High mortality risk among women with acromegaly still persists.

Introduction: The mortality ratio in patients with acromegaly has improved over the last few decades. We aimed to determine the mortality rate and correlated factors in patients with acromegaly before and after the introduction of national protocols for treatment. In addition, we determined whether there are sex-related differences in mortality of patients with acromegaly. Methods: This observational retrospective study included 399 consecutive patients with acromegaly between January 2001-December 2022. Paraclinical data included random growth hormone (GH) and insulin-like growth factor-I (IGF1) levels, maximal pituitary tumor diameter at diagnosis, first visit, and last evaluation. Standardized mortality ratio (SMR) was calculated by dividing the observed and expected mortality rates. Cox regression analysis revealed the independent factors associated with mortality. Results: At the last visit, 31.07% (124) of patients were cured, 22.05% (88) had controlled acromegaly with medication, and 45.31% (181) had not controlled acromegaly. During follow-up (13.03 ± 5.65 years, 5216.62 person-years), 89 patients died (0.017%), resulting in an SMR of 1.18 [95% CI 0.95-1.45]. The independent factors associated with mortality were the last IGF1 level/last random GH level, absence of surgery, gonadotropin deficiency, and age. Patients with normal IGF1 after treatment showed an SMR of 0.71, whereas patients with IGF1 ratio > 1 showed SMR=1.51. Patients diagnosed between 1975-2007 and 2008-2022 had SMR = 1.25 [95% CI 0.97-1.58] and SMR = 1.09 [95% CI 0.68-1.65], respectively. In females with acromegaly, SMR was 1.63 [95% CI 1.24-2.11]; 1.76 [95% CI 1.30-2.34] in women diagnosed before 2008 and 1.33 [95% CI 0.69-2.33] in those diagnosed after 2008. Males with acromegaly had a mortality ratio similar to males from the general population (SMR = 0.99, [95% CI 0.66-1.41]). Conclusion: Patients diagnosed with acromegaly in the last 15 years had lower mortality rates than those diagnosed before 2008, due to the availability of new medications, primarily somatostatin receptor analogs and to a higher proportion of patients undergoing surgery. Females still have a high mortality ratio owing to older age at diagnosis and higher risk of metabolic complications. Therefore, efforts should be made for early diagnosis of acromegaly in women.

Pituitary and SARS CoV-2: An unremitting conundrum.

There is increased interest related to the impact of coronavirus disease 19 (COVID-19) on the endocrine system and in particular on the pituitary gland. Over the course of the severe infection with acute respiratory syndrome coronavirus 2 (SARS-CoV-2), there are both acute and delayed effects on the pituitary, related to infection and/or treatment. Hypopituitarism, pituitary apoplexy and hypophysitis have been all reported, as well as arginine vasopressin deficiency (diabetes insipidus) and syndrome of inappropriate antidiuretic hormone secretion. Furthermore, patients with acromegaly, Cushing's disease and hypopituitarism are theoretically at increased risk of complications with COVID-19 and require close monitoring. Evidence regarding pituitary dysfunction in patients with COVID-19 continues to be gathered, as the breadth and depth of knowledge also continues to rapidly evolve. This review summarizes data analysis to date on the possible effects of COVID-19 and COVID-19 vaccination on patients with normal pituitary function and patients with known pituitary pathology. Though clinical systems were significantly affected, it seems there is no overall loss of biochemical control in patients with certain pituitary pathologies.

Pituitary Apoplexy: A Retrospective Study of 36 Cases From a Single Center.

Background and objective Pituitary apoplexy (PA) is a possible life-threatening disorder due to spontaneous hemorrhage or impaired blood supply in the pituitary gland. It may present as an acute or subclinical form, and treatment options include either surgery or a conservative approach. The purpose of this study was to retrospectively analyze the clinical, imaging, and hormonal features, as well as the therapeutic outcomes, in a relatively short period of time in a series of consecutive patients with pituitary apoplexy (PA). Results Thirty-six patients were included, 50% presenting typical symptoms of PA. The presenting symptoms were headache (44.4%), visual abnormalities (44.4%), and digestive symptoms (22.2%). At diagnosis, hormonal deficiency was observed in 22 (61.1%) patients. Of the evaluated patients, 78.2% of the 23 operated cases and all unoperated cases presented tumor remnants. Vision improved in 81.8% of the operated and 100% of conservatively managed cases. Of all cases, 69.4% remained with long-term hypopituitarism. Conclusion Complex management of PA frequently leads to visual improvement but long-standing hypopituitarism.

