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Prevalence of Autoimmune Disease in Patients with Prolactinomas and Non-Functioning Pituitary Adenomas
Abstracts / Can J Diabetes 39 (2015) 529e547
535
Table: BETA-2 Score Over Time. Data are mean ± sd. * p<0.01.^1 week post second transplant ˇ
Week
0
1
4
12
16
17
18-24
1TX 2TX
0.23 0.42 0.25 + 0.65
14.9 2.5 8.4 2.6*
21.6 5.1 12.0 4.5*
24.4 6.0 10.8 5.9*
26.3 4.1 11.8 7.5*
24.6 5.2 18.9 8.7
26.6 3.0 18.8 6.4*
known about its time course. BETA-2 score is a novel, validated, composite score of graft function (integrating glucose, c-peptide, HbA1c and insulin use) based on a single fasting blood sample. We measured BETA-2 weekly to examine islet engraftment over 24 weeks in 16 c-peptide negative islet recipients who achieved II after one (1TX, n¼9), or two (2TX, n¼7) islet infusions. 1TX were II >1 year, 2TX required a second infusion within 3-6 months. Baseline characteristics were similar (1TX v 2TX: age 5511 vs. 4913 years, male 2/9 vs. 4/7, diabetes duration 3212 vs. 3713 years, weight 64.97.8 vs. 68.915.4 kg; p¼ns) although HbA1c was higher in 1TX (9.11.0% vs. 8.20.6%, p<0.05). BETA-2 increased rapidly by W1, further at W4, remaining stable until W16, but was significantly higher in 1TX at each time point (table). In 2TX, BETA-2 increased further 1 week after second infusion, but remained lower than in 1TX between W18-W24. Islet engraftment takes place rapidly over the first week and is almost complete by 1 month. BETA-2 can identify subjects with poor engraftment who require a second infusion and may be useful as a tool to monitor changes in graft function over time.
022-2015.
ADRENAL
Latrogenic Myxoedema Madness Following Radioactive Iodine Ablation for Graves’ Disease with a Concurrent Diagnosis of Primary Hyperaldosteronism VINCENT LAROUCHE*, LINDA SNELL, DAVID V. MORRIS Montréal, QC Myxoedema madness was first described as a consequence of severe hypothyroidism in 1949. Most cases were secondary to longstanding untreated primary hypothyroidism. We here present the first case of iatrogenic myxoedema madness following radioactive iodine ablation for Graves’ disease, with a second concurrent diagnosis of primary hyperaldosteronism. A 29-year-old woman treated with radioactive iodine ablation for Graves’ disease presented three months later with se-vere hypothyroidism, a oneweek history of psychotic behaviour and paranoid delusions. Her psychiatric symptoms abated with levothyroxine replacement. She was concurrently found to be hypertensive and hypokalemic. Primary hyperaldosteronism from bilateral adrenal hyperplasia was diagnosed. As the patient was planning to become pregnant, management had to be modified to account for this. This case report serves as a reminder that myxoedema madness can be a complication of acute hypothyroidism following radioactive iodine ablation of Graves disease and that primary hyperaldosteronism can be associated with autoimmune hyperthyroidism.
023-2015.
PITUITARY
Prevalence of Autoimmune Disease in Patients with Prolactinomas and Non-Functioning Pituitary Adenomas VINCENT LAROUCHE*, JUAN RIVERA, CATHERINE BEAUREGARD, NATASHA GARFIELD Montréal, QC Background: Immune and autoimmune response can be chronically and acutely affected by prolactin. Prolactin receptors are expressed on the membrane of all immune cells. There is growing evidence showing that hyperprolactinemia can primarily
precipitate autoimmune disease (AID). We postulate that patients with prolactinomas may be more prone to autoimmunity. Methods: We conducted a retrospective case-control study comparing the prevalence of AID in 100 newly diagnosed prolactinomas and 100 age- and gender-matched non-functioning pituitary adenomas (NFPA, controls) followed at the Neuroendocrine Clinic of the M.U.H.C. between January 2005 and December 2014. Results: There were 63 women and 37 men in each group. Mean age was 39.7 years for prolactinomas and 45.4 years for NFPA. While in a reference North-American population the prevalence of autoimmunity is 5-8%, 28 cases vs 20 controls were diagnosed with AID in our study. Odds Ratio for AID in prolactinomas compared with NFPA was 1.56, ([0.81 - 2.99], p: 0.19). When adjusting for age, autoimmunity was associated with prolactinomas compared to NFPA (OR 2.20 [1.12 - 4.30], p: 0.02). Subgroup analysis showed a trend to higher rates of autoimmunity in nearly all subgroups. This trend was significant for cases with mild hyperprolactinemia compared with controls (OR 2.40, ([1.01 - 5.71], p: 0.0479). Conclusion: Our study showed a trend to higher prevalence of AID in prolactinomas compared to NFPA. If confirmed in larger studies, this trend may have significant implications for management of patients with prolactinomas. Our data suggests mild hyperprolactinemia may be more deleterious for immune self-tolerance than severe hyperprolactinemia.
