Pituitary Disease Research Articles

MON-622 Can Calcitonin Replacement Improve Quality of Life in Hypothyroid Patients?

Background: Hypothyroidism is one of the most common endocrine hormone deficiencies and is associated with symptoms of cold intolerance, fatigue and weight gain. Many patients with a history of hypothyroidism continue to report persistent symptoms despite treatment with hormone replacement and normalization of Thyroid Stimulating Hormone (TSH) levels. Saravanan et al., reported that approximately 15% of the population studied reported fatigue or psychological symptoms on L-thyroxine even with normal TSH levels. This can prove challenging for physicians as there are few available options for adjunctive therapy for patients reporting significant symptoms that negatively impact their quality of life. Primary hypothyroidism is a common cause of hypothyroidism and is characterized by thyroid gland dysfunction due to radioactive ablation, surgical removal, or autoimmune Hashimoto’s thyroiditis. This dysfunction also impacts calcitonin production in the parafollicular C cells. Calcitonin treatment for persistent symptoms of hypothyroidism despite euthyroidism on replacement hormone has not been studied. However, the use of calcitonin has shown improvements in QoL in patients with osteoporosis and osteoarthritis (Shohrati et al, 2015; Esenyel et al, 2013). We proposed a pilot study in treating subjects with ongoing psychologic or metabolic symptoms and euthyroidism on thyroid hormone replacement with calcitonin. Methods: Subjects with symptomatic hypothyroidism were recruited for the study. Any patient between the age of 18-89, on levothyroxine treatment with normal TSH levels in the past 3 months qualified. Those who were considering pregnancy or had a history of PPI use, smoking, hypocalcemia, glucocorticoid use, congenital hypothyroidism, pituitary disease or thyroid cancer were excluded. Study participants filled out a Modified City of Hope Quality of Life (QoL) questionnaire that included questions about social concerns, physical health and physical well-being rated on a 10 point scale. Preliminary laboratory evaluation included calcitonin, Parathyroid Hormone panel, Phosphorus, TSH, Free T4 and Total T3. Participants were then instructed to use calcitonin nasal spray 200 International Units (IU) daily for 6 weeks. At the conclusion of the study, subjects were asked to fill out the same questionnaire to assess change in QoL. Results: We have undertaken a study to evaluate the effects of calcitonin treatment on subjects with hypothyroidism and suboptimal QoL despite thyroid hormone replacement and normal TSH.

SAT-280 Body Mass Index at Diagnosis and Hypothalamic-Pituitary Dysfunction during Follow-Up in Childhood Brain Tumor Survivors

Background Childhood Brain Tumor Survivors (CBTS) are at increased risk of hypothalamic-pituitary (HP) dysfunction, which may be caused by radiotherapy , be a complication of the tumor itself or due to brain injury. Being overweighted or underweighted (body mass index (BMI) more than 2 SDS or lower than -2 SDS, respectively) at brain tumor diagnosis may reflect early hypothalamic dysfunction and may be a risk factor to develop HP dysfunction during follow-up. This has, to date, not been investigated. The objective of this study was to examine whether BMI at brain tumor diagnosis is associated with the development of HP dysfunction, independent of brain tumor treatment. Methods Children surviving a brain tumor, excluding craniopharyngioma or a pituitary tumor, for minimally two years, in whom BMI at diagnosis of their brain tumor had been recorded were included from a previous cohort study (n=685 of 718). Odds-ratios (OR) for developing HP dysfunction were calculated using multivariable logistic regression, including BMI at diagnosis, gender, age at follow-up, radiotherapy, histology, location of the primary tumor, hydrocephalus and state of disease. Results Of all, 10.8% (n=74) was overweighted and 5.0% (n=34) was underweighted at diagnosis. Median follow-up time was 7.1 years (5.0-9.6). Being overweighted or underweighted at diagnosis was significantly associated with the development of HP dysfunction (anterior or posterior pituitary deficiency or central precocious puberty , OR 2.43, 95% CI 1.46-4.05) and obesity at follow-up (OR 3.75, 95% CI 2.36-5.97).Development of HP dysfunction was also significantly associated with radiotherapy (OR 11.25, 95% CI 6.76-18.72) and location of primary tumor (OR 2.24, 95% CI 1.60-3.13). In children not treated with radiotherapy (n=430), underweight and overweight at brain tumor diagnosis were also both significantly associated with HP dysfunction and precocious puberty (OR 2.91, 95% CI 1.16-7.28 and 3.00 , 95% CI 1.12-8.01, respectively). In this group, other significant risk factors for HP dysfunction included location of primary tumor (OR 8.90, 95% CI 4.11-19.24), hydrocephalus (2.27, 95% CI 1.06-4.88) and state of disease at follow-up (OR 6.38, 95% CI 1.37-29.58). Conclusions Being overweighted or underweighted at brain tumor diagnosis in childhood is associated with the development of anterior pituitary deficiencies, posterior pituitary deficiencies and CPP, independently of given treatment. This suggests that in these children hypothalamic dysfunction may already be present at brain tumor diagnosis. These findings may be used for future studies on hypothalamic dysfunction in CBTS and can be used to develop recommendations on monitoring the development of pituitary disorders in CBTS.

