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University of Melbourne, Parkville, Victoria, Australia
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Summary
Acanthosis nigricans (AN) is a common dermatosis associated with hyperinsulinemia and insulin resistance. However, AN has been rarely reported in patients with insulinoma, a state of persistent hyperinsulinemia. We present a case of metastatic insulinoma, in whom AN manifested after the first cycle of peptide receptor radionuclide therapy (PRRT). A 40-year-old man was diagnosed with metastatic insulinoma after 5 months of symptomatic hypoglycemia. Within 1 month post PRRT, the patient became euglycemic but developed a pigmented, pruritic rash which was confirmed on biopsy as AN. We discuss the rare manifestation of AN in subjects with insulinoma, the role of insulin in the pathogenesis of AN, malignant AN in non-insulin-secreting malignancies and association with other insulin-resistant endocrinopathies such as acromegaly.
Learning points
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Acanthosis nigricans (AN) is a common dermatosis which is typically asymptomatic and associated with the hyperinsulinemic state.
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Malignant AN can rapidly spread, cause pruritus and affect mucosa and the oral cavity.
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AN is extremely rare in patients with insulinoma despite marked hyperinsulinemia.
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Peptide receptor radionuclide therapy might have triggered TGF-α secretion in this subject which led to malignant AN.
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Rapid spread or unusual distribution of pruritic AN warrants further investigation to exclude underlying malignancy.
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Department of Medicine, Macquarie University, Sydney, Australia
Department of Medicine, University of Western Sydney, Sydney, Australia
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Summary
Thyrotoxic periodic paralysis (TPP) is a rare condition characterised by acute onset hypokalaemia and paralysis which most commonly affects men of Asian descent between the ages of 20 and 40 years (1, 2). It has been reported in approximately 2% of patients with thyrotoxicosis in China and Japan (1, 2, 3). Hypokalaemia in TPP results from a massive intracellular shift of potassium induced by the thyroid hormone sensitisation of Na+/K+-ATPase (4). Treatment of TPP includes prevention of this shift by using beta-blockade, rapid potassium replacement and treatment of the underlying hyperthyroidism. We present two cases of TPP with differing outcomes. In the first case, a 33-year-old Filipino gentleman presented to our emergency department (ED) with a 3-month history of recurrent proximal lower limb weakness. Serum potassium was 2.2 mmol/L (3.3–5.1) and he was given i.v. potassium replacement. Thyroid function tests (TFTs) and thyroid antibodies were consistent with Graves thyrotoxicosis. He was discharged home on carbimazole and remains well controlled on long-term medical therapy. In the second case, a 22-year-old Malaysian gentleman presented to our ED with new-onset bilateral lower limb painless paralysis. Serum potassium was 1.9 mmol/L with TFTs demonstrating Graves thyrotoxicosis. He was treated with i.v. potassium replacement and discharged home on carbimazole and propranolol. He represented to the hospital on two further occasions with TPP and was advised to consider total thyroidectomy given his refractory Graves’ disease. These cases highlight the importance of prompt recognition of this rare life-threatening complication of Graves’ disease, especially in patients of Asian descent.
Learning points
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Thyrotoxic periodic paralysis is a rare condition characterised by hypokalaemia and acute painless muscle weakness in the presence of thyrotoxicosis.
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The signs and symptoms of thyrotoxicosis can be subtle in these patients.
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It is most commonly seen in Asian males between the ages of 20 and 40 and is most frequently caused by Graves’ disease.
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Prompt recognition is essential as it is a life-threatening condition.
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Urgent i.v. potassium replacement and beta-blockade with a non-selective beta-blocker are the mainstays of treatment.
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i.v. potassium replacement should not be given in dextrose as this can potentiate hypokalaemia.
Search for other papers by Ray Wang in
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Sir Peter MacCallum Department of Oncology, The University of Melbourne, Victoria, Australia
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Sir Peter MacCallum Department of Oncology, The University of Melbourne, Victoria, Australia
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Sir Peter MacCallum Department of Oncology, The University of Melbourne, Victoria, Australia
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Search for other papers by Nirupa Sachithanandan in
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Summary
Adrenocortical carcinoma is a rare disease with poor prognosis whose clinical heterogeneity can at times present a challenge to accurate and timely diagnosis. We present the case of a patient who presented with extensive pulmonary lesions, mediastinal and hilar lymphadenopathy and an adrenal mass in whom the oncological diagnosis was initially uncertain. Through the use of immunohistochemistry, biochemistry and genomic testing, an accurate diagnosis of adrenocortical carcinoma was ultimately made which resulted in more directed treatment being administered. The use of multidisciplinary input and genomics to aid in diagnosis and prognosis of adrenocortical carcinoma is discussed.
