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Endocrine Reviews Dec 2016The genetic basis for combined pituitary hormone deficiency (CPHD) is complex, involving 30 genes in a variety of syndromic and nonsyndromic presentations. Molecular... (Review)
Review
The genetic basis for combined pituitary hormone deficiency (CPHD) is complex, involving 30 genes in a variety of syndromic and nonsyndromic presentations. Molecular diagnosis of this disorder is valuable for predicting disease progression, avoiding unnecessary surgery, and family planning. We expect that the application of high throughput sequencing will uncover additional contributing genes and eventually become a valuable tool for molecular diagnosis. For example, in the last 3 years, six new genes have been implicated in CPHD using whole-exome sequencing. In this review, we present a historical perspective on gene discovery for CPHD and predict approaches that may facilitate future gene identification projects conducted by clinicians and basic scientists. Guidelines for systematic reporting of genetic variants and assigning causality are emerging. We apply these guidelines retrospectively to reports of the genetic basis of CPHD and summarize modes of inheritance and penetrance for each of the known genes. In recent years, there have been great improvements in databases of genetic information for diverse populations. Some issues remain that make molecular diagnosis challenging in some cases. These include the inherent genetic complexity of this disorder, technical challenges like uneven coverage, differing results from variant calling and interpretation pipelines, the number of tolerated genetic alterations, and imperfect methods for predicting pathogenicity. We discuss approaches for future research in the genetics of CPHD.
Topics: Animals; Genomics; Humans; Hypopituitarism
PubMed: 27828722
DOI: 10.1210/er.2016-1101 -
Frontiers in Endocrinology 2022Hypothalamic dysfunction (HD) results in various endocrine disorders and is associated with an increased risk of metabolic comorbidities. This study aimed to analyze the...
OBJECTIVE
Hypothalamic dysfunction (HD) results in various endocrine disorders and is associated with an increased risk of metabolic comorbidities. This study aimed to analyze the clinical characteristics and metabolic abnormalities of adults with HD of various causes.
METHODS
This study retrospectively reviewed adults with HD treated at our center between August 1989 and October 2020. Metabolic characteristics of patients were compared to those of age-, sex-matched lean, and body mass index (BMI)-matched controls.
RESULTS
Temperature dysregulation (61.0%) was the most common hypothalamic physiological dysfunction. At least one anterior pituitary hormone deficiency was observed in 50 patients (84.7%), with hypogonadotropic hypogonadism being the most frequently observed. Metabolic syndrome was confirmed in 31 patients (52.5%) and was significantly more prevalent in those with panhypopituitarism or overweight/obesity. Metabolic syndrome (MetS) was significantly more common in patients with HD than in both lean and BMI-matched controls (P < 0.001 and P = 0.030, respectively). Considering the components of MetS, elevated fasting glucose levels were significantly more common in patients with HD than in BMI-matched controls (P = 0.029). Overweight/obesity and panhypopituitarism were significant risk factors for MetS in the multivariate analysis on patients with HD. Moreover, in the multivariate analysis on patients and BMI-matched control, HD was a significant risk factor of MetS (P=0.035, OR 2.919) after adjusted for age, sex and BMI.
CONCLUSIONS
Temperature dysregulation and hypogonadotropic hypogonadism are the most common physiological and endocrine dysfunctions, respectively. MetS and unfavorable metabolic profiles were prevalent in adults with HD. HD was a significant risk factor of MetS after adjusted for BMI.
Topics: Adult; Humans; Metabolic Syndrome; Overweight; Retrospective Studies; Obesity; Hypogonadism; Comorbidity
PubMed: 36313753
DOI: 10.3389/fendo.2022.973299 -
BMC Endocrine Disorders Oct 2019Pituitary metastasis is a rare condition with a poor prognosis. Very few patients with pituitary metastasis are symptomatic. It is often associated with presence of... (Review)
Review
BACKGROUND
Pituitary metastasis is a rare condition with a poor prognosis. Very few patients with pituitary metastasis are symptomatic. It is often associated with presence of co-existing metastases to other organs. Isolated pituitary metastasis as the first presentation of primary malignancy is uncommon.