MON-597 Association of Serum TSH with Atrial Fibrillation in the Elderly

INTRODUCTION: Hypothyroidism and atrial fibrillation (Afib) are both common conditions in elderly patients. Levothyroxine, the most common therapy for hypothyroidism, has a narrow therapeutic window and requires monitoring to ensure that thyroid-stimulating hormone (TSH) remains within the reference range. Subclinical hyperthyroidism whether endogenous or induced by over-treatment with levothyroxine, has been associated with higher rates of Afib. Therefore, the American Thyroid Association has proposed that thyroid hormone replacement be adjusted to maintain a higher TSH in the elderly, with a proposed goal of 4-6 mcIU/mL; however, the evidence behind this target is limited. The purpose of our study was to determine whether TSH outside this target, but within the reference range for young adults, is associated with higher rates of AFib in elderly patients treated with levothyroxine. METHODS: This was a retrospective cohort study of patients aged 65 and older who were treated with levothyroxine therapy. Exclusion criteria included: pre-existing diagnosis of AFib; use of amiodarone in the prior year; recent diagnosis of thyroid cancer; history of pituitary disorders. Patients were followed from their first visit in 2010 through the end of 2017 and stratified into four groups based on median TSH value obtained in 2010. This grouping was maintained throughout the course of the study regardless of changes in TSH values in subsequent years. Primary outcome was incidence of AFib. Descriptive and comparative statistics were performed with continuous variables being assessed with one-way ANOVA or Kruskal-Wallis tests, as appropriate. Categorical variables were assessed with the chi-squared test. Rates of AFib between groups were assessed via Poisson regression with control of underlying confounders. RESULTS: Patients (n=11274) were divided into the following groups: TSH <0.5 (n=989), TSH 0.5-2 (n=3827), TSH 2.0-6.0 (n=5574), and TSH >6.0 (n=883). Age and sex distribution between TSH quartiles was fairly matched, although a trend was seen toward older age and male sex with higher TSH values. Incidence of AFib in the entire cohort was 17%. No association was found between TSH quartile and incidence or severity of AFib. Increased risk of AFib was seen with increasing age and with male sex. DISCUSSION: When compared to patients with subclinical hyperthyroidism, no significant difference was found in incidence of AFib in any of the TSH quartiles. Interestingly, patients with subclinical hyperthyroidism did not have a higher rate of AFib. A limitation of the study is that only TSH during one calendar year was used to form cohorts, which does not allow correlation with TSH changes over time. However, it is reassuring that at least in the short term, a TSH outside recommended ranges does not convey an increased risk of AFib in the elderly.

SUN-LB047 Two Unusual Cases of Pituitary Tumors Presenting with Acromegaly

Introduction: Acromegaly is a rare pituitary disorder. Only seen 1-2 times in most endocrinologist careers. In one study, 0.6% of the cases of pituitary adenomas had pituitary gigantism. Most of what is known is from isolated case reports in the adult population. Over 95% of patients with acromegaly have a growth hormone secreting pituitary adenoma. Case 1: A 16-year-old female presented for evaluation of primary amenorrhea. Initiation of puberty was at 12. She was very tall for age. Mom reported a rapid growth after the age of 9. Her height was at the 95th percentile while her target height was at the 50th percentile. On exam, she had coarse facial features and large hands and feet. Initial evaluation revealed a serum prolactin of 8.5 ng/ml, LH 0.1 IU/L (L), free testosterone 2.1 ng/dl, total testosterone 10.01 ng/dl, GH 7.03 ng/ml (H), IGF-1 at 1162 ng/ml (H) and normal TFTs. Growth hormone suppression test confirmed growth hormone excess. The lowest growth hormone level was 4.1 ng/ml at 30 minutes after a 75 gm load of glucose. An MRI of the pituitary gland revealed a 1.9 x 1.3 x 1.3 cm lobular mass within the sella and suprasellar region, with some displacement of the pituitary stalk and optic chiasm. She successfully underwent transphenoidal resection of the pituitary mass. After surgery: She presented with DI post operatively that has resolved. Normal cortisol levels. She has secondary hypothyroidism and is on levothyroxine. IGF-1 started dropping 4 days post-op (738mg/ml) and normalized 2 months later (373 ng/ml) 22 months post op: cortisol and IGF-1 are normal. No evidence of DI. She remains on levothyroxine and is on an estradiol patch. Case 2: A 15-year-old girl presented for evaluation of irregular periods. On exam, she had coarse facial features, large hands and feet, acanthosis nigricans, hirsutism and a deep voice. Height was at the 50th percentile with MPH at the 25th percentile. Initial evaluation revealed a very elevated serum prolactin of 260 ng/dL. Serum LH was low at 0.14 mIU/ml, free testosterone was elevated at 5.6 pg/mL. She had mixed hyperlipidemia. TFTs were normal. Repeat labs confirmed hyperprolactinemia and she was started on carbergoline. Further evaluation revealed an elevated IGF-I level at 1374 ng/mL (208-619), elevated IGFBP-3 of 11.2 mg/L (3.4-9.5) with a normal cortisol and serum sodium. Growth hormone suppression test confirmed excessive growth hormone production with the lowest growth hormone level being 11.7 ng/mL 120 minutes after 75 gm load of glucose. An MRI of the pituitary gland revealed a pituitary macroadenoma measuring 1.7 x 1.5 x 2 cm invading into the cavernous sinus and wrapping around the ICA. She successfully underwent trans-sphenoidal resection of the pituitary mass and is post op. Conclusion: Acromegaly is rare in children and may present with unusual symptoms of other pituitary hormone dysfunction. Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. s presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.

