Oral Octreotide Capsules and Paltusotine in Management of Acromegaly.

Injectable somatostatin receptor ligands (iSRL) are the most frequently utilized medical therapy in patients with acromegaly; however, satisfaction rates are suboptimal. Injections can result in local erythema, discomfort and subcutaneous nodule formation, encompassed with the inconvenience of attending either primary or secondary care medical facilities for injections every 4 weeks. Some patients also note breakthrough of acromegaly-related symptoms towards the end of the injection cycle. To improve acceptance and ultimately improve wellbeing of these individuals, two oral SRLs, oral octreotide capsules (OOC) and paltusotine, have been developed. The OOC combines an enteric coating to allow delivery to the small intestines and a transient permeability enhancer to enable oral bioavailability. Comparable octreotide levels are obtained with twice-daily OOC and subcutaneous octreotide 100 µg. Phase III studies show OOC to maintain equivalent biochemical control in at least 60% of patients previously receiving a stable dose of iSRL. In longer-term studies, the response to OOC was durable up to 3 years. Paltusotine is a novel potent orally available non-peptidyl somatostatin receptor subtype-2 ligand. Studies in healthy volunteers show dose-dependent suppression of growth hormone-releasing hormone-induced growth hormone secretion and suppression of insulin-like growth factor-I (IGF-I) with repeat doses. In the recent phase II study, patients with acromegaly who were partial responders (IGF-I 1.0 - 2.5 x upper limit of normal) to monotherapy with iSRL when switched to once-daily paltusotine maintained control of IGF-I within 20% of baseline or lower in 87% after 13 weeks. Adverse events with both OOC and paltusotine were reflective of those recognized with iSRL and occurred at a similar frequency. OOC and paltusotine are well-received additions to the therapeutic armamentarium in medical therapy for the management of acromegaly; however, further data on efficacy, tumour control and shrinkage are required to allow positioning of this medication within the management algorithm for acromegaly.

Symptoms and steroid dose adjustments following the Covid-19 vaccine in patients with adrenal insufficiency.

BACKGROUND: A proportion of patients with adrenal insufficiency (AI) require increases in their maintenance glucocorticoids following the Covid-19 vaccine as a result of vaccine-related symptoms or development of incipient or frank adrenal crisis. In a large cohort of AI patients, we aim to characterise symptoms, changes in glucocorticoid dosage, occurrence of adrenal crises and whether there are differences between the mRNA and adenovirus vector vaccines. PATIENTS AND METHODS: Patients with AI of any aetiology were invited to complete a short, structured questionnaire of their experience of the Covid-19 vaccination. RESULTS: 279 of the 290 patients enrolled to this study fully completed the questionnaires. 176, 100 and 3 received the Astra Zeneca (AZ), Pfizer-BioNTech (PB) and Moderna (MD) as initial vaccine respectively; and for the second vaccine, 170, 99 and 10 received AZ, PB and MD respectively. Moderate to severe symptoms occurred in 44.8 and 39.7% after the first and second vaccines respectively, were of early onset (6.0 h, IQR 2-12 &. 6.0 h, IQR 2-24 h) and short duration (24 h, IQR 12-72 h & 26 h, IQR 12-72 h). 34.4 and 29.7% increased their maintenance glucocorticoid dose. DISCUSSION: The Covid-19 vaccines appear well-tolerated in patients with AI, with similar frequency of symptoms to that reported in the background population. The AZ vaccine leads to slightly greater post-vaccination symptom burden and need to increase glucocorticoid dosage, but this does not translate to greater adverse outcomes.

The impact of radiotherapy on the hypothalamo-pituitary axis: old vs new radiotherapy techniques.

