EVOLVING ADRENAL DYSFUNCTION AFTER BILATERAL ADRENAL INFARCTION: A CASE REPORT.

OBJECTIVE: To describe a case of sequential bilateral adrenal infarction and hemorrhage resulting in an unusual pattern of adrenal function over time. METHODS: A 50-year-old male with autoimmune antiphospholipid syndrome (APS) presented to the emergency room with severe abdominal pain. Diagnostic studies performed included contrast-enhanced computerized tomographic (IV-CT) imaging of abdomen and pelvis, and laboratory assessment of the hypothalamic-pituitary-adrenal axis. RESULTS: IV-CT of abdomen and pelvis on day 1 showed acute left adrenal gland infarction; cortisol level was 19.9 µg/dL and serum sodium was 133 mEq/L. The patient subsequently developed hyponatremia and hypotension. Repeat IV-CT of abdomen and pelvis on day 3 showed hemorrhagic conversion of the left infarcted adrenal gland and a new right adrenal gland infarction. Cosyntropin stimulation test (CST) confirmed primary glucocorticoid insufficiency. Plasma renin activity and the serum aldosterone level were within normal limits with normokalemia. At 7-month follow-up, CST demonstrated cortisol and aldosterone deficiency. CONCLUSION: Adrenal infarction is a rare complication of APS but is the most common endocrine complication. Evidence of bilateral adrenal infarction on imaging does not predict the type of adrenal dysfunction that might ensue, as demonstrated in this case. Thorough evaluation of glucocorticoid, mineralocorticoid, and androgen deficiency should be conducted both at the time of the event and in follow-up.

Obesity and the diagnostic accuracy for primary aldosteronism.

The effects of body mass index on the diagnostic accuracy of primary aldosteronism (PA) are inconsistent and yet important considering the high prevalence and frequent co-occurrence of obesity and hypertension. The current study included 59 adult patients who underwent a stepwise evaluation for PA, using aldosterone to renin ratio for case detection and plasma aldosterone concentration after saline suppression test and/or 24-hour urinary aldosterone after oral sodium loading for case confirmation. Body mass index had a quadratic (U-shaped) correlation with plasma aldosterone concentration, plasma renin activity, aldosterone to renin ratio, and plasma aldosterone concentration after saline suppression test. Among patients with a body mass index ≥30 kg/m2 , the aldosterone to renin ratio yielded lower case detection accuracy of PA. We conclude that obesity results in a nonlinear correlation with plasma aldosterone concentration, plasma renin activity, and aldosterone to renin ratio, which affects the accuracy of case detection for PA. Patients with a body mass index ≥30 kg/m2 are less accurately identified as having PA when saline suppression and/or oral salt loading tests are used for case confirmation.

Pseudohypoaldosteronism type 1 due to novel variants of SCNN1B gene.

UNLABELLED: Autosomal recessive pseudohypoaldosteronism type 1 (PHA1) is a rare disorder characterized by sodium wasting, failure to thrive, hyperkalemia, hypovolemia and metabolic acidosis. It is due to mutations in the amiloride-sensitive epithelial sodium channel (ENaC) and is characterized by diminished response to aldosterone. Patients may present with life-threatening hyperkalemia, which must be recognized and appropriately treated. A 32-year-old female was referred to the National Institutes of Health (NIH) for evaluation of hyperkalemia and muscle pain. Her condition started in the second week of life, when she was brought to an outside hospital lethargic and unresponsive. At that time, she was hypovolemic, hyperkalemic and acidotic, and was eventually treated with sodium bicarbonate and potassium chelation. At the time of the presentation to the NIH, her laboratory evaluation revealed serum potassium 5.1 mmol/l (reference range: 3.4-5.1 mmol/l), aldosterone 2800 ng/dl (reference range: ≤21 ng/dl) and plasma renin activity 90 ng/ml/h (reference range: 0.6-4.3 ng/ml per h). Diagnosis of PHA1 was suspected. Sequencing of the SCNN1B gene, which codes for ENaC, revealed that the patient is a compound heterozygote for two novel variants (c.1288delC and c.1466+1 G>A), confirming the suspected diagnosis of PHA1. In conclusion, we report a patient with novel variants of the SCNN1B gene causing PHA1 with persistent, symptomatic hyperkalemia. LEARNING POINTS: PHA1 is a rare genetic condition, causing functional abnormalities of the amiloride-sensitive ENaC.PHA1 was caused by previously unreported SCNN1B gene mutations (c.1288delC and c.1466+1 G>A).Early recognition of this condition and adherence to symptomatic therapy is important, as the electrolyte abnormalities found may lead to severe dehydration, cardiac arrhythmias and even death.High doses of sodium polystyrene sulfonate, sodium chloride and sodium bicarbonate are required for symptomatic treatment.

Primary Aldosteronism and ARMC5 Variants.

CONTEXT: Primary aldosteronism is one of the leading causes of secondary hypertension, causing significant morbidity and mortality. A number of genetic defects have recently been identified in primary aldosteronism, whereas we identified mutations in ARMC5, a tumor-suppressor gene, in cortisol-producing primary macronodular adrenal hyperplasia. OBJECTIVE: We investigated a cohort of 56 patients who were referred to the National Institutes of Health for evaluation of primary aldosteronism for ARMC5 defects. METHODS: Patients underwent step-wise diagnosis, with measurement of serum aldosterone and plasma renin activity followed by imaging, saline suppression and/or oral salt loading tests, plus adrenal venous sampling. Cortisol secretion was also evaluated; unilateral or bilateral adrenalectomy was performed, if indicated. DNA, protein, and transfection studies in H295R cells were conducted by standard methods. RESULTS: We identified 12 germline ARMC5 genetic alterations in 20 unrelated and two related individuals in our cohort (39.3%). ARMC5 sequence changes in 6 patients (10.7%) were predicted to be damaging by in silico analysis. All affected patients carrying a variant predicted to be damaging were African Americans (P = .0023). CONCLUSIONS: Germline ARMC5 variants may be associated with primary aldosteronism. Additional cohorts of patients with primary aldosteronism and metabolic syndrome, particularly African Americans, should be screened for ARMC5 sequence variants because these may underlie part of the known increased predisposition of African Americans to low renin hypertension.