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Open access

N Ayub, A J A T Braat, H J L M Timmers, M G E H Lam, and R S van Leeuwaarde

Summary

Von Hippel–Lindau’s disease (VHL) is a hereditary tumor syndrome characterized by its prototype lesions, hemangioblastomas, and renal cell carcinomas. Treatment for renal cell carcinomas can ultimately result in long-term dialysis. Pancreatic neuroendocrine tumors (pNET) can also occur in the course of the disease. Currently, peptide receptor radionuclide therapy (PRRT) is the standard treatment for progressive neuroendocrine tumors. However, little is known about treatment with PRRT in patients on dialysis, an infrequent presentation in patients with VHL. We present a 72-year-old man with VHL on hemodialysis and a progressive pNET. He received four cycles of PRRT with a reduced dose. Only mild thrombopenia was seen during treatments. The patient died 9 months after the last PRRT because of acute bleeding in a hemangioblastoma. Hemodialysis is not a limiting factor for PRRT treatment and it should be considered as it seems a safe short-term treatment option for this specific group.

Learning points

  • Von Hippel–Lindau disease (VHL) is a complex disease in which former interventions can limit optimal treatment for following VHL-related tumors later in life.

  • Metastasized pancreatic neuroendocrine tumors occur as part of VHL disease.

  • Peptide receptor radionuclide therapy seems a safe short-term treatment option in patients on hemodialysis.

Open access

Nikitas S Skarakis, Irene Papadimitriou, Labrini Papanastasiou, Sofia Pappa, Anastasia Dimitriadi, Ioannis Glykas, Konstantinos Ntoumas, Penelope Lampropoulou, and Theodora Kounadi

Summary

Juxtaglomerular cell tumour (JGCT) is an unusually encountered clinical entity. A 33-year-old man with severe long-standing hypertension and hypokalaemia is described. The patient also suffered from polyuria, polydipsia, nocturia and severe headaches. On admission, laboratory investigation revealed hypokalaemia, kaliuresis, high aldosterone and renin levels, and the abdomen CT identified a mass of 4 cm at the right kidney. Kidney function was normal. Following nephrectomy, the histological investigation revealed the presence of a JGCT. Immunostaining was positive for CD34 as well as for smooth muscle actin and vimentin. Following surgery, a marked control of his hypertension with calcium channel blockers and normalization of the serum potassium, renin or aldosterone levels were reached. According to our findings, JGCT could be included in the differential diagnosis of secondary hypertension as it consists of a curable cause. The association of JGCT with hypertension and hypokalaemia focusing on the clinical presentation, diagnostic evaluation and management is herein discussed and a brief review of the existing literature is provided.

Learning points

  • Juxtaglomerular cell tumours (JGCT), despite their rarity, should be included in the differential diagnosis of secondary hypertension as they consist of a curable cause of hypertension.

  • JGCT could be presented with resistant hypertension along with hypokalaemia, kaliuresis and metabolic alkalosis. Early recognition and management can help to prevent cardiovascular complications.

  • Imaging (enhanced CT scans) may be considered as the primary diagnostic tool for the detection of renal or JGCT.

  • For the confirmation of the diagnosis, a histopathologic examination is needed.

Open access

Clare E Bonnar, John F Brazil, Julie O Okiro, Louise Giblin, Yvonne Smyth, Paula M O’Shea, and Francis M Finucane

