Medicine (St Vincent's) - Research Publications
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ItemNo Preview AvailableThe Role of 68Ga-DOTA-Octreotate PET/CT in Follow-Up of SDH-Associated Pheochromocytoma and Paraganglioma(ENDOCRINE SOCIETY, 2019-11-01)Purpose: Germline succinate dehydrogenase (SDHx) mutation carriers, especially SDHB, are at increased risk for malignancy and require life-long surveillance. Current guidelines recommend periodic whole-body MRI imaging. We assessed the incremental value of 68Ga-DOTA-octreotate (GaTate) positron emission tomography (PET)/CT compared with conventional imaging in such patients. Methods: SDHx mutation carriers who had GaTate PET/CT were retrospectively reviewed. Detection of lesions were compared with MRI or CT on a per-patient and per-lesion basis. Proof of lesions were based on histopathology or clinical/imaging follow-up. Results: Twenty consecutive patients (median age, 46 years; 10 males) were reviewed. Fourteen patients had SDHB, four, SDHD, one SDHC, and one SDHA mutation. Fifteen had prior surgery and/or radiotherapy. Indications for PET/CT were as follows: 7 patients for surveillance for previously treated disease, 9 residual disease, 2 asymptomatic mutation carriers, and 2 for elevated catecholamines. Median time between modalities was 1.5 months. GaTate PET/CT had higher sensitivity and specificity than conventional imaging. On a per-patient basis: PET/CT sensitivity 100%, specificity 100%; MRI/CT 85% and 50%. Per-lesion basis: PET/CT sensitivity 100%, specificity 75%; MRI/CT 80% and 25%. PET/CT correctly identified additional small nodal and osseous lesions. MRI/CT had more false-positive findings. Change of management resulted in 40% (8/20 patients): 3 received localized treatment instead of observation, 1 changed to observation given extra disease detected, 4 with metastases had radionuclide therapy. Conclusions: GaTate PET/CT provided incremental diagnostic information with consequent management impact in SDHx-pheochromocytoma and paraganglioma. Incorporating this modality as part of a surveillance program seems prudent. Further research is needed to define the optimal surveillance strategy including use of MRI.
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ItemNo Preview AvailableTwo cases of adrenocortical carcinoma(Wiley, 2018-06)Adrenocortical carcinomas are rare but patients often present with advanced disease and display symptoms of hormone hypersecretion or tumour burden/mass effect. Here we present two cases of adrenocortical carcinoma to highlight the challenges of managing this condition. Case 1: A 48 year old female initially presented with an incidental adrenal mass measuring 42 mm. On triple-phase CT the mass was reported as an adrenal myelolipoma and no further followup was arranged. She represented 3 years later with abdominal bloating, facial plethora, hirsutism and weight gain. Investigations revealed hypercortisolism and hyperandrogenism in the setting of a 16 cm adrenal mass with retroperitoneal lymphadenopathy but no distant metastases. She underwent an open right adrenalectomy and histology was consistent with a 17 cm adrenocortical carcinoma with a high Ki-67 index of 40% and positive lymph nodes. Post-operative workup revealed residual local disease as well as pulmonary metastases. She then received adjuvant therapy with etoposide/doxorubicin/cisplatin and mitotane. Progressive disease was further treated with radionucleotide therapy (I131-metomidate), immunotherapy (PD-1 antibody BGB-A317) and sunitinib. Despite multiple lines of treatment, disease control was never achieved and the patient died 2 years following her initial surgery. Case 2: A 35 year old female presented with weight gain, amenorrhoea, hirsutism and abdominal striae. Workup revealed hyperandrogenism and hypercortisolism with a large right adrenal mass. A 94 mm adrenocortical carcinoma with a Ki-67 index of 30% was resected. She underwent adjuvant therapy with mitotane however follow-up imaging revealed new pulmonary and hepatic metastases. She received first-line chemotherapy with etoposide/doxorubicin/cisplatin as well as mitotane and metyrapone to control florid Cushing's syndrome. She progressed to second-line chemotherapy with capecitabine/gemcitabine however died soon after. An actionable mutation suitable for targeted therapy was not identified on next-generation sequencing in either case. These cases emphasise the need for improved treatments for metastatic disease.
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ItemNo Preview AvailableDecrease in serum potassium levels post saline suppression test in primary aldosteronism: an under-recognised phenomenon?(NATURE PUBLISHING GROUP, 2016-11)Seventeen subjects with confirmed primary aldosteronism and stable serum potassium (K) levels ≥ 3.5 mmol l-1 underwent saline suppression testing. They were retrospectively evaluated for changes in serum K levels post test. We found that there was a significant decrease in serum K levels post saline suppression test (3.7 ± 0.05 vs 3.5 ± 0.08, P = 0.01). This effect of saline suppression testing on serum K levels is not well described. We conclude that a decrease in serum K is common post-saline suppression test, even in subjects who are normokalemic pretest. The factors which predispose to the decrease in serum K level post saline load remain unclear.
