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Objective: To clarify the selection of medical therapy following transsphenoidal surgery in patients with acromegaly, based on growth hormone (GH)/insulin-like growth factor 1 (IGF-1) response and glucometabolic control. Methods: We carried out a systematic literature review on three of the best studied and most practical predictive markers of the response to somatostatin analogues (SSAs): somatostatin receptor (SSTR) expression, tumor morphologic classification, and T2-weighted magnetic resonance imaging (MRI) signal intensity. Additional analyses focused on glucose metabolism in treated patients. Results: The literature survey confirmed significant associations of all three factors with SSA responsiveness. SSTR expression appears necessary for the SSA response; however, it is not sufficient, as approximately half of SSTR2-positive tumors failed to respond clinically to first-generation SSAs. MRI findings (T2-hypo-intensity) and a densely granulated phenotype also correlate with SSA efficacy, and are advantageous as predictive markers relative to SSTR expression alone. Glucometabolic control declines with SSA monotherapy, whereas GH receptor antagonist (GHRA) monotherapy may restore normoglycemia. Conclusion: We propose a decision tree to guide selection among SSAs, dopamine agonists (DAs), and GHRA for medical treatment of acromegaly in the postsurgical setting. This decision tree employs three validated predictive markers and other clinical considerations, to determine whether SSAs are appropriate first-line medical therapy in the postsurgical setting. DA treatment is favored in patients with modest IGF-1 elevation. GHRA treatment should be considered for patients with T2-hyperintense tumors with a sparsely granulated phenotype and/or low SSTR2 staining, and may also be favored for individuals with diabetes. Prospective analyses are required to test the utility of this therapeutic paradigm. Abbreviations: DA = dopamine agonist; DG = densely granulated; GH = growth hormone; GHRA = growth hormone receptor antagonist; HbA1c = glycated hemoglobin; IGF-1 = insulin-like growth factor-1; MRI = magnetic resonance imaging; SG = sparsely granulated; SSA = somatostatin analogue; SSTR = somatostatin receptor.

To review the current literature regarding the prevalence of macroprolactin (macroPRL) in hyperprolactinemic patients and determine recommendations for testing.An electronic United States National Library of Medicine PubMed search (through October, 2014) was conducted for search term "macroprolactin." Only English-language articles were considered.MacroPRL is an under-recognized cause of elevated prolactin (PRL) and is present in approximately 4% to 40% of hyperprolactinemic patients depending on the referral population. Clinical findings which could be due to hyperprolactinemia are the impetus for testing for PRL. Because of this there is significant overlap in the clinical presentation of patients with true hyperprolactinemia and those with macroPRL, differentiation cannot always be made on the basis of symptoms. A lack of recognition of the presence of macroPRL can lead to unnecessary laboratory investigations, imaging, and pharmacologic or surgical treatment.Until there is a commercially available PRL assay that is not subject to interference by macroPRL, clinicians should consider the possibility of macroPRL, especially if the clinical presentation, imaging findings, and/or response to therapy reveal inconsistencies.

Objective Malignant pheochromocytoma is rare and may be sporadic or have a genetic basis. Vasoactive intestinal peptide (VIP)-secreting pheochromocytoma has rarely been described in the literature, and treatment remains challenging in the absence of well-controlled randomized trials. The hypoxia-inducible factor-vascular endothelial growth factor axis has been implicated in pheochromocytoma when associated with germline Von-Hippel-Lindau (VHL) or succinate dehydrogenase (SDH) mutations, suggesting potential clinical activity of sunitinib in this setting. Methods We present a case report of a patient with a VIP-secreting malignant pheochromocytoma manifested as severe watery diarrhea, with an exquisite clinical response to sunitinib. We review this rare clinical entity and the potential role of sunitinib in this context. Results A 51-year-old male initially presented with a pheochromocytoma causing symptoms related to norepinephrine excess. He underwent adrenalectomy, which resulted in complete resolution of his symptoms. Three years later, he developed multifocal metastatic disease from his primary tumor, showing immunohistochemical evidence of VIP production accompanied by severe watery diarrhea and hypokalemia. The patient had a rapid, complete, and durable clinical response to sunitinib, but with only a minor radiological response and without significant toxicity. Genetic testing was negative for germline mutations in VHL, SDHB, SDHC, SDHD, transmembrane protein 127 (TMEM127) and for neurofibromatosis type 1 (NF-1). Conclusion To the best of our knowledge, this is the first report of a case of malignant VIP-producing pheochromocytoma that was responsive to sunitinib.

