Endocrinology, Diabetes and Metabolism Case Reports最新文献

Summary: A 39-year-old woman presented with a 5-year history of severe intermittent headaches, rhinitis, hemoptysis, unintentional weight loss of 40 kg over a year, and unilateral vision loss. Then, she noticed polyuria, amenorrhea, muscle weakness, and cold intolerance. Diagnosis of granulomatosis with polyangiitis (GPA) was confirmed with elevated c-ANCA levels and PR3-positive antibodies. Physical examination revealed hypotension, absence of pubic and axillary hair, and classical signs of hypothyroidism. The patient reported multiple previous hospitalizations due to episodes of hypernatremia, hypotension, and hypoglycemia. The biochemical evaluation showed early signs of chronic kidney disease and central adrenal, thyroid, and gonadotropin deficiencies. Pituitary MRI revealed a heterogeneous pituitary gland with peripheral enhancement, central necrosis, and extension to adjacent structures, as well as the absence of posterior pituitary bright spot on T1-weighted imaging. A diagnosis of GPA with pituitary involvement was established. Remission therapy with corticosteroids and rituximab was started. After disease control, pituitary hormonal deficiencies persisted, requiring long-term hormone replacement therapy.

Learning points: Pituitary involvement in cases with GPA is a rare manifestation frequently misdiagnosed. It is important to be aware of hypophysitis as a GPA activity complication that warrants a prompt diagnostic approach and treatment. The pathophysiology of hypophysitis may be mediated by a granulomatous lesion or due to vascular damage. Pituitary dysfunction in GPA may occur at any moment, as an initial manifestation or as a concomitant syndrome together with other organ compromise. Deficiency of arginine vasopressin and central hypogonadism are the most frequent pituitary hormonal alterations. Pituitary dysfunction usually persists despite remission of systemic activity, requiring long-term hormone replacement therapy and surveillance.

Summary: This case series presents two postmenopausal women with beta-thalassemia trait who developed osteoporosis. Case 1 involves a woman in her 70s presenting with persistent lower back pain; imaging revealed a compression fracture at L2, and a DEXA scan confirmed osteoporosis with a forearm T-score of -3.8 and a femoral neck T-score of -2.5. Case 2 describes a woman in her late 50s with generalized bone pain and severe osteoporosis identified through DEXA scanning, with a lumbar spine T-score of -3.3. Both patients lacked classical secondary causes of bone loss, and laboratory evaluations were unremarkable. Family history was notable for osteoporosis in first-degree relatives, though the relatives' thalassemia status was unknown. Both patients declined injectable therapies and were managed with oral alendronate, calcium, and vitamin D supplementation. These cases highlight beta-thalassemia trait as a potential underrecognized risk factor for osteoporosis in postmenopausal women, suggesting the need for further research and consideration in clinical guidelines.

Learning points: Beta-thalassemia trait may predispose to osteoporosis, even without iron overload or transfusion dependence. Postmenopausal women with beta-thalassemia trait should undergo early DEXA screening to prevent fractures. Patient preference impacts management: oral bisphosphonates are viable when injectables are refused. Guideline gaps: current osteoporosis protocols do not address beta-thalassemia trait as a risk factor.

Summary: Hypercalcemia is a prevalent electrolyte disturbance commonly associated with primary hyperparathyroidism, cancer, or medication adverse effects. Thiazide diuretics reduce urinary calcium excretion, increasing calcium reabsorption and hypercalcemia. Tirzepatide, a dual GIP and GLP-1 receptor agonist, is increasingly used for type 2 diabetes and obesity. While GIP/GLP-1 agonists typically have negligible effects on calcium homeostasis, the interaction between tirzepatide and thiazides remains unstudied. We report a 65-year-old female with obesity, hypertension, CKD3, and T2DM on chronic HCTZ who developed symptomatic hypercalcemia (corrected calcium: 4.58 mmol/L; normal range: 2.12-2.62 mmol/L), resulting in altered mental status days after initiating tirzepatide. PTH and vitamin D levels were low, and imaging ruled out malignancy. Discontinuation of tirzepatide/HCTZ, IV hydration, and calcitonin normalized her calcium by hospital day 4. This case highlights a potential association between HCTZ and tirzepatide in causing severe hypercalcemia. No prior reports link tirzepatide (or its combination with thiazides) to hypercalcemia. The mechanism likely involves thiazide-induced calcium reabsorption and tirzepatide's effects on bone turnover. As the use of tirzepatide and other GLP-1/GIP agonists becomes more prevalent, clinicians need to closely monitor calcium levels in thiazide-treated individuals, particularly those with CKD. Additional research is also needed to elucidate the drug's interaction with calcium metabolism.