Multimodality cancer therapy has led to remarkable improvements in survival of childhood and young adult cancer, with survival rates exceeding 85%. Such remission rates come with their own adverse sequelea or 'late effects'. Although the cause of these late effects is multi-factorial, radiation-related adverse effects are one of the most prevalent. Hypopituitarism is a recognised complication of irradiation of brain tumours distant to the hypothalamo-pituitary (HP) axis when the axis is included within the exposed field. Much of the data concerning the development of hypopituitarism, however, relate to early forms of photon-based radiotherapy. In this narrative review, we discuss advances in individual radiotherapy techniques currently used in treating brain tumours and their theoretical benefits based primarily on dosimetric studies. Increasingly precise radiation techniques, including advances in the delivery of photons (i.e. intensity-modulated radiotherapy) and proton beam therapy, are now available options. The premise behind these newer techniques is to reduce the dose and volume of normal tissue irradiated whilst maintaining an effective radiation dose to target tissue. When treating brain tumours distant to the HP axis the expectation, based upon dosimetric studies, is that newer forms of radiotherapy will less frequently involve the HP axis in the exposed field, and where incorporated within the field it will be exposed to a lower radiotherapy dosage. Intuitively the dosimetric studies should translate into significant reductions in the prevalence of HP dysfunction. These data are promising; however, to date there are minimal robust clinical data to determine if the theoretical benefits of these newer techniques on HP dysfunction is to be realised.

Natural history of non-functioning pituitary microadenomas: results from the UK non-functioning pituitary adenoma consortium.

OBJECTIVE: The optimal approach to the surveillance of non-functioning pituitary microadenomas (micro-NFPAs) is not clearly established. Our aim was to generate evidence on the natural history of micro-NFPAs to support patient care. DESIGN: Multi-centre, retrospective, cohort study involving 23 endocrine departments (UK NFPA consortium). METHODS: Clinical, imaging, and hormonal data of micro-NFPA cases between January, 1, 2008 and December, 21, 2021 were analysed. RESULTS: Data for 459 patients were retrieved [median age at detection 44 years (IQR 31-57)-152 males/307 females]. Four hundred and nineteen patients had more than two magnetic resonance imagings (MRIs) [median imaging monitoring 3.5 years (IQR 1.71-6.1)]. One case developed apoplexy. Cumulative probability of micro-NFPA growth was 7.8% (95% CI, 4.9%-8.1%) and 14.5% (95% CI, 10.2%-18.8%) at 3 and 5 years, respectively, and of reduction 14.1% (95% CI, 10.4%-17.8%) and 21.3% (95% CI, 16.4%-26.2%) at 3 and 5 years, respectively. Median tumour enlargement was 2 mm (IQR 1-3) and 49% of micro-NFPAs that grew became macroadenomas (nearly all >5 mm at detection). Eight (1.9%) patients received surgery (only one had visual compromise with surgery required >3 years after micro-NFPA detection). Sex, age, and size at baseline were not predictors of enlargement/reduction. At the time of detection, 7.2%, 1.7%, and 1.5% patients had secondary hypogonadism, hypothyroidism, and hypoadrenalism, respectively. Two (0.6%) developed hypopituitarism during follow-up (after progression to macroadenoma). CONCLUSIONS: Probability of micro-NFPA growth is low, and the development of new hypopituitarism is rare. Delaying the first follow-up MRI to 3 years and avoiding hormonal re-evaluation in the absence of tumour growth or clinical manifestations is a safe approach for micro-NFPA surveillance.

Evaluation of cardiovascular risk factors in long-term survivors of adult- and childhood-onset brain tumours: a pilot study.

Background: Survivors of childhood brain tumours (SCBT) and teenage and young adult cancer survivors have an adverse cardiovascular risk profile, which translates into an increased vascular mortality. Data on cardiovascular risk profiles in SCBT are limited, and furthermore, there are no data in adult-onset (AO) brain tumours. Patients and: methods: Fasting lipids, glucose, insulin, 24-h blood pressure (BP), and body composition were measured in 36 brain tumour survivors (20 AO; 16 childhood-onset (CO)) and 36 age- and gender-matched controls. Results: Compared with controls, patients had elevated total cholesterol (5.3 ± 1.1 vs 4.6 ± 1.0 mmol/L, P = 0.007), LDL-C (3.1 ± 0.8 vs 2.7 ± 0.9 mmol/L, P = 0.011), insulin (13.4 ± 13.1 vs 7.6 ± 3.3 miu/L, P = 0.014), and increased insulin resistance (homeostatic model assessment for insulin resistance (HOMA-IR) 2.90 ± 2.84 vs 1.66 ± 0.73, P = 0.016). Patients showed adverse body composition, with increased total body fat mass (FM) (24.0 ± 12.2 vs 15.7 ± 6.6 kg, P < 0.001) and truncal FM (13.0 ± 6.7 vs 8.2 ± 3.7 kg, P < 0.001). After stratification by timing of onset, CO survivors showed significantly increased LDL-C, insulin, and HOMA-IR compared with controls. Body composition was characterized by the increased total body and truncal FM. Truncal fat mass was increased by 84.1% compared with controls. AO survivors showed similar adverse cardiovascular risk profiles, with increased total cholesterol and HOMA-IR. Truncal FM was increased by 41.0% compared with matched controls (P = 0.029). No difference in mean 24-h BP was noted between patients and controls irrespective of the timing of cancer diagnosis. Conclusion: The phenotype of both CO and AO brain tumour survivors is characterized by an adverse metabolic profile and body composition, putatively placing long-term survivors at increased risk of vascular morbidity and mortality.

