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The Journal of Clinical Endocrinology... Apr 2023Hypothalamic obesity (HO) is defined as abnormal weight gain due to physical destruction of the hypothalamus. Suprasellar tumors, most commonly craniopharyngiomas, are a...
Hypothalamic obesity (HO) is defined as abnormal weight gain due to physical destruction of the hypothalamus. Suprasellar tumors, most commonly craniopharyngiomas, are a classic cause of HO. HO often goes unnoticed initially as patients, families, and medical teams are focused on oncologic treatments and management of panhypopituitarism. HO is characterized by rapid weight gain in the first year after hypothalamic destruction followed by refractory obesity due to an energy imbalance of decreased energy expenditure without decreased food intake. Currently available pharmacotherapies are less effective in HO than in common obesity. While not a cure, dietary interventions, pharmacotherapy, and bariatric surgery can mitigate the effects of HO. Early recognition of HO is necessary to give an opportunity to intervene before substantial weight gain occurs. Our goal for this article is to review the pathophysiology of HO and to discuss available treatment options and future directions for prevention and treatment.
Topics: Humans; Pituitary Neoplasms; Hypothalamic Diseases; Craniopharyngioma; Obesity; Weight Gain
PubMed: 36413492
DOI: 10.1210/clinem/dgac678 -
Frontiers in Endocrinology 2022Heterozygous variants in cause MIRAGE syndrome, a complex multisystem disorder involving Myelodysplasia, Infection, Restriction of growth, Adrenal hypoplasia, Genital...
BACKGROUND
Heterozygous variants in cause MIRAGE syndrome, a complex multisystem disorder involving Myelodysplasia, Infection, Restriction of growth, Adrenal hypoplasia, Genital phenotypes, and Enteropathy. The range of additional clinical associations is expanding and includes disrupted placental development, poor post-natal growth and endocrine features. Increasingly, milder phenotypic features such as hypospadias in small for gestational age (SGA) boys and normal adrenal function are reported. Some children present with isolated myelodysplastic syndrome (MDS/monosomy 7) without MIRAGE features.
OBJECTIVE
We aimed to investigate: 1) the range of reported variants, clinical features, and possible genotype-phenotype correlations; 2) whether SAMD9 disruption affects placental function and leads to pregnancy loss/recurrent miscarriage (RM); 3) and if pathogenic variants are associated with isolated fetal growth restriction (FGR).
METHODS
Published data were analyzed, particularly reviewing position/type of variant, pregnancy, growth data, and associated endocrine features. Genetic analysis of was performed in products of conception (POC, n=26), RM couples, (couples n=48; individuals n=96), children with FGR (n=44), SGA (n=20), and clinical Silver-Russell Syndrome (SRS, n=8), (total n=194).
RESULTS
To date, variants are reported in 116 individuals [MDS/monosomy 7, 64 (55.2%); MIRAGE, 52 (44.8%)]. Children with MIRAGE features are increasingly reported without an adrenal phenotype (11/52, 21.2%). Infants without adrenal dysfunction were heavier at birth (median 1515 g versus 1020 g; P < 0.05) and born later (median 34.5 weeks versus 31.0; P < 0.05) compared to those with adrenal insufficiency. In MIRAGE patients, hypospadias is a common feature. Additional endocrinopathies include hypothyroidism, hypo- and hyper-glycemia, short stature and panhypopituitarism. Despite this increasing range of phenotypes, genetic analysis did not reveal any likely pathogenic variants/enrichment of specific variants in in the pregnancy loss/growth restriction cohorts studied.
CONCLUSION
MIRAGE syndrome is more phenotypically diverse than originally reported and includes growth restriction and multisystem features, but without adrenal insufficiency. Endocrinopathies might be overlooked or develop gradually, and may be underreported. As clinical features including FGR, severe infections, anemia and lung problems can be non-specific and are often seen in neonatal medicine, SAMD9-associated conditions may be underdiagnosed. Reaching a specific diagnosis of MIRAGE syndrome is critical for personalized management.
Topics: Adrenal Insufficiency; Chromosome Deletion; Chromosomes, Human, Pair 7; Female; Fetal Growth Retardation; Humans; Hypospadias; Intracellular Signaling Peptides and Proteins; Male; Myelodysplastic Syndromes; Phenotype; Placenta; Pregnancy; Syndrome
PubMed: 36060959
DOI: 10.3389/fendo.2022.953707 -
Acta Otorhinolaryngologica Italica :... Apr 2021The endoscopic endonasal transsphenoidal approach to the sella and parasellar regions is now increasingly used for removal of a variety of lesions localized in the...
