Hypopituitarism and bone disease: pathophysiology, diagnosis and treatment outcomes.

Hypopituitarism is a rare but significant endocrine disorder characterized by the inadequate secretion of one or more pituitary hormones. The intricate relationship between hypopituitarism and bone health is a topic of growing interest in the medical community. In this review the authors explore associations between hypopituitarism and bone health, with specific examination of the impact of growth hormone deficiency, central hypogonadism, central hypocortisolism, and central hypothyroidism. Pathogenesis, diagnosis, and treatment options as well as challenges posed by osteopenia, osteoporosis, and fractures in hypopituitarism are discussed.

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.

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.

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.

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.

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.

Medical Treatment Landscape for Active Acromegaly in A Pituitary Center in Israel.

OBJECTIVE: To evaluate current real-life experience with medical treatment for active acromegaly in a large cohort. METHODS: Data on demographic parameters, blood tests, imaging studies, and treatments were extracted from the medical records. RESULTS: The cohort included 87 patients (43 male) with active acromegaly. The mean age at diagnosis was 40.2±11.4 years, and the mean duration of follow-up was 7.9±5.8 years. Seventy patients presented with a macroadenoma. Mean baseline insulin growth factor 1 (IGF-1) (n = 67) was 3.2±1.9 × upper limit of normal (ULN). Surgery and radiotherapy were performed in 75 and 10 patients, respectively. Currently, 38 subjects receive somatostatin analogues, pegvisomant as a monotherapy is given to 8 patients, pasireotide is given to 17 patients, cabegoline to 4 patients, estrogen to 2 females, and SSAs combined with pegvisomant to 10 patients. Eight patients are not being actively treated, including 4 following radiotherapy. Good biochemical control (IGF-1 <1.3 × ULN) was achieved in 76 patients (87%), and 11 patients (13%) are currently uncontrolled (IGF-1 >1.3 × ULN). Seventy-eight percent of controlled patients are being given 1 medication; 11% are on combination therapy; 4 patients are well controlled after radiotherapy and 2 are partially controlled without any treatment. The main adverse effects of treatment were diabetes mellitus in 7 patients (on pasireotide) and symptomatic cholelithiasis in 5 patients. CONCLUSION: Active acromegaly can be controlled medically in most patients, with a low rate of adverse effects. This study displays the characteristic variety of treatment options available for active acromegaly.

Low serum albumin levels predict short- and long-term mortality risk in patients hospitalised to general surgery wards.

BACKGROUND: Previous studies have reported conflicting results on the association between hypoalbuminaemia and morbidity and mortality in hospitalised patients. AIMS: To investigate the association of albumin levels on admission and change in levels during hospitalisation of patients in general surgery wards with hospitalisation outcomes. METHODS: Historical prospective data of patients hospitalised between January 2011 and December 2017. Albumin levels were classified as follows: marked hypoalbuminaemia (<2.5 mg/dL), mild hypoalbuminaemia (2.5-3.5 mg/dL), normal albumin (3.5-4.5 mg/dL) and hyperalbuminaemia (>4.5 mg/dL). Main outcomes were length of hospitalisation, 30-days and long-term mortality. RESULTS: The cohort included 17 930 patients (mean age 58 ± 20 years, 49% male). Most had normal albumin levels on admission (n = 11 087, 62%), 16% had mild hypoalbuminaemia (n = 2824) and 3% had marked hypoalbuminaemia (n = 529). Hyperalbuminaemia on admission was evident in 20% of the patients (n = 3490). Follow-up time was up to 7.2 years (median ± SD = 3 ± 2 years). Compared to 30-day mortality with normal albumin on admission (2%), mortality was higher with mild (9%) and marked hypoalbuminaemia (22%) and lower with hyperalbuminaemia (0.4%). The mortality rate at the end of follow up was 14% with normal albumin levels, and 35% and 58% with mild and marked hypoalbuminaemia respectively. Patients with hyperalbuminaemia on admission and before discharge had the best short- and long-term survival. This pattern was similar when analysed separately in different age groups. In patients with hypoalbuminaemia on admission, normalisation of albumin levels before discharge was associated with lower short- (12% vs 1%) and long-term mortality risk (42% vs 17%). CONCLUSIONS: Low albumin levels on admission to general surgery wards are associated with increased short- and long-term mortality. Normalisation of albumin levels before discharge was associated with lower mortality, compared to hypoalbuminaemia before discharge.

