Endocrinology, Diabetes and Metabolism Case Reports最新文献

Summary: The case report outlines a 33-year-old woman with neurofibromatosis type 1 (NF1) presenting complex symptomatology including a cervical mass, bone pain and significantly elevated calcium and parathyroid hormone levels, indicative of parathyroid carcinoma accompanied by cystic fibrous osteitis. Intriguingly, an incidental finding of an adrenal nodule prompted investigation, leading to the diagnosis of pheochromocytoma. Surgical intervention confirmed the presence of pheochromocytoma and parathyroid carcinoma. Genetic analysis corroborated NF1 with a pathogenic variant in the NF1 gene. The patient's clinical manifestations, coupled with the presence of café-au-lait spots and axillary freckles, supported the diagnosis of NF1. This case not only highlights the challenging diagnostic landscape of NF1 but also underscores the rarity of the co-occurrence of parathyroid carcinoma and pheochromocytoma within the context of NF1. It emphasizes the necessity for heightened clinical suspicion and comprehensive evaluation in patients with NF1, particularly in those presenting with endocrine abnormalities. Further investigation into the underlying mechanisms linking these conditions is warranted to elucidate their pathophysiological interplay and inform optimal therapeutic strategies for affected individuals. This case underscores the importance of multidisciplinary collaboration in the management of complex NF1-associated manifestations, with an emphasis on early detection and tailored intervention to optimize patient outcomes.

Learning points: Rare but real: multiple endocrine tumors can coexist in patients with neurofibromatosis type 1 (NF1), not only pheochromocytoma. Early detection matters: prompt diagnosis and a multidisciplinary approach are crucial for managing NF1 patients presenting with symptoms suggestive of these rare endocrine tumors. Genetic insights guide care: genetic testing aids in confirming NF1 and guiding treatment decisions, emphasizing the role of genetics in personalized medicine for NF1 patients.

Summary: Cushing syndrome (CS) is an endocrine disorder with far-reaching complications that extend beyond the disease remission. Diagnosis of the aetiology of CS can be challenging, whether it is dependent or independent of adrenocorticotrophic hormone (ACTH). Here, we describe a case of ACTH-independent CS due to primary pigmented nodular adrenocortical disease (PPNAD) in a 33-year-old female patient with several complications of CS, including diabetes, hypertension, osteoporosis and severe depression with suicidal ideation. In this case, following the demonstration of ACTH independence of CS, it was challenging to localise the lesion as there were bilateral adrenal lesions. Furthermore, preoperative efforts in localisation in the form of adrenal venous sampling (AVS) failed. However, the diagnosis of PPNAD was confirmed using an intraoperative frozen section and macroscopy, and the patient underwent bilateral adrenalectomy during the same surgery. This case highlights a novel approach to diagnosing and managing PPNAD intraoperatively in a resource-limited setting where preoperative localisation studies have failed.

Learning points: AVS can assist in localising the functional lesion in ACTH-independent CS due to bilateral adrenal lesions. PPNAD diagnosis can be made through a frozen section intraoperatively, thus giving further confirmation needed to justify bilateral adrenalectomy in such cases.

Summary: Heterozygous insulin receptor (INSR) mutations cause type A insulin resistance (IR), associated with a phenotype of IR; hyperandrogenism, oligomenorrhoea and acanthosis nigricans in the absence of obesity or lipoatrophy. The phenotype is variable, ranging from neonatal hyperinsulinaemic hypoglycaemia to fasting or post-prandial hypoglycaemia in adults to diabetes. We report a 29-year-old woman presenting at 13 weeks gestation in her second pregnancy. Diabetes was diagnosed at 13-years-old following presentation with lethargy and polyuria and she was treated with metformin 500 mg po bd. She also had polycystic ovarian syndrome, hypothyroidism and epilepsy. Metformin was changed to insulin with good glycaemic control throughout pregnancy. She delivered a 3.95 kg male infant at 39 weeks gestation without neonatal hypoglycaemia. At 18 months post-partum, her body mass index was 26.3 kg/m2, with no evidence of acanthosis nigricans or features of lipodystrophy. As her sister was also diagnosed with diabetes at 13-years-old, next-generation sequencing was performed for known maturity onset diabetes of the young (MODY) genes and a p.(Met1180Lys) mutation in the INSR gene was detected. She reported nocturnal hypoglycaemia and a 5-h oral glucose tolerance test revealed post-prandial hyperinsulinaemic hypoglycaemia at 210 min. Her subsequent pregnancy was spontaneously treated with metformin 500 mg po od from 8 to 25 weeks gestation and discontinued due to intrauterine growth restriction. She delivered a 1.8 kg female infant at 34 plus 3 weeks gestation (25th centile) via elective caesarean section. The infant had transient neonatal hypoglycaemia for two days. Post-partum, she remains diet controlled, with a haemoglobin A1c of 32 mmol/mol. This case highlights the importance of genetic testing to establish optimal diabetes treatment.

