of GH, characteristic of Laron syndrome, leads to an increase in the size of the pituitary gland. Eleven patients (six females, five males) with Laron syndrome underwent magnetic resonance imaging of the pituitary region with a system operating at 0.5 T. There were nine adults aged 36-68 Years and two children, a 4-Year-old boy and a 9-Year-old girl. The latter patient had been treated with IGF-I (150-180 mg/kg per day) since the age of 3 Years; all the other patients were untreated. The height of the adenohypophysis was measured on the sagittal images and compared with reference values for age and sex. The height of the adenohypophysis was within the normal range for age and gender in all patients, except for one male, who had a small gland. No congenital anomalies of the pituitary-hypothalamic region were detected. Despite the lifelong high levels of GH, no pituitary hypertrophy was detected. The anatomy of the pituitary-hypothalamic region in Laron syndrome is normal.

Pituitary corticotroph ontogeny and regulation in transgenic zebrafish.

We characterized zebrafish proopiomelanocortin (POMC) gene promoter, and sequence analysis revealed that the promoter contains regulatory elements conserved among vertebrate species. To monitor the ontogeny of the pituitary POMC lineage in living vertebrates, we generated transgenic zebrafish expressing green fluorescent protein (GFP) driven by the POMC promoter. Zebrafish POMC-GFP is first expressed asymmetrically as two bilateral groups of cells most anterior to the neural ridge midline at 18-20 h post fertilization (hpf). POMC-GFP-positive cells then fuse into a single-cell mass within the pituitary anlage after 24 hpf and subsequently organize as distinct anterior and posterior domains between 48 and 64 hpf. Immunohistochemical studies with ACTH and alphaMSH antisera showed that POMC-GFP was mainly targeted to both anterior and posterior pituitary corticotrophs, whereas posterior pituitary region melanotrophs did not express GFP. To determine in vivo zebrafish corticotroph responses, dexamethasone (10(-5) m) was added to live embryos, which selectively suppressed POMC-GFP expression in the anterior group of corticotrophs, suggesting a distinct domain that is responsive to glucocorticoid feedback. Transgenic zebrafish with specific POMC-GFP expression in pituitary corticotrophs offers a powerful genetic system for in vivo study of vertebrate corticotroph lineage development.

Immunohistochemical proliferation markers may overestimate the growth potential after ionizing radiation: in vivo study in the rat anterior pituitary gland.

The effect of ionizing radiation on the expression of immunohistochemical proliferation markers was examined in the rat pituitary gland. Rats were irradiated in the pituitary region with a dose of 40 Gy, or were sham-irradiated as controls. Bromodeoxyuridine (BrdU) was given to the rats after one week, either one hour (Br-1 group) or 17 hours (Br-17 group) before perfusion fixation. Immunohistochemical staining for BrdU, topoisomerase II-alpha (TopoII), Ki-67 (MIB-5), p21WAF1/Cip1 (p21), and p27Kip1 (p27) was performed. Apoptotic cells were detected by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end-labeling method. The mean BrdU labeling index (LI) and MIB-5 LI were significantly higher in the irradiated rats than in the sham rats in the Br-1 group. TopoII LI was higher in the irradiated rats than in the sham rats, although not significantly. p27-positive cells decreased in irradiated rats, but p21-positive cells increased more than in the sham rats. The number of apoptotic cells increased significantly after radiation. BrdU LIs were lower in the irradiated rats than in the sham rats in the Br-17 group. A few small BrdU-positive fragments with apoptotic features were phagocytosed in the anterior lobe cells. These results indicate that some "immunohistochemically proliferating cells" subsequently undergo apoptosis in the irradiated pituitary gland. The values of proliferative indices should be cautiously interpreted after irradiation of tissue.

