Induction of Abortion in the Second Trimester by Misoprostol or Misoprostol with Letrozole

Background Abortion is the termination of pregnancy by any means (surgical or medical) before the age of viability. The definition varies in duration of gestational age according to the countries and available facilities. Estrogen is important in the maintenance of pregnancy. Aromatase inhibitors such as letrozole, suppress the peripheral conversion of androgen to estrogen, the use of letrozole combined with vaginal misoprostol was more effective than misoprostol alone in termination of pregnancy. Objective Assessing the efficacy of addition of letrozole to Misoprostol in medically induced abortion in the second trimester of pregnancy in the Maternity hospital of Ain Shams University. Methods This clinical trial was conducted at Ain Shams University Maternity hospital in the period between December 2018 and May 2019. Patients that seem to be fulfilling the inclusion criteria were recruited, then informed written consent was taken from every patient before starting the examination That was followed by detailed history and examination of all patients to confirm fulfilling the inclusion and exclusion criteria. Results This study demonstrated that 10 mg letrozole for three days followed by 800 mcg of vaginal misoprostol is more effective than misoprostol alone for second trimester abortion. In the total of 72 women were recruited the complete abortion rate of the letrozole group was significantly higher than that of the control group (61,1% in the letrozole group compared with 33,3% in the control group). Conclusion s: The use of letrozole in addition to misoprostol was associated with a higher complete abortion rate, shorter induction to abortion interval and shorter curettage rates compared to a placebo followed by misoprostol in patients undergoing induction of abortion between 12 & 24 weeks gestation.

Vitamin D, Thyroid Hormones and Cardiovascular Risk: Exploring the Components of This Novel Disease Triangle

The role of thyroid hormones (THs) in the cardiovascular (CV) system, through several direct and indirect effects is recognized. Even very small modification in TH levels (as those observed in subclinical hypothyroidism or hyperthyroidism, and low triiodothyronine syndrome) may adversely affect the CV system, whereas thyroid hormones benefit the CV system and improve the prognosis. There is also evidence of vitamin D effects on cardiometabolic disease (e.g., through modulation of endothelial and smooth muscle cell activity, renin-angiotensin-aldosterone system, nitric oxide, oxidative stress, and inflammatory response), as well as an association between vitamin D [25(OH)D] deficiency and autoimmune thyroid diseases or cancer, and a relationship between vitamin D concentration and titers of antibodies and thyroid autoimmunity replacement. Interestingly, experimental data indicate a direct effect of vitamin D on Type 2 deiodinase expression causing subsequential peripheral conversion of T4 into T3. However, the functional links among THs, vitamin D and the cardiovascular system, and clinical effects of coexisting abnormalities in this new troublesome triad, have not yet been reviewed. The main aim of this review is to discuss pathophysiology of this relationship, proposing new mechanistic insights involving vitamin D in the modulation of cardiometabolic disease and thyroid profile.

Aspects of hormonal testing of thyroid function in patients with type 1 diabetes mellitus and chronic kidney disease

Background. Chronic kidney disease (CKD) is known to affect the thyroid axis, including thyroid hormone metabolism. It has been established that a decrease in renal function can be combined with changes in thyroid function. Thyroid dysfunction also has implications for renal blood flow, glomerular filtration rate (GFR), tubular transport, electrolyte homeostasis, and glomerular structure. The purpose of the study was to determine the features of thyroid function in patients with type 1 diabetes mellitus (T1DM) and CKD and develop recommendations for hormonal testing of thyroid pathology. Materials and methods. One hundred and twenty-one patients with T1DM with CKD were divided into 3 groups: group 1 — 78 individuals with GFR ≤ 60 ml/min/1.73 m2, group 2 — 20 people receiving renal replacement therapy (RRT), group 3 — 23 patients after renal transplantation (RT) with adequate graft function (the duration of the renal transplant is 3.62 (1.47; 4.28) years). Results. In T1DM and CKD group, the diagnostic value of thyroid-stimulating hormone is reduced due to the absence of differences in its values with a decrease in T4 and T3. Free T3 is the most sensitive marker of thyroid dysfunction in CKD. Thyroid disorders in T1D and CKD patients have a non-immune genesis. T1DM patients on RRT after hemodialysis (HD) procedure have an increase in total and free T4 and free T3, consequently, monitoring of thyroid disorders should be done immediately after the HD session. The restoration of normal values of peripheral conversion index and free T3 occurs within 1–2 years after TR, depending on the duration of RRT receiving. After more than 3 post-transplantation years, there is an increase in peripheral conversion index, which characterizes the imbalance of peripheral thyroid hormones towards a decrease in free T3 with relatively stable free T4. Conclusions. Thyroid dysfunctions are typical for all stages of the pathological process in CKD in patients with type 1 diabetes mellitus, including patients at the terminal stage and after successful kidney transplantation. The changes in thyroid hormones are associated with the RRT experience and can potentially affect the survival of patients.