Learning points: This case highlights the less severe phenotype of IR in a subject with an INSR p.Met1180Lys mutation. It demonstrates the existence of symptomatic post-prandial hypoglycaemia in an adult subject associated with hyperinsulinaemia. This case highlights the importance of genetic testing to establish diagnosis and allows for precision medicine. The role of metformin use in Type A-IR and pregnancy needs to be established.

Summary: Type 2 diabetes (T2D) is a chronic metabolic disorder that affects millions of people worldwide, particularly the elderly population. Remission of T2D in elderly patients through lifestyle modifications has been well documented, especially in newly diagnosed patients with good glycemic control and without obesity. It is also common in patients with obesity undergoing bariatric surgery. In this report, we present the case of a 66-year-old male patient with a 30-year history of T2D and mild obesity who achieved remission of T2D through customized integrated intensive lifestyle modifications, including a vegan diet, exercise and psychological support. The patient showed an improvement in HbA1c (7.7 to 5.3%) and insulin resistance (HOMA-IR; 6.2 to 1.8) and a shift in BMI (25.3 to 23.7 kg/m2) through weight loss (73 to 67 kg). The patient remains in remission 33 months after the completion of the intervention. This case suggests the possibility of long-term remission with lifestyle changes in patients with advanced age, a longer duration of diabetes and mild obesity.

Learning points: Long-term sustained remission is possible in a geriatric patient with long-standing type 2 diabetes (T2D) of more than 30 years. Customized integrated intensive lifestyle intervention can lead to a significant improvement in glycemic control and insulin resistance in elderly patients with T2D. Integrated lifestyle interventions, including a vegan diet, exercise and psychological support, have the potential to stop the usage of oral hypoglycemic agents and insulin in an elderly patient with a prolonged history of T2D and mild obesity.

Summary: Rett syndrome (RS) is an X-linked neurodevelopmental disorder primarily affecting females. RS and diabetes mellitus (DM) type 1 are rare disorders with distinct etiologies. Although some cases of RS complicated by DM type 1 have been reported, the association between these distinct conditions is poorly understood and warrants further studies to elucidate the underlying mechanisms and inform clinical management. We report the case of a 10-year-old girl diagnosed with RS and DM type 1. The patient initially presented at 3 years of age with polydipsia, polyuria and decreased appetite over several weeks. Physical examination showed signs of dehydration, and laboratory evaluation revealed hyperglycemia, elevated HbA1c, glycosuria, ketonuria and low C-peptide levels. Anti-glutamic acid decarboxylase antibodies were positive, confirming autoimmune DM type 1. Fluid resuscitation and insulin therapy were initiated with good glycemic control on continuous subcutaneous insulin infusion. A review of her history revealed normal early developmental milestones, including the onset of stereotypical hand movements at 3 years, communication impairment and seizures at 4 years and a diagnosis of autism spectrum disorder. At 10 years of age, genetic testing revealed a pathogenic MECP2 mutation. Clinical features, including breathing abnormalities, bruxism, abnormal tone and inappropriate laughing, met the diagnostic criteria for RS. This is the reported first case of RS with a confirmed MECP2 mutation complicated by DM type 1. Our case report contributes to the increasing evidence supporting the potential association between RS and DM type 1.

