Visual morbidity in macroprolactinoma: A retrospective cohort study.

OBJECTIVE: The management of visual field damage in patients with macroprolactinomas is a major therapeutic challenge. We aimed to study the visual morbidity associated with macroprolactinoma and its outcomes following medical and surgical treatment. We aimed to identify predictors of visual recovery. METHODS: We retrospectively reviewed patient's data including clinical presentation, serial pituitary magnetic resonance imaging, laboratory tests, visual symptoms and neuro-ophthalmologic examination, visual field tests and optical coherence tomography tests. The main outcome was complete visual field recovery. Descriptive analyses were conducted. Predictors of visual recovery were investigated. PATIENTS: The study cohort included 150 patients with macroprolactinoma [median follow-up, 6.0 years (interquartile range (IQR) 2.9-10.6)]. RESULTS: At diagnosis, visual field defects were evident in 40 patients (26.7%). At the end of follow-up, 24 out of 39 available visual field tests (61.5%) exhibited complete recovery. Patients that achieved complete visual recovery had smaller macroadenomas at diagnosis [30.5 mm (15.0-80.0) vs. 42.0 mm (30.0-85.0), p < .01], lower baseline serum prolactin levels [1414 mcg/L (489-3586) vs. 4119 mcg/L (2715-6315), p < .01], lower rates of central hypogonadism (78.3% vs. 93.3%, p = .05) and central hypothyroidism (20.8% vs. 53.3%, p = .04), lower rates of compressive optic neuropathy (35.3% vs. 87.5%, p = .02) and a better visual acuity (better than 6/8 in both eyes, 93.7% vs. 28.6%, p < .01). CONCLUSIONS: In our cohort of 150 patients with macroprolactinoma, 40 patients (26.7%) presented with visual field defects, of which 61.5% achieved complete visual recovery with treatment. Patients that achieved complete visual recovery presented with smaller macroadenomas, lower serum prolactin levels, lower rates of central hypogonadism and central hypothyroidism, lower rates of compressive optic neuropathy and better visual acuity.

Prolactin deficiency in the context of other pituitary hormone abnormalities : Special issue: hypoprolactinemia: a neglected endocrine disorder.

Prolactin deficiency is rare. It generally occurs when pituitary disorders, such as large pituitary tumors, pituitary apoplexy, and other conditions associated with sellar mass effect lead to global failure of pituitary function and hypopituitarism. In these situiations, prolactin is commonly the last pituitary hormone affected, after growth hormone and gonadotropins are lost and thyroid-stimulating hormone and adrenocorticotopic hormone secretion is impaired. Prolactin deficiency accompanies several congenital syndromes due to mutations in PROP1 and Pit1/ POU1F and in X-linked IGSF1 deficiency syndrome, and several aqcuired conditions including Sheehan syndrome, IgG4-related hypophysitis, and immune checkpoint-inhibitor-induced hypophysitis. In women, prolactin deficiency prevents lactation following childbirth among other symptoms associated with hypopituitarism. Human prolactin is not available commercially as replacement therapy. However, recombinant human prolactin administered daily to women with hypoprolactinemia and alactogenesis was found to lead to the production of significant milk volume sufficient for lactation.

Erythropoietin-producing hepatocellular receptor B6 is highly expressed in non-functioning pituitary neuroendocrine tumors and its expression correlates with tumor size.

BACKGROUND: Erythropoietin-producing hepatocellular (EPH) receptors are the largest known family of receptor tyrosine kinases characterized in humans. These proteins are involved in tissue organization, synaptic plasticity, vascular development and the progression of various diseases including cancer. The Erythropoietin-producing hepatocellular receptor tyrosine kinase member EphB6 is a pseudokinase which has not attracted an equivalent amount of interest as its enzymatically-active counterparts. The aim of this study was to assess the expression of EphB6 in pituitary tumors. METHODS AND RESULTS: Human normal pituitaries and pituitary tumors were examined for EphB6 mRNA expression using real-time PCR and for EphB6 protein by immunohistochemistry and Western blotting. EphB6 was highly expressed in non-functioning pituitary neuroendocrine tumors (NF-PitNETs) versus the normal pituitary and GH-secreting PitNETs. EphB6 mRNA expression was correlated with tumor size. CONCLUSIONS: Our results suggest EphB6 aberrant expression in NF-PitNETs. Future studies are warranted to determine the role and significance of EphB6 in NF-PitNETs tumorigenesis.