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ItemNo Preview AvailableAceruloplasminaemia: a disorder of diabetes and neurodegeneration(Wiley, 2017-01)Aceruloplasminaemia is a rare, autosomal recessive disorder of iron metabolism which results in iron deposition in the pancreas, brain, retina and liver. The clinical phenotype is distinctive: it typically leads to diabetes, anaemia and progressive neurodegeneration, but does not appear to cause functional retinal or hepatic impairment. We report an early case of aceruloplasminaemia in Australia and summarise the clinical sequelae and interesting aspects of their pathophysiology, especially that of diabetes. A Sri Lankan male was diagnosed with aceruloplasminaemia in 1994 age 44 years, after presenting with type 2 diabetes mellitus in 1989 associated with mild microcytic anaemia and abnormal iron studies. Significantly, he had low serum iron 6.4 (14.0–32 mmol/L) and serum copper 2.0 (12.5–18 μmol/L); normal transferrin 3.0 (2.0–3.6 g/L); and high ferritin 838 (40–20 μg/L). Liver biopsy showed an elevated iron content 9.91 mg/g dry weight (0.40–1.30 mg/g) with normal copper concentration 46 (15–70 μg/g), and no evidence of fibrosis. Empirical treatment with venesection resulted in profound anaemia suggesting a disorder of iron mobilisation. Ceruloplasmin was subsequently tested and found to be undetectable with a level of <0.05 (0.18–0.45 g/L) confirming a diagnosis of aceruloplasminaemia. Since diagnosis, his clinical sequelae have comprised insulin dependent diabetes, anaemia and ultimately progressive neurodegeneration involving psychosis, depression, dementia and Parkinsonism. Treatment has involved iron chelation together with insulin, oral hypoglycaemics, antipsychotics, antidepressants and donepezil. The patient now requires assistance with all activities of daily living. Aceruloplasminaemia was first described in 1987 and there are 56 case reports to date. Diabetes was developed by 85% of these patients and appears to be an early manifestation of this condition. The devastating neurodegenerative sequelae make early diagnosis and treatment essential. Screening should thus be considered when adult onset, antibody negative, insulin dependent diabetes is associated with anaemia and corroborative iron studies or unexplained neurodegenerative symptoms.
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ItemNo Preview AvailableHypokalaemia post-saline suppression test in primary hyperaldosteronism(Wiley, 2016-03)Background: Primary hyperaldosteronism (PHA) accounts for 5–10% of patients with hypertension (1). Saline suppression test (SST) is a commonly used confirmatory test in the diagnosis of PHA. Although potassium (K) is checked at baseline with recommendations to adequately replace prior to SST, there are no recommendations to routinely check potassium post-SST. This contrasts guidelines for the fludrocortisone suppression test (FST) which is known to cause hypokalaemia. A previous study monitored K levels post-SST in a subgroup of patients, and found a non-significant decrease (-0.05 0.2 mmol/L) in potassium levels post-SST (2). We report a retrospective series of patients who became hypokalaemic in the 2 h period post-SST. Methods: A retrospective audit was conducted of patients with con-firmed PHA who underwent SST between 2005 and 2015. Pre- and 2 h post-test potassium, aldosterone and renin levels were measured. Results are expressed as mean standard error of the mean (SEM) and number (%). Results: Twenty five patients were included in the final analysis; 13(52%) were males, and mean age 53 10.5 years. Overall, there was no difference in the mean pre- and post-SST potassium levels (p = 0.08). However, there was an inverse correlation between pre-SST K and the change in post-test K levels (p = 0.01); with the highest pre-test K patients experiencing the greatest decline in post-K levels. Eight (32%) were hypokalaemic (K < 3.5 mmol/L) pre-SST and required intravenous or oral K supplements. For patients that were normokalaemic pre-SST, there was a significant decrease in serum potassium levels post-SST (3.7 0.05 vs. 3.5 0.08,p = 0.01). Seven subjects (41%) who were normokalaemic pre-test became hypokalaemic post-SST; and 5 (29%) remained hypokalaemic on day 2. Conclusion: Hypokalaemia is common post-saline suppression test in primary hyperaldosteronism. The pathophysiology remains unclear. We recommend that potassium levels be routinely measured post-test and on day 2 to detect persistent hypokalaemia.