Summary

A 32-year-old Caucasian male presented to the emergency department with a one-day history of acute severe bilateral lower limb weakness, three days after competing in a bodybuilding competition. He consumed large quantities of carbohydrate-rich foods following the competition. His past medical history was significant for anxiety, and family history was non-contributory. Examination was normal except for reduced power and hyporeflexia in both legs, despite his muscular physique. He was noted to have severe hypokalaemia (K+= 1.9 mmol/L). His thyroid function tests were consistent with thyrotoxicosis. He reported taking thyroxine and several other agents to facilitate muscle mass generation before the bodybuilding competition. His presentation was reminiscent of thyrotoxic periodic paralysis, albeit uncommon with Caucasian ethnicity. He also had transient hyperglycaemia at presentation with concomitant hyperinsulinaemia, which could be attributed to the carbohydrate load and may have exacerbated his hypokalaemia through a transcellular shift. Urine toxicology screen subsequently ruled out the use of diuretics but confirmed the presence of a long-acting beta agonist (clenbuterol) which, along with other substances, may have aggravated the hypokalaemia further. After 12 h of i.v. replacement, the potassium level normalised and leg weakness resolved. The patient agreed to stop taking thyroxine and beta agonists and was well during the clinic visit at one month follow-up. This case highlights the potential for thyrotoxicosis factitia to exacerbate hypokalaemia and muscle weakness from other causes in bodybuilders presenting with acute severe weakness, irrespective of ethnicity.

Learning points

  • In patients presenting with muscle weakness and hypokalaemia, early consideration of thyrotoxicosis is essential, even in the absence of a past history of thyroid disease or specific symptoms of thyrotoxicosis, in order to allow prompt initiation of appropriate treatment and to prevent recurrence.

  • Bodybuilders may constitute a uniquely ‘at-risk’ group for thyrotoxic periodic paralysis secondary to thyrotoxicosis factitia, especially where there is concomitant use of beta-adrenergic agonists, even in the absence of diuretic use.

  • Although rare and usually described in patients of Asian or Polynesian ethnicity, this case highlights that thyrotoxic periodic paralysis secondary to thyrotoxicosis factitia can also occur in patients with Caucasian ethnicity.

  • We speculate that consuming large quantities of carbohydrates may induce hyperinsulinaemia, which could theoretically contribute to worse hypokalaemia, though mechanistic studies would be needed to explore this further.

Open access

Lachlan M Angus, Jun Yang, and Ada S Cheung

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

  • 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.

  • Routine electrolyte monitoring is recommended post-adrenalectomy.

  • Risk factors for hypoaldosteronism include age >50 years, duration of hypertension >10 years, pre-existing renal impairment and adrenal adenoma size >2 cm.

  • 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.

Open access

Darija Tudor, Iva Kolombo, Ana Tot, Drasko Cikojevic, Marko Simunovic, and Veselin Skrabic

Summary

This is a case report of a child with chronic hyponatremia due to the syndrome of inappropriate antidiuretic hormone secretion (SIADH) as a paraneoplastic manifestation of olfactory neuroblastoma (OFN). We hereby report a clinical presentation as well as a pragmatic approach to one of the most common electrolytic disorders in the pediatric population and have emphasized the necessity of involving the sinonasal area in the diagnostic procedure while evaluating possible causes of SIADH. This report indicates that the chronicity of the process along with the gradual onset of hyponatremia occurrence is responsible for the lack of neurological symptoms at the moment of disease presentation.

Learning points

  • Hyponatremia is not infrequently attributed to SIADH.

  • Paraneoplastic syndromes are uncommon but they should be considered in the differential diagnosis of pediatric SIADH.

  • Chronic insidious hyponatremia may not be associated with clear neurological symptoms despite its severity.

Open access

Ryizan Nizar, Nathan W P Cantley, and Jonathan C Y Tang

Summary

A 33-year-old gentleman of Egyptian heritage presented with a 21 years history of unexplained and recurrent hypercalcaemia, nephrolithiasis, nephrocalcinosis, and myocarditis. A similar history was also found in two first-degree relatives. Further investigation into the vitamin D metabolism pathway identified the biochemical hallmarks of infantile hypercalcaemia type 1 (IIH). A homozygous, likely pathogenic, variant in CYP24A1 was found on molecular genetic analysis confirming the diagnosis. Management now focuses on removing excess vitamin D from the metabolic pathway as well as reducing calcium intake to achieve serum-adjusted calcium to the middle of the reference range. If undiagnosed, IIH can cause serious renal complications and metabolic bone disease.