Updating the Landscape for Functioning Gonadotroph Tumors.

Functioning gonadotroph adenomas (FGAs) are rare tumors, as the overwhelming majority of gonadotroph tumors are clinically silent. Literature is based on case reports and small case series. Gonadotroph tumors are poorly differentiated and produce and secrete hormones inefficiently, but in exceptional cases, they cause clinical syndromes due to hypersecretion of intact gonadotropins. The clinical spectrum of endocrine dysfunction includes an exaggerated response of ovaries characterized as ovarian hyperstimulation syndrome (OHSS) in premenopausal females and adolescent girls, testicular enlargement in males, and isosexual precocious puberty in children. Transsphenoidal surgery and removal of tumor reduces hormonal hypersecretion, improves endocrine dysfunction, and provides tissue for further analysis. Medical therapies (somatostatin analogues, dopamine agonists, GnRH agonists/antagonists) are partially or totally ineffective in many cases, especially with respect to antitumor effect. This review aims to update recent literature on these rare functioning tumors and highlight their therapeutic management.

Thromboembolic disease in hypercortisolism.

PURPOSE OF REVIEW: Endogenous Cushing's syndrome (CS) is associated with increased patient morbidity (hypertension, diabetes mellitus, dyslipidemia, visceral obesity, osteoporosis, cognitive alterations, and impaired quality of life). Both arterial and venous thromboembolic events (TE) due to alterations in the hemostatic system and prothrombotic state are widely reported in patients with CS, more so postoperatively. Increased mortality, if not appropriately treated, is largely due to cardiovascular events and infections. RECENT FINDINGS: Patients with CS have markedly increased risk of thromboembolic episodes compared to the general population. The prothrombotic state is mediated by increased levels of procoagulant factors, but also by an impaired fibrinolytic capacity. All contribute to TE, atherosclerosis, and subsequent cardiovascular morbidity and mortality. Some abnormalities progressively improve after CS remission, but do not fully normalize for at least 1 year or more. SUMMARY: Due to the additional thrombotic risk of surgery or any invasive procedure, anticoagulation prophylaxis should be at least considered in patients with CS and balanced with individual bleeding risk. However, a clear protocol of thromboprophylaxis is lacking and increased awareness regarding risks per se is needed. Large prospective trials will clarify, which patients with CS are at the highest risk and the optimal prevention protocol to minimize risks and maximize efficacy.

Pituitary Macroadenoma Presenting as Acromegaly and Subacute Pituitary Apoplexy: Case Report and Literature Review.

We report a case of a patient who presented to our endocrinology department for gradual onset with headache, fatigue, and weight loss over the course of one month. On physical examination, the patient showcased coarse facial features, acral enlargement, and other features suggestive of acromegaly. However, despite a clinical picture consistent with this diagnosis, serum growth hormone and insulin-like growth factor 1 were below reference range. Furthermore, secondary adrenal insufficiency, secondary hypothyroidism, and hypogonadotropic hypogonadism were discovered. Imaging revealed a pituitary macroadenoma and after a neurosurgical consult, the patient underwent transsphenoidal hypophysectomy and the suspected diagnosis of subacute pituitary adenoma apoplexy (SPAA) was confirmed via histology of resected tissue. Additionally, we review the literature for other case reports of patients with acromegaly or acromegalic features who underwent pituitary apoplexy to identify patient characteristics, presumed etiologies, and presence of biochemical cure of acromegaly following SPAA.

Management of patients with persistent or recurrent Cushing's disease after initial pituitary surgery.

