Erythropoietin and miRNA profiles during the menstrual cycle in relation to hematological and lipid biomarkers

Background: Circulatory micro RNAs (miRNA) have been discussed as complementary diagnostic markers in cardiovascular diseases, and in anti-doping testing. MiR-144 and miR-486 have been associated with cholesterol homeostasis and hematopoiesis, respectively. In addition, they have been suggested as putative biomarkers for autologous blood transfusion and erythropoietin (EPO) doping. The aim of the present study was to assess the variability of miR-144-3p/5p, miR-486-5p/3p and EPO during the menstrual cycle. Secondary aim was to study the correlations between miRNAs, EPO and hematological parameters and lipids. Methods: 13 healthy women with regular menses were followed with weekly blood sampling during two whole menstrual cycles. MiRNAs were analyzed using TaqMan and PCR followed by calculation of the relative expression for each miRNA using ddCT approach. Results: There was no menstrual cycle variability in miRNAs and EPO. MiRNA-144-3p was associated with HDL-C (rs=-0.34, p=0.036) and miRNA-486-5p with Hb (rs=0.32, p=0.046). EPO concentrations correlated to lymphocytes (rs=-0.062, p=0.0002)), Hb (rs= -0.42, p=0.0091), HDL-C (rs=0.36, p=0.030) and triglycerides (rs=-0.54, p=0.0006). Conclusions: The results of this study may increase the understanding of how miR486-5p and miR144-3p as well as EPO correlate to hematopoietic and lipid biomarkers.

Menstrual hygiene practices among high school girls in urban areas in Northeastern Ethiopia: A neglected issue in water, sanitation, and hygiene research

Background Poor menstrual hygiene practices influence school girls’ dignity, well-being and health, school-absenteeism, academic performance, and school dropout in developing countries. Despite this, menstrual hygienic practices are not well understood and have not received proper attention by school WASH programs. Therefore, this study examined the extent of good menstrual hygiene practices and associated factors among high school girls in Dessie City, Amhara Region, northeastern Ethiopia. Methods A school-based cross-sectional study was employed to examine 546 randomly selected high school students in Dessie City, northeastern Ethiopia. Pretested interviewer-administered questionnaires and a school observational checklist were used for data collection. EpiData Version 4.6 and the Statistical Package for the Social Sciences Version 25.0 were used for data entry and analysis, respectively. Bivariate and multivariable logistics regression analyses were employed to identify factors associated with good menstrual hygiene practices. During bivariable analysis, variables with P-values less than 0.25 were retained for multivariable analysis. In the multivariable analysis, variables with a P-value less than 0.05 were declared to be significantly associated with good menstrual hygiene practices. Results Of the respondents, 53.9% (95% CI [49.6, 58.2]) reported good menstrual hygiene practices. The following factors were found to be significantly associated with good menstrual hygiene practices: age range 16–19 years (AOR = 1.93, 95% CI: [1.22–3.06]); school grade level 10 (AOR = 1.90, 95% CI: [1.18–3.07]); maternal education (primary) (AOR = 3.72, 95% CI: [1.81–7.63]), maternal education (secondary) (AOR = 8.54, 95% CI: [4.18–17.44]), maternal education (college) (AOR = 6.78, 95% CI: [3.28–14.02]) respectively]; having regular menses [AOR = 1.85, 95% CI: (1.03–3.32); good knowledge regarding menstruation (AOR = 2.02, 95% CI: [1.32–3.09]); discussing menstrual hygiene with friends (AOR = 1.79, 95% CI: [1.12–2.86]), and obtaining money for pads from the family (AOR = 2.08, 95% CI: [1.15–3.78]). Conclusion We found that more than half of high school girls had good menstrual hygiene practices. Factors significantly associated with good menstrual hygiene practices include high school girls age 16–18 years, girls grade level 10, maternal education being completed primary, secondary and college level, having regular menses, good knowledge regarding menstruation, discussing menstrual hygiene with friends and obtaining money for pads from the family. Therefore, educating of high school student mothers about MHP should be a priority intervention area to eliminate the problem of menstrual hygiene among daughters. Furthermore, in order to improve the MHP among high school girls, further attention is needed to improving knowledge regarding menstruation among high school girls, encouraging high school girls’ families to support their daughters by buying sanitary pads and promoting discussions among friends about menstrual hygiene. Schools need to focus on making the school environment conducive to managing menstrual hygiene by increasing awareness of safe MHP and providing adequate water/sanitation facilities.

