Endocrinology, Diabetes and Metabolism Case Reports最新文献

Summary: An 11-year-old girl presented to the emergency department with hypophosphataemia. Subsequent investigations repeatedly demonstrated elevated serum parathyroid hormone (PTH) associated with normal serum total calcium, phosphate, vitamin D, and bone turnover markers. Imaging studies were initially interpreted as being consistent with the effects of hyperparathyroidism; however, follow-up review by specialists with paediatric expertise concluded otherwise. Further laboratory studies ultimately demonstrated that there was a false elevation in PTH, determined to be due to interference in the PTH assay from the formation of macromolecular complexes. This case highlights the effects of a phenomenon known as 'Ulysses syndrome', whereby a patient is sent on an unnecessary journey of extensive diagnostic investigation conducted because of a false-positive result. Recognition of macromolecular complexes and antibody interferences in patients with PTH results that are discordant with the overall clinical picture and other biochemistry results may prevent this phenomenon, with all its psychological and financial consequences.

Learning points: PTH results that are discordant with the clinical picture or other biochemistry results should be suspicious for assay interference. Macro-PTH complexes and other antibody interferences are rarely reported, although they are a potential cause of spuriously elevated PTH. Recognition of potentially spurious results early can reduce unnecessary investigations and prevent potential misdiagnosis.

Summary: This is a report of a patient with acromegaly that was ameliorated by pemafibrate, a peroxisome proliferator-activated receptor-α (PPAR-α) activator. Baseline acromegaly medication for this patient was lanreotide (90 mg/month). A marked reduction in insulin-like growth factor-1 levels was observed after initiating pemafibrate and remained during 12 months of follow-up. PPAR-α agonists might prove useful in pharmacotherapy for acromegaly.

Learning points: Pemafibrate was effective for regulating dyslipidemia in the present case. A concomitant decrease in plasma IGF-1 levels was observed following initiation of pemafibrate treatment. Some in vitro studies have described beneficial effects of pemafibrate. Pemafibrate warrants investigation as a new treatment for acromegaly.

Summary: Non-ketotic hyperglycaemic hemichorea, also known as diabetic striatopathy (DS), is a rare but reversible hyperglycaemia-related movement disorder. It typically affects elderly patients and may occasionally represent the first manifestation of diabetes mellitus. The hallmark features include involuntary, unilateral choreiform or ballistic movements, with characteristic striatal neuroimaging changes. Early recognition is critical to avoid misdiagnosis and ensure timely intervention. We report a 78-year-old woman with a one-month history of progressive, involuntary right-sided limb movements, which subsided during sleep and severely impaired daily function. She had no prior diagnosis of diabetes but presented with osmotic symptoms for one year. Laboratory tests revealed hyperglycaemia (random blood glucose: 22 mmol/L; HbA1c: 15.9%) without ketosis. Neuroimaging demonstrated hyperdensity in the left caudate and lentiform nucleus on CT and corresponding T1-weighted hyperintensity with asymmetrical striatal atrophy on MRI, consistent with DS. Treatment with insulin, haloperidol, and tetrabenazine achieved a gradual symptomatic improvement, with a marked reduction in involuntary movements at three months, although resolution was protracted compared to the typical cases. This case underscores the importance of considering DS in elderly patients presenting with acute choreiform movements, even in the absence of known diabetes. Awareness of its clinical and radiological features is crucial to prevent misdiagnosis as cerebrovascular disease. While optimal glycaemic control remains the cornerstone of management, persistent or severe cases may require prolonged anti-chorea therapy, reflecting potential irreversible striatal injury.

Learning points: DS can occur as the first manifestation of diabetes mellitus. Therefore, hyperglycaemia should be ruled out in patients presenting with chorea, even in the absence of known diabetes. MRI is more sensitive than CT scan in detecting abnormalities in DS, with a reported mismatch rate of 17.5%. However, there is no consistent correlation between the pattern of striatal involvement on the radiological imaging and the distribution of clinical symptoms. Some patients can achieve symptom resolution by glucose control alone. However, the majority require additional anti-chorea medications.