Impact of etiology, sex, diabetes mellitus and remission status on erythrocytic profile in patients with cushing's syndrome: a large population database study.

PURPOSE: The study aimed to characterize the erythrocytic profile in patients with cushing's syndrome (CS) versus controls from the normal population according to etiology, sex, presence of diabetes mellitus (DM) and hypercortisolemia remission status. METHODS: This retrospective cohort analysis compared erythrocytic parameters between patients with CS of pituitary (CD) and adrenal (aCS) etiology and age, sex, body mass index (BMI) and socioeconomic status-matched controls in a 1:5 ratio. Laboratory values at baseline were calculated as mean values during the year preceding CS diagnosis, and over one year thereafter. RESULTS: The cohort included 397 CS patients (68.26% female; mean age 51.11 ± 16.85 years) and 1970 controls. Patients with CS had significantly higher baseline median levels of hemoglobin (Hgb) (13.70 g/dL vs. 13.12 g/dL [p < 0.0001]) and hematocrit (Hct) (41.64% vs. 39.80% [p < 0.0001]) compared to controls. These differences were observed for both CD and aCS and for both sexes. Patients who attained remission had Hgb and Hct levels comparable to controls (13.20 g/dL and 40.08% in patients with CD and aCS vs. 13.20 g/dL and 39.98% in controls). Meanwhile, those with persistent/recurrent disease maintained elevated levels. Patients with comorbid DM had similar Hgb but higher Hct (p = 0.0419), while patients without DM showed elevated erythrocytic values compared to controls (p < 0.0001). CONCLUSION: Our data illustrates that erythrocytic parameters are directly influenced by glucocorticoid excess as Hgb and Hct are higher in patients with CS, and normalize after remission. We have identified the influence of DM on erythrocytic parameters in patients with CS for the first time.

Cabergoline treatment for surgery-naïve non-functioning pituitary macroadenomas.

PURPOSE: The treatment strategy of non-functioning pituitary adenomas (NFPAs) includes surgery, radiotherapy, medical therapy, or observation without intervention. Cabergoline, a dopaminergic agonist, was suggested for the treatment of NFPA remnants after trans-sphenoidal surgery. This study investigates the efficacy of cabergoline in surgery-naive patients with NFPA. METHODS: Retrospective cohort study including surgery-naive patients with NFPA ≥ 10 mm, treated with cabergoline at a dose of ≥ 1 mg/week for at least 24 months. Patients with chiasmal damage were excluded. Data collected included symptoms, in particular visual disturbances, hormonal levels, tumor characteristics and size evaluated by MRI. Tumor growth was defined as an increase in maximal diameter of ≥ 2 mm, and shrinkage as reduction of ≥ 2 mm. RESULTS: Our cohort included 25 patients treated with cabergoline as primary therapy. Mean age was 63.3 ± 17.3 years, 56% (14/25) were males. Mean tumor size at diagnosis was 18.6 ± 6.3 mm (median 17 mm, range 10-36), and the average follow-up period with cabergoline was 4.6 ± 3.4 years. Out of the 25 tumors, five tumors (20%) decreased in size (mean decrease of 5.0 ± 3.0 mm), 12 tumors (48%) remained stable, and eight (32%) increased in size (mean growth of 5.0 ± 3.3 mm) with cabergoline treatment. During the first two years of cabergoline treatment, the median tumor size exhibited a reduction of 0.5 mm. Patients with an increase in tumor size had larger adenomas at diagnosis and a longer follow-up. Two patients (8%) underwent surgery due to tumor enlargement. CONCLUSION: Primary treatment with cabergoline is a reasonable approach for selected patients with NFPAs without visual threat.

