Hypophysitis is defined as inflammation of the pituitary gland that is primary or secondary to a local or systemic process. Differential diagnosis is broad (including primary tumors, metastases, and ...lympho-proliferative diseases) and multifaceted. Patients with hypophysitis typically present with headaches, some degree of anterior and/or posterior pituitary dysfunction, and enlargement of pituitary gland and/or stalk, as determined by imaging. Most hypophysitis causes are autoimmune, but other etiologies include inflammation secondary to sellar tumors or cysts, systemic diseases, and infection or drug-induced causes. Novel pathologies such as immunoglobulin G4-related hypophysitis, immunotherapy-induced hypophysitis, and paraneoplastic pituitary-directed autoimmunity are also included in a growing spectrum of this rare pituitary disease. Typical magnetic resonance imaging reveals stalk thickening and homogenous enlargement of the pituitary gland; however, imaging is not always specific. Diagnosis can be challenging, and ultimately, only a pituitary biopsy can confirm hypophysitis type and rule out other etiologies. A presumptive diagnosis can be made often without biopsy. Detailed history and clinical examination are essential, notably for signs of underlying etiology with systemic manifestations. Hormone replacement and, in selected cases, careful observation is advised with imaging follow-up. High-dose glucocorticoids are initiated mainly to help reduce mass effect. A response may be observed in all auto-immune etiologies, as well as in lymphoproliferative diseases, and, as such, should not be used for differential diagnosis. Surgery may be necessary in some cases to relieve mass effect and allow a definite diagnosis. Immunosuppressive therapy and radiation are sometimes also necessary in resistant cases.
The anterior pituitary gland plays a central role in regulating various physiological processes, including body growth, reproduction, metabolism and stress response. Here, we perform single-cell ...RNA-sequencing (scRNA-seq) of 4113 individual cells from human fetal pituitaries. We characterize divergent developmental trajectories with distinct transitional intermediate states in five hormone-producing cell lineages. Corticotropes exhibit an early intermediate state prior to full differentiation. Three cell types of the PIT-1 lineage (somatotropes, lactotropes and thyrotropes) segregate from a common progenitor coexpressing lineage-specific transcription factors of different sublineages. Gonadotropes experience two multistep developmental trajectories. Furthermore, we identify a fetal gonadotrope cell subtype expressing the primate-specific hormone chorionic gonadotropin. We also characterize the cellular heterogeneity of pituitary stem cells and identify a hybrid epithelial/mesenchymal state and an early-to-late state transition. Here, our results provide insights into the transcriptional landscape of human pituitary development, defining distinct cell substates and subtypes and illustrating transcription factor dynamics during cell fate commitment.
Zusammenfassung Hintergrund und Ziele Der Tumor des follikulären Infundibulums (TFI) wurde als Neoplasie – isoliert und multipel – und in Assoziation mit anderen epithelialen Läsionen beschrieben. ...Seine endgültige histopathologische Definition wird kontrovers diskutiert. Patienten und Methodik Wir präsentieren eine retrospektive Serie von 28 Patienten mit TFI beziehungsweise TFI‐ähnlichen Veränderungen. Ergänzend wurde die in MEDLINE aufgeführte Literatur zum Thema TFI recherchiert und die darin publizierten Abbildungen interaktiv diskutiert und analysiert. Ergebnisse Unsere Patienten waren 16 Frauen und 12 Männer. TFI‐ähnliche Veränderungen fanden sich bei fünf Patienten mit Nävus sebaceus, zwei Trichofollikulomen, einer erweiterten Pore Winer, acht Virusakanthomen, einem Dermatofibrom, sechs seborrhoischen Keratosen, drei aktinischen Keratosen, einem invasiven Plattenepithelkarzinom und einem Basalzellkarzinom in Kombination mit Plattenepithelkarzinom/aktinischer Keratose. Nach Sichtung der Literatur, insbesondere von solitären Fällen von TFI, betrachten wir diese größtenteils als Variante von seborrhoischen Keratosen mit variablem Ausmaß von infundibulärer, isthmischer und/oder sebazärer Differenzierung mit oder ohne Regression. Schlussfolgerungen Wir werten TFI insgesamt als ein epitheliales Wachstumsmuster, das bei hamartomatösen, entzündlichen inkludierend infektiösen, reaktiven oder neoplastischen Prozessen auftreten und in den meisten solitären Formen am ehesten innerhalb des histologischen Spektrums seborrhoischer Keratosen eingeordnet werden kann.
