Browse

You are looking at 1 - 10 of 37 items for :

  • Refine by Access: All content x
Clear All
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

Paweena Chunharojrith, Kanapon Pradniwat, and Tanawan Kongmalai

Summary

Ectopic adrenocorticotropic hormone (ACTH) secretion is responsible for 5–15% of Cushing’s syndrome (CS). Neuroendocrine tumor (NET) is a common cause of ectopic ACTH syndrome (EAS). However, primary renal NET is exceedingly rare. Fewer than 100 cases have been reported and only a few cases presented with CS. Because of its rarity and lack of long-term follow-up data, clinical manifestations, biological behavior and prognosis are not well understood. Here, we report the case of a 51-year-old man who presented with clinical and laboratory findings compatible with EAS. CT scan revealed a lesion of uncertain nature at the lower pole of the left kidney. Octreotide scan found a filling defect at the lower pole of left kidney. It was difficult to determine if this finding was the true etiology or an incidental finding. Unfortunately, the patient’s clinical status rapidly deteriorated with limited medical treatment. The patient underwent left nephrectomy and left adrenalectomy. Histopathological examination confirmed NET with oncocytic features. Immunohistochemistry staining was positive for ACTH. The patient’s condition gradually improved. Additionally, glucocorticoid replacement was required only 6 months during a gradual recovery of hypothalamic pituitary adrenal axis achieved approximately three years after tumor removal. Although extremely rare, primary renal NET should be considered as a cause of EAS particularly in a patient with rapid clinical deterioration. Thorough investigation, early diagnosis and careful management are crucial to reduce morbidity and mortality.

Learning points

  • Primary renal NET is an extremely rare cause of ectopic ACTH syndrome.

  • Ectopic ACTH syndrome has a rapid onset with severe clinical manifestations. In this case, the patient’s condition deteriorated rapidly, resulting from severe hypercortisolism. Resection of the tumor is the most effective treatment.

  • Localization of ectopic ACTH-secreting tumors is very challenging. Multimodality imaging including CT, MRI, octreotide scan, and positron emission tomography plays a crucial role in identifying the tumors. However, each imaging modality has limitations.

Open access

Katsuo Tao, Midori Awazu, Misa Honda, Hironori Shibata, Takayasu Mori, Shinichi Uchida, Tomonobu Hasegawa, and Tomohiro Ishii

Summary

We report a male infant with congenital nephrogenic diabetes insipidus (NDI) who presented with hypercalcemia and hyperphosphatemia since birth. Serum sodium started to increase at 39 days. Although there was no polyuria, urine osmolality was 71 mOsm/kg, when serum osmolality was 296 mOsm/kg with plasma arginine vasopressin 22.5 pg/mL. He was thus diagnosed as NDI. An undetectable level of urine calcium and unsuppressed intact parathyroid hormone suggested hyperparathyroidism including calcium-sensing receptor mutations that could cause hypercalcemia-induced NDI. Polyuria became apparent after the initiation of i.v. infusion for the treatment of hypernatremia. Low calcium and low sodium formula with hypotonic fluid infusion did not correct hypernatremia, hypercalcemia, or hyperphosphatemia. Hydrochlorothiazide and subsequently added celecoxib effectively decreased urine output and corrected electrolytes abnormalities. Normal serum electrolytes were maintained after the discontinuation of low calcium formula. The genetic analysis revealed a large deletion of the arginine vasopressin receptor-2 (AVPR2) gene but no pathogenic variant in the calcium-sensing receptor (CASR) gene. Whether hypercalcemia and hyperphosphatemia were caused by dehydration alone or in combination with other mechanisms remains to be clarified.

Learning points

  • Congenital NDI can present with neonatal hypercalcemia and hyperphosphatemia.

  • Hypercalcemia and hyperphosphatemia can be treated with low calcium and low sodium formula, hydration, hydrochlorothiazide, and celecoxib.

  • Genetic testing is sometimes necessary in the differentiating diagnosis of hypercalcemia associated with NDI.

Open access

Jean Marc Mizzi, Christopher Rizzo, and Stephen Fava

Summary

An 82-year-old female was admitted to a general hospital due to progressive bilateral lower limb weakness. A T8–T9 extramedullary meningioma was diagnosed by MRI, and the patient was referred for excision of the tumour. During the patient’s admission, she was noted to have persistent hyperkalaemia which was refractory to treatment. Following a review by an endocrinology team, a diagnosis of pseudohyperkalaemia secondary to thrombocytosis was made. This case demonstrates the importance of promptly identifying patients who are susceptible to pseudohyperkalaemia, in order to prevent its potentially serious consequences.

Learning points

  • Pseudohyperkalaemia should be considered in patients with unexplained or asymptomatic hyperkalaemia. It should also be considered in those patients who are resistant to the classical treatment of hyperkalaemia.

  • A diagnosis of pseudohyperkalaemia is considered when there is a difference of >0.4 mmol/L of potassium between serum and plasma potassium in the absence of symptoms and ECG changes.

  • In patients who are presenting with consistently elevated serum potassium levels, it may be beneficial to take venous blood gas and/ or plasma potassium levels to rule out pseudohyperkalaemia.

  • Pseudohyperkalaemia may subject patients to iatrogenic hypokalaemia which can be potentially fatal.

  • Pseudohyperkalaemia can occur secondary to thrombocytosis, red cell haemolysis due to improper blood letting techniques, leukaemia and lymphoma.

