JCEM case reports最新文献

Hypothyroidism is a common clinical condition with nonspecific symptoms such as fatigue, cold intolerance, and constipation. Rarely, severe primary hypothyroidism presents with rhabdomyolysis. We present a 12-year-old boy with several months of fatigue, muscle cramping, and elevated creatine kinase (CK) who was found to have severe primary hypothyroidism. Initial laboratory evaluation was significant for CK 2056 U/L (reference, 0-300 U/L; 34.34 µkat/L) and creatinine 1.39 mg/dL (reference, 0.4-1 mg/dL; 122.88 µmol/L). He was admitted for management of rhabdomyolysis with acute kidney injury. Further biochemical testing revealed profound hypothyroidism-thyrotropin 494 mIU/mL (reference, 0.40-6.00 mIU/mL) and free thyroxine (T4) less than 0.4 ng/dL (reference, 0.80-1.80 ng/dL; <5.15 pmol/L). Thyroglobulin and thyroid peroxidase autoantibodies were positive, confirming autoimmune hypothyroidism. Low-dose levothyroxine was initiated. With aggressive rehydration, creatinine and CK levels improved. The patient was discharged home with instructions to escalate thyroid hormone replacement over 8 weeks. While the etiology of CK elevation in severe hypothyroidism is poorly understood, it is hypothesized that T4 deficiency alters mitochondrial oxidative capacity and glycogenolysis precipitating muscle atrophy and breakdown with CK release. This case highlights that clinicians should consider thyroid function testing in patients with symptoms of muscle pain and unexplained elevations in CK.

The transformation of an adrenocortical adenoma (ACA) to an adrenocortical carcinoma (ACC) is extremely rare. Current guidelines suggest against further imaging studies and follow-up in patients with nonfunctional adrenal incidentalomas (NFAIs) with benign imaging characteristics. Herein, we present a 64-year-old male patient diagnosed initially with a NFAI of 3 cm in size with imaging characteristics consistent with an ACA. However, 13 years after initial diagnosis, this apparent ACA developed into a high-grade cortisol and androgen-secreting ACC with synchronous metastases. The literature review revealed a further 9 case reports of adrenal incidentalomas initially characterized as ACA that subsequently developed into ACC within a period ranging from 1 to 10 years. The pathogenesis of transformation of an initially denoted ACA to ACC is not fully delineated, although the existing literature focuses on the preexisting or changing genetic background of these lesions, highlighting the need to develop robust prognostic markers to identify patients at risk and individualize the follow-up of these unique cases.

Medullary thyroid carcinoma (MTC) can often have an indolent course despite distant metastatic disease. Additionally, given that metastatic MTC is incurable and systemic therapies have non-negligeable toxicities, localized treatments are often favored in presence of oligo-progressive disease. Transarterial radioembolization (TARE) with yttrium-90 (Y90) has emerged as a safe and efficacious treatment for nonresectable primary and metastatic liver tumors, yet data supporting its use in metastatic MTC are limited. We present the case of a patient with hereditary MTC and large bilobar liver metastases who demonstrated tumor response and resolution of their paraneoplastic diarrhea following TARE with Y90 microspheres.

Thyroid autoimmunity is extremely common in the adult population and can affect pregnancy outcomes. Signs in the newborn can range from absent to severe, making the diagnosis easy to miss. We present an interesting case of neonatal Graves disease associated with intrauterine growth restriction, premature delivery, and liver failure with severely high ferritin, thought to be secondary to hemochromatosis. Treatment of the underlying hyperthyroidism caused a rapid resolution of the elevated ferritin and liver failure. This report highlights the importance of considering Graves disease in newborns with liver failure of unknown etiology.

A 71-year-old woman was diagnosed with unresectable metastatic follicular thyroid carcinoma (FTC) and thyrotoxicosis. She was negative for the presence of thyroxine receptor antibody and thyroid-stimulating antibody. Whole-body scintigraphy revealed increased ^99mTc-pertechnetate uptake in metastatic bone lesions but not in the thyroid nodule. Since radioactive iodine therapy was not applicable because the canalis vertebralis had been invaded, treatment with lenvatinib was initiated, along with methimazole and potassium iodide. The serum level of thyroid hormone decreased. The patient developed hypothyroidism, which continued after the methimazole was stopped, suggesting that lenvatinib suppressed the hyperthyroidism. To our best knowledge, this is the first report of a patient with functioning bone lesions of metastatic FTC in whom hyperthyroidism was controlled by lenvatinib without radioactive iodine therapy.

A 51-year-old woman with a history of primary hyperparathyroidism (PHPT) with prior parathyroidectomy, osteoporosis, and learning disability was referred for hypercalcemia discovered after a fall. Family history was negative for PHPT, pituitary, enteropancreatic neuroendocrine, or jaw tumors. Dysmorphic facies, multiple cutaneous melanocytic nevi, café au lait macules, long fingers, and scoliosis were observed. Laboratory evaluation showed an elevated parathyroid hormone (PTH) level, hypercalcemia, and hypophosphatemia, all consistent with PHPT. Preoperative imaging revealed a right inferior candidate parathyroid lesion. The patient underwent right inferior parathyroidectomy with normalization of PTH, calcium, and phosphorus. Genetic testing showed a likely pathogenic de novo heterozygous germline missense variant p.R764W in the ZFX gene that encodes a zinc-finger transcription factor previously shown to harbor somatic missense variants in a subset of sporadic parathyroid tumors. Germline variants in ZFX have been reported in patients with an X-linked intellectual disability syndrome with an increased risk for congenital anomalies and PHPT. Further research may determine if genetic testing for ZFX could be of potential benefit for patients with PHPT and developmental anomalies, even in the absence of a family history of parathyroid disease.

