Danae A. Delivanis

DIAGNOSIS OF ENDOCRINE DISEASE: The diagnostic performance of adrenal biopsy: a systematic review and meta-analysis

OBJECTIVE To perform a systematic review of published literature on adrenal biopsy and to assess its performance in diagnosing adrenal malignancy. METHODS Medline In-Process and Other Non-Indexed Citations, MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trial were searched from inception to February 2016. Reviewers extracted data and assessed methodological quality in duplicate. RESULTS We included 32 observational studies reporting on 2174 patients (39.4% women, mean age 59.8 years) undergoing 2190 adrenal mass biopsy procedures. Pathology was described in 1621/2190 adrenal lesions (689 metastases, 68 adrenocortical carcinomas, 64 other malignancies, 464 adenomas, 226 other benign, 36 pheochromocytomas, and 74 others). The pooled non-diagnostic rate (30 studies, 2013 adrenal biopsies) was 8.7% (95%CI: 6-11%). The pooled complication rate (25 studies, 1339 biopsies) was 2.5% (95%CI: 1.5-3.4%). Studies were at a moderate risk for bias. Most limitations related to patient selection, assessment of outcome, and adequacy of follow-up. Only eight studies (240 patients) could be included in the diagnostic performance analysis with a sensitivity and specificity of 87 and 100% for malignancy, 70 and 98% for adrenocortical carcinoma, and 87 and 96% for metastasis respectively. CONCLUSIONS Evidence based on small sample size and moderate risk of bias suggests that adrenal biopsy appears to be most useful in the diagnosis of adrenal metastasis in patients with a history of extra-adrenal malignancy. Adrenal biopsy should only be performed if the expected findings are likely to alter the management of the individual patient and after biochemical exclusion of catecholamine-producing tumors to help prevent potentially life-threatening complications.

Pembrolizumab-Induced Thyroiditis: Comprehensive Clinical Review and Insights Into Underlying Involved Mechanisms

Context Thyroid immune-related adverse events (irAEs) in patients treated with programmed death receptor-1 (PD-1) blockade are increasingly recognized as one of the most common adverse effects. Our aim was to determine the incidence and examine the potential mechanisms of anti-PD-1-induced thyroid irAEs. Design Single-center, retrospective cohort study. Patients and Measurements We studied 93 patients with advanced cancer (ages 24 to 82 years; 60% males) who received at least one infusion of pembrolizumab. Thyroid test results and thyroid imaging modalities were reviewed. Comprehensive 10-color flow cytometry of peripheral blood was performed. Results Thirteen (14%) thyroid irAEs were observed. Thyroiditis occurred in seven patients (54%), from which four recovered. New onset of hypothyroidism overt/subclinical developed in three patients. Levothyroxine dosing required doubling in three patients with a known history of hypothyroidism. Thyroperoxidase antibodies were positive in the minority of the patients [4/13 (31%)] and diffuse increased 18fludeoxyglucose uptake of the thyroid gland was observed in the majority [7/11 (64%)] of patients. We observed more circulating CD56+CD16+ natural killer (NK) cells and an elevated HLA-DR surface expression in the inflammatory intermediate CD14+CD16+ monocytes in anti-PD-1-treated patients. Conclusions Thyroid dysfunction is common in cancer patients treated with pembrolizumab. Reversible destructive thyroiditis and overt hypothyroidism are the most common clinical presentations. The mechanism of thyroid destruction appears independent of thyroid autoantibodies and may include T cell, NK cell, and/or monocyte-mediated pathways. Because the thyroid is a frequent target of anti-PD-1 therapies, patients with therapeutically refractory thyroid cancer may be ideal candidates for this treatment.

THERAPY OF ENDOCRINE DISEASE: Improvement of cardiovascular risk factors after adrenalectomy in patients with adrenal tumors and subclinical Cushing’s syndrome: a systematic review and meta-analysis

