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Article ; Online: Acromegaly Type 1: A Representative Patient.

Cuevas-Ramos, Daniel / Melmed, Shlomo

JCEM case reports

2024 Volume 2, Issue 4, Page(s) luae053

Abstract: A 46-year-old woman was troubled by a 3-year history of constant headaches and arthralgias. She was treated with paracetamol with no symptom resolution. An abnormal fasting glucose level prompted endocrine evaluation. On physical examination, she ... ...

Abstract	A 46-year-old woman was troubled by a 3-year history of constant headaches and arthralgias. She was treated with paracetamol with no symptom resolution. An abnormal fasting glucose level prompted endocrine evaluation. On physical examination, she casually mentioned that her wedding ring no longer fit, and she also confirmed an increase in shoe size. There were no characteristic facial features for acromegaly and there was no evidence of acral enlargement. Biochemical evaluation, including insulin-like growth factor type 1 (IGF-1) measurement and oral glucose loading with growth hormone (GH) measurement confirmed excess GH production and a diagnosis of acromegaly. Pituitary magnetic resonance imaging showed a central pituitary microadenoma. After transsphenoidal surgical resection, tissue immunohistochemistry revealed a densely granulated somatotroph adenoma. Currently, the patient is asymptomatic with biochemical disease control, normal fasting glucose levels, and no pituitary hormone deficiencies. This patient is illustrative of a type 1 acromegaly with mild clinical manifestations. Clinicians should be aware of acromegaly subtypes to avoid delay in diagnosis and to individualize therapy.
Language	English
Publishing date	2024-04-17
Publishing country	England
Document type	Case Reports
ISSN	2755-1520
ISSN (online)	2755-1520
DOI	10.1210/jcemcr/luae053
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Article ; Online: The definition of remission and recurrence of Cushing's disease.

Hinojosa-Amaya, José Miguel / Cuevas-Ramos, Daniel

Best practice & research. Clinical endocrinology & metabolism

2021 Volume 35, Issue 1, Page(s) 101485

Abstract: Accurate classification of postsurgical remission, and early recognition of recurrence are crucial to timely treat and prevent excess mortality in Cushing's Disease, yet the criteria used to define remission are variable and there is no consensus to ... ...

Abstract	Accurate classification of postsurgical remission, and early recognition of recurrence are crucial to timely treat and prevent excess mortality in Cushing's Disease, yet the criteria used to define remission are variable and there is no consensus to define recurrence. Remission is defined as postsurgical hypocortisolemia, but delayed remission may occur. Recurrence is the return of clinical manifestations with biochemical evidence of hypercortisolism. The proper combination of tests and their timing are controversial. Reliable predicting tools may lead to earlier diagnosis upon recurrence. Many factors have been studied independently for prediction with variable performance. Novel artificial intelligence approaches seek to integrate these variables into risk calculators and machine-learning algorithms with an acceptable short-term predictive performance but lack longer-term accuracy. Prospective studies using these approaches are needed. This review summarizes the evidence behind the definitions of remission and recurrence and provide an overview of the available tools to predict and/or diagnose them.
MeSH term(s)	ACTH-Secreting Pituitary Adenoma/diagnosis ; ACTH-Secreting Pituitary Adenoma/pathology ; ACTH-Secreting Pituitary Adenoma/surgery ; Adenoma/diagnosis ; Adenoma/metabolism ; Adenoma/pathology ; Adenoma/surgery ; Adrenal Insufficiency/diagnosis ; Adrenal Insufficiency/etiology ; Diagnostic Techniques, Endocrine ; Humans ; Neoplasm Recurrence, Local/diagnosis ; Pituitary ACTH Hypersecretion/diagnosis ; Pituitary ACTH Hypersecretion/metabolism ; Pituitary ACTH Hypersecretion/surgery ; Postoperative Complications/diagnosis ; Postoperative Complications/etiology ; Prognosis ; Recurrence ; Remission Induction/methods ; Risk Assessment
Language	English
Publishing date	2021-01-13
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	2052339-7
ISSN	1878-1594 ; 1532-1908 ; 1521-690X
ISSN (online)	1878-1594 ; 1532-1908
ISSN	1521-690X
DOI	10.1016/j.beem.2021.101485
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Article: Recent Understanding and Future Directions of Recurrent Corticotroph Tumors.

