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Hormones (Athens, Greece) Mar 2024The most commonly identified genetic cause of combined pituitary hormone deficiency (CPHD) is PROP1 gene mutations. The aim of the study was to compare selected clinical... (Comparative Study)
Comparative Study
UNLABELLED
The most commonly identified genetic cause of combined pituitary hormone deficiency (CPHD) is PROP1 gene mutations. The aim of the study was to compare selected clinical features of patients with CPHD caused by variants of the PROP1 gene (CPHD-PROP1) and patients with inborn CPHD of other etiology (CPHD-nonPROP1).
MATERIAL AND METHODS
The retrospective analysis included childhood medical records of 74 patients (32 female) with CPHD, including 43 patients (23 female) with the mutation in the PROP1 gene.
RESULTS
Patients with CPHD-PROP1 compared to the CPHD-nonPROP1 presented with the following: significantly higher median birth weight (0.21 vs. - 0.29 SDS, p = 0.019), lower growth velocity within 3 years preceding growth hormone administration (- 2.7 vs. - 0.8 SDS, p < 0.001), higher mean maximal blood concentration of growth hormone within the stimulation process (1.2 vs. 1.08 ng/mL, p = 0.003), lower TSH (1.8 vs. 2.4 µIU/mL, p < 0.001), significantly lower prolactin concentrations (128 vs. 416.3 µIU/mL, p < 0.001), and less frequent typical signs of hypogonadism at birth in boys (n = 6; 30% vs. n = 12, 54%, p < 0.001). Secondary adrenal insufficiency was less frequent in CPHD-PROP1 (20 vs. 25 cases, p = 0.006) and occurred at a later age (13.4 vs. 10.4 years). MRI of the pituitary gland in CPHD-PROP1 revealed a small pituitary gland (21 cases), pituitary gland enlargement (eight cases), and one pituitary stalk interruption and posterior lobe ectopy, while it was normal in nine cases.
CONCLUSION
Patients with the PROP1 mutations present a clinical picture significantly different from that of other forms of congenital hypopituitarism. Certain specific clinical results may lead to the successful identification of children requiring diagnostics for the PROP1 gene mutation.
Topics: Child; Female; Humans; Infant, Newborn; Male; Growth Hormone; Homeodomain Proteins; Hypopituitarism; Mutation; Retrospective Studies
PubMed: 38147295
DOI: 10.1007/s42000-023-00510-1 -
Endocrinology, Diabetes & Metabolism... Oct 2023IgG4-related disease is a multiorgan disorder in which nodules and hypertrophic lesions are observed simultaneously, or separately, in areas including the pancreas,...
SUMMARY
IgG4-related disease is a multiorgan disorder in which nodules and hypertrophic lesions are observed simultaneously, or separately, in areas including the pancreas, liver, lungs, salivary glands, thyroid glands, and pituitary glands. IgG4-related hypophysis is one of several IgG4-related diseases and is characterized by pituitary gland and pituitary stalk thickening, various degrees of hypopituitarism, and increased serum IgG4 levels. Steroid therapy is effective for patients with IgG4-related hypophysis, but the reported effectiveness of steroid therapy for restoring pituitary function differs between studies. Following an episode of autoimmune pancreatitis 10 years prior, enlargement of the pituitary gland and stalk along with panhypopituitarism and polyuria developed in a 73-year-old male. A high serum IgG4 level and biopsy of the submandibular gland showing infiltration of IgG4-positive plasma cells led to a clinical diagnosis of IgG4-related hypophysitis. Prednisolone treatment reduced the swelling of the pituitary gland and stalk and improved anterior pituitary function. Although arginine vasopressin secretion remained insufficient, polyuria was relieved and kept in remission even after prednisolone treatment was completed. This is the first reported case in which prednisolone was able to maintain both normal anterior pituitary function and remission of polyuria caused by IgG4-related hypophysitis. IgG4-related hypophysitis has previously been associated with a relapse of symptoms during treatment. However, the patient reported in this case study remained in remission for over 3 months after completion of steroid treatment and should be monitored closely for changes in pituitary function.
