Ovarian antibodies among SLE women with premature menopause after cyclophosphamide.

BACKGROUND: Women with systemic lupus erythematosus (SLE) are at risk of premature ovarian failure when treated with cyclophosphamide. This risk is increased when autoimmune thyroid disease is present. We undertook this study to determine whether the presence of ovarian autoimmunity also increased the risk of early ovarian failure among women receiving cyclophosphamide. METHODS: We examined the records of women enrolled in the Lupus Family Registry and Repository, a cross-sectional study of ~3300 SLE subjects, for treatment with cyclophosphamide as well as menopausal status. We defined premature menopause as permanent, spontaneous cessation of menstruation before age 45. We measured anti-ovarian antibodies by enzyme-linked immunosorbent assay using stored sera. RESULTS: There were 258 women treated with cyclophosphamide in whom presence of absence or premature menopause could by defined. A total of 169 (65.6%) had premature ovarian failure, while 89 (34.6%) did not. While anti-ovarian antibodies were present in a small percentage of patients, there was no association of premature menopause to either level of these antibodies (16.2 ± 20.3 units vs 17.4 ± 21.7 units, P = NS by Fisher's exact test), or positivity on this testing (11 of 169 [6.5%] positive vs 8 of 89 [8.9%], χ2  = 0.53, P = .46, 95% CI 0.95-1.1). Neither renal disease nor hypothyroidism increased the risk of premature ovarian failure in these women receiving cyclophosphamide. CONCLUSION: Anti-ovarian antibodies among women with SLE are not associated with premature ovarian failure after treatment with cyclophosphamide.

SPONTANEOUS CEREBROSPINAL FLUID LEAK AFTER INITIATION OF DOPAMINE AGONIST THERAPY IN MACROPROLACTINOMAS: TWO CASE REPORTS AND A LITERATURE REVIEW.

OBJECTIVE: To describe 2 spontaneous cerebrospinal fluid (CSF) leaks complicating treatment of macroprolactinoma (MPRL) with dopamine agonist (DA) therapy. METHODS: We present the 2 cases of spontaneous, DA-related CSF leaks. Prolactin levels were used to assess hyperprolactinemia. Beta-2 transferrin was tested in rhinorrhea fluid, and magnetic resonance imaging was used to assess the sella. RESULTS: Case 1 was a 45-year-old woman with a history of MPRL, recently started on bromocriptine at 15 mg/day, presented with clear rhinorrhea, headache, and nuchal rigidity. Magnetic resonance imaging showed a large sellar lesion extending into the cavernous sinuses, posterior sphenoid sinuses, and suprasellar cistern. Computed tomography revealed areas concerning for bony erosion, likely representing leak sites, and the rhinorrhea fluid was positive for beta-2 transferrin, confirming the CSF source. Empiric antibiotics for meningitis were given and she underwent urgent neuroendoscopic, transsphenoidal CSF leak repair and debulking of the pituitary mass. Case 2 was a 55-year-old man with a 10-year history of untreated MPRL who was started on bromocriptine at 5 mg/day 2 weeks prior to admission. He presented with clear rhinorrhea and a metallic taste in his mouth, worse with the Valsalva maneuver. Imaging confirmed clinical suspicion and he was taken for surgery. A high-flow CSF leak was encountered once the tumor was debulked. This was repaired with an abdominal fat pad graft. Both patients developed diabetes insipidus and required postoperative adjuvant DA therapy. CONCLUSION: Spontaneous CSF leaks can complicate medical therapy of large MPRL with underlying skull defects, typically within weeks of initiation of DA. This should prompt clinicians to educate patients about the symptoms of potential CSF rhinorrhea and encourage them to promptly report them.

Diabetes-related events in adolescents and young adults: opportunities for psychosocial interventions.

This study was conducted to evaluate predictive factors of diabetes-related emergency room (ER) visits and hospitalizations among adolescents and young adults (AYA) with type 1 diabetes (T1D). Baseline demographic, medical, and psychosocial variables were collected for 177 AYA with T1D. Medical records were reviewed to identify ER visits and hospitalizations related to diabetes. Those with diabetes-related events had significantly higher hemoglobin A1c (A1c) values at baseline (p = 0.0001) and during an average 3.36 years of follow-up (p < 0.0001). Participants with events were more likely to have Medicaid or no insurance vs. private insurance (p = 0.0006) and were more likely to be on multiple daily injections vs. insulin pumps (p = 0.0159). Participants with events reported greater diabetes impact on their lives and their parents reported less autonomy in AYA with events (p = 0.0435). These results suggest that when participants were transferring from pediatric to adult care services, factors such as A1c, insurance status and diabetes treatment are associated with diabetes-related events. Further research is needed to elucidate a causative relationship and develop focused interventions to reduce diabetes-related events during this high-risk time. Autonomy should be further explored to determine its role in diabetes-related events during this transition period.

Prevalence of dyslipidemia and factors affecting dyslipidemia in young adults with type 1 diabetes: evaluation of statin prescribing.

Background There is limited information about cardiovascular complications among young adults (YA) with type 1 diabetes mellitus (T1DM) who are transitioning from pediatric to adult care. We aimed to study the prevalence and associated factors of dyslipidemia (DLD) and statin treatment in these patients. Methods We recruited 129 YA with T1DM aged 15-25 years. In a cross-sectional analysis, the prevalence of DLD (low-density lipoprotein cholesterol [LDL-C] ≥ 100 mg/dL, high-density lipoprotein cholesterol [HDL-C] <40 mg/dL [males] or <50 mg/dL [females], total cholesterol [TC] ≥200 mg/dL or triglycerides [TG] ≥150 mg/dL) was reported. Socioeconomic and clinical characteristics were compared between YA with and without DLD. We also assessed statin use among YA with DLD. Results DLD was found in 64% of YA, predominantly increased LDL-C (34.9%). Higher mean glycated hemoglobin (HbA1c) was associated with DLD (p < 0.043). Of all YA who met the criteria for statin therapy, only 42% had one prescribed. Conclusions The prevalence of DLD is high in YA with T1DM and is associated with poor glycemic control, and use of statin therapy in this high-risk population is low.