Hinojosa-Amaya, José Miguel / Lam-Chung, César Ernesto / Cuevas-Ramos, Daniel

Frontiers in endocrinology

2021 Volume 12, Page(s) 657382

Abstract: Corticotroph tumors (CTs) are pituitary neoplasms arising from the Tpit lineage, which may or not express adrenocorticotrophic hormone (ACTH). Functioning CTs cause Cushing's disease (CD), which has high morbidity and mortality due to hypercortisolemia. " ...

Abstract	Corticotroph tumors (CTs) are pituitary neoplasms arising from the Tpit lineage, which may or not express adrenocorticotrophic hormone (ACTH). Functioning CTs cause Cushing's disease (CD), which has high morbidity and mortality due to hypercortisolemia. "Non-functioning" or silent CTs (SCT) and the Crooke's cell subtypes do not cause CD and may be asymptomatic until manifested by compressive symptoms and are more frequently found as macroadenoma. Both tend toward more aggressive behavior, recurrence, and a higher rate of malignant transformation to pituitary carcinoma. Tumorigenesis involves genetic, epigenetic, and post-transcriptional disruption of cell-cycle regulators, which increase cell proliferation,
MeSH term(s)	Adenoma/metabolism ; Adenoma/pathology ; Corticotrophs/metabolism ; Corticotrophs/pathology ; Gene Expression Regulation, Neoplastic ; Humans ; Neoplasm Recurrence, Local/metabolism ; Neoplasm Recurrence, Local/pathology
Language	English
Publishing date	2021-04-26
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2592084-4
ISSN	1664-2392
ISSN	1664-2392
DOI	10.3389/fendo.2021.657382
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Article ; Online: Pituitary Infiltration by Lymphoma.

Tovar-Méndez, Víctor Hugo / Cuenca, Dalia / Gómez-Pérez, Francisco J / Cuevas-Ramos, Daniel

Journal of the Endocrine Society

2022 Volume 6, Issue 12, Page(s) bvac161

Abstract: Lymphoma infiltration to the pituitary is rare. It represents less than 0.5% of all reported pituitary metastases (PMs). Here we present a case series of 3 patients with PMs from a systemic lymphoma. Also, we performed a literature review of the cases ... ...

Abstract	Lymphoma infiltration to the pituitary is rare. It represents less than 0.5% of all reported pituitary metastases (PMs). Here we present a case series of 3 patients with PMs from a systemic lymphoma. Also, we performed a literature review of the cases reported. We identified additional 31 cases in which non-Hodgkin lymphoma (NHL) was the most common (n = 28, 90%), with large B-cell NHL the most frequent histological subtype (n = 14, 45%). Central hypothyroidism (n = 21, 67%) was the most frequent pituitary deficiency followed by adrenal insufficiency (n = 19, 61%) and diabetes insipidus (DI; n = 18, 58%). Full endocrine recovery was found in only 12% (n = 4) of patients after treatment, and magnetic resonance imaging showed tumor regression in 22% of them. In our series, 2 patients were diagnosed with diffuse large B-cell lymphoma, and 1 had mixed cellularity of classic Hodgkin lymphoma. The mean age was 54 ± 6.92 years. Hypopituitarism and DI were present in all of them, with 100% of mortality because of advanced systemic disease.
Language	English
Publishing date	2022-10-27
Publishing country	United States
Document type	Case Reports
ISSN	2472-1972
ISSN (online)	2472-1972
DOI	10.1210/jendso/bvac161
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Article ; Online: Medical treatment of Cushing's Disease.

Cuevas-Ramos, Daniel / Fleseriu, Maria

Minerva endocrinologica

2016 Volume 41, Issue 3, Page(s) 324–340

Abstract: Cushing's Syndrome (CS) is a serious endocrine disease that results from the adverse clinical consequences of chronic exposure to high levels of glucocorticoids. Most patients with endogenous CS have an adrenocorticotropin (ACTH)-secreting pituitary ... ...