A study of acromegaly-associated headache with somatostatin analgesia.

The aim of this study is to characterise somatostatin analogue-responsive headache in acromegaly, hitherto not systematically documented in a significant cohort. Using the UK pituitary network, we have clinically characterised a cohort of 18 patients suffering from acromegaly-related headache with a clear response to somatostatin analogues. The majority of patients had chronic migraine (78%) as defined by the International Headache Society diagnostic criteria. Headache was present at the time of acromegaly presentation and clearly associated temporally with disease activity in all cases. Short-acting somatostatin analogues uniquely resolved pain within minutes and the mean duration of analgesia was 1-6 h. Patients on long-acting analogues required less short-acting injections (mean: 3.7 vs 10.4 injections per day, P = 0.005). 94% used somatostatin analogues to control ongoing headache pain. All patients presented with macroadenoma, most had incomplete resection (94%) and headache was ipsilateral to remnant tissue (94%). Although biochemical control was achieved in 78% of patients, headache remained in 71% of them. Patients selected for this study had ongoing headache post-treatment (mean duration: 16 years after diagnosis); only four patients reached headache remission 26 years (mean range: 14-33) after the diagnosis. Headache in acromegaly patients can be persistent, severe, unrelieved by surgery, long-lasting and uncoupled from biochemical control. We show here that long-acting analogues allow a decrease in the number of short-acting analogue injections for headache relief. Further studies are needed to understand the mechanisms, markers and tumour tissue characteristics of acromegaly-related headache. Until then, this publication serves to provide the clinical characteristics as a reference point for further study.

ChAdOx1 SARS-CoV-2 vaccination: A putative precipitant of adrenal crises.

BACKGROUND: Patients with adrenal insufficiency (AI) have excess mortality, in part due to the occurrence of life-threatening adrenal crises. Infective processes, including that of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), are recognised as the major precipitant of adrenal crises. Adverse reactions to the ChAdOx1 SARS-CoV-2 vaccine occur in a significant proportion of individuals, however, are mild-moderate in the majority of cases. DESIGN: Case series. PATIENTS & RESULTS: We describe five cases where more severe adverse reactions to the ChAdOx1 SARS-CoV-2 vaccine led to actual or incipient adrenal crises requiring parenteral hydrocortisone within 24 h of receiving the first ChAdOx1 SARS-CoV-2 vaccination. CONCLUSION: In individuals with adrenal insufficiency, adverse reactions to the initial dose of the ChAdOx1 SARS-CoV-2 vaccination can precipitate adrenal crises. We recommend that patients with AI should immediately increase their maintenance glucocorticoid dosage 2-3 fold on experiencing any symptoms in the initial 24 h following vaccination.

Young Child Nutrition: Knowledge and Surveillance Gaps across the Spectrum of Feeding.

The first 1000 days is a critical window to optimize nutrition. Young children, particularly 12-24 month-olds, are an understudied population. Young children have unique nutrient needs and reach important developmental milestones when those needs are met. Intriguingly, there are differences in the dietary patterns and recommendations for young children in the US vs. globally, notably for breastfeeding practices, nutrient and food guidelines, and young child formulas (YCFs)/toddler drinks. This perspective paper compares these differences in young child nutrition and identifies both knowledge gaps and surveillance gaps to be filled. Parental perceptions, feeding challenges, and nutrition challenges are also discussed. Ultimately, collaboration among academia and clinicians, the private sector, and the government will help close young child nutrition gaps in both the US and globally.