Summary: Haematopoietic stem cell transplant (HSCT) is a novel treatment utilised in a number of malignant and non-malignant conditions, with promising results in multiple sclerosis (MS), particularly in those not responding to previous disease-modifying therapies. There is existing evidence to suggest that HSCT has been linked to, in rare cases, autoimmune thyroid dysfunction. Much of the current literature highlights paediatric occurrences. The most common dysfunction noted is hypothyroidism, seen in 40% of cases, with other autoimmune thyroid dysfunctions reported less commonly. A 34-year-old female represents a unique case of autoimmune hyperthyroidism secondary to haematopoietic stem cell transplant completed for relapsing-remitting MS. One year following her HSCT, she presented with fatigue, brain fog, palpitations and tremors, and blood tests revealed thyrotoxicosis with elevated thyroid receptor antibody levels (TSH receptor antibodies). She was diagnosed with Graves' disease and treated with carbimazole and propranolol acutely; she is currently under regular endocrine follow-up. Ongoing multidisciplinary collaboration to holistically support her complex health needs continues, and a symptomatic improvement has been noted.

Learning points: Secondary autoimmune diseases, such as Graves' disease, can develop in 2-14% of patients following autologous HSCT for MS. In our case, the timeline for development of Graves' disease post-HSCT is 10-12 months, which aligns with a previous reported case in the literature of between 8 and 32 months. Thyroid function test should be monitored regularly post-HSCT for MS as both autoimmune hyperthyroidism (Graves' disease) and hypothyroidism can develop. We aim to highlight to clinicians about this rare occurrence of Graves' disease post-HSCT.

Summary: Primary adrenal lymphoma (PAL) is a rare malignancy typically considered in patients presenting with features of adrenal insufficiency and bilateral adrenal gland enlargement. Early diagnosis and differentiation from other causes of bilateral adrenal masses are essential to guide appropriate management. Prompt initiation of chemotherapy can significantly improve survival outcomes. We present the case of a 72-year-old patient with adrenal insufficiency and imaging-confirmed large bilateral adrenal masses with widespread lymph node involvement. Core biopsy of the adrenal mass confirmed high-grade diffuse large B-cell lymphoma (DLBCL), consistent with a diagnosis of PAL. She was initially managed with systemic chemotherapy with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP), achieving a complete metabolic response. Two months later, she presented with relapsed central nervous system disease and died despite intrathecal cytarabine and methotrexate chemotherapy. Given the rarity of this condition, we use the case to illustrate and discuss key aspects of PAL, including demographics, pathogenesis, diagnosis, management, and prognosis.

Learning points: PAL is a rare but important diagnosis to consider in patients presenting with bilateral adrenal masses and adrenal insufficiency, especially in the absence of a known primary. In this case, the patient presented repeatedly with constitutional symptoms before the diagnosis was made through imaging. Whether an earlier diagnosis would have changed the clinical outcome remains unclear. This suggests that early imaging is important to initiate the diagnostic and management cascade in patients presenting with persistent, unexplained symptoms. Following exclusion of phaeochromocytoma, early biopsy and histopathological confirmation is crucial for accurate diagnosis and guiding management. Immunochemotherapy is the mainstay of treatment and may improve survival even in the setting of widespread disease. CNS involvement is important to exclude through MR scan of the brain and CSF sampling. Further research into predictors of recurrence and CNS relapse may improve long-term outcomes in PAL.