Abstract	Cushing's Syndrome (CS) is a serious endocrine disease that results from the adverse clinical consequences of chronic exposure to high levels of glucocorticoids. Most patients with endogenous CS have an adrenocorticotropin (ACTH)-secreting pituitary corticotroph adenoma, i.e. Cushing's Disease (CD). The first-line therapy for CD is transsphenoidal pituitary surgery. If tumor removal is incomplete or unsuccessful, persistent hypercortisolism will require further treatment. Repeat surgery, medical therapy, radiation and bilateral adrenalectomy are all second line therapy options; however, medical therapy can be also used as first line therapy in patients who cannot undergo surgery, or to decrease cortisol values and/or improve co-morbidities. Medications used in the treatment of CD, classified into three groups: pituitary directed drugs, adrenal steroidogenesis inhibitors and glucocorticoid receptor blockers, are reviewed. Future 'on the horizon' treatment options are also discussed.
MeSH term(s)	Drug Therapy, Combination ; Hormone Antagonists/therapeutic use ; Humans ; Hydrocortisone/blood ; Pituitary ACTH Hypersecretion/drug therapy ; Pituitary ACTH Hypersecretion/radiotherapy ; Pituitary ACTH Hypersecretion/surgery
Chemical Substances	Hormone Antagonists ; Hydrocortisone (WI4X0X7BPJ)
Language	English
Publishing date	2016-09
Publishing country	Italy
Document type	Journal Article ; Review
ZDB-ID	423687-7
ISSN	1827-1634 ; 0391-1977
ISSN (online)	1827-1634
ISSN	0391-1977
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Article ; Online: Pasireotide: a novel treatment for patients with acromegaly.

Cuevas-Ramos, Daniel / Fleseriu, Maria

Drug design, development and therapy

2016 Volume 10, Page(s) 227–239

Abstract: Morbidity and mortality rates in patients with active acromegaly are higher than the general population. Adequate biochemical control restores mortality to normal rates. Now, medical therapy has an increasingly important role in the treatment of patients ...

Abstract	Morbidity and mortality rates in patients with active acromegaly are higher than the general population. Adequate biochemical control restores mortality to normal rates. Now, medical therapy has an increasingly important role in the treatment of patients with acromegaly. Somatostatin receptor ligands (SRLs) are considered the standard medical therapy, either after surgery or as a first-line therapy when surgery is deemed ineffective or is contraindicated. Overall, octreotide and lanreotide are first-generation SRLs and are effective in ~20%-70% of patients. Pegvisomant, a growth hormone receptor antagonist, controls insulin-like growth factor 1 in 65%-90% of cases. Consequently, a subset of patients (nonresponders) requires other treatment options. Drug combination therapy offers the potential for more efficacious disease control. However, the development of new medical therapies remains essential. Here, emphasis is placed on new medical therapies to control acromegaly. There is a focus on pasireotide long-acting release (LAR) (Signifor LAR®), which was approved in 2014 by the US Food and Drug Administration and the European Medicine Agency for the treatment of acromegaly. Pasireotide LAR is a long-acting somatostatin multireceptor ligand. In a Phase III clinical trial in patients with acromegaly (naïve to medical therapy or uncontrolled on a maximum dose of first-generation SRLs), 40 and 60 mg of intramuscular pasireotide LAR achieved better biochemical disease control than octreotide LAR, and tumor shrinkage was noted in both pasireotide groups. Pasireotide LAR tolerability was similar to other SRLs, except for a greater frequency and degree of hyperglycemia and diabetes mellitus. Baseline glucose may predict hyperglycemia occurrence after treatment, and careful monitoring of glycemic status and appropriate treatment is required. A precise definition of patients with acromegaly who will derive the greatest therapeutic benefit from pasireotide LAR remains to be established. Lastly, novel therapies and new potential delivery modalities (oral octreotide) are summarized.
MeSH term(s)	Acromegaly/drug therapy ; Acromegaly/physiopathology ; Animals ; Delayed-Action Preparations ; Drug Delivery Systems ; Drug Design ; Humans ; Octreotide ; Somatostatin/administration & dosage ; Somatostatin/adverse effects ; Somatostatin/analogs & derivatives ; Somatostatin/therapeutic use
Chemical Substances	Delayed-Action Preparations ; Somatostatin (51110-01-1) ; pasireotide (98H1T17066) ; Octreotide (RWM8CCW8GP)
Language	English
Publishing date	2016
Publishing country	New Zealand
Document type	Comparative Study ; Journal Article ; Review
ZDB-ID	2451346-5
ISSN	1177-8881 ; 1177-8881
ISSN (online)	1177-8881
ISSN	1177-8881
DOI	10.2147/DDDT.S77999
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Article ; Online: Patients with Gilbert syndrome and type 2 diabetes have lower prevalence of microvascular complications.