ENDOCRINE COMPLICATIONS IN PATIENTS WITH GVHD.

Objective: Graft-versus-host disease (GVHD) is an immune phenomenon that occurs in 30 to 70% of patients after allogeneic hematopoietic stem cell transplantation (HST). Chronic GVHD is a state of immune dysregulation wherein, depending on the severity and organ involved, patients may require prolonged treatment with additional or higher corticosteroids and other immunosuppressive agents. The objective of this study was to review the endocrine manifestations following HST that can arise as a consequence of the primary disease or its treatment, including chemotherapeutic agents, corticosteroids, radiation, or GVHD. Methods: We performed a narrative review of GVHD after HST. An English-language search for relevant studies was conducted on PubMed from inception to August 1, 2018, using the following search terms: "endocrine complications," "bone marrow transplantation," "graft-versus-host disease," and "GVHD." The reference lists of relevant studies were also reviewed. Results: Chronic GVHD may be associated with considerable pediatric growth impairment and may also contribute to thyroid gland dysfunction and thyroid cancer. These patients may also be at increased risk for low bone mineral density, reduced fertility, metabolic syndrome, and suppression of the pituitary-adrenal axis with adrenal insufficiency. Conclusion: This review indicates the importance of monitoring, diagnosing, and properly treating the endocrine complications in this population. More studies are needed to investigate the independent impact of GVHD on the endocrine system and treatment for complications. Abbreviations: BMD = bone mineral density; GH = growth hormone; GVHD = graft-versus-host disease; HST = hematopoietic stem cell transplantation; IGF-1 = insulin-like growth factor 1.

DISEASE PRESENTATION AND REMISSION RATE IN GRAVES DISEASE TREATED WITH ANTITHYROID DRUGS: IS GENDER REALLY A FACTOR?

OBJECTIVE: Male gender is considered an adverse prognostic factor for remission of Graves disease treatment with antithyroid drugs (ATDs), although published data are conflicting. This often results in early consideration of radioiodine treatment and surgery for men. Our objective was to compare disease presentation and outcome in men versus women treated with ATDs. METHODS: Retrospective study of 235 patients (64 men, 171 women) with Graves disease who were evaluated for features at presentation and outcome at the end of follow-up between 2010 and 2015. RESULTS: Disease presentation was similar in men and women for age at diagnosis (41.4 ± 14 years vs. 40 ± 15 years), duration of follow-up (6.6 ± 7 years vs. 7.7 ± 6 years), rates of comorbid autoimmune diseases, and rate of Graves ophthalmopathy. Smoking was more prevalent in males (31% vs. 15%; P = .009). Free thyroxine and triiodothyronine levels were comparable. ATDs were first-line treatment in all males and in 168 of 171 females, for a median duration of 24 and 20 months, respectively ( P = .55). Remission rates were 47% in men and 58% in women ( P = .14). Males had fewer adverse events (9% vs. 18%) and treatment discontinuation (5% vs. 16%). Disease recurrence was comparable (14% vs. 20%; P = .32), as was requirement for second-line treatment, either radioiodine therapy or thyroidectomy. CONCLUSION: Graves disease presentation is similar in men and women. Men treated with ATDs have high remission rates and similar recurrence rates compared to women, with fewer adverse events and less discontinuation of treatment. ATDs are an attractive first-line treatment for both genders. ABBREVIATIONS: ATA = American Thyroid Association; ATD = antithyroid drug; GO = Graves ophthalmopathy; T3 = triiodothyronine; T4 = thyroxine; TSH = thyroid-stimulating hormone.

Body mass index and mortality in patients with and without diabetes mellitus.

