Subramanian Kannan

Evaluation of patients with adrenal incidentalomas

Purpose of reviewAdrenal incidentalomas are common in this era of ubiquitous imaging. There is a lack of consensus on the mode and extent of evaluation, and follow-up of adrenal incidentalomas. Recent findingsThere is increasing evidence of morbidity associated with subclinical hormone excess from functioning adrenal masses. Improved radiological techniques and interpretation have helped identify lipid-rich adenomas more accurately and tailor the evaluation of adrenal incidentalomas. SummaryA practical outline in the investigation and follow-up of adrenal incidentalomas incorporating the recent evidence is presented.

Biochemical and radiological relationships in patients with pheochromocytoma: lessons from a case control study.

An elevation of fractionated plasma or urinary metanephrine (MN) or nor‐metanephrine (NMN), collectively called metanephrines (MN and NMN), >4‐fold above the upper limit of normal (ULN) is usually considered to be diagnostic for pheochromocytoma (PHEO). There are a greater number of false positive results when the elevations are more modest.

Insulin Pump Patient Characteristics and Glucose Control in the Hospitalized Setting

Introduction: Patients’ knowledge of their insulin pumps and glucose control during hospitalization has not been studied. Aim: The aim was to study the determinants of glycemic control in patients using continuous subcutaneous insulin infusion (CSII) in the hospital. Methods: Three groups of patients were identified: those who did not need any inpatient education and continued on CSII (gorup A), those who received education then continued on CSII (group B), and those for whom CSII was not appropriate and were treated with multiple daily insulin injections (gorup C). We compared the measures of glycemic control between the 3 groups and analyzed which variables impacted glucose control. Results: There were 50 patients, with 51 hospital admissions, 57% males, mean age 48 ± 13 years, 86% had type 1 diabetes (T1DM). The mean DM duration was 26 ± 14 years, mean duration of CSII use was 8.7 ± 6 years, and mean HbA1c was 7.6 ± 1.4%. The mean duration of hospital stay was 5.6 ± 4.6 days. Mean blood glucose (BG) and frequency of hyperglycemia and hypoglycemic events among the 3 groups adjusted for their duration of hospital stay were not statistically different. None of the patients developed diabetic ketoacidosis while using their pump. Stepwise multivariate analysis revealed knowledge of hypoglycemia correction was the single most important predictor of mean BG (P < .001). Conclusion: Patients who received inpatient education performed similarly to patients who did not need inpatient education. Patients who receive inpatient education on CSII fare similar as patients who did not require inpatient education.

A Rare Corticotroph-Secreting Tumor with Coexisting Prolactin and Growth Hormone Staining Cells

Pituitary adenomas can express and secrete different hormones. Expression of pituitary hormones in nonneoplastic pituitary cells is regulated by different transcription factors. Some pituitary adenomas show plurihormonal expression. The most commonly reported plurihormonal adenomas are composed of somatotrophs, lactotrophs, thyrotrophs and gonadotrophs. Pituitary adenomas composed of both corticotroph and somatolactotroph secreting cells are not common because transcription factors regulating the expression of these hormones are different. We report a rare case of pituitary adenoma with concomitant corticotroph, prolactin, and growth hormone staining cells, review literature on similar cases, and discuss possible biological mechanisms underlying these plurihormonal tumors.

Hypercalcemia and acromegaly--clarifying the connections. A case report and review of the literature.

OBJECTIVE Hypercalcemia in patients with acromegaly is rare and usually due to co-existent primary hyperparathyroidism. The etiology of hypercalcemia directly related to acromegaly is debated. METHODS We present a case report of 1,25(OH)2D3-mediated hypercalcemia in a patient with acromegaly and discuss potential pathophysiological mechanisms contributing to the development of hypercalcemia late in the course of the disease. RESULTS A 67-year-old female presented with classical features of acromegaly. A review of her previous photographs suggested a disease duration of approximately 10 years, and her serum calcium (Ca) was normal during this period. A biochemical work up confirmed a combined growth hormone (GH-) and prolactin (PRL-) cosecreting tumor with a GH level of 92.03 ng/mL (normal 0-3.61), an insulin-like growth factor-1 (IGF-1) level of 1,498 ng/mL (59-225), and a PRL level of 223.3 ng/mL (2-17.4). Magnetic resonance imaging (MRI) of the pituitary showed a 1.9-cm macroadenoma. Her preoperative work up revealed new onset hypercalcemia with a corrected serum Ca level of 10.7 mg/dL (8.5-10.5), an ionized Ca level of 1.37 mmol/L (1.08-1.30), a parathyroid hormone (PTH) level of 13.0 pg/mL (10-60), and a high 1,25(OH)2D3 level of 72.6 pg/mL (15-60). She underwent resection of the pituitary adenoma with normalization of GH and PRL levels, and her IGF-1 level decreased to 304 ng/mL. Her serum Ca (9.3 mg/dL), ionized Ca(1.22) and 1,25(OH)2D3 levels (38.6 pg/mL) normalized after surgery. CONCLUSION While overt hypercalcemia in acromegaly is rare, it tends to occur late in the disease course. The hypercalcemia is mediated by elevated 1,25(OH)2D3 levels rather than PTH.