Learning points: There is a possible link between RS and DM type 1. This is the first case report of RS with a confirmed MECP2 mutation complicated by DM type 1. In cases where patients with RS develop diabetic ketoacidosis, it may manifest as mild acidosis or normal pH despite the presence of high blood sugar levels and dehydration.

Summary: Solid pseudopapillary neoplasm (SPN) is classified as an epithelial tumor identified from benign to low-grade malignant tumor. It is a relatively rare tumor among various pancreatic tumors and is generally observed in young women. Therefore, the identification of an SPN should be considered in cases where a solid/cystic mass is detected in the pancreas of a young woman. Distal pancreatectomy is performed for a large size of SPN located in the tail of the pancreas. Here, we report a 15-year-old Japanese female who brought about Type 3C diabetes mellitus (T3C-DM) after a distal pancreatectomy due to SPN. This case highlights the importance of management after pancreatectomy to detect early T3C-DM and prevent its development even in young patients. Although it is not surprising that a massive pancreatic tumor or pancreatectomy can lead to pancreatic diabetes at any age, we believe that it is important for clinicians to know this subject for educational purposes.

Learning points: SPN is a relatively rare tumor that accounts for 1-3% of all pancreatic tumors and is predominantly located in the tail of the pancreas.Since SPN is generally observed in young women, the presence of an SPN should be considered in cases where a solid/cystic mass is detected in the pancreas of a young woman.Pancreatic DM after pancreatectomy is classified as T3C-DM in the American Diabetes Association (ADA) classification.This case indicates that even in young individuals, it is important to consider the possibility of impaired glucose tolerance after distal pancreatectomy.

Summary: We presented a case of a 72-year-old male with severe hypercalcaemia of 3.84 mmol/L following the second cycle of immunotherapy with ipilimumab and nivolumab in the setting of metastatic melanoma with known bone metastases. Further investigations demonstrated hilar lymphadenopathy, which was not present in previous imaging, and subsequent hypercalcaemia work-up demonstrated a significantly elevated serum calcitriol level as high as 429 pmol/L. A diagnosis of drug-induced sarcoid-like reactions or DISRs was made on the basis of hypercalcaemia and hilar lymphadenopathy following immunotherapy. Hypercalcaemia was effectively treated with intravenous fluids and medical therapy including a short course of subcutaneous calcitonin, a total of 120 mg of denosumab and oral prednisolone.

Learning points: DISRs are a rare complication of immunotherapy and may mimic metastases. A temporal relationship between commencement of therapy and progression on clinical imaging is important in making an accurate diagnosis.Calcitriol-mediated hypercalcaemia secondary to DISRs is an important differential diagnosis to hypercalcaemia of malignancy and should be considered in patients who have undergone immunotherapy.Prednisolone should be considered as the next line of treatment after fluid therapy in patients with calcitriol-mediated hypercalcaemia. Prednisolone and denosumab both reach maximum clinical efficacy between 7 and 10 days. Therefore, treatment administration should be spaced out by at least five days to avoid iatrogenic hypocalcaemia.

Summary: A 17-year-old girl presented with recurrent attacks of acute pancreatitis, associated with severe hyperglycemia and hypertriglyceridemia, despite being on intensive insulin therapy for the last 10 years. She had severe acanthosis nigricans, generalized loss of subcutaneous fat and prominent veins over extremities. The serum levels of glucose and triglyceride did not reduce significantly, even with maximally tolerated doses of metformin (2 g), pioglitazone (45 mg) and fenofibrate (160 mg), not uncommonly seen in poor rural families in West Bengal, India. A detailed dietary recall revealed a very high carbohydrate intake (70% of total calorie) with very low protein and fat intake. A switch to a very low carbohydrate (30% of total calorie) diet led to a remarkable improvement in glucose and lipid profiles (the daily insulin requirement came down by 50% and triglyceride level came down to 600 mg/dL from 950 mg/dL). A whole-exome sequencing study confirmed congenital generalized lipodystrophy type 4. A carbohydrate restriction strategy may improve difficult-to-control glycometabolic profile in lipodystrophic subjects on high-carbohydrate diet.