024-2015.
GLUCOSE AND METABOLISM
Relationships Between Insulin Resistance, Acyl Ghrelin, Deacyl Ghrelin and Ghrelin O-Acyltransferase in Middle Aged Men SANG YEOUP LEE*, YOUNG HYE CHO Yangsan, South Korea Objective: Des-acyl ghrelin (DAG) is acylated by ghrelin O-acyltransferase (GOAT), and thus, converted to acyl ghrelin (AG). Little is known of the relationships between plasma ghrelin levels and GOAT levels on metabolic status and glucose homeostasis. To test the hypothesis that patients with metabolic syndrome (MS) have higher plasma AG and GOAT levels, but lower total ghrelin (TG) and DAG levels than normal healthy controls, and to determine the relationships between insulin resistance and plasma AG, DAG, and GOAT levels. Materials and methods: The study subjects were 78 asymptomatic middle aged men. We examined relations between plasma AG, DAG, and GOAT levels and socio-demographic, dietary, anthropometric, and metabolic parameters, and associations between insulin resistance and AG, DAG, and GOAT levels in human plasma. Results: DAG and TG level were significantly lower in the MS group than in the non-MS group (P < 0.017, P ¼ 0.01). HOMA-IR values showed a significant negative correlation with DAG (r ¼ -0.271, P¼0.017) and TG (r ¼ -0.271, P¼0.016) levels. AG and GOAT were not significantly correlated with HOMA-IR, and no correlation was found between plasma levels of the two ghrelin types and GOAT. Conclusions: Plasma DAG and TG levels with MS were lower than in subjects without MS. In addition, a significant negative correlation was observed between DAG levels and HOMA-IR, but no correlation was found between plasma AG and GOAT levels and HOMA-IR.
535
Table: BETA-2 Score Over Time. Data are mean ± sd. * p<0.01.^1 week post second transplant ˇ
Week
0
1
4
12
16
17
18-24
1TX 2TX
0.23 0.42 0.25 + 0.65
14.9 2.5 8.4 2.6*
21.6 5.1 12.0 4.5*
24.4 6.0 10.8 5.9*
26.3 4.1 11.8 7.5*
24.6 5.2 18.9 8.7
26.6 3.0 18.8 6.4*
known about its time course. BETA-2 score is a novel, validated, composite score of graft function (integrating glucose, c-peptide, HbA1c and insulin use) based on a single fasting blood sample. We measured BETA-2 weekly to examine islet engraftment over 24 weeks in 16 c-peptide negative islet recipients who achieved II after one (1TX, n¼9), or two (2TX, n¼7) islet infusions. 1TX were II >1 year, 2TX required a second infusion within 3-6 months. Baseline characteristics were similar (1TX v 2TX: age 5511 vs. 4913 years, male 2/9 vs. 4/7, diabetes duration 3212 vs. 3713 years, weight 64.97.8 vs. 68.915.4 kg; p¼ns) although HbA1c was higher in 1TX (9.11.0% vs. 8.20.6%, p<0.05). BETA-2 increased rapidly by W1, further at W4, remaining stable until W16, but was significantly higher in 1TX at each time point (table). In 2TX, BETA-2 increased further 1 week after second infusion, but remained lower than in 1TX between W18-W24. Islet engraftment takes place rapidly over the first week and is almost complete by 1 month. BETA-2 can identify subjects with poor engraftment who require a second infusion and may be useful as a tool to monitor changes in graft function over time.
022-2015.