OBJECTIVE Beneficial effects of adrenalectomy on cardiovascular risk factors in patients with subclinical Cushings syndrome (SCS) are uncertain. We sought to conduct a systematic review and meta-analysis with the following objectives: (i) determine the effect of adrenalectomy compared with conservative management on cardiovascular risk factors in patients with SCS and (ii) compare the effect of adrenalectomy on cardiovascular risk factors in patients with SCS vs those with a nonfunctioning (NF) adrenal tumor. METHODS MEDLINE In-Process & Other Non-Indexed Citations, MEDLINE, EMBASE and Cochrane Central Register of Controlled Trial were searched on 17 November 2015. Reviewers extracted data and assessed methodological quality in duplicate. RESULTS We included 26 studies reporting on 584 patients with SCS and 457 patients with NF adrenal tumors. Studies used different definitions of SCS. Patients with SCS undergoing adrenalectomy demonstrated an overall improvement in cardiovascular risk factors (61% for hypertension, 52% for diabetes mellitus, 45% for obesity and 24% for dyslipidemia). When compared with conservative management, patients with SCS undergoing adrenalectomy experienced improvement in hypertension (RR 11, 95% CI: 4.3-27.8) and diabetes mellitus (RR 3.9, 95% CI: 1.5-9.9), but not dyslipidemia (RR 2.6, 95% CI: 0.97-7.2) or obesity (RR 3.4, 95% CI: 0.95-12). Patients with NF adrenal tumors experienced improvement in hypertension (21/54 patients); however, insufficient data exist for comparison to patients with SCS. CONCLUSIONS Available low-to-moderate-quality evidence from heterogeneous studies suggests a beneficial effect of adrenalectomy on cardiovascular risk factors in patients with SCS overall and compared with conservative management.

Procedural and clinical outcomes of percutaneous adrenal biopsy in a high-risk population for adrenal malignancy.

The role of percutaneous adrenal biopsy in a high‐risk population for adrenal malignancy has not been fully investigated. Our aim was to describe the clinical presentation leading to the adrenal biopsy and evaluate the diagnostic performance, complications and non diagnostic rate of adrenal biopsy.

Diagnostic performance of unenhanced computed tomography and 18F-fluorodeoxyglucose positron emission tomography in indeterminate adrenal tumours

Evidence on the diagnostic performance of adrenal imaging is limited. We aimed to assess the diagnostic performance of unenhanced computed tomography (CT) and 18F‐fluorodeoxyglucose (18FDG) positron emission tomography (PET)/CT imaging in a high‐risk population for adrenal malignancy using an optimal reference standard.

Improvement of cardiovascular risk factors after adrenalectomy in patients with adrenal tumors and subclinical Cushing's syndrome: A systematic review and meta-Analysis

OBJECTIVE Beneficial effects of adrenalectomy on cardiovascular risk factors in patients with subclinical Cushings syndrome (SCS) are uncertain. We sought to conduct a systematic review and meta-analysis with the following objectives: (i) determine the effect of adrenalectomy compared with conservative management on cardiovascular risk factors in patients with SCS and (ii) compare the effect of adrenalectomy on cardiovascular risk factors in patients with SCS vs those with a nonfunctioning (NF) adrenal tumor. METHODS MEDLINE In-Process & Other Non-Indexed Citations, MEDLINE, EMBASE and Cochrane Central Register of Controlled Trial were searched on 17 November 2015. Reviewers extracted data and assessed methodological quality in duplicate. RESULTS We included 26 studies reporting on 584 patients with SCS and 457 patients with NF adrenal tumors. Studies used different definitions of SCS. Patients with SCS undergoing adrenalectomy demonstrated an overall improvement in cardiovascular risk factors (61% for hypertension, 52% for diabetes mellitus, 45% for obesity and 24% for dyslipidemia). When compared with conservative management, patients with SCS undergoing adrenalectomy experienced improvement in hypertension (RR 11, 95% CI: 4.3-27.8) and diabetes mellitus (RR 3.9, 95% CI: 1.5-9.9), but not dyslipidemia (RR 2.6, 95% CI: 0.97-7.2) or obesity (RR 3.4, 95% CI: 0.95-12). Patients with NF adrenal tumors experienced improvement in hypertension (21/54 patients); however, insufficient data exist for comparison to patients with SCS. CONCLUSIONS Available low-to-moderate-quality evidence from heterogeneous studies suggests a beneficial effect of adrenalectomy on cardiovascular risk factors in patients with SCS overall and compared with conservative management.

THERAPY OF ENDOCRINE DISEASE: Improvement of cardiovascular risk factors after adrenalectomy in patients with adrenal tumors and Subclinical Cushing Syndrome: a systematic review and meta-analysis.