MRI findings of the pituitary gland in short children born small for gestational age (SGA) in comparison with growth hormone‐deficient (GHD) children and children with normal stature

Disturbances in the GH/IGF-I axis are reported in 25-60% of short children born small for gestational age (SGA). We hypothesized that these abnormalities might be related to abnormalities in the pituitary region. Therefore, the results of magnetic resonance imaging (MRI) of short SGA children were compared to MRI results of other groups of short children and to normal controls. MRI was performed in four groups of short children: SGA children without GH deficiency (SGA group; n = 17), SGA children with isolated GH deficiency (SGA + IGHD group; n = 10), non-SGA children with isolated GH deficiency (IGHD group; n = 24) and non-SGA children with multiple pituitary hormone deficiencies (MPHD group; n = 15). MRI was also performed in children with normal stature (control group; n = 13). Pituitary height (PH) and thickness of the pituitary stalk (PS) were measured and their relationship with the maximum GH peak during a GH stimulation test, serum IGF-I and IGFBP-3 levels was evaluated. Short SGA children either with or without IGHD did not show major anatomical abnormalities in the hypothalamic-pituitary region in contrast to 58% of the non-SGA IGHD children and 87% of the MPHD children who had anatomical abnormalities. PH in SGA children without GHD was normal whereas it was significantly lower in SGA children with IGHD. The lowest PHs were measured in non-SGA children with MPHD. A moderate decrease in PH was associated with significantly lower maximum serum GH peaks and lower serum IGF-I and IGFBP-3 levels. Measuring PHs in children with less severe GHD, who underwent MRI as part of the diagnostic process, might support the diagnosis of GHD even in the absence of anatomical abnormalities. Our study demonstrates that there is no indication to perform MRI of the pituitary region in short children born SGA without GHD.

Tumor-like Lesions of the Pituitary and Sellar Region

Tumor-like Lesions of the Pituitary and Sellar Region

Giant prolactinomas presenting as skull base tumors

Background Prolactinomas invading the skull base are rare, and could easily be confused with skull base tumors of nonpituitary origin. Case description We report a series of 4 cases of giant prolactinomas invading the skull base and presenting with atypical symptoms. Case 1 presented with a short history of headache and nasal obstruction. Case 2 presented with progressive hypoacusia, dizziness, and ophthalmoplegia. In Case 3, the patient developed rapid progressive visual failure and psychiatric symptoms. Case 4 presented with a 1-year history of headache and retrorbital pain. The diagnosis of prolactinoma was made on the basis of tumor immunohistochemistry and/or high plasma prolactin levels (range from 650–6,500 ng/mL). Medical treatment with the dopamine agonist cabergoline was given; it was effective in normalizing prolactin levels and inducing tumor shrinkage. Conclusion Prolactin levels should be measured in all large skull base tumors involving the pituitary region before any surgery or inappropriate radiotherapy is performed.

Syndromic Short Stature in Patients with a Germline Mutation in the LIM Homeobox LHX4

Studies of genetically engineered flies and mice have revealed the role that orthologs of the human LIM homeobox LHX4 have in the control of motor-neuron-identity assignment and in pituitary development. Remarkably, these mouse strains, which bear a targeted modification of Lhx4 in the heterozygous state, are asymptomatic, whereas homozygous animals die shortly after birth. Nevertheless, we have isolated the human LHX4 gene, as well as the corresponding cDNA sequence, to test whether it could be involved in developmental defects of the human pituitary region. LHX4, which encodes a protein 99% identical to its murine counterpart, consists of six coding exons and spans >45 kb of the q25 region of chromosome 1. We report a family with an LHX4 germline splice-site mutation that results in a disease phenotype characterized by short stature and by pituitary and hindbrain (i.e., cerebellar) defects in combination with abnormalities of the sella turcica of the central skull base. This intronic mutation, which segregates in a dominant and fully penetrant manner over three generations, abolishes normal LHX4 splicing and activates two exonic cryptic splice sites, thereby predicting two different proteins deleted in their homeodomain sequence. These findings, which elucidate the molecular basis of a complex Mendelian disorder, reveal the fundamental pleiotropic role played by a single factor that tightly coordinates brain development and skull shaping during head morphogenesis.

Ablation of pituitary pro-opiomelanocortin (POMC) cells produces alterations in hypothalamic POMC mRNA levels and midbrain mu opioid receptor binding in a conditional transgenic mouse model.