Exogenous Cushing’s Syndrome, Hypogonadism and Diabetes Secondary to Megestrol Acetate

Introduction: Megestrol acetate (MA) is a synthetic progestin that is often prescribed for anorexic patients with HIV due to its effects on weight gain and appetite stimulation. It can cause several endocrine/metabolic abnormalities. Chronic use of MA can cause exogenous Cushing’s Syndrome (ECS) and iatrogenic adrenal insufficiency (AI) due to its stronger affinity for the glucocorticoid receptor (GR). It can also cause gonadotropin suppression, diabetes and hyperprolactinemia. We present a case of a young woman with perinatal HIV/AIDS that developed ECS secondary to MA treatment in the setting of fatigue, rapid weight gain and irregular menses. Case: A 19 year old female with perinatal HIV/AIDS (CD4<200) was treated with MA (200mg/day for 5 months) for anorexia and weight loss. On exam she was pre-hypertensive (BP 138/62), obese (BMI 43.07, SDS +2.25; weight 114kg, SDS +2.34) with increased fat deposition over upper back and abdominal striae, excessive weight gain (21.5 kg in 5 months) suggestive of ECS. She had menarche at 13 years of age and had regular menses until starting MA, upon which she developed oligomenorrhea. A random serum cortisol level was <0.5ug/dl at 1pm with a low ACTH <1.5pg/ml and DHEAS of 13.4ug/dl. Her FSH was 3.4 mIU/L and LH 0.82 mIU/L, estradiol was <2pg/dl and total testosterone <2.5ng/dl consistent with secondary hypogonadism. Liver/kidney function, prolactin and lipid profile were normal. HbA1c increased from 5.3 to 6.4% in 8 months so she was started on metformin. ECS with AI, central hypogonadism and diabetes were all attributed to MA therapy. MA was discontinued gradually over two weeks. Stress dosing of glucocorticoids were advised as needed. Results: Gradual recovery of HPA axis was noted after discontinuation of MA. Two months after taper, serum ACTH level rose to 2.5pg/ml but AM cortisol level remained low at <0.5ug.dl. Her HPA axis showed partial recovery by 5 months with ACTH level of 53.2pg/ml and AM cortisol level of 5.5ug/dl. By 8 months after discontinuing MA therapy, AM cortisol was 9.3ug/dl, suggesting complete HPA axis recovery. Her HPG axis also normalized by 8 months with FSH 6.6 mIU/L and LH of 14.6 mIU/L, estradiol 32pg/dl with regular menses. Metformin was discontinued at 4 months due to hypoglycemia and HbA1C of 5.7%. Subsequently, euglycemia was achieved (HbA1C of 5.4%) within 9 months. BMI was stable (BMI 43.07, SDS +2.25; weight 114kg, SDS +2.34). Conclusion: Multiple endocrine abnormalities may occur due to MA therapy due to its affinity to bind with glucocorticoid and progesterone/androgen receptors. ECS and AI are known to occur with various forms of glucocorticoid use, but rarely can be seen with MA therapy. HPA axis, HPG axis and metabolic parameters should be evaluated and monitored carefully during MA therapy.

Ovarian Leydig cell tumor and postmenopausal hirsutism with signs of virilisation

A 71-year-old woman was referred to the endocrinology clinic to investigate postmenopausal hirsutism with 10 years of evolution. She had history of regular menses and menopause with 50 years old. Physical examination showed a male pattern facies, deepening of the voice, androgenic alopecia and hirsutism with a score of 23 according to the modified Ferriman-Gallwey scale. Testosterone and androstenedione were increased. Transvaginal ultrasound, abdominal and pelvic CT showed uterine fibroids with no pathological findings in the adrenals or ovaries. Since she had postmenopausal vaginal bleeding, uterine fibroids and suspicion of an ovarian source for her hyperandrogenism, total hysterectomy and bilateral oophorectomy were performed. Histopathological diagnosis was a Leydig cell tumour located in left ovary and endometrial carcinoma. Improvement of hirsutism was started to notice 1 month after the surgery and she was referred to the oncology clinic for adjuvant treatment.

Hepatomegaly and short stature in a 14-year-old with type 1 diabetes mellitus: case report

Background Mauriac syndrome is a rare consequence of poorly controlled insulin-dependent diabetes, characterized by hepatomegaly, growth failure, delayed onset of puberty, and cushingoid features. Case reports of patients with Mauriac syndrome are found infrequently in the literature given historic improvements in diabetes management due to readily available insulin therapy. Methods We describe a case of a 14-year-old girl who presented with acute onset abdominal pain, distention, and orthopnea. Results She had a history of poorly controlled insulin-dependent diabetes as well as short stature. Abdominal imaging revealed impressive hepatomegaly. Laboratory testing showed markedly elevated triglycerides and cholesterol. Mauriac syndrome was suspected and diagnosed by liver biopsy, which demonstrated significant glycogenic hepatopathy. Conclusions This case provides an illustrative example of Mauriac syndrome in a child who did not experience delayed onset of puberty and continued to have regular menses unlike what has been previously described. Furthermore, this case highlights the important consideration for significant dyslipidemia in patients with Mauriac syndrome and discusses the challenges of controlling insulin-dependent diabetes in the adolescent population.

