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Endocrine Connections Aug 2022Children with suprasellar brain damage are at risk of hypothalamic dysfunction (HD). HD may lead to decreased resting energy expenditure (REE). Decreased REE, however,...
OBJECTIVE
Children with suprasellar brain damage are at risk of hypothalamic dysfunction (HD). HD may lead to decreased resting energy expenditure (REE). Decreased REE, however, is not present in all children with HD. Our aim was to assess which children suspect for HD have low REE, and its association with clinical severity of HD or radiological hypothalamic damage.
PATIENTS AND METHODS
A retrospective cohort study was performed. Measured REE (mREE) of children at risk of HD was compared to predicted REE (pREE). Low REE was defined as mREE <90% of predicted. The mREE/pREE quotient was associated to a clinical score for HD symptoms and to radiological hypothalamic damage.
RESULTS
In total, 67 children at risk of HD (96% brain tumor diagnosis) with a mean BMI SDS of +2.3 ± 1.0 were included. Of these, 45 (67.2%) had low mREE. Children with severe HD had a significant lower mean mREE/pREE quotient compared to children with no, mild, or moderate HD. Mean mREE/pREE quotient of children with posterior hypothalamic damage was significantly lower compared to children with no or anterior damage. Tumor progression or tumor recurrence, severe clinical HD, and panhypopituitarism with diabetes insipidus (DI) were significant risk factors for reduced REE.
CONCLUSION
REE may be lowered in children with hypothalamic damage and is associated to the degree of clinical HD. REE is, however, not lowered in all children suspect for HD. For children with mild or moderate clinical HD symptoms, REE measurements may be useful to distinguish between those who may benefit from obesity treatment that increases REE from those who would be better helped using other obesity interventions.
PubMed: 35904233
DOI: 10.1530/EC-22-0276 -
Molecular Genetics & Genomic Medicine Feb 2021Pilomyxoid astrocytomas are an aggressive subtype of astrocytoma, not graded by WHO, frequently located in hypothalamic/chiasmatic region, affecting diencephalic...
BACKGROUND
Pilomyxoid astrocytomas are an aggressive subtype of astrocytoma, not graded by WHO, frequently located in hypothalamic/chiasmatic region, affecting diencephalic structures, and characterized by shorter survival and high recurrence rates. Pilomyxoid astrocytoma management remains controversial, with pathologic tissue diagnosis and relief of mass effect being the main goals of surgery while avoiding treatment-related morbidity, including vision loss, panhypopituitarism, and hypothalamic dysfunction. Chemotherapy (typically vincristine and carboplatin) in all pediatric patients and radiation therapy in pediatric patients over 5 years of age are used for treatment.
METHODS
We report clinical presentation, surgical management, and whole exome sequencing results in a pediatric patient with the subtotally resected pilomyxoid astrocytoma.
RESULTS
We identified two somatic activating missense mutations affecting FGFR1, including FGFR1 p.K656E and FGFR1 p.V561M. While the former is a known hotspot mutation that is both activating and transforming, the latter has been described as a gatekeeper mutation imparting resistance to FGFR inhibitors. Interestingly, both mutations were present with similar variant allele frequency within the tumor.
CONCLUSION
Similar variant allele frequencies of FGFR1 p.K656E and FGFR1 p.V561M mutations in our patient's tumor suggest that these mutations may have occurred at similar time points. Use of FGFR inhibitors in addition to STAT3 or PI3K/mTOR inhibition may prove a useful strategy in targeting our patient's pilomyxoid astrocytoma.
Topics: Astrocytoma; Brain Neoplasms; Humans; Infant; Male; Mutation, Missense; Receptor, Fibroblast Growth Factor, Type 1
PubMed: 33448156
DOI: 10.1002/mgg3.1597 -
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 -
Molecular and Cellular Pediatrics Nov 2020Isolated growth hormone deficiency (GHD) is defined by growth failure in combination with retarded bone age, low serum insulin-like growth factor-1, and insufficient GH... (Review)
Review
Isolated growth hormone deficiency (GHD) is defined by growth failure in combination with retarded bone age, low serum insulin-like growth factor-1, and insufficient GH peaks in two independent GH stimulation tests. Congenital GHD can present at any age and can be associated with significant malformations of the pituitary-hypothalamic region or the midline of the brain. In rare instances, genetic analysis reveals germline mutations of transcription factors involved in embryogenesis of the pituitary gland and the hypothalamus. Acquired GHD is caused by radiation, inflammation, or tumor growth. In contrast to organic GHD, idiopathic forms are more frequent and remain unexplained.There is a risk of progression from isolated GHD to combined pituitary hormone deficiency (> 5% for the total group), which is clearly increased in children with organic GHD, especially with significant malformation of the pituitary gland. Therefore, it is prudent to exclude additional pituitary hormone deficiencies in the follow-up of children with isolated GHD by clinical and radiological observations and endocrine baseline tests. In contrast to primary disorders of endocrine glands, secondary deficiency is frequently milder in its clinical manifestation. The pituitary hormone deficiencies can develop over time from mild insufficiency to severe deficiency. This review summarizes the current knowledge on diagnostics and therapy of additional pituitary hormone deficits occurring during rhGH treatment in children initially diagnosed with isolated GHD. Although risk factors are known, there are no absolute criteria enabling exclusion of children without any risk of progress to combined pituitary hormone deficiency. Lifelong monitoring of the endocrine function of the pituitary gland is recommended in humans with organic GHD. This paper is the essence of a workshop of pediatric endocrinologists who screened the literature for evidence with respect to evolving pituitary deficits in initially isolated GHD, their diagnosis and treatment.