SAT-022 Adrenal Androgen Production Is Maintained While Ovarian Estrogens Fall Following the Final Menstrual Period in the Study of Women’s Health Across the Nation (SWAN)

The aim of this study was to clarify changes in sex steroids at the final menstrual period (FMP). We have shown previously that estradiol (E2) declines substantially in the 4-year period around the FMP, but hypothesize that testosterone (T) declines modestly and adrenal Δ5 androgens dehydroepiandrosterone (DHEA) and androstenediol (Adiol) remain unchanged. Methods: Liquid chromatography tandem mass spectrometry (LC-MS/MS) and immunoassay was used in approximately annual samples collected before and following FMP in 1490 women. We estimated time-related changes in each log-transformed androgen using piecewise linear mixed modeling, with knots (slope changes) at FMP-2 yrs and FMP+2 yrs as seen for E2. These models then were re-estimated for subgroups with different time courses identified using group-based trajectory modeling. Results: In the full sample, T was generally stable, although time course varied by subgroup, with a significant decrease of 5%/year in T in [FMP-2yrs, FMP+2yrs] only in the lowest T women. For DHEA and Adiol, declines were similar across all 3 time segments and across subgroups. Mean circulating androgen concentration declined modestly (P> 0.05) from five years before to five years following FMP. However, when stratified only the lowest 7% of circulating T declined significantly (p< 0.05) in the four years surrounding FMP when mean circulating E2 declined. This trajectory divergence of the lower circulating T suggests a different, non-adrenal source that is decreased at FMP which may be useful in clarifying ovarian versus adrenal testosterone production during the post-menopause. Paired results from samples collected before and following FMP in the same subjects indicate mean circulating E2 is less than 5% of mean circulating T suggesting that a relatively large portion of circulating E2 may be largely a result of peripheral conversion of adrenal androgens. Longitudinal LC-MS/MS analyses of circulating E2 and T indicate that the principal change in sex steroid influence at menopause is largely a decrease and dampening of ovarian and not adrenal steroid production.

SAT-468 Anticoagulation Conundrum: A Case Of Embolic Stroke Due To Thyrotoxic Atrial Fibrillation