The hypothalamic-pituitary-adrenal (HPA) axis is regulated by stress-related excitatory inputs, and various inhibitory and negative-feedback controls by glucocorticoids and opioids, including pro-opiomelanocortin (POMC)-derived peptides. The role of POMC-derived peptides of pituitary origin in the modulation of brain POMC mRNA expression and opioid receptor binding was investigated using a line of transgenic mice that express a fusion gene composed of the pituitary expression-specific promoter region of the POMC gene driving the herpes simplex viral-1 thymidine kinase (TK). Male adult mice were treated with the antiherpes agent ganciclovir that selectively ablates cells expressing TK. Following treatment, POMC mRNA levels, measured by quantitative solution hybridization/RNase protection assays, were decreased by 48% in the pituitary of the TK+/+ mice, reflecting an expected loss of the pituitary corticotrope POMC cells. This treatment also significantly lowered pituitary beta-endorphin immunoreactivity content and plasma concentrations of corticosterone. In contrast, POMC mRNA levels were increased by 79% in the hypothalamus of the TK+/+ mice with pituitary POMC cell ablation. Binding of [(3)H]DAMGO to mu opioid receptors, as measured by quantitative autoradiography, was significantly reduced in several brain regions including the central grey, median raphe and superficial grey layer of the superior colliculus. These regions are innervated by hypothalamic POMC neurones. No significant differences in binding to either kappa or delta opioid receptors were found in the brain regions studied. These results suggest that POMC-derived peptides of pituitary origin may exert a tonic negative-feedback effect on hypothalamic POMC neurones. In turn, the downregulation of central mu opioid receptors in this model may be mediated through a mechanism related to hypothalamic POMC overexpression.

Pituitary Lymphoma Presenting as Fever of Unknown Origin*

An 86-yr-old woman presented with fever of unknown origin. When laboratory evaluation revealed partial hypopituitarism, a magnetic resonance imaging scan of the head was performed and revealed a sellar mass consistent with a pituitary adenoma. Only after other possible etiologies for fever were excluded did she undergo transsphenoidal resection of the sellar mass, which proved to be a B-cell lymphoma. Primary central nervous system lymphoma of the pituitary region is a rare cause of a sellar mass, and this is the first reported case of pituitary lymphoma whose presenting manifestation was fever of unknown origin. Several disease processes can manifest themselves as fever and a sellar mass, including lymphomas. In our case, only surgical biopsy could make a diagnosis and distinguish this process from the more common pituitary adenoma.

Molecular Cloning of Newt Prolactin (PRL) cDNA: Effect of Temperature on PRL mRNA Expression

A partial prolactin (PRL) cDNA was specifically PCR amplified from a cDNA library constructed from pituitary mRNAs of the newt (Cynops pyrrhogaster) and cloned into plasmid vectors. One clone thus obtained contained a 739-bp insert encoding the C-terminal amino acid sequence of the mature hormone molecule. Using this clone as a probe, the full-length newt PRL cDNA was screened from the cDNA library. The PRL cDNA clone thus obtained consisted of 1024 bp encoding the entire sequence of the mature PRL molecule in addition to its signal peptide. The amino acid sequence of newt PRL deduced from its nucleotide sequence showed higher homologies with those PRL sequences of tetrapod animals than with those of teleosts. Northern blot analysis revealed the newt PRL mRNA size to be approximately 1 kb. In situ hybridization using the newt PRL cDNA as a probe revealed that the pituitary region expressing PRL mRNA corresponded to that immunoreactive with antiserum against PRL. PRL mRNA levels in the pituitary of newts subjected to room and low temperatures were determined by Northern analysis employing the PRL cDNA as a probe. PRL mRNA levels were significantly higher in the pituitaries of newts subjected to 10° than in those of newts kept at 23°. Likewise, immunoassayable plasma PRL levels were higher in animals subjected to 10° than in those kept at 23°.

Unilateral congenital oculomotor nerve palsy, optic nerve hypoplasia and pituitary malformation: a preliminary report

A newborn male presented with complete external third nerve palsy of his right eye immediately at birth. Pediatric examination and MRI of the skull revealed no abnormalities. At the age of six weeks, strabismus surgery was performed to facilitate amblyopia treatment. The muscles appeared small and fibrotic. At the age of ten weeks, a brow suspension of the upper lid and a second strabismus surgery were performed. The amblyopia treatment and patching, applied for half of the waking hours over a period of six weeks, were unsuccessful. At the age of six months, a relative pallor of the right optic nerve head became evident. At the age of three years, at a new examination because of growth deficiency, a second MRI revealed defects involving the pituitary region. We concluded that extraocular muscle abnormality or oculomotor nerve palsy was present together with optic nerve dysplasia and pituitary gland malformation.

