JCEM case reports最新文献

Familial dysalbuminemic hyperthyroxinemia (FDH) is a rare condition caused by pathogenic ALB variants, typically involving Arg242. We describe 2 Indian families with FDH. Case 1 showed elevated total (TT4) and free thyroxine (fT4) with normal thyroid-stimulating hormone (TSH). Her 2 children displayed a similar pattern. All 3 had ∼2-6-fold TT4 and 2-4-fold fT4 elevations on Roche COBAS and Beckman ACCESS assays, while Ortho VITROS reported low-normal fT4 and Abbott ARCHITECT showed minimal or no hormone elevation. Genetic analysis identified a novel heterozygous ALB variant, p.Asn415Ile. Case 2 was evaluated after markedly high TT4 was detected during routine screening. He demonstrated 11-13-fold TT4 elevation on most assays, except Ortho VITROS, and only a modest increase on Abbott ARCHITECT. Genetic testing confirmed the p.Arg242Ser ALB variant. To conclude, we report a novel ALB variant and show that Abbott ARCHITECT exhibits the least assay interference among the contemporary immunoassay platforms in FDH.

Ectopic Cushing syndrome is an uncommon cause of hypercortisolism that needs rapid recognition and treatment to reduce complications. Here, we present the case of a 33-year-old man with a 1-year history of severe Cushing syndrome. Biochemical findings showed both high ACTH and 24-hour urine free cortisol, and nonsuppressed morning serum cortisol. The 18fluorine-1,4,7-triazacyclononane-1,4,7-triacetate-octreotide positron emission tomography/computed tomography revealed a large mediastinal tumor with high uptake. Initial biopsy reported a grade 1 neuroendocrine tumor with positive ACTH immunostaining. Treatment was initiated with ketoconazole and somatostatin analog. To achieve rapid Cushing syndrome control, etomidate intravenous infusion was started. After multidisciplinary assessment and because of high surgical risk (concern for airway compromise from tumor location above the trachea, size, and possible mechanical lung compression with laparoscopic adrenalectomy) debulking surgery of the primary tumor was performed first, followed by bilateral adrenalectomy. Pathology findings of the R2 tumor showed a higher grade tumor than previously reported and an 18 Fluorodeoxyglucose positron emission tomography/computed tomography demonstrated distant metastatic disease. In summary, severe hypercortisolism usually occurs in the setting of ectopic production, it can be debilitating with increased mortality, and in this case, tumor aggressiveness and location made management particularly challenging, requiring a multidisciplinary approach.

Type B insulin resistance syndrome (TBIRS) is rare, with an unknown prevalence, characterized by antibodies directed against the insulin receptor. TBIRS may present with hypoglycemia and/or hyperglycemia. A case of hypoglycemia secondary to TBIRS is reported. A 24-year-old woman presented with hypoglycemia associated with the adrenergic and neuroglycopenic symptoms. Clinical examination was normal. After workup, including a 72-hour fast, glucagon test, autoimmune screen, computerized tomography of the abdomen and calcium stimulation test, no cause was apparent. The results of the 72-hour fast were equivocal. Given the lack of a diagnosis, antibodies to insulin receptors were measured and found to be positive, confirming TBIRS as the cause. Oral glucocorticoid therapy was initiated, and no further hypoglycemic episodes occurred. Steroid therapy resulted in iatrogenic Cushing syndrome. Steroid therapy was discontinued after 1 year of initiation. She delivered a healthy baby with no neonatal hypoglycemia. Hypoglycemic episodes recurred 3 years later, at which point she had relocated and was treated elsewhere. Although rare, autoimmune causes of hypoglycemia should be considered when other causes are excluded or when results are equivocal. Management with pharmacotherapy can be effective in inducing remission but long-term monitoring is necessary as patients may relapse.

Somatostatin receptor scanning with radiolabeled somatostatin analogues is an important modality for localizing neuroendocrine tumors (NETs) but may also show activity in normal tissues and non-NET pathologies. A patient with a history of a parathyroid adenoma, papillary thyroid carcinoma, and acoustic neuroma was suspected of harboring a NET based upon 2 circulating tumor nucleic acid tests that used different methodology and a positive ⁶⁸gallium-dodecanetetraacetic acid-tyrosine-3-octreotate (⁶⁸Ga-DOTATATE) scan corresponding to a 2.2-cm right gluteal mass, which was found to be an intramuscular hemangioma expressing somatostatin receptor 2 subtype (SSTR2) in the endothelial cells. Hemangiomas are among the most frequently reported lesions mimicking a NET and should be considered when somatostatin receptor scanning localizes an isolated lesion in an unusual anatomic area.

Lipedema is a lipodystrophic disease characterized primarily by a disproportionate increase in lower body subcutaneous fat. Although moderate weight loss decreases lower body fat mass in women with obesity and lipedema, it is possible that this decrease is due to a reduction in normal subcutaneous fat, rather than lipedema-affected fat. We evaluated the effect of moderate (11%) diet-induced weight loss on body fat mass and distribution, assessed by dual-energy X-ray absorptiometry and magnetic resonance imaging, in a 56-year-old woman with lipedema who was normal weight (body mass index: 23.9 kg/m²) at baseline. Approximately 85% of the decrease in body weight comprised body fat. The relative reduction in upper body fat (abdominal subcutaneous, arm and trunk fat) was similar to the relative reduction in lower body (total leg fat and thigh subcutaneous fat). Accordingly, weight loss did not change the proportion of total body fat comprising leg fat (44.8% and 45.1% before and after weight loss, respectively) or arm fat (9.1% and 9.6% before and after weight loss, respectively). These data suggest weight loss decreases lipedema-affected adipose tissue and demonstrate the therapeutic effect of weight loss on body composition in women with lipedema even if they are normal weight.