Subacute Thyroiditis Following COVID-19 and COVID-19 Vaccination.

OBJECTIVE: COVID-19 infection and immunizations have been implicated in developing a range of thyroid diseases, including subacute thyroiditis (SAT). This study aimed to evaluate the association between COVID-19 infection and/or COVID-19 vaccination with SAT. METHODS: A population of 3 million adults insured by Clalit Health Services was evaluated from March 2020 to September 2022. Patients with a new diagnosis of SAT were identified and matched in a 1:10 ratio to a control group. Each control was assigned an index date that was identical to that of their matched case, defined as the date of SAT diagnosis. Multivariate conditional logistic regression models were used to evaluate the association between COVID-19 infection, vaccine, and thyroiditis. RESULTS: A total of 3221 patients with SAT were matched with 32 210 controls. Rates of COVID-19 vaccination (first, second, or third dose) and COVID-19 infection were evaluated prior to the date of SAT diagnosis (disease group) or index date (control group) to detect a possible association. No difference was detected between the groups in relation to vaccinations at the 30 days, 60 days, and 90 days of time points (P = .880/0.335/0.174, respectively). No difference was found between groups in relation to COVID-19 infection at these time points (P = .735/0.362/0.956, respectively). There was higher use of medications for the treatment of thyroiditis, including nonsteroidal anti-inflammatory drugs (28.6% vs 7.9%, P < .01), steroids (10.3% vs 1.8%, P < .01), and beta-blockers (18.3% vs 5.4%, P < .01). CONCLUSION: Based on this large population study, no association was found between COVID-19 infection and/or the COVID-19 vaccine and SAT.

Breast Cancer risk in patients with dopamine agonist-treated hyperprolactinemia.

PURPOSE: Given prolactin's (PRL) multifaceted roles in mammary tissue, an association between hyperprolactinemia and breast cancer has been hypothesized. Despite previous studies not identifying this risk, we aimed to investigate whether a connection exists. METHODS: This retrospective cohort study compared breast cancer incidence in patients with dopamine agonist (DA)-treated hyperprolactinemia versus matched controls in a 1:5 ratio. The primary outcome was a breast cancer diagnosis following hyperprolactinemia diagnosis. RESULTS: The cohort consisted of 1484 female patients with DA-treated hyperprolactinemia matched to 7418 female controls (mean age at diagnosis 32.70 ± 11.12 years; BMI 25.60 ± 5.84 kg/m2). Breast cancer was diagnosed in 27 patients with hyperprolactinemia (1.82%) and 97 controls (1.31%) (HR 1.40, 95% CI 0.91-2.14, p = 0.12). Patients who developed breast cancer were diagnosed with hyperprolactinemia later in life than those who did not (median age 42.63 vs. 29.79 years; p < 0.0001). Patients with PRL < 5× upper limit of normal (ULN) at diagnosis developed breast cancer at a higher rate than controls (2.25% vs. 1.33%; HR 1.73, 95% CI 1.09-2.75), but the difference was not significant in patients with PRL ≥ 5×ULN. Patients who exhibited longer times to PRL normalization had higher incidence of breast cancer (median 2.60 vs. 1.41 years in those who did not develop breast cancer; p = 0.03). CONCLUSION: Overall, patients with DA-treated hyperprolactinemia did not show an increased risk for breast cancer compared to controls. However, the risk was significantly higher among those whose PRL levels were < 5×ULN, had advanced age of diagnosis, or prolonged time to PRL normalization.

Natural history of nonfunctioning pituitary macroadenomas followed without intervention: A retrospective cohort study.

