Steroid Replacement Therapy Research Articles

Quality of Life in Prader-Willi Syndrome Patients

ning, speech therapy, and growth and sex hormone replacement therapy. Serotonin reuptake inhibitors (SRIs) are also helpful for most teenagers and adults in managing mood-related symptoms. The complex genetics, etiology, multiple phenotypes, and evolving natural history of PWS suggest that a multidisciplinary professional, parental, societal, and environmental approach to the management of these patients is required for overcoming the many challenges of reducing morbidity and mortality and im- proving patient quality of life (QoL) 1) . The multidisciplinary team involved in the care of PWS patients and their families should include several medical and non-medical professional figures (e.g. child psychiatrists, pediatric endocrinologists, clinical geneti- cists, orthopedic specialists, educational psychologists, and social workers). However, all these professional figures should know what the patient wants and what kind of relationship there is be- tween the traditional clinical outcome measures and the patient's perspective

Sex Steroid Replacement Therapy in Female Hypogonadism from Childhood to Young Adulthood.

The overall goal of pubertal sex hormone replacement therapy (HRT) in girls is not only about development of secondary sexual characteristics, but also to establish an adult endocrine and metabolic milieu, as well as adult cognitive function. Estradiol (E2) is the first choice for HRT compared to ethinyl estradiol (EE2). E2 is the most potent endogenous estrogen in the circulation, with established levels during spontaneous puberty. Transdermal E2, compared to oral administration, is the first choice to start pubertal HRT. Transdermal application avoids liver exposure to supraphysiologic estrogen concentrations and provides a more physiologic mechanism for hormone delivery. By cutting E2 matrix patches in doses of 0.05-0.07 µg/kg or administrate E2 gel in doses of 0.1 mg/day, serum concentrations of E2 seen in early spontaneous puberty can be obtained. Patches can be removed in the morning and thereby mimic the normal circadian rhythm. For those clinics with access to sensitive E2 determinations methods (extraction followed by radioimmunoassay or mass spectrometry) monitoring the attained E2 serum levels is recommended in order to optimally mimic the levels seen in early puberty as well as growth velocity, breast and uterus development. Mid- and late pubertal HRT is obtained by increased doses of E2, adding cyclic oral or transdermal progestin, as well as testosterone gel over the pubic area if indicated.

Association Between Chronic Hepatitis B Virus Infection and Risk of Osteoporosis: A Nationwide Population-Based Study.

The effect of hepatitis B virus (HBV) infection on bone mineral density in patients without advanced liver disease remains unclear. Hence, we assessed the association between HBV infection and the risk of osteoporosis.From 2000 to 2011, patients older than 20 years with HBV infection were identified from the Longitudinal Health Insurance Database 2000. Of the 180,730 sampled patients, 36,146 and 144,584 patients were categorized into HBV infection and comparison cohorts, respectively.Compared with the comparison cohort, the HBV infection patients had a higher risk of osteoporosis (adjusted hazard ratio [aHR]: 1.14, 95% confidence interval [CI]: 1.03–1.25) after adjusting for age, sex, frequency of medical visits, and comorbidities of diabetes, hypertension, hyperlipidemia, heart failure, cirrhosis, chronic kidney disease, thyroid diseases, medication of steroid, PPI, warfarin, aspirin, and estrogen replacement therapy. The patients with HBV infection exhibited a 1.13-fold (95% CI = 1.03–1.25) higher risk of developing osteoporosis, but the risk of osteoporotic fracture was comparable between patients with HBV infection and the comparison cohort (aHR = 1.20, 95% CI = 0.77–1.86). The incidence of osteoporosis increased with the increment of age (age ≤ 49: aHR = 1; age 50–64: aHR = 5.67, 95% CI = 5.09–6.32; age ≧ 65: aHR = 13.3, 95% CI = 11.8–14.9) and coexisting cirrhosis (aHR = 1.62, 95% CI = 1.24–2.12). However, the osteoporosis risk contributed by HBV infection decreased with age and the age-specific risk analyses showed that patients with HBV infection exhibited the highest risk of osteoporosis than patients without HBV infection for the patients aged ≤49 (aHR = 1.42, 95% CI = 1.19–1.70). Furthermore, the osteoporosis risk contributed by HBV infection has decreased with the presence of comorbidity (aHR = 1.27, 95% CI = 1.09–1.48 vs aHR = 1.04, 95% CI = 0.91–1.15).HBV increases the risk of osteoporosis, but HBV infection may be less influential than other risk factors. Moreover, HBV has no detrimental effect on osteoporotic fracture in this study.