LEARNING POINTS
Steroid therapy is the first-line therapy for pituitary dysfunction and pituitary stalk swelling in IgG4-related hypophysitis. In this case, although posterior pituitary function remained insufficient, polyuria was relieved and kept in remission for over 3 months even after prednisolone treatment was completed. IgG4-related hypophysitis has been associated with the relapse of symptoms during steroid tapering, and changes in pituitary function and symptoms should be monitored closely. When we encounter cases of adrenal insufficiency and polyuria during observation of autoimmune pancreatitis or other IgG4-related disease, we should consider the possibility of IgG4-related hypophysitis in mind.
PubMed: 38131878
DOI: 10.1530/EDM-23-0007 -
Cureus Nov 2023Chondromas are rare benign tumors composed of hyaline cartilage that can arise in various locations in the body. Their occurrence in the clivus, leading to...
Chondromas are rare benign tumors composed of hyaline cartilage that can arise in various locations in the body. Their occurrence in the clivus, leading to panhypopituitarism, is exceptionally rare. This case report describes a 93-year-old female with a known clival chondroma who presented with altered mental status, presumed to be secondary to toxic metabolic encephalopathy due to an infectious cause. Further diagnostic evaluation revealed pituitary hormone levels below the normal range. This case report aims to highlight a unique case of panhypopituitarism attributed to a chondroma in the clivus with tumor extension to the sellar region, emphasizing the diagnostic challenges and treatment options for this unusual pathology.
PubMed: 38125262
DOI: 10.7759/cureus.49110 -
Annals of Medicine and Surgery (2012) Dec 2023Secretory pituitary macroadenoma also known as prolactinoma are benign neoplasm comprising very minimal cases of intracranial masses. Among the various presentation...
INTRODUCTION AND IMPORTANCE
Secretory pituitary macroadenoma also known as prolactinoma are benign neoplasm comprising very minimal cases of intracranial masses. Among the various presentation suggestive of panhypopituitarism, psychosis, and features of schizophrenia is very rarely seen. In the majority of cases, neurosurgical intervention for the excision of tumor is considered a standard treatment modality but conservative management with dopamine agonist and steroids have also been shown to provide an optimal level of care also improving the quality of level of patient.
CASE PRESENTATION
A 42-year-old Asian male presented with a history of talking to self, delusion of persecution, over talkativeness, hallucination, increased suspiciousness, and history of lost and found in the streets where he was working as a migrant worker. The patient was initially managed in line of schizophrenia with the antipsychotics drug of choice. On further assessment there was no improvement of psychiatric symptoms but they further deteriorated with additional neuropsychiatric symptoms; hence, MRI brain was carried out. Following which, the diagnosis of pituitary macroadenoma was confirmed and further more hormonal analysis was done, which showed findings suggestive of panhypopituitarism. The patient was then managed conservatively with dopamine agonist and steroids, which showed rapid improvement of psychiatric symptoms with a massive reduction in the size of the pituitary macroadenoma.
CLINICAL DISCUSSION
With the incidence of 100 per million cases pituitary adenomas are considered locally invading with the characteristic compression of the surrounding structure, presenting as visual hallucinations, olfactory hallucinations, episodes of losing time, apathy, and features suggestive of adrenal insufficiency, hypogonadotrophic hypogonadism, and symptoms secondary to hormonal imbalance such as hypothyroidism. Psychiatric symptomatic presentations are considered a very rare presentation in cases of pituitary macroadenoma. Also, psychiatric features and symptoms of psychosis are associated with prolcatinomas through idiopathic mechanism and the basic casualty has not been established. Surgical intervention such as trans-sphenoidal resection of the mass can be undertaken in case where mass effects is present but long-term remission and prognosis is found not to be fruitful. Conservative treatment with dopamine agonist such as cabergoline and steroids also plays a meaningful role in abrupt management in such cases.
CONCLUSION
Pituitary macroadenoma presenting as a patient of schizophrenia is noted very rarely in medical literature; hence, investigations in view of neurosurgical diagnosis in cases presenting as psychosis should be considered for ideal holistic management. Conservative management can also be a breakthrough treatment modality in complete recovery of pituitary macroadenoma.