OBJECTIVE: Investigate the association between body mass index (BMI), length of stay (LOS), and mortality in hospitalized patients with and without diabetes mellitus (DM). METHODS: Historical prospectively collected data of adult patients hospitalized between 2011 and 2013. Body mass index was calculated according to measurement or self-report on admission and classified as follows: underweight (<18.5), normal weight (18.5-24.9), overweight (25-29.9), obese (30-34.9), and severely obese (≥35). The main outcomes were LOS, in-hospital, and end-of-follow-up mortality. RESULTS: Cohort included 24 233 patients (53% male; mean age ± SD, 65 ± 18), including 7397 patients with DM (31%). Among patients with normal BMI, LOS was shorter compared with underweight patients, but it was longer compared with overweight and obese patients. Following multivariate adjustment, this difference remained significant only for patients with DM. There was a significant interaction between DM status and BMI group, in the models for in-hospital and end-of-follow-up mortality. Compared with normal BMI, in-hospital mortality risk was increased by 80% and 100% for the underweight with and without DM, respectively. For patients with and without DM, in-hospital mortality risk was 30% to 40% lower among overweight and obese patients, and there was no difference between severely obese and normal weight patients. At the end-of-follow-up, mortality risk was 1.6-fold and 1.7-fold higher among underweight patients with and without DM, respectively. For overweight, obese, and severely obese patients, mortality risk was decreased by 30% to 40% in those with DM and by 20% to 30% in those without DM. CONCLUSIONS: In hospitalized patients with and without DM, there was an inverse association between BMI and mortality.

Outcomes of hyperglycemia in patients with and without diabetes hospitalized for infectious diseases.

OBJECTIVE: To examine the prognostic implications of diabetes mellitus (DM) and the importance of glycemic control during hospitalization for infectious diseases. METHODS: Historical prospectively collected data of patients hospitalized between 2011 and 2013. Infection-related hospitalizations were classified according to site of infection. Median follow-up was 4.5 years. Outcome measures included in-hospital and end-of-follow-up mortality. RESULTS: The cohort included 8051 patients (50% female, mean age ± SD, 68 ± 20 years) with a primary diagnosis of an infectious disease. Of these, 2363 patients (29%) had type 2 DM. The most common infectious sites included respiratory tract (n = 3285), genitourinary tract (n = 1804), skin and soft tissue (n = 934) and gastrointestinal tract (n = 571). There was no difference in admission rates of patients with and without DM according to the site of infection, except for skin and soft tissue infection which were more common among patients with DM (16% vs 10%). In-hospital mortality risk was greater in patients with DM (aOR = 1.3, 95% CI = 1.1-1.7). In the entire cohort, adjusted mortality risk (aHR, 95% CI) at the end-of-follow-up was greater among patients with DM (1.2, 1.1-1.4), with increased mortality risk following hospitalization for respiratory (1.1, 1.0-1.4) and skin and soft tissue infections (1.7, 1.3-2.3). In-hospital and end-of-follow-up mortality risk were highest among patients with and without DM with median glucose >180 mg/dL during hospitalization. CONCLUSIONS: In patients hospitalized for infectious diseases, DM is associated with increased long-term mortality risk, specifically following hospitalization for respiratory and skin and soft tissue infections. Poor glycemic control during hospitalization is associated with increased long-term mortality.

IGF-1 levels may increase paradoxically with dopamine agonist treatment for prolactinomas.

OBJECTIVE: Hyperprolactinemia is common in acromegaly and in these patients, insulin-like growth factor (IGF)-1 level may decrease with dopamine agonist. We report a series of patients with prolactinoma and a paradoxical increase of IGF-1 levels during cabergoline treatment. METHODS: Clinical characteristics and response to treatment of patients with prolactinomas, in whom normal or slightly elevated baseline IGF-1 levels increased with cabergoline. RESULTS: The cohort consisted of ten prolactinoma patients (nine males, mean age 48 ± 14 years). Mean adenoma size was 23.8 ± 16.2 mm, with cavernous sinus invasion in eight. In five patients baseline IGF-1 levels were normal and in four levels were 1.2-1.5-fold the upper limit of the normal (ULN). One patient had IGF-1 measured shortly after initiating cabergoline and it was 1.4 × ULN. During cabergoline treatment (dose range 0.5-2 mg/week) PRL normalization was achieved in all and tumor shrinkage occurred in seven patients. The mean IGF-1 increase on cabergoline was 1.7 ± 0.4 × ULN. Cabergoline dose reduction or interruption was attempted in five patients and resulted in decreased IGF-1 levels in all, including normalization in two patients. Three patients were eventually diagnosed with acromegaly, one was referred for pituitary surgery followed by complete remission, another patient was switched to somatostatin analogue, and the third was treated by combination of somatostatin analogues with pegvisomant, with reduction of IGF-1 in all these patients. CONCLUSION: IGF-1 levels may increase to clinically significant levels during cabergoline treatment for PRL-adenoma. We suggest IGF-1 monitoring in all patients treated with dopamine agonists and not only in those presenting symptoms of acromegaly.

