Somapacitan-induced reversible lipoatrophy in an adult woman with hypopituitarism.

BACKGROUND: Lipoatrophy is rare adverse event (AE) in daily recombinant human growth hormone (rhGH). Data on lipoatrophy in newly developed long-acting GH (LAGH) are scarce. We report the first case of lipoatrophy in adult patient treated with LAGH somapacitan. CASE PRESENTATION: A 38-year-old woman with congenital panhypopituitarism was transitioned from daily rhGH 0.4 mg QD to somapacitan dose 4 mg QW due to non-adherence to daily rhGH. Despite adequate education and regular changing of injection sites, the patient reported reduced subcutaneous tissue at all four injection sites, after the 4th application of somapacitan. Somapacitan was discontinued at patient preference and lipoatrophy completely reversed after 3 months. CONCLUSIONS: Lipoatrophy caused by somapacitan was completely reversible. We speculate that high initial dose and volume of somapacitan caused delayed diffusion and a direct local lipolytic effect in our patient. Although, titration of somapacitan was initiated as previously reported in REAL2 study protocol, recent clinical guidelines advise more gradual increase of somapacitan dose also in women on oral estogens that are switched from daily rhGH. Importantly, our case and the two previously described cases in children in the REAL 3 study showed that lipoatrophy caused by somapacitan was transient and completely reversible, and that discontinuation of the drug is not always mandatory.

Sex- and Gender-Related Differences in Obesity: From Pathophysiological Mechanisms to Clinical Implications.

Obesity, primarily characterized by excessive fat accumulation, is a multifactorial chronic disease with an increasing global prevalence. Despite the well-documented epidemiology and significant advances in understanding its pathophysiology and clinical implications, the impact of sex is typically overlooked in obesity research. Worldwide, women have a higher likelihood to become obese compared to men. Although women are offered weight loss interventions more often and at earlier stages than men, they are more vulnerable to psychopathology. Men, on the other hand, are less likely to pursue weight loss intervention and are more susceptible to the metabolic implications of obesity. In this narrative review, we comprehensively explored sex- and gender-specific differences in the development of obesity, focusing on a variety of biological variables, such as body composition, fat distribution and energy partitioning, the impact of sex steroid hormones and gut microbiota diversity, chromosomal and genetic variables, and behavioural and sociocultural variables influencing obesity development in men and women. Sex differences in obesity-related comorbidities and varying effectiveness of different weight loss interventions are also extensively discussed.

Traumatic Brain Injury during the SARS-CoV-2 Pandemics in Slovenia: A Single Center Study.

(1) Background: The SARS-CoV-2 pandemic had a significant impact on the management of traumatic brain injury (TBI). We aimed to compare the clinical characteristics and outcomes of TBI patients before and during the SARS-CoV-2 pandemic.; (2) Methods: We analyzed depicted data from existing medical records on sex, age, mechanism of injury, clinical performance at admission and discharge, neuroimaging, laboratory values at admission, mortality, duration of hospitalization, and referrals after discharge from the traumatology department for all adult patients during the SARS-CoV-2 pandemic and a year before. Variables were compared using the Chi-square or t-test between both groups.; (3) Results: Most patients had mild (n = 477), followed by moderate (11) and severe (11) TBI. Mild TBI was less frequent during the SARS-CoV-2 period (n = 174 vs. n = 303). The incidence of high falls increased during the SARS-CoV-2 period (14.5% vs. 24.7%; p < 0.05) in the group with mild TBI. Patients had similar mean Glasgow Coma Scales (GCS), Glasgow Outcome Scales-Extended (GOSE), and glucose levels at admission before and during the pandemic. Serum ethanol levels were significantly lower during the SARS-CoV-2 period (1.3 ± 0.7 mmol/L vs. 0.7 ± 1.2 mmol/L; p < 0.001). At discharge, the mean GCS was significantly lower (14.7 ± 1.8 vs. 14.1 ± 0.5; p < 0.05) for patients treated during the SARS-CoV-2 period than before the SARS-CoV-2 period. There were no differences in GOSE; (4) Conclusions: our results demonstrated a significant impact of SARS-CoV-2 pandemic on the frequency, mechanism, and consequences of TBI, and may help improve care for our patients.

Comparison of plasma metanephrines in patients with cyanotic and acyanotic congenital heart disease.