INTRODUCTION
The endoscopic endonasal transsphenoidal approach to the sella and parasellar regions is now increasingly used for removal of a variety of lesions localized in the ventral skull base. The advantage of the endoscope is enhanced visualization and improved panoramic view that can result in more complete removal of the tumor. An extensive knowledge of the anatomy is mandatory to approach this region.
MATERIALS AND METHODS
From February 2009 to March 2020, the endoscopic endonasal approach was used in 153 patients with sellar and parasellar lesions, at our Institution: 136 pituitary adenomas, 7 craniopharyngiomas, 3 Rathke's cysts, a tuberculum sellae meningioma, an aneurysm of the internal carotid artery (ICA), a clivus chordoma, a papillary glioneuronal tumor, an histiocytosis, a pituitary metastasis from breast cancer and a chondrosarcoma.
RESULTS
The most common surgical complications were cerebral spinal fluid leak (9), bleeding (2), pituitary abscess (2). Among endocrinological complications, the most important were diabete insipidus (23) and panhypopituitarism (3). Two patients complicated with meningitis. There were no visual worsening and no operative mortality. We had persistence of disease in 20 cases. Twelve patients underwent surgical revision for recurrence of the disease.
CONCLUSIONS
Pre-operative planning and collaboration with several specialists are necessary in order to offer the patient the best treatment, minimizing complications.
Topics: Craniopharyngioma; Humans; Meningeal Neoplasms; Meningioma; Neoplasm Recurrence, Local; Pituitary Neoplasms; Retrospective Studies
PubMed: 34060518
DOI: 10.14639/0392-100X-suppl.1-41-2021-03 -
Annals of African Medicine 2021While hypopituitarism is known to be associated with increased cardiovascular morbidity and mortality, panhypopituitarism as a complication of myocardial infarction (MI)...
While hypopituitarism is known to be associated with increased cardiovascular morbidity and mortality, panhypopituitarism as a complication of myocardial infarction (MI) is very rare. Here, we report a case of rapidly developing empty sella syndrome with florid manifestations of panhypopituitarism after MI (due to critical stenosis in the left anterior descending artery) complicated by cardiogenic shock in a 65-year-old man. The patient was initially stabilized with conservative management of non-ST-elevated MI and cardiogenic shock, but after initial improvement, he again deteriorated with refractory shock (not adequately responding to vasopressors), seizures, hypoglycemia, hyponatremia, hyperkalemia, and metabolic acidosis. After ruling out recurrent cardiogenic shock or other causes of refractory hypotension, panhypopituitarism was diagnosed with the help of hormonal assays and imaging. With no prior evidence of hypopituitarism, we suspect that panhypopituitarism developed due to acute pituitary apoplexy secondary to initial cardiogenic shock. The patient was successfully survived by the emergency endocrine management followed by secondary coronary angioplasty.
Topics: Aged; Heart Failure; Humans; Hypopituitarism; Male; Myocardial Infarction
PubMed: 34213484
DOI: 10.4103/aam.aam_66_19 -
Clinical Neuropathology 2020Cystic sellar salivary gland-like lesions (CSSLs) are exceedingly rare, with fewer than a dozen case reports. They contain amorphous colloid identical to Rathke cleft...
INTRODUCTION
Cystic sellar salivary gland-like lesions (CSSLs) are exceedingly rare, with fewer than a dozen case reports. They contain amorphous colloid identical to Rathke cleft cyst contents, but the cyst wall additionally shows cohesive aggregates of benign salivary glands. We report three new examples.
MATERIALS AND METHODS
Two cases were seen at University of Colorado Denver and one at Memorial Sloan Kettering (MSK). Molecular testing was attempted on two of three.
RESULTS
Case 1 is a 20-year-old female who presented with panhypopituitarism and was found to have a suprasellar mass that proved to be a CSSL. She received no postoperative adjuvant therapy, but recurrence of headaches and blurred vision 2 years later prompted return to medical attention. A much smaller local cyst recurrence was now accompanied by a thickened, bulbous infundibular stalk. Second resection yielded a gliotic infundibular stalk and amorphous mucin, but no residual salivary-like glands. She is without further recurrence on 6-year follow-up. Case 2 is a 29-year-old female with headache; while seen initially at a tertiary care center, diagnosis was only made after consultation at MSK. Case 3 is 68-year-old female who had originally presented with apoplexy to an outside hospital 7 years prior to surgery and diagnosis. Molecular testing was uninformative on case 1 and negative for mutations or fusions on case 3.