INTRODUCTION: Treatment options for persistent and recurrent Cushing's disease (CD) include an individualized approach for repeat surgery, medical treatment, radiation therapy (RT), and bilateral adrenalectomy (BLA). AREAS COVERED: In this expert opinion perspective, the authors review the latest treatment(s) for persistent/recurrent CD. A PubMed search was undertaken (English articles through May 2020) and relevant articles discussed. Repeat pituitary surgery should be considered in most patients with proven hypercortisolism; there is potential for cure with low risk of major complications. Medical therapy is valuable either alone, while awaiting the effects of RT, or in preparation for BLA. Medical therapy includes steroidogenesis inhibitors, agents that act at the pituitary or glucocorticoid receptor level, and novel agents in development. Radiation therapy has been used successfully to treat CD, but hypopituitarism risk and delayed efficacy (improved with radiosurgery) are major drawbacks. Laparoscopic BLA is safe and effective in patients with severe, difficult-to-manage hypercortisolism, but long-term follow-up is required as corticotroph tumor progression can develop. EXPERT OPINION: Treatment of persistent/recurrent CD is challenging. Most patients require >1 therapy to achieve long-lasting remission. There is currently no ideal single treatment option that provides high and rapid efficacy, low adverse effects, and preserves normal pituitary-adrenal axis function.

Improvement of acromegaly control with multimodal therapy in Romania.

INTRODUCTION: In Romania, there is no acromegaly national register and there are no nationwide data available. However, some studies have reported the control rates in the country's main referral centres. Our aim was to assess the overall control rate in our tertiary referral centre. Also, we assessed the control rate in the last three years, and we compared the results with our previous reports. MATERIAL AND METHODS: We reviewed the charts of 186 patients with acromegaly assessed in our department between January 1st, 2012 and May 31st, 2019. We also compared the control rates for patients treated between April 1st, 2016 and May 31st, 2019 with historical controls (assessed between January 1st, 2012 and March 31st, 2016). RESULTS: Primary analysis: There were 19 untreated and 167 treated patients, mean age 52.46 years, surgery being the most commonly used treatment. The surgical cure rate was 14.8%, and disease control with medical treatment was 35.3%. Secondary analysis: In the first group there were 45 patients, surgery also being the most commonly used treatment. The surgical cure rate was 26.9%, and disease control was 30.4%. In the second group (historical controls) there were 42 patients, surgery being the most commonly used treatment. The surgical cure rate was 9.7%, and disease control with medical treatment was 15.4%. Random GH and IGF-1 after surgery were lower in the first group (p < 0.05) CONCLUSIONS: Changes in the Romanian protocol and highly specialised pituitary centres has improved the cure rate and disease control in patients with acromegaly.

Cystic appearance - a new feature of solid fibrous tumours in the lacrimal gland: a case report with literature review.

BACKGROUND: Solitary fibrous tumours (SFTs) rarely occur in the orbit, especially in the lacrimal area. These tumours are mostly solid. Cystic changes have been documented, but they remain very rare. Only three cases of primary orbital solitary fibrous tumours with cystic changes have been reported in the literature, but no cases have been reported to occur in the lacrimal gland. Solitary fibrous tumours generally follow a benign course and are treated definitively with surgical excision. Data from the literature suggest that the cystic nature of SFT presents a risk of recurrence and could be a harbinger of malignancy. CASE PRESENTATION: A 42-year-old woman was admitted to the endocrinology department for right unilateral exophthalmia and epiphora in the last 8 months. An ophthalmological evaluation showed exophthalmia only in the right eye (22 mm) and normal visual acuity, visual field and extraocular movements. Investigations revealed normal thyroid function. Orbital magnetic resonance imaging detected a 4 × 2,2 × 2,7 cm septate pseudocystic mass in the right lacrimal gland. Given her lacrimal gland tumour diagnosis, the patient was submitted for neurosurgical intervention with total ablation of the tumoural mass and complete right dacryoadenectomy. Although the intraoperative extemporaneous examination results were suggestive of a haemangiopericytoma, histological and immunocytochemical examination showed an extrapleural SFT. The postoperative clinical evolution was favourable, with remission of the exophthalmia. Fifteen months after surgery, no signs of recurrence were noticed. CONCLUSIONS: We report the first case of an SFT with cystic changes in the lacrimal gland. Although the presence of cavitary lesions alone does not necessarily indicate aggressive behaviour, cystic changes pose a risk of recurrence and may suggest malignant transformation over time. As a result, our case requires long-term follow-up due to recurrence and malignant potential.

