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Advances in the Diagnosis and Therapy of Pituitary Disorders
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Advances in the Diagnosis and Therapy of Pituitary Disorders

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Endocrinology & Metabolism".

Deadline for manuscript submissions: closed (30 September 2019) | Viewed by 61070

Special Issue Editor

Prof. Dr. Sylvia L. Asa

E-Mail Website
Guest Editor
Department of Pathology, Case Western Reserve University and University Hospitals Cleveland, Cleveland, OH 44106, USA
Interests: endocrine pathology; endocrine oncology; neuroendocrine tumors; pathophysiology; molecular pathology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The pituitary gland is a critical mediator of endocrine homeostasis. Pituitary pathology results in significant morbidity. This Special Issue will focus on recent advances in the understanding of congenital abnormalities that result in hypopituitarism, as well as acquired infectious and inflammatory lesions and a wide range of tumors that can also cause hormone excess syndromes. Experts in various fields will summarize the clinical, biochemical, radiologic, pathologic, and molecular features of various disease entities to provide the reader with a clear understanding of the spectrum of pituitary disorders. Advances in the understanding of the epidemiology of pituitary tumors, their nomenclature, and etiology will also be discussed. New and emerging therapies will be reviewed and innovations that are expected to enhance diagnosis and management of pituitary patients will be proposed for future studies.

Prof. Dr. Sylvia L. Asa
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Journal of Clinical Medicine is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Pituitary
  • Hypopituitarism
  • Hypophysitis
  • Pituitary neuroendocrine tumors: epidemiology and terminology
  • Acromegaly
  • Cushing disease
  • Hyperprolactinemia
  • Tumors of the hypothalamus and posterior pituitary
  • Unusual pituitary neoplasms
  • Novel treatments

Published Papers (7 papers)

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Review

19 pages, 568 KiB  
Review
The Genetics of Pituitary Adenomas
by Christina Tatsi and Constantine A. Stratakis
J. Clin. Med. 2020, 9(1), 30; https://doi.org/10.3390/jcm9010030 - 21 Dec 2019
Cited by 42 | Viewed by 7654
Abstract
The genetic landscape of pituitary adenomas (PAs) is diverse and many of the identified cases remain of unclear pathogenetic mechanism. Germline genetic defects account for a small percentage of all patients and may present in the context of relevant family history. Defects in [...] Read more.
The genetic landscape of pituitary adenomas (PAs) is diverse and many of the identified cases remain of unclear pathogenetic mechanism. Germline genetic defects account for a small percentage of all patients and may present in the context of relevant family history. Defects in AIP (mutated in Familial Isolated Pituitary Adenoma syndrome or FIPA), MEN1 (coding for menin, mutated in Multiple Endocrine Neoplasia type 1 or MEN 1), PRKAR1A (mutated in Carney complex), GPR101 (involved in X-Linked Acrogigantism or X-LAG), and SDHx (mutated in the so called “3 P association” of PAs with pheochromocytomas and paragangliomas or 3PAs) account for the most common familial syndromes associated with PAs. Tumor genetic defects in USP8, GNAS, USP48 and BRAF are some of the commonly encountered tissue-specific changes and may explain a larger percentage of the developed tumors. Somatic (at the tumor level) genomic changes, copy number variations (CNVs), epigenetic modifications, and differential expression of miRNAs, add to the variable genetic background of PAs. Full article
(This article belongs to the Special Issue Advances in the Diagnosis and Therapy of Pituitary Disorders)
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24 pages, 563 KiB  
Review
Hyperprolactinaemia
by Irene Samperi, Kirstie Lithgow and Niki Karavitaki
J. Clin. Med. 2019, 8(12), 2203; https://doi.org/10.3390/jcm8122203 - 13 Dec 2019
Cited by 74 | Viewed by 9999
Abstract
Hyperprolactinaemia is one of the most common problems in clinical endocrinology. It relates with various aetiologies (physiological, pharmacological, pathological), the clarification of which requires careful history taking and clinical assessment. Analytical issues (presence of macroprolactin or of the hook effect) need to be [...] Read more.
Hyperprolactinaemia is one of the most common problems in clinical endocrinology. It relates with various aetiologies (physiological, pharmacological, pathological), the clarification of which requires careful history taking and clinical assessment. Analytical issues (presence of macroprolactin or of the hook effect) need to be taken into account when interpreting the prolactin values. Medications and sellar/parasellar masses (prolactin secreting or acting through “stalk effect”) are the most common causes of pathological hyperprolactinaemia. Hypogonadism and galactorrhoea are well-recognized manifestations of prolactin excess, although its implications on bone health, metabolism and immune system are also expanding. Treatment mainly aims at restoration and maintenance of normal gonadal function/fertility, and prevention of osteoporosis; further specific management strategies depend on the underlying cause. In this review, we provide an update on the diagnostic and management approaches for the patient with hyperprolactinaemia and on the current data looking at the impact of high prolactin on metabolism, cardiovascular and immune systems. Full article
(This article belongs to the Special Issue Advances in the Diagnosis and Therapy of Pituitary Disorders)
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Figure 1