Learning points: Lipodystrophy should be suspected in patient presenting with hyperglycemia, hypertriglyceridemia and low BMI. A very low carbohydrate diet (30% of total daily calorie intake) may significantly improve glucose and lipid profiles in patients with lipoatrophic diabetes. Blood glucose may be the most important initial step to control hypertriglyceridemia and risk of pancreatitis in this group of patients.

Summary: Hypophosphatasia (HPP) is a genetic disorder due to pathological variants in ALPL, the gene encoding tissue-nonspecific alkaline phosphatase (ALP). HPP is typically associated with bone-related symptoms, such as bone deformity, fractures and bone pain in children, but can appear in adults with symptoms resembling arthritis. A 22-year-old male experienced repeated and severe sudden attacks of joint pain in the elbows and knees. Magnetic resonance imaging and joint ultrasonography showed joint effusions indicating chronic inflammation. Blood biochemical tests revealed a remarkably low serum ALP level, and repeated examination confirmed a sustained low ALP level; urine phosphoethanolamine, plasma inorganic pyrophosphate and plasma pyridoxal-5'-phosphate levels were elevated, raising concern for HPP. While the patient had no history of premature loss of primary teeth, fragility fractures, muscle weakness or abnormalities in growth, genetic testing revealed a likely pathogenic and a pathogenic heterozygous variant in the ALPL gene, i.e., c.979T>C (p.Phe327Leu) and c.1559del (p.Leu520Argfs), confirming HPP. Additional genetic testing of his parents showed a heterozygous c.1559del variant in his father and a heterozygous c.979T>C variant in his mother. A diagnosis of adult HPP due to compound heterozygous mutations was therefore confirmed. Enzyme replacement therapy with asfotase alfa was then introduced; no attacks of arthralgia occurred in the 1-year period since then. This case highlights the possibility of HPP in adults who present clinically with repeated joint symptoms and low serum ALP levels but without bone-related symptoms.

Learning points: A diagnosis of adult HPP without bone-related symptoms can be challenging. A reduction in tissue-nonspecific ALP activity leads to an accumulation of pyrophosphate in the joints, which can cause arthralgia. Some cases of adult HPP have arthralgia as the only presenting symptom. At one-year follow-up, enzyme replacement therapy with asfotase alfa might lead to a reduction in arthralgia attacks due to HPP.

Summary: Oral levothyroxine (LT4) is prescribed worldwide for hypothyroidism. Bariatric surgery for patients with obesity has shown a substantial, long-term weight loss and considerable improvement of obesity-related diseases. LT4 malabsorption represents a significant cause of refractory hypothyroidism, well known after malabsorptive bariatric surgery such as Roux-en-Y gastric bypass. However, few studies have shown an increase in oral LT4 needed after sleeve gastrectomy. We present a 47-year-old woman with class III obesity and a history of papillary thyroid cancer, with an excellent biochemical and structural response after total thyroidectomy and radioactive iodine. She underwent sleeve gastrectomy 3 years later and developed refractory hypothyroidism despite taking high doses of oral LT4 and ensuring compliance. The T4 absorption test confirmed gastrointestinal LT4 malabsorption. She was initiated on intramuscular LT4 and oral T3 (liothyronine) with improving symptoms and levels of thyroid-stimulating hormone.

Learning points: Monitoring thyroid function tests is essential after bariatric surgery, including sleeve gastrectomy. Oral LT4 malabsorption should be considered in cases of refractory hypothyroidism. The T4 absorption test is a useful tool for distinguishing true malabsorption from pseudo-malabsorption. Decreased LT4 absorption after bariatric surgery might be explained by higher gastric pH and reduced stomach volume (impaired dissolution) and by interference with food, vitamin/mineral supplements or other drugs. When LT4 malabsorption is confirmed, a trial of other oral formulations (LT4 tablet crushed, soft gel or liquid preparation) or parenteral administrations is suggested.