PURPOSE: The co-occurrence of cyanotic congenital heart disease (CCHD) and PHEO/PGL has been reported, but the role of the hypoxic environment in the pathogenesis of PHEO/PGL remains unclear. Our aim was to compare plasma metanephrine and normetanephrine levels between patients with CCHD and patients with acyanotic congenital heart disease (ACCHD). METHODS: We performed a cross-sectional study in a prospective cohort of 44 patients with congenital heart disease (CHD) (31 (70.5%) females) with a median age of 37.5 (31.0-55.6) years at the time of evaluation. Thirty-two (73%) patients had CCHD and 12 (27%) patients had ACCHD. Morning blood samples for plasma determination of metanephrine and normetanephrine were collected. RESULTS: Plasma normetanephrine levels were significantly higher in patients with CCHD compared to ACCHD (p = 0.002). Ten (31.3%) patients with CCHD had plasma normetanephrine levels elevated above the reference range, while all ACCHD patients had normal levels. Patients with lower oxygen saturation and higher proBNP had significantly higher normetanephrine levels (ρ = -0.444, p = 0.003 and ρ = 0.449, p = 0.002, respectively). No chromaffin cell tumors were detected. CONCLUSION: Increased plasma normetanephrine levels in patients with CCHD can be explained by the effect of hypoxia. Future research is needed to better understand the impact of chronic hypoxia in CCHD on increased sympathetic outflow, hyperplastic response of chromaffin tissue, and the role of somatic mutations in CCHD-PHEO/PGL pathogenesis related to hypoxia.

Natural history of nonfunctioning adrenal incidentalomas: a 10-year longitudinal follow-up study.

Most data on the natural history of nonfunctioning adrenal incidentalomas (NFAI) are provided by follow-ups up to 5 years. We conducted a 10.5 (9.1-11.9)-year prospective follow-up study of NFAI in 67 participants (20 (29.9%) males, 47 (70.1%) females) of mean age 57.9 (52.3-63.9) years and BMI 27.42 (24.07-30.56) kg/m2). We also evaluated the associations between baseline BMI and changes of NFAIs' characteristics at follow-up. Progression to mild autonomous cortisol excess (MACE) was observed in 15 (22 %) patients, with 14 of them having post overnight dexamethasone suppression test (ODST) cortisol between 50 and138 nmol/L and only one > 138 nmol/L. The progression rate was significantly higher in overweight and obese than in normal-weight subjects. Patients that developed MACE had a significantly higher baseline mean cortisol after 1 mg ODST. Tumor enlargement ≥10 mm occurred in 8.9% of patients. In comparison with reports of shorter observational periods, we observed a higher growth rate ≥ 10 mm and higher progression rate from NFAI to MACE, particularly in overweight and obese subjects. All tumors had persistent radiological characteristics typical for adrenal adenoma. We concluded that the duration of the follow-up period is an important factor in characterizing the natural history of NFAI. Higher baseline BMI and higher baseline cortisol after ODST might predict the long-term likelihood of progression in hormonal activity. The magnitudes of observed progressions in growth or hormonal activity were clinically insignificant. Our long-term follow-up, therefore, clearly supports the general view that a long-term monitoring of patients with NFAI is not necessary.

Factors associated with degraded trabecular bone score in heart transplant recipients.

Trabecular bone score (TBS) is a textural index that provides indirect evaluation of trabecular microarchitecture. It improves fracture risk assessment in several high-risk populations. We aimed to evaluate the role of TBS assessment in heart transplant recipients (HTR). In a cross-sectional study with 87 HTR (69 males and 18 females), we assessed TBS and evaluated potential associations between TBS and factors related to increased fracture risk. We also evaluated the correlations between the presence of vertebral fractures (VF) and degraded TBS. We confirmed degraded TBS in the majority of HTR. 27.6% of HTR had partially degraded, 27.6% had degraded TBS. HTR with degraded TBS were older, had higher body mass index, lower bone mineral density (BMD), and T-score. As opposed to stable BMD over different time points, TBS significantly differed among different post-transplant time periods. TBS did not correlate with current methylprednisolone or past zoledronic acid treatment, presence of hypogonadism or diabetes. TBS did not have additional value over BMD in predicting the presence of VF. Most fractures occurred in patients with osteopenia and in patients with partly degraded TBS. Studies with longitudinal designs and larger sample sizes are warranted to further assess the potential role of TBS in HRT.

Endocrine disorders after heart transplantation: national cohort study.