Steroids Improve Hemodynamics in Infants With Adrenal Insufficiency After Cardiac Surgery.

To investigate whether steroid replacement therapy improved hemodynamics in infants after surgery for congenital heart disease only when they develop adrenal insufficiency. The authors retrospectively investigated adrenal function and evaluated hemodynamic responses to steroid replacement therapy in infants after surgery for congenital heart disease. Retrospective, cohort study. Intensive care unit in the National Cerebral and Cardiovascular Center Hospital in Japan. Thirty-two neonates and infants<3 months old who underwent cardiovascular surgery. The patients were divided into 2 groups based on corticotropin stimulation test results: group AI with adrenal insufficiency (baseline cortisol<15 µg/dL or incremental increase after testing of<9 µg/dL, with baseline cortisol of 15-34 µg/dL); and group N with normal adrenal function. The corticotropin stimulation test was performed by injecting 3.5 µg/kg of tetracosactide acetate. Hydrocortisone (1 mg/kg) was administered every 6 hours, and hemodynamics were compared before and after steroid administration between the groups. Seven patients were classified into group AI, and demonstrated a mean blood pressure increase from 53±8 mmHg before treatment to 68±9 mmHg 18 hours after steroid administration (p<0.01). Urine output also increased, from 2.7±1.0 mL/kg/h to 4.8±1.9 mL/kg/h (p<0.05). In group N, neither mean blood pressure nor urine output increased after steroid administration. After surgery for congenital heart disease, one-fifth of infants developed adrenal insufficiency. Steroid replacement therapy improved hemodynamics only in the subgroup with adrenal insufficiency.

Pure endoscopic transsphenoidal surgery for functional pituitary adenomas: outcomes with Cushing's disease.

This study was performed to examine patient outcomes following pure endoscopic transsphenoidal surgery (ETS) for Cushing's disease (CD). We studied 64 consecutive patients who underwent 69 endoscopic transsphenoidal procedures. Radiological evaluation comprised detailed examination of preoperative magnetic resonance images (MRI), including positron emission tomography (PET) for select cases. Inferior petrosal sinus sampling (IPSS) was not performed for any patient. Remission was defined by the presence of hypocortisolemia with requirement for steroid replacement therapy or eucortisolemia with suppression to <1.8μg/dl after 1mg dexamethasone on evaluation at least 3months after surgery. Preoperative MRI was abnormal in 87.5% of cases and included 11 macroadenomas (17.2%). PET was used to localize the adenoma in four cases. For microadenomas, operative procedures executed were as follows: selective adenomectomy (n = 15), enlarged adenomectomy (n = 21) and subtotal/hemihypophysectomy (n = 17). Overall, pathological confirmation of an adenoma was possible in 58 patients (90.6%). Forty-nine patients (76.6%) developed hypocortisolemia (<5μg/dl) in the early postoperative period. Mean follow-up was 20months (range 6-18 months). Remission was confirmed in 79.7% of the 59 cases followed up for >3months and was superior for microadenomas (86.4%) versus macroadenomas (55.6%) and equivocal MRI adenomas (66.7%). Postoperative CSF rhinorrhea occurred in five patients, and new endocrine deficits were noted in 17.1% patients. A nadir postoperative cortisol <2μg/dl in the 1st week after surgery was highly predictive of remission (p = 0.001). ETS allows for enhanced intrasellar identification of adenomatous tissue, providing remission rates that are comparable to traditional microsurgery for CD. The best predictor of remission remains induction of profound hypocortisolemia in the early postoperative period.

