Use of a dosimetry-based RAI protocol for treatment of benign hyperthyroidism optimises response while minimising exposure to ionising radiation.

BACKGROUND: The optimal treatment strategy for radioiodine (RAI) treatment protocols for benign hyperthyroidism remains elusive. Although individualised activities are recommended in European Law, many centres continue to provide fixed activities. Our institution implemented a dosimetry protocol in 2016 following years of fixed dosing which facilitates the calculation of individualised activities based on thyroid volume and radioiodine uptake. METHODS: This was a retrospective study comparing success rates using a dosimetry protocol targeting an absorbed dose of 150 Gy for Graves' disease (GD) and 125 Gy for Toxic Multinodular Goiter (TMNG) with fixed dosing (200MBq for GD and 400MBq for TMNG) among 204 patients with hyperthyroidism. Success was defined as a non-hyperthyroid state at 1 year for both disease states. Results were analysed for disease specific or patient specific modulators of response. RESULTS: This study included 204 patients; 74% (n = 151) received fixed activities and 26% (n = 53) of activities administered were calculated using dosimetry. A dosimetry-based protocol was successful in 80.5% of patients with GD and 100% of patients with TMNG. Differences in success rates and median activity administered between the fixed (204Mbq) and dosimetry (246MBq) cohort were not statistically significant (p = .64) however 44% of patients with GD and 70% of patients with TMNG received lower activities following treatment with dosimetry as opposed to fixed activities. Use of dosimetry resulted in successful treatment and reduced RAI exposure for 36% of patients with GD, 70% of patients with TMNG, and 44% of patients overall. CONCLUSION: This retrospective clinical study demonstrated that treatment with a dosimetry-based protocol for TMNG and GD achieved comparable success rates to fixed protocols while reducing RAI exposure for over a third of patients with GD and most patients with TMNG. This study also highlighted that RAI can successfully treat hyperthyroidism for some patients with activities lower than commonplace in clinical practise. No patient or disease specific modulators of treatment response were established in this study; however, the data supports a future prospective trial which further scrutinises the individual patient factors governing treatment response to RAI.

Tissue Glucocorticoid Metabolism in Adrenal Insufficiency: A Prospective Study of Dual-release Hydrocortisone Therapy.

BACKGROUND: Patients with adrenal insufficiency (AI) require life-long glucocorticoid (GC) replacement therapy. Within tissues, cortisol (F) availability is under the control of the isozymes of 11ß-hydroxysteroid dehydrogenase (11ß-HSD). We hypothesize that corticosteroid metabolism is altered in patients with AI because of the nonphysiological pattern of current immediate release hydrocortisone (IR-HC) replacement therapy. The use of a once-daily dual-release hydrocortisone (DR-HC) preparation, (Plenadren®), offers a more physiological cortisol profile and may alter corticosteroid metabolism in vivo. STUDY DESIGN AND METHODS: Prospective crossover study assessing the impact of 12 weeks of DR-HC on systemic GC metabolism (urinary steroid metabolome profiling), cortisol activation in the liver (cortisone acetate challenge test), and subcutaneous adipose tissue (microdialysis, biopsy for gene expression analysis) in 51 patients with AI (primary and secondary) in comparison to IR-HC treatment and age- and BMI-matched controls. RESULTS: Patients with AI receiving IR-HC had a higher median 24-hour urinary excretion of cortisol compared with healthy controls (72.1 µg/24 hours [IQR 43.6-124.2] vs 51.9 µg/24 hours [35.5-72.3], P = .02), with lower global activity of 11ß-HSD2 and higher 5-alpha reductase activity. Following the switch from IR-HC to DR-HC therapy, there was a significant reduction in urinary cortisol and total GC metabolite excretion, which was most significant in the evening. There was an increase in 11ß-HSD2 activity. Hepatic 11ß-HSD1 activity was not significantly altered after switching to DR-HC, but there was a significant reduction in the expression and activity of 11ß-HSD1 in subcutaneous adipose tissue. CONCLUSION: Using comprehensive in vivo techniques, we have demonstrated abnormalities in corticosteroid metabolism in patients with primary and secondary AI receiving IR-HC. This dysregulation of pre-receptor glucocorticoid metabolism results in enhanced glucocorticoid activation in adipose tissue, which was ameliorated by treatment with DR-HC.

A Pilot Study of Gut-Brain Signaling After Octreotide Therapy for Unintentional Weight Loss After Esophagectomy.