Risk of second brain tumour after radiotherapy for pituitary adenoma or craniopharyngioma: a retrospective, multicentre, cohort study of 3679 patients with long-term imaging surveillance.

BACKGROUND: Radiotherapy is a valuable treatment in the management algorithm of pituitary adenomas and craniopharyngiomas. However, the risk of second brain tumour following radiotherapy is a major concern. We assessed this risk using non-irradiated patients with the same primary pathology and imaging surveillance as controls. METHODS: In this multicentre, retrospective cohort study, 4292 patients with pituitary adenoma or craniopharyngioma were identified from departmental registries at six adult endocrine centres (Birmingham, Oxford, Leeds, Leicester, and Bristol, UK and Ferrara, Italy). Patients with insufficient clinical data, known genetic predisposition to or history of brain tumour before study entry (n=532), and recipients of proton beam or stereotactic radiotherapy (n=81) were excluded. Data were analysed for 996 patients exposed to 2-dimensional radiotherapy, 3-dimensional conformal radiotherapy, or intensity-modulated radiotherapy, and compared with 2683 controls. FINDINGS: Over 45 246 patient-years, second brain tumours were reported in 61 patients (seven malignant [five radiotherapy, two controls], 54 benign [25 radiotherapy, 29 controls]). Radiotherapy exposure and older age at pituitary tumour detection were associated with increased risk of second brain tumour. Rate ratio for irradiated patients was 2·18 (95% CI 1·31-3·62, p<0·0001). Cumulative probability of second brain tumour was 4% for the irradiated and 2·1% for the controls at 20 years. INTERPRETATION: Irradiated adults with pituitary adenoma or craniopharyngioma are at increased risk of second brain tumours, although this risk is considerably lower than previously reported in studies using general population controls with no imaging surveillance. Our data clarify an important clinical question and guide clinicians when counselling patients with pituitary adenoma or craniopharyngioma on the risks and benefits of radiotherapy. FUNDING: Pfizer.

Hypothalamic-Pituitary and Other Endocrine Surveillance Among Childhood Cancer Survivors.

Endocrine disorders in survivors of childhood, adolescent, and young adult (CAYA) cancers are associated with substantial adverse physical and psychosocial effects. To improve appropriate and timely endocrine screening and referral to a specialist, the International Late Effects of Childhood Cancer Guideline Harmonization Group (IGHG) aims to develop evidence and expert consensus-based guidelines for healthcare providers that harmonize recommendations for surveillance of endocrine disorders in CAYA cancer survivors. Existing IGHG surveillance recommendations for premature ovarian insufficiency, gonadotoxicity in males, fertility preservation, and thyroid cancer are summarized. For hypothalamic-pituitary (HP) dysfunction, new surveillance recommendations were formulated by a guideline panel consisting of 42 interdisciplinary international experts. A systematic literature search was performed in MEDLINE (through PubMed) for clinically relevant questions concerning HP dysfunction. Literature was screened for eligibility. Recommendations were formulated by drawing conclusions from quality assessment of all evidence, considering the potential benefits of early detection and appropriate management. Healthcare providers should be aware that CAYA cancer survivors have an increased risk for endocrine disorders, including HP dysfunction. Regular surveillance with clinical history, anthropomorphic measures, physical examination, and laboratory measurements is recommended in at-risk survivors. When endocrine disorders are suspected, healthcare providers should proceed with timely referrals to specialized services. These international evidence-based recommendations for surveillance of endocrine disorders in CAYA cancer survivors inform healthcare providers and highlight the need for long-term endocrine follow-up care in subgroups of survivors and elucidate opportunities for further research.

Adjuvant Rituximab-Exploratory Trial in Young People With Graves Disease.