CASE PRESENTATION
A 72-year-old woman presented with a 2-month history of polyuria, increasing thirst and unexplained weight loss. Esophagogastroduodenoscopy (EGD) was scheduled as part of the investigation. She was kept nil per os for 10 h prior to EGD, after which she developed alteration of consciousness. Further investigation revealed hypernatremia with sodium level of 161 mmol/L and low urine osmolality of 62 mOsm/kg. Her urine output was 300 mL per hour. Diabetes insipidus (DI) was diagnosed based on evidence of polyuria, hypernatremia, and low urine osmolality. Her urine output decreased and urine osmolality increased to 570 mOsm/kg in response to subcutaneous desmopressin acetate, confirming central DI. Pituitary magnetic resonance imaging showed a heterogeneous gadolinium enhancing lesion at the sellar and suprasellar regions, measuring 2.4 × 2.6 × 3.9 cm compressing both the hypothalamus bilaterally and the inferior aspect of optic chiasm as well as displacing the residual pituitary gland anteriorly. The posterior pituitary bright spot was absent. These MRI findings suggested pituitary macroadenoma. There were also multiple small gadolinium-enhancing lesions up to 0.7 cm in size with adjacent vasogenic brain edema at the subcortical and subpial regions of the left frontal and parietal areas, raising the concern of brain metastases. Pituitary hormonal evaluation was consistent with panhypopituitarism. Histopathological and immunohistochemical studies of the pituitary tissue revealed an adenocarcinoma, originating from the lung. Computed tomography of the chest and abdomen was subsequently performed, showing a 2.2-cm soft tissue mass at the proximal part of right bronchus. There was no evidence of distant metastases elsewhere. The final diagnosis was adenocarcinoma of the lung with pituitary metastasis manifesting as panhypopituitarism and central DI. Palliative care along with hormonal replacement therapy was offered to the patient. She died 4 months after diagnosis.
CONCLUSION
Diagnosis of pituitary metastasis is challenging, especially in patients with previously undiagnosed primary cancer. It should be considered in the elderly patients presenting with new-onset central DI with or without anterior pituitary dysfunction.
Topics: Adenocarcinoma of Lung; Aged; Diabetes Insipidus; Female; Humans; Hypopituitarism; Lung Neoplasms; Prognosis
PubMed: 31664980
DOI: 10.1186/s12902-019-0445-5 -
Surgical Neurology International 2021Lymphocytic hypophysitis (LH) is a rare condition that mostly affects women of the reproductive age. Because it is infrequently encountered, it is not often considered...
BACKGROUND
Lymphocytic hypophysitis (LH) is a rare condition that mostly affects women of the reproductive age. Because it is infrequently encountered, it is not often considered as a differential diagnosis of sellar masses. The diagnosis is made clinically with the aid of magnetic resonance imaging (MRI) and should be considered if the patient has endocrine derangements in addition to a sellar mass.
CASE DESCRIPTION
A 37-year-old female presents with a complaint of headaches and CT imaging showed a sellar mass. She was also being investigated simultaneously by the endocrine department and was diagnosed with panhypopituitarism. She proceeded to surgery for a presumed pituitary adenoma but histopathology returned as LH.
CONCLUSION
It is important to have a wide differential diagnosis when managing pituitary masses. Clinical correlation with atypical MRI findings is useful to determine the diagnosis of LH.
PubMed: 34221594
DOI: 10.25259/SNI_225_2021 -
AACE Clinical Case Reports 2022We report a case of pituitary metastasis (PM) presenting with acute anterior and posterior pituitary dysfunction following a two-decade-long oncologic course marked by...
OBJECTIVE
We report a case of pituitary metastasis (PM) presenting with acute anterior and posterior pituitary dysfunction following a two-decade-long oncologic course marked by disease progression.
CASE REPORT
An elderly woman with a history of stage IIA invasive ductal carcinoma of the breast presented with confusion. Her laboratory evaluation was significant for panhypopituitarism and central diabetes insipidus, and magnetic resonance imaging findings were suggestive of PM. She was treated with hormone replacement, resulting in the reversal of her metabolic and cognitive derangements.
DISCUSSION
PM is a rare complication of advanced malignancy. Although several malignancies may spread to the pituitary, the most common are breast cancer in women and lung cancer in men. Unlike pituitary adenomas, which predominantly involve the anterior pituitary, PM has a predilection for the posterior lobe and infundibulum due to direct access via systemic circulation. The clinical presentation of PM depends on the size of the metastatic deposit and other structures involved in the vicinity of the sella. Magnetic resonance imaging with gadolinium is the gold standard for the evaluation of sellar masses. The diagnosis of PM involves a thorough history, physical examination, biochemical evaluation of the hypothalamic-pituitary axis, and imaging studies.
CONCLUSION
Metastatic involvement of the pituitary is a rare condition seen in <2% of resected pituitary masses. The clinical presentation is heterogeneous and can include headache, visual impairment, and panhypopituitarism. Unfortunately, the presence of PM portends a poor prognosis, and the median survival rate after diagnosis is 6 to 13.6 months.