OBJECTIVE: The treatment strategy for nonfunctioning pituitary adenomas (NFPA) includes surgery, radiotherapy, medical treatment, or follow-up. Prior series of patients with NFPAs followed without intervention include small numbers of patients with macroadenomas. This study investigated the natural history of patients with macroadenomas followed without treatment. DESIGN AND PATIENTS: Retrospective cohort study included patients>18 years, with a diagnosis of NFPA ≥ 10 mm who were naïve to surgery or medical treatment and followed more than 12 months after diagnosis. Patients with chiasmal threat were excluded. Follow-up terminated if the patient underwent surgery, received cabergoline or was lost to follow-up. MEASUREMENTS: Data collected included evaluation of tumour characteristics and size by MRI, symptoms including visual disturbances, and hormonal levels. Tumour growth was defined as maximal diameter increase of ≥2 mm. RESULTS: The cohort included 49 patients (30 males, mean age 68.0 ± 12.0 years). At diagnosis, the average tumour size was 17.8 ± 5.9 mm. Mean follow-up time was 4.9 ± 4.9 years. Increase in tumour size occurred in 16 patients (33%), with an average growth of 5.1 ± 4.4 mm. Reduction in tumour size occurred in 10 patients (20%), with a mean decrease of 3.5 ± 1.3 mm. Twenty-three patients remained with stable tumours. Overall, 33 patients (67%) were observed without any intervention; 3 patients were operated and 13 were treated with cabergoline. None of the parameters including age, gender, baseline tumour size, invasiveness, visual disturbances, or hypopituitarism at diagnosis, predicted tumour growth. CONCLUSION: Observation of NFPAs without surgery or medical therapy is a reasonable approach in selected patients. In our study, no parameter predicted tumour growth.

Cushing's syndrome in women: age-related differences in etiology and clinical picture.

OBJECTIVE: To evaluate the clinical presentation, biochemical profile, and etiology of Cushing's syndrome (CS) in women stratified by age. METHODS: Retrospective study of patients with CS, treated at Rabin Medical Center from 2000 to 2020, or Maccabi Healthcare Services in Israel from 2005 to 2017. Disease etiology, presentation and biochemical profile were compared according to age at diagnosis: ≤ 45, 46-64, or ≥ 65 years. Study was approved by the Ethics Review Boards of both facilities with waiver of consent. RESULTS: The cohort included 142 women (mean age, 46.0 ± 15.1 years):81 (57.0%) with Cushing's disease (CD), and 61 (43.0%) with adrenal CS. Pituitary etiology was more common among women < 45 (70.6%), compared with patients ≥ 65 years (31.6%) (P < 0.05). Among CS patients, hypercortisolism was diagnosed in the context of screening after an adrenal incidentaloma detection in 15.0% of patients < 45 and 53.8% of ≥ 65 years (P < 0.001). Weight gain was evident in 57.4% of women < 45 (56.3% CD, 60.0% CS), and 15.8% of women ≥ 65 years (50% CD, 0% CS) (P = 0.011). Mean UFC levels were highest for women < 45 (3.8 × ULN) and lowest for ≥ 65 years (2.3 × ULN) (P < 0.001). CONCLUSION: We have shown for the first time that women with CS ≥ 65 years of age more commonly have adrenal etiology. The initial presentation of CS also differs between age groups, where women < 45 years are likely to present with weight gain, while those ≥ 65 years are frequently diagnosed incidentally, when screening for hypercortisolism in the presence of an adrenal incidentaloma.

The Association Between Hypothyroidism Treatment and Mortality in Patients Hospitalized in Surgical Wards.

Limited data are available regarding the association between pre-admission thyroid-stimulating hormone (TSH) levels and prognosis in hospitalized surgical patients treated for hypothyroidism. We retrospectively evaluated a cohort of 1,451 levothyroxine-treated patients, hospitalized to general surgery wards. The 30-day mortality risk was 2-fold higher for patients with TSH of 5.0-10.0 mIU/L (adjusted OR, 2.3; 95% CI 1.1-5.1), and 3-fold higher for those with TSH > 10.0 mIU/L (3.4; 95% CI 1.3-8.7). Long-term mortality risk was higher in patients with TSH of 5.0-10.0 and above 10.0 mIU/L (adjusted HR, 1.2; 95% CI, 1.0-1.6, and 1.7; 95% CI 1.2-2.4, respectively). We found that in levothyroxine-treated adults hospitalized to surgical wards, increased pre-admission TSH levels are associated with increased short- and long-term mortality.