Learning points: Clinicians should be aware of the potential for severe hypercalcemia when tirzepatide is co-administered with chronic thiazide diuretics, particularly hydrochlorothiazide (HCTZ), in patients with pre-existing CKD. Tirzepatide, a dual GIP and GLP-1 receptor agonist, may influence calcium metabolism through mechanisms including increased osteoblastic activity and altered PTH regulation, especially in individuals with impaired renal clearance. Baseline and follow-up serum calcium monitoring is strongly recommended within 1-2 weeks of initiating tirzepatide in patients receiving thiazide diuretics or those with CKD. This case suggests a possible drug-drug interaction between tirzepatide and HCTZ leading to symptomatic hypercalcemia, highlighting the need for pharmacovigilance as newer agents are integrated into routine diabetes care. Severe hypercalcemia can present with nonspecific symptoms such as altered mental status, fatigue, constipation, and polyuria; clinicians should maintain a high index of suspicion in susceptible populations. Prompt cessation of the suspected offending agents, hydration, and short-term use of calcitonin can result in rapid and sustained normalization of calcium levels without the need for bisphosphonates.

Summary: Primary hyperparathyroidism (PHPT) is a rare condition during pregnancy, but it is associated with significant maternal and fetal risks, including miscarriage, preeclampsia, and preterm birth. Hyperparathyroidism-jaw tumor (HPT-JT) syndrome is a rare genetic form of PHPT caused by mutations in the CDC73 gene. Managing PHPT during pregnancy is particularly challenging. While surgery remains the definitive treatment, it carries increased risk of complications during pregnancy. Pharmacological options are generally contraindicated or have limited safety data, limiting available therapeutic strategies. We report the case of a 19-year-old woman with genetically confirmed HPT-JT syndrome who became pregnant while awaiting parathyroidectomy. Given the stability of serum calcium levels, absence of complications, and concerns regarding adherence to follow-up, a conservative management strategy was adopted, consisting of oral hydration, dietary calcium restriction, and close monitoring throughout gestation. The pregnancy progressed uneventfully, and a successful postpartum parathyroidectomy led to biochemical normalization. This case illustrates the challenges in managing PHPT during pregnancy and supports the potential safety of individualized conservative approaches in selected cases with stable disease.

Learning points: Primary hyperparathyroidism (PHPT) during pregnancy is rare but may be associated with significant maternal and fetal risks; individualized management is essential. While parathyroidectomy is the only definitive treatment for PHPT, deferring surgery until the postpartum period may be a reasonable option in selected stable cases without complications. Conservative management with hydration and dietary calcium restriction may be a safe alternative in selected pregnant patients with stable, mild-to-moderate hypercalcemia. Genetic evaluation is critical in young patients with PHPT and relevant family history, as hereditary syndromes such as HPT-JT syndrome require long-term multidisciplinary surveillance.

Summary: Pheochromocytomas are rare neuroendocrine tumors derived from adrenal chromaffin cells that result in hyperactivity of the sympathetic nervous system. We present the case of a patient with biochemical evidence of pheochromocytoma, but surgical pathology revealed absence of tumor. This is an 80-year-old female with a past medical history of metastatic follicular lymphoma and hypertension with an incidental 1.4 cm right-sided adrenal nodule noted on a PET-CT scan. Her hypertension was treated with three different antihypertensive agents. Subsequent imaging with non-contrast CT of abdomen and pelvis showed a right adrenal incidentaloma with 16 Hounsfield units. Abdominal MRI with and without contrast revealed atypical signal loss on the out-of-phase imaging. Plasma normetanephrines were approximately 2.4 times higher than the upper limit of normal. Her urinary normetanephrines were higher than the upper limit of normal, suggestive of pheochromocytoma. The patient proceeded with robotically assisted laparoscopic right adrenalectomy and postoperatively required vasopressors. Surgical pathology showed adrenal cortical hyperplasia and medullary infarction associated with fibrosis. However, the noted phases of necrosis with predominant fibrosis match the time interval between clinical diagnosis and surgical management. Postoperative metanephrines normalized 4 weeks after surgery, indicating successful surgical resection of autonomous secretion of metanephrines. This is the only known case of biochemical evidence of pheochromocytoma with no histologic evidence of tumor.