PubMed: 35097195
DOI: 10.1016/j.aace.2021.06.006 -
Pituitary Dec 2021Leptospirosis is a common tropical febrile illness which may manifest with the hepatorenal syndrome and systemic hemorrhagic manifestations. Pituitary apoplexy is a rare...
Leptospirosis is a common tropical febrile illness which may manifest with the hepatorenal syndrome and systemic hemorrhagic manifestations. Pituitary apoplexy is a rare but life-threatening condition characterized by a hemorrhage within the pituitary gland or a pituitary adenoma. Apoplexy is very rarely associated with some inducing events such as infectious diseases such as dengue hemorrhagic fever, Hantaan virus, Puumala virus have also been reported to cause pituitary apoplexy. We present the first case of pituitary apoplexy in a patient who was being treated for leptospirosis and discuss the possible mechanisms of apoplexy in the scenario presented. We also review other reports of infectious causes that may result in pituitary apoplexy.
Topics: Humans; Hypopituitarism; Leptospirosis; Male; Middle Aged; Pituitary Apoplexy; Pituitary Neoplasms
PubMed: 34021443
DOI: 10.1007/s11102-021-01156-1 -
Archives of Endocrinology and Metabolism May 2019The first description of patients with combined pituitary hormone deficiencies (CPHD) caused by PROP1 mutations was made 20 years ago. Here we updated the clinical and... (Review)
Review
The first description of patients with combined pituitary hormone deficiencies (CPHD) caused by PROP1 mutations was made 20 years ago. Here we updated the clinical and genetic characteristics of patients with PROP1 mutations and summarized the phenotypes of 14 patients with 7 different pathogenic PROP1 mutations followed at the Hospital das Clínicas of the University of Sao Paulo. In addition to deficiencies in GH, TSH, PRL and gonadotropins some patients develop late ACTH deficiency. Therefore, patients with PROP1 mutations require permanent surveillance. On magnetic resonance imaging, the pituitary stalk is normal, and the posterior lobe is in the normal position. The anterior lobe in patients with PROP1 mutations is usually hypoplastic but may be normal or even enlarged. Bi-allelic PROP1 mutations are currently the most frequently recognized genetic cause of CPHD worldwide. PROP1 defects occur more frequently among offspring of consanguineous parents and familial cases, but they also occur in sporadic cases, especially in countries in which the prevalence of PROP1 mutations is relatively high. We classified all reported PROP1 variants described to date according to the American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG-AMP) guidelines: 29 were pathogenic, 2 were likely pathogenic, and 2 were of unknown significance. An expansion of the phenotype of patients with PROP1 mutations was observed since the first description 20 years ago: variable anterior pituitary size, different pathogenic mutations, and late development of ACTH deficiency. PROP1 mutations are the most common cause of autosomal recessive CPHD with a topic posterior pituitary lobe. Arch Endocrinol Metab. 2019;63(2):167-74.
Topics: Female; Homeodomain Proteins; Humans; Hypopituitarism; Male; Mutation; Phenotype; Septo-Optic Dysplasia
PubMed: 31090814
DOI: 10.20945/2359-3997000000139 -
Journal of Medical Case Reports Nov 2019Pituitary abscess is a rare condition with nonspecific symptoms that can be delayed. Proper diagnosis needs to occur preoperatively so that the management can be set up...
BACKGROUND
Pituitary abscess is a rare condition with nonspecific symptoms that can be delayed. Proper diagnosis needs to occur preoperatively so that the management can be set up accordingly. Accurate diagnosis is challenging because many differential diagnoses can exhibit the same magnetic resonance imaging features.
CASE PRESENTATION
We report two cases of pituitary abscess. The first patient was a 66-year-old Arab woman who underwent a surgical procedure for a pituitary macroadenoma and presented 3 months later with chronic headaches and panhypopituitarism. A pituitary abscess was found on the follow-up magnetic resonance imaging. The second patient was a 64-year-old Arab man with no medical history who presented with a chiasmal syndrome with headaches and panhypopituitarism. Brain magnetic resonance imaging showed a heterogeneous pituitary mass that turned out to be a pituitary abscess intraoperatively. These two patients were treated with hormone substitution, endoscopic transsphenoidal drainage, and antibiotherapy, with excellent outcomes.
CONCLUSIONS
Pituitary abscess is a rare and serious condition. Preoperative diagnosis can be challenging because of the many existing differential diagnoses upon imaging. Magnetic resonance imaging is the mainstay technique of imaging due to its multimodal nature. These cases demonstrate the variable patterns of a pituitary abscess seen on magnetic resonance imaging and the potential difficulties in achieving an accurate diagnosis preoperatively due to many other conditions potentially exhibiting the same magnetic resonance imaging features.