Wingless (Wnt)/β-catenin signaling plays an essential role during normal development, is a critical regulator of stem cells, and has been associated with cancer in many tissues. Here we demonstrate ...that genetic expression of a degradation-resistant mutant form of β-catenin in early Rathke's pouch (RP) progenitors leads to pituitary hyperplasia and severe disruption of the pituitary-specific transcription factor 1-lineage differentiation resulting in extreme growth retardation and hypopituitarism. Mutant mice mostly die perinatally, but those that survive weaning develop lethal pituitary tumors, which closely resemble human adamantinomatous craniopharyngioma, an epithelial tumor associated with mutations in the human β-catenin gene. The tumorigenic effect of mutant β-catenin is observed only when expressed in undifferentiated RP progenitors, but tumors do not form when committed or differentiated cells are targeted to express this protein. Analysis of affected pituitaries indicates that expression of mutant β-catenin leads to a significant increase in the total numbers of pituitary progenitor/stem cells as well as in their proliferation potential. Our findings provide insights into the role of the Wnt pathway in normal pituitary development and demonstrate a causative role for mutated β-catenin in an undifferentiated RP progenitor in the genesis of murine and human craniopharyngioma.
Context:
Acromegaly is a systemic disorder caused by a GH-secreting pituitary adenoma. As with other rare diseases, acromegaly registries developed in various European countries have provided us with ...important information.
Objective:
The objective of the study was to analyze the epidemiological, clinical, biochemical, and therapeutic data from the Mexican Acromegaly Registry (MAR).
Setting:
The setting of the study was a nationwide patient registry.
Design and Methodology:
The MAR was created in 2009. It gathers data from 24 participating centers belonging to three different institutions using a specifically designed on-line platform. Only patients diagnosed after 1990 were included in the program.
Results:
A total of 2057 patients (51% female, mean age at diagnosis 41.1 ± 24.5 y) have been registered for an estimated prevalence of 18 cases per 1 million inhabitants. Hypertension, glucose intolerance, diabetes, and dyslipidemia were present in 27%, 18.4%, 30%, and 24% of the patients, respectively. The IGF-1 level at diagnosis and the concomitant presence of hypertension were significantly associated with the development of diabetes. Transsphenoidal surgery was the primary treatment in 72% of the patients. Pharmacological treatment, mostly with somatostatin analogs, was administered primarily and adjunctively in 26% and 54% of the patients, respectively. Treatment choice varied among the three participating institutions, with the predominance of pharmacological therapy in two of them and of radiation therapy in the third. Therapeutic outcomes were similar to those reported in the European registries.
Conclusions:
The MAR is the largest and first non-European registry of the disease. Our findings highlight important within-country differences in treatment choice due to variations in the availability of resources.
The MAR collects data on 2057 patients with acromegaly showing a considerable interinstitutional variation in treatment modality choice due to differences in the availability of resources.
Summary
Context
Pituitary stalk interruption syndrome (PSIS) is a rare cause of combined pituitary hormone deficiency characterized by a triad shown in pituitary imaging, yet it has never been ...evaluated due to the visibility of pituitary stalk (PS) in imaging findings.
Objective
The major objective of the study was to systematically describe the disease including clinical presentations, imaging findings and to estimate the severity of anterior pituitary hormone deficiency based on the visibility of the PS.
Methods
This was a retrospective study including 74 adult patients with PSIS in Shanghai Clinical Center for Endocrine and Metabolic Diseases between January 2010 and June 2014. Sixty had invisible PS according to the findings on MRI, while the rest had a thin or intersected PS. Basic characteristics and hormonal status were compared.
Results
Of the 74 patients with PSIS, age at diagnosis was 25 (22–28) years. Absent pubertal development (97·3%) was the most common presenting symptom, followed by short stature. Insulin tolerance test (ITT) and gonadotrophin‐releasing hormone (GnRH) stimulation test were used to evaluate the function of anterior pituitary. The prevalence of isolated deficiency in growth hormone (GH), gonadotrophins, corticotrophin and thyrotrophin were 100%, 97·2%, 88·2% and 70·3%, respectively. Although the ratio of each deficiency did not vary between patients with invisible PS and with visible PS, panhypopituitarism occurred significantly more frequent in patients with invisible PS. Patients with invisible PS had significantly lower levels of luteinizing hormone (LH), follicle stimulation hormone (FSH) and hormones from targeted glands including morning cortisol, 24‐h urine free cortisol, free triiodothyronine (FT3), free thyroxine (FT4) and testosterone (T) in male than patients with visible PS. Moreover, patients with invisible PS had lower peak LH and FSH in GnRH stimulation test, and higher peak cortisol in ITT while peak GH remained unchanged between two groups.
Conclusions
The prevalence of multiple anterior pituitary hormone deficiency was high in adult patients with PSIS. And more importantly, we found the visibility of PS shown on MRI might be an indication of the severity of PSIS.
Introduction
With the goal of generate uniform criteria among centers dealing with pituitary tumors and to enhance patient care, the Pituitary Society decided to generate criteria for developing ...Pituitary Tumors Centers of Excellence (PTCOE).