Learning points: Biochemical evidence, clinical presentation and imaging studies of pheochromocytoma are crucial for its diagnosis. Due to the vascular nature of pheochromocytoma, there is a potential for the tumor to infarct. Plasma normetanephrines of greater than twice the upper limit of normal have high specificity for pheochromocytoma.

Summary: Thyroid storm represents a severe expression of thyrotoxicosis and is commonly associated by multiple organ dysfunction and liver abnormality. Thyrotoxicosis with concurrent autoimmune hepatitis is rare but could confound liver dysfunction, hence complicating diagnosis and subsequent management. We present the case of a 37-year-old woman with thyroid storm complicated by multiple organ failure and resistant hyperthyroidism. Despite initial medical therapy, her condition deteriorated with rising bilirubin and worsening right heart failure. Therapeutic plasma exchange (TPE) was initiated, leading to transient clinical and biochemical improvements. However, subsequent neurological decline and hepatic decompensation revealed an underlying autoimmune hepatitis, confirmed via biopsy at later stage. Intensive multimodal management, including further TPE sessions, ultimately stabilized her condition, allowing a safe and successful thyroidectomy. This report underscores the diagnostic challenge posed by overlapping autoimmune pathologies, the need for vigilant monitoring of thyroid and hepatic parameters, and the pivotal role of TPE as a rescue therapy.

Learning points: Dual autoimmune pathologies, such as autoimmune hepatitis and Graves' disease, can overlap and complicate diagnosis. Persistent or worsening liver dysfunction despite improvement in other thyroid parameter may signal underlying liver pathology. Importance of monitoring for rebound thyrotoxicosis and liver dysfunction in thyroid storm. Therapeutic plasma exchange (TPE) as a critical rescue therapy in thyroid storm and metabolic or hepatic encephalopathy.

Summary: Carboxyl ester lipase (CEL) is a major component of pancreatic juice and is responsible for the duodenal hydrolysis of cholesteryl esters. Maturity-onset diabetes of the young (MODY) is a form of diabetes mellitus characterized by early onset and dominant inheritance of beta-cell dysfunction. CEL gene mutations cause the type of MODY denoted as MODY8. Herein, we describe a Japanese patient who harbored a heterozygous A689P mutation in the variable number of tandem repeats (VNTRs)-containing exon 11 of the CEL gene. The patient was not obese and his diabetes was characterized by onset in late adolescence, impaired insulin secretion and metabolic dysfunction-associated steatotic liver disease (MASLD). The C-terminal region of CEL has been postulated to be critical for its secretion and activity. Therefore, the A689P mutation may cause pancreatic exocrine insufficiency and eventually contribute to MASLD, which is associated with reduced lipid catabolism. MODY8 is also considered to be a protein-misfolding disease because a heterozygous single nucleotide deletion causes the production of mutant CEL protein leading to diabetes and exocrine dysfunction. In the present case, MASLD and diabetes characterized by impaired insulin secretion were observed. The CEL A689P missense mutation will expand the known genotype-phenotype correlation in diabetes if it can be demonstrated that the variant is pathogenic.

Learning points: The CEL gene encodes the digestive enzyme carboxyl ester lipase, also known as bile salt-stimulated/dependent lipase. CEL is expressed in pancreatic acinar tissue but not in pancreatic β cells. MODY caused by mutations in the CEL gene (MODY8) is characterized by dominantly inherited diabetes mellitus manifesting in early adulthood. A classical feature of MODY8 is pancreatic exocrine dysfunction, often with onset in childhood. Known pathogenic mutations in the CEL gene affect the variable number tandem repeat (VNTR) region in exon 11. Our case suggests that some missense mutations of the CEL VNTR could have a phenotypic implication by being associated with impaired glucose-stimulated insulin secretion and reduced utilization of lipid as an energy source which leads to MASLD.