CONTEXT: Remission rates in young people with Graves hyperthyroidism are less than 25% after 2 years of thionamide antithyroid drug (ATD). OBJECTIVE: We explored whether rituximab (RTX), a B-lymphocyte-depleting agent, would increase remission rates when administered with a short course of ATD. METHODS: This was an open-label, multicenter, single-arm, phase 2 trial in young people (ages, 12-20 years) with Graves hyperthyroidism. An A'Hern design was used to distinguish an encouraging remission rate (40%) from an unacceptable rate (20%). Participants presenting with Graves hyperthyroidism received 500 mg RTX and 12 months of ATD titrated according to thyroid function. ATDs were stopped after 12 months and primary outcome assessed at 24 months. Participants had relapsed at 24 months if thyrotropin was suppressed and free 3,5,3'-triiodothyronine was raised; they had received ATD between months 12 and 24; or they had thyroid surgery/radioiodine. RESULTS: A total of 27 participants were recruited and completed the trial with no serious side effects linked to treatment. Daily carbimazole dose at 12 months was less than 5 mg in 21 of 27 participants. Thirteen of 27 participants were in remission at 24 months (48%, 90% one-sided CI, 35%-100%); this exceeded the critical value (9) for the A'Hern design and provided evidence of a promising remission rate. B-lymphocyte count at 28 weeks, expressed as a percentage of baseline, was related to likelihood of remission. CONCLUSION: Adjuvant RTX, administered with a 12-month course of ATD, may increase the likelihood of remission in young people with Graves hyperthyroidism. A randomized trial of adjuvant RTX in young people with Graves hyperthyroidism is warranted.

Outcomes of 756 patients with differentiated thyroid cancer and excellent response to treatment: An evidence-based paradigm for long-term surveillance strategies.

BACKGROUND: The 2014 British Thyroid Association thyroid cancer guidelines recommend lifelong follow-up of all thyroid cancer patients. This is probably unnecessary, particularly for differentiated thyroid cancer (DTC) patients with an excellent response to treatment and places significant demand on health service resources. DESIGN: Single centre retrospective cohort analysis of patients diagnosed and treated at the Leeds Cancer Centre between 2001 and 2014. PATIENTS: A total of 756 patients were dynamically risk-stratified (DRS) as having 'excellent response to treatment' after total thyroidectomy and radioiodineremnant ablation (RRA) for DTC. RESULTS: Median follow-up was 11.2 (range: 6.5-18.5) years. Radiological recurrence occurred in 15/756 (2.0%) patients and was always preceded by a raised thyroglobulin or thyroglobulin antibody level. The vast majority of tumour recurrences (13/15, 85%) were identifiable within 5 years of diagnostic surgery. Patients classified as having high-risk disease as per American Thyroid Association (ATA) guidelines had an almost threefold higher recurrence rate (2/34 [5.9%] vs. 13/722 [1.8%]) than those with ATA low-risk or intermediate-risk disease. Tumour histology subtype was a significant contributing factor, with Hürthle cell cancer having a worse prognosis than papillary thyroid cancer (PTC) (5/68 [7.4%] vs. 9/582 [1.5%]; relative risk: 4.76 [95% confidence interval: 1.64-13.8]). CONCLUSIONS: The recurrence rate of DRS patients with excellent response to treatment is low. It is reasonable to consider discharge of ATA low-risk or intermediate-risk patients with PTC who remain disease-free after 5 years of secondary care follow-up. Lifelong follow-up, however, currently remains the standard for subgroups at greater risk.

Characterisation of the onset and severity of adrenal and thyroid dysfunction associated with CTLA4-related hypophysitis.