Ectopic adrenocorticotropin syndrome (EAS) is usually associated with severe multiple complications and high mortality. Several adrenal steroidogenesis inhibitors can be used to control hypercortisolism when curative surgery is not feasible, but with different availability worldwide. It was long considered that mitotane (MTT) was not suitable for severe Cushing syndrome (CS) due to its delayed onset of action. We present a case of a 17-year-old girl with rapid-onset CS and an extremely high 24-hour urinary free cortisol (UFC) level (>300 times the upper limit of normal). An anterior mediastinal nodule with contrast enhancement was identified in computed tomography, with positive ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography with computed tomography (PET/CT) uptake (maximum standardized uptake value = 10.1), suggestive of a thymic neuroendocrine tumor as the most likely cause of EAS. Preoperative MTT monotherapy titrated to 2 g/day reduced UFC by 85% within 13 days without adverse effects, stabilized severe neuropsychiatric disturbances and opportunistic infections, thus enabling successful thymectomy. The tumor turned out to be an adrenocorticotropin-secreting thymic typical carcinoid. Other EAS cases treated with MTT reported in the literature were reviewed, and the time needed to control hypercortisolism using MTT was shorter than previously reported. Instead of an "add-on drug," we should reconsider the role of MTT in the treatment of severe hypercortisolism in EAS.

Non-parathyroid hormone (PTH)-mediated hypercalcemia has diverse etiologies, including granulomatous disorders such as sarcoidosis, in which extrarenal 1-α-hydroxylase activity leads to excess production of 1,25-dihydroxyvitamin D (1,25(OH)₂D). We report a rare case of sarcoidosis presenting as isolated hypercalcemia without pulmonary involvement, complicated by initially normal 1,25(OH)₂D levels and a false-negative core biopsy. A 44-year-old man with hypertension and type 2 diabetes presented with malaise, polyuria, and polydipsia. Laboratory evaluation showed severe hypercalcemia with suppressed PTH. PTH-related peptide, 25-hydroxyvitamin D, TSH, and albumin were normal. Imaging revealed no osseous lesions or lymphadenopathy. He improved with intravenous fluids, calcitonin, and zoledronic acid. Three months later, he re-presented with recurrent hypercalcemia and elevated 24-hour urinary calcium excretion. Outpatient evaluation revealed elevated 1,25(OH)₂D and retroperitoneal lymphadenopathy. Core needle biopsy was nondiagnostic, but subsequent excisional biopsies of retroperitoneal lymph node confirmed nonnecrotizing granulomatous inflammation. He was diagnosed with sarcoidosis and started on high-dose steroids, later transitioning to mycophenolate. With that treatment, calcium levels normalized quickly. This case highlights the diagnostic complexities of non-PTH-mediated hypercalcemia and underscores the importance of a comprehensive workup, including medication review, laboratory tests, radiography, and biopsy, with consideration for excisional biopsy.

X-linked congenital adrenal hypoplasia (X-linked AHC) is a rare endocrine disorder causing primary adrenal insufficiency (PAI) and often associated with hypogonadotropic hypogonadism (HH). We report a 23-year-old male with early-onset PAI, normal puberty, and azoospermia despite normal testosterone levels. Whole-exome sequencing revealed a novel NR0B1 pathogenic variant (c.625C>T; p.Gln209). NR0B1, also known as DAX1, is critical for adrenal and gonadal development, and animal models suggest that Sertoli cell dysfunction is a key mechanism of infertility, occurring independently of gonadotropin or androgen deficiencies. Taken together, this case expands the clinical spectrum of NR0B1-related disease and underscores the importance of early genetic testing and consideration of this diagnosis even in patients with X-linked AHC and atypical presentations.

Treatment of hypoparathyroidism with activated vitamin D and calcium carbonate is associated with increased risk of hypercalcemia, hypercalciuria, and nephrocalcinosis. These complications are usually due to inadvertent overdose of medications. We present a case of a 6-year-old boy with hypoparathyroidism, sensorineural deafness, and renal dysplasia (HDR) syndrome and feeding difficulties who developed severe hypercalcemia twice, which was caused not just by medication. Both episodes of calcium overload were related to excessive dietary calcium intake from enteral formula. After rehydration and diet change, his blood calcium and urine calcium/creatinine ratio normalized and remained normal with the same dose of calcitriol without calcium carbonate during the following 2 years. This case underscores the importance of assessment of dietary calcium intake in children with hypoparathyroidism, especially those receiving enteral formula. It shows that calcium intake from enteral formula may even become excessive when the volume of formula is increased in pursuit of more calories, and long-term treatment of hypoparathyroidism could be successful with calcitriol without calcium supplement if dietary calcium intake is sufficient. Use of blenderized tube feeding instead of commercial enteral formula in a child with hypoparathyroidism makes it possible to increase calorie intake without causing dietary calcium excess.