ABSTRACT
Summary: Low high-density lipoprotein cholesterol (HDL-C) is a risk factor for cardiovascular disease. Very low HDL-C levels (less than 20 mg/dL), however, were uncommonly seen and can be due to genetic defects involving the metabolic pathway of high-density lipoprotein (HDL). We encountered a 50-year-old Chinese man who was only noticed to have extremely low HDL-C levels after surviving recurrent episodes of myocardial infarction. Further workup revealed the undetectable level of apolipoprotein A-I, the absence of HDL on gel electrophoresis, and a novel heterozygous splicing variant in the ABCA1 gene, which was predicted to be pathogenic by in silico analysis. To the best of our knowledge, this is the first reported Hong Kong Chinese with ABCA1 deficiency and probable Tangier disease. The association of ABCA1 deficiency/Tangier disease and accelerated atherosclerosis is discussed. Learning points: Clinicians should be aware of the differential diagnoses of very low HDL-C, which could be divided into genetic and acquired causes. Genetic low HDL syndromes include apoA-I deficiency, Tangier disease, and familial LCAT deficiency, each of which has characteristic clinical features and can be differentiated from the other further by apoA-I measurement, lipoprotein analysis, and genetic testing. Patients with ABCA1 deficiency and Tangier disease are at risk of premature coronary artery disease and should be aggressively screened and treated for cardiovascular risk factors and established cardiovascular diseases. Revascularization strategy and indications for coronary artery bypass grafting in patients with Tangier disease and coronary artery disease follow that as for patients without Tangier disease.
ABSTRACT
Background: Adrenocortical carcinoma (ACC) is a rare endocrine malignancy. An accurate diagnosis of ACC is of paramount importance as it greatly impacts the management and prognosis of a patient. However, the differentiation between early stage, low-grade ACC and adrenocortical adenoma (ACA) may not always be straightforward. The recommended classification system, namely, the Weiss scoring system, is not without flaws. We herein report two cases of ACC which were initially diagnosed as ACA according to the Weiss scoring system but developed distant metastases in subsequent years. Case Presentation. Case 1: A 60-year-old Chinese woman presented with a recent onset of worsening of blood pressure control and clinical features of Cushing's syndrome. Investigations confirmed ACTH-independent endogenous hypercortisolism, and a CT abdomen showed a 6 cm right adrenal mass. Twenty-four-hour urine steroid profiling revealed co-secretion of adrenal androgens and atypical steroid metabolites. Laparoscopic right adrenalectomy was performed, and pathology of the tumor was classified as an ACA by the Weiss scoring system. Four years later, the patient presented with an abrupt onset of severe hypercortisolism and was found to have a metastatic recurrence in the liver and peritoneum. The patient received a combination of mitotane, systemic chemotherapy, and palliative debulking surgery and succumbed 8.5 years after the initial presentation due to respiratory failure with extensive pulmonary metastases. Case 2: A 68-year-old Chinese woman presented with acute bilateral pulmonary embolism and was found to have a 3 cm left adrenal mass. Hormonal workup confirmed ACTH-independent endogenous hypercortisolism, and laparoscopic left adrenalectomy revealed an ACA according to the Weiss scoring system. Five years later, she presented with recurrent hypercortisolism due to hepatic and peritoneal metastases. The patient had progressive disease despite mitotane therapy and succumbed 7 years after initial presentation. Conclusions: Although the Weiss scoring system is recommended as the reference pathological classification system to diagnose adrenocortical carcinoma, there remain tumors of borderline malignant potential which may escape accurate classification. Various alternative classification systems and algorithms exist but none are proven to be perfect. Clinicians should recognize the potential limitation of these histological criteria and scoring systems and incorporate other clinical parameters, such as the pattern of hormonal secretion, urinary steroid profiling, and radiographic features, to improve the prognostication and surveillance strategy of these tumors.
ABSTRACT
We report a case of elderly Chinese lady with neurofibromatosis type-1 presenting with longstanding palpitation, paroxysmal hypertension and osteoporosis. Biochemical testing showed mild hypercalcaemia with non-suppressed parathyroid hormone level suggestive of primary hyperparathyroidism, and mildly elevated urinary fractionated normetanephrine and plasma-free normetanephrine pointing to a catecholamine-secreting pheochromocytoma/paraganglioma. Further scintigraphic investigation revealed evidence of a solitary parathyroid adenoma causing primary hyperparathyroidism and a left pheochromocytoma. Resection of the parathyroid adenoma and pheochromocytoma resulted in normalization of biochemical abnormalities and hypertension. The rare concurrence of primary hyperparathyroidism and pheochromocytoma in neurofibromatosis type-1 is discussed. LEARNING POINTS: All NF-1 patients who have symptoms suggestive of a pheochromocytoma/paraganglioma (PPGL), even remotely, should undergo biochemical testing.The initial biochemical tests of choice for PPGL in NF-1 are either plasma-free metanephrines or urinary fractionated metanephrines. Any elevations of metanephrines should be carefully evaluated for the presence of PPGLs in NF-1 patients.Primary hyperparathyroidism (PHPT) is described in subjects with NF-1. Due to the lack of epidemiological and functional studies, their association is yet to be substantiated. Meanwhile, PHPT may further exacerbate the metabolic bone defect in these patients and should be treated when present according to published guidelines.Coexistence of PPGL and PHPT can occur in subjects with NF-1, mimicking multiple endocrine neoplasia type 2 (MEN2).