CONTEXT: The use of the CTLA4 inhibitor, ipilimumab, has proven efficacious in the treatment of melanoma, renal carcinoma and non-small cell lung cancer; however, it is associated with frequent immune-related adverse events (irAE). Ipilimumab-induced hypophysitis (IIH) is a well-recognised and not infrequent endocrine irAE. OBJECTIVE: To investigate the timing of onset and severity of adrenal and thyroid hormone dysfunction around the development of IIH in patients treated for melanoma. DESIGN: Aretrospective review of hormone levels in consecutive adult patients treated with ipilimumab (3 mg/kg) for advanced melanoma as monotherapy or in combination with a PD-1 inhibitor. RESULTS: Of 189 patients, 24 (13%; 13 males; 60.5 ± 12.2 years) presented with IIH at a median of 16.1 (range: 6.7-160) weeks after commencing treatment, occurring in 14 (58%) after the fourth infusion. At the presentation of IIH, corticotroph deficiency was characterised by an acute and severe decrease in cortisol levels to ≤83 nmol/L (≤3 µg/dL) in all patients, often only days after a previously recorded normal cortisol level. Free thyroxine (fT4) levels were observed to decline from 12 weeks prior to the onset of cortisol insufficiency, with the recovery of thyroid hormone levels by 12 weeks after the presentation of IIH. A median fall in fT4 level of 20% was observed at a median of 3 weeks (IQR: 1.5-6 weeks) prior to the diagnosis of IIH. CONCLUSION: IIH is characterised by an acute severe decline in cortisol levels to ≤83 nmol/L at presentation. A fall in fT4 can herald the development of ACTH deficiency and can be a valuable early indicator of IIH.

Iron-Rich Complementary Foods: Imperative for All Infants.

Nearly 1 in 5 (18%) infants in the United States is not consuming sufficient iron. A deficiency of iron during early life may be associated with long-term neurodevelopmental consequence(s). The 2020-2025 Dietary Guidelines for Americans (DGA) are the first DGA to address recommendations for children under 2 y of age. The 2020 Dietary Guidelines Advisory Committee scientific report includes food-group combinations emphasizing iron-rich foods for 6-12-mo-old infants, but these examples did not meet criteria to establish DGA recommended dietary patterns; consequently, iron-rich dietary patterns for ages 6-12 mo are not provided in the 2020-2025 DGA. The 2020-2025 DGA encourage iron-rich foods by 6 mo of age while emphasizing the importance "particularly for infants fed human milk." Early feeding transitions are dynamic and milk feeding groups are rarely static or exclusive such that emphasizing milk feeding groups may become confusing. Risk-to-benefit favors iron-rich complementary feeding for all infants.

Bone mineral density surveillance for childhood, adolescent, and young adult cancer survivors: evidence-based recommendations from the International Late Effects of Childhood Cancer Guideline Harmonization Group.

Childhood, adolescent, and young adult cancer survivors are at increased risk of reduced bone mineral density. Clinical practice surveillance guidelines are important for timely diagnosis and treatment of these survivors, which could improve bone mineral density parameters and prevent fragility fractures. Discordances across current late effects guidelines necessitated international harmonisation of recommendations for bone mineral density surveillance. The International Late Effects of Childhood Cancer Guideline Harmonization Group therefore established a panel of 36 experts from ten countries, representing a range of relevant medical specialties. The evidence of risk factors for very low and low bone mineral density and fractures, surveillance modality, timing of bone mineral density surveillance, and treatment of very low and low bone mineral density were evaluated and critically appraised, and harmonised recommendations for childhood, adolescent, and young adult cancer survivors were formulated. We graded the recommendations based on the quality of evidence and balance between potential benefits and harms. Bone mineral density surveillance is recommended for survivors treated with cranial or craniospinal radiotherapy and is reasonable for survivors treated with total body irradiation. Due to insufficient evidence, no recommendation can be formulated for or against bone mineral density surveillance for survivors treated with corticosteroids. This surveillance decision should be made by the survivor and health-care provider together, after careful consideration of the potential harms and benefits and additional risk factors. We recommend to carry out bone mineral density surveillance using dual-energy x-ray absorptiometry at entry into long-term follow-up, and if normal (Z-score > -1), repeat when the survivor is aged 25 years. Between these measurements and thereafter, surveillance should be done as clinically indicated. These recommendations facilitate evidence-based care for childhood, adolescent, and young adult cancer survivors internationally.

Characterization of patients with adrenal insufficiency and frequent adrenal crises.

