Browse

You are looking at 31 - 38 of 38 items for :

  • Myasthaenia x
Clear All
Open access

Harish Venugopal, Katherine Griffin and Saima Amer

Summary

Resection of primary tumour is the management of choice in patients with ectopic ACTH syndrome. However, tumours may remain unidentified or occult in spite of extensive efforts at trying to locate them. This can, therefore, pose a major management issue as uncontrolled hypercortisolaemia can lead to life-threatening infections. We present the case of a 66-year-old gentleman with ectopic ACTH syndrome from an occult primary tumour with multiple significant complications from hypercortisolaemia. Ectopic nature of his ACTH-dependent Cushing's syndrome was confirmed by non-suppression with high-dose dexamethasone suppression test and bilateral inferior petrosal sinus sampling. The primary ectopic source remained unidentified in spite of extensive anatomical and functional imaging studies, including CT scans and Dotatate-PET scan. Medical adrenolytic treatment at maximum tolerated doses failed to control his hypercortisolaemia, which led to recurrent intra-abdominal and pelvic abscesses, requiring multiple surgical interventions. Laparoscopic bilateral adrenalectomy was considered but decided against given concerns of technical difficulties due to recurrent intra-abdominal infections and his moribund state. Eventually, alcohol ablation of adrenal glands by retrograde adrenal vein approach was attempted, which resulted in biochemical remission of Cushing's syndrome. Our case emphasizes the importance of aggressive management of hypercortisolaemia in order to reduce the associated morbidity and mortality and also demonstrates that techniques like percutaneous adrenal ablation using a retrograde venous approach may be extremely helpful in patients who are otherwise unable to undergo bilateral adrenalectomy.

Learning points

  • Evaluation and management of patients with ectopic ACTH syndrome from an unidentified primary tumour can be very challenging.

  • Persisting hypercortisolaemia in this setting can lead to debilitating and even life-threatening complications and hence needs to be managed aggressively.

  • Bilateral adrenalectomy should be considered when medical treatment is ineffective or poorly tolerated.

  • Percutaneous adrenal ablation may be considered in patients who are otherwise unable to undergo bilateral adrenalectomy.

Open access

G K Dimitriadis, K Gopalakrishnan, R Rao, D K Grammatopoulos, H S Randeva, M O Weickert and N Murthy

Summary

We report the case of a 70-year-old previously healthy female who presented acutely to the Accident and Emergency department with left-sided vasomotor symptoms including reduced muscle tone, weakness upon walking and slurred speech. Physical examination confirmed hemiparesis with VIIth nerve palsy and profound hepatomegaly. A random glucose was low at 1.7 mmol/l, which upon correction resolved her symptoms. In hindsight, the patient recalled having had similar episodes periodically over the past 3 months to which she did not give much attention. While hospitalized, she continued having episodes of symptomatic hypoglycaemia during most nights, requiring treatment with i.v. dextrose and/or glucagon. Blood tests including insulin and C-peptide were invariably suppressed, in correlation with low glucose. A Synacthen stimulation test was normal (Cort (0′) 390 nmol/l, Cort (30′) 773 nmol/l). A computed tomography scan showed multiple lobulated masses in the abdomen, liver and pelvis. An ultrasound guided biopsy of one of the pelvic masses was performed. Immunohistochemistry supported the diagnosis of a gastrointestinal stromal tumour (GIST) positive for CD34 and CD117. A diagnosis of a non islet cell tumour hypoglycaemia (NICTH) secondary to an IGF2 secreting GIST was confirmed with further biochemical investigations (IGF2=96.5 nmol/l; IGF2:IGF1 ratio 18.9, ULN <10). Treatment with growth hormone resolved the patient's hypoglycaemic symptoms and subsequent targeted therapy with Imatinib was successful in controlling disease progression over an 8-year observation period.

Learning points

  • NICTH can be a rare complication of GISTs that may manifest with severe hypoglycaemia and neuroglucopenic symptoms.

  • NICTH can masquerade as other pathologies thus causing diagnostic confusion.

  • Histological confirmation of GIST induced NICTH and exclusion of other conditions causing hypoglycaemia is essential.

  • Mutational analysis of GISTs should be carried out in all cases as it guides treatment decision.

  • Tailored management of hypoglycaemia, in this case using growth hormone and targeted cyto-reductive therapy, minimizes the risk of possible life-threatening complications.