Kratom, an Emerging Drug of Abuse, Raises Prolactin and Causes Secondary Hypogonadism: Case Report.

Background. Kratom is a drug derived from the leaves of the tree Mitragyna speciose, which is native to southern Thailand. The route of administration is oral. Kratom has become increasingly available in the United States. The active ingredients in the drug bind the opioid mu-receptor; therefore, kratom has similar physiological effects as mu-opioids. Elevated prolactin is a common medical condition frequently caused by a variety drugs, including opioids. Case Report. A 42-year-old man presented with poor energy and low libido. He had mildly elevated serum prolactin with hypogonadotropic hypogonadism as evidenced by low serum testosterone with luteinizing hormone and follicle-stimulating hormone in the normal range. At his initial visit, he reported no use of any recreational or therapeutic drug. Two months later when seen in follow-up, both the testosterone and prolactin levels had returned to normal. At that visit he reported frequent use of kratom, which he had discontinued a few days after the first visit. Discussion. Kratom is now widely available in health food stores and online and is considered an emerging drug of abuse. At present kratom is legal in the United States, but recently the Drug Enforcement Administration served noticed of its intention of making kratom a Schedule I drug. A number of adverse events or side effects have been reported, but this is the first report of hyperprolactinemia as the result of ingestion of kratom.

Familial Pallister-Hall in adulthood.

Pallister Hall syndrome is autosomal dominant disorder usually diagnosed in infants and children. Current diagnostic criteria include presence of hypothalamic hamartoma, post axial polydactyly and positive family history, but the disease has variable manifestations. Herein we report Pallister Hall syndrome diagnosed in a family where both patients were adults. A 59 year old man developed seizures 4 years prior to our evaluation of him, at which time imaging showed a hypothalamic hamartoma. The seizures were controlled medically. He did well until he had visual changes after a traumatic head injury. Repeat MRI showed slight expansion of the mass with formal visual field testing demonstrating bitemporal hemianopsia. There was no evidence of pituitary dysfunction except for large urine volume. He underwent surgery to debulk the hamartoma and the visual field defects improved. There was no hypopituitarism post-operatively, and the polydyspia resolved. His 29 year old daughter also had seizures and hypothalamic hamartoma. Both patients had had polydactyly with prior surgical correction in childhood. The daughter underwent genetic testing, which revealed a previously undescribed heterozygous single base pair deletion in exon 13 of the GLI3 gene causing a frameshift mutation. Further investigation into family history revealed multiple members in previous generations with polydactyly and/or seizures. Pallister-Hall syndrome is caused by an inherited autosomal dominant or de novo mutation in GLI3 gene. This rare syndrome has not had prevalence defined, however. Generally, diagnoses are made in the pediatric population. Our report adds to the few cases detected in adulthood.

Menopause and Rheumatic Disease.

Menopause occurs naturally in women at about 50 years of age. There is a wealth of data concerning the relationship of menopause to systemic lupus erythematosus, rheumatoid arthritis, and osteoarthritis; there are limited data concerning other rheumatic diseases. Age at menopause may affect the risk and course of rheumatic diseases. Osteoporosis, an integral part of inflammatory rheumatic diseases, is made worse by menopause. Hormone replacement therapy has been studied; its effects vary depending on the disease and even different manifestations within the same disease. Cyclophosphamide can induce early menopause, but there is underlying decreased ovarian reserve in rheumatic diseases.

X Chromosome Dose and Sex Bias in Autoimmune Diseases: Increased Prevalence of 47,XXX in Systemic Lupus Erythematosus and Sjögren's Syndrome.

OBJECTIVE: More than 80% of autoimmune disease predominantly affects females, but the mechanism for this female bias is poorly understood. We suspected that an X chromosome dose effect accounts for this, and we undertook this study to test our hypothesis that trisomy X (47,XXX; occurring in ∼1 in 1,000 live female births) would be increased in patients with female-predominant diseases (systemic lupus erythematosus [SLE], primary Sjögren's syndrome [SS], primary biliary cirrhosis, and rheumatoid arthritis [RA]) compared to patients with diseases without female predominance (sarcoidosis) and compared to controls. METHODS: All subjects in this study were female. We identified subjects with 47,XXX using aggregate data from single-nucleotide polymorphism arrays, and, when possible, we confirmed the presence of 47,XXX using fluorescence in situ hybridization or quantitative polymerase chain reaction. RESULTS: We found 47,XXX in 7 of 2,826 SLE patients and in 3 of 1,033 SS patients, but in only 2 of 7,074 controls (odds ratio in the SLE and primary SS groups 8.78 [95% confidence interval 1.67-86.79], P = 0.003 and odds ratio 10.29 [95% confidence interval 1.18-123.47], P = 0.02, respectively). One in 404 women with SLE and 1 in 344 women with SS had 47,XXX. There was an excess of 47,XXX among SLE and SS patients. CONCLUSION: The estimated prevalence of SLE and SS in women with 47,XXX was ∼2.5 and ∼2.9 times higher, respectively, than that in women with 46,XX and ∼25 and ∼41 times higher, respectively, than that in men with 46,XY. No statistically significant increase of 47,XXX was observed in other female-biased diseases (primary biliary cirrhosis or RA), supporting the idea of multiple pathways to sex bias in autoimmunity.