ADRENAL
Latrogenic Myxoedema Madness Following Radioactive Iodine Ablation for Graves’ Disease with a Concurrent Diagnosis of Primary Hyperaldosteronism VINCENT LAROUCHE*, LINDA SNELL, DAVID V. MORRIS Montréal, QC Myxoedema madness was first described as a consequence of severe hypothyroidism in 1949. Most cases were secondary to longstanding untreated primary hypothyroidism. We here present the first case of iatrogenic myxoedema madness following radioactive iodine ablation for Graves’ disease, with a second concurrent diagnosis of primary hyperaldosteronism. A 29-year-old woman treated with radioactive iodine ablation for Graves’ disease presented three months later with se-vere hypothyroidism, a oneweek history of psychotic behaviour and paranoid delusions. Her psychiatric symptoms abated with levothyroxine replacement. She was concurrently found to be hypertensive and hypokalemic. Primary hyperaldosteronism from bilateral adrenal hyperplasia was diagnosed. As the patient was planning to become pregnant, management had to be modified to account for this. This case report serves as a reminder that myxoedema madness can be a complication of acute hypothyroidism following radioactive iodine ablation of Graves disease and that primary hyperaldosteronism can be associated with autoimmune hyperthyroidism.
023-2015.
PITUITARY
Prevalence of Autoimmune Disease in Patients with Prolactinomas and Non-Functioning Pituitary Adenomas VINCENT LAROUCHE*, JUAN RIVERA, CATHERINE BEAUREGARD, NATASHA GARFIELD Montréal, QC Background: Immune and autoimmune response can be chronically and acutely affected by prolactin. Prolactin receptors are expressed on the membrane of all immune cells. There is growing evidence showing that hyperprolactinemia can primarily
precipitate autoimmune disease (AID). We postulate that patients with prolactinomas may be more prone to autoimmunity. Methods: We conducted a retrospective case-control study comparing the prevalence of AID in 100 newly diagnosed prolactinomas and 100 age- and gender-matched non-functioning pituitary adenomas (NFPA, controls) followed at the Neuroendocrine Clinic of the M.U.H.C. between January 2005 and December 2014. Results: There were 63 women and 37 men in each group. Mean age was 39.7 years for prolactinomas and 45.4 years for NFPA. While in a reference North-American population the prevalence of autoimmunity is 5-8%, 28 cases vs 20 controls were diagnosed with AID in our study. Odds Ratio for AID in prolactinomas compared with NFPA was 1.56, ([0.81 - 2.99], p: 0.19). When adjusting for age, autoimmunity was associated with prolactinomas compared to NFPA (OR 2.20 [1.12 - 4.30], p: 0.02). Subgroup analysis showed a trend to higher rates of autoimmunity in nearly all subgroups. This trend was significant for cases with mild hyperprolactinemia compared with controls (OR 2.40, ([1.01 - 5.71], p: 0.0479). Conclusion: Our study showed a trend to higher prevalence of AID in prolactinomas compared to NFPA. If confirmed in larger studies, this trend may have significant implications for management of patients with prolactinomas. Our data suggests mild hyperprolactinemia may be more deleterious for immune self-tolerance than severe hyperprolactinemia.
024-2015.
GLUCOSE AND METABOLISM
Relationships Between Insulin Resistance, Acyl Ghrelin, Deacyl Ghrelin and Ghrelin O-Acyltransferase in Middle Aged Men SANG YEOUP LEE*, YOUNG HYE CHO Yangsan, South Korea Objective: Des-acyl ghrelin (DAG) is acylated by ghrelin O-acyltransferase (GOAT), and thus, converted to acyl ghrelin (AG). Little is known of the relationships between plasma ghrelin levels and GOAT levels on metabolic status and glucose homeostasis. To test the hypothesis that patients with metabolic syndrome (MS) have higher plasma AG and GOAT levels, but lower total ghrelin (TG) and DAG levels than normal healthy controls, and to determine the relationships between insulin resistance and plasma AG, DAG, and GOAT levels. Materials and methods: The study subjects were 78 asymptomatic middle aged men. We examined relations between plasma AG, DAG, and GOAT levels and socio-demographic, dietary, anthropometric, and metabolic parameters, and associations between insulin resistance and AG, DAG, and GOAT levels in human plasma. Results: DAG and TG level were significantly lower in the MS group than in the non-MS group (P < 0.017, P ¼ 0.01). HOMA-IR values showed a significant negative correlation with DAG (r ¼ -0.271, P¼0.017) and TG (r ¼ -0.271, P¼0.016) levels. AG and GOAT were not significantly correlated with HOMA-IR, and no correlation was found between plasma levels of the two ghrelin types and GOAT. Conclusions: Plasma DAG and TG levels with MS were lower than in subjects without MS. In addition, a significant negative correlation was observed between DAG levels and HOMA-IR, but no correlation was found between plasma AG and GOAT levels and HOMA-IR.