Open access

Maria P Yavropoulou, Nikolina Gerothanasi, Athanasios Frydas, Evangelia Triantafyllou, Chris Poulios, Prodromos Hytiroglou, Panagiotis Apostolou, Ioannis Papasotiriou, Symeon Tournis, Isaak Kesisoglou and John G Yovos

Summary

Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome caused primarily by benign mesenchymal tumors. These tumors typically follow a benign clinical course and local recurrence occurs in <5% of cases. We investigated a 49-year-old man with a recurrent mesenchymal phosphaturic tumor showing no signs of malignancy. The patient suffered from chronic muscle weakness, myalgia and cramps. His medical record included the diagnosis of oncogenic osteomalacia, for which he was submitted to tumor resection in the left leg three times before. Laboratory examination showed hypophosphatemia, hyperphosphaturia and an elevated serum FGF23 level. A radical surgical approach (amputation) was advised, however, complete biochemical and clinical remission was not reached. Molecular analysis of the tumor cells demonstrated overexpression of growth factor receptors implicated in tumor angiogenesis and metastatic potential (platelet derived growth factor type A (PDGFRA), PDGFRB and vascular endothelial growth factor receptor) together with increased expression of FGF23, x-linked-phosphate-regulating endopeptidase and KLOTHO. TIO is usually associated with benign phosphauturic tumors and, when identified, resection of the tumor leads to complete remission in the majority of cases. The underlying pathophysiology of recurrences in these tumors is not known. This is the first report showing increased expression of growth factor receptors in a locally aggressive but histopathologically benign phosphaturic mesenchymal tumor.

Learning points

  • TIO is usually associated with benign soft tissue or bone neoplasms of mesenchymal origin.

  • These tumors typically follow a benign clinical course and even in the rare malignant cases local recurrence occurs in <5%.

  • Successful identification and removal of the tumor leads to full recovery in the majority of cases.

Open access

Annika Sjoeholm, Cassandra Li, Chaey Leem, Aiden Lee, Maria P Stack, Paul L Hofman and Benjamin J Wheeler

Summary

Phaeochromocytomas are a rare clinical entity, with dual hormone-secreting lesions particularly uncommon, seen in <1%. ACTH is the most common hormone co-produced, and is potentially lethal if not diagnosed. We present the case of a previously well 10-year-old boy, who presented acutely with a hypertensive crisis and was found to have a unilateral, non-syndromic phaeochromocytoma. Medical stabilization of his hypertension was challenging, and took 3 weeks to achieve, before proceeding to unilateral adrenalectomy. Post-operatively the child experienced severe fatigue and was subsequently confirmed to have adrenal insufficiency. He improved markedly with hydrocortisone replacement therapy, which is ongoing 6 months post-operatively. In retrospect this likely represents unrecognized, sub-clinical ACTH-dependent Cushing's syndrome secondary to an ACTH/or precursor dual-hormone secreting phaeochromocytoma. At follow-up, his hypertension had resolved, there was no biochemical evidence of recurrence of the phaeochromocytoma, and genetic analysis was indicative of a sporadic lesion.

Learning points

  • Dual hormone secreting phaeochromocytomas with ACTH/or a precursor may cause secondary adrenal insufficiency following surgical removal.

  • The concurrent features of Cushing's syndrome can be mild and easily overlooked presenting diagnostic and management pitfalls.

  • As concomitant syndromes of hormone excess are rare in phaeochromocytomas; the diagnosis requires a high index of suspicion.

  • Serial/diurnal cortisol levels, ACTH measurement +/− low dose dexamethasone suppression (when clinically stable, appropriate adrenergic blockade in place, and well supervised), can all be considered as needed.

Open access

Julien Ducry, Fulgencio Gomez, John O Prior, Ariane Boubaker, Maurice Matter, Matteo Monti, Yan Pu, Nelly Pitteloud and Luc Portmann

Summary

Ectopic ACTH Cushing's syndrome (EAS) is often caused by neuroendocrine tumors (NETs) of lungs, pancreas, thymus, and other less frequent locations. Localizing the source of ACTH can be challenging. A 64-year-old man presented with rapidly progressing fatigue, muscular weakness, and dyspnea. He was in poor condition and showed facial redness, proximal amyotrophy, and bruises. Laboratory disclosed hypokalemia, metabolic alkalosis, and markedly elevated ACTH and cortisol levels. Pituitary was normal on magnetic resonance imaging (MRI), and bilateral inferior petrosal sinus blood sampling with corticotropin-releasing hormone stimulation showed no significant central-to-periphery gradient of ACTH. Head and neck, thoracic and abdominal computerized tomography (CT), MRI, somatostatin receptor scintigraphy (SSRS), and 18F-deoxyglucose-positron emission tomography (FDG-PET) failed to identify the primary tumor. 18F-dihydroxyphenylalanine (F-DOPA)-PET/CT unveiled a 20-mm nodule in the jejunum and a metastatic lymph node. Segmental jejunum resection showed two adjacent NETs, measuring 2.0 and 0.5 cm with a peritoneal metastasis. The largest tumor expressed ACTH in 30% of cells. Following surgery, after a transient adrenal insufficiency, ACTH and cortisol levels returned to normal values and remain normal over a follow-up of 26 months. Small mid-gut NETs are difficult to localize on CT or MRI, and require metabolic imaging. Owing to low mitotic activity, NETs are generally poor candidates for FDG-PET, whereas SSRS shows poor sensitivity in EAS due to intrinsically low tumor concentration of type-2 somatostatin receptors (SST2) or to receptor down regulation by excess cortisol. However, F-DOPA-PET, which is related to amine precursor uptake by NETs, has been reported to have high positive predictive value for occult EAS despite low sensitivity, and constitutes a useful alternative to more conventional methods of tumor localization.