Pregnancy and lactation, a challenge for the skeleton

In this review we discuss skeletal adaptations to the demanding situation of pregnancy and lactation. Calcium demands are increased during pregnancy and lactation, and this is effectuated by a complex series of hormonal changes. The changes in bone structure at the tissue and whole bone level observed during pregnancy and lactation appear to largely recover over time. The magnitude of the changes observed during lactation may relate to the volume and duration of breastfeeding and return to regular menses. Studies examining long-term consequences of pregnancy and lactation suggest that there are small, site-specific benefits to bone density and that bone geometry may also be affected. Pregnancy- and lactation-induced osteoporosis (PLO) is a rare disease for which the pathophysiological mechanism is as yet incompletely known; here, we discuss and speculate on the possible roles of genetics, oxytocin, sympathetic tone and bone marrow fat. Finally, we discuss fracture healing during pregnancy and lactation and the effects of estrogen on this process.

Turner syndrome with rapidly progressive puberty: a case report and literature review

This report describes a clinically rare and atypical case of 46,X,idic(X)(q21.32)/45,X-type Turner syndrome with rapidly progressive puberty development. After 11 months of treatment with recombinant human growth hormone (rhGH), the child’s height increased. After 18 months of treatment with rhGH, the child showed secondary sex characteristics. The child was followed up for 1 year after the appearance of the secondary sex characteristics, and regular menses were still present. This case indicates that modern molecular biology techniques should be used rationally to further investigate the existence of X-chromosome translocations and occult chimeras to prevent misdiagnosis.

SAT-LB51 The Unique Etiology and Management of a Third Cranial Nerve Palsy

Background: Cranial nerve palsies (CNP) in association with a hypophyseal process can be uni/bilateral, single, multiple, with or without visual deficits and pain. It is reported 14-30% of pituitary tumors lead to a palsy. Often the acute cause of palsy is apoplexy (1) but other rare etiologies exist such as abscess or prolactinoma (2, 3). Clinical Case: A 40 year old woman with no PMH presented to the ED for acute on chronic headaches. Two days prior she started having blurry vision in her R eye. The headache improved with medications and she was sent home. Two days later she returned with new symptoms of the R eye deviating laterally and down, associated ptosis and a 6 mm nonreactive pupil. A stat MRI brain was obtained for her new CN III palsy, showing a 1.4 cm sellar mass with suprasellar extension. Further history revealed that two months prior her regular menses had stopped. Labs were obtained that included a prolactin 127 (nl 4.8-23.3); fT4 1.2 (nl .93-1.7); IGF1 129 (nl 52-328); 9 am cortisol 16.6 (nl 4-22); FSH 5.5 (nl 3.5-12.5); LH 3.8 (nl 2.4-12.6). Neurosurgery (NSGY) was consulted, recommending a trial of medical therapy since her visual fields were intact. Endocrine then advised cabergoline 0.5 mg twice weekly. In NSGY clinic ten days later, her prolactin was 0.2 but her symptoms remained the same. One month later, she was seen in Neuro-ophthalmology clinic where it was noted that her diplopia had subjectively resolved. Her eye exam was documented as normal except for sluggish pupils. Conclusion: CNP are more common in larger pituitary tumors and often associated with panhypopituitarism and necrosis. About 90% of cases resolve by one year after pituitary surgery. Although our patient had a tumor that was slightly larger than 1 cm, she did not need hormonal replacement, did not have hemorrhage/necrosis, and her symptoms resolved with a dopamine agonist. There is one other case in the literature of medically treated macroprolactinoma with resolution of CN III palsy (3). References: (1) Hage R, et al. Third, Fourth, and Sixth Cranial Nerve Palsies in Pituitary Apoplexy. World Neurosurgery. 2016; 94:447-452.(2) Wang L, et al. Pituitary abscess resulting in isolated abducens palsy. Journal of the Formosan Medical Association. 2016;115:134-135.(3) Harries A, et al. Resolution of third nerve palsy following treatment of prolactinoma with cabergoline. Acta Neurochir. 2010; 152:1741-1743.