The diagnosis, treatment and following up of 7 patients with 45, X/46, XY mixed gonadal dysgenesis

To investigate the clinical features, therapeutic regimens and follow-up information of patients with 45, X/46, XY mixed gonadal dysgenesis in order to improve the diagnosis and treatment of the disease. We performed a retrospective review of patients with 45, X/46, XY mosaicism hospitalized in Chinese PLA General Hospital between 2000 and 2014. The clinical features,sex hormones,treatment and follow-up information were summarized. (1) Seven patients ranging 12-17 years old were diagnosed as having 45, X/46, XY mixed gonadal dysgenesis. Six of them had female sex of rearing and one had male. (2) All of them presented with short stature and growth retardation, and had similar specific somatic signs to Turner syndrome. (3) The external genitalia presented with a wide variety of phenotypes. One patient presented with male phenotype with hypospadia, one presented with clitoridauxe, and five presented with female phenotype. The masculinization scores for the external genitalia showed that five patients presented with female phenotype, one patient with mild undervirilization and one patient with ambiguous genitalia. (4) By surgical exploration and ultrasound, two patients were found with testes and one was with ovary-like gonads. No gonad could be detected in the other four patients. (5) Five patients were treated with recombinant human growth hormone (rhGH). Two patients received sex hormone replacement therapy with one patient taking testosterone, whose penis became enlarged and erect after treatment, and one taking artificial cycle. The patients with 45, X/46, XY mosaicism share similar specific somatic signs to Turner syndrome. The 45, X/46, XY mosaicism presents with a wide spectrum of phenotypes with the highest proportion of being genital ambiguity. RhGH, testosterone and artificial cycle can be used accordingly.

Is peri-operative steroid replacement therapy necessary for the pituitary adenomas treated with surgery? A systematic review and meta analysis.

BackgroundPatients with pituitary adenomas usually receive “stress dose” steroids in the peri-operative peroids. Though randomized controlled trials(RCT) have not been performed to assess the necessity of steroid coverage, there are several studies that explained the changes of adrenal function during peri-operative peroids. The aim of the present study is to investigate whether it is necessary to employ conventional peri-operative glucocorticoid replacement therapy to all the patients undergoing surgery.MethodsWe searched studies addressing peri-operative steroids coverage for pituitary adenomas in the Web of Science, Medline and the Cochrane Library. Then we extracted studies about peri-operative morning serum cortisol(MSC) levels, morbidity of early postoperative adrenal insufficiency, postoperative diabetes insipidus, relationships between MSC levels and adrenal integrity. We used RevMan Software to combine the results for meta-analysis. We used fixed-effects models for there was no significant heterogeneity existed.FindingsThere are 18 studies from 11 countries published between 1987 and 2013 including 1224 patients. The postoperative serum cortisol levels were significantly increased compared with the preoperative one in hypothalamic-pituitary-adrenal axis(HPAA) functions preserved patients(P<0.00001). The morbidity of early postoperative adrenal insufficiency ranged from 0.96% to 12.90%, with the overall morbidity of 5.55%(41/739). There was no significant differences of early postoperative diabetes insipidus between no supplementation patients and in supplementation patients(P=0.82). Conversely, there may be some disadvantages of high levels of cortisols such as high incidence of osteopenia and bone derangement and even the increased mortality rate. The patients with MSC levels of less than 60 nmol/l at 3 days after operation is considered as adrenal insufficient and more than 270 nmol/l as adrenal sufficient. To patients with MSC levels of 60–270 nmol/l, we need more clinical data to establish further cortisol supplementation criteria.

Gender Dysphoria in 46,XX Persons with Adrenogenital Syndrome Raised as Females: An Addendum.

Gender Dysphoria in 46,XX Persons with Adrenogenital Syndrome Raised as Females: An Addendum.

Clinical, endocrinological, and molecular characterization of Kallmann syndrome and normosmic idiopathic hypogonadotropic hypogonadism: a single center experience.