Learning points

  • Infantile hypercalcaemia type 1 (IIH) is an autosomal recessive disorder characterised by homozygous mutations in the CYP24A1 gene that encodes the 24-hydroxylase enzyme used to convert active vitamin D metabolites such as 1,25-(OH)2-vitamin D into their inactive form.

  • IIH should be questioned in individuals presenting with a history of unexplained hypercalcaemia, especially if presenting from childhood and/or where there is an accompanying family history of the same in first and/or second degree relatives, causing complications such as nephrocalcinosis, pericarditis, and calcium-based nephrolithiasis.

  • Associated biochemistry of IIH is persistent mild to moderate hypercalcaemia, normal or raised 25-(OH)-vitamin D and elevated 1,25-(OH)2-vitamin D. An elevated ratio of 25-(OH)-vitamin D to 24,25-(OH)2-vitamin D can be a useful marker of defects in the 24-hydroxylase enzyme, whose measurement can be facilitated through the supra-regional assay service.

  • Management should focus on limiting the amount of vitamin D introduced into the body either via sunlight exposure or supplementation in addition to calcium dietary restriction to try and maintain appropriate calcium homeostasis

Open access

Ayesha Ghayur, Qurrat Elahi, Chinmay Patel, and Rishi Raj

Summary

Hypothyroidism is a common medical condition and is often easily managed with excellent outcomes, when treated adequately. Compliance with levothyroxine (LT4) therapy is often compromised because of the need for a daily and lasting schedule. Overt rhabdomyolysis due to under-treatment or non-compliance is a rare occurrence. We report a case of rhabdomyolysis leading to acute kidney injury (AKI) on chronic kidney disease (CKD) requiring hemodialysis (HD) in a 68-year-old Caucasian male due to non-compliance with levothyroxine (LT4) therapy. Our patient 'ran out of levothyroxine' for approximately 4 weeks and developed gradually progressive muscle pain. The diagnosis of severe AKI due to rhabdomyolysis was made based on oliguria, elevated creatinine kinase (CK), and renal failure. Resuming the home dose of LT4 failed to correct CK levels, and there was a progressive decline in renal function. Although increasing doses of LT4 and three cycles of HD improved CK levels, they remained above baseline at the time of discharge. The patient recovered gradually and required HD for 4 weeks. CK levels normalized at 6 weeks. Through this case report, we highlight that non-compliance with LT4 therapy can lead to life-threatening complications such as renal failure and hence the need to educate patients on the significance of compliance with LT4 therapy should be addressed.

Learning points

  • Non-compliance to levothyroxine therapy is common and can lead to serious complications, including rhabdomyolysis.

  • Rhabdomyolysis is an uncommon presentation of hypothyroidism and severe rhabdomyolysis can result in renal failure requiring hemodialysis.

  • Rhabdomyolysis associated with hypothyroidism can be further exacerbated by concomitant use of statins.

Open access

Rachel Wurth, Abhishek Jha, Crystal Kamilaris, Anthony J Gill, Nicola Poplawski, Paraskevi Xekouki, Martha M Quezado, Karel Pacak, Constantine A Stratakis, and Fady Hannah-Shmouni

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

  • 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.

  • Carney triad is a rare multiple-neoplasia syndrome presenting as an association of PGLs, GISTs, and CHOs.

  • 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.

  • Although SDHB pathogenic variants are most commonly reported in SDH-deficient renal cell carcinoma, SDHA disease-causing variants have been reported in rare cases.