Uribe-Weichers, Ana Cecilia / Gómez-Pérez, Francisco J / Lam-Chung, César Ernesto / Cuevas-Ramos, Daniel

Metabolism open

2021 Volume 11, Page(s) 100114

Abstract: Objective: Accumulating clinical evidence indicates an inverse relationship between oxidative stress and unconjugated hyperbilirubinemia. This study aimed to compare the prevalence of diabetes microvascular complications in patients with Gilbert ... ...

Abstract	Objective: Accumulating clinical evidence indicates an inverse relationship between oxidative stress and unconjugated hyperbilirubinemia. This study aimed to compare the prevalence of diabetes microvascular complications in patients with Gilbert syndrome and type 2 diabetes mellitus (T2D). Methods: A total of 1200 electronic records with T2D were reviewed. From them, 50 patients with Gilbert syndrome (cases [indirect bilirubin ≥1.2 mg/dl without evidence of hemolysis or liver disease]) and 50 controls (T2D without hyperbilirubinemia) were included. Linear and logistic regression models were performed to evaluate the independent association between indirect hyperbilirubinemia with microvascular complications related with T2D. Results: Both case and control group had the same proportion of gender (female = 20 [40 %]) and diabetes duration (14.0 ± 6.5 years) and similar mean of age (60 ± 9.6 and 60 ± 9.2 years, respectively, Conclusions: Patients with Gilbert syndrome and T2D had a lower prevalence of diabetes microvascular complications.
Language	English
Publishing date	2021-07-28
Publishing country	England
Document type	Journal Article
ISSN	2589-9368
ISSN (online)	2589-9368
DOI	10.1016/j.metop.2021.100114
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Article: Fibroblast Growth Factor 21 and Browning of White Adipose Tissue.

Cuevas-Ramos, Daniel / Mehta, R / Aguilar-Salinas, Carlos A

Frontiers in physiology

2019 Volume 10, Page(s) 37

Abstract: Interest has been focused on differentiating anatomical, molecular, and physiological characteristics of the types of mammalian adipose tissues. White adipose tissue (WAT) and brown adipose tissue (BAT) are the two main forms of adipose tissue in humans. ...

Abstract	Interest has been focused on differentiating anatomical, molecular, and physiological characteristics of the types of mammalian adipose tissues. White adipose tissue (WAT) and brown adipose tissue (BAT) are the two main forms of adipose tissue in humans. WAT functions as an endocrine organ and serves as a reservoir of energy in the form of triglycerides. The hormones released by WAT are called adipokines. BAT consists of a group of specialized cells with abundant uncoupling protein 1 (UCP1) in the inner mitochondrial membrane and also fulfills endocrine functions. Following the identification of functional (BAT) in human adults, there has been a great deal of interest in finding out how it is induced, its localization, and the mechanisms by which it regulates thermogenesis. Fibroblast growth factor 21 (FGF21) is a key regulator of the differentiation to brown adipocytes. The main mechanisms occur through enhancing UCP1 expression. In addition, following exposure to cold or exercise, FGF21 induces upregulation of local peroxisome proliferator-activated receptor gamma co-activator (PGC)-1-alfa and thus promotes thermogenesis in adipose tissue and skeletal muscle. FGF21 integrates several pathways allowing the regulation of human energy balance, glucose levels, and lipid metabolism. Such mechanisms and their clinical relevance are summarized in this review.
Language	English
Publishing date	2019-02-05
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2564217-0
ISSN	1664-042X
ISSN	1664-042X
DOI	10.3389/fphys.2019.00037
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Article ; Online: Medical Management of Cushing's Syndrome: Current and Emerging Treatments.

Hinojosa-Amaya, José Miguel / Cuevas-Ramos, Daniel / Fleseriu, Maria

Drugs

2019 Volume 79, Issue 9, Page(s) 935–956

Abstract: Endogenous Cushing's syndrome is a chronic disease associated with increased morbidity and mortality if not appropriately treated. Recurrence and/or persistence of hypercortisolemia after surgical treatment, especially for Cushing's disease, are high, ... ...