Background: Thyrotoxicosis is not incorporated into any of the atrial fibrillation (AF) CVA risk stratification methods, including CHADS2VASc, as neither the American College of Cardiology/American Heart Association nor the American College of Chest Physicians view it as an independent risk factor of CVA. However, the literature has reported numerous cases of patients with thyrotoxic AF and low CHADS2VASc scores who developed CVA. It is unclear which patients with thyrotoxic AF would benefit from prophylactic anticoagulation (AC). Clinical Case: A 50-year-old male without past medical history presented for palpitations. He was found to be in AF with rapid ventricular rate. Labs revealed thyrotoxicosis (TSH <0.010 [RR 0.34-5.6 μIU/mL], FT4 3.57 [RR 0.61-1.64 ng/dL], FT3 5.26 [RR 2.5-4.5 pg/mL], and TSI negative). He was started on methimazole but no AC, as his CHADS2VASc score was 0. A few hours after admission, he developed a right-sided facial droop and weakness & aphasia. CT head showed acute left MCA infarct. CTA head/neck revealed occlusive embolus in the distal left M1 segment. He underwent IR-guided embolectomy and received intra-arterial tPA. Echocardiogram did not show thrombi or atrial level shunt but showed right atrial dilation. After extensive work-up, etiology of CVA was determined most likely a cardioembolic source due to thyrotoxic AF. Patient was treated with PTU and steroids initially for two days due to recent contrast exposure (CTA and embolectomy) and poor neurologic status, in order to obtain the added benefit of decreased T4 to T3 peripheral conversion. Patient was started on AC two weeks after his CVA (given initial risk of hemorrhagic conversion due to large CVA burden), at which time his weakness and aphasia were slowly improving, but he remained with significant neurologic deficits. Discussion : The current thought that thyrotoxicosis is not an independent risk factor of CVA in patients with AF has led to recommendations against prophylactic AC for this specific group. Although recent research has suggested that patients with thyrotoxic AF are at a lower risk of CVA than patients with non-thyrotoxic AF, there have still been many reported cases of CVA in patients who have thyrotoxic AF but no other risk factors for CVA. This discrepancy in association between thyrotoxic AF and CVA needs to be clarified. Conclusion: This case of a middle-aged man with thyrotoxic AF who developed a debilitating CVA after being treated according to his CHADS2VASC score of 0 (he was not given prophylactic AC) mirrors multiple cases in the literature. It highlights the potential benefit of examining thyrotoxic patients with AF more closely in order to more effectively risk stratify them for CVA or further exploring the relationship between thyrotoxicosis and CVA. This may help to identify more patients who could benefit from AC and thus prevent devastating consequences of CVA.

HSD3B1 genotype identifies glucocorticoid responsiveness in severe asthma

Asthma resistance to glucocorticoid treatment is a major health problem with unclear etiology. Glucocorticoids inhibit adrenal androgen production. However, androgens have potential benefits in asthma. HSD3B1 encodes for 3β-hydroxysteroid dehydrogenase-1 (3β-HSD1), which catalyzes peripheral conversion from adrenal dehydroepiandrosterone (DHEA) to potent androgens and has a germline missense-encoding polymorphism. The adrenal restrictive HSD3B1(1245A) allele limits conversion, whereas the adrenal permissive HSD3B1(1245C) allele increases DHEA metabolism to potent androgens. In the Severe Asthma Research Program (SARP) III cohort, we determined the association between DHEA-sulfate and percentage predicted forced expiratory volume in 1 s (FEV1PP). HSD3B1(1245) genotypes were assessed, and association between adrenal restrictive and adrenal permissive alleles and FEV1PP in patients with (GC) and without (noGC) daily oral glucocorticoid treatment was determined (n = 318). Validation was performed in a second cohort (SARP I&II; n = 184). DHEA-sulfate is associated with FEV1PP and is suppressed with GC treatment. GC patients homozygous for the adrenal restrictive genotype have lower FEV1PP compared with noGC patients (54.3% vs. 75.1%; P < 0.001). In patients with the homozygous adrenal permissive genotype, there was no FEV1PP difference in GC vs. noGC patients (73.4% vs. 78.9%; P = 0.39). Results were independently confirmed: FEV1PP for homozygous adrenal restrictive genotype in GC vs. noGC is 49.8 vs. 63.4 (P < 0.001), and for homozygous adrenal permissive genotype, it is 66.7 vs. 67.7 (P = 0.92). The adrenal restrictive HSD3B1(1245) genotype is associated with GC resistance. This effect appears to be driven by GC suppression of 3β-HSD1 substrate. Our results suggest opportunities for prediction of GC resistance and pharmacologic intervention.