Summary: Neurofibromatosis type 1 (NF1) is an autosomal dominant condition predisposing to tumors, including pheochromocytomas and paragangliomas. Reported penetrance is close to 100%, but clinical presentation is highly variable. We present a case of a 79-year-old woman with an atypical and late presentation of NF1 with bilateral pheochromocytomas. She presented with long-standing abdominal pain. Her medical history included takotsubo cardiomyopathy and two episodes of intraoperative cardiogenic shock, 12 and 19 years before. A CT-scan revealed a 61 mm mass in the left adrenal gland (spontaneous density of 39 HU (hounsfield units)) and a 12 mm mass in the right adrenal gland (43 HU). The MIBG (metaiodobenzylguanidine) scan demonstrated high uptake in the left adrenal gland lesion. Urinary fractionated metanephrines were elevated. She underwent a left adrenalectomy, and pathology findings revealed a composite pheochromocytoma-ganglioneuroma. Genetic testing disclosed a pathogenic variant in the NF1 gene. After surgery, urinary fractionated metanephrines normalized but became elevated again one year later. She underwent a right adrenalectomy, and pathology confirmed a 'typical' pheochromocytoma. Other than bilateral pheochromocytoma, the patient had no other clinical manifestations of NF1, including café-au-lait macules or cutaneous neurofibromas. This case highlights the importance of offering genetic testing to all patients with pheochromocytoma, which may reveal cases of NF1 with subtler and atypical clinical presentation.

Learning points: Genetic testing should be offered to all patients with pheochromocytoma. Bilateral pheochromocytomas should raise suspicion for an underlying genetic syndrome, even in elderly patients or those without a known family history. Some patients with neurofibromatosis type 1 (NF1) may have a later and subtler presentation, including isolated pheochromocytoma.

Summary: Mitochondrial diseases cause systemic failure of energy production and can manifest as various disorders of hormone production and secretion from endocrine organs. These effects can prevent normal growth in children, resulting in adults of short stature. We therefore explored the nutritional and endocrinological status of pediatric mitochondrial disease patients with impaired growth. Four Japanese patients with genetically diagnosed mitochondrial disease were studied (one male and three females, aged 4-22 years). The age of onset ranged from 0 months to 7 years, and the causal genes identified were mtDNA, PDHA1, and NARS2 (in two sibling patients). Two patients were diagnosed with small for gestational age at birth, and their current height standard deviation scores ranged from -1.9 SD to -6.4 SD. Mitochondrial diseases can present as impaired growth with dysfunction of various organs, depending on the causal gene and the degree of heteroplasmy. Our patients had demonstrated low T3 syndrome and reduced IGF1 levels, which appeared to be influenced by impaired nutritional status. These findings emphasize the need for careful monitoring of growth trajectories alongside nutritional and endocrine evaluations to improve clinical management.

Learning points: Mitochondrial diseases can disrupt endocrine function involving the GH-IGF1 axis and the thyroid and gonadal systems, leading to impaired growth during childhood. Patients with early-onset mitochondrial disease tend to experience severe symptoms and pronounced growth impairment. Children with mitochondrial diseases often show low IGF1 levels, low T3 syndrome, and delayed bone age, reflecting endocrine dysfunction commonly observed in chronic systemic diseases and the further influence of suboptimal nutritional status.

Summary: Hepatogenous diabetes, a secondary form of diabetes arising from chronic liver disease, particularly cirrhosis, is a well-documented complication. However, diabetic ketoacidosis (DKA) in the context of hepatogenous diabetes has not been reported in the literature. We report the case of a 60-year-old male with alcoholic liver cirrhosis and no prior history of diabetes who presented with altered mental status and was diagnosed with DKA. Initial lab tests revealed severe hyperglycemia, high-anion gap metabolic acidosis, and an elevated HbA1C of 10.2%, a significant increase from 5.2% five months earlier. The patient was managed with insulin and lactulose, resulting in clinical improvement. Follow-up revealed normalization of HbA1C and a reduction in insulin requirements. This is the first documented case of DKA as the initial presentation of hepatogenous diabetes, emphasizing the need for heightened awareness and further research into its clinical manifestations and management.

Key clinical messages: DKA can be the first clinical manifestation of hepatogenous diabetes, even in patients with normal HbA1C and no prior diabetes history. HbA1C is an unreliable marker for diagnosing diabetes in cirrhotic patients due to shortened red blood cell lifespan; OGTT should be considered when hepatogenous diabetes is suspected despite normal glycemic markers. Subclinical infections can precipitate DKA in cirrhosis through stress-induced insulin resistance.

