Case Report: Hypercalcemia as a manifestation of acute adrenal crisis precipitated by fluconazole use, and a review of the literature.

Acute adrenal crisis classically presents with vomiting, altered sensorium, and hypotension. We describe a unique case manifesting with severe hypercalcemia. Addisonian crisis was unusually precipitated by fluconazole use. We reviewed other reported cases and discuss the possible mechanisms of hypercalcemia in adrenal insufficiency. This 67-year-old man presented with fever, cough, and vomiting for 1 week and with anorexia and confusion for 3 weeks. He was hypotensive and clinically dehydrated. Investigations revealed left-sided lung consolidation, acute renal failure, and severe non-parathyroid hormone (PTH)-mediated hypercalcemia (calcium, 3.55mol/L; PTH, 0.81pmol/L). Initial impression was pneumonia complicated by septic shock and hypercalcemia secondary to possible malignancy. He received mechanical ventilation; treatment with intravenous fluids, inotropes, and hydrocortisone for septic shock; and continuous renal replacement therapy with low-calcium dialysate. Although hypercalcemia resolved and he was weaned off inotropes, dialysis, and hydrocortisone, his confusion persisted. When hypercalcemia recurred on day 19 of admission, early morning cortisol was <8 nmol/L, with low ACTH level (3.2 ng/L). Other pituitary hormones were normal. Hypercalcemia resolved 3 days after reinstating stress doses of hydrocortisone, and his mentation normalized. On further questioning, he recently received fluconazole for a forearm abscess. He previously consumed traditional medications but stopped several years ago, which may have contained glucocorticoids. He was discharged on oral hydrocortisone. Cortisol levels improved gradually, and glucocorticoid replacement was ceased after 8 years, without any recurrence of hypercalcemia or Addisonian crisis. Both hypercalcemia and adrenal insufficiency may present with similar non-specific symptoms. It is important to consider adrenal insufficiency in hypercalcemia of unclear etiology.

Cardiovascular outcomes and all-cause mortality in primary aldosteronism after adrenalectomy or mineralocorticoid receptor antagonist treatment: a meta-analysis.

Background: In patients with primary aldosteronism (PA), long-term cardiovascular and mortality outcomes after adrenalectomy vs mineralocorticoid receptor antagonist (MRA) have not been compared yet. We aim to compare the clinical outcomes of these patients after treatment. Design and Methods: A systematic review and meta-analysis was conducted by searching PubMed, Cochrane library, and Embase from no start date restriction to 18 December 2021. Our composite primary outcomes were long-term all-cause mortality and/or major adverse cardiovascular events (MACE), including coronary artery disease (CAD), stroke, arrhythmia, and congestive heart failure. We adopted the random-effects model and performed subgroup analyses, meta-regression, and trial sequential analysis (TSA). Results: A total of 9 studies with 8473 adult patients with PA (≥18 years) were enrolled. A lower incidence of composite primary outcomes was observed in the adrenalectomy group (odds ratio (OR): 0.46 (95% CI: 0.38-0.56), P < 0.001). We found a lower incidence of all-cause mortality (OR: 0.33 (95% CI: 0.15-0.73), P = 0.006) and MACE (OR: 0.55, (95% CI: 0.40-0.74), P = 0.0001) in the adrenalectomy group. The incidence of CAD (OR: 0.33 (95% CI: 0.15-0.75), P = 0.008), arrhythmias (OR: 0.46 (95% CI: 0.27-0.81), P = 0.007), and congestive heart failure (OR: 0.52 (95% CI: 0.33-0.81), P = 0.004) was also lower in adrenalectomy group. The metaregression showed patient's age may attenuate the benefits of adrenalectomy on composite primary outcomes (coefficient: 1.084 (95% CI: 1.005-1.169), P = 0.036). TSA demonstrated that the accrued sample size and effect size were sufficiently large to draw a solid conclusion, and the advantage of adrenalectomy over MRA was constant with the chronological sequence. Conclusions: In conclusion, adrenalectomy could be preferred over MRA for patients with PA in reducing the risk of all-cause mortality and/or MACE and should be considered as the treatment of choice. That patients with PA could get less benefit from adrenalectomy as they age warrants further investigation.

Improvement in quality of life and psychological symptoms after treatment for primary aldosteronism: Asian Cohort Study.

BACKGROUND: In addition to increased cardiovascular risk, patients with primary aldosteronism (PA) also suffer from impaired health-related quality of life (HRQoL) and psychological symptoms. We assessed for changes in HRQoL and depressive symptoms in a cohort of Asian patients with PA, after surgical and medical therapy. METHODS: Thirty-four patients with PA were prospectively recruited and completed questionnaires from 2017 to 2020. HRQoL was assessed using RAND-36 and EQ-5D-3L, and depressive symptoms were assessed using Beck Depression Inventory (BDI-II) at baseline, 6 months, and 1 year post-treatment. RESULTS: At 1 year post-treatment, significant improvement was observed in both physical and mental summative scores of RAND-36, +3.65, P = 0.023, and +3.41, P = 0.033, respectively, as well as four subscale domains (physical functioning, bodily pain, role emotional, and mental health). Significant improvement was also seen in EQ-5D dimension of anxiety/depression at 1 year post-treatment. Patients treated with surgery (n = 21) had significant improvement in EQ-5D index score post-treatment and better EQ-5D outcomes compared to the medical group (n = 13) at 1 year post-treatment. 37.9, 41.6 and 58.6% of patients had symptoms in the cognitive, affective and somatic domains of BDI-II, respectively. There was a significant improvement in the affective domain of BDI-II at 1 year post-treatment. CONCLUSION: Both surgical and medical therapy improve HRQoL and psychological symptoms in patients with PA, with surgery providing better outcomes. This highlights the importance of early diagnosis, accurate subtyping and appropriate treatment of PA.

Secondary hypertension in adults.

Secondary hypertension occurs in a significant proportion of adult patients (~10%). In young patients, renal causes (glomerulonephritis) and coarctation of the aorta should be considered. In older patients, primary aldosteronism, obstructive sleep apnoea and renal artery stenosis are more prevalent than previously thought. Primary aldosteronism can be screened by taking morning aldosterone and renin levels, and should be considered in patients with severe, resistant or hypokalaemia-associated hypertension. Symptoms of obstructive sleep apnoea should be sought. Worsening of renal function after starting an angiotensin-converting enzyme inhibitor suggests the possibility of renal artery stenosis. Recognition, diagnosis and treatment of secondary causes of hypertension lead to good clinical outcomes and the possible reversal of end-organ damage, in addition to blood pressure control. As most patients with hypertension are managed at the primary care level, it is important for primary care physicians to recognise these conditions and refer patients appropriately.