BACKGROUND: Recurrence-free patients after esophageal cancer surgery face long-term nutritional consequences, occurring in the context of an exaggerated postprandial gut hormone response. Acute gut hormone suppression influences brain reward signaling and eating behavior. This study aimed to suppress gut hormone secretion and characterize reward responses and eating behavior among postesophagectomy patients with unintentional weight loss. METHODS: This pilot study prospectively studied postoperative patients with 10% or greater body weight loss (BWL) beyond 1 year who were candidates for clinical treatment with long-acting octreotide (LAR). Before and after 4 weeks of treatment, gut hormone secretion, food cue reactivity (functional magnetic resonance imaging), eating motivation (progressive ratio task), ad libitum food intake, body composition, and symptom burden were assessed. RESULTS: Eight patients (7 male, age: mean ±â€…SD 62.8 ±â€…9.4 years, postoperative BWL: 15.5 ±â€…5.8%) participated. Octreotide LAR did not significantly suppress total postprandial plasma glucagon-like peptide-1 response at 4 weeks (P = .08). Postprandial symptom burden improved after treatment (Sigstad score median [range]: 12 [2-28] vs 8 [3-18], P = .04) but weight remained stable (pre: 68.6 ±â€…12.8 kg vs post: 69.2 ±â€…13.4 kg, P = .13). There was no significant change in brain reward system responses, during evaluation of high-energy or low-energy food pictures, nor their appeal rating. Moreover, treatment did not alter motivation to eat (P = .41) nor ad libitum food intake(P = .46). CONCLUSION: The protocol used made it feasible to characterize the gut-brain axis and eating behavior in this cohort. Inadequate suppression of gut hormone responses 4 weeks after octreotide LAR administration may explain the lack of gut-brain pathway alterations. A higher dose or shorter interdose interval may be required to optimize the intervention.

Gender differences in estimating I-131 thyroid uptake from Tc-99m thyroid uptake for benign thyroid disease.

OBJECTIVE: For radioactive Iodine-131 (131I) treatments of thyroid diseases, increased efficacy has been reported for personalized dosimetry treatments. The measurement of Iodine-131 thyroid uptake (131IU) is required in these cases. This study aims to investigate whether 99mTc thyroid uptake (99mTcU) may be used in place of 131IU for implementing personalised treatments. METHODS: A retrospective study of 152 benign thyroid disease 131I treatments was carried out during 2012-2020; 117 treatments were for female patients while 35 were for male patients diagnosed with either Graves' disease, multinodular goitre or toxic nodules. RESULTS: A statistically significant correlation was found between 131IU and 99mTcU data, with the data more correlated for male than female patients (r = 0.71 vs 0.38, p-value < 0.001). Patient age and time difference between the two respective uptake measurements significantly influenced the uptake correlation in females but not for the male cohort, although there was no significant difference between the parameters across gender. Thyroid diagnosis and hormone levels showed a significant correlation with uptakes in both genders. Estimating 131IU based on 99mTcU was shown to be predictive for male but not in female patients (R2 = 91% vs 16%). CONCLUSION: Estimating 131IU based on 99mTcU is not recommended for females at our centre. Males reported good correlation, but a larger sample would be needed for validation. ADVANCES IN KNOWLEDGE: The initial findings showed a significant gender difference in benign thyroid uptake parameters at our centre, highlighting the potential need for gender consideration when planning 131IU patient management and when reporting studies results.

A Surviving Case of Acanthamoeba Granulomatous Amebic Encephalitis in a Hematopoietic Stem Cell Transplant Recipient.

BACKGROUND Acanthamoeba are free-living amoebae with potential to infect immunocompromised hosts. The mortality rate of granulomatous amebic encephalitis (GAE) due to Acanthamoeba exceeds 90% and there are currently no reports of survival of this infection in recipients of hematopoietic stem cell transplant. CASE REPORT We report herein the case of a 32-year-old man presenting to our service with abrupt neurological deterioration and seizures 5 months after allogeneic stem cell transplantation for Hodgkin lymphoma. Clinical and imaging findings were non-specific at presentation. Multiple circumscribed, heterogenous, mass-like lesions were identified on MRI. Brain biopsy was performed and revealed multiple cysts and trophozoites suggesting a diagnosis of granulomatous amebic encephalitis. PCR testing confirmed Acanthamoeba. Treatment with miltefosine, metronidazole, azithromycin, fluconazole, pentamidine isethionate, and co-trimoxazole was instituted and the patient survived and shows continued improvement with intensive rehabilitation. CONCLUSIONS We report the first successful outcome in this setting. The diagnosis would have been missed on cerebrospinal fluid analysis alone, but was rapidly made by histological analysis of brain biopsy. This diagnostically challenging infection is likely under-recognized. Early brain biopsy and commencement of a prolonged miltefosine-containing anti-ameba regimen can be curative.