PurposeIsolated gonadotropin-releasing hormone (GnRH) deficiency (IGD) is classified as Kallmann syndrome (KS) with anosmia and normosmic idiopathic hypogonadotropic hypogonadism (nIHH). This study was undertaken to investigate the clinical, endocrinological, and molecular characteristics in Korean patients with KS and nIHH.MethodsTwenty-six patients from 25 unrelated families were included. Their clinical, endocrinological, and radiological findings were analyzed retrospectively. Mutation analysis of the GNRH1, GNRHR, KISS1, KISS1R, PROK2, PROKR2, TAC3, TACR3, FGF8, FGFR1, and KAL1 genes was performed in all patients. CHD7 and SOX10 were analyzed in patients with CHARGE (Coloboma, Heart defects, choanae Atresia, Growth retardation, Genitourinary abnormality, Ear abnormality) features or deafness.ResultsOf the 26 patients, 16 had KS and 10 had nIHH. At diagnosis, mean chronologic age was 18.1 years in males and 18.0 years in females; height SDS were -0.67±1.35 in males, -1.12±1.86 in females; testis volume was 2.0±1.3 mL; and Tanner stage was 1.5. There were associated anomalies in some of the KS patients: hearing loss (n=6) and congenital heart disease (n=4). Absence or hypoplasia of the olfactory bulb/sulci was found in 84.62% of patients with KS. Molecular defects in KAL1, SOX10, and CHD7 were identified in 5 patients from 4 families (16.0%, 4/25 pedigrees). After sex hormone replacement therapy, there were improvement in sexual characteristics and the sexual function.ConclusionThis study described the clinical, endocrinological, and molecular genetic features in IGD patients in Korea. Although the mutation screening was performed in 10 genes that cause IGD, molecular defects were identified in relatively small proportions of the cohort.

A case of Sheehan’s syndrome in early postpartum period presenting partial recovery of pituitary function after immediate steroid replacement therapy

A case of Sheehan’s syndrome in early postpartum period presenting partial recovery of pituitary function after immediate steroid replacement therapy

Primary Granulomatous Hypophysitis Presenting with Panhypopituitarism and Central Diabetes Insipidus

Primary granulomatous hypophysitis is a rare inflammatory disorder of the pituitary gland and patients commonly present with symptoms of sellar compression and hypopituitarism. A 48-year-old woman was admitted due to headache and fatigue. Magnetic resonance imaging showed a 21 × 18 × 13-mm round sellar mass with a thickened pituitary stalk. The endocrinological examination revealed panhypopituitarism and diabetes insipidus. Suspecting hypophysitis, the patient was given steroid and hormone replacement therapy. Six months later, she continued to complain of severe headaches and nausea. Computed tomography showed no significant change in the sellar mass. Subsequently, transsphenoidal surgery was performed. The pathological examination revealed granulomatous changes with multinucleated giant cells and primary granulomatous hypophysitis was diagnosed. Her headache resolved, but the pituitary functions did not improve. This is the first reported case in Korea of primary granulomatous hypophysitis with dysfunction of anterior and posterior pituitary gland, including the stalk, without optic chiasm compression. (Korean J Med 2015;88:581-586)

On the postoperative steroid replacement in patients with ACTH independent Cushing's Syndrome

Objective To investigate the preoperative factors in influencing the postoperative steroid replacement in patients with ACTH-independent Cushing's syndrome.Methods One hundred and eighty-one patients with adrenal cortical adenoma underwent unilateral adrenalectomy from 2003 to 2013.All preoperative and postoperative follow-up clinical parameters were acquired and analyzed.Results All patients need glucocorticoid (GC) replacement during and after surgery.At the median follow-up of 32 months (14-64 months),104 patients withdrew the cortisone acetate replacement,with a median replacement duration of 12 months (6-15 months) and an average cumulative dosage of(8.12 ± 5.07) g.Spearman correlation analysis showed that the age at diagnosis was positively correlated with the duration of GC replacement therapy (r =0.250,P =0.010) as well as the cumulative dosage of GC(r=0.244,P =0.013).Multiple stepwise regression analysis indicated that age at diagnosis was the independent factor that influenced both the duration and cumulative dosage of postoperative cortisone acetate replacement(P＜0.05).Plasma ACTH levels gradually increased and peaked during the 9th month,there was a lag of several months in the recovery of normal adrenal responsiveness.After that period,corticosteroid rose to normal levels,and followed by plasma ACTH concentrations,which fell to normal.2.88％ (3/104) of the patients presented with steroid withdrawal syndrome (SWS).Most features of hypercortisolism resolved within 6 months after surgery.Conclusion An empirical experience in Ruijin hospital in using cortisol replacement therapy for patients with ACTH-independent Cushing's syndrome after unilateral adrenalectomy was herewith reported.The older patients tended to prolong the replacement therapy of steroids and thus had to deal with a larger cumulative dosage.We should be aware of the risk of development of SWS postoperatively. Key words: Cushing's syndrome ; Adrenalectomy ; Steroid replacement therapy ; Hypothalamic-pituitary-gonad axis