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

Shunsuke Shimazaki, Itsuro Kazukawa, Kyoko Mori, Makiko Kihara, and Masanori Minagawa

Summary

Ammonium acid urate (AAU) crystals are rare in industrialized countries. Furthermore, the number of children with diabetic ketoacidosis (DKA) who develop severe acute kidney injury (AKI) after hospitalization is small. We encountered two patients with AKI caused by AAU crystals during the recovery phase of DKA upon admission. They were diagnosed with severe DKA and hyperuricemia. Their urine volume decreased and AKI developed several days after hospitalization; however, acidosis improved in both patients. Urine sediment analysis revealed AAU crystals. They were treated with urine alkalization and diuretics. Excretion of ammonia in the urine and urine pH levels increased after treatment of DKA, which resulted in the formation of AAU crystals. In patients with severe DKA, the urine and urine sediment should be carefully examined as AAU can form in the recovery phase of DKA.

Learning points:

  • Ammonium acid urate crystals could be formed in the recovery phase of diabetic ketoacidosis.

  • Diabetic ketoacidosis patients may develop acute kidney injury caused by ammonium acid urate crystals.

  • Urine and urine sediment should be carefully checked in patients with severe DKA who present with hyperuricemia and volume depletion.

Open access

Alicja Szwilling, Katarzyna Dzygalo, and Jędrzej Nowaczyk

Summary

Kearns–Sayre syndrome (KSS) is a multi-system mitochondrial disease with wide clinical presentation. We describe the case of a 16-year-old girl with KSS accompanied by insulin-dependent diabetes, eosinophilic esophagitis (EoE), Fanconi syndrome, insufficiency of parathyroid gland and severe nutritional problems. Based on recent knowledge, ketogenic diet was introduced to improve metabolic and neurological condition, however in our patient we observed its bad consequences. Unresolved nutritional disorders forced us to proceed with esophagogastroduodenoscopy which revealed EoE. PEG procedure was performed and elemental diet with PPI’s was introduced leading to general improvement in the patient’s health condition.

Learning points:

  • Nutrition is an important factor in supportive care of patients with KSS.

  • Ketogenic diet in patients affected by mitochondrial diseases and diabetes requires careful selection and monitoring.

  • To the best of our knowledge, this is the first case that shows the coexistence of EoE, insulin-dependent diabetes and KSS.

Open access

Tomomi Nakao, Ken Takeshima, Hiroyuki Ariyasu, Chiaki Kurimoto, Shinsuke Uraki, Shuhei Morita, Yasushi Furukawa, Hiroshi Iwakura, and Takashi Akamizu

Summary

Thyroid storm (TS) is a life-threatening condition that may suffer thyrotoxic patients. Therapeutic plasma exchange (TPE) is a rescue approach for TS with acute hepatic failure, but it should be initiated with careful considerations. We present a 55-year-old male patient with untreated Graves’ disease who developed TS. Severe hyperthyroidism and refractory atrial fibrillation with congestive heart failure aggregated to multiple organ failure. The patient was recovered by intensive multimodal therapy, but we had difficulty in introducing TPE treatment considering the risk of exacerbation of congestive heart failure due to plasma volume overload. In addition, serum total bilirubin level was not elevated in the early phase to the level of indication for TPE. The clinical course of this patient instructed delayed elevation of bilirubin until the level of indication for TPE in some patients and also demonstrated the risk of exacerbation of congestive heart failure by TPE.

Learning points:

  • Our patient with thyroid storm could be diagnosed and treated promptly using Japan Thyroid Association guidelines for thyroid storm.

  • Delayed elevation of serum bilirubin levels could make the decision of introducing therapeutic plasma exchange difficult in cases of thyroid storm with acute hepatic failure.

  • The risk of worsening congestive heart failure should be considered carefully when performing therapeutic plasma exchange.

Open access

Shanika Samarasinghe, Simge Yuksel, and Swati Mehrotra

Summary

We report a rare case of concurrent medullary thyroid cancer (MTC) and papillary thyroid cancer (PTC) with intermixed disease in several of the lymph node (LN) metastases in a patient who was subsequently diagnosed with clear cell renal cell carcinoma (RCC). A 56 year old female presented with dysphagia and was found to have a left thyroid nodule and left superior cervical LN with suspicious sonographic features. Fine needle aspiration biopsy (FNAB) demonstrated PTC in the left thyroid nodule and MTC in the left cervical LN. Histopathology demonstrated multifocal PTC with 3/21 LNs positive for metastatic PTC. One LN in the left lateral neck dissection exhibited features of both MTC and PTC within the same node. In the right lobe, a 0.3 cm focus of MTC with extra-thyroidal extension was noted. Given persistent calcitonin elevation, a follow-up ultrasound displayed an abnormal left level 4 LN. FNAB showed features of both PTC and MTC on the cytopathology itself. The patient underwent repeat central and left radical neck dissection with 3/6 LNs positive for PTC in the central neck and 2/6 LNs positive for intermixed PTC and MTC in the left neck. There was no evidence of distant metastases on computed tomography and whole body scintigraphy, however a 1.9 x 2.5 cm enhancing mass within the right inter-polar kidney was discovered. This lesion was highly suspicious for RCC. Surgical pathology revealed a 2.5 cm clear cell RCC, Fuhrman grade 2/4, with negative surgical margins. She continues to be observed with stable imaging of her triple malignancies.

Learning points:

  • Mixed medullary-papillary thyroid neoplasm is characterized by the presence of morphological and immunohistochemical features of both medullary and papillary thyroid cancers within the same lesion. Simultaneous occurrence of these carcinomas has been previously reported, but a mixed disease within the same lymph node is an infrequent phenomenon.

  • Prognosis of mixed medullary-papillary thyroid carcinomas is determined by the medullary component. Therefore, when PTC and MTC occur concurrently, the priority should be given to the management of MTC, which involves total thyroidectomy and central lymph node dissection.

  • Patients with thyroid cancer, predominantly PTC, have shown higher than expected rates of RCC. To our knowledge, this is the first report describing the combination of MTC, PTC, and RCC in a single patient.