MON-605 Hypothyroidism in Erdheim-Chester Disease: Experience from a Tertiary Care National Referral Center

Background: Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis affecting multiple organs, including the endocrine system. While endocrine involvement in ECD is well characterized, infiltration of the hypothalamic-pituitary-thyroid axis may cause either primary or central hypothyroidism that is often underdiagnosed. The prevalence of hypothyroidism and the occurrence of isolated central hypothyroidism in ECD has not been thoroughly investigated. Methods: A prospective cohort study of biopsy-confirmed cases of ECD was conducted at the National Institutes of Health. Clinical, radiographic, and biochemical characteristics were assessed. All subjects underwent baseline evaluation with a thyroid function test, including TSH, free thyroxine (fT4) and total thyroxine (T4).Results: Sixty-one subjects with ECD (46 males, 54.3 ± 10.8 years) were evaluated. Sixteen subjects (26%) hadprimary hypothyroidism and were receiving thyroid hormone supplementation before enrollment, with a mean TSH 2.00 ±1.63 mcIU/mL (normal 0.27-4.20 mcIU/mL), fT4 1.52 ±1.51 ng/dL (normal 0.9-1.7 ng/dL), and T4 7.42 ±2.15 mcg/dL (normal 4.5-11.7 mcg/dL). The prevalence of primary hypothyroidism was higher than general population estimates (26% vs. 3.7%, P<0.05). No subject presented with myxedema coma or thyrotoxicosis. One subject (1.6%), a 61-year-old Caucasian female with ECD-related cerebellar dysfunction, retroperitoneal fibrosis, and osteosclerosis, harbored the BRAF V600E pathogenic variant and had a biochemical pattern suggestive of isolated central hypothyroidism: TSH 0.16 mcIU/mL, fT4 1.2 ng/dL and a normal baseline pituitary function test. She did not report symptoms suggestive of clinical thyroid disease and her physical examination was unremarkable. Pituitary MRI showed a small hypoenhancing lesion in the posterior aspect of the pituitary gland that is clinically insignificant. Dynamic TSH-secretion testing with a thyrotropin releasing hormone (200 μg IV synthetic TRH with serial TSH testing) demonstrated a blunted response in keeping with central hypothyroidism; baseline TSH 0.35 mcIU/mL, peak 2.90 mcIU/mL (ΔTSH <7 mcIU/mL). Conclusion: The prevalence of hypothyroidism (1 in 4) is high in subjects with ECD. Clinicians should have a low threshold to screen for hypothyroidism in this at-risk population. Central hypothyroidism is a rare manifestation of ECD and should be suspected in the setting of pituitary disease with a fT4 level below the laboratory reference range or low-normal levels in conjunction with a low, normal, or mildly elevated TSH.