The computed tomographic enhancement pattern of the normal canine pituitary gland.

Dynamic computed tomography (CT) of the pituitary gland was performed on four healthy male dogs of similar size, weight and age. The pituitary gland region was first identified on lateral scout and transverse non-contrast images. After localization, water soluble iodinated contrast medium was administered intravenously as a bolus at a dose of 1 ml/lb using a pressure injector at an injection rate of 10 ml/sec and a total of 40 post contrast images of the pitutary gland were acquired. No images were made after 400 seconds. The same pituitary region was imaged in each slice. The slice thickness was 1.5 mm, with a two second scan time and an eight second delay between images (resulting in images every ten seconds). The contrast medium injection and initial image were acquired simultaneously, resulting in a non-contrast enhanced initial image. At the completion of the CT scan, a region of interest (ROI) was drawn around the pituitary gland and time density data were obtained. The mean pituitary Hounsfield number was plotted as a function of time. A bi-exponential least squares model was used to derive the best fitting line through the data. The mean relative peak increase in pituitary Hounsfield Units (HU) was 65.9% +/- 2.1%. After the initial increase there was a decrease in pituitary Hounsfield number with a half-time of 16.1 seconds, followed by a slower phase with a half-time of 16.5 minutes. The mean pituitary gland HU value during the period of gradual opacity decline was 35.0% +/- 4.4% above that of the pre-contrast image. Establishing the enhancement pattern in the canine pituitary gland is the precursor to the clinical application of dynamic CT of the pituitary gland to diagnose pituitary microadenomas and/or small macroadenomas before they become exceptionally large.

Diabetes insipidus in metastatic cancer: Two case reports with review of the literature

Tumour metastase masy cause a numbe or f endocrinesyndromes. One of these syndromes is diabetes insipiduscaused by metastatic infiltratio of thn hypothalamice -pituitary region. Although these metastase are rarely srecognised ante mortem, diabete iss insipidu a well srecognised complication in particula, irn patients withadvanced cance orf th brease ant d lung [1-3 24], . Yetdiabetes insipidu is rarels y mentione as manifesta d -tion of metastase is n th majoe r oncological text books[4-6].Here, we describe and discus ths e clinical presenta-tion, diagnosis, treatmen andt outcome in two patientswith cance irn whom diabetes insipidus developed In .addition a review of the literature is presented.tration was elevated wit 1.0h 3 umol/1 and remained at alevel of 1.13 umol/1 after stimulation The seru. m growthhormone concentration rose 4. fro6m to 5 mU/5 1 afterinjection of 50 ug growth hormone-releasing hormone.Computed tomography (CT) showed enlargemen oft thepituitary gland with bulgin of thge diaphragm a sellae.Magnetic resonance imagin (MRI showe)g ad masslesion in th neurohypophysise , with o deviatiof the npituitary stal tko th lefte an, increased d contras en- thancement of th stale k with gadolineum The ocula . rfundu appeared normal. n Thero visuae werl fieldedefects. A 99mTc-diphosphate bone scan revealed bonemetastases in th convexite ofy th skulle , spine, ribs,sternum, left clavicle, left humeru and femoras . Ultra-sonography of th abdomee n showe a lesiod n suspectfor a metastasi ins th livere . Based upo th clinicaen lCase AIn a 53-year-old, postmenopausal a woma carcinomn aof the breast wa s diagnosed (stage pTiN

Prospective assessment of pituitary size and shape on MR imaging after suppressive hormonal therapy in central precocious puberty.

The diagnostic significance of an enlarged pituitary gland regarding both shape and size parameters on MR imaging has previously been demonstrated in children with central precocious puberty. This study was designed to assess changes in these parameters following successful suppressive therapy of central precocious puberty with the gonadotropin-releasing hormone (GnRH) analogue. Twelve girls (mean age 7.3 years) with central precocious puberty were prospectively enrolled in our study protocol. Sagittal and coronal MR images of the pituitary region were obtained in all patients before treatment and after at least 6 months of GnRH analogue therapy (mean 18.0 months). Parameters measured included pituitary gland height, length, width, sagittal cross-sectional area, and volume. All patients had excellent clinical response to treatment with arrest of secondary sexual development, normalization of serum estradiol levels, and complete obliteration of the LH response to diagnostic GnRH stimulation. No significant change occurred in any pituitary size or shape parameter following GnRH analogue therapy. Favorable clinical response to GnRH analogue therapy in central precocious puberty is not accompanied by significant a change in pituitary gland size and shape.