Spurious HbA1c results in patients with diabetes treated with dapsone.

SUMMARY: Measurement of glycated haemoglobin (HbA1c) has been utilised in assessing long-term control of blood glucose in patients with diabetes, as well as diagnosing diabetes and identifying patients at increased risk of developing diabetes in the future. HbA1c reflects the level of blood glucose to which the erythrocyte has been exposed during its lifespan, and there are a number of clinical situations affecting the erythrocyte life span in which HbA1c values may be spuriously high or low and therefore not reflective of the true level of glucose control. In the present case series, we describe the particulars of three patients with diabetes who had spuriously low HbA1c levels as a result of dapsone usage. Furthermore, we discuss the limitations of HbA1c testing and the mechanisms by which it may be affected by dapsone in particular. LEARNING POINTS: Various conditions and medications can result in falsely low HbA1c. Dapsone can lead to falsely low HbA1c by inducing haemolysis and by forming methaemoglobin. Capillary glucose measurement, urine glucose measurements and fructosamine levels should be used as alternatives to HbA1c for monitoring glycaemic control if it was falsely low or high.

Management of squamous cell cancer of the oesophagus in a patient with a polyglandular endocrinopathy (APECED) and achalasia.

INTRODUCTION: We report a case of a 37-year-old man, with a background of a rare polyglandular autoimmune syndrome and achalasia, who developed an oesophageal tumour. Both autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED) or type I polyglandular syndrome and achalasia confer increased risk of development of oesophageal squamous cell carcinoma. METHODS: Despite having had multiple endoscopic examinations and dilatations in the recent past, this patient presented with dysphagia, and on endoscopy, he was found to have a mid-oesophageal tumour. A multidisciplinary team approach was vital in his management as careful monitoring of underlying disorders including Addison's disease and hypoparathyroidism were challenging during neoadjuvant chemoradiotherapy and in the perioperative period. RESULTS: He made an uneventful recovery after a three-stage oesophagectomy, and histologically, he had a complete pathological response. CONCLUSION: To our knowledge, this is the first successful outcome of a patient with APECED and oesophageal carcinoma in the literature.

Metastatic insulinoma in a patient with type 2 diabetes mellitus: case report and review of the literature.

Pancreatic neuroendocrine tumors (NETs) are extremely rare, and although insulinomas are the commonest, less than 10% of insulinomas are malignant. Most patients with insulinomas present with neuroglycopenic symptoms and weight gain attributable to insulin excess. Here, we report a case where a 67-year-old lady with a background history of type 2 diabetes mellitus and breakthrough hyperinsulinism who presented with coma. The biochemical profile revealed features typical of insulinoma, and CT and endosonography confirmed a pancreatic tumor with large volume right-sided liver metastases (biopsy confirming a neuroendocrine tumor). The patient underwent successful one-step RO surgical resection, distal pancreatectomy, splenectomy, and right hepatectomy, and 9 months postoperatively, she remains free of recurrent disease. She remains a diabetic.

Diagnosis, misdiagnosis and management of hyperprolactinemia.

Hyperprolactinemia is a commonly encountered disorder that suppresses both male and female gonadal function. The etiology includes pituitary tumors, hypothalamic or pituitary stalk lesions, drugs and hypothyroidism. In women, the hyperprolactinemic syndrome is characterized by menstrual disorders with or without galactorrhea, while men present with hypogonadism and related symptoms. Occasionally, a pituitary macroadenoma may be associated with pressure symptoms and/or hypopituitarism. Clinically, the most important cause of hyperprolactinemia is a prolactin-secreting pituitary adenoma. The majority of patients with prolactinomas are successfully managed medically with dopamine agonists such as cabergoline or bromocriptine. Misdiagnosis of hyperprolactinemia owing to immunoassay interference by a biologically minimally active form of prolactin termed macroprolactin is common in laboratory medicine . Alhough the etiology of macroprolactinemia is unclear, the condition is commonly associated with the presence of circulating antiprolactin antibodies. In the absence of specific testing, macroprolactin represents a diagnostic pitfall resulting in misdiagnosis and mismanagement of patients. This review examines the investigation and treatment of hyperprolactinemia in the broadened context of screening for macroprolactin and the consequences of failure to identify its presence.