Propranolol-Induced Circulatory Collapse in a Patient With Thyroid Crisis and Underlying Thyrocardiac Disease: A Word of Caution

Thyrotoxic crisis or thyroid storm is a severe form of hyperthyroidism and a rare endocrinological emergency. The cornerstones of medical therapy in thyroid storm include decreasing the levels of circulating T3 in the blood as well as inhibiting the hormone’s peripheral effects through β-adrenergic blockade. Propranolol is the preferred agent for β-blockade in hyperthyroidism and thyroid storm due to its additional effect of blocking the peripheral conversion of inactive T4 to active form T3. We report a typical clinical scenario where propranolol was administered in treatment of thyroid storm but an uncommon adverse outcome: circulatory failure from cardiogenic shock warranting vasopressor and inotropic support. Caution with regard to the use long-acting β-blocking agents in patients with underling thyrocardiac disease may prevent this life-threatening adverse effect. Ultra–short-acting β-blockers that are easy to titrate maybe a suitable alternative in this subset of patients.

INFLUENCE OF DISTURBED CONDITIONS OF REPARATIVE REGENERATION OF BONE TISSUE ON THE DYNAMICS OF THYROID HORMONES

Managing bone tissue regeneration is a key problem in traumatology and orthopedics. The researches proved that thyroid hormones affect hemostasis and reparative regeneration of bone tissue favorably and promote osteogenesis and bone consolidation.The aim of this research is to study the influence of disturbed reparative regeneration on the concentration of thyroid hormones in blood in the dynamics. Experimental research on rabbits (n=12) with modelling of disturbed reparative regeneration revealed disorder in thyroid hormones synthesis and different directions of T3 and unbound T3 production on the 35th day when the maxi-mum decrease of T3 (2times) and unbound T3 (1.5times) compared to normal values was registered. The analysis of production of T4 and unbound T4 revealed suppression of the values from the 1st to 50th day and gradual increase in unbound T4 from the 50th day. The most significant manifestation of thyroid gland reaction on the disturbed reparative regeneration of shin bones was the decrease in T3 and peripheral conversion of thyroid hormones up to 50th day with formation of false joint in these terms.

A case of thyroid storm complicated by acute hepatitis due to propylthiouracil treatment

Summary A 57-year-old female presented 17 days after treatment with radioactive iodine (RAI) for difficult-to-control hyperthyroidism. She was febrile, had a sinus tachycardia, and was clinically thyrotoxic. Her thyroid function tests showed a suppressed TSH <0.02 mU/l, with free thyroxine (FT4) >75 pmol/l and total triiodothyronine (TT3) 6.0 nmol/l. She was diagnosed with thyroid storm and was managed with i.v. fluids, propylthiouracil (PTU) 200 mg four times a day, prednisolone 30 mg once daily and propanolol 10 mg three times a day. She gradually improved over 2 weeks and was discharged home on PTU with β blockade. On clinic review 10 days later, it was noted that, although she was starting to feel better, she had grossly abnormal liver function (alanine transaminase (ALT) 852 U/l, bilirubin 46 μmol/l, alkaline phosphatase (ALP) 303 U/l, international normalized ratio (INR) 0.9, platelets 195×109/l). She was still mildly thyrotoxic (TSH <0.02 mU/l, FT4 31 pmol/l, TT3 1.3 nmol/l). She was diagnosed with acute hepatitis secondary to treatment with PTU. Ultrasound showed mild hepatic steatosis. PTU was stopped and she was managed with fluids and prednisolone 60 mg once daily and continued β blockade. Her liver function gradually improved over 10 days (bilirubin 9 μmol/l, ALT 164 U/l, ALP 195 U/l, INR 0.9, platelets 323×109/l) with conservative management and had normalised by clinic review 3 weeks later. This case highlights the potentially fatal, but rare, complications associated with both RAI and PTU, namely, thyroid storm and acute hepatitis respectively. Learning points Thyroid storm is an important, albeit rare, endocrinological emergency. Thyroid storm following RAI treatment is extremely rare. Management is with i.v. fluids, β blockade, anti-thyroid drugs and steroids. High dose glucocorticoid steroids can block the peripheral conversion of T4 to active T3. Liver dysfunction, acute hepatitis and potential hepatic failure are significant adverse drug reactions known to occur with PTU treatment. Supervising clinicians should be vigilant for evidence of this developing and intervene accordingly. Clinicians need to be aware of possible interactions between regular paracetamol use and PTU in predisposing to liver impairment.