BACKGROUND: Endocrine disorders in patients after heart transplantation (HT) remain understudied. We aimed to assess endocrine profiles and management of HT recipients in the early post- transplant period. METHODS: We conducted a retrospective cohort study on 123 consecutive HT recipients in the Advanced Heart Failure and Transplantation Programme between 2009 and 2018. All recipients had per-protocol endocrine follow-up within the first postoperative year. The median time to first post-transplant endocrine follow-up was 3 months (IQR 2-4). We assessed the incidence of vitamin D deficiency, bone mineral density, history of low energy fractures, hypogonadism in male recipients, posttransplant diabetes mellitus, and thyroid and parathyroid function. RESULTS: We enrolled 22 women and 101 men of median age 57 years (IQR 50-63). Post-transplant diabetes mellitus developed in 14 patients (11.4%). 18 of 25 patients (14.6%) with preexisting type 2 diabetes mellitus required intensification of antidiabetic therapy. 38 male patients (40.4%) had hypogonadism. 5 patients (4.6%) were hypothyroid and 10 (9.3%) latent hyperthyroid. Secondary hyperparathyroidism was present in 19 (17.3%), 25-hydroxyvitamin D deficiency in 64 (54.7%) of patients. Osteoporosis was present in 26 (21.1%), osteopenia in 59 (48.0%) patients. 47 vertebral fractures, 3 hip and 1 humerus fractures occurred in 21 patients. Most of the patients had coincidence of two or three disorders, while less than 5% did not have any endocrine irregularities. All patients received calcium and vitamin D supplements. Forty-six patients (37.4%) were treated with zoledronic acid, 12 (9.8%) with oral bisphosphonates. Two patients were treated with teriparatide. CONCLUSIONS: The prevalence of multiple endocrine disorders early after heart transplantation is high. Assessment and management of increased fracture risk and all other potentially affected endocrine axes should be considered as a standard of care in this early period.

Increased Coagulation and Decreased Fibrinolysis as Measured with Overall Hemostatic Potential Are Dependent on BMI and Not Associated with PCOS.

BACKGROUND: Overall hemostatic potential (OHP) captures all factors that affect coagulation and fibrinolysis cascade. It has not yet been assessed in polycystic ovary syndrome (PCOS). The aim of the study was to identify the relationship of OHP with a syndrome per se and body mass index (BMI). METHODS: In 90 women with PCOS aged 30.9 ± 8.1 years (50 obese, 13 overweight, and 27 lean) and 21 healthy age-matched controls (11 obese and 10 lean), OHP with overall coagulation potential (OCP) and overall fibrinolytic potential (OFP) was determined spectrophotometrically. OFP was calculated. RESULTS: OHP increased with BMI in PCOS (9.6 ± 2.3 in lean, 12.5 ± 5.1 in overweight, and 15.5 ± 3.8 Abs-sum in obese) and in controls (9.1 ± 1.0 in lean and 17.3 ± 4.6 Abs-sum in obese). There was significant difference between lean and obese PCOS (P < 0.001) and between lean and obese controls (P < 0.001). OCP also increased with BMI in PCOS (P < 0.001 for lean vs. obese) and in controls (P < 0.001 for lean vs. obese). OFP decreased with BMI in PCOS (P < 0.001 for obese vs. overweight vs. lean) and in controls (P < 0.001 for obese vs. lean). OHP in healthy obese and obese PCOS did not differ significantly, while OHP for healthy obese was increased in comparison to overweight and lean PCOS (P < 0.001). CONCLUSION: PCOS was not associated with increased OHP compared with BMI and age-matched controls. However, increase in OHP was positively associated with BMI in PCOS and healthy women.

Variation in platelet function testing has a major influence on detection of aspirin resistance in healthy subjects.

INTRODUCTION: An increased demand for monitoring aspirin treatment by platelet function tests has been observed, but data on the biological variation of these tests are insufficient. The aim of this study was to assess the biological variation of optical platelet aggregometry and closure time in healthy subjects without aspirin and after aspirin ingestion. SUBJECTS AND METHODS: In 20 healthy subjects, blood was sampled 4 times: on 2 consecutive mornings a day after aspirin ingestion (100 mg/daily) and on 2 consecutive days of no treatment. In all samples, arachidonic acid-, ADP- and collagen-induced optical platelet aggregation was measured, and closure times were determined by collagen/epinephrine (CEPI) and collagen/ADP (CADP) cartridges in a platelet function analyzer-100. RESULTS: Aspirin significantly reduced arachidonic acid- and ADP-induced platelet aggregation and significantly prolonged CEPI closure time, but had no significant effect on collagen-induced platelet aggregation and CADP closure time. Aspirin increased both within- and between-subject coefficients of variation. Arachidonic acid-induced platelet aggregation was the most sensitive to aspirin and no aspirin-resistant subjects were detected on either day after aspirin. According to ADP-induced platelet aggregation or CEPI closure time, 25 and 30% of healthy subjects, respectively, changed from aspirin resistant to aspirin responsive or vice versa from one day to another. There was no agreement between platelet function tests in determining aspirin resistance. CONCLUSIONS: A significant variation in optical platelet aggregometry and closure time exists and is presumed to have a major effect on determination of aspirin resistance.