PubMed: 33140249
DOI: 10.1186/s40348-020-00108-2 -
Cureus Aug 2022Hypophysitis is the inflammation of the pituitary gland primary or secondary to local or systemic disease. It tends to occur more with cytotoxic T-lymphocyte-associated...
Hypophysitis is the inflammation of the pituitary gland primary or secondary to local or systemic disease. It tends to occur more with cytotoxic T-lymphocyte-associated protein 4 inhibitors (10-15% of cases), which is a different entity compared to that associated with anti-program death 1 (anti-PD1) inhibitors. We describe a case of pembrolizumab-associated hypophysitis and conduct a systematic review of the literature. A 55-year-old woman with stage pT3aN1a (TNM stadium IIIb) melanoma presented with headache, nausea and fatigue three and a half months after starting pembrolizumab. Blood analyses revealed secondary adrenal failure, thyrotropic insufficiency and defective gonadotrophin secretion. An imaging study showed an enlarged pituitary gland with a homogeneous enhancement of the gland and pituitary stalk. Interruption of anti-PD1 therapy and administration of hormonal supplementation lead to clinical, biological and radiologic improvement after eight months. We identified 17 studies (20 patients) on single-agent pembrolizumab-associated hypophysitis. Patients were treated for melanoma (n=7; 33.3%), urogenital (n=5 ; 23.8%), lung (n=4 ; 19.0%), larynx (n=1 ; 4.8%), pharynx (n=1, 4.8%), breast (n=1, 4.8%) and colon (n=1, 4.8%) neoplasia. The time to onset of pituitary insufficiency was most frequently six months (range 1.5-39.0 months) after treatment initiation. The most prevalent hormonal defect was isolated adrenocorticotropic hormone (ACTH) deficiency. Four cases were reported with multiple central hormonal defects. In those patients, an enlarged pituitary gland was also observed. Our case has distinct features, including early disease onset after single-agent pembrolizumab initiation, panhypopituitarism and increased pituitary mass. These findings are in contrast with the majority of other cases of pembrolizumab-induced hypophysitis, as most patients present an isolated ACTH deficiency. Whether or not this is a new clinical entity warrants further investigation.
PubMed: 36127991
DOI: 10.7759/cureus.27763 -
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 -
Neurology India 2020This study was performed to examine the efficacy of endoscopic transsphenoidal surgery (ETS) for Cushing's disease at a single institute and to review past reports. (Review)
Review
BACKGROUND
This study was performed to examine the efficacy of endoscopic transsphenoidal surgery (ETS) for Cushing's disease at a single institute and to review past reports.
MATERIAL AND METHODS
We studied eight consecutive patients who underwent ETS for Cushing's disease. The radiological evaluation comprised a detailed examination of preoperative magnetic resonance images (MRIs), including inferior petrosal sinus sampling, for cases with normal renal function. Remission was evaluated at least three months after surgery and was defined by the presence of hypocortisolemia that required steroid replacement therapy or eucortisolemia with suppression to <1.8 μg/dL after 1mg of dexamethasone.
RESULTS
In all cases preoperative MRI was abnormal and included two macroadenomas (25 %). Pathological confirmation of an adenoma was possible in all patients. The mean follow-up period was 5.6 (2-7) years. Remission was confirmed in 75.0% of the cases and was higher in rate for microadenoma (100%) than for macroadenoma (50%). Postoperatively , no cerebrospinal fluid rhinorrhea occurred, but new endocrine deficits were noted in 25% of patients.
CONCLUSION
Based on this study, ETS enhanced the intrasellar identification of adenomatous tissue, which led to low remission and complication rates that were comparable with those of traditional microsurgery for Cushing's disease.