Open access

Ana M Lopes and Sofia Teixeira

Summary

Molecular alterations of the transcription factor hepatocyte nuclear factor 1B (HNF1B) are associated with systemic disease, with kidney disease and maturity-onset diabetes of the young (MODY) as the most characteristic manifestations. Other features comprise pancreatic exocrine insufficiency, liver and biliary anomalies, and genital tract malformations. HNF1B-associated disease is clinically heterogeneous, and therefore the diagnosis is challenging. The authors describe the case of a 19-year-old man with new-onset diabetes after kidney transplantation (NODAT). The kidney disease presented during fetal life as bilateral hyperechogenic kidneys. Renal function progressively deteriorated during childhood, and at the age of 19, the patient was submitted to a living-kidney transplant. Two weeks after transplant, NODAT developed. Given the young age and normal body weight, NODAT was unexpected, and the possibility of HNF1B-associated disease was considered. Screening for mutations in HNF1B was undertaken, and a known mutation was found. As this case highlights, HNF1B-associated disease should be considered when NODAT unexpectedly develops in young kidney transplant recipients with a suggestive renal disease.

Learning points:

  • HNF1B anomalies are associated with systemic disease, including kidney disease, diabetes mellitus, pancreatic exocrine insufficiency, liver test abnormalities and genital tract malformations.

  • Phenotype is variable and there are no pathognomonic manifestations, but kidney disease appears to be the most common feature and diabetes the most frequent extra-renal phenotype.

  • Spontaneous gene alterations are common, and the lack of family history should not exclude the diagnosis.

  • HNF1B defects should be considered when NODAT develops in a young adult kidney transplant recipient with a suggestive kidney disease and without extensive risk factors for diabetes.

  • The most appropriate treatment for HNF1B-associated diabetes is not established, but immunosuppressive therapy superimposed on a beta-cell dysfunction seems to determine the need for insulin therapy after a variable period.

  • Immunosupressive regimens free of calcineurin inhibitors should be considered in patients with HNF1B-associated disease to minimize the risk of developing NODAT.

Open access

Ravikumar Ravindran, Justyna Witczak, Suhani Bahl, Lakdasa D K E Premawardhana, and Mohamed Adlan

Summary

A 53-year-old man who used growth hormone (GH), anabolic steroids and testosterone (T) for over 20 years presented with severe constipation and hypercalcaemia. He had benign prostatic hyperplasia and renal stones but no significant family history. Investigations showed – (1) corrected calcium (reference range) 3.66 mmol/L (2.2–2.6), phosphate 1.39 mmol/L (0.80–1.50), and PTH 2 pmol/L (1.6–7.2); (2) urea 21.9 mmol/L (2.5–7.8), creatinine 319 mmol/L (58–110), eGFR 18 mL/min (>90), and urine analysis (protein 4+, glucose 4+, red cells 2+); (3) creatine kinase 7952 U/L (40–320), positive anti Jo-1, and Ro-52 antibodies; (4) vitamin D 46 nmol/L (30–50), vitamin D3 29 pmol/L (55–139), vitamin A 4.65 mmol/L (1.10–2.60), and normal protein electrophoresis; (5) normal CT thorax, abdomen and pelvis and MRI of muscles showed ‘inflammation’, myositis and calcification; (6) biopsy of thigh muscles showed active myositis, chronic myopathic changes and mineral deposition and of the kidneys showed positive CD3 and CD45, focal segmental glomerulosclerosis and hypercalcaemic tubular changes; and (7) echocardiography showed left ventricular hypertrophy (likely medications and myositis contributing), aortic stenosis and an ejection fraction of 44%, and MRI confirmed these with possible right coronary artery disease. Hypercalcaemia was possibly multifactorial – (1) calcium release following myositis, rhabdomyolysis and acute kidney injury; (2) possible primary hyperparathyroidism (a low but detectable PTH); and (3) hypervitaminosis A. He was hydrated and given pamidronate, mycophenolate and prednisolone. Following initial biochemical and clinical improvement, he had multiple subsequent admissions for hypercalcaemia and renal deterioration. He continued taking GH and T despite counselling but died suddenly of a myocardial infarction.

Learning points:

  • The differential diagnosis of hypercalcaemia is sometimes a challenge.

  • Diagnosis may require multidisciplinary expertise and multiple and invasive investigations.

  • There may be several disparate causes for hypercalcaemia, although one usually predominates.

  • Maintaining ‘body image’ even with the use of harmful drugs may be an overpowering emotion despite counselling about their dangers.