Pituitary acting drugs: cabergoline and pasireotide.

First-line treatment for Cushing´s disease is transsphenoidal surgery. But in cases of persistent or recurrent disease after surgery, contraindications to surgery, severe hypercortisolism control before surgery, or for patients waiting for radiotherapy effects, medical therapy may be indicated. Pituitary-directed agents include cabergoline and pasireotide. Both drugs present similar potential for biochemical control and pasireotide has additionally been proved to reduce tumor volume. Moreover, pasireotide was evaluated in high quality studies. In respect to safety, both drugs are well tolerated and safe, but special attention should be given for cardiac valve disease and psychiatric disorder for cabergoline, and hyperglycemia for pasireotide.

Predicting hypogonadotropic hypogonadism persistence in male macroprolactinoma.

PURPOSE: To study the baseline characteristics predicting hypogonadotropic hypogonadism (HH) persistence in men with macroprolactinoma that achieved prolactin normalization. DESIGN: Retrospective cohort study. METHODS: Male patients diagnosed with macroprolactinoma and HH that received cabergoline treatment with subsequent prolactin normalization were included: men that achieved eugonadism, and men that remained hypogonadal. Patient's demographic, clinical and biochemical parameters, sellar imaging, and visual fields tests were obtained. Univariate and multivariate models were used to identify predictors of HH persistence. RESULTS: Fifty-eight male patients (age 49.2 ± 12.6 years) with a median baseline prolactin of 1154 ng/mL (IQR 478-2763 ng/mL) and adenoma (maximal) diameter of 25.9 ± 14.8 mm were followed for a median of 5.6 years (IQR 3.0-10.7). Twelve men (21%) suffered from HH persistence at the end of follow-up and 46 men achieved eugonadism. Forty-two out of 46 men (91%) accomplished eugonadism within the first year following prolactin normalization. In a multivariate logistic regression model, hypopituitarism (OR 10.1; 95% CI 1.10-101.94), visual field defect (OR 9.9; 95% CI 1.07-92.33), and low baseline testosterone levels (OR 0.5; 95% CI 0.29-0.93) were independent predictors of HH persistence. CONCLUSION: In our cohort of men with macroprolactinoma that reached prolactin normalization with cabergoline treatment, 21% had HH persistence. Pituitary hormone deficiency, visual field defects, and low baseline testosterone levels were independently associated with HH persistence. 91% of men achieved eugonadism within the first year following prolactin normalization. These findings may support informed clinical decision-making regarding the initiation of testosterone replacement in men with macroprolactinomas.

Levoketoconazole in the treatment of patients with endogenous Cushing's syndrome: a double-blind, placebo-controlled, randomized withdrawal study (LOGICS).

PURPOSE: The efficacy of levoketoconazole for endogenous Cushing's syndrome was demonstrated in a phase 3, open-label study (SONICS). This study (LOGICS) evaluated drug-specificity of cortisol normalization. METHODS: LOGICS was a phase 3, placebo-controlled, randomized-withdrawal study with open-label titration-maintenance (14-19 weeks) followed by double-blind, randomized-withdrawal (~ 8 weeks), and restoration (~ 8 weeks) phases. RESULTS: 79 patients received levoketoconazole during titration-maintenance; 39 patients on a stable dose (~ 4 weeks or more) proceeded to randomization. These and 5 SONICS completers who did not require dose titration were randomized to levoketoconazole (n = 22) or placebo (n = 22). All patients with loss of response (the primary endpoint) met the prespecified criterion of mean urinary free cortisol (mUFC) > 1.5 × upper limit of normal. During randomized-withdrawal, 21 patients withdrawn to placebo (95.5%) lost mUFC response compared with 9 patients continuing levoketoconazole (40.9%); treatment difference: - 54.5% (95% CI - 75.7, - 27.4; P = 0.0002). At the end of randomized-withdrawal, mUFC normalization was observed among 11 (50.0%) patients receiving levoketoconazole and 1 (4.5%) receiving placebo; treatment difference: 45.5% (95% CI 19.2, 67.9; P = 0.0015). Restoration of levoketoconazole reversed loss of cortisol control in most patients who had received placebo. Adverse events were reported in 89% of patients during treatment with levoketoconazole (dose-titration, randomized-withdrawal, and restoration phases combined), most commonly nausea (29%) and hypokalemia (26%). Prespecified adverse events of special interest with levoketoconazole were liver-related (10.7%), QT interval prolongation (10.7%), and adrenal insufficiency (9.5%). CONCLUSIONS: Levoketoconazole reversibly normalized urinary cortisol in patients with Cushing's syndrome. No new risks of levoketoconazole treatment were identified.