SUN-420 Pituitary Apoplexy Associated With Apixaban

Background: Pituitary apoplexy (PA) is a relatively rare condition associated with sudden hemorrhagic pituitary infarction, and usually occurs in the setting of a pituitary adenoma. Patients typically present with the acute onset of headache, visual changes and pituitary hormonal deficiencies. Oral anticoagulation therapy is a known risk factor for PA and has recently been described in association with the newer anticoagulants, including both thrombin and Factor Xa inhibitors. Clinical Case: An 82 year-old woman with a history of renal cell carcinoma and recent post-operative pulmonary embolism treated with apixiban, presented with acute-onset headache, diplopia, and vomiting. Mental status remained intact. Vital signs were normal. Her physical exam was significant for a left superior temporal quandrantanopsia and was otherwise normal. Brain imaging revealed an 8 x 11 x 12 mm hyperdense mass within the sella representing hemorrhage. She had no known history of pituitary disease. The patient was admitted to the neurosurgical service for close monitoring of her neurologic and hemodynamic status. She was treated with conservative management and empiric glucocorticoids. Pituitary hormone assessment on admission was significant for inappropriately low LH of 0.5 mIU/mL (reference range 10-60) and FSH of 8.6 mIU/mL (reference range 17-114) in a postmenopausal woman. TSH was <0.03 mIU/L (reference range 0.4-5), and free T4 was elevated at 3.31 ng/dL (reference range 0.6-1.2). IGF-1 was within normal limits at 85ng/mL (reference range 31-208). Serum prolactin level was 13.7 ng/mL (normal <20). Cortisol and ACTH were measured after the patient had received empiric stress dose steroids and were thus unreliable. Of note, the patient did not exhibit signs or symptoms of adrenal insufficiency, such as hypotension or electrolyte derangements. Her headache and visual field deficit resolved with conservative treatment and she was discharged on physiologic glucocorticoid replacement therapy. Approximately two months after her initial presentation, the patient generally felt well except mild tremor and insomnia. Repeat endocrine evaluation confirmed central hypogonadism and primary hyperthyroidism. She was diagnosed with Graves’ disease and treated with methimazole. An ACTH stimulation test was normal and hydrocortisone replacement was discontinued. A repeat pituitary MRI demonstrated resolution of the hemorrhage and no evidence of a pituitary adenoma. Conclusion: Anticoagulation therapy, including the newer anticoagulants, is a risk factor for PA and is typically associated with an underlying pituitary tumor. To our knowledge, this is the first case of pituitary hemorrhage in a patient treated with apixaban without evidence of a pituitary tumor.

Harvey Cushing's Influence on Norman Dott's Work on Acromegaly: Pituitary Research, Treatment Modalities, and Research Dissemination c.1900−c.1960

To review Dr. Harvey Cushing's influence on Mr. Norman Dott's work on acromegaly and other subjects surrounding the pituitary gland such as pituitary research, treatment modalities, and research dissemination. Dott was the first Professor of Neurosurgery in Scotland during 1947 and was considered a pioneer of the understanding and treatment modalities for pituitary disorders such as acromegaly. During 1923, he published an article regarding pituitary physiology that won him the award for the Rockefeller Fellowship Trust, to travel to Boston Massachusetts, giving him the opportunity to train under Cushing's supervision for the years of 1923-1924. However, similarities can be seen between Dott's physiology project that was completed before he ever met Cushing, as well as his treatment suggestions for acromegaly, after he had finished his training under Cushing's supervision. This was a historical perspective based on literature review. We reviewed Norman Dott's archives held by University of Edinburgh Library or online sources and we compared these with the work Cushing had previously performed in a chronological fashion. Cushing's work on the pituitary gland and acromegaly can be largely found online, in biographical books, and in other secondary sources. The search included words such as "transsphenoidal surgery," "x-ray," "Harvey Cushing," "Norman Dott," "Acromegaly," "Annual Meetings," and "Pituitary physiology." We excluded any primary sources that were not published between 1900 and 1960 regarding either pituitary physiology or the treatments for acromegaly. Sir Norman Dott was the first Professor of Neurosurgery in Scotland during 1947 and is well known for his pioneering work on intracranial aneurysms. Although less well known for his contribution to pituitary pathologies, we would like to share his contribution in this regard and correlate it with Cushing's influence.

Isolated adrenocorticotropic hormone deficiency and thyroiditis associated with nivolumab therapy in a patient with advanced lung adenocarcinoma: a case report and review of the\xa0literature