SOX 2 Expression in Human Pituitary Adenomas-Correlations With Pituitary Function.

BACKGROUND/AIM: The aim of this study was to evaluate SOX2 expression in pituitary adenomas and its correlation to their secretory state and clinicopathological parameters. PATIENTS AND METHODS: Thirty-four patients were clinically evaluated and surgery was recommended for tumor removal. Histopathological diagnosis by hematoxylin eosin staining was followed by immunohistochemistry for pituitary hormones and SOX2 co-expression. RESULTS: Fourteen of the 34 cases were GH-secreting adenomas, 10 were prolactinomas and 10 non-functioning pituitary adenomas. SOX2-positive expression was detected in 47.05% of total cases: 8 GH-secreting adenomas (57.14%), 6 prolactinomas (60%) and 2 non-functioning adenomas (20%). SOX2 positivity was significantly higher amongst secreting adenomas (p=0.041). SOX2-negative tumors were significantly associated with corticotrophin deficiency (p=0.047) and gonadotrophin deficiency (p=0.041). No correlation with tumor size or extrasellar extension was detected. CONCLUSION: SOX2 is differentially expressed in pituitary adenomas and influences the secretory state or clinical behavior of pituitary adenomas.

Seasonal variation of serum vitamin D levels in Romania.

We measured serum vitamin D in 8024 Romanian subjects and found a marked seasonal variation with highest levels in September and lowest levels in March. The seasonal variation (early autumn vs. early spring) persisted in all age and sex groups. The prevalence of vitamin D deficiency was very high. PURPOSE: Romania is located in Eastern Europe, roughly between 44°N and 48°N latitude. Seasonal variation of serum vitamin D in Romanian subjects is unknown. We assessed the seasonal variation of 25-hydroxy vitamin D [25(OH)D] in Romanian population. METHODS: We retrieved from our endocrinology center database all 25(OH)D measurements between 2012 and 2016. We also evaluated age, sex, diagnosis, and date of blood sampling. The 25(OH)D was measured by two different chemiluminescence or electrochemiluminescence assays. RESULTS: There were 8024 subjects (median age 50 (37, 62); 1429 men (17.8%)) without a diagnosis of low bone mass (osteopenia or osteoporosis). The median serum 25(OH)D was 18.6 (12.7, 25.4) ng/mL. Of the subjects, 0.73, 14.4, 55.6, and 86.1% had a serum 25(OH)D level below 4, 10, 20, and 30 ng/mL, respectively. Serum 25(OH)D showed a marked seasonal variation with highest levels in September (24.1 [18.3, 30.3] ng/mL) and lowest levels in March (13.5 [9.4, 19.6] ng/mL) (p < 0.001). The seasonal variation (early autumn vs. early spring) persisted in all age and sex groups and was maximal for 21-40 years of age (26.5 (20.8, 33.1) vs. 12.9 (9.7, 17.9) ng/mL) and minimal for >65 years of age (18.6 (13.0, 27.2) vs. 12.7 (7.8, 19.7) ng/mL). Men and women showed similar amplitude of serum 25(OH)D variation. CONCLUSION: The prevalence of vitamin D deficiency is high, particularly in the elderly. The data show a strong seasonal variation of serum 25(OH)D in all subgroups of our Romanian population with highest levels in September and lowest levels in March.

Acromegaly treatment in Romania. How close are we to disease control?