OBJECTIVE Beneficial effects of adrenalectomy on cardiovascular risk factors in patients with subclinical Cushings syndrome (SCS) are uncertain. We sought to conduct a systematic review and meta-analysis with the following objectives: (i) determine the effect of adrenalectomy compared with conservative management on cardiovascular risk factors in patients with SCS and (ii) compare the effect of adrenalectomy on cardiovascular risk factors in patients with SCS vs those with a nonfunctioning (NF) adrenal tumor. METHODS MEDLINE In-Process & Other Non-Indexed Citations, MEDLINE, EMBASE and Cochrane Central Register of Controlled Trial were searched on 17 November 2015. Reviewers extracted data and assessed methodological quality in duplicate. RESULTS We included 26 studies reporting on 584 patients with SCS and 457 patients with NF adrenal tumors. Studies used different definitions of SCS. Patients with SCS undergoing adrenalectomy demonstrated an overall improvement in cardiovascular risk factors (61% for hypertension, 52% for diabetes mellitus, 45% for obesity and 24% for dyslipidemia). When compared with conservative management, patients with SCS undergoing adrenalectomy experienced improvement in hypertension (RR 11, 95% CI: 4.3-27.8) and diabetes mellitus (RR 3.9, 95% CI: 1.5-9.9), but not dyslipidemia (RR 2.6, 95% CI: 0.97-7.2) or obesity (RR 3.4, 95% CI: 0.95-12). Patients with NF adrenal tumors experienced improvement in hypertension (21/54 patients); however, insufficient data exist for comparison to patients with SCS. CONCLUSIONS Available low-to-moderate-quality evidence from heterogeneous studies suggests a beneficial effect of adrenalectomy on cardiovascular risk factors in patients with SCS overall and compared with conservative management.

Impact of hypercortisolism on skeletal muscle mass and adipose tissue mass in patients with adrenal adenomas

Abdominal visceral adiposity and central sarcopenia are markers of increased cardiovascular risk and mortality.

Subungual exostosis in an osteoporotic patient treated with teriparatide.

OBJECTIVE To report an unusual case of subungual exostosis in a patient on teriparatide. METHODS We describe the presentation and symptoms of the patient and review of the relevant literature. RESULTS Teriparatide is used for the treatment of osteoporosis. Rat studies using 3-60x the approved human dose have shown an association between teriparatide and an increased risk of osteosarcoma. Subungual exostosis, to our knowledge, has not been reported. We report the case of a 54-year-old female who presented with a 4-month history of pain and swelling in the medial side of her right thumb with no preceding trauma. The patient had history of severe osteoporosis with multiple fractures and was on teriparatide for 16 months. On examination, the right thumb was swollen and tender with no superficial erythema or signs of an infection. X-ray imaging revealed a trabecular bony overgrowth consistent with subungual exostosis. The patient was treated with subungual excision. Pathology showed endochondral bone formation with reactive atypia, consistent with osteocartilaginous exostosis. CONCLUSION To our knowledge, this is the first case hypothesizing an association between teriparatide and subungual exostosis. Subungual exostosis is a benign growth of bone that arises in the distal phalanx, under or adjacent to the nail bed. The pathophysiology is not clearly understood, but the lesion has base of trabecular bone with a proliferating fibrocartilaginous cap. Teriparatide can stimulate the trabecular bone formation. Hence, an association between the use of teriparatide and the development of subungal exostosis cannot be excluded. Further studies delineating this relationship are needed.

Clinical, Biochemical, and Radiological Characteristics of a Single-Center Retrospective Cohort of 705 Large Adrenal Tumors

Objective To characterize large adrenal tumors (≥4 cm in diameter) and to identify features associated with malignancy. Patients and Methods We investigated the clinical, biochemical, and imaging characteristics in a large retrospective single-center cohort of patients with adrenal tumors of 4 cm or more in diameter during the period of January 1, 2000, through December 31, 2014. Results Of 4085 patients with adrenal tumors, 705 (17%) had adrenal masses measuring 4 cm or more in diameter; of these, 373 (53%) were women, with a median age of 59 years (range, 18-91 years) and median tumor size of 5.2 cm (range, 4.0-24.4 cm). Underlying diagnoses were adrenocortical adenomas (n=216 [31%]), pheochromocytomas (n=158 [22%]), other benign adrenal tumors (n=116 [16%]), adrenocortical carcinomas (n=88 [13%]), and other malignant tumors (n=127 [18%]). Compared with benign tumors, malignant tumors were less frequently diagnosed incidentally (45.5% vs 86.7%), were larger (7 cm [range, 4-24.4 cm] vs 5 cm [range, 4-20 cm]), and had higher unenhanced computed tomographic (CT) attenuation (34.5 Hounsfield units [HU] [range, 14.1-75.5 HU] vs 11.5 HU [range, −110 to 71.3 HU]; P<.001). On multivariate analysis, older age at diagnosis, male sex, nonincidental mode of discovery, larger tumor size, and higher unenhanced CT attenuation were all found to be statistically significant predictors of malignancy. Conclusion The prevalence of malignancy in patients with adrenal tumors of 4 cm or more in diameter was 31%. Older age, male sex, nonincidental mode of discovery, larger tumor size, and higher unenhanced CT attenuation were associated with an increased risk for malignancy. Clinical context should guide management in patients with adrenal tumors of 4 cm or more in diameter.