Pituitary Society Delphi Survey: An international perspective on endocrine management of patients undergoing transsphenoidal surgery for pituitary adenomas.

PURPOSE: In adults and children, transsphenoidal surgery (TSS) represents the cornerstone of management for most large or functioning sellar lesions with the exception of prolactinomas. Endocrine evaluation and management are an essential part of perioperative care. However, the details of endocrine assessment and care are not universally agreed upon. METHODS: To build consensus on the endocrine evaluation and management of adults undergoing TSS, a Delphi process was used. Thirty-five statements were developed by the Pituitary Society's Education Committee. Fifty-five pituitary endocrinologists, all members of the Pituitary Society, were invited to participate in two Delphi rounds and rate their extent of agreement with statements pertaining to perioperative endocrine evaluation and management, using a Likert-type scale. Anonymized data on the proportion of panelists' agreeing with each item were summarized. A list of items that achieved consensus, based on predefined criteria, was tabulated. RESULTS: Strong consensus (≥ 80% of panelists rating their agreement as 6-7 on a scale from 1 to 7) was achieved for 68.6% (24/35) items. If less strict agreement criteria were applied (ratings 5-7 on the Likert-type scale), consensus was achieved for 88% (31/35) items. CONCLUSIONS: We achieved consensus on a large majority of items pertaining to perioperative endocrine evaluation and management using a Delphi process. This provides an international real-world clinical perspective from an expert group and facilitates a framework for future guideline development. Some of the items for which consensus was not reached, including the assessment of immediate postoperative remission in acromegaly or Cushing's disease, represent areas where further research is needed.

Subclinical acromegaly: to treat or not to treat?

Patients with acromegaly usually present with the classical signs of acromegaly, whereas patients without the specific signs or symptoms are rarely diagnosed. This unique entity can be named "subclinical acromegaly". This was a retrospective study. Our study group consisted of 6 patients (4 females) with incidentally diagnosed acromegaly, most following head MRI for unrelated reasons and without the specific signs of acromegaly. Mean age at diagnosis was 48.8 ± 19.2 years. Baseline IGF-1 ranged between 1.3-2.0 × upper limit of normal (ULN). MRI depicted a pituitary microadenoma in 5 patients, and one patient presented with a 12 mm intra-sellar macroadenoma. Mean calculated SAGIT clinical score was 4.8. Three patients underwent trans-sphenoidal resection; two achieved hormonal remission and one improved but did not normalize IGF-1 following surgery. Four patients (including one following surgery) were given somatostatin analogs, and three normalized IGF-1. Several patients improved clinically following treatment, reporting improvement in snoring, hypertension, or weight loss, and pituitary adenoma decreased in size in 2 patients that responded to medical treatment. We report a series of 6 patients with very mild and subclinical acromegaly. It is uncertain whether all such patients will gain clinical benefit from treatment, but most experienced clinical improvement due to treatment.

High Prevalence of Acromegaly in Different Industrial Areas: A Population-based Study from Haifa and Western Galilee District in Northern Israel.