PubMed: 38098557
DOI: 10.1097/MS9.0000000000001413 -
Heliyon Dec 2023Testosterone as replacement therapy for male hypogonadism or as gender-affirming hormone therapy for transgender and non-binary patients has increased worldwide....
Testosterone as replacement therapy for male hypogonadism or as gender-affirming hormone therapy for transgender and non-binary patients has increased worldwide. Commonly used formulations of testosterone include intramuscular, transdermal patch, and topical gel, each of which has differing pharmacokinetics and practical challenges. In monitoring testosterone serum concentrations, contamination of the phlebotomy site by testosterone topical gel can lead to supraphysiologic (>1000 ng/dL or 34.7 nmol/L) serum concentrations of testosterone, as demonstrated in a few published case reports. The frequency of this issue is currently not known. The present study involves a retrospective search over a 13-year period across all clinical sites at an academic medical center. Out of 578 unique patients using testosterone topical gel, a total of 48 patients had at least 1 testosterone serum concentration exceed 1000 ng/dL. Documentation in the electronic health record revealed 7 patients where contamination of the phlebotomy site by topical gel was strongly supported as the cause of supraphysiologic testosterone serum concentrations. These included 5 males with primary hypogonadism, 1 male with panhypopituitarism, and a non-binary patient with gender dysphoria. The high testosterone concentrations prompted further work-up, including retesting and endocrinology consultation. There were additional cases of high testosterone serum concentration that may have been falsely elevated due to gel contamination but without sufficient supporting evidence available in the health record. Overall, we present 7 cases of spuriously high testosterone concentrations strongly suspected to be due to venipuncture performed near or at the location of prior testosterone gel application. Gel contamination should be considered as a possible cause of otherwise unexplained high testosterone serum concentration in patients receiving topical testosterone gel formulations. Patient counseling and provider awareness of this potential cause of spuriously high testosterone serum concentrations is important.
PubMed: 38094062
DOI: 10.1016/j.heliyon.2023.e22819 -
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 -
Brain & Spine 2023Aneurysms extending into the sella are uncommon with only a few cases reported till date. Most of these arise from either the supraclinoidal or infraclinoidal segments...
INTRODUCTION
Aneurysms extending into the sella are uncommon with only a few cases reported till date. Most of these arise from either the supraclinoidal or infraclinoidal segments of the internal carotid artery.
RESEARCH QUESTION
Can Anterior communication artery aneurysm present with hypopituitarism due to compression of pituitary gland?
MATERIALS & METHODS
Case report and literature review.
RESULTS
We discuss this rare presentation in a middle-aged patient its surgical management and the follow-up course with a review of available literature.
DISCUSSION & CONCLUSION
Anterior communicating artery aneurysms extending into the sella are extremely uncommon with only 4 cases reported in literature. They are usually giant aneurysms which are partially thrombosed with presenting with predominantly with mass effect in this case visual impairment and hypofunction of the pituitary.
PubMed: 38020978
DOI: 10.1016/j.bas.2023.101792 -
Archives of Endocrinology and Metabolism Nov 2023Congenital hypopituitarism (CH) is a rare disease characterized by one or more hormone deficiencies of the pituitary gland. To date, many genes have been associated with...
OBJECTIVE
Congenital hypopituitarism (CH) is a rare disease characterized by one or more hormone deficiencies of the pituitary gland. To date, many genes have been associated with CH. In this study, we identified the allelic variant spectrum of 11 causative genes in Turkish patients with CH.
MATERIALS AND METHODS
This study included 47 patients [21 girls (44.6%) and 26 boys (55.4%)] from 45 families. To identify the genetic etiology, we screened 11 candidate genes associated with CH using next-generation sequencing. To confirm and detect the status of the specific familial variant in relatives, Sanger sequencing was also performed.
RESULTS
We identified 12 possible pathogenic variants in GHRHR, GH1, GLI2, PROP-1, POU1F1, and LHX4 in 11 patients (23.4%), of which six were novel variants: two in GHRHR, two in POU1F1, one in GLI2, and one in LHX4. In all patients, these variants were most frequently found in GLI2, followed by PROP-1 and GHRHR.