CONCLUSION
Few pathologists or neuropathologists have encountered CSSLs in their practices; case 1 produced recurrence and significant infundibular stalk damage, and case 3 originally manifested apoplexy, features not previously reported.
Topics: Adult; Central Nervous System Cysts; Cysts; Female; Humans; Hypopituitarism; Magnetic Resonance Imaging; Neoplasm Recurrence, Local; Neurosurgical Procedures; Pituitary Gland; Salivary Glands; Young Adult
PubMed: 31845864
DOI: 10.5414/NP301235 -
Internal Medicine (Tokyo, Japan) Feb 2023A 59-year-old man suspected of having myocardial infarction with sinus bradycardia, a decreased blood pressure, and ST-change on an electrocardiogram was referred to our...
A 59-year-old man suspected of having myocardial infarction with sinus bradycardia, a decreased blood pressure, and ST-change on an electrocardiogram was referred to our hospital's emergency department. Emergent coronary angiography revealed no significant findings. However, the patient experienced shock and required intensive care. Curiosity rose when his urination volume was not disturbed; we suspected hormonal abnormalities. A hormonal examination and imaging analysis revealed panhypopituitarism caused by a Rathke's cyst. Appropriate hormonal replacement therapy improved his symptoms and led to normalization of his electrocardiogram findings. Acute coronary syndrome (ACS) is a fatal disease; however, clinicians must not discount panhypopituitarism, as it may mimic ACS symptoms.
Topics: Male; Humans; Middle Aged; Acute Coronary Syndrome; Hypopituitarism; Cysts; Emergency Service, Hospital
PubMed: 35705269
DOI: 10.2169/internalmedicine.0031-22 -
Orphanet Journal of Rare Diseases Mar 2022Craniopharyngioma (CP) and cranial fibrous dysplasia (CFD) are rare embryonic benign cranial diseases that most commonly present during childhood or adolescence. The... (Review)
Review
BACKGROUND
Craniopharyngioma (CP) and cranial fibrous dysplasia (CFD) are rare embryonic benign cranial diseases that most commonly present during childhood or adolescence. The coexistence of CP and CFD is extremely rare and has not yet been reported.
METHODS
We retrospectively reviewed the data of five patients with concomitant CP and CFD treated at Beijing Tiantan Hospital from January 2003 to January 2021 and summarized their clinicopathological features, treatment modalities, and outcomes. We also performed a comprehensive literature review, tested the patients for characteristic GNAS gene mutations related to CFD, and tested the CP specimens for corresponding Gsα protein to explore the potential connection leading to the coexistence of CP and CFD.
RESULTS
The cohort comprised four men and one woman (median age, 39 years). The symptoms mainly included headache, dizziness, fatigue, polyuria/polydipsia, hypogonadism, and blurred vision. CFD most commonly involved the sphenoid bone (n = 4). Four patients underwent surgery to remove the CP (one trans-sphenoidal and three transcranial resections); complete and subtotal resection were achieved in two patients, respectively. The tumor subtype was adamantinomatous in three patients and unknown in one. The common postoperative complications were panhypopituitarism, diabetes insipidus, and hypothyroidism. The mean follow-up duration was 57.2 months. Two patients required postoperative hormone replacement therapy. Three patients underwent genetic study of the tumor specimens; GNAS mutations were not detected, but these patients were positive for Gsα protein.
CONCLUSIONS
Although a definite causative relationship has not been proved, the coexistence of CP and CFD means that potential interplay or an atypical fibrous dysplasia course as uncommon manifestations of CP cannot be excluded. It is more challenging to initiate prompt diagnosis and appropriate treatment for concomitant CP and CFD than for solitary CP because of skull base deformations. Current management strategies are aimed at surgical treating the CP and regularly monitoring the CFD.
Topics: Adolescent; Adult; Craniopharyngioma; Female; Fibrous Dysplasia of Bone; Humans; Male; Pituitary Neoplasms; Retrospective Studies; Skull
PubMed: 35303908
DOI: 10.1186/s13023-022-02281-1 -
IScience Nov 2023-GlcNAcylation is a key post-translational modification, playing a vital role in cell signaling during development, especially in the brain. In this study, we...