PERIOPERATIVE SUPERVISION OF CHILDREN WITH ADRENAL NEOPLASMS

Aim. To optimize the perioperative safety and to improve the results of surgical treatment of children with adrenal neoplasms. Materials and methods. The perioperative supervision of 18 patients (children aged 2 months to 15 years) with adrenal neoplasms who underwent laparoscopic adrenalectomy for different adrenal neoplasms was analyzed. The following two groups of patients were formed depending on the hormone activity of neoplasm originating from the adrenal gland: children with hormonally inactive adrenal tumors (14 cases) and patients with hormone-producing neoplasms (4 cases). Patients underwent complex examination confirming the character and localization of pathological process. Operative intervention - endoscopic adrenalectomy - was performed in conditions of multicomponent anesthesia and perioperative replacement steroid therapy. Results. The study indicated that the applied methods of general anesthesia are adequate anesthetic measures. So as to ensure safety of patients during operative intervention, uninterrupted monitoring of electrocardiography, noninvasive arterial pressure, pulsoxymetry, carbonic acid concentration in the expired gas-narcotic mixture, control of glycemia level, monitoring of blood gas composition and acid-base balance, temperature control, hourly diuresis were used. An obligatory condition for adequate perioperative supervision of children is replacement steroid hydrocortisone therapy in the perioperative period by the age dosage scheme irrespective of hormonal activity of neoplasms. The postoperative period in all cases, except one, was smooth, on the days 1-2 patients were transferred from resuscitation unit to the ward. Conclusions. For the purpose of preventing development of hypoadrenal crisis in the postoperative period after unilateral adrenalectomy irrespective of presence or absence of hormonal activity of adrenal neoplasm, it is necessary to carry out replacement steroid therapy since before the surgery it is not possible to assess the function of contrlateral adrenal gland.

Transition in endocrinology: induction of puberty.

Puberty is the period during which we attain adult secondary sexual characteristics and reproductive capability. Its onset depends upon reactivation of pulsative GNRH, secretion from its relative quiescence during childhood, on the background of intact potential for pituitary-gonadal function. This review is intended: to highlight those current practices in diagnosis and management that are evidence based and those that are not; to help clinicians deal with areas of uncertainty with reference to physiologic first principles; by sign-posting relevant data arising from other patient groups with shared issues; to illustrate how recent scientific advances are (or should be) altering clinician perceptions of pubertal delay; and finally, to emphasise that the management of men and women presenting in advanced adult life with absent puberty cannot simply be extrapolated from paediatric practice. There is a broad spectrum of pubertal timing that varies among different populations, separated in time and space. Delayed puberty usually represents an extreme of the normal, a developmental pattern referred to as constitutional delay of growth and puberty (CDGP), but organic defects of the hypothalamo-pituitary-gonadal axis predisposing to hypogonadism may not always be initially distinguishable from it. CDGP and organic, or congenital hypogonadotrophic hypogonadism are both significantly more common in boys than girls. Moreover, around 1/3 of adults with organic hypogonadotrophic hypogonadism had evidence of partial puberty at presentation and, confusingly, some 5-10% of these subsequently may exhibit recovery of endogenous gonadotrophin secretion, including men with Kallmann syndrome. However, the distinction is crucial as expectative ('watch-and-wait') management is inappropriate in the context of hypogonadism. The probability of pubertal delay being caused by organic hypogonadism rises exponentially both with increasing age at presentation and the presence of associated 'red flag' clinical features. These 'red flags' comprise findings indicating lack of prior 'mini-puberty' (such as cryptorchidism or micropenis), or the presence of non-reproductive congenital defects known to be associated with specific hypogonadal syndromes, e.g. anosmia, deafness, mirror movements, renal agenesis, dental/digital anomalies, clefting or coloboma would be compatible with Kallmann (or perhaps CHARGE) syndrome. In children, interventions (whether in the form or treatment or simple reassurance) have been historically directed at maximising height potential and minimising psychosocial morbidity, though issues of future fertility and bone density potential are now increasingly 'in the mix'. Apubertal adults almost invariably harbour organic hypogonadism, requiring sensitive acknowledgement of underlying personal issues and the timely introduction of sex hormone replacement therapy at more physiological doses.