Topics: Abscess; Aged; Anti-Bacterial Agents; Combined Modality Therapy; Decompression, Surgical; Drainage; Endoscopy; Female; Headache; Hormone Replacement Therapy; Humans; Magnetic Resonance Imaging; Male; Pituitary Diseases; Treatment Outcome
PubMed: 31759391
DOI: 10.1186/s13256-019-2280-8 -
Frontiers in Endocrinology 2020A prolactinoma is the most common pituitary adenoma, but it is relatively rare in childhood and adolescence. There is only limited research about the clinical spectrum,...
A prolactinoma is the most common pituitary adenoma, but it is relatively rare in childhood and adolescence. There is only limited research about the clinical spectrum, treatment, and outcomes of prolactinomas in childhood and adolescence. In this single-center cohort study, we assessed the clinical, hormonal, and neuroradiological characteristics and therapeutic outcomes of children and adolescents with prolactinomas. This retrospective cohort study included 25 patients with prolactinomas diagnosed before 19 years of age, who presented at Samsung Medical Center during a 15-year period (March 2005 to August 2019). The median age at diagnosis was 16.9 (range 10.1-18.5) years, and 80% of the patients were female. The common clinical manifestations at diagnosis were galactorrhea (10/20, 50%) and amenorrhea (9/20, 45%) among females and visual field defects (3/5, 60%) and headaches (2/5, 40%) among males. In our cohort, macroadenomas accounted for 56% of cases, and the rate of overall responsiveness to dopamine agonists (DAs) was 56% (10/18). Male gender, the prolactin (PRL) level at diagnosis, and the presence of panhypopituitarism were positively correlated with maximum tumor diameter ( = 0.443, = 0.026; = 0.710, < 0.001; and = 0.623, = 0.001, respectively). After the trans-sphenoidal approach (TSA), 53% (8/15) of patients showed normalization of the PRL level. Three patients, who underwent gamma knife surgery (GKS) owing to either resistance or intolerance to DAs or recurrence after the TSA, achieved a normal PRL level accompanied with marked tumor reduction and symptom remission. A macroprolactinoma is more prevalent than a microprolactinoma in children and adolescents than in adults. Male gender, increased PRL levels, and the presence of panhypopituitarism at diagnosis are closely related to macroprolactinomas in children and adolescents.
Topics: Adenoma; Adolescent; Adult; Amenorrhea; Bromocriptine; Child; Dopamine Agonists; Female; Follow-Up Studies; Galactorrhea; Humans; Male; Pituitary Neoplasms; Prolactin; Prolactinoma; Retrospective Studies; Treatment Outcome; Vision Disorders; Young Adult
PubMed: 32849307
DOI: 10.3389/fendo.2020.00527 -
Endocrine, Metabolic & Immune Disorders... Nov 2017The current meta-analysis aims at evaluating whether the existing clinical evidence may ascertain the effects of growth hormone (GH) replacement therapy on... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND OBJECTIVE
The current meta-analysis aims at evaluating whether the existing clinical evidence may ascertain the effects of growth hormone (GH) replacement therapy on cardiovascular risk, both in isolated GH deficiency (GHD) and in compensated panhypopituitarism including GH deficit.
METHODS
Original articles published from 1991 to 2015 were searched on Medline (Pubmed). Among an overall number of 181 potentially suitable studies, 24 fulfilled the selection criteria and were included in the analysis. Data aggregation was carried out through the calculation of the absolute risk reduction. The meta-analysis was then conducted by means of a fixed-effects model, according to the heterogeneity test (Chi-square statistic).
RESULTS
Fat-free mass (FFM) increase and fat mass (FM) reduction were found, together with a C-LDL reduction, a wide variation in glycaemia and a neutral effect on glycated haemoglobin (HbA1c) and blood pressure. These effects were valid both for isolated GHD patients and for those with compensated panhypopituitarism. The global outcome D showed a nonsignificant reduction of the overall cardiovascular risk (0.53; 95% C.I. -1.23, 2.85).
CONCLUSION
Our meta-analysis shows no signnificatly positive trend in cardiovascular risk after both short and long-term GH supplementation therapy in adult GHD patients. However, a reduction of LDL cholesterol levels has been found. No differences were found between isolated GHD participants and those affected by panhypopituitarism well compensated since at least 3 months.
Topics: Cardiovascular Diseases; Dietary Supplements; Dwarfism, Pituitary; Hormone Replacement Therapy; Human Growth Hormone; Humans; Risk Factors; Treatment Outcome
PubMed: 28925898
DOI: 10.2174/1871530317666170919121729