-GlcNAcylation is a key post-translational modification, playing a vital role in cell signaling during development, especially in the brain. In this study, we investigated the role of -GlcNAcylation in regulating the homeobox protein OTX2, which contributes to various brain disorders, such as combined pituitary hormone deficiency, retinopathy, and medulloblastoma. Our research demonstrated that, under normal physiological conditions, the proteasome plays a pivotal role in breaking down endogenous OTX2. However, when the levels of OTX2 rise, it forms oligomers and/or aggregates that require macroautophagy for clearance. Intriguingly, we demonstrated that -GlcNAcylation enhances the solubility of OTX2, thereby limiting the formation of these aggregates. Additionally, we unveiled an interaction between OTX2 and the chaperone protein CCT5 at the -GlcNAc sites, suggesting a potential collaborative role in preventing OTX2 aggregation. Finally, our study demonstrated that while OTX2 physiologically promotes cell proliferation, an -GlcNAc-depleted OTX2 is detrimental to cancer cells.
PubMed: 38026167
DOI: 10.1016/j.isci.2023.108184 -
Journal of Mid-life Health 2022Lymphocytic hypophysitis (LYH) is a rare inflammatory disease in which lymphoplasmacytic infiltration of the pituitary gland can potentially lead to panhypopituitarism....
Lymphocytic hypophysitis (LYH) is a rare inflammatory disease in which lymphoplasmacytic infiltration of the pituitary gland can potentially lead to panhypopituitarism. This entity was first recognized in 1962 by Goudie and Pinkerton. We report the case of a 36-year-old nonpregnant female operated for a presumed nonsecreting pituitary adenoma. On intraoperative squash cytology and histology of excision biopsy confirmed the diagnosis of LYH. Review of the literature shows that most reported cases have occurred in women during pregnancy or during postpartum period. Many were accurately diagnosed only after biopsy or at necropsy. It is suspected to be an autoimmune endocrinopathy as concomitant lymphocytic infiltration of the thyroid and pituitary glands has been noted and antipituitary antibodies have been found in some instances. Clinically and radiologically, LYH may mimic a nonsecretory pituitary adenoma. Intraoperative diagnosis may prevent unnecessary excision of potentially functioning pituitary.
PubMed: 36950203
DOI: 10.4103/jmh.jmh_32_21 -
International Journal of Endocrinology 2019IgG4-related hypophysitis (IgG4-RH) is a rare disease, and its prevalence remains unclear. In recent years, an increasing number of cases have been reported because of... (Review)
Review
BACKGROUND
IgG4-related hypophysitis (IgG4-RH) is a rare disease, and its prevalence remains unclear. In recent years, an increasing number of cases have been reported because of the increasing recognition of this disease. We aimed to summarize case reports of IgG4-RH and outline the clinical features and outcomes.
METHODS
We performed PubMed search of articles using the search terms "hypophysitis [AND] IgG4." Consequently, only 54 English articles (76 cases) met Leporati's diagnostic criteria.
RESULTS
Of the 76 cases, the ratio of men to women was 1.5 : 1, and the age at diagnosis was 54.1 ± 17.8 years. The median IgG4 concentration was 405.0 mg/dl. Anterior hypopituitarism, isolated central diabetes insipidus, and panhypopituitarism were observed in 14 (18.4%), 12 (15.8%), and 44 (57.9%) cases, respectively. The sequence of anterior hormone deficiency was as follows: gonadotropin (68.4%), ACTH (63.2%), TSH (59.2%), GH (48.7%), and prolactin (42.1%). The median number of involved organs was 1.5, and the lung (18.4%), retroperitoneum (17.1%), kidney (15.8%), submandibular glands (14.5%), and pancreas (13.2%) were the common involved organs. Elevated IgG4 concentration and normal IgG4 level were in 42 (76.4%) and 13 (23.6%) cases, respectively. Patients with elevated serum IgG4 concentration were older (60.9 ± 14.3 vs 45.6 ± 17.4, =0.001) and male-prone (78.6% vs 40.4%, =0.003) and had a susceptibility of multiple organ involvement (78.6% vs 35.0%, =0.001) compared to those with normal serum IgG4 levels. Males were older at disease onset (61.5 ± 12.6 vs 42.9 ± 18.8, < 0.001) and had a higher IgG4 concentration (425.0 vs 152.5, =0.029) and a greater number of involved organs (2.0 vs 0.0, =0.001), while isolated hypophysitis was more prominent in female (63.3% vs 26.1%, =0.001).
CONCLUSION
In this review, we found that there were different characteristics between different genders. Patients with elevated serum IgG4 level in terms of some clinical features were also different from those with normal serum IgG4 level. However, the data in this review were limited by bias and confounding. Further clinical studies with larger sample sizes are warranted.
PubMed: 31929792
DOI: 10.1155/2019/5382640