IntroductionImmune checkpoint inhibitors are a promising class of anticancer drugs. The clinical benefits afforded by immune checkpoint inhibitors can be accompanied by immune-related adverse events that affect multiple organs, and endocrine immune-related adverse events include thyroiditis and hypophysitis. Hypophysitis is less frequent and has a less severe clinical presentation in patients treated with other immune checkpoint inhibitors, such as nivolumab, pembrolizumab, and atezolizumab, than in those treated with ipilimumab. However, studies have described isolated adrenocorticotropic hormone deficiency cases associated with nivolumab, pembrolizumab, and atezolizumab therapy, most of which occurred during the course of immune checkpoint inhibitor therapy. We report a rare case of patient with isolated adrenocorticotropic hormone deficiency that occurred after nivolumab therapy.Case presentationA 69-year-old Japanese woman with advanced lung adenocarcinoma developed painless thyroiditis with transient elevations of serum thyroid hormones during 3 months of cancer treatment with nivolumab and began thyroid hormone replacement therapy for subsequent primary hypothyroidism. Four months after nivolumab therapy was discontinued, she developed isolated adrenocorticotropic hormone deficiency; corticosteroid replacement therapy relieved her secondary adrenal insufficiency symptoms, such as anorexia and fatigue. Human leukocyte antigen typing revealed the presence of DRB1*04:05-DQB1*04:01-DQA1*03:03 and DRB1*09:01-DQB1*03:03-DQA1*03:02 haplotypes, which increase susceptibility to autoimmune polyendocrine syndrome associated with thyroid and pituitary disorders in the Japanese population.ConclusionsOur patient developed thyroiditis during cancer treatment with nivolumab and subsequently exhibited isolated adrenocorticotropic hormone deficiency 4 months after discontinuing the drug. Administration of nivolumab in combination with a genetic predisposition to polyglandular autoimmunity probably caused both the thyroiditis and hypophysitis, resulting in primary hypothyroidism and isolated adrenocorticotropic hormone deficiency, respectively, in our patient. The present case highlights the need for physicians to be aware that endocrine immune-related adverse events, including hypophysitis, can occur more than several months after discontinuing a drug.

Phosphodiesterases and cAMP Pathway in Pituitary Diseases.

Human phosphodiesterases (PDEs) comprise a complex superfamily of enzymes derived from 24 genes separated into 11 PDE gene families (PDEs 1–11), expressed in different tissues and cells, including heart and brain. The isoforms PDE4, PDE7, and PDE8 are specific for the second messenger cAMP, which is responsible for mediating diverse physiological actions involving different hormones and neurotransmitters. The cAMP pathway plays an important role in the development and function of endocrine tissues while phosphodiesterases are responsible for ensuring the appropriate intensity of the actions of this pathway by hydrolyzing cAMP to its inactive form 5'-AMP. PDE1, PDE2, PDE4, and PDE11A are highly expressed in the pituitary, and overexpression of some PDE4 isoforms have been demonstrated in different pituitary adenoma subtypes. This observed over-expression in pituitary adenomas, although of unknown etiology, has been considered a compensatory response to tumorigenesis. PDE4A4/5 has a unique interaction with the co-chaperone aryl hydrocarbon receptor-interacting protein (AIP), a protein implicated in somatotroph tumorigenesis via germline loss-of-function mutations. Based on the association of low PDE4A4 expression with germline AIP-mutation-positive samples, the available data suggest that lack of AIP hinders the upregulation of PDE4A4 protein seen in sporadic somatotrophinomas. This unique disturbance of the cAMP-PDE pathway observed in the majority of AIP-mutation positive adenomas could contribute to their well-described poor response to somatostatin analogs and may support a role in tumorigenesis.

Pituitary Disease in Pregnancy: Special Aspects of Diagnosis and Treatment?

The diagnosis and treatment of pituitary disease in pregnancy represents a special clinical challenge. Not least because there is very little data on the treatment of pregnant patients with pituitary disorders. A selective search of the literature was carried out with the aim of compiling evidence about the diagnosis and treatment of pituitary disease in pregnancy. The search covered the databases PubMed/MEDLINE including PubMed Central and also used the Livivo (ZB MED) search engine. Recent studies were evaluated for recommendations about the care of pregnant patients with hormone-inactive and hormone-active pituitary adenomas (prolactinoma, acromegaly and Cushingʼs disease), pituitary insufficiency, pituitary apoplexy and hypophysitis. The most well-established forms of treatment are for prolactinoma, due to the incidence of this disease and its impact on fertility. When pregnancy has been confirmed, prolactinoma treatment with dopamine agonists should be paused. Although microprolactinomas rarely increase significantly in size after the administration of dopamine agonists is discontinued, symptomatic tumor growth of macroprolactinomas can occur. In such cases, treatment with dopamine agonists can be resumed. If the primary tumor is large and the risk that it will continue to grow is high, it may be necessary to continue medical treatment from the start of pregnancy. If one of the partners has a pituitary disorder, it is often still possible for many couples to achieve their wish of having children if they receive medical support to plan and the pregnancy is carefully monitored. Given the complexity of pituitary disease, pregnant patients with pituitary disorders should be cared for and treated by a multidisciplinary team in centers specializing in the diagnosis and treatment of pituitary disease.

Feasibility of simple machine learning approaches to support detection of non-glaucomatous visual fields in future automated glaucoma clinics.