Methods
To develop that task, a group of ten experts served as a Task Force and through two years of iterative work an initial draft was elaborated. This draft was discussed, modified and finally approved by the Board of Directors of the Pituitary Society. Such document was presented and debated at a specific session of the Congress of the Pituitary Society, Orlando 2017, and suggestions were incorporated. Finally the document was distributed to a large group of global experts that introduced further modifications with final endorsement.
Results
After five years of iterative work a document with the ideal criteria for a PTCOE is presented.
Conclusions
Acknowledging that very few centers in the world, if any, likely fulfill the requirements here presented, the document may be a tool to guide improvements of care delivery to patients with pituitary disorders. All these criteria must be accommodated to the regulations and organization of Health of a given country.
The pituitary gland of vertebrates consists of two major parts, the neurohypophysis (NH) and the adenohypophysis (AH). As a central part of the hypothalamo-hypophyseal system (HHS), it constitutes a ...functional link between the nervous and the endocrine system to regulate basic body functions, such as growth, metabolism and reproduction. The development of the AH has been intensively studied in mouse, serving as a model for organogenesis and differential cell specification. However, given that the AH is a relatively recent evolutionary advance of the chordate phylum, it is also interesting to understand its development in lower chordate systems. In recent years, the zebrafish has emerged as a powerful lower vertebrate system for developmental studies, being amenable for large-scale genetic approaches, embryological manipulations, and in vivo imaging.
Here, we present an overview of current knowledge of the mechanisms and genetic control of pituitary formation during zebrafish development. First, we describe the components of the zebrafish HHS, and the different pituitary cell types and hormones, followed by a description of the different steps of normal pituitary development. The central part of the review deals with the genes found to be essential for zebrafish AH development, accompanied by a description of the corresponding mutant phenotypes. Finally, we discuss future directions, with particular focus on evolutionary aspects, and some novel functional aspects with growing medical and social relevance.
Aberrant embryonic development of the hypothalamus and/or pituitary gland in humans results in congenital hypopituitarism (CH). Transcription factor 7-like 1 (TCF7L1), an important regulator of the ...WNT/β-catenin signaling pathway, is expressed in the developing forebrain and pituitary gland, but its role during hypothalamo–pituitary (HP) axis formation or involvement in human CH remains elusive. Using a conditional genetic approach in the mouse, we first demonstrate that TCF7L1 is required in the prospective hypothalamus to maintain normal expression of the hypothalamic signals involved in the induction and subsequent expansion of Rathke’s pouch progenitors. Next, we reveal that the function of TCF7L1 during HP axis development depends exclusively on the repressing activity of TCF7L1 and does not require its interaction with β-catenin. Finally, we report the identification of two independent missense variants in human TCF7L1, p.R92P and p.R400Q, in a cohort of patients with forebrain and/or pituitary defects. We demonstrate that these variants exhibit reduced repressing activity in vitro and in vivo relative to wild-type TCF7L1. Together, our data provide support for a conserved molecular function of TCF7L1 as a transcriptional repressor during HP axis development in mammals and identify variants in this transcription factor that are likely to contribute to the etiology of CH.
In the adenohypophysis (anterior pituitary) of all gnathostomes, there are six tropic cell types: corticotropes, melanotropes, somatotropes, lactotropes, gonadotropes and thyrotropes; each cell type ...produces specific tropic hormones. In contrast, we report in this study that there are only four tropic cell types in the sea lamprey (
Petromyzon marinus
) adenohypophysis. We specifically focused on the cell types that produce the glycoprotein hormones (GpHs). The gnathostome adenohypophyseal GpHs are follicle-stimulating hormone (FSH), luteinizing hormone (LH), thyroid-stimulating hormone (TSH), and thyrostimulin. However, lampreys only have two heterodimeric adenohypophyseal GpHs consisting of unique α and β subunits, lamprey GpH (lGpH) (lGpA2/lGpHβ) and thyrostimulin (lGpA2/lGpB5). We used an array of histological techniques to determine the (co)-localization and (co)-expression of the lGpH and thyrostimulin subunits in the lamprey adenohypophysis at different life stages (larval, parasitic, adult) and to identify their synthesizing cell(s). The thyrostimulin subunits (lGpA2/lGpB5) were co-expressed throughout the adenohypophysis (larval, parasitic, and adult), while the GpH β-subunit (lGpHβ) exhibited localized distribution (adult); all three subunits were co-localized and co-expressed, suggesting that both GpHs are synthesized in the same cells, novel proto-glycotropes, in specific adenohypophyseal regions at different life stages. In summary, we provide the first comprehensive study using histology, transmission electron microscopy, in situ hybridization and immunohistochemistry that strongly supports further evidence for four definitive adenohypophyseal cell types in the lamprey, including: corticotropes, somatotropes, melanotropes, and the first identification of a novel proto-glycotrope. In addition, our studies show that there is developmental and region-specific co-localization and co-expression of lGpH and thyrostimulin in the lamprey adenohypophysis.
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