JCEM case reports最新文献

Despite tall stature being a characteristic feature of Klinefelter syndrome, occasional cases of short stature have been reported. These cases are often attributed to GH deficiency. This case report details a unique case of a 16-year-old male with Klinefelter syndrome exhibiting proportionate short stature resulting from a heterozygous, likely pathogenic, variant in the ACAN gene c.7141G > A (p.Asp2381Asn). This specific variant, previously identified once in a family with a recessive inheritance pattern is reported here for the first time in an individual with Klinefelter syndrome. This report emphasizes the importance of a thorough evaluation and consideration of genetic testing for an underlying diagnosis in short-statured individuals with Klinefelter syndrome. Timely detection would enable appropriate therapeutic interventions.

Primary pigmented nodular adrenocortical disease (PPNAD) is a rare cause of ACTH-independent Cushing syndrome (CS), presenting diagnostic challenges due to its rarity and its difficult clinical differentiation from other causes of CS. Here, we report the case of a 22-year-old female who developed classical symptoms of hypercortisolism including progressive weight gain, moon facies, and various skin manifestations. Despite biochemical screening confirming ACTH-independent CS, imaging modalities including computed tomography and magnetic resonance imaging showed normal adrenal gland morphology, complicating the localization of cortisol hypersecretion. Subsequent nuclear imaging methods were not indicative of ectopic cortisol production until adrenal vein sampling (AVS) conclusively identified the adrenal glands as the only possible source of cortisol hypersecretion. Eventually, bilateral adrenalectomy led to a significant improvement in symptoms. Pathological examination confirmed the diagnosis of PPNAD, and genetic testing revealed a mutation in the PRKAR1A gene associated with the Carney complex. This case highlights the importance of considering rare etiologies in hypercortisolism diagnosis and describes their challenging diagnostic workup and the utility of AVS in localizing cortisol hypersecretion in PPNAD patients.

Vitamin D-dependent rickets type 1A is caused by pathogenic variants of CYP27B1 gene, which is inherited in autosomal recessive pattern. These variants lead to defective 1α-hydroxylase enzymatic activity, leading to impaired renal formation of 1,25(OH)₂ vitamin D. We report a case of a 16-year-old Asian male patient, with short stature and progressive bone deformity, whose biochemical parameters revealed low levels of 1,25(OH)₂ vitamin D, low serum calcium levels, along with high phosphorus and raised levels of intact parathyroid hormone. These biochemical parameters suggested the diagnosis of pseudohypoparathyroidism. The patient also had concurrent extrapulmonary tuberculosis during the time of presentation to our endocrine unit. However, on molecular testing, it was revealed that the patient was harboring pathogenic variants of the CYP27B1 gene, in a compound heterozygous manner, with a novel missense mutation in exon 6 of the CYP27B1 gene, c.1136G > C (p.Arg379Thr), suggesting the diagnosis of vitamin D-dependent rickets type 1A. The cause of high phosphorus at the time of presentation, which led to a diagnostic dilemma of pseudohypoparathyroidism, was later explained by presence of active extra pulmonary tuberculosis. This report describes a case of vitamin D-dependent rickets type 1A, mimicking pseudohypoparathyroidism owing to presence of concurrent illness like extrapulmonary tuberculosis.

Neuroendocrine neoplasms (NENs) encompass a heterogeneous spectrum of tumors originating from the diffuse neuroendocrine cell system. Approximately 30% of NEN exhibit functional activity with clinical syndromes through hormone-mediated effects. Synchronous and metachronous functioning syndromes, resulting from the simultaneous release of distinct hormones, are exceptionally rare. Of note, hormonal excess syndromes can have a greater effect on patients' morbidity and mortality than the tumor mass itself. We present the case of a 49-year-old male patient affected by an oligo-metastatic ileal NEN, concurrently demonstrating vasointestinal peptide (VIP) and serotonin excretion, complicated by pulmonary tuberculosis. After the first cycle of Lutetium-177-DOTATATE peptide-radio-receptor therapy, the patient developed a severe watery diarrhea, hypokalemia, and achlorhydria (WDHA) syndrome, despite receiving high-dose somatostatin analogues, everolimus, and telotristat ethyl, without any surgical options. The WDHA syndrome necessitated intensive-care-unit (ICU) admission with continual intravenous administration of electrolytes and fluids. With limited alternatives, an off-label intervention using the enkephalinase inhibitor racecadotril was initiated. After 5 days of treatment, the WDHA syndrome exhibited sufficient control, facilitating the patient's discharge from the ICU. This case report underscores racecadotril as an individualized, off-label treatment strategy for patients with severe VIPoma and serotonin-driven WDHA syndrome, where conventional therapeutic avenues have been exhausted.

