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Advances in Molecular Biology of Pituitary Diseases
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Advances in Molecular Biology of Pituitary Diseases

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Endocrinology and Metabolism".

Deadline for manuscript submissions: closed (31 October 2024) | Viewed by 2426

Special Issue Editor

Dr. Rosa Maria Paragliola

E-Mail Website
Guest Editor
Department of Translational Medicine and Surgery, Unit of Endocrinology, Università Cattolica del Sacro Cuore—Fondazione Policlinico “Gemelli” IRCCS, Largo Gemelli 8, I-00168 Rome, Italy
Interests: pituitary; acromegaly; Cushing’s syndrome; hyperprolactinemia; TSH-secreting pituitary adenoma; syndrome of reduced sensitivity to thyroid hormones; thyroid; adrenal gland
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This Special Issue aims to present the latest research on the molecular biology of pituitary diseases. Pituitary adenoma is a common disease, accounting for about 10% of the general population, and generally presents as a benign tumor. However, in rare cases, tumors can become malignant and metastasize. Pituitary adenomas are also associated with specific syndromes (e.g., acromegaly, Cushing’s syndrome, prolactinoma, syndrome of inappropriate TSH secretion) due to inappropriate hormone secretion. Continuous advances in molecular biology techniques have improved our understanding of the pathogenesis and biology of these tumors, and this knowledge can be applied to the development of diagnostic methods and treatment options. Interestingly, molecular biology techniques have uncovered the pathophysiological mechanisms of non-neoplastic pituitary diseases, such as thyroid hormone resistance syndrome or inappropriate non-neoplastic TSH secretion. An important topic regarding syndromes of reduced thyroid hormone sensitivity is the discovery of polymorphisms in gene encoding type 2 deiodinase. Finally, genetic analysis can identify mutations in genes encoding transcription factors involved in pituitary development that may be involved in the pathogenesis of pituitary hormone deficiency.

Dr. Rosa Maria Paragliola
Guest Editor

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Keywords

  • pituitary adenomas
  • pituitary carcinomas
  • hypopituitarism
  • acromegaly
  • somatostatin receptor ligands
  • prolactinoma
  • Cushing’s syndrome
  • TSH-secreting adenomas
  • syndromes of reduced sensitivity to thyroid hormones

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Published Papers (3 papers)