Peri-portal lymphedema in association with an acute adrenal insufficiency: case report

IntroductionWe report the case of a patient with peri-portal lymphedema in association with severe adrenal insufficiency. To the best of our knowledge, this association was not previously reported in the literature. Peri-portal lymphedema is usually seen in cases such as blunt abdominal trauma, hepatic congestion and post–liver transplantation.Case presentationWe present the case of a 28-year-old Indian man who presented to our hospital with adrenal crisis and was treated accordingly. Computed tomography of his abdomen showed evidence of peri-portal lymphedema (edema) with some free fluid collection. We excluded other causes of this pathology and followed the patient’s condition after steroid replacement therapy. We found no other contributing factors to the patient’s peri-portal lymphedema apart from the adrenal crisis, which was more consolidated when we followed the patient after steroid replacement therapy, during which follow-up computed tomography showed complete resolution of the pathology.ConclusionsWe conclude following an extensive MEDLINE® search that this is the first case to be reported for the association between peri-portal lymphedema and adrenal insufficiency, after having excluded all other causes of peri-portal lymphedema. This signifies reporting of this case as the first one in the medical literature.

Fatal Candida Septic Shock During Systemic Chemotherapy in Lung Cancer Patient Receiving Corticosteroid Replacement Therapy for Hypopituitarism: A Case Report

Invasive candidiasis has increased as nosocomial infection recently in cancer patients who receive systemic chemotherapy, and the timely risk assessment for developing such specific infection is crucial. Especially in those concomitantly with hypopituitarism, febrile neutropenia with candidiasis can cause severe stress and lead potentially to sudden fatal outcome when the temporal steroid coverage for the adrenal insufficiency is not fully administered. We report a 72-year-old male case diagnosed as non-small-cell lung cancer, Stage IIIA. He had received a steroid replacement therapy for the prior history of hypophysectomy due to pituitary adenoma with hydrocortisone of 3.3 mg/day, equivalent to prednisolone of 0.8 mg/day. This very small dosage of steroid was hardly supposed to weaken his immune system, but rather potentially led to an inappropriate supplementation of his adrenal function, assuming that the serum sodium and chlorine levels decreased. On Day 6 of second cycle of chemotherapy with carboplatin and paclitaxel, he developed sudden febrile neutropenia, septic shock and ileus, leading to death. After his death, the venous blood culture on Day 7 detected Candida albicans. Autopsy findings showed a massive necrotizing enterocolitis with extensive Candida invasion into submucous tissue. In conclusion, this case may suggest that (i) immediate initiation of antifungal therapy soon after the careful risk assessment of Candida infection and (ii) adequate administration of both basal steroid replacement therapy and temporal steroid coverage for febrile neutropenia might have improved his fatal outcome.

Osteoporosis and obesity: Role of Wnt pathway in human and murine models.

Studies concerning the pathophysiological connection between obesity and osteoporosis are currently an intriguing area of research. Although the onset of these two diseases can occur in a different way, recent studies have shown that obesity and osteoporosis share common genetic and environmental factors. Despite being a risk factor for health, obesity has traditionally been considered positive to bone because of beneficial effect of mechanical loading, exerted by high body mass, on bone formation. However, contrasting studies have not achieved a clear consensus, suggesting instead that excessive fat mass derived from obesity condition may not protect against osteoporosis or, even worse, could be rather detrimental to bone. On the other hand, it is hitherto better established that, since adipocytes and osteoblasts are derived from a common mesenchymal stem cell precursor, molecules that lead to osteoblastogenesis inhibit adipogenesis and vice versa. Here we will discuss the role of the key molecules regulating adipocytes and osteoblasts differentiation, which are peroxisome proliferators activated receptor-γ and Wnts, respectively. In particular, we will focus on the role of both canonical and non-canonical Wnt signalling, involved in mesenchymal cell fate regulation. Moreover, at present there are no experimental data that relate any influence of the Wnt inhibitor Sclerostin to adipogenesis, although it is well known its role on bone metabolism. In addition, the most common pathological condition in which there is a simultaneous increase of adiposity and decrease of bone mass is menopause. Given that postmenopausal women have high Sclerostin level inversely associated with circulating estradiol level and since the sex hormone replacement therapy has proved to be effective in attenuating bone loss and reversing menopause-related obesity, we hypothesize that Sclerostin contribution in adipogenesis could be an active focus of research in the coming years.