Hormone levels and tumour size response to quinagolide and cabergoline in patients with prolactin-secreting and clinically non-functioning pituitary adenomas: predictive value of pituitary scintigraphy with 123 I-methoxybenzamide

Dopamine agonists are indicated as primary therapy for PRL-secreting pituitary adenomas, while controversial results have been reported in nonfunctioning adenomas (NFA). To evaluate whether the in vivo visualization of dopamine D2 receptor expression detected by pituitary scintigraphy using 123I-methoxybenzamide (123I-IBZM) was correlated with the response to chronic treatment with quinagolide or cabergoline. 10 patients affected with NFA (5 men and 5 women, age ranging between 25 and 50 years), and 10 with PRL-secreting naive macroadenomas (3 men and 7 women, age ranging between 22 and 59 years), serving as control. All patients underwent an acute test with quinagolide: at 3-day intervals and in random order all patients received the drug (0.075 mg at 0800 h), or placebo. Blood samples were taken 15 and 5 minutes before and every 30 minutes for 6 h after drug or placebo administration. The test was considered positive when PRL and/or alpha-subunit levels decreased >/=50% as compared to baseline levels. After 6 months of treatment, 10 patients were randomised to continue the treatment with quinagolide and the remaining 10 received cabergoline for the remaining 6 months. The doses of quinagolide and cabergoline ranged from 0.075 to 0.6 mg/day and from 0.5 to 3 mg/week, respectively. At study entry, a magnetic resonance imaging (MR) study of the pituitary region and 123I-IBZM pituitary scintigraphy were performed. MR was repeated after 12 months of treatment to evaluate tumour shrinkage: reduction of tumour volume = 80% in prolactinomas and = 50% in NFA was considered significant. Basal PRL levels were 9495.0 +/- 1131.6 mU/l in prolactinomas and 602.4 +/- 50.5 mU/l in NFA. The scintigraphy was negative in 6 out of 10 patients with NFA. Moderate uptake was observed in 3 patients with prolactinoma and 2 patients with NFA whereas intense uptake was observed in the remaining 7 patients with prolactinoma and 2 patients with NFA. Among the 8 patients with NFA and high circulating alpha-subunit levels, the acute test was negative in 5 while it was positive in the remaining 3 patients. The acute test was positive in all 10 patients with prolactinoma. After 12 months of treatment with quinagolide and cabergoline, circulating PRL levels were decreased in all 10 patients with prolactinoma (571.8 +/- 255.9 mU/l), being normalized in 7 patients. Suppression of PRL levels was found in all 10 patients with NFA (89.5 +/- 2.3 mU/l). A significant reduction of alpha-subunit levels was obtained in 9 out of 10 patients with NFA: in 4 out of 8 patients alpha-subunit levels were normalized. Significant adenoma shrinkage was recorded in 4 patients with prolactinoma among the 7 with intense pituitary uptake of 123I-IBZM. Significant adenoma shrinkage was recorded only in the 2 out of 10 patients with NFA with intense pituitary uptake of 123I-IBZM. A significant positive correlation was found between the degree of uptake (considered as score) and the response to quinagolide or cabergoline treatment (considered as percent hormone suppression) either in patients affected with PRL-secreting adenoma (r = 0.856, P < 0.005) or in those affected with NFA (r = 0.787, P < 0.05). An intense 123I-IBZM uptake in patients with non-functioning adenomas was predictive of a good response to a chronic treatment with quinagolide and cabergoline. This result suggests that a pituitary 123I-IBZM scintigraphy could be considered in selected patients with non-functioning adenomas before starting medical treatment with dopamine agonists.