OBJECTIVE: This study aimed to characterize the clinical and biochemical features of patients with primary (PAI) and secondary (SAI) adrenal insufficiency who developed adrenal crises (ACs) and estimate the incidence of ACs in these patients. DESIGN: Retrospective case-control analysis of the European Adrenal Insufficiency Registry (EU-AIR; NCT01661387). METHODS: Two thousand six hundred and ninety-four patients with AI (1054 PAI; 1640 SAI) enrolled in EU-AIR. Patients who developed ≥ 1 AC were matchd 1:3 with patients without ACs for age, sex and AI type. Data were collected at baseline and follow-up (mean ± s.d.: PAI 3.2 ± 1.7 years; SAI 2.9 ± 1.7 years). RESULTS: One hundred and forty-eight out of 2694 patients (5.5%; n = 84 PAI; n = 64 SAI) had an AC during the study: 6.53 (PAI) and 3.17 (SAI) ACs/100 patient-years. Of patients who experienced an AC, 16% (PAI) and 9.4% (SAI) experienced ≥ 1 AC/year. The incidence of adverse events, infectious intercurrent illnesses and infectious serious adverse events were higher in patients with ACs than without ACs. No differences were observed in BMI, HbA1c, blood pressure and frequencies of diabetes mellitus or hypertension between subgroups (PAI and SAI, with and without ACs). At baseline, PAI patients with AC had higher serum potassium (4.3 ± 0.5 vs 4.2 ± 0.4 mmol/L; P = 0.03) and lower sodium (138.5 ± 3.4 vs 139.7 ± 2.9 mmol/L; P = 0.004) than patients without AC. At last observation, SAI patients with AC had higher hydrocortisone doses than patients without AC (11.9 ± 5.1 vs 10.1 ± 2.9 mg/m2; P < 0.001). CONCLUSIONS: These results demonstrate that concomitant diseases and cardiovascular risk factors do not feature in the risk profile of AC; however, patients with AC had a higher incidence of infectious events.

Safety and effectiveness of replacement with biosimilar growth hormone in adults with growth hormone deficiency: results from an international, post-marketing surveillance study (PATRO Adults).

PURPOSE: To evaluate safety and effectiveness of biosimilar recombinant human growth hormone (rhGH; Omnitrope®) in adults with growth hormone deficiency (GHD), using data from the PATRO Adults study. METHODS: PATRO Adults was a post-marketing surveillance study conducted in hospitals and specialized endocrinology units across Europe. The primary objective was to assess the safety of rhGH in adults treated in routine clinical practice. All adverse events (AEs) were monitored and recorded for the complete duration of Omnitrope® treatment. Effectiveness was evaluated as a secondary objective. RESULTS: As of January 2020, 1447 patients (50.9% male) had been enrolled from 82 centers in 9 European countries. Most patients had adult-onset GHD (n = 1179; 81.5%); 721 (49.8%) were rhGH-naïve at study entry. Overall, 1056 patients (73.0%) reported adverse events (AEs; n = 5397 events); the majority were mild-to-moderate in intensity. Treatment-related AEs were reported in 117 patients (8.1%; n = 189 events); the most commonly reported (MedDRA preferred terms) were arthralgia (n = 19), myalgia (n = 16), headache (n = 14), and edema peripheral (n = 10). In total, 495 patients (34.2%) had serious AEs (SAEs; n = 1131 events); these were considered treatment-related in 28 patients (1.9%; n = 35 events). Mean (standard deviation) IGF-I SDS increased from - 2.34 (1.47) at baseline to - 0.23 (1.65) at 12 months, and remained relatively stable thereafter (up to 3 years). Body mass index remained stable between baseline and 3 years. CONCLUSION: Data from PATRO Adults indicate biosimilar rhGH (Omnitrope®) is not associated with any unexpected safety signals, and is effective in adults with GHD treated in real-world clinical practice.

Interpretation of the endocrinology of hospital inpatients.

Blood tests to assess the endocrine system are commonly performed in patients admitted to hospital. This may be because an endocrinopathy is thought to be aetiological in the presenting disease or suspected as an incidental occurrence by the clinician. Many patients, in addition to the pathology leading to admission, frequently have one or more comorbidities, a change in nutritional status and polypharmacy. Added to this, presentation with acute illness is a major life stress. All of these are likely to impact on one or more endocrine axes, although often only transiently. Endocrine evaluation in the vast majority of cases can be safely deferred to the outpatient setting. This article considers the most common endocrine anomalies discovered in hospital, the confounders, and provides guidance on how to investigate these further.