Disorders Of Pituitary Gland Research Articles

Increased risk of breast cancer among premenopausal women with pituitary gland disorders in Taiwan: a population-based matched-cohort study.

An association between pituitary gland disorders and breast cancer remains controversial. We examined the prevalence and risk of breast cancer over a 15-year follow-up period or until diagnosed as breast cancer among premenopausal women (12-49 years old) with pituitary gland disorders in Taiwan. This retrospective matched-cohort study included 52,265 individuals each in the study group (women with pituitary gland disorders) and the matched control group from 2000 to 2004 identified using Taiwan's National Health Insurance Research Database. We compared sociodemographic characteristics and medical disorders between the two groups and examined the differences in clinicopathological characteristics of breast cancer. We also estimated the risk of breast cancer over 15 years of follow-up (median follow-up time = 11.2 years). Overall, 924 (1.8%) and 734 (1.4%) patients in the study and control groups, respectively, were diagnosed as having breast cancer (p < 0.001). Over the 15-year follow-up period, the study group had a 1.16-fold (95% confidence interval [CI] = 1.04-1.29, p < 0.05) increased risk of breast cancer compared with the control group. This risk was particularly pronounced in the 20-29 and 30-39 age groups (adjusted hazard ratio = 1.46 and 1.25, respectively; 95% CI = 1.15-1.86 and 1.07-1.44, p value < 0.01, respectively). Our findings reveal a relationship between pituitary gland disorders and breast cancer among premenopausal women in an Asian country. Physicians should check for signs of breast cancer in premenopausal women with pituitary gland disorders for early detection and treatment. Future studies should confirm our findings and clarify the causal relationship.

THU627 Fertility Outcomes And Anti Mullerian Hormone Levels In Women With Hypopituitarism

Abstract Disclosure: V.W. Fitz: None. C.O. Sailer: None. I. Remba-Shapiro: None. N. Bomani Gonzalez: None. W. Pierre: None. C. Bormann: None. I. Souter: None. L.B. Nachtigall: None. Background: Disruption of the hypothalamic-pituitary-gonadal (HPG) axis due to pituitary gland disorders presents a challenge for patients who desire conception. Women with hypopituitarism often require assisted reproductive technology (ART) to conceive. Anti-Mullerian Hormone (AMH) has been established as a marker of ovarian reserve in patients with normal HPG function, however, levels in women with hypopituitarism have not been reported. In this cohort, we investigate pre-conception AMH levels, reproductive treatments and fertility outcomes in women with hypopituitarism. Methods: We reviewed a large database and identified 19 patients with hypopituitarism who had undergone fertility treatment and 142 age-matched controls with male factor infertility. Clinical characteristics and AMH levels are shown using mean (SD) or median (IQR). AMH ratio using the lower limit of normal as denominator is used to normalize to the reference range as several assays with different reference ranges were used during the timeframe of data collection. Mann-Whitney U was used to compare AMH levels. A p value of &amp;lt;0.05 was considered statistically significant. Results: Patients with hypopituitarism and controls had a mean age of 33.4 years (2.5) and 33.3 years (2.2) p=0.857, at initial fertility evaluation, respectively. 17/19 (89.5%) patients in the hypopituitarism group experienced spontaneous menarche and had a post-pubertal onset of hypopituitarism. Hormonal deficiencies included GH (9), ACTH (8), TSH (10), FSH/LH (13), and vasopressin (3). Causes of hypopituitarism included 8 pituitary adenomas (7 functioning and 1 non-functioning), 3 Rathke’s cleft cysts, 4 intracranial neoplasms, 2 congenital or idiopathic hypopituitarism and 1 intracranial trauma. Median AMH level was 2.60 ng/mL (0.90-3.50) vs. 3.48ng/mL (1.99-4.70) p=0.017, and AMH ratio was 3.11ng/mL (1.13-4.17) vs. 4.11ng/mL (2.60-6.25) p=0.070, in the hypopituitary group and in controls, respectively. Among the 19 patients with hypopituitarism, 13 underwent ovulation induction (OI) with intrauterine insemination (IUI) or timed intercourse (TIC), 12 underwent in vitro fertilization (IVF), and 6 were treated with both OI and IVF. 18/19 (94.7%) conceived and 16/19 (84.2%) had a livebirth. Four patients (21%) conceived spontaneously. Among the patients who underwent OI, 4/13 (30.8%) had ≥1 livebirth with a median of 2 cycles (range 1-4) until first birth. Among the patients who underwent IVF, 10/12 (83.3%) had ≥ 1 livebirth with a median of 1.50 cycles (range 1-4) until first birth. Conclusions/Impact: Patients with hypopituitarism conceive through a variety of assisted reproductive technologies and may conceive spontaneously. Overall, AMH levels are comparable to age matched controls. Reproductive interventions among women with hypopituitarism are successful, with most patients achieving at least one livebirth. Presentation: Thursday, June 15, 2023