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Research

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14 pages, 2588 KiB  
Article
Cushing’s Disease Manifestation in USP8-Mutated Corticotropinoma May Be Mediated by Interactions Between WNT Signaling and SST Trafficking
by Elena Nerubenko, Pavel Ryazanov, Natalia Kuritsyna, Artem Paltsev, Oksana Ivanova, Elena Grineva, Anna Kostareva, Renata Dmitrieva and Uliana Tsoy
Int. J. Mol. Sci. 2024, 25(23), 12886; https://doi.org/10.3390/ijms252312886 - 29 Nov 2024
Viewed by 305
Abstract
In the current work, we aimed to evaluate the association of clinical data of Cushing’s disease (CD) patients with USP8 mutation status and to study USP8-related molecular mechanisms connected to the regulation of corticotropinoma growth and activity. 35 CD patients were enrolled; the [...] Read more.
In the current work, we aimed to evaluate the association of clinical data of Cushing’s disease (CD) patients with USP8 mutation status and to study USP8-related molecular mechanisms connected to the regulation of corticotropinoma growth and activity. 35 CD patients were enrolled; the sequencing of exon 14 in USP8 revealed variants in eighteen adenomas, two of which were described for the first time in CD. USP8 variants were more common in women (94% vs. 76%; p = 0.001), and microadenomas and tumor recurrence were prevalent in the USP8-mutant group (44% vs. 29%; p = 0.04 and 44% vs. 22%; p = 0.0015). Preoperative ACTH and serum cortisol did not differ in the USP8-WT and USP8-mutant patients. All USP8-mutant adenomas were SST5-positive, and 73% of them were double-positive (SST5+/SST2+). A total of 50% of USP8-WT adenomas were double-negative (SST5−/SST2−), and 40% of them were SST5-positive. Analysis of transcriptome was performed for nine USP8-mutant and six USP8-WT adenomas and revealed the that the bidirectional dysregulation of Wnt signaling, including both the agonist RSPO2 and antagonist SFRP1, in the USP8-mutant corticotropinomas was downregulated. These alterations may indicate the existence of regulatory connections between USP8 enzyme activity, Wnt signaling, EGFR signaling and somatostatin receptors’ trafficking, which can explain, at least in part, the clinical manifestations of CD in patients with corticotropinomas harboring USP8 variants. Full article
(This article belongs to the Special Issue Advances in Molecular Biology of Pituitary Diseases)
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17 pages, 3470 KiB  
Article
Predicting Response to Medical Treatment in Acromegaly via Granulation Pattern, Expression of Somatostatin Receptors Type 2 and 5 and E-Cadherin
by Maximilian Cosma Gliga, Laura Chinezu and Ionela Maria Pascanu
Int. J. Mol. Sci. 2024, 25(16), 8663; https://doi.org/10.3390/ijms25168663 - 8 Aug 2024
Cited by 1 | Viewed by 866
Abstract
Resistance to first-generation somatostatin receptor ligand (fgSRL) treatment in acromegaly is common, making the identification of biomarkers that predict fgSRL response a desired goal. We conducted a retrospective analysis on 21 patients with acromegaly who underwent surgery and subsequent pharmacological treatment. Through immunohistochemistry [...] Read more.
Resistance to first-generation somatostatin receptor ligand (fgSRL) treatment in acromegaly is common, making the identification of biomarkers that predict fgSRL response a desired goal. We conducted a retrospective analysis on 21 patients with acromegaly who underwent surgery and subsequent pharmacological treatment. Through immunohistochemistry (IHC), we assessed the expression of the somatostatin receptor subtypes SSTR2 and SSTR5, E-Cadherin, and cytokeratin granulation pattern (sparsely or densely). Patients were divided into responders and non-responders based on their biochemical response to fgSRL and/or the newer agent, Pasireotide, or the GH-blocker, Pegvisomant. Patients resistant to fgSRL (n = 12) exhibited lower SSTR2 and E-Cadherin expressions. Sparsely granulated tumors were more frequent in the non-responder group. SSTR2 (p = 0.024, r = 0.49) and E-Cadherin (p = 0.009, r = 0.64) positively correlated with the Insulin-like Growth Factor 1 (IGF-1) decrease after fgSRL, while SSTR5 (p = 0.107, r = −0.37) showed a trend towards negative correlation. SSTR5 positivity seemed to be associated with Pasireotide response, albeit the number of treated patients was too low (n = 4). No IHC markers correlated with Pegvisomant response. Our findings suggest that densely granulated tumors, with positive SSTR2 and E-Cadherin seem to be associated with favorable fgSRL responses. The strongest predictive value of the studied markers was found for E-Cadherin, which seems to surpass even SSTR2. Full article
(This article belongs to the Special Issue Advances in Molecular Biology of Pituitary Diseases)
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Review

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18 pages, 1032 KiB  
Review
Implications of Dysnatremia and Endocrine Disturbances in COVID-19 Patients
by Mihaela Zlosa, Barbara Grubišić, Luka Švitek, Dario Sabadi, Silvija Canecki-Varžić, Ivica Mihaljević, Ines Bilić-Ćurčić and Tomislav Kizivat
Int. J. Mol. Sci. 2024, 25(18), 9856; https://doi.org/10.3390/ijms25189856 - 12 Sep 2024
Viewed by 961
Abstract
Sodium imbalance is a common electrolyte disturbance in COVID-19, often linked to disruptions in hormonal regulation. This review explores the relationship between sodium dysregulation and endocrine disturbances, particularly focusing on primary and secondary hypothyroidism, hypocortisolism, and the renin–angiotensin–aldosterone system (RAAS). Hypocortisolism in COVID-19, [...] Read more.
Sodium imbalance is a common electrolyte disturbance in COVID-19, often linked to disruptions in hormonal regulation. This review explores the relationship between sodium dysregulation and endocrine disturbances, particularly focusing on primary and secondary hypothyroidism, hypocortisolism, and the renin–angiotensin–aldosterone system (RAAS). Hypocortisolism in COVID-19, due to adrenal insufficiency or secondary to pituitary dysfunction, can lead to hyponatremia through inadequate cortisol levels, which impair renal free water excretion and enhance antidiuretic hormone (ADH) secretion. Similarly, hypothyroidism is associated with decreased renal blood flow and the glomerular filtration rate (GFR), which also increases ADH activity, leading to water retention and dilutional hyponatremia. Furthermore, COVID-19 can disrupt RAAS (primarily through its interaction with the angiotensin-converting enzyme 2 (ACE2) receptor), diminishing aldosterone secretion and further contributing to sodium loss and hyponatremia. These hormonal disruptions suggest that sodium imbalance in COVID-19 is multifactorial and warrants further investigation into the complex interplay between COVID-19, endocrine function, and sodium homeostasis. Future research should focus on understanding these mechanisms to develop management algorithms that address both sodium imbalance and underlying hormonal disturbances in order to improve prognosis and outcomes in COVID-19 patients. Full article
(This article belongs to the Special Issue Advances in Molecular Biology of Pituitary Diseases)
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