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ItemNo Preview AvailableFalse negative Ga68-DOTA-exendin-4 PET/CT in a patient with occult insulinomas(Wiley, 2017-01)Benign insulinomas are rare neuroendocrine tumours most commonly located in the pancreas. They are the most frequent cause of hyperinsulinaemia hypoglycaemia in adults without diabetes. Diagnosis can be challenging, and accurate localisation with surgical excision is the only cure. There is a growing body of evidence for the efficacy of Ga68-DOTA-exendin-4 (glucagon-like peptide-1 (GLP-1)) PET/CT scans, which centres on the premise that a near majority of insulinomas are ubiquitous for the GLP-1 receptor. We describe an 82 year-old woman with a history of fasting hyperinsulinaemic hypoglycaemia associated with neuroglycopaenic symptoms. Triple phase CT scan of the pancreas and a Ga68-DOTATATE PET/CT scan were both unremarkable. A Ga68-GLP-1 PET/CT scan showed diffuse pancreatic uptake consistent suggestive of pancreatic beta cell hyperplasia, or nesidioblastosis. The patient had further testing including an endoscopic ultrasound and calcium stimulation test which localised insulin hypersecretion to the body and tail of pancreas. Surgery revealed an insulinoma which was later con-firmed on immunohistochemistry to be GLP-1 receptor negative. Although GLP-1 scans are being increasingly used in clinical practice for work-up of hypoglycaemic disorders, they are expensive and not readily available. Clinical judgment is always crucial, and the differential of an insulinoma should not be ruled out on the basis of this scan.
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ItemDilemmas in metastatic differentiated thyroid cancer: To irradiate, medicate, or palliate?(Jaypee Brothers Medical Publishing, 2016-05-01)ABSTRACT Aims To explore the challenges in the management of metastatic differentiated thyroid cancer. Introduction Differentiated thyroid cancer (DTC) is the most common form of thyroid cancer. The initial diagnosis of thyroid carcinoma and the distinction between benign and neoplastic disease can be challenging. Radioiodine-refractory metastatic DTC also presents a therapeutic dilemma. Novel targeted agents for advanced radioiodine-refractory metastatic thyroid cancer, such as tyrosine kinase inhibitors (TKIs), are being increasingly used with clinical success, broadening current available therapeutic options. Case report We present the case of a 61-year-old woman with radioiodine-refractory metastatic follicular thyroid carcinoma, which was initially misdiagnosed as benign Hurthle cell adenoma. We focus on the challenges in both the initial diagnosis and the subsequent management of her advanced disease with skeletal dominant metastases. Conclusion The advent of targeted systemic therapies as emerging frontline and salvage therapy is a novel addition to the management of radioiodine-refractory advanced DTC. Further studies to expand the role of sequential and redifferentiation therapy for advanced disease and strategies to reduce skeletalrelated events are still required. How to cite this article Lee MH, Moxey JE, McLachlan S-A, MacIsaac RJ, Sachithanandan N. Dilemmas in Metastatic Differentiated Thyroid Cancer: To irradiate, medicate, or palliate? World J Endoc Surg 2016;8(2):168-171.
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ItemNo Preview AvailableHyponatraemia and hypopituitarism: an easily missed entity(Wiley, 2017-10)
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ItemNo Preview AvailableOutcomes of long-term surveillance of succinate dehydrogenase mutation carriers followed in a familial endocrine cancer clinic(Wiley, 2018-06)Background: Carriers of germline succinate dehydrogenase mutations (SDH) need life-long surveillance for the possible development of phaeochromocytomas and paragangliomas. However, there is no consensus about appropriate surveillance strategies. The aim of this study was to describe the long-term outcomes of a cohort of SDH carriers followed in our clinic. Method: 49 patients were included in this study, 12 were index cases (9 SDHB, 3 SDHD) and 37 were mutation-positive asymptomatic carriers (22 SDHB, 9 SDHD and 6 SDHC). Patients were followed for a mean of 4.4 years (range 1-10). All patients are recommended to undergo biennial MRI imaging of neck/thorax/abdomen/pelvis, annual clinic review and plasma or urine metanephrine testing. Results: 16 paragangliomas (10 SDHB, 6 SDHD) and 1 renal cell carcinoma (SDHB) and no phaeochromocytomas occurred in the 12 index cases (9 SDHB, 3 SDHD). Two index patients with paragangliomas (one abdominal, one head and neck) had widespread metastases on the initial scan. One SDHB and one SDHD index patient developed additional tumours during surveillance. Among the asymptomatic carriers, a total of 23 paragangliomas (22 SDHD and 1 SDHC) were detected in 8 (16%) patients (7 SDHD, 1 SDHC). Of these, 15 were detected on the first surveillance scan (14 SDHD, 1 SDHC) and 8 (all SDHD) were detected on subsequent scans. One patient (SDHD) developed a liver metastasis during surveillance. Of the seven SDHD carriers who had tumours on initial surveillance scan, six had the c.274G>T exon mutation. Average change in tumour size in those undergoing watchful surveillance was −0.12 mm/year (range −4 mm/year to +2 mm/year). Adherence was suboptimal, only 45% of patients attended annual clinic visits, 67% underwent biennial MRIs and 45% had yearly metanephrine testing. Conclusion: Biennial MRI scans appear to be an effective surveillance strategy in the long-term follow up of patients with SDH mutations.