Learning points
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Adrenocortical carcinomas can present a diagnostic challenge to clinicians given it is a rare malignancy with significant clinical heterogeneity.
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Specialist multidisciplinary team input is vital in the diagnosis and management of adrenocortical carcinomas.
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Hormonal testing is recommended in the diagnostic workup of adrenal masses, even in the absence of overt clinical signs/symptoms of hormone excess.
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Immunostaining for the highly sensitive and specific steroidogenic factor-1 is vital for accurate diagnosis.
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Genomics can provide prognostic utility in management of adrenocortical carcinoma.
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School of Medicine and Public Health, University of Newcastle, Newcastle, New South Wales, Australia
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Surgical Services, John Hunter Hospital, Newcastle, New South Wales, Australia
University of Newcastle, Newcastle, New South Wales, Australia
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Department of Endocrinology, John Hunter Hospital, Newcastle, New South Wales, Australia
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Summary
We report concurrent metastatic prostatic adenocarcinoma (PC) and functioning androgen-secreting adrenocortical carcinoma (ACC) in a 77-year-old man. The failure to achieve adequate biochemical castration via androgen deprivation therapy (ADT) as treatment for PC metastases, together with elevated DHEA-S, androstenedione, and discordant adrenal tracer uptake on FDG-PET and PSMA-PET, suggested the presence of a concurrent functional primary adrenal malignancy. On histopathological analysis, scant foci of PC were present throughout the ACC specimen. Castration was achieved post adrenalectomy with concurrent drop in prostate-specific antigen. We outline the literature regarding failure of testosterone suppression on ADT and salient points regarding diagnostic workup of functioning adrenal malignancies.
Learning points
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Failure to achieve castration with androgen deprivation therapy is rare and should prompt careful review to identify the underlying cause.
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All adrenal lesions should be evaluated for hormone production, as well as assessed for risk of malignancy (either primary or secondary).
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Adrenocortical carcinomas are commonly functional, and can secrete steroid hormones or their precursors (androgens, progestogens, glucocorticoids and mineralocorticoids).
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In this case, a co-incident, androgen-producing adrenocortical carcinoma was the cause of failure of testosterone suppression from androgen deprivation therapy as treatment for metastatic prostate cancer. Pathological adrenal androgen production contributed to the progression of prostate cancer.
Department of Medicine, Austin Health, The University of Melbourne, Heidelberg, Victoria, Australia
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Department of Medicine, Monash University, Victoria, Australia
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Department of Medicine, Austin Health, The University of Melbourne, Heidelberg, Victoria, Australia
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Summary
Primary aldosteronism is one of the most common (affecting up to 10%) yet treatable causes of hypertension in our community, notable due to an associated elevated risk of atrial fibrillation, stroke and myocardial infarction compared to essential hypertension. Guidelines have focussed on improving case detection due to significant underdiagnosis in the community. While our case experienced significant delay in diagnosis, we highlight a state of protracted, persistent post-operative hypoaldosteronism which manifested with severe hyponatraemia and hyperkalaemia, necessitating long-term mineralocorticoid replacement. We discuss whether pre-operative mineralocorticoid receptor antagonists to stimulate aldosterone secretion from the contralateral gland may have prevented this complication.
Learning points
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Hypoaldosteronism is an uncommon complication of adrenalectomy for primary aldosteronism, typically manifesting with hyperkalaemia and hyponatraemia. While most cases are transient, it may be persistent, necessitating ongoing mineralocorticoid replacement.
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Routine electrolyte monitoring is recommended post-adrenalectomy.
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Risk factors for hypoaldosteronism include age >50 years, duration of hypertension >10 years, pre-existing renal impairment and adrenal adenoma size >2 cm.
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Mineralocorticoid receptor antagonists may assist in the management of hypokalaemia and hypertension pre-operatively. However, it is unclear whether this reduces the risk of post-operative hypoaldosteronism.
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Monash Centre for Health Research and Implementation, School of Public Health and Preventive Medicine, Monash University, Victoria, Australia
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Department of Endocrinology, Monash Health, Victoria, Australia
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Department of Endocrinology, Monash Health, Victoria, Australia
Department of Medicine, School of Clinical Sciences, Monash University, Victoria, Australia
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Monash Centre for Health Research and Implementation, School of Public Health and Preventive Medicine, Monash University, Victoria, Australia
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Summary
Insulin autoimmune syndrome (IAS) is a rare cause of non-islet cell hypoglycaemia. Treatment of this condition is complex and typically involves long-term use of glucocorticoids. Immunotherapy may provide an alternative in the management of this autoimmune condition through the suppression of antibodies production by B-lymphocyte depletion. We present a case of a 62-year-old male, with refractory hypoglycaemia initially presenting with hypoglycaemic seizure during an admission for acute psychosis. Biochemical testing revealed hypoglycaemia with an inappropriately elevated insulin and C-peptide level and no evidence of exogenous use of insulin or sulphonylurea. Polyethylene glycol precipitation demonstrated persistently elevated free insulin levels. This was accompanied by markedly elevated anti-insulin antibody (IA) titres. Imaging included CT with contrast, MRI, pancreatic endoscopic ultrasound and Ga 68-DOTATATE position emission tomography (DOTATATE PET) scan did not reveal islet cell aetiology for hyperinsulinaemia. Maintenance of euglycaemia was dependent on oral steroids and dextrose infusion. Complete resolution of hypoglycaemia and dependence on glucose and steroids was only achieved following treatment with plasma exchange and rituximab.