Changes of Thyrotropin-Releasing Hormone (Trh) Levels in Brain Regions and Pituitary During Induced Metamorphosis of Ambystoma Mexicanum

Axolotls (Ambystoma mexicanum) are neotenic amphibians: they keep larval features during their entire lifetime. However, metamorphosis can be induced by injection of thyroid hormones or thyrotropin (TSH). The role played by thyrotropin-releasing hormone (TRH) in amphibian metamorphosis is not clear, since TRH treatment never succeeded in inducing metamorphosis in amphibian larvae. We studied the changes of TRH and plasma thyroid hormone levels in axolotls during thyroxine (T4)-induced metamorphosis. TRH levels in skin, hypothalamus, pituitary and extrahypothalamic region of the brain as well as plasma T4 and triiodothyronine (T3) levels were measured by radioimmunoassay (RIA). Preliminary data on the expression of TRH receptors in the pituitary of a neotenic and a metamorphosed animal were obtained by in situ hybridisation with an antisense oligonucleotide probe, based on nucleotides 1011 to 1060 of chicken TRH receptor mRNA. In general, TRH RIA showed that hypothalamus, extrahypothalamic region and pituitary contained high TRH levels. During metamorphosis, TRH levels decreased in hypothalamus (and extrahypothalamic region) and increased in pituitary; postmetamorphic values did not differ from neotenic controls. TRH levels in skin did not change significantly. During metamorphosis, plasma thyroid hormone levels were high, followed by a decrease to premetamorphic values after metamorphosis. Preliminary in situ hybridisation results suggested that the expression of TRH receptors is low in neotenic animals and increases during T4-induced metamorphosis.

Long-term treatment with the dopamine agonist quinagolide of patients with clinically non-functioning pituitary adenoma.

This study was performed to evaluate the effect of prolonged treatment with the dopamine agonist quinagolide on serum gonadotropin and alpha-subunit concentrations and tumor volume in patients with clinically non-functioning pituitary adenomas (CNPA). Ten patients with CNPA were treated with quinagolide (0.3 mg daily). The median duration of treatment was 57 months (range 36-93 months). Blood samples for measurement of serum gonadotropin and alpha-subunit concentrations were drawn before treatment, after 5 days, and at each outpatient visit. Computerized tomography or magnetic resonance imaging of the pituitary region and Goldmann perimetry were done before and at regular intervals during treatment. A significant decrease of serum FSH, LH or alpha-subunit concentrations was found in nine patients. The levels remained low during the entire treatment period. In two out of three patients with pre-existing visual field defects a slight improvement was shown during the first months of treatment, but eventually deterioration occurred in all three patients. A fourth patient developed unilateral ophthalmoplegia during treatment. During the first year tumor volume decreased in three patients, but in two of them regrowth occurred after a few months. In six patients progressive tumor growth occurred despite sustained suppression of gonadotropin or alpha-subunit levels. Long-term treatment of patients with CNPA with high doses of the dopamine agonist quinagolide could not prevent progressive increase in tumor size in most patients. It remains unproven whether quinagolide retards CNPA growth. Additional studies are needed to investigate whether subgroups of patients, e.g. those with positive dopamine receptor scintigraphy or those with marked hypersecretion of intact gonadotropins or subunits, will respond more favorably to treatment with dopamine agonists.

Vascularization of the pituitary of the Australian lungfish and Neoceratodus forsteri

The vascularization of the brain and the pituitary region of the Australian lungfish, Neoceratodus forsteri is described from serial section reconstruction. The distal lobe has no direct arterial blood supply and receives blood solely from a pituitary portal system basically similar to that of other sarcopterygians. The primary capillary plexus of the median eminence receives its arterial blood from the infundibular arteries, which on their way distribute some small branches to the prechiasmatic region. The primary plexus also receives capillaries from the adjacent pial hypothalamic plexus. The primary capillary plexus of the median eminence comprises a rostral ‘uncovered’ and caudal ‘covered’ part which are not sharply delineated. Distinct portal vessels connect the ‘uncovered’ rostral part of the primary plexus with the secondary capillary plexus supplying the rostral subdivision of the pars distalis. The ‘covered’ caudal part of the primary plexus merges into the proximal subdivision of the pars distalis, apparently without formation of distinct portal vessels. The primary plexus has some connections with the plexus intermedius via a hypophysial stem capillary plexus. The plexus intermedius has a substantial arterial supply and gives off capillaries to the parenchyma of the pars intermedia. The adenohypophysis is drained into an unpaired hypophysial vein. The significance of the vascular pathways is discussed from comparative, functional, and evolutionary viewpoints.