A pilot study on the effect of three hydrocortisone dosing regimen on 17 hydroxyprogesterone levels in patients with congenital adrenal hyperplasia

The 2004 Newborn Screening Act has saved a lot of Filipinos from Congenital Adrenal Hyperplasia (CAH). The increase in the number of patients living with CAH challenges us to find the optimal steroid replacement therapy. In the Philippines, there is no locally published data on this. The objectives of the paper are to compare the effect of different hydrocortisone dosing regimen on the 17 hydroxyprogesterone (17 OHP) levels of patients with CAH and to report adverse effects. The pilot study is a single-blinded randomized control trial comparing the 17 OHP levels of infants with CAH given higher evening hydrocortisone dose (HED), higher morning hydrocortisone dose (HMD) and equal hydrocortisone dose (EHD) who consulted in a tertiary hospital from January 2011 to July 2011. Nine patients completed the study (3 males and 6 females) with mean age of 16 (+11) months. One patient was randomized to HMD, 5 to HED and 3 to EHD. A marginally significant difference (p-value=0.0515) in the 17 OHP levels was observed between treatment groups. Adverse effects included increased BMI with concomitant presence of cushingoid facies in 33% (3/9) of the patients and an increased growth velocity in one patient in the HED group. A significant difference was observed between treatment groups. The decrease in 17OHP was best appreciated in the EHD group but no definitive conclusion can be made on the optimal treatment schedule due to the small sample size. It is recommended that a larger study be done on newly diagnosed neonates with CAH using 525 patients (11 for HMD, 257 for HED and 257 for EHD) and ACTH levels be included in the outcome measures. Also, the use of oral steroids available in the country such as Prednisone or Dexamethasone as an alternative treatment be investigated.

A case of simultaneous neuromyelitis optica spectrum disorder and subacute combined degeneration

A 36-year-old woman was admitted to our hospital because of progressive numbness of her extremities and trunk. She was asymptomatic until approximately 1 month prior to admission, when she developed numbness in her left arm and hand. Two weeks before admission, she experienced neck pain and dysuria. Over the next 2 weeks, the numbness gradually progressed to her left lower extremity, right extremities, and trunk. She experienced no visual disturbances, and took no medications. Her past medical and family histories were unremarkable. She had no history of gastritis, gastrectomy, or other gastrointestinal disorders. She was not a vegetarian and her diet was unremarkable. On admission, the patient was well nourished with a body mass index of 21.5. A general medical examination revealed no abnormalities. Neurological examination showed positive Lhermitte’s phenomenon, and dysesthesia in the upper limbs and below the thoracic 6th dermatome. She demonstrated moderately decreased vibration sensation. The reflexes of both upper limbs were decreased while those of both lower limbs were increased. There were no pathological reflexes. The remainder of the neurological examination was normal. Initial routine laboratory examinations were unremarkable. A complete blood count showed no anemia and normocytosis. Biochemical examination of the blood revealed no abnormalities. Additional laboratory data were as follows: antinuclear antibodies, negative; vitamin B12, 96 pg/dL (233–914); folate, 3.1 ng/dL (3.6–12.9); serum copper, 48 lg/dL (70–132); serum ceruloplasmin, 12.2 mg/dL (21–37); urine copper, 56 lg/L (14–63); gastric parietal cell antibodies, negative; anti-intrinsic factor antibodies, negative. Anti-aquaporin 4 (AQP4) antibodies were found to be positive using the cell-based assay described in Ref. [1]. Cerebrospinal fluid (CSF) examination showed no leukocytosis, a protein level of 27 mg/dL (\40), albumin ratio of 4.9 (CSF albumin, 18.9 mg/dL; serum albumin, 3,840 mg/dL), no oligoclonal bands, and normal levels of myelin basic protein. T2-weighted magnetic resonance images (MRIs) of the cervical spinal cord showed hyperintensity in the posterior columns extending from the level of C2 to C6, and in the spinal cord around the central canal from the level of C4 to C7. Both types of spinal cord lesions were present between C4 and C6 (Fig. 1). Left median nerve somatosensory evoked potential (SEP) showed no detectable N11 or P13/14 components, with abnormally extended latency between N9 and N20 onsets (9.54 ms; normal range, under 8.10 ms) (Fig. 2). The patient was diagnosed with NMO spectrum disorder (NMOSD) with concurrent subacute combined degeneration (SCD). We performed steroid pulse therapy (methylprednisolone 1 g, 3 days) and replacement therapy with vitamin B12. These treatments improved the patient’s trunk and right hand numbness and she was discharged 32 days after admission. N. Ishii H. Mochizuki (&) K. Shiomi M. Nakazato Division of Neurology, Respirology, Endocrinology and Metabolism, Department of Internal Medicine, University of Miyazaki, 5200 Kibana, Kiyotake, Miyazaki 889-1692, Japan e-mail: mochizuki-h@umin.ac.jp