To assess the performance of feed-forward back-propagation artificial neural networks (ANNs) in detecting field defects caused by pituitary disease from among a glaucomatous population. 24-2 Humphrey Visual Field reports were gathered from 121 pituitary patients and 907 glaucomatous patients. Optical character recognition was used to extract the threshold values from PDF reports. Left and right eye visual fields were coupled for each patient in an array to create bilateral field representations. ANNs were created to detect chiasmal field defects. We also assessed the ability of ANNs to identify a single pituitary field among 907 glaucomatous distractors. Mean field thresholds across all locations were lower for pituitary patients (20.3 dB, SD = 5.2 dB) than for glaucoma patients (24.4 dB, SD = 5.0 dB) indicating a greater degree of field loss (p < 0.0001) in the pituitary group. However, substantial overlap between the groups meant that mean bilateral field loss was not a reliable indicator of aetiology. Representative ANNs showed good performance in the discrimination task with sensitivity and specificity routinely above 95%. Where a single pituitary field was hidden among 907 glaucomatous fields, it had one of the five highest indexes of suspicion on 91% of 2420 ANNs. Traditional artificial neural networks perform well at detecting chiasmal field defects among a glaucoma cohort by inspecting bilateral field representations. Increasing automation of care means we will need robust methods of automatically diagnosing and managing disease. This work shows that machine learning can perform a useful role in diagnostic oversight in highly automated glaucoma clinics, enhancing patient safety.

Neonatal Hypopituitarism: Approaches to Diagnosis and Treatment

Hypopituitarism is defined as a decreased release of hypophyseal hormones, which may be caused by disease of the pituitary gland disease or hypothalamus. The clinical findings of neonatal hypopituitarism depend on the causes and on presence and extent of hormonal deficiency. Patients may be asymptomatic or may demonstrate non-specific symptoms, but may still be at risk for development of pituitary hormone deficiency over time. Patient history, physical examination, endocrinological, radiological and genetic evaluations are all important for early diagnosis and treatment. The aim of this paper was to present a review of etiological factors, clinical findings, diagnosis and treatment approaches in neonatal hypopituitarism.

Validation of a clinicopathological score for the prediction of post-surgical evolution of pituitary adenoma: retrospective analysis on 566 patients from a tertiary care centre.

Objective and design A clinicopathological score has been proposed by Trouillas et al. to predict the evolution of pituitary adenomas. Aim of our study was to perform an independent external validation of this score and identify other potential predictor of post-surgical outcome. Methods The study sample included 566 patients with pituitary adenomas, specifically 253 FSH/LH-secreting, 147 GH-secreting, 85 PRL-secreting, 72 ACTH-secreting and 9 TSH-secreting tumours with at least 3-year post-surgical follow-up. Results In 437 cases, pituitary adenomas were non-invasive, with low (grade 1a: 378 cases) or high (grade 1b: 59 cases) proliferative activity. In 129 cases, tumours were invasive, with low (grade 2a: 87 cases) or high (grade 2b: 42 cases) proliferative activity. During the follow-up (mean: 5.8 years), 60 patients developed disease recurrence or progression, with a total of 130 patients with pituitary disease at last follow-up. Univariate analysis demonstrated a significantly higher risk of disease persistence and recurrence/progression in patients with PRL-, ACTH- and FSH/LH-secreting tumours as compared to those with somatotroph tumours, and in those with high proliferative activity (grade 1b and 2b) or >1 cm diameter. Multivariate analysis confirmed tumour type and grade to be independent predictors of disease-free-survival. Tumour invasion, Ki-67 and tumour type were the only independent prognostic factors of disease-free survival. Conclusions Our data confirmed the validity of Trouillas' score, being tumour type and grade independent predictors of disease evolution. Therefore, we recommend to always consider both features, together with tumour histological subtype, in the clinical setting to early identify patients at higher risk of recurrence.

Clinical and hormonal characteristics of patients with different types of hypophysitis: a single-center experience.

The inflammation of the pituitary gland is known as hypophysitis. It is a rare disease accounting for approximately 0.24%-0.88% of all pituitary diseases. The natural course of hypophysitis is variable. Main forms are histologically classified as lymphocytic, granulomatous, IgG4 related and xanthomatous. We aim to present our patients with hypophysitis and compare clinical, laboratory and radiological features. We retrospectively reviewed our database of 1.293 patients diagnosed with pituitary diseases between 2010 and 2017. Twelve patients with hypophysitis were identified. Demographical data, clinical features, endocrinological dysfunction, imaging findings, treatment courses and follow-up periods were evaluated. The frequency of hypophysitis was found 0.93% in all cases of the pituitary disease. Twelve patients (nine females and three males), ages between 17-61 years, were evaluated. The characteristic features of our patients tended to be predominantly female and young. Diagnosis of hypophysitis was made after pituitary biopsy in four patients, and in eight patients after pituitary operation due to adenoma. Headache (67%) and visual problems (33%) were the most frequent nonendocrine symptoms. Anterior pituitary hormone deficiencies (63.7%) and/or diabetes insipidus (17%) were seen among patients. According to histopathological forms, four had lymphocytic, seven had granulomatous and one had xanthogranulomatous types. Contrast enhancement heterogeneous and thickened pituitary stalk were the most common radiological alterations. Hypophysitis should be considered in the differential diagnosis of sellar masses. It can mimic pituitary adenomas in radiological and endocrinological aspects. The different patterns of pituitary hormone deficiencies may be seen in the course of the disease.