Dihydropteridine reductase (DHPR) deficiency is a disorder that prevents regeneration of tetrahydrobiopterin (BH4), causing hyperphenylalaninemia (HPA) and low levels of neurotransmitters, including dopamine. Due to low levels of dopamine, patients present with hyperprolactinemia. Treatment consists of a phenylalanine (Phe)-restricted diet, hydroxytryptophan and levodopa (L-Dopa) supplementation, leading to a rapid normalization of prolactin (PRL) levels. We report a case of a patient with DHPR deficiency presenting with new symptomatic hyperprolactinemia and amenorrhea in adolescence despite appropriate management. The prolactinoma was confirmed with pituitary magnetic resonance imaging. The patient was started on cabergoline with rapid normalization of PRL levels and resolution of symptoms, in keeping with previous reports. Cabergoline has a stronger affinity for the D2R receptor and longer half-life than L-Dopa, leading to lactotroph apoptosis, tumor shrinkage, and rapid and maintained normalization of PRL levels, with a better side-effect profile. Patients with DHPR deficiency need to be actively monitored for symptomatic hyperprolactinemia, as L-Dopa monotherapy is insufficient to suppress PRL secretion, leading to lactotroph hypertrophy and proliferation over time and development of prolactinomas in later life.

Gonadotropin-releasing hormone (GnRH(-independent premature puberty in boys, characterized by elevated β-human chorionic gonadotropin (β-hCG) levels, can indicate a secreting germ cell tumor (GCT). These tumors are rare but more common in individuals with Klinefelter syndrome (KS). We present a case of a 7.3-year-old boy with precocious puberty. Physical examination revealed bilateral testicular volumes of 8 to 10 mL and Tanner stage 3 secondary sexual characteristics (genitalia G3, pubic hair P3). His skeletal age was 12 years. Biochemical tests showed suppressed gonadotropin levels, elevated testosterone, and increased β-hCG of 86.6 mIU/mL (86.6 IU/L, reference range: <5 mIU/mL, <5 IU/L). Imaging, including magnetic resonance imaging (MRI), chest x-ray, whole-body computed tomography (CT), and testicular ultrasound, were interpreted as normal except for a small pineal cyst. Karyotype testing confirmed KS. Over 10 months, β-hCG levels fluctuated between 1 to 105 mIU/mL (1-105 IU/L). When β-hCG was 3.6 mIU/mL (3.6 IU/L), a fluorodeoxyglucose positron emission tomography-CT (FDG PET-CT) scan revealed a mediastinal tumor. The tumor was surgically removed and identified as a mature teratoma. This case underscores the importance of karyotype testing and repeated imaging in boys with premature puberty and elevated β-hCG levels, even if β-hCG levels decrease spontaneously and remain low.

Metastatic calcifications are a rare but potentially fatal complication of primary hyperparathyroidism (PHPT). In this case, a 76-year-old man with a previously asymptomatic PHPT developed a hypercalcemic crisis with severe pancreatitis following elective urologic surgery. Despite initial treatment focused on pancreatitis and subsequent organ failure, hypercalcemia persisted, leading to rapid progressive metastatic calcifications in multiple organs. Parathyroidectomy during ongoing pancreatitis successfully reduced calcium levels but not the calcifications. After 4 months of complications and persistent pain, the patient declined further treatment and ultimately succumbed to the disease. The current literature primarily reports single-organ metastatic calcifications due to PHPT. This case represents the only lethal case of systemic metastatic calcifications in the current century. Physicians should be aware of the potential deterioration of hypercalcemia following elective surgery, particularly in the context of renal impairment. Rapid correction of calcium levels may prevent severe complications such as fatal metastatic calcifications.