INTRODUCTION: In Romania, no nationwide data for acromegaly treatment and control rate are available. Our objective was to assess the acromegaly control rate in a tertiary referral centre, which covers an important part of Romanian territory and population of patients with acromegaly. MATERIALS AND METHODS: We reviewed the records of all 164 patients (49 males and 115 females; median age 55 [47, 63.5] years) with newly or previously diagnosed acromegaly, who have been assessed at least once in our tertiary referral centre between January 1, 2012 and March 31, 2016. This sample represents 13.6% of the total expected 1200 Romanian patients with acromegaly and covers 82.9% of the counties in Romania. Control of acromegaly was defined as a random serum growth hormone (GH) < 1 ng/mL and an age-normalised serum insulin-like growth factor-I (IGF-I) value. The GH and IGF-I values used for calculation of the control rate were those at the last evaluation. The same assays for GH and IGF-I measurement were used in all patients. RESULTS: There were 147 treated and 17 untreated patients. Of the 147 patients assessed after therapy, 137 (93.2%) had pituitary surgery, 116 (78.9%) were on medical treatment at the last evaluation, and 67 (45.5%) had radiotherapy. Seventy-one (48.3%) had a random GH < 1 ng/mL, 54 (36.7%) had a normalised, age-adjusted IGF-I, and 42 (28.6%) had both normal random serum GH and IGF-I. CONCLUSIONS: In Romania, acromegaly benefits from the whole spectrum of therapeutic interventions. However, the control rate remains disappointing.

Fracture Risk Assessment in Patients With Diabetes Mellitus.

Diabetes mellitus, both type 1 and type 2 (T2DM), is associated with decreased bone strength as well as increased fracture risk. Bone mineral density is decreased in type 1 diabetes but increased in T2DM, compared with controls. This suggests alterations in bone quality are a major player in the pathogenesis of fragility fractures in patients with diabetes. The link between diabetes and bone appears to be mediated by complex pathways, including the insulin-insulin growth factors system, accumulation of advanced glycation end-products in bone collagen, microangiopathy, and increased bone marrow fat content. Bone fragility in T2DM, which is not reflected by bone mineral density and bone mass reduction, depends on deterioration of bone quality. Also, at least in T2DM, the classical diagnosis of osteoporosis by dual-energy X-ray absorptiometry and the fracture risk estimation by FRAX (fracture risk assessment tool) are only partially useful in assessing fracture risk. Trabecular bone score and trabecular bone score-adjusted FRAX offer an enhanced estimation of fracture risk in these patients. Specific risk stratification criteria are needed in the future. The development of improved methods to assess the material properties of bone to better characterize fracture risk is also a priority. Adequate glycemic control is generally associated with decreased fracture risk, with the exception of specific antidiabetics (thiazolidinediones, canagliflozin) that have been shown to have a detrimental effect. Most currently used antiosteoporotic treatments seem equally effective in diabetic patients as compared with patients without diabetes, but clinical data regarding the reduction in fracture risk specifically in patients with diabetes mellitus are lacking.

SERIAL CHANGES OF LIVER FUNCTION TESTS BEFORE AND DURING METHIMAZOLE TREATMENT IN THYROTOXIC PATIENTS.

OBJECTIVE: Overt hyperthyroidism and methimazole (MMI) treatment are frequently associated with abnormal liver function tests (LFTs). We describe the serial changes of LFTs in MMI-treated hyperthyroid patients. METHODS: We retrospectively analyzed all 77 patients presenting with newly diagnosed overt hyperthyroidism (59 Graves diseases, 11 toxic nodular goiters, 4 toxic adenomas, 3 amiodarone-induced thyrotoxicosis) between 2012 and 2014. All patients started MMI at 10 to 60 mg/day that was gradually tapered. We measured thyroid-stimulating hormone, free thyroxine, alanine aminotransferase (ALT) and aspartate aminotrasnferase (AST) at baseline and at 6 weeks, 4.5 months and 10 months after starting the MMI treatment. The concomitant medication was stable during MMI treatment. RESULTS: At baseline, 25 patients (32.5%) had abnormal LFT, of which 5 had ALT or AST levels >2× the upper limit of normal (ULN). In most patients with baseline abnormal LFT, MMI treatment resulted in a normalization of serum ALT and AST. Thirteen patients with normal baseline LFT had <2× the ULN elevations of LFT sometime during treatment. There was a case of significant hepatotoxicity. During treatment, there were no significant differences in LFT levels between patients with initially normal or abnormal LFT. In a Cox proportional hazard regression model, abnormal LFT at baseline, abnormal thyroid function at the last evaluation, and MMI dose were not predictors of abnormal LFT at the final evaluation. CONCLUSION: MMI treatment can induce insignificant LFT elevation, <2× the ULN. MMI can be safely administered in hyperthyroid patients with abnormal LFT, and normalization of increased AST and ALT levels should be anticipated. ABBREVIATIONS: ALT = alanine aminotransferase AST = aspartate aminotransferase fT4 = free thyroxine HCV = hepatitis C virus LFT = liver function test LOCF = last observation carried forward MMI = methimazole PTU = propylthiouracil TSH = thyroid-stimulating hormone ULN = upper limit of normal.