To identify clinical variables associated with the presence of a structurally advanced sellar mass (ASM).We performed a retrospective study of patients referred for evaluation of suspected new pituitary disease or sellar mass to the Endocrine Oncology Unit of Mount Sinai Hospital in Toronto, Ontario, Canada. By multivariate analysis, we examined predictors of a structurally ASM (a sellar lesion with any of the following characteristics: diameter ofor=1 cm on magnetic resonance imaging [MRI], optic chiasmal compression on MRI, or clinical or biochemical evidence of hypopituitarism).Data from 152 patients were analyzed. Of the 152 sellar masses, 142 (93%) were pituitary adenomas. An ASM was noted in 85 of the 152 patients (56%). In the final multivariate model, male sex (odds ratio [OR], 6.23; 95% confidence interval [CI], 2.84 to 13.56; P0.001) and self-reported visual field defect (OR, 3.62; 95% CI, 1.07 to 12.25; P = 0.039) were significantly independently associated with the presence of an ASM. The presence of new or changed headaches also tended to be associated with an ASM (OR, 2.11; 95% CI, 0.96 to 4.64; P = 0.063). Age and self-reported galactorrhea were not independently associated with the presence of an ASM and were conditionally removed from the final model.In patients with suspected sellar or pituitary disease, male sex and self-reported visual field defects independently predict the presence of an ASM. New or changed headaches also tend to be related to the presence of an ASM. The presence of predictors of an ASM should prompt expedited sellar MRI and biochemical evaluation.

To report a diagnostically challenging case of preeclampsia.We present a case report with clinical, biochemical, imaging, and immunohistochemical findings. In addition, the clinical features of pheochromocytoma during pregnancy are reviewed, and the challenges in distinguishing it from preeclampsia are discussed.A 33-year-old woman presented at 14 weeks' gestational age with severe hypertension. Evaluation for secondary causes of hypertension were prompted by difficulty controlling the blood pressure and associated symptoms of headache and nausea. Investigations revealed high levels of urinary catecholamines, in conjunction with increased uptake of (111)In-labeled octreotide in the midabdominal area. At 28 weeks' gestation, worsening of blood pressure, high liver enzyme levels, and proteinuria necessitated a cesarean delivery and concomitant hysterectomy. Blood pressure and urinary catecholamine excretion promptly normalized after delivery. Pathologic examination of the uterus and placenta demonstrated no expression of neuroendocrine markers including chromogranin, but the trophoblast demonstrated strong immunostaining for tyrosine hydroxylase. Expression of this rate-limiting enzyme responsible for catecholamine synthesis may have contributed to the pathogenesis of preeclampsia in this patient.This case demonstrates that severe pre-eclampsia may mimic pheochromocytoma.

Objective To determine costs and outcomes over time for surgical and various medical regimens in the management of patients with acromegaly. Methods We studied a sample of 53 consecutive Canadian patients with acromegaly who underwent a transsphenoidal pituitary surgical procedure only (N = 27) or in conjunction with medical therapy (N = 26). Outcomes were analyzed as person-months spent in various health state outcomes, which were defined on the basis of growth hormone and insulin-like growth factor I levels. Costs are reported in 1998 Canadian dollars. Results The mean duration of follow-up was 49 months. Of the 53 patients, 25 (47%) had microadenomas at admission. Patients spent as much as 65% of the time in “uncured” health states. Patients with less extensive disease had better outcomes. The mean annual cost per patient was $8,111 (95% confidence interval, $5,848 to $10,374). Medications were the largest contributor to overall cost (38%). Although per patient surgical costs themselves were high (ranging from approximately $2,800 to $9,200), when averaged over the 4 years the mean annual cost was approximately $2,400, less than the cost of medications. Treatment of macroadenomas cost more than treatment of microadenomas ($11,425 versus $4,442 annually). The treatment of acromegaly costs $14.7 million annually in Canada (95% confidence interval, $10.6 to $18.8 million) and, if patterns of care are similar, about $139 million annually in the United States. Conclusion Treatment of acromegaly is no more costly than therapy for other chronic diseases, especially those with a surgical component. Early diagnosis (at the stage of microadenoma) resulted in better outcomes and lower costs. Thus, from the standpoint of economics and well-being, a continued aggressive attitude toward screening programs and treatment of persistently active acromegaly seems warranted. (Endocr Pract. 2001;7: 170-180)