SUN-167 Treatment Considerations for a Healthy Pregnancy in Women with Classical Congenital Adrenal Hyperplasia (CAH)

Background: CAH is caused by an enzyme deficiency involved in cortisol synthesis leading to an increase in ACTH. Increased ACTH causes elevated levels of steroid hormone precursors & chronic stimulation of the adrenal glands resulting in hyperplasia. The most common form of CAH is due to 21OH deficiency (21OHD) with the classic, salt-wasting form causing glucocorticoid & mineralocorticoid deficiency & androgen excess. Poorly controlled CAH causes increased production of androgens & progesterone & decreased fertility. Fertility in woman with 21OHD can be challenging due to decreased sexual interest & anatomical abnormalities. Despite these challenges, the pregnancy rate is not significantly lower in women with well controlled 21OHD. However, as these patients are uncommon recommendations for pregnancy can be challenging for endocrinologists. Clinical Case: A 27-year old G0P0 female with classic, salt losing CAH presented to discuss pregnancy. Her medications were hydrocortisone 10mg qAM & 5mg qHS & fludrocortisone 0.1mg daily. She denied symptoms of dehydration, nausea, vomiting, dizziness, or fatigue. She was diagnosed with CAH while in-utero & started on steroid therapy after birth. She did not require any surgical genital reconstruction. Menarche occurred at age 11 and she had regular menses every 35-40 days, with no evidence of excessive androgen exposure including excess body hair, deepening of her voice, or cliteromegaly. On physical exam she was normotensive & had no evidence of virilization or cushingoid features. She exhibited minor darkening of the palmar creases. Her labs were significant for free testosterone of 9.1 pg/ml (0.2-5.0 pg/ml), total testosterone of 115 ng/dl (2-45 ng/dl), ACTH of 780 pg/ml (6-50 pg/ml), androstenedione of 636 ng/dl (41-262 ng/dl), & 17 OHP of 1560 ng/dl (15-290 ng/dl). Her hydrocortisone dose was increased to 20 mg qAM & 10 mg qHS & fludrocortisone 0.1mg daily was continued. Our objectives were to normalize the androgen level & suppress serum progesterone to less than 2 nmol/L. If the objectives were not reached she would be converted to prednisone BID. Conclusion: Endocrine providers are the primary resource for fertility recommendations for 21OHD patients & must understand the challenges in this very rare group of patients. Collaboration with the perinatologist is crucial for success. The goals of preconception endocrine assessment in a patient with classic CAH are to adjust hormone therapy to ensure optimal endocrine milieu for conception & risk assessment of having a child affected with 21OHD. The patient will need a higher dose of fludrocortisone during the later part of pregnancy. Counseling that stress doses of glucocorticoids for intercurrent illness and during labor and delivery are required for both the patient and the obstetrician.

MON-258 Hyperprolactinemia: An Unusual Initial Presenting Manifestation of Multiple Sclerosis

Hyperprolactinemia and multiple sclerosis (MS) have a direct relationship and hyperprolactinemia may precede clinical signs of MS as a heralding manifestation of disease. Prolactin has significant pro-inflammatory effects in addition to its lactotrophic properties and can also lower the body’s immune tolerance, inducing autoimmunity. High levels of prolactin have been thought to contribute to the inflammation of multiple sclerosis. However, elevated levels of prolactin, especially in pregnant women, can be protective for MS patients and induce remission. Prolactin is neuroregenerative and stimulates the precursors for oligodendrocytes, the cells responsible for myelination. Our hypothesis is that an elevated prolactin level detected during an MS flare should not be treated with dopamine agonist, but rather allowed to decrease as the MS improves with treatment. Case Presentation A 24 year old woman with a history of marijuana use is referred to our clinic for elevated prolactin levels associated with galactorrhea for 3 months duration. In addition to marijuana use, patient was also sexually active and having regular menses, with menarche at age 11 years old. On physical exam, the patient was found to have bilateral nipple discharge with stimulation, and visual fields were intact to confrontation. At the time of referral, the patient’s prolactin was 92.3 ng/dL (4.8−23.3 ng/mL) TSH was normal, and pregnancy test negative.An MRI showed multiple areas of enhancement compatible with active demyelination, concerning for multiple sclerosis. The pituitary gland was enlarged, without evidence of adenoma. A follow up prolactin level was 101 ng/dL and upon further discussion, patient also admitted to some “funny feeling” and weakness in her right hand and a feeling of being “off balance” diagnosed as a left ear infection. Patient was advised to seek urgent treatment for multiple sclerosis. She was admitted, where she was seen by neurology and diagnosed with relapsing remitting multiple sclerosis. She was initially treated with a course of IV methylprednisolone. She was discharged after this course and followed with neurology as an outpatient. For a few months our patient went into remission and her prolactin improved to 24 ng/dL. A few months later, she had a significant increase in her prolactin to 71.5 ng/dL accompanied by evidence of disease progression on MRI and symptoms of weakness and falls. Neurologists changed her medication from Copaxone to Tecfidera and patient improved clinically and has not had any further flares. Notably, she never received any dopaminergic agent to treat her prolactin level, which improved significantly.Our case illustrates that prolactin may be a disease marker in the acute phase of MS and can be restorative. Further more it will improve when the MS is treated and we should not use any dopamine agonist.