Topics: ACTH-Secreting Pituitary Adenoma; Adenoma; Adrenal Cortex Function Tests; Adult; Aged; Diabetes Insipidus; Female; Hormone Replacement Therapy; Humans; Hypopituitarism; Magnetic Resonance Imaging; Male; Middle Aged; Nasal Cavity; Natural Orifice Endoscopic Surgery; Neuroendoscopy; Petrosal Sinus Sampling; Pituitary ACTH Hypersecretion; Postoperative Complications; Sphenoid Sinus; Treatment Failure; Treatment Outcome; Tumor Burden
PubMed: 32415015
DOI: 10.4103/0028-3886.284363 -
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 -
Frontiers in Endocrinology 2022There has been limited focus on sweating failure in patients with brain tumor. We report two patients with generalized anhidrosis caused by germinoma. We also review... (Review)
Review
PURPOSE
There has been limited focus on sweating failure in patients with brain tumor. We report two patients with generalized anhidrosis caused by germinoma. We also review previous reports of generalized anhidrosis due to brain tumor.
CASE REPORTS
Patient 1 was a 12-year-old boy with repetitive heat shock-like episodes even in winter. Based on Minor's test, he was diagnosed with generalized anhidrosis. Magnetic resonance imaging (MRI) revealed the absence of high signal intensity of the posterior pituitary. He was initially diagnosed with central diabetes insipidus. However, an MRI scan performed after 3 months revealed an enlarged pituitary stalk. He was finally diagnosed with germinoma by pituitary biopsy. After chemotherapy and radiation, sweating was partially resolved. Patient 2 was a 12-year-old girl with growth hormone deficiency and generalized anhidrosis. She was diagnosed with germinoma based on MRI and pituitary biopsy findings. After chemotherapy and radiation, the sweating resolved completely.
DISCUSSION
In our literature search, we identified four patients with anhidrosis due to brain tumor, including our cases. All patients had germinoma and continued to require hormone replacement therapy after treatment of germinoma. Two patients with incomplete recovery of sweating had the involvement in the hypothalamus, whereas one patient with complete recovery showed a lack of evident hypothalamic involvement. Improvement in sweating in one patient was not described.
CONCLUSION
Germinoma can cause anhidrosis, and involvement in the hypothalamus may be relevant to incomplete recovery of sweating.
Topics: Brain Neoplasms; Child; Diabetes Insipidus, Neurogenic; Female; Germinoma; Humans; Hypohidrosis; Male; Pituitary Diseases
PubMed: 35721739
DOI: 10.3389/fendo.2022.877715 -
Endocrinology and Metabolism (Seoul,... Jun 2021Decreased heart rate variability (HRV) has been reported to be associated with cardiac autonomic dysfunction. Hypopituitarism in nonfunctioning pituitary adenoma (NFPA)...
BACKGROUND
Decreased heart rate variability (HRV) has been reported to be associated with cardiac autonomic dysfunction. Hypopituitarism in nonfunctioning pituitary adenoma (NFPA) is often linked to increased cardiovascular mortality. We therefore hypothesized that postoperative NFPA patients with hormone deficiency have an elevated risk of HRV alterations indicating cardiac autonomic dysfunction.
METHODS
A total of 22 patients with NFPA were enrolled in the study. Between 3 and 6 months after surgery, a combined pituitary function test (CPFT) was performed, and HRV was measured. The period of sleep before the CPFT was deemed the most stable period, and the hypoglycemic period that occurred during the CPFT was defined as the most unstable period. Changes in HRV parameters in stable and unstable periods were observed and compared depending on the status of hormone deficiencies.
RESULTS
In patients with adrenocorticotropic hormone (ACTH) deficiency with other pituitary hormone deficiencies, the low frequency to high frequency ratio, which represents overall autonomic function and is increased in the disease state, was higher (P=0.005). Additionally, the standard deviation of the normal-to-normal interval, which decreases in the autonomic dysfunction state, was lower (P=0.030) during the hypoglycemic period. In panhypopituitarism, the low frequency to high frequency ratio during the hypoglycemic period was increased (P=0.007).
CONCLUSION
HRV analysis during CPFT enables estimation of cardiac autonomic dysfunction in patients with NFPA who develop ACTH deficiency with other pituitary hormone deficiencies or panhypopituitarism after surgery. These patients may require a preemptive assessment of cardiovascular risk.
Topics: Adenoma; Adrenal Insufficiency; Heart Rate; Humans; Hypopituitarism; Pituitary Neoplasms
PubMed: 34107675
DOI: 10.3803/EnM.2021.978