Vanishing testes syndrome-related osteoporosis and high cardio-metabolic risk in an adult male with long term untreated hypergonadotropic hypogonadism.

The male hypogonadism-related bone mass loss is often under diagnosed. Peak bone mass is severely affected if the hypogonadism occurs during puberty and is left untreated. We present an interesting; almost bizarre case of a male with non-functional testes early during childhood and undiagnosed and untreated hypogonadism until his fifth decade of life. Forty six year male is referred for goitre, complaining of back pain. Phenotype suggested intersexuality: gynoid proportions, micropenis, no palpable testes into the scrotum, no facial or truncal hair. His medical history had been unremarkable until the previous year when primary hypothyroidism was diagnosed and levothyroxine replacement was initiated. Later, he was diagnosed with ischemic heart disease, with inaugural unstable angina. On admission, the testosterone was 0.2 ng/mL (normal: 1.7-7.8 ng/mL), FSH markedly increased (56 mUI/mL), with normal adrenal axis, and TSH (under thyroxine replacement). High bone turnover markers, and blood cholesterol, and impaired glucose tolerance were diagnosed. The testes were not present in the scrotum. Abdominal computed tomography suggested bilateral masses of 1.6 cm diameter within the abdominal fat that were removed but no gonadal tissue was confirmed histopathologically. Vanishing testes syndrome was confirmed. The central DXA showed lumbar bone mineral density of 0.905 g/cm2, Z-score of -2.9SD. The spine profile X-Ray revealed multiple thoracic vertebral fractures. Alendronate therapy together with vitamin D and calcium supplements and trans-dermal testosterone were started. Four decades of hypogonadism associate increased cardiac risk, as well as decreased bone mass and high fracture risk.

Vanishing testes syndrome-related osteoporosis and high cardio-metabolic risk in an adult male with long term untreated hypergonadotropic hypogonadism

SUMMARY The male hypogonadism-related bone mass loss is often under diagnosed. Peak bone mass is severely affected if the hypogonadism occurs during puberty and is left untreated. We present an interesting; almost bizarre case of a male with non-functional testes early during childhood and undiagnosed and untreated hypogonadism until his fifth decade of life. Forty six year male is referred for goitre, complaining of back pain. Phenotype suggested intersexuality: gynoid proportions, micropenis, no palpable testes into the scrotum, no facial or truncal hair. His medical history had been unremarkable until the previous year when primary hypothyroidism was diagnosed and levothyroxine replacement was initiated. Later, he was diagnosed with ischemic heart disease, with inaugural unstable angina. On admission, the testosterone was 0.2 ng/mL (normal: 1.7-7.8 ng/mL), FSH markedly increased (56 mUI/mL), with normal adrenal axis, and TSH (under thyroxine replacement). High bone turnover markers, and blood cholesterol, and impaired glucose tolerance were diagnosed. The testes were not present in the scrotum. Abdominal computed tomography suggested bilateral masses of 1.6 cm diameter within the abdominal fat that were removed but no gonadal tissue was confirmed histopathologically. Vanishing testes syndrome was confirmed. The central DXA showed lumbar bone mineral density of 0.905 g/cm2, Z-score of -2.9SD. The spine profile X-Ray revealed multiple thoracic vertebral fractures. Alendronate therapy together with vitamin D and calcium supplements and trans-dermal testosterone were started. Four decades of hypogonadism associate increased cardiac risk, as well as decreased bone mass and high fracture risk.

Mortality in patients with non-functioning pituitary adenoma is increased: systematic analysis of 546 cases with long follow-up.

