Elevated Serum Androstenedione Level in a Patient With Ectopic Adrenocorticotropic Hormone Syndrome.

Background/Objective: Ectopic Cushing syndrome can be challenging to diagnose when its presentation is atypical. Herein, we highlight features of ectopic adrenocorticotropic hormone (ACTH) syndrome in a patient with worsening hypertension, hypokalemia, ACTH-dependent hypercortisolism, and disproportionate elevation in serum androstenedione levels. Case Report: A 59-year-old woman presented with rapidly progressing hypertension, severe hypokalemia, confusion, and weakness. Her medical history included well-controlled hypertension receiving amlodipine 5 mg/day, which worsened 3 months prior to admission requiring losartan and spironolactone therapy, with twice daily potassium supplementation. Physical examination was notable for bruising, muscle wasting, thin extremities, facial fullness, and abdominal adiposity despite body mass index 17 kg/m2. Laboratory evaluation showed potassium 2.6 mEq/L (3.5-5.3), morning cortisol >50 mcg/dL (8-25), 24-hour urine cortisol 8369 mcg/day (<50), ACTH 308 pg/mL (<46), androstenedione 398 ng/dL (20-75), dehydroepiandrosterone sulfate 48 mcg/dL (≤430), and testosterone 11 ng/dL (≤4.5) levels. A 3.8-cm carcinoid right lung tumor was identified, and resection was performed with clean margins. Cortisol, androstenedione, and potassium levels rapidly normalized postoperatively and blood pressure returned to baseline, well-controlled on amlodipine. Discussion: Our case illustrates disproportionate elevation in androstenedione levels despite normal dehydroepiandrosterone sulfate and testosterone in a woman with ectopic ACTH syndrome. Limited reports have observed similar discordance in androgen profiles in ectopic versus pituitary ACTH hypersecretion, potentially attributable to differential activation of androgen biosynthesis. Conclusion: Adrenal androgen assessment may help differentiate pituitary versus ectopic ACTH secretion in which androstenedione is elevated, but studies are needed to determine whether disproportionate androstenedione elevation reliably predicts the origin of ACTH excess.

Ten-year Thyroid Cancer Incidence in an Integrated Healthcare Delivery System.

INTRODUCTION: The incidence of papillary thyroid cancer (PTC) has increased in recent decades, but data from community-based settings are limited. This study characterizes PTC trends in a large, integrated healthcare system over 10 years. METHODS: The annual incidence of PTC (2006-2015) was examined among Kaiser Permanente Northern California adults aged 21 to 84 years using Cancer Registry data, including tumor size and stage. Incidence estimates were age-adjusted using the 2010 US Census. RESULTS: Of 2990 individuals newly diagnosed with PTC (76.8% female, 52.7% non-Hispanic White), 38.5% and 61.5% were aged < 45 and < 55 years, respectively. At diagnosis, 60.9% had PTC tumors ≤ 2 cm, 9.2% had tumors > 4 cm, and 66.1% had Stage I disease. The annual age-adjusted incidence of PTC increased from 9.4 (95% confidence interval [CI] = 8.1-10.7) to 14.5 (95% CI = 13.1-16.0) per 100,000 person-years and was higher for female patients than for male patients. Incidence tended to be higher in Asian/Pacific Islanders and lower in Black individuals. Increasing incidence was notable for Stage I disease (especially 2006-2012) and evident across a range of tumor sizes (3.0-4.6 for ≤ 1 cm, 2.5-3.5 for 1-2 cm, and 2.4-4.7 for 2-4 cm) but was modest for large tumors (0.9-1.5 for > 4 cm) per 100,000 person-years. DISCUSSION: Increasing PTC incidence over 10 years was most evident for tumors ≤ 4 cm and Stage I disease. Although these findings may be attributable to greater PTC detection, the increase across a range of tumor sizes suggests that PTC burden might also have increased.

Ectopic Acromegaly Arising from a Pituitary Adenoma within the Bony Intersphenoid Septum of a Patient with Empty Sella Syndrome.

OBJECTIVE: To describe the work-up and treatment of rare ectopic acromegaly caused by a biopsy-proven somatotroph pituitary adenoma located within the bony intersphenoid septum of a patient with empty sella syndrome (ESS). METHODS: We report the presentation, clinical course, diagnostic work-up, and lesion localization and treatment challenges encountered in a 55-year-old patient, with a brief review of relevant literature. RESULTS: A 55-year-old African-American man presented with acromegaly and ESS. Attempts to definitively localize the causative tumor were unsuccessful, though petrosal sinus sampling supported central growth hormone production and imaging suggested bone-enclosed subsellar pituitary tissue. Endoscopic endonasal transphenoidal exploration was undertaken with resection of a somatotroph pituitary microadenoma, and subsequent clinical improvement and biochemical remission. Retrospective review revealed the patient's pituitary to have been located ectopically within a unique bony intersphenoid septum. CONCLUSION: This report describes the first known case of an ectopic pituitary adenoma located within the midline bony intersphenoid septum, which we postulate to have resulted from anomalous embryological pituitary migration. Intra-intersphenoid septal tumors should be considered in cases of apparent central acromegaly with ESS or absence of tumor tissue within the paranasal sinuses or other peripheral locations. INDEXING: Acromegaly, ESS, pituitary adenoma, sphenoid sinus septum.

Inpatient studies of a Kalman-filter-based predictive pump shutoff algorithm.

BACKGROUND: An insulin pump shutoff system can prevent nocturnal hypoglycemia and is a first step on the pathway toward a closed-loop artificial pancreas. In previous pump shutoff studies using a voting algorithm and a 1 min continuous glucose monitor (CGM), 80% of induced hypoglycemic events were prevented. METHODS: The pump shutoff algorithm used in previous studies was revised to a single Kalman filter to reduce complexity, incorporate CGMs with different sample times, handle sensor signal dropouts, and enforce safety constraints on the allowable pump shutoff time. RESULTS: Retrospective testing of the new algorithm on previous clinical data sets indicated that, for the four cases where the previous algorithm failed (minimum reference glucose less than 60 mg/dl), the mean suspension start time was 30 min earlier than the previous algorithm. Inpatient studies of the new algorithm have been conducted on 16 subjects. The algorithm prevented hypoglycemia in 73% of subjects. Suspension-induced hyperglycemia is not assessed, because this study forced excessive basal insulin infusion rates. CONCLUSIONS: The new algorithm functioned well and is flexible enough to handle variable sensor sample times and sensor dropouts. It also provides a framework for handling sensor signal attenuations, which can be challenging, particularly when they occur overnight.