CONCLUSION
Genetic causes were determined in only 23.4% of all patients with CH and 63% of molecularly diagnosed patients (7/11) from consanguineous families. Despite advances in genetics, we were unable to identify the genetic etiology of most patients with CH, suggesting the effect of unknown genes or environmental factors. More genetic studies are necessary to understand the etiology of CH.
Topics: Female; Humans; Male; Alleles; Hypopituitarism; Mutation; Nuclear Proteins; Transcription Factor Pit-1; Transcription Factors; Zinc Finger Protein Gli2
PubMed: 37948564
DOI: 10.20945/2359-4292-2022-0254 -
JCEM Case Reports May 2023Herpes simplex virus (HSV) is one of the most common causes of viral encephalitis. Hypothalamic-pituitary dysfunction has rarely been reported in HSV encephalitis, with...
Herpes simplex virus (HSV) is one of the most common causes of viral encephalitis. Hypothalamic-pituitary dysfunction has rarely been reported in HSV encephalitis, with few reports into the longer term outcomes for these patients. A 46-year-old male presented with a 10-day history of delirium, fever, and polydipsia. Initial computed tomography of the brain and cerebrospinal fluid cell counts were normal. Magnetic resonance imaging showed T2-hyperintensity affecting bilateral infundibuli, hypothalami, subthalamic nuclei, and optic radiations. Serial cerebrospinal fluid detected HSV1 DNA and we diagnosed him with HSV diencephalitis. He had marked biochemical abnormalities from the outset, with dramatic changes in serum sodium levels. He was ultimately diagnosed with permanent central diabetes insipidus and panhypopituitarism following evidence of central hypothyroidism, hypogonadotrophic hypogonadism, and a flat cortisol response to an insulin tolerance test. Neurocognitive recovery took several months, but subtle deficits in executive function and information processing remain. Hypothalamic hyperphagia developed as well as temperature dysregulation. He requires lifelong hormonal replacement and is undergoing regular endocrine follow up. This case highlights hypothalamic-pituitary dysfunction as a rare endocrine complication of HSV diencephalitis and illustrates the complexity of managing this in the long term.
PubMed: 37908572
DOI: 10.1210/jcemcr/luad050 -
Clinical Diabetes and Endocrinology Oct 2023Pituitary adenomas (PPAs) are uncommon in childhood and adolescence, accounting for 2-6% of all intracranial neoplasms. Delayed puberty, growth retardation, galactorrhea...
BACKGROUND
Pituitary adenomas (PPAs) are uncommon in childhood and adolescence, accounting for 2-6% of all intracranial neoplasms. Delayed puberty, growth retardation, galactorrhea and weight gain are common features at presentation in pediatric patients. Functional tumors constitute a vast majority (90%) of PPAs, with the most frequent being prolactinomas.
CASE PRESENTATION
A retrospective review of the clinical features and outcomes of 7 pediatric patients with pituitary macroadenomas was conducted. We included PPAs in patients under 18 years at diagnosis with diameters larger than 10 mm by magnetic resonance (MRI). Six patients were males (85%), with age at diagnosis ranging from 8 to 15 (median 14 ± 2.8SDS). The primary symptoms that led to medical attention were growth retardation, gigantism and secondary amenorrhea. The visual field was reduced in three cases (42%). Suprasellar extension was present in 3 subjects, and one had a giant adenoma. Adenomas were clinically functioning in 6 patients (85%) (three prolactinomas, two somatropinomas, one secreting FSH and one no-producer). The prolactinomas responded to treatment with cabergoline. For the rest, one required transsphenoidal surgery and the other three both surgery and radiotherapy. All patients undergoing radiotherapy had secondary panhypopituitarism. In relation to the genetic studies, two patients presented a pathogenic mutation of the AIP gene and one of the MEN1.
DISCUSION AND CONCLUSION
Pediatric pituitary macroadenomas are a distinct entity, mostly found in males and with a predominance of functional tumors leading to detrimental effects on growth and puberty in addition to neuro-ophthalmological manifestations. It is important to perform genetic studies in patients with macroadenomas appearing under the age of 18 years as genetic and syndromic associations are more frequent in this age group.
PubMed: 37908013
DOI: 10.1186/s40842-023-00153-6