Learning points
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Insulin autoimmune syndrome (IAS) should be considered in patients with recurrent hyperinsulinaemic hypoglycaemia in whom exogenous insulin administration and islet cell pathologies have been excluded.
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Biochemical techniques play an essential role in establishing high insulin concentration, insulin antibody titres, and eliminating biochemical interference. High insulin antibody concentration can lead to inappropriately elevated serum insulin levels leading to hypoglycaemia.
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Plasma exchange and B-lymphocyte depletion with rituximab and immunosuppression with high dose glucocorticoids are effective in reducing serum insulin levels and hypoglycaemia in insulin autoimmune syndrome (IAS).
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Based on our observation, the reduction in serum insulin level may be a better indicator of treatment efficacy compared to anti-insulin antibody (IA) titre as it demonstrated greater correlation to the frequency of hypoglycaemia and to hypoglycaemia resolution.
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Faculty of Health and Medicine, Institute of Health and Biomedical Innovation, Queensland University of Technology, University of Queensland, Queensland, Australia
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Summary
Although pituitary macroadenomas often cause mass effects on surrounding structures, it is extremely rare for pituitary lesions to disturb cerebrospinal fluid circulation. Sellar gangliocytoma-pituitary adenomas (SGPAs) are also extremely rare. Here we report the unique case of a man with the unusual combination of acromegaly from an SGPA, who presented with unilateral hydrocephalus. A 60-year-old man presented with rapid neurological deterioration, bitemporal hemianopia, and acromegalic features. Neuroimaging revealed a large sellar lesion extending superiorly into the left foramen of Monro, causing acute obstructive unilateral hydrocephalus. External ventricular drain placement improved consciousness immediately. Biochemical assessment confirmed acromegaly. Following trans-sphenoidal debulking, histology revealed a mixed gangliocytoma/sparsely-granulated somatotrophinoma. Despite the residual disease, his vision recovered remarkably, low-dose cabergoline controlled residual excess growth hormone (GH) secretion, and the residual tumour has remained extremely stable over 2 years. Hydrocephalus is an extremely rare complication of pituitary lesions, and unilateral hydrocephalus has never been reported previously. GH secretion in SGPAs is more common than for pituitary adenomas in general, raising questions regarding the aetiology and therapeutic approach to this rare combination tumour.
Learning points
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Pituitary tumours most commonly present with symptoms related to endocrine disturbance or mass effects upon visual pathways (e.g. optic chiasm, nerves in the lateral cavernous sinus). However, extremely rarely, pituitary masses may disrupt cerebrospinal fluid (CSF) circulation resulting in hydrocephalus.
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Sellar gangliocytomas are very rare tumours and most of them are hybrid tumours with pituitary adenomas (SGPAs).
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SGPAs are typically indolent and may be functioning or non-functioning tumours.
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Growth hormone (GH)-producing SGPAs are less likely to respond to somatostatin agonists than classic somatotrophinomas.
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Primary surgical debulking via a trans-sphenoidal approach was effective in this individual, leading to the restoration of CSF circulation and improvement in visual disturbance, while also negating the need for permanent CSF diversion despite the residual tumour burden.
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Adelaide Medical School, University of Adelaide, Adelaide, South Australia, Australia
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Summary
Succinate dehydrogenase deficiency has been associated with several neoplasias, including renal cell carcinoma (RCC) and those associated with hereditary paraganglioma (PGL)/ pheochromocytoma (PHEO) syndromes, Carney dyad, and Carney triad. Carney triad is a rare multitumoral syndrome characterized by co-existing PGL, gastrointestinal stromal tumor (GIST), and pulmonary chondroma (CHO). We report a case of a 57-year-old male who presented with para-aortic and gastroesophogeal masses, and a right renal superior pole lesion, which were classified as multiple PGLs, a GIST, and a clear cell renal carcinoma, respectively, on pathology following surgical resection. Additionally, a CHO was diagnosed radiologically, although no biopsy was performed. A diagnosis of Carney triad was made. SDHB immunohistochemical staining was negative for the PGL and the GIST, indicating SDH-deficiency. Interestingly, the renal cell carcinoma (RCC) stained positive for both SDHB and SDHA. Subsequent genetic screening of SDH subunit genes revealed a germline inactivating heterozygous SDHA pathogenic variant (c.91 C>T, p.R31X). Loss of heterozygosity was not detected at the tumor level for the RCC, which likely indicated the SDHA variant would not be causative of the RCC, but could still predispose to the development of neoplasias. To the knowledge of the authors this is the first reported case of an SDHA pathogenic variant in a patient with Carney triad complicated by RCC.