BACKGROUND: National registries for acromegaly and population-based data make an important contribution to disease understanding and management. Data concerning the epidemiology of acromegaly in Israel is scanty. OBJECTIVES: To evaluate the epidemiology of acromegaly in different industrial areas in northern Israel. METHODS: Data from adult patients diagnosed with acromegaly from 2000 to 2020, living in Haifa and the western Galilee District were collected using the electronic database and medical records from Clalit Health Services. The prevalence of acromegaly in three distinct areas and overall were reported. In addition, other epidemiological data including associated co-morbidities, pituitary tumor size, and treatment modalities were collected. RESULTS: We identified 77 patients with a confirmed diagnosis of acromegaly. The overall prevalence was 155 cases/106 inhabitants without statistically significant differences between the three areas. The mean age at diagnosis was 50 ± 1.8 years and the male to female ratio was 1.1. Macroadenoma and microadenoma were identified in 44 (57%) and 25 (33%), respectively. The frequency rate of acromegaly-associated co-morbidities such as diabetes, hypertension, carpal tunnel syndrome, and osteoporosis was similar to previously reported studies. The mean body mass index (BMI) was 29 ± 5.6 kg/m2 .Obesity, with a BMI ≥ of 30 kg/m2, was found in 29 patients (38%). The majority of patients underwent transsphenoidal surgery 67 (87%). Normalized insulin-like growth factor 1 was reported in 64 (83%). CONCLUSIONS: A high prevalence of acromegaly was found in northern Israel. The pituitary microadenoma frequency rate is the highest reported.

Long-term response to cabergoline and multi-modal treatment in men with macroprolactinoma: Does size really matter?

OBJECTIVE: To study the outcome of men with macroprolactinoma following cabergoline treatment based on tumour size. DESIGN: Retrospective cohort study. METHODS: The study included 94 men, divided into three groups according to adenoma diameter: 10-19 mm (Group A, n = 36); 20-39 mm (Group B, n = 41); or ≥40 mm (Group C, giant prolactinomas, n = 17). Patients were followed for a mean of 7.5 years with sellar magnetic resonance imaging, visual fields and hormone measurements. RESULTS: Mean baseline prolactin was 767, 2090 and 24,806 ng/ml in Groups A, B and C, respectively (p < .01). Prolactin suppression below three times the upper limit of normal (ULN) was achieved in 34 (94%; mean weekly cabergoline dose of 1.2 mg), 37 (90%; cabergoline dose, 2.1 mg) and 15 (88%; cabergoline dose, 2.8 mg) men (p = .31) in each group. After excluding patients who underwent surgery and radiotherapy, cabergoline suppressed prolactin below three times ULN in 32/35 (91%), 29/37 (78%) and 11/14 (79%) men in Groups A, B and C, respectively (p = .27). Visual deficits were observed in 5 (14%), 12 (29%) and 10 (59%) patients (p < .01); improvement was achieved in 5/5 (100%), 11/12 (92%) and 10/10 (100%) of men in Groups A, B and C. Low baseline testosterone was measured in 26 (72%), 39 (95%) and 17 (100%) patients in the three groups (p < .01). Following multi-modal treatment, hypogonadism persisted in 3 (8%), 5 (12%) and 2 (12%) men, respectively (p = .85). CONCLUSION: Macroprolactinomas in men were controlled with cabergoline in 84% of cases, independent of tumour size. Pituitary surgery and adjuvant radiotherapy further improved long-term response to 91%.

Features and long-term outcomes of patients hospitalized for diabetic ketoacidosis.