Survey on Endocrinology and Nutrition undergraduate teaching in Spain-2021

ObjectivesAdvances in endocrinology and nutrition (E&N) and the importance of its associated disorders require that its teaching within the medical degree meets adequate standards of quality and homogeneity Our objective was to expand the data on E&N undergraduate teaching in Spain. MethodsWe designed an observational, cross-sectional web-based study addressed to the coordinators of E&N teaching at the 42 faculties of medicine that had taught the subject during the 2020–2021 academic year. ResultsOne in three faculties had a professor who was an E&N specialist, but less than half had a full professor of E&N. There is great variability in teaching programmes, although most of them dedicate 6 ECTS credits to the subject. Over two-thirds of the faculties maintain theoretical lessons with over 50 students per class. Most programmes dedicate between four and six hours to hypothalamic pituitary disorders, thyroid diseases and adrenal gland disorders. However, there is great variability in the time dedicated to diabetes and nutrition. In one-third of the faculties, students are not required to do a rotation in the E&N department. Teachers at the universities widely participate in undergraduate/master’s students’ final projects and master’s degree studies. ConclusionsThe E&N specialty maintains a good position within universities, but there is still great heterogeneity in the teaching structure of the subject.

Proximal myopathy: causes and associated conditions.

Proximal myopathy presents as generalized muscle weakness commonly involving the muscles of upper and/or lower limbs. Toxins, long-term use of statins, corticosteroids, alcohol, SGLT2 inhibitors, COVID-19 vaccination, and antimalarials have been attributed to its development. In endocrine and metabolic disorders, adrenal dysfunction including both overproduction and insufficiency of the adrenal gland hormones has been reported to cause myopathy. Moreover, parathyroid and thyroid disorders along with pituitary gland disorders can also directly or indirectly contribute to this condition. In idiopathic inflammatory myopathies including polymyositis, dermatomyositis, inclusion body myositis (IBM), and Systemic Lupus Erythematosus (SLE), Sjögren's Syndrome, and overlap syndromes, moderate to severe muscle weakness has been observed. IBM has been reported to be the most prevalent acquired myopathy above the age of 50. Hereditary or congenital myopathies include limb girdle muscular dystrophies, facioscapulohumeral muscular dystrophy, Duchenne and Becker muscular dystrophy, and proximal myotonic myopathy. In addition to these, glycogen storage diseases such as the McArdle disease can also cause fast exhaustion, myalgia, and cramping in working muscles. It is pertinent to mention here that a class of hereditary metabolic myopathies, referred to as "lipid deposition myopathy" causes lipids to accumulate in skeletal muscle fibers, leading to lesions and degeneration. Among viral causes, HIV, dengue virus, influenza virus, hepatitis B virus, hepatitis C virus, SARS-CoV2 are also associated with muscle weakness. Sarcoidosis, an inflammatory disease, can also manifest as muscle weakness and myalgia. Owing to this complicated pathophysiology of proximal myopathy, this review aims to summarize the existing literature on conditions associated with this phenomenon and other recent developments that have been made regarding events leading to development of generalized muscle weakness. To the authors' knowledge this is the first narrative review that discusses causes and conditions associated with proximal myopathy in thorough detail.

ODP036 Cortisol Values During the Standard-Dose Cosyntropin Stimulation Test: Personal Experience with Elecsys Cortisol II Assay

Abstract Background There has been debate regarding the appropriate cortisol cutoffs during the cosyntropin stimulation test (CST) when the newer cortisol assays are used. Recent studies have recommended cortisol cutoffs lower than previously recommended. We aimed to evaluate the cortisol levels during the standard dose CST in patients evaluated for adrenal insufficiency and found to have a normal HPA axis using the Elecsys ® Cortisol II (Roche Diagnostics)assay. METHODS: This was a retrospective chart review study of adult patients who had the CST performed within an academic ambulatory setting from January 2018 to December 2020. They had ICD-10 codes of pituitary gland disorders in their problem list or diagnoses at the time of data extraction. Only patients with a normal HPA axis were included in the analysis, which was defined based on evaluation by an endocrinologist, restrictive exclusion criteria, and a lack of glucocorticoid administration for at least 6 months after CST. Exclusion criteria included oral glucocorticoid use within 6 months before the CST or 3 months for other routes, albumin &amp;lt; 2.5 g/dL, liver disease, pituitary insult within 6 weeks before the CST, estrogen and opioid use within 3 months before the CST, and pregnancy. The results are reported in the median (range). Results Out of 305 patients, 63 (20.6) met the study criteria. The median age was 54.7 (27.6-89.1) years; 32 (51%) were females, and 27 (43%) were white. The duration of follow-up after the CST was 13.9 (6.3-43.9) months. Cortisol values at 30- and 60-minutes post-CST were available for 43 (68.2%), and 61 patients (96.8%), respectively. The cortisol levels at 30- and 60-minutes after the CST were 21.7 (15.7-29.1) µg/dL and 24.4 (17.9-35