Learning points

  • Uncontrolled high cortisol levels in EAS can be lethal if untreated.

  • Surgical excision is the keystone of NETs treatment, thus tumor localization is crucial.

  • Most cases of EAS are caused by NETs, which are located mainly in the lungs. However, small gut NETs are elusive to conventional imaging and require metabolic imaging for detection.

  • FDG-PET, based on tumor high metabolic rate, may not detect NETs that have low mitotic activity. SSRS may also fail, due to absent or low concentration of SST2, which may be down regulated by excess cortisol.

  • F-DOPA-PET, based on amine-precursor uptake, can be a useful method to localize the occult source of ACTH in EAS when other methods have failed.

Open access

Manas Ghosh, Ambarish Bhattacharya, Kaushik Ghosh, Atri Chatterjee, Sisir Chakraborty and Sanat Kumar Jatua

Summary

Motor neuron disease (MND) is a progressive devastating neurodegenerative disease, which universally progresses towards death. Hence, every attempt should be made to find out if there are any treatable conditions, which can mimic MND. Herein, we describe a case of hypercalcaemia due to primary hyperparathyroidism confused as MND and subsequently cured with parathyroid surgery.

Learning points

  • Any patient with neurological disorder should have a screening of all the common electrolytes including calcium as electrolyte imbalance can present with paralysis (e.g. hypokalaemia) to amyotrophic lateral sclerosis (e.g. hypercalcaemia).

  • No patient should be stamped as having MND without having a proper work-up of all its differentials as there might be a treatable condition masquerading as MND.

Open access

M A W Hermans, B M L Stelten, H R Haak, W W de Herder and M W Dercksen

Summary

This paper reports on two patients with a long-standing diagnosis of an ENETS stage IV neuroendocrine tumour (NET) of the small intestine who developed neurological symptoms. The first patient only had bulbar symptoms and tested positive for acetylcholine receptor antibodies. The second patient had more classical symptoms of fatigable diplopia and muscle weakness of the legs, but no detectable antibodies. The diagnosis of paraneoplastical myasthenia gravis (MG) was postulated. Both patients were treated with pyridostigmine for MG and octreotide for the NETs. Interestingly, treatment of the NETs resulted in improvement of myasthenic symptoms. Paraneoplastic MG has been described to occur with certain malignancies, mainly thymoma. Herein, we prove that the association with gastrointestinal NETs, however, rare, is also one to be considered by clinicians dealing with either of these diseases. The pathogenesis has yet to be elucidated.

Learning points

  • NETs are rare malignancies with a wide variety of symptoms.

  • Paraneoplastic MG can occur with various types of malignancies.

  • Herein, we provide evidence of paraneoplastic MG in association with a grade IV NET of the small intestine.

  • Treatment of the NETs resulted in remission of myasthenic symptoms in one patient.

Open access

A Tabasum, C Shute, D Datta and L George

Summary

Hypokalaemia may present as muscle cramps and Cardiac arrhythmias. This is a condition commonly encountered by endocrinologists and general physicians alike. Herein, we report the case of a 43-year-old gentleman admitted with hypokalaemia, who following subsequent investigations was found to have Gitelman's syndrome (GS). This rare, inherited, autosomal recessive renal tubular disorder is associated with genetic mutations in the thiazide-sensitive sodium chloride co-transporter and magnesium channels in the distal convoluted tubule. Patients with GS typically presents at an older age, and a spectrum of clinical presentations exists, from being asymptomatic to predominant muscular symptoms. Clinical suspicion should be raised in those with hypokalaemic metabolic alkalosis associated with hypomagnesaemia. Treatment of GS consists of long-term potassium and magnesium salt replacement. In general, the long-term prognosis in terms of preserved renal function and life expectancy is excellent. Herein, we discuss the biochemical imbalance in the aetiology of GS, and the case report highlights the need for further investigations in patients with recurrent hypokalaemic episodes.

Learning points

  • Recurrent hypokalaemia with no obvious cause warrants investigation for hereditary renal tubulopathies.

  • GS is the most common inherited renal tubulopathy with a prevalence of 25 per million people.

  • GS typically presents at an older age and clinical suspicion should be raised in those with hypokalaemic metabolic alkalosis associated with hypomagnesaemia.

  • Confirmation of diagnosis is by molecular analysis for mutation in the SLC12A3 gene.