Summary: We present the case of a 52-year-old Caucasian woman with insulin autoimmune syndrome (IAS) uncovered after corticosteroid treatment for lumbar pain due to disc herniation. We confirmed hypoglycemic episodes 4-5 h after food ingestion, associated with extremely high levels of insulin and the presence of anti-insulin antibodies, establishing the diagnosis of IAS. The most probable cause of the disease was glucocorticoid medication, considering she had no other autoimmune or hematologic disease associated. As the hypoglycemic episodes were mild, the patient received dietary recommendations (small, frequent, low-carbohydrate meals), and 3 months later, she had no more clinical episodes of hypoglycemia, with improved blood insulin level.

Learning points: IAS is a very rare form of hypoglycemia in the Caucasian population, which is why critical thinking and active search are needed. Moreover, drug-induced cases of IAS in the Caucasian population are exceptional, with only one report of glucocorticoid medication as a trigger in the literature. Recognizing IAS is very important in order to avoid unnecessary investigations and choose the right treatment.

Summary: Duchenne and Becker muscular dystrophy (DMD/BMD) are genetic disorders characterized by progressive muscle degeneration due to alterations of the dystrophin protein. The degeneration of skeletal muscles and subsequent replacement with adipose tissue affect motor function as well as insulin sensing and glucose uptake in skeletal muscle, leading to the impairment of systemic glucose tolerance. Although several cases of glucose intolerance accompanied by DMD/BMD have been reported, the development of diabetes is clinically rare in adult cases with DMD/BMD. A 25-year-old man with BMD developed diabetes after receiving heart transplantation due to dilated cardiomyopathy and being on immunosuppressive drugs. Although he did not show evident glucose intolerance before heart transplantation, he demonstrated decreased β-cell function. Despite the shared background of BMD, his older brother, who had not undergone heart transplantation, showed only slightly impaired glucose tolerance and preserved β-cell function. The difference in glucose tolerance in the siblings with BMD clarifies the critical role of β-cell dysfunction in the development of diabetes in individuals with compensatory increasing demand for insulin such as DMD/BMD. In addition, the clinical importance of vigilance for post-transplant diabetes in BMD cases with immunosuppressive agents should be noted.

Learning points: Muscle disease such as Duchenne and Becker muscular dystrophy (DMD/BMD) impairs motor function as well as insulin sensing and glucose uptake in skeletal muscle. While the development of diabetes is very rare in adult cases with DMD/BMD, diabetes can develop with concomitant loss of beta-cell function. Vigilance for post-transplant diabetes in people with muscle disease as well as DMD/BMD with immunosuppressive agents is clinically important.

Summary: Mauriac syndrome is a rare complication in patients with type 1 diabetes. It presents with poor glycemic control and hepatomegaly due to extensive liver glycogen deposition. Whether behavioral or genetic factors play key roles in its pathophysiology remains a subject of debate. We present the case of a 19-year-old woman with poorly controlled type 1 diabetes mellitus and persistently elevated liver enzymes who arrived at the emergency department with diabetic ketoacidosis and hepatomegaly. Blood tests revealed the absence of an associated viral or autoimmune liver disease. Transient liver elastography showed moderate steatosis. Liver biopsy results were consistent with glycogen hepatopathy. Sequencing of genes associated with glycogen storage diseases revealed no pathogenic variants, supporting a non-genetic mechanism for Mauriac syndrome. Insulin regimen and dietary plan were reviewed. Distinction of glycogenic hepatopathy from metabolic dysfunction-associated fatty liver disease is often difficult and frequently only possible through liver biopsy. An accurate diagnosis of Mauriac syndrome carries important prognostic information, as associated hepatomegaly tends to regress through optimization of glycemic control.

Learning points: Mauriac syndrome is a rare complication of poorly controlled type 1 diabetes, presenting with elevated liver enzymes and hepatomegaly due to extensive liver glycogen deposition. Liver biopsy plays a key role in distinguishing glycogenic hepatopathy from metabolic-associated steatotic liver disease. Adequate glycemic control often leads to hepatomegaly regression and normalization of liver enzyme levels in Mauriac syndrome.