Summary: It is relatively rare to find a significant increase in creatine kinase (CK) related to hypothyroidism through a health examination. This case report describes an asymptomatic adult patient in whom an asymptomatic elevation of serum CK was discovered incidentally during a routine health check. The patient reported no significant muscle weakness, pain, or other classic symptoms of proximal myopathy or hypothyroidism. A comprehensive diagnostic workup was initiated to investigate the common causes of high CK level, including cardiac injury, strenuous exercise, statin use, and inflammatory myopathies, all of which were excluded. Thyroid function tests revealed severe primary hypothyroidism with significantly elevated thyroid-stimulating hormone (TSH; >100 mIU/L) and decreased free thyroxine levels. A diagnosis of hypothyroid myopathy was established. Upon initiation of levothyroxine replacement therapy, the patient's thyroid function normalized, and this was followed by a complete normalization of the serum CK level on subsequent follow-up. This case highlights that hypothyroidism is an important, reversible, notable, and treatable cause of an asymptomatic unexplained CK elevation, particularly in the context of severe biochemical hypothyroidism. It underscores the critical importance of including thyroid function tests in the routine differential diagnosis of any unexplained high CK level, even in the absence of overt clinical myopathic symptoms or recognized signs of hypothyroidism. For clinicians and general practitioners interpreting routine health screening results, this case serves as a vital reminder that a simple thyroid function test can prevent unnecessary and costly investigations and lead to the correct diagnosis and effective treatment.

Learning points: In asymptomatic individuals undergoing routine health screening, an isolated elevation of creatine kinase (CK) may be an early biochemical indicator of underlying hypothyroidism, warranting simple thyroid function testing. This case underscores the public health value of routine biochemical panels that include CK, as they can identify individuals with subclinical endocrine dysfunction before the development of overt clinical disease. For primary care and preventive medicine physicians, integrating thyroid function tests into the initial workup for incidentally discovered hyperCKemia is a cost-effective strategy that can prevent unnecessary specialist referrals and invasive investigations.

Summary: Activating mutations in the ABCC8 gene are extremely rare and cause ABCC8-MODY. The phenotype is variable with onset of diabetes in childhood/early adulthood. Retinopathy is the most common reported complication. We describe a 31-year-old primigravida woman referred to and seen at our antenatal ambulatory diabetes clinic at 6 weeks plus 5 days gestation. She had a strong family history of diabetes and was diagnosed at the age of 11 years. Genetic testing revealed an activating pathogenic c.4139G>A variant in the ABCC8 gene. She was managed with glibenclamide, sitagliptin, and dapagliflozin. Her complications included mild bilateral non-proliferative retinopathy and necrobiosis lipoidica. Her BMI was 19 kg/m2, and HbA1c was 68 mmol/mol. Oral agents were discontinued, and insulin therapy was commenced. At 22 weeks gestation, routine retinal screening identified progression to bilateral active proliferative diabetic retinopathy (time in range for pregnancy (TIRp) 68%, HbA1c 39 mmol/mol). She received four sessions of panretinal photocoagulation (PRP) bilaterally between 22 and 33 weeks gestation. There was no associated loss of vision or nephropathy. TIRp was ≥70% for the remainder of the pregnancy. She delivered a 3.9 kg unaffected female infant at 38 weeks via elective caesarean section without maternal or neonatal complications. Bilateral active proliferative retinopathy persisted up to 61 weeks postnatally and required additional PRP. Forty-six weeks post-partum, after ceasing breastfeeding, insulin was switched to glibenclamide and dapagliflozin. This is the first case report of rapid progression of clinically significant diabetic retinopathy during pregnancy in a woman with ABCC8-MODY. This is an unusual finding as there is a relatively low risk of significant progression of diabetic retinopathy in women with type 2 diabetes during pregnancy.

Learning points: Rapid progression of diabetic retinopathy during pregnancy is an uncommon complication in women with type 2 diabetes. This woman with ABCC8-MODY developed rapidly progressive clinically significant diabetic retinopathy without nephropathy during pregnancy. There is a paucity of literature regarding pregnancy-related complications of ABCC8-MODY. This case highlights the risks of end organ disease in a rare form of diabetes.