BACKGROUND: Diabetic ketoacidosis (DKA) is an acute metabolic complication characterized by hyperglycaemia, ketones in blood or urine, and acidosis. OBJECTIVE: The aim of this study was to characterize features of patients hospitalized for DKA, to identify triggers for DKA and to evaluate the long-term effects of DKA on glycaemic control, complications of diabetes, re-hospitalizations, and mortality. METHODS: Historical prospectively collected data of patients hospitalized to medical wards for DKA between 2011 and 2017. Data regarding comorbidities, mortality, triggers, and re-hospitalizations for DKA were also collected. RESULTS: The cohort consisted of 160 patients (mean age 38 ± 18 years, 43% male). One fifth of the patients (34 patients, 21%) were newly diagnosed with diabetes, and DKA was their first presentation of the disease. Among the 126 patients with pre-existing diabetes, the common identified triggers for DKA were poor compliance to treatment (22%) and infectious diseases (18%). During over 7 years of follow-up, mortality rate was 9% (15 patients), and re-hospitalization for DKA rate was 31% (50 patients). Risk factors for re-hospitalization for DKA included young age (OR = 1.02, 95% CI, 1.00-1.04), pre-existing diabetes compared to DKA as the first presentation (OR = 5.4, 95% CI, 1.7-18), and poorer glycaemic control before initial hospitalization (10.5 ± 2.5% vs. 9.4 ± 2.2%; OR = 0.8, 95% CI [0.68-0.96]) and after discharge (10.3 ± 2.4% vs. 9.0 ± 1.9%; OR = 0.73, 95% CI [0.61-0.87]). Laboratory tests during the initial hospitalization, smoking, alcohol, or comorbidities did not increase the risk for re-hospitalization for DKA. CONCLUSIONS: The risk for readmission for DKA is higher for young patients with long duration of diabetes, poor compliance of insulin treatment and poorly controlled diabetes.

The Association Between BMI and Mortality in Surgical Patients.

BACKGROUND: While obesity is commonly associated with increased morbidity and mortality, in patients with chronic diseases, it has have been associated with a better prognosis, a phenomenon known as the 'obesity paradox'. OBJECTIVE: We investigated the relationship between mortality, length of hospital stay (LOHS), and body mass index (BMI) in patients hospitalized to general surgical wards. METHODS: We extracted data of patients admitted to the hospital between January 2011 and December 2017. BMI was classified according to the following categories: underweight (< 18.5), normal weight (18.5-24.9), overweight (25-29.9), obesity (30-34.9) and severe obesity (≥ 35). Main outcomes were mortality at 30-day mortality and at the end-of-follow-up mortality), as well as LOHS. RESULTS: A total of 27,639 patients (mean age 55 ± 20 years; 48% males; 19% had diabetes) were included in the study. Median LOHS was longer in patients with diabetes vs. those without diabetes (4.0 vs 3.0 days, respectively), with longest LOHS among underweight patients. A 30-day mortality was 2% of those without (371/22,297) and 3% of those with diabetes (173/5,342). In patients with diabetes, 30-day mortality risk showed a step-wise decrease with increased BMI: 10% for underweight, 6% for normal weight, 3% for overweight, 2% for obese and only 1% for severely obese patients. In patients without diabetes, 30-day mortality was found to be 6% for underweight, 3% for normal weight and 1% across the overweight and obese categories. Mortality rate at the end-of-follow-up was 9% of patients without diabetes and 18% of those with diabetes (adjusted OR = 1.3, 95% CI, 1.2-1.5). In patients with diabetes, mortality risk showed an inverse association with respect to BMI: 52% for underweight, 29% for normal weight, 17% for overweight, 14% for obesity and 7% for severely obese patients, with similar trend in patients without diabetes. CONCLUSIONS: The results support the 'obesity paradox' in the general surgical patients as those with and without diabetes admitted to surgical wards, BMI had an inverse association with short- and long-term mortality.

Multidisciplinary management of acromegaly: A consensus.

The 13th Acromegaly Consensus Conference was held in November 2019 in Fort Lauderdale, Florida, and comprised acromegaly experts including endocrinologists and neurosurgeons who considered optimal approaches for multidisciplinary acromegaly management. Focused discussions reviewed techniques, results, and side effects of surgery, radiotherapy, and medical therapy, and how advances in technology and novel techniques have changed the way these modalities are used alone or in combination. Effects of treatment on patient outcomes were considered, along with strategies for optimizing and personalizing therapeutic approaches. Expert consensus recommendations emphasize how best to implement available treatment options as part of a multidisciplinary approach at Pituitary Tumor Centers of Excellence.