OBJECTIVE: Non-functioning pituitary adenomas (NFAs) have a prevalence of 7-22/100,000 people. A significant number of patients suffer from morbidities related to the tumor, possible recurrence(s), and treatments utilized. Our aim was to assess mortality of patients with macroNFA and predictive factors. DESIGN: Retrospective cohort study in a tertiary referral center in the UK. METHODS: A total of 546 patients operated for a macroNFA between 1963 and 2011 were studied. Mortality data were retrieved through the National Health Service Central Register and hospital records and recorded as standardized mortality ratio (SMR). Mortality was estimated for the total and various subgroups with clinical follow-up data. RESULTS: Median follow-up was 8 years (range: 1 month-48.5 years). SMR was 3.6 (95% CI, 2.9-4.5), for those operated before 1990, 4.7 (95% CI, 2.7-7.6) and for those after 1990, 3.5 (95% CI, 2.8-4.4). Main causes of death were cardio/cerebrovascular (33.7%), infections (30.1%), and malignancy (28.9%). Cox regression analysis demonstrated that only age at diagnosis remained an independent predictor of mortality (hazard ratio 1.10; 95% CI, 1.07-1.13, P<0.001), whereas sex, presentation with acute apoplexy, extent of tumor removal, radiotherapy, recurrence, untreated GH deficiency, FSH/LH deficiency, ACTH deficiency, TSH deficiency, and treatment with desmopressin had no impact. CONCLUSIONS: Despite the improvement of treatments over the last three decades, the mortality of patients with NFAs in our series remains high. Apart from age, factors related with the management/outcome of the tumor are not independent predictors, and pituitary hormone deficits managed with the currently-used substitution protocols do not adversely affect mortality.

Diabetes Insipidus after Traumatic Brain Injury.

Traumatic brain injury (TBI) is a significant cause of morbidity and mortality in many age groups. Neuroendocrine dysfunction has been recognized as a consequence of TBI and consists of both anterior and posterior pituitary insufficiency; water and electrolyte abnormalities (diabetes insipidus (DI) and the syndrome of inappropriate antidiuretic hormone secretion (SIADH)) are amongst the most challenging sequelae. The acute head trauma can lead (directly or indirectly) to dysfunction of the hypothalamic neurons secreting antidiuretic hormone (ADH) or of the posterior pituitary gland causing post-traumatic DI (PTDI). PTDI is usually diagnosed in the first days after the trauma presenting with hypotonic polyuria. Frequently, the poor general status of most patients prevents adequate fluid intake to compensate the losses and severe dehydration and hypernatremia occur. Management consists of careful monitoring of fluid balance and hormonal replacement. PTDI is associated with high mortality, particularly when presenting very early following the injury. In many surviving patients, the PTDI is transient, lasting a few days to a few weeks and in a minority of cases, it is permanent requiring management similar to that offered to patients with non-traumatic central DI.

60 YEARS OF NEUROENDOCRINOLOGY: Acromegaly.

Acromegaly (ACM) is a chronic, progressive disorder caused by the persistent hypersecretion of GH, in the vast majority of cases secreted by a pituitary adenoma. The consequent increase in IGF1 (a GH-induced liver protein) is responsible for most clinical features and for the systemic complications associated with increased mortality. The clinical diagnosis, based on symptoms related to GH excess or the presence of a pituitary mass, is often delayed many years because of the slow progression of the disease. Initial testing relies on measuring the serum IGF1 concentration. The oral glucose tolerance test with concomitant GH measurement is the gold-standard diagnostic test. The therapeutic options for ACM are surgery, medical treatment, and radiotherapy (RT). The outcome of surgery is very good for microadenomas (80-90% cure rate), but at least half of the macroadenomas (most frequently encountered in ACM patients) are not cured surgically. Somatostatin analogs are mainly indicated after surgical failure. Currently their routine use as primary therapy is not recommended. Dopamine agonists are useful in a minority of cases. Pegvisomant is indicated for patients refractory to surgery and other medical treatments. RT is employed sparingly, in cases of persistent disease activity despite other treatments, due to its long-term side effects. With complex, combined treatment, at least three-quarters of the cases are controlled according to current criteria. With proper control of the disease, the specific complications are partially improved and the mortality rate is close to that of the background population.