Insulin-producing pancreatic tumors are a common subtype of neuroendocrine tumor. Standard of care includes surgical resection of the pancreatic tumor and medical management with somatostatin analogs. For patients with metastatic disease, tumor control and hypoglycemic symptom relief can be achieved through surgical resection of the tumor, hepatic artery embolization, radiofrequency ablation, or radioembolization using radioactive isotopes as well as with systemic therapy such as somatostatin analogs and everolimus. We present the case of a 74-year-old male with metastatic insulin-producing pancreatic carcinoma. After a long history of successfully controlling his hypoglycemic episodes post-liver wedge resection, bland embolizations subsequently failed to maintain control of the frequency and severity of his hypoglycemic symptoms. Stereotactic body radiotherapy (SBRT) with protons was used to achieve symptomatic control and led to partial radiographic response with complete resolution of his hypoglycemic episodes. This case demonstrates the potential utility of proton SBRT in metastatic insulinomas.

The differential diagnosis between malignant and benign adrenal cortical tumors is challenging, and concurrent androgen and cortisol production should raise  suspicion of a malignant tumor. We present the case of a 36-year-old woman who exhibited pronounced hirsutism, clitoromegaly, and secondary amenorrhea. A contrast-enhanced computed tomography (CT) scan revealed a 35 × 27 mm right adrenal mass with unenhanced CT attenuation of 40 Hounsfield units (HUs). The mass exhibited absolute and relative washout rates of 50% and 28%, respectively, and was accompanied by a 25 × 20 mm adenopathy located in the hepatogastric space. Total testosterone was elevated by 247 ng/dL (8.56 nmol/L) (normal reference range, 10-75 ng/dL; 0.34-2.6 nmol/L). A 1-mg dexamethasone suppression test revealed an elevated serum morning cortisol concentration of 10.57 μg/dL (291.58 nmol/L) (reference range, <1.8 μg/dL; < 49.66 nmol/L). A fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) scan revealed increased uptake in both the adrenal mass and the adenopathy. Subsequently, the patient underwent an open right adrenalectomy and lymphadenectomy. Histological examination revealed the presence of an adrenal adenoma with myelolipomatous metaplasia, as well as a positive polymerase chain reaction (PCR) for Mycobacterium tuberculosis in the adenopathy.

Autoimmune polyglandular syndrome 1 (APS1) is an autosomal recessive disorder due to biallelic pathogenic variants in the autoimmune regulator (AIRE) gene that manifests with chronic mucocutaneous candidiasis, primary hypoparathyroidism, and adrenal insufficiency. We report a 39-year-old woman with APS1 who developed partial lipodystrophy during adulthood. She presented with diaper rashes, oral thrush, and tetany during infancy due to candidiasis and hypoparathyroidism. During childhood, she developed hypothyroidism, primary adrenal insufficiency, and ovarian insufficiency. At age 14, she received a sibling-matched allogenic bone marrow transplant due to multiple antibiotic-refractory fungal infections. At age 35, her serum triglycerides were 914 mg/dL (10.32 mmol/L) and she had loss of subcutaneous fat from the upper and lower extremities and hips. A whole-body dual-energy x-ray absorptiometry revealed lower-extremity fat at less than the first percentile. Whole-exome sequencing on DNA extracted from saliva revealed pathogenic variants, p.Leu28Pro and p.Arg257* in AIRE but none in the known lipodystrophy genes. Phage-immunoprecipitation-sequencing revealed the presence of autoantibodies to MAGEB1, MAGEB4, and RFX6, which have been previously reported in APS1. Our case suggests that patients with APS1 may develop partial lipodystrophy due to autoantibodies against novel adipocyte-expressed proteins. A causal relationship of high levels of autoantibodies in our patient to adipose tissue-expressed ODC1, NUCKS1, or FNBP1L and lipodystrophy remains uncertain.