Jennifer Rabaglia

The Impact of Obesity on the Presentation of Primary Hyperparathyroidism

CONTEXT Obesity has been associated with elevated serum PTH (sPTH) in the general population. Obesity may also alter the clinical presentation in patients with primary hyperparathyroidism (PHPT). OBJECTIVES The objectives of the study were to compare the clinical presentation of obese (OB) vs nonobese (NO) PHPT patients and to assess the impact of obesity on the presentation of PHPT independent of serum calcium and PTH. PATIENTS Consecutive PHPT patients who underwent parathyroidectomy between 2003 and 2012 by a single surgical group participated in the study. SETTING The study was conducted at an academic medical center. DESIGN Cross-sectional review of records of preoperative demographic, historical, laboratory, and densitometry findings and intraoperative pathological findings were compared in OB vs NO patients. MAIN OUTCOME MEASURES The prevalence of nephrolithiasis and osteoporosis was measured. RESULTS Two hundred forty-seven PHPT patients were included in this analysis. Fifty percent were OB and 79% were women. Mean body mass index was 25.3 ± 3.3 and 36.0 ± 5.2 kg/m(2) in the NO and OB groups, respectively. Age, gender, and race distribution was similar between the two groups. Serum calcium was similar between the groups (11.0 ± 0.7 mg/dL in NO vs 11.1 ± 0.9 mg/dL in OB, P = .13), whereas sPTH was higher in OB (151 ± 70 vs 136 ± 69 pg/mL, P = .03). The OB group exhibited higher prevalence of hypercalciuria (urine calcium > 400 mg per 24 h) (41% vs 23% in NO, P = .01) and nephrolithiasis (36% vs 21% in NO, P = .03). Despite higher sPTH, OB patients showed higher bone mineral density and a lower rate of osteoporosis (21% vs 35%, P = .05). Differences in the prevalence of hypercalciuria and osteoporosis between the groups persisted after adjustment for age, race, estimated glomerular filtration rate, gender, sPTH, and calcium. CONCLUSIONS In PHPT patients, obesity is a risk factor for hypercalciuria and nephrolithiasis and is protective against osteoporosis. The impact of parathyroidectomy on the clinical features of obese PHPT patients merits further evaluation.

AN AGGRESSIVE TEMPORAL BONE SDHC PARAGANGLIOMA ASSOCIATED WITH INCREASED HIF-2α SIGNALING

OBJECTIVE To describe a patient with a germline succinate dehydrogenase (SDHC) gene mutation presenting with primary hyperparathyroidism and a large catecholamine-producing temporal bone paraganglioma (PGL). METHODS Evaluation of a SDHC mutation-positive PGL tumor biology using staining for tyrosine hydroxylase (TH), hypoxia-inducible factors 1α (HIF-1α) and 2α (HIF-2α). RESULTS A 66-year-old man was noted to have a lytic skull base mass during work-up for his primary hyperparathyroidism. Biochemical evaluation with 24-hour urine catecholamines and metanephrines revealed marked elevation of norepinephrine and normetanephrine. Genetic testing revealed a germline SDHC mutation. A partial excision of skull base tumor was performed, which upon further examination revealed PGL. Immunohistochemistry of skull base PGL demonstrated heavy expression of TH and HIF-2α but reduced expression of HIF-1α. The remaining skull base PGL was treated with adjuvant radiation therapy. The patients normetanephrine levels significantly decreased after surgery and radiation. CONCLUSION Here, we report an unusual case of a patient presenting with a germline SDHC mutation-related functional PGL along with concomitant primary hyperparathyroidism. The present case illustrates that overexpression of HIF-2α but not of HIF-1α is linked to the pathogenesis of SDHC mutation-related PGL, and it may be responsible for the aggressive clinical behavior of a usually indolent course of SDHC-related PGLs.

Benign adrenal adenomas secreting excess mineralocorticoids and glucocorticoids.

Objective: To recognize that benign adrenal adenomas can co-secrete excess aldosterone and cortisol, which can change clinical management. Methods: We reviewed the clinical and histological features of an adrenal tumor co-secreting aldosterone and cortisol in a patient. Biochemical testing as well as postoperative immunohistochemistry was carried out on tissue samples for assessing enzymes involved in steroidogenesis. Results: A patient presented with hypertension, hypokalemia, and symptoms related to hypercortisolism. The case demonstrated suppressed renin concentrations with an elevated aldosterone:renin ratio, abnormal dexamethasone suppression test results, and elevated midnight salivary cortisol concentrations. The patient had a right adrenal nodule with autonomous cortisol production and interval growth. Right adrenalectomy was carried out. Postoperatively, the patient tolerated the surgery, but he was placed on a short course of steroid replacement given a subnormal postoperative serum cortisol concentration. Long-term follow-up of the patient showed that his blood pressure and glucose levels had improved. Histopathology slides showed positive staining for 3β-hydroxysteroid dehydrogenase, 11β-hydroxylase, and 21 hydroxylase. Conclusion: In addition to the clinical manifestations and laboratory values, the presence of these enzymes in this type of tumor provides support that the tumor in this patient was able to produce mineralocorticoids and glucocorticoids. The recognition of patients with a tumor that is co-secreting aldosterone and cortisol can affect decisions to treat with glucocorticoids perioperatively to avoid adrenal crisis. Learning points Recognition of the presence of adrenal adenomas co-secreting mineralocorticoids and glucocorticoids. Consideration for perioperative and postoperative glucocorticoid use in the treatment of co-secreting adrenal adenomas.

Pooled human albumin primes neutrophils.

Abstract Human pooled albumin has traditionally been used both to pacify the artificial surfaces in a cardiopulmonary bypass circuit and also for volume repletion following surgery. In evaluating the routine use of albumin in multiple phases of cardiac surgery, conscientious surgical teams must assess both the physiological and financial price of albumin. Albumin indiscriminately binds many plasma proteins and lipids. In this series of experiments, we explored the influence of highly purified albumin devoid of bound lipids and globulins on both receptor‐dependent (FMLP) and receptor‐independent (PMA) priming/activation of human neutrophils. We believe that it is important to distinguish the direct influence of albumin from the albumin‐bound proteins and lipids. We, therefore, also examined the effect of clinically accessible human pooled albumin on human neutrophils. We observed a dose‐dependent priming/activation (elastase release) of human neutrophils by both pooled and purified albumin. We conclude that it is increasingly difficult to justify the routine use of albumin in cardiac surgical patients.

SDHD GENE MUTATIONS: LOOKING BEYOND HEAD AND NECK TUMORS

Objective: Succinate dehydrogenase complex, subunit D (SDHD) gene mutations are most commonly associated with head and neck paragangliomas. We describe a pair of cases with early-onset, bilateral pheochromocytoma (PCC) and paraganglioma (PGL) syndrome associated with SDHD mutation. Methods: We describe 2 cases of hereditary, early-onset, bilateral PCC/PGL syndrome associated with SDHD mutation. Results: Both cases presented under the age of 30 with bilateral PCC and PGL with SDHD mutations. Case 1 is a female who was initially diagnosed with hypertension and later work-up revealed elevated norepinephrine levels. Positron emission tomography coupled with computed tomography showed avid uptake of fluorodeoxyglucose by the right adrenal gland, the organ of Zuckerkandl, and the left carotid bifurcation. Surgical resection was performed and resulted in normalization of her catecholamines. Case 2 is a male who similarly presented with hypertension and elevated norepinephrine levels. Imaging revealed head, neck,...