The effect of somatostatin analogues on Ki-67 levels in GH-secreting adenomas

PurposeSomatostatin analogues (SSAs) can slow down the growth of neuroendocrine tumors. However, the mechanism remains unclear. Recent studies on patients with acromegaly suggest that SSAs may induce apoptosis, increase autophagy, and decrease cell proliferation of pituitary adenoma. Ki-67-labeling index is a marker of cellular proliferation; therefore, decreased levels are associated with inhibition of proliferation. The aim of this study was to evaluate and compare the Ki-67-labeling index of GH-secreting pituitary adenoma tissues in patients who had undergone pituitary surgery twice due to residual or recurrent tumors and had received SSA treatment between the two surgeries. MethodThirty acromegaly patients who met the above criteria were identified and evaluated for the demographic, clinical and radiological features retrospectively. Surgical pathology samples of each operation were stained for Ki-67 and evaluated blindly by a staff pathologist specialized in pituitary diseases. ResultsAmong patients who received SSA treatment between the first and second operations, the Ki-67 index of the adenoma at the second operation was significantly lower than the Ki-67 index at the first operation. There were no differences in clinical and radiological prognostic markers between the groups with decreased and unchanged Ki-67 index. ConclusionWe concluded that SSA treatment appears to decrease Ki-67 proliferation index independent of tumor features, SSA type, dose and treatment duration. This result suggests that SSA treatment may decrease cellular proliferation, supporting the previous studies.

Metabolomics-A Promising Approach to Pituitary Adenomas.

Background: Metabolomics—the novel science that evaluates the multitude of low-molecular-weight metabolites in a biological system, provides new data on pathogenic mechanisms of diseases, including endocrine tumors. Although development of metabolomic profiling in pituitary disorders is at an early stage, it seems to be a promising approach in the near future in identifying specific disease biomarkers and understanding cellular signaling networks.Objectives: To review the metabolomic profile and the contributions of metabolomics in pituitary adenomas (PA).Methods: A systematic review was conducted via PubMed, Web of Science Core Collection and Scopus databases, summarizing studies that have described metabolomic aspects of PA.Results: Liquid chromatography tandem mass spectrometry (LC-MS/MS) and nuclear magnetic resonance (NMR) spectrometry, which are traditional techniques employed in metabolomics, suggest amino acids metabolism appears to be primarily altered in PA. N-acetyl aspartate, choline-containing compounds and creatine appear as highly effective in differentiating PA from healthy tissue. Deoxycholic and 4-pyridoxic acids, 3-methyladipate, short chain fatty acids and glucose-6-phosphate unveil metabolite biomarkers in patients with Cushing's disease. Phosphoethanolamine, N-acetyl aspartate and myo-inositol are down regulated in prolactinoma, whereas aspartate, glutamate and glutamine are up regulated. Phosphoethanolamine, taurine, alanine, choline-containing compounds, homocysteine, and methionine were up regulated in unclassified PA across studies. Intraoperative use of ultra high mass resolution matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI), which allows localization and delineation between functional PA and healthy pituitary tissue, may contribute to achievement of complete tumor resection in addition to preservation of pituitary cell lines and vasopressin secretory cells, thus avoiding postoperative diabetes insipidus.Conclusion: Implementation of ultra high performance metabolomics analysis techniques in the study of PA will significantly improve diagnosis and, potentially, the therapeutic approach, by identifying highly specific disease biomarkers in addition to novel molecular pathogenic mechanisms. Ultra high mass resolution MALDI-MSI emerges as a helpful clinical tool in the neurosurgical treatment of pituitary tumors. Therefore, metabolomics appears to be a science with a promising prospect in the sphere of PA, and a starting point in pituitary care.

The Neuroanatomy of Reproduction: Seeing Is Believing.