22q11.2 deletion syndrome (22.q11.2 DS) is a genetic syndrome resulting from a microdeletion on chromosome 22. It has a diverse array of manifestations, and most cases are diagnosed early in childhood. We present the case of a 38-year-old female born in a developing country who presented to our clinic to establish care for a history of primary hypothyroidism. She was clinically and biochemically euthyroid on thyroid supplementation. She was also noted to have hypocalcemia in the setting of low PTH, for which the patient was previously prescribed calcitriol. Given a history of cleft palate, abnormal facial features, mild recurrent sinopulmonary infections, and her endocrine history (including short stature with height in the 6th percentile), genetic testing was obtained. She was diagnosed with a heterozygous whole gene deletion of the TBX1 gene. Additional genetic evaluation demonstrated a 2.6-Mb microdeleted segment of the 22a11.2 region encompassing 62 genes. The patient was referred to cardiology for evaluation of cardiac involvement given a history of tachyarrhythmia. This case highlights challenges in diagnosis and the implications of a delayed diagnosis of 22.q11.2 DS.

Multiple myeloma commonly manifests with symptoms arising from the involvement of various organs, particularly the bone and kidneys. In this report, we detail the case of a 44-year-old man who was diagnosed with multiple myeloma associated with reduced bone density. He exhibited clinical findings of osteomalacia due to Fanconi syndrome (characterized clinically by bone pain and proximal weakness and biochemically by elevated serum alkaline phosphatase, hypophosphatemia, hypouricemia, and glucosuria). With phosphate replacement, there was a notable improvement in bone pain, osteomalacia, and bone mineral density. Nevertheless, the patient continued to experience renal wasting of phosphate, uric acid, and glucose despite achieving remission from multiple myeloma for nearly 2 years. Our case highlights several important clinical features of myeloma-associated Fanconi syndrome, including the need to recognize this complication to appropriately treat the underlying bone disease while avoiding osteoclast inhibitors and the long-term persistence of the proximal renal tubulopathy despite achieving remission from myeloma and correction of osteomalacia.

Beckwith-Wiedemann syndrome (BWS) is a genetic overgrowth syndrome with multiple clinical manifestations, including hypoglycemia. Various genetic alterations leading to BWS have been described. Literature has also described the association between BWS and congenital diabetes, but little is known about the association with type 1 diabetes (T1D). We report a 4-year-old female patient with co-occurring BWS and T1D. The patient presented with 2.4-kilogram weight loss in 3 months accompanied by headache, polyuria, and polydipsia. Initial workup showed blood glucose of 681 mg/dL (37.8 mmol/L). Additional workup revealed marked elevation of the glutamic acid decarboxylase 65 and insulin antibodies, confirming the diagnosis of T1D. The patient's initial genetic test results revealed BWS caused by hypomethylation of the imprinting center 2 (IC2) found on maternal chromosome 11. Concurrence of BWS and T1D is rare and there are cases previously described where BWS has co-occurred with congenital diabetes but not T1D. Although the etiology of acquired autoimmunity is unclear, the answer may lie in genetic analysis or autoimmunity secondary to preceding viral illness. Regardless of the etiology, this case emphasizes further exploration of the association between BWS and T1D.

Primary aldosteronism (PA) is a subtype of secondary hypertension categorized as either unilateral PA (eg, aldosterone-producing adenoma [APA]) or bilateral PA. CYP11B2, an aldosterone synthase, is highly expressed in APA. Recent studies have revealed a high prevalence of pathogenic variants in KCNJ5 and the role of DNA methylation on CYP11B2 in APA. We present a case of unilateral PA with pathogenic variants in KCNJ5 and suppressed CYP11B2 expression. A 55-year-old woman with hypertension was referred to our hospital. A high aldosterone-renin ratio was observed; PA was confirmed using the captopril challenge test and the furosemide upright test. Although computed tomography showed no evident tumors in either adrenal gland, adrenal vein sampling revealed left gland dominance. Postoperatively, the aldosterone-renin ratio decreased and captopril challenge test showed negative findings. Pathogenic variants in the KCNJ5 were detected in the adenoma. Although immunohistochemistry for CYP11B2 was negative in adenoma, an aldosterone-producing cell cluster was confirmed in the adjacent left adrenal gland. Furthermore, DNA methylation analysis of the adenoma indicated hypermethylation in the CYP11B2 promoter region. The pathogenic variant in KCNJ5, specific to APA, induces CYP11B2 overexpression, resulting in excess aldosterone. However, these effects can be suppressed by DNA methylation.