Hypoglycemia mediated by paraneoplastic production of Insulin like growth factor–2 from a malignant renal solitary fibrous tumor – clinical case and literature review

BACKGROUND: Hypoglycemic episodes are infrequent in individuals without a history of diabetes mellitus or bariatric surgery. When hypoglycemia does occur in such individuals, an uncommon but important diagnosis to consider is non-islet cell tumor hypoglycemia (NICTH). We report a case of NICTH associated with paraneoplastic insulin-like growth factor-2 (IGF-2) production and review current relevant medical literature. CASE PRESENTATION: A 60 year old male with no relevant past medical history was referred to the endocrinology clinic with 18 month history of episodic hypoglycemic symptoms and, on one occasion was noted to have a fingerstick glucose of 36 mg/dL while having symptoms of hypoglycemia. Basic laboratory evaluation was unrevealing. Further evaluation however showed an elevated serum IGF-2 level at 2215 ng/mL (reference range 411–1248 ng/mL). Imaging demonstrated a large right suprarenal mass. A right nephrectomy with resection of the mass demonstrated a malignant solitary fibrous tumor. Post resection, the patient’s IGF-2 levels normalized and hypoglycemic symptoms resolved. CONCLUSION: Due to the structural and biochemical homology between IGF-2 and insulin, elevated levels of IGF-2 can result in hypoglycemia. A posttranslational precursor to IGF-2 known as “big IGF” also possesses biologic activity. Review of recent reported cases of NICTH identified widespread anatomic locations and varied pathologic diagnoses of tumors associated with paraneoplastic production of IGF-2 causing hypoglycemia. Definitive management of hypoglycemia associated with paraneoplastic production of IGF-2 consists of resection of the tumor responsible for IGF-2 production. Accumulating literature provides a firm basis for routine IGF-2 laboratory evaluation in patients presenting with spontaneous hypoglycemia with no readily apparent cause

Glycemia and β-cell function before and after elexacaftor/tezacaftor/ivacaftor in youth and adults with cystic fibrosis

BACKGROUND: Diabetes is prevalent among people with CF (PwCF) and associated with worse clinical outcomes. CFTR modulators are highly effective in improving the disease course of CF. However, the effects of elexacaftor/tezacaftor/ivacaftor (ETI) on glucose metabolism in PwCF are unclear. METHODS: Twenty youth and adults with CF underwent frequently sampled oral glucose tolerance tests (fsOGTT) before and after ETI initiation. Glucose, insulin, and C-peptide were collected at 0, 10, 30, 60, 90, and 120 min after 1.75 g/kg (max 75 g) of dextrose. HbA1c and continuous glucose monitoring (CGM) were collected in a subset. Estimates of insulin secretion (C-peptide index), insulin resistance (HOMA2 IR and IS(OGTT Cpep)), and β-cell function (C-peptide oral disposition index, oDI RESULTS: Participants were a median (IQR) of 20.4 (14.1, 28.6) years old, 75 % male. Follow-up occurred 10.5 (10.0, 12.3) months after ETI initiation. BMI z-score increased from 0.3 (-0.3, 0.8) to 0.8 (0.4, 1.5), p = 0.013 between visits. No significant differences were observed in glucose tolerance, glucose area under the curve, nor fsOGTT glucose concentrations before and after ETI. Median (IQR) C-peptide index increased from 5.7 (4.1, 8.3) to 8.8 (5.5, 10.8) p = 0.013 and HOMA2 IR increased (p \u3c 0.001), while oDI CONCLUSIONS: BMI z-score and measures of both insulin resistance and insulin secretion increased within the first year of ETI initiation. β-cell function adjusted for insulin sensitivity (oD

A Theory of Elites but a Story of Challengers: Authoritarian Institutions, Elite Factionalism, and Regime Resilience in the Islamic Republic of Iran

Ph.D. University of Hawaii at Manoa 2016.Includes bibliographical references.The Islamic Republic of Iran has steadily exhibited an uncanny institutional capacity to resist democracy that has been absent elsewhere where “Spring” uprisings succeeded in expelling long-standing authoritarian incumbents from office, such as in Tunisia and Egypt. Moreover, the Iranian regime’s remarkable resilience has emerged in spite of the presence of a ruling party, long considered to be the most important institution that sustains authoritarian rule. How has the Iranian regime survived decades of elite factionalism, electoral uncertainty, and recurrent outbreaks of mass popular unrest despite the absence of the very institution that theoretical expectation suggests should make it particularly prone to collapse? What explains the dramatic divergence in democratic outcomes among single-party authoritarian regimes throughout the region? This dissertation situates Iran within the context of the comparative literature on authoritarian institutions, specifically the role of political parties in prolonging authoritarian rule. Critically, I contend that the coalitional strength of authoritarianism is determined not necessarily by the presence of a centralized ruling party—long considered to be the climax of authoritarianism’s institutional muscle—but by discrete patterns of contentious politics that erupted before the establishment of authoritarian rule. I argue that disparities in the institutional strength of authoritarian regimes are the product of distinct socio-historical patterns that shape state capacity to overcome problems associated with elite collective action and mass mobilization over the long-term. The social, political and institutional norms generated during protracted, ideologically based social conflict—or social revolution—I contend, are more robust sources for sustaining elite collective action amid particularly threatening episodes of contentious politics. Given that prerevolutionary contentious politics in Iran was grounded in an antiauthoritarian struggle pitting populist social forces against the state, I argue that the coalitional strength of prerevolutionary social forces would later engender the type of contentious politics that continues to punctuate the postrevolutionary political order: endemic factionalism and popular protest. Simply put, strong prerevolutionary coalitions produced strong postrevolutionary factions. Yet the Iranian regime’s incorporation strategies are not what we would expect. Whereas almost all revolutionary regimes and postcolonial states born of protracted, ideologically based violent struggle construct broad-based ruling parties to institutionalize their rule, due to factional bickering and the underlying strength of social-democratic coalitions, the Iranian regime was forced to abolish its brief experiment with party-based politics. By leveraging the counterintuitive expectations generated by these dynamics, I aim to bridge the gulf between theoretical expectation of ruling party strength with empirical observation of its ensuing weakness