The brain is the central controller of reproduction and the menstrual cycle. Reproductive endocrinologists spend their days treating patients with perturbations in reproduction as a result of pituitary diseases and manipulate pituitary hormones to enhance fertility and quality of life. Microscopic neuroanatomical images will allow a better understanding of how a tumor in the pituitary might affect vision, or a mass in the brain might cause amenorrhea. Clinical correlations that are taught every day become much clearer once the anatomical relationships are explored. The objective of this pictorial tour is to elucidate anatomical and clinical relationships while showcasing the neuroanatomy of reproduction.

Eye Signs in Pituitary Disorders.

The eye is a vital sense organ and plays a vital role in conveying the underlying physical and mental state of wellbeing of an individual. A comprehensive examination of the eye is often required in patients presenting with systemic complaints. Many endocrine disorders have characteristic manifestations pertaining to the eye, the classical being the exophthalmos in thyrotoxicosis. However, a cursory eye evaluation may lead to the identification of early features that can help in the diagnosis of other endocrine disorders. This is more common in cases of pituitary mass lesions, who often present with the functional hormonal alterations rather than the visual symptoms. The definitive therapy during the late stages of the disease leads to persisting visual disabilities and affects the quality of life. Hence, the endocrinologists and ophthalmologists need to be aware of various ophthalmic features in the pituitary disorders. In this review, we highlight the eye signs in pituitary disorders, along with a brief description of uncommon ocular-pituitary syndromes.

Severe hyponatremia as a presenting sign of panhypopituitarism due to non-functioning pituitary adenoma: a case report

ABSTRACT BACKGROUND: Hyponatremia is a commonest electrolyte imbalance which is defined as \&amp;quot;serum sodium level less than 135mEq/L\&amp;quot;. It is seen especially in elderly patients presenting in emergency department of hospitals. There are wide range of differentials in hyponatremic patients but it can be the initial sign of pituitary disease specifically in old age population. Diagnosis can often be challenging because symptoms can be attributed to normal aging process and high index of clinical suspicion is necessary. CASE PRESENTATION: Here we present the case of 61-year old female presented in our facility with history of vomiting, drowsiness and fatigue for 2 days before admission. On investigating, her CBC, LFT\&amp;apos;s, RFT\&amp;apos;s and urine R/E were within normal limits. Serum electrolytes showed hyponatremia. CXR was also normal. As patient was not in fluid overload, so our differentials based on euvolumic hyponatremia included syndrome of inappropriate anti-diuretic hormone secretion(SIADH), severe hypothyroidism or glucocorticoid insufficiency. Urine osmolarity was not in range of SIADH. Serum cortisol was normal. FSH, LH, estrogen and progesterone were low although these should be high as patient was post-menopausal. Prolactin was normal. MRI brain with contrast showed supra and intrasellar mass consistent with pituitary macroadenoma. Depending on presentation and investigations, Non-functioning pituitary adenoma(NFPA) presenting with panhypopituitarism complicated by hyponatremia was the final diagnosis. CONCLUSION: Our case highlights the importance of diagnosing NFPA in elderly patients who present with hyponatemia which can often be challenging and should not be delayed as this is life-saving, hence targeted treatment should be started as soon as possible.

Pseudohyperkalemia: in vitro phenomenon or misdiagnosis. A case report

&lt;b&gt;Introduction:&lt;/b&gt; Hyperkalemia is a common electrolyte disturbance that occurs within many patients. The more often prevalence of cardiovascular or renal diseases is, the more frequent medical issue hyperkalemia will be. An increasing quantity of entities requires taking medications that affect electrolyte hemostasis. Therefore, reasons for hyperkalemia should be deeply reflected. One of them is pseudohyperkalemia. &lt;b&gt;Purpose:&lt;/b&gt; In this study diagnostics and treatment of hypokalemia were presented based on the case report of a 56-year-old man. &lt;b&gt;Case presentation:&lt;/b&gt; A 56-year-old man was admitted to the Department of Invasive Cardiology of Medical Hospital of Białystok for complaints of strong chest pain associated with palpitations, cold sweats, feelings of general weakness and anxiety. The patient had no medical history of chronic diseases and neglected to take any medications at length. The laboratory tests performed at admission showed an increased serum concentration of potassium. Through the whole hospitalization, many medications were implicated to overcome hyperkalemia (diuretics, calcium resonium, inhalation with beta2-adrenergic agonists, intravenous infusion of glucose with insulin) with no effect. Hormone test was performed, the results excluded Addison’s or pituitary disease. Differential diagnosis with arterial blood draw showed normal potassium serum concentration. &lt;b&gt;Conclusions:&lt;/b&gt; Hyperkalemia is encountered in a broad spectrum of patients. The severely elevated level of potassium could lead to life-threating conditions. Therefore, proper diagnosis making process is a matter of great importance. As clinicians, we need to base not only on laboratory but also examine the whole picture of the patient. Misdiagnosing pseudohyperkalemia might result in unnecessary medical management.