Abstract	Endogenous Cushing's syndrome is a chronic disease associated with increased morbidity and mortality if not appropriately treated. Recurrence and/or persistence of hypercortisolemia after surgical treatment, especially for Cushing's disease, are high, and long-term medical treatment is used to decrease cortisol levels and risk of metabolic comorbidities. Medical treatment is also often required while waiting for radiation effects to take place. In some cases, severe or life-threatening hypercortisolism must be urgently and medically treated, via intravenous medications or with combination therapy, before patients can undergo surgery. In the last decade, medical treatment has progressed from a few steroidogenesis inhibitors to three novel drug groups: new inhibitors for steroidogenic enzymes with possibly fewer side effects, pituitary-directed drugs that aim to inhibit the pathophysiological pathways of Cushing's disease, and glucocorticoid receptor antagonists that block cortisol's action. Understanding the pathophysiology of Cushing's syndrome has also led to the identification of potential targets that may decrease adrenocorticotrophic hormone and/or cortisol excess, and/or decrease tumor cell proliferation, and induce senescence or apoptosis. We provide here a review of current and near-future medical options to treat Cushing's syndrome, and discuss updates on clinical trials and the efficacy and safety of novel or in-development drugs, as well as future potential targets.
MeSH term(s)	Adrenocorticotropic Hormone/antagonists & inhibitors ; Clinical Trials as Topic ; Cushing Syndrome/drug therapy ; Cushing Syndrome/metabolism ; Drug Therapy, Combination ; Endocrinology/methods ; Endocrinology/trends ; Enzyme Inhibitors/pharmacology ; Enzyme Inhibitors/therapeutic use ; Humans ; Hydrocortisone/biosynthesis ; Pituitary Gland/drug effects ; Pituitary Gland/metabolism ; Receptors, Glucocorticoid/antagonists & inhibitors ; Receptors, Glucocorticoid/metabolism ; Treatment Outcome
Chemical Substances	Enzyme Inhibitors ; Receptors, Glucocorticoid ; Adrenocorticotropic Hormone (9002-60-2) ; Hydrocortisone (WI4X0X7BPJ)
Language	English
Publishing date	2019-05-16
Publishing country	New Zealand
Document type	Journal Article ; Review
ZDB-ID	120316-2
ISSN	1179-1950 ; 0012-6667
ISSN (online)	1179-1950
ISSN	0012-6667
DOI	10.1007/s40265-019-01128-7
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Article ; Online: Treatment of Cushing's disease: a mechanistic update.

Cuevas-Ramos, Daniel / Fleseriu, Maria

The Journal of endocrinology

2014 Volume 223, Issue 2, Page(s) R19–39

Abstract: Cushing's disease (CD) is characterized by an ACTH-producing anterior corticotrope pituitary adenoma. If hypothalamus-pituitary-adrenal (HPA) axis physiology is disrupted, ACTH secretion increases, which in turn stimulates adrenocortical steroidogenesis ... ...

Abstract	Cushing's disease (CD) is characterized by an ACTH-producing anterior corticotrope pituitary adenoma. If hypothalamus-pituitary-adrenal (HPA) axis physiology is disrupted, ACTH secretion increases, which in turn stimulates adrenocortical steroidogenesis and cortisol production. Medical treatment plays an important role for patients with persistent disease after surgery, for those in whom surgery is not feasible, or while awaiting effects of radiation. Multiple drugs, with different mechanisms of action and variable efficacy and tolerability for controlling the deleterious effects of chronic glucocorticoid excess, are available. The molecular basis and clinical data for centrally acting drugs, adrenal steroidogenesis inhibitors, and glucocorticoid receptor antagonists are reviewed, as are potential novel molecules and future possible targets for CD treatment. Although progress has been made in the understanding of specific corticotrope adenoma receptor physiology and recent clinical studies have detected improved effects with a combined medical therapy approach, there is a clear need for a more efficacious and better-tolerated medical therapy for patients with CD. A better understanding of the molecular mechanisms in CD and of HPA axis physiology should advance the development of new drugs in the future.
MeSH term(s)	Animals ; Humans ; Hypothalamo-Hypophyseal System/drug effects ; Ligands ; Molecular Targeted Therapy/methods ; Pituitary ACTH Hypersecretion/drug therapy ; Pituitary-Adrenal System/drug effects ; Receptors, Somatostatin/agonists ; Receptors, Somatostatin/metabolism ; Signal Transduction/drug effects ; Somatostatin/analogs & derivatives ; Somatostatin/therapeutic use ; Steroid Synthesis Inhibitors/therapeutic use
Chemical Substances	Ligands ; Receptors, Somatostatin ; Steroid Synthesis Inhibitors ; Somatostatin (51110-01-1)
Language	English
Publishing date	2014-11
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	3028-4
ISSN	1479-6805 ; 0022-0795
ISSN (online)	1479-6805
ISSN	0022-0795
DOI	10.1530/JOE-14-0300
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