NR0B1 (DAX1) mutations in patients affected by congenital adrenal hypoplasia with growth hormone deficiency as a new finding

X-linked adrenal hypoplasia congenita (AHC,OMIM#300200) is a rare disorder of the adrenal cortex caused bymutations in the NR0B1 (DAX1) (dosage-sensitive sex reversal, adrenal hypoplasia critical region, on chromosome X, gene 1) gene (OMIM*300473). NR0B1 (DAX1) is located on the short arm of the X chromosome (Xp21.3-p21.2) and encodes for an orphan nuclear hormone receptor (transcription factor) (Zanaria et al. 1994). NR0B1 (DAX1) is expressed in the adrenals, gonads, hypothalamus, and pituitary gland, and it is responsible for controlling the development and function of these tissues. NR0B1 (DAX1) protein functions as a dominant negative regulator (transcriptional repressor) in the hypothalamic– pituitary–adrenal–gonadal axis. It regulates the expression of other proteins involved in the adrenal steroidogenesis pathway, such as steroidogenic factor 1 (SF-1), steroidogenic acute regulatory protein (StAR), P450scc and 3β-hydroxysteroid dehydrogenase (Lalli et al. 2000; Iyer and McCabe 2004). Almost 200 mutations in theNR0B1 (DAX1) gene have been identified to date (The Human Gene Mutation Database—data for 10.08.11) (http://www.hgmd.org). The most commonly found mutations in AHC patients are frameshift and nonsense mutations, which are located throughout the entire length of the NR0B1 (DAX1) gene. Missense mutations are not so common and are located mainly in the region that encodes for a ligandbinding domain at the C-terminus of the NR0B1 (DAX1) protein (Achermann et al. 2001a). Some patients have more complex X-chromosome rearrangements that include the deletion of larger parts of the X chromosome, including NR0B1 (DAX1), DMD (dystrophin), GK (glycerol kinase) and IL1RAPL (interleukin 1 receptor accessory protein-like) genes (Choi et al. 2005). AHC symptoms are noticed very early in postnatal life. The disorder is characterized by salt-wasting syndrome, hypoglycemia in early infancy or childhood, poor weight gain, vomiting, prolonged neonatal jaundice, and skin hyperpigmentation. In laboratory tests, hyponatremia, hyperkalemia, low levels of cortisol, aldosterone, and adrenal androgens are found, in contrast to high levels of adrenocorticotropic hormone (ACTH) and plasma renin activity (Achermann et al. 2000; Nakae et al. 1997; Wiltshire et al. 2001; Verrijn Stuart et al. 2007). Very frequently, patients are admitted to hospital in a life-threatening condition. AHC is lethal unless appropriate steroid replacement therapy is provided to these patients. Most patients with AHC also suffer from hypogonadotropic hypogonadism, since mutations in the NR0B1 (DAX1) gene A. Rojek (*) :M. Niedziela 2nd Chair of Pediatrics, Department of Pediatric Endocrinology and Rheumatology, Molecular Endocrinology Laboratory, Poznan University of Medical Sciences, 27/33 Szpitalna Street, 60-572 Poznan, Poland e-mail: aleksandra.rojek@gmail.com