LONG-TERM OUTCOMES AND PROGNOSTIC FACTORS IN PATIENTS WITH DIFFERENTIATED THYROID CANCER AND DISTANT METASTASES.

OBJECTIVE: Distant metastatic spread is the most frequent cause of thyroid cancer-related death. The objective of this study was to evaluate overall and disease-related survival of patients with differentiated thyroid cancer (DTC) and distant metastases (DM) attending a single medical center and to investigate variables predictive of better long-term outcomes. METHODS: The Rabin Medical Center Thyroid Cancer Registry was searched for patients with DM from DTC. RESULTS: The cohort included 138 patients (58.7% female) diagnosed at age 54.7 ± 19.5 years. Mean primary tumor size was 33.9 ± 26 mm. Most patients (57.7%) were stage T3/T4; 48.7% had extrathyroidal extension; 53.5% had lymph node metastases. Histopathology yielded papillary and follicular thyroid carcinoma in 66.7% and 13.8%, respectively, and intermediate/poorly differentiated carcinoma in 19.6%. All but 2 patients underwent total thyroidectomy, and 133/138 (96.4%) received radioactive iodine (RAI) therapy. DM were synchronous in 55.1%. The mean follow-up was 8.2 years from detection of metastases. The common sites of metastases were the lungs (85.6% of patients), bones (39.9%), brain (5.8%) and liver (3.6%). At last follow-up, resolution was documented in 24.6% of patients, improvement/stable disease in 31.6%, and structurally progressive disease in 43.4%. By the end of the study, 40.6% of patients died, 23.2% of DTC. Improved overall survival and disease progression were associated with younger age, lung-only DM, and metastatic RAI avidity. CONCLUSION: Patients with DTC and DM treated by standard-of-care approaches frequently achieve favorable long-term outcomes. Novel therapies might be necessary in only a minority of these patients, and the reported prognostic factors can aid in their identification. ABBREVIATIONS: CR = complete response; DM = distant metastases; DTC = differentiated thyroid cancer; ETE = extra-thyroidal extension; M0 = detected during follow-up; M1 = detected at diagnosis; MSKCC = Memorial Sloan Kettering Cancer Center; NED = no evidence of disease; OS = overall survival; PFS = progression free survival; PTC = papillary thyroid cancer; RAI = radioactive iodine; Tg = thyroglobulin.

High blood pressure variability predicts 30-day mortality but not 1-year mortality in hospitalized elderly patients.

BACKGROUND: The association of blood pressure (BP) variability (BPV) in hospitalized patients, which represents day-to-day variability, with mortality has been extensively reported in patients with stroke, but poorly defined for other medical conditions. AIM AND METHOD: To assess the association of day-to-day blood pressure variability in hospitalized patients, 10 BP measurements were obtained in individuals ≥75 years old hospitalized in a geriatric ward. Day-to-day BPV, measured 3 times a day, was calculated in each patient as the coefficient of variation of systolic BP. Patients were stratified by quartiles of coefficient of variation of systolic BP, and 30-day and 1-year mortality data were compared between those in the highest versus the lowest (reference) group. RESULTS: Overall, 469 patients were included in the final analysis. Mean coefficient of variation of systolic BP was 12.1%. 30-day mortality and 1-year mortality occurred in 29/469 (6.2%) and 95/469 (20.2%) individuals respectively. Patients in the highest quartile of BPV were at a significantly higher risk for 30-day mortality (HR =4.12, CI 1.12-15.10) but not for 1-year mortality compared with the lowest BPV quartile (HR =1.61, CI 0.81-3.23). CONCLUSIONS: Day-to-day BPV is associated with 30-day, but not with 1-year mortality in hospitalized elderly patients.