Diagnosis of acromegaly: state of the art

INTRODUCTION Biochemical diagnosis of acromegaly relies on measurement of insulin-like growth factor-1 (IGF-1) and growth hormone (GH). An elevated IGF-1 level above the age- and gender-specific normal range and nonsuppression of GH to oral glucose load to a nadir < 0.4 ng/ml in sensitive assays are currently considered diagnostic of acromegaly. Lack of normative data for both IGF-1 and GH across a wide range of populations and ethnicities, interassay and intraassay laboratory variability, pulsatility of GH secretion, and effects of medications and hormones may confound interpretation of these biochemical tests. AREAS COVERED Clinical situations in which acromegaly should be suspected and/or investigated. Strengths and limitations of current IGF-1/GH assays are discussed. Clinical scenarios with discordant GH suppression test and IGF-1 levels and, briefly, acromegaly in pregnancy, prolactin-cosecreting tumors, familial acromegaly, and nonpituitary acromegaly are also discussed. EXPERT OPINION Serum IGF-1 is the cornerstone and in most cases the stand-alone test in the diagnosis and follow-up in patients with acromegaly. Diagnosis depends on the accurate and reliable measurement of serum IGF-1. GH suppression testing is currently used in limited clinical setting. Standardization of IGF-1 assay and development of normative data across a wide population base are needed. Newer bioassays for IGF-1 hold promise for future.

LIMITED CARBOHYDRATE REFEEDING INSTRUCTION FOR LONG-TERM WEIGHT MAINTENANCE FOLLOWING A KETOGENIC, VERY-LOW-CALORIE MEAL PLAN

OBJECTIVE Weight-loss maintenance following very-low-calorie meal plans is poorly studied. This report describes weight-loss efficacy and predictors of weight-loss maintenance of a ketogenic, very-low-calorie meal plan (protein-sparing modified fast, PSMF) in people with obesity. METHODS A total of 127 consecutive adults in the PSMF meal plan (27.2 ± 19.5 weeks) and 48 adults on a conventional, hypocaloric meal plan (23.6 ± 20.8 weeks) were retrospectively studied for percent weight change from baseline to end of intervention and at 6, 12, and 24 months postintervention. Baseline factors were analyzed for correlations with weight-loss maintenance. RESULTS At end of intervention, weight loss from baseline was greater for the PSMF group compared to the conventional intervention group (-12.4% vs. -2.6%; P<.001) but was similar between groups by 12 months postintervention. PSMF subjects who attended follow-up visits to receive instruction on gradual and limited carbohydrate refeeding after ketosis saw significant weight loss at the end of PSMF compared to those who did not follow-up to receive instruction (-17.5% vs. -8.0%; P<.001) and maintained greater weight loss through 12 months post-PSMF (-9.8% vs. -1.5%; P<.001). Higher baseline body mass index correlated with less weight loss at 12 months post-PSMF (P = .035). CONCLUSION PSMF results in effective short-term weight loss of more than 5% from baseline weight. Follow-up for limited carbohydrate refeeding instruction is important for weight-loss maintenance up to 2 years after initial weight loss. ABBREVIATIONS BMI = body mass index; PSMF = protein-sparing modified fast.

Early radiological clues in diagnosis of adrenocortical carcinoma: Lessons from a missed opportunity

A 54-year-old woman found to have a 2.6-cm irregularly shaped, right adrenal incidentaloma (AI) during work up for appendicitis. The mass had a non-contrast CT attenuation of 35 HU and a focal speck of calcification (Fig. 1a). A follow-up CT scan 6 months later showed a stable size adrenal mass with a delayed absolute and relative washout of 58 and 41 %, respectively. Work up was negative for hormonal hypersecretion. Patient underwent right adrenalectomy. Unfortunately the mass was not resected along with the right adrenal gland. The surgical pathology reported a normal adrenal gland with an adjacent area of mature adipose tissue consistent with a lipoma. This lipomatous tissue was assumed to be the visualized adrenocortical tumor and patient was discharged from clinical care. A repeat CT abdomen, 4 years later for unrelated reasons, showed 11 cm 9 9 cm heterogeneously enhancing mass arising from the right adrenal bed with areas of necrosis (Fig. 1a) and patient was referred to our institution. The surgical resection of this mass was aborted intraoperatively as it had invaded the aorta and vertebrae. Core biopsies confirmed the adrenocortical neoplasm (Fig. 1b) and given its clinical behavior is consistent with adrenocortical carcinoma. Pathology slides from the previous institution were reviewed and it was confirmed that the original specimen did not contain the tumor. Discussion

Testicular “Hyperstimulation” Syndrome: A Case of Functional Gonadotropinoma

Gonadotropins secreting pituitary tumors tend to present as sellar mass with hypogonadism. Biologically active LH secretion by these tumors resulting in elevated testosterone is extremely rare. We report a case of a 48-year-old male patient who presented with giant pituitary tumor, elevated testosterone, and elevated levels of gonadotropins. Surgical resection of the tumor resulted in normalization of gonadotropins and fall in serum testosterone to subnormal levels in the postoperative period confirming that the tumor was secreting bioactive luteinizing hormone (LH).

Incidental Lipid Poor Adrenal Mass in a Patient with Antiphospholipid Syndrome

Adrenal incidentalomas are commonly encountered in this era of ubiquitous imaging. The attenuation of the incidentaloma measured in Hounsfield units (HU) is an important step in the work up. Attenuation less than 10 HU indicates a benign lesion in more than 98% of cases, whereas attenuation greater than 30 HU is highly suspicious for adrenocortical cancer (ACC). Adrenal hematoma is rarely suspected clinically and exhibits no specific clinical symptoms or laboratory findings. There are multiple radiological features of adrenal hemorrhage and can mimic ACC. We present a case of an adrenal mass in a patient with antiphospholipid syndrome and discuss radiological clues to differentiate adrenal hematomas from ACC and thus avoid unnecessary surgical intervention.