Learning points
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The succinate dehydrogenase enzyme is encoded by four subunit genes (SDHA, SDHB, SDHC, and SDHD; collectively referred to as SDHx), which have been implicated in several neoplasias and are classified as tumor suppressor genes.
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Carney triad is a rare multiple-neoplasia syndrome presenting as an association of PGLs, GISTs, and CHOs.
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Carney triad is most commonly associated with hypermethylation of SDHC as demonstrated in tumor tissue, but approximately 10% of cases are due to pathogenic SDHx variants.
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Although SDHB pathogenic variants are most commonly reported in SDH-deficient renal cell carcinoma, SDHA disease-causing variants have been reported in rare cases.
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Monash University, Central Clinical School, Melbourne, Victoria, Australia
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Monash University, Central Clinical School, Melbourne, Victoria, Australia
Department of Endocrinology and Diabetes, Western Health, Melbourne, Victoria, Australia
Department of Medicine, Western Clinical School, The University of Melbourne, Melbourne, Victoria, Australia
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Summary
Despite improvements in localisation techniques and surgical advances, some patients with insulinoma will not be cured by surgery or may not be suitable for surgery. Medical management with diazoxide is an option for such cases. This case report details 27 years of successful management of insulinoma using diazoxide. It has been effective and safe, with only minor adverse effects.
Learning points:
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Long term diazoxide use can be a safe, effective option for insulinoma when it cannot be localised or removed surgically.
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Common adverse effects include peripheral oedema, hyperuricaemia, and hirsutism.
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68Ga-NOTA-exendin-4 PET/CT scan should be considered for insulinoma localisation when other modalities have been unhelpful.
University of Queensland, Herston, Queensland, Australia
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University of Queensland, Herston, Queensland, Australia
Pathology Queensland, Australia
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Griffith University, Southport, Queensland, Australia
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Summary
Distinguishing primary hyperparathyroidism (PHPT) from familial hypocalciuric hypercalcaemia (FHH) can be challenging. Currently, 24-h urinary calcium is used to differentiate between the two conditions in vitamin D replete patients, with urinary calcium creatinine clearance ratio (UCCR) <0.01 suggestive of FHH and >0.02 supportive of PHPT. A 26-year-old Caucasian gentleman presented with recurrent mild hypercalcaemia and inappropriately normal parathyroid hormone (PTH) following previous parathyroidectomy 3 years prior. He had symptoms of fatigue and light-headedness. He did not have any other symptoms of hypercalcaemia. His previous evaluation appeared to be consistent with PHPT as evidenced by hypercalcaemia with inappropriately normal PTH and UCCR of 0.0118 (borderline low using guidelines of >0.01 consistent with PHPT). He underwent parathyroidectomy and three parathyroid glands were removed. His calcium briefly normalised after surgery, but rose again to pre-surgery levels within 3 months. Subsequently, he presented to our centre and repeated investigations showed 24-h urinary calcium of 4.6 mmol/day and UCCR of 0.0081 which prompted assessment for FHH. His calcium-sensing receptor (CASR) gene was sequenced and a rare inactivating variant was detected. This variant was described once previously in the literature. His mother was also confirmed to have mild hypercalcaemia with hypocalciuria and, on further enquiry, had the same CASR variant. The CASR variant was classified as likely pathogenic and is consistent with the diagnosis of FHH. This case highlights the challenges in differentiating FHH from PHPT. Accurate diagnosis is vital to prevent unnecessary surgical intervention in the FHH population and is not always straightforward.
Learning points:
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Distinguishing FHH from PHPT with co-existing vitamin D deficiency is difficult as this can mimic FHH. Therefore, ensure patients are vitamin D replete prior to performing 24-h urinary calcium collection.
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Individuals with borderline UCCR could have either FHH or PHPT. Consider performing CASR gene sequencing for UCCR between 0.01 and 0.02.
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Parathyroid imaging is not required for making the diagnosis of PHPT. It is performed when surgery is considered after confirming the diagnosis of PHPT.