23 pages, 351 KiB  
Review
Management of Hypopituitarism
by Krystallenia I. Alexandraki and Ashley B. Grossman
J. Clin. Med. 2019, 8(12), 2153; https://doi.org/10.3390/jcm8122153 - 05 Dec 2019
Cited by 32 | Viewed by 10067
Abstract
Hypopituitarism includes all clinical conditions that result in partial or complete failure of the anterior and posterior lobe of the pituitary gland’s ability to secrete hormones. The aim of management is usually to replace the target-hormone of hypothalamo-pituitary-endocrine gland axis with the exceptions [...] Read more.
Hypopituitarism includes all clinical conditions that result in partial or complete failure of the anterior and posterior lobe of the pituitary gland’s ability to secrete hormones. The aim of management is usually to replace the target-hormone of hypothalamo-pituitary-endocrine gland axis with the exceptions of secondary hypogonadism when fertility is required, and growth hormone deficiency (GHD), and to safely minimise both symptoms and clinical signs. Adrenocorticotropic hormone deficiency replacement is best performed with the immediate-release oral glucocorticoid hydrocortisone (HC) in 2–3 divided doses. However, novel once-daily modified-release HC targets a more physiological exposure of glucocorticoids. GHD is treated currently with daily subcutaneous GH, but current research is focusing on the development of once-weekly administration of recombinant GH. Hypogonadism is targeted with testosterone replacement in men and on estrogen replacement therapy in women; when fertility is wanted, replacement targets secondary or tertiary levels of hormonal settings. Thyroid-stimulating hormone replacement therapy follows the rules of primary thyroid gland failure with L-thyroxine replacement. Central diabetes insipidus is nowadays replaced by desmopressin. Certain clinical scenarios may have to be promptly managed to avoid short-term or long-term sequelae such as pregnancy in patients with hypopituitarism, pituitary apoplexy, adrenal crisis, and pituitary metastases. Full article
(This article belongs to the Special Issue Advances in the Diagnosis and Therapy of Pituitary Disorders)
17 pages, 13036 KiB  
Review
The Clinicopathological Spectrum of Acromegaly
by Amit Akirov, Sylvia L. Asa, Lama Amer, Ilan Shimon and Shereen Ezzat
J. Clin. Med. 2019, 8(11), 1962; https://doi.org/10.3390/jcm8111962 - 13 Nov 2019
Cited by 36 | Viewed by 5852
Abstract
Background: Acromegaly results from a persistent excess in growth hormone with clinical features that may be subtle or severe. The most common cause of acromegaly is a pituitary tumor that causes excessive production of growth hormone (GH), and rare cases are due to [...] Read more.
Background: Acromegaly results from a persistent excess in growth hormone with clinical features that may be subtle or severe. The most common cause of acromegaly is a pituitary tumor that causes excessive production of growth hormone (GH), and rare cases are due to an excess of the GH-releasing hormone (GHRH) or the ectopic production of GH. Objective: Discuss the different diseases that present with manifestations of GH excess and clinical acromegaly, emphasizing the distinct clinical and radiological characteristics of the different pathological entities. Methods: We performed a narrative review of the published clinicopathological information about acromegaly. An English-language search for relevant studies was conducted on PubMed from inception to 1 August 2019. The reference lists of relevant studies were also reviewed. Results: Pituitary tumors that cause GH excess have several variants, including pure somatotroph tumors that can be densely or sparsely granulated, or plurihormonal tumors that include mammosomatotroph, mixed somatotroph-lactotroph tumors and mature plurihomonal Pit1-lineage tumors, acidophil stem cell tumors and poorly-differentiated Pit1-lineage tumors. Each tumor type has a distinct pathophysiology, resulting in variations in clinical manifestations, imaging and responses to therapies. Conclusion: Detailed clinicopathological information will be useful in the era of precision medicine, in which physicians tailor the correct treatment modality to each patient. Full article
(This article belongs to the Special Issue Advances in the Diagnosis and Therapy of Pituitary Disorders)
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56 pages, 14351 KiB  
Review
Cushing’s Disease
by Hiroshi Nishioka and Shozo Yamada
J. Clin. Med. 2019, 8(11), 1951; https://doi.org/10.3390/jcm8111951 - 12 Nov 2019
Cited by 40 | Viewed by 17035
Abstract
In patients with Cushing’s disease (CD), prompt diagnosis and treatment are essential for favorable long-term outcomes, although this remains a challenging task. The differential diagnosis of CD is still difficult in some patients, even with an organized stepwise diagnostic approach. Moreover, despite the [...] Read more.
In patients with Cushing’s disease (CD), prompt diagnosis and treatment are essential for favorable long-term outcomes, although this remains a challenging task. The differential diagnosis of CD is still difficult in some patients, even with an organized stepwise diagnostic approach. Moreover, despite the use of high-resolution magnetic resonance imaging (MRI) combined with advanced fine sequences, some tumors remain invisible. Surgery, using various surgical approaches for safe maximum tumor removal, still remains the first-line treatment for most patients with CD. Persistent or recurrent CD after unsuccessful surgery requires further treatment, including repeat surgery, medical therapy, radiotherapy, or sometimes, bilateral adrenalectomy. These treatments have their own advantages and disadvantages. However, the most important thing is that this complex disease should be managed by a multidisciplinary team with collaborating experts. In addition, a personalized and individual-based approach is paramount to achieve high success rates while minimizing the occurrence of adverse events and improving the patients’ quality of life. Finally, the recent new insights into the pathophysiology of CD at the molecular level are highly anticipated to lead to the introduction of more accurate diagnostic tests and efficacious therapies for this devastating disease in the near future. Full article
(This article belongs to the Special Issue Advances in the Diagnosis and Therapy of Pituitary Disorders)
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Figure 1

11 pages, 3906 KiB  
Review
Hypothalamic Endocrine Tumors: An Update
by Sylvia L. Asa and Ozgur Mete
J. Clin. Med. 2019, 8(10), 1741; https://doi.org/10.3390/jcm8101741 - 20 Oct 2019
Cited by 13 | Viewed by 4820
Abstract
The hypothalamus is the site of synthesis and secretion of a number of endocrine peptides that are involved in the regulation of hormonal activity of the pituitary and other endocrine targets. Tumors of the hypothalamus have been recognized to have both structural and [...] Read more.
The hypothalamus is the site of synthesis and secretion of a number of endocrine peptides that are involved in the regulation of hormonal activity of the pituitary and other endocrine targets. Tumors of the hypothalamus have been recognized to have both structural and functional effects including hormone hypersecretion. The classification of these tumors has advanced over the last few years, and biomarkers are now available to classify these tumors and provide accurate structure–function correlations. This review provides an overview of tumors in this region that is critical to metabolic homeostasis with a focus on advances in the diagnosis of gangliocytomas, neurocytomas, and pituicytomas that are unique to this region. Full article
(This article belongs to the Special Issue Advances in the Diagnosis and Therapy of Pituitary Disorders)
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17 pages, 326 KiB  
Review
Emerging and Novel Treatments for Pituitary Tumors
by Mirela Diana Ilie, Hélène Lasolle and Gérald Raverot
J. Clin. Med. 2019, 8(8), 1107; https://doi.org/10.3390/jcm8081107 - 25 Jul 2019
Cited by 38 | Viewed by 4494
Abstract
A subset of pituitary neuroendocrine tumors (PitNETs) have an aggressive behavior, showing resistance to treatment and/or multiple recurrences in spite of the optimal use of standard therapies (surgery, conventional medical treatments, and radiotherapy). To date, for aggressive PitNETs, temozolomide (TMZ) has been the [...] Read more.
A subset of pituitary neuroendocrine tumors (PitNETs) have an aggressive behavior, showing resistance to treatment and/or multiple recurrences in spite of the optimal use of standard therapies (surgery, conventional medical treatments, and radiotherapy). To date, for aggressive PitNETs, temozolomide (TMZ) has been the most used therapeutic option, and has resulted in an improvement in the five-year survival rate in responders. However, given the fact that roughly only one third of patients showed a partial or complete radiological response on the first course of TMZ, and even fewer patients responded to a second course of TMZ, other treatment options are urgently needed. Emerging therapies consist predominantly of peptide receptor radionuclide therapy (20 cases), vascular endothelial growth factor receptor-targeted therapy (12 cases), tyrosine kinase inhibitors (10 cases), mammalian target of rapamycin (mTOR) inhibitors (six cases), and more recently, immune checkpoint inhibitors (one case). Here, we present the available clinical cases published in the literature for each of these treatments. The therapies that currently show the most promise (based on the achievement of partial radiological response in a certain number of cases) are immune checkpoint inhibitors, peptide receptor radionuclide therapy, and vascular endothelial growth factor receptor-targeted therapy. In the future, further improvement of these therapies and the development of other novel therapies, their use in personalized medicine, and a better understanding of combination therapies, will hopefully result in better outcomes for patients bearing aggressive PitNETs. Full article
(This article belongs to the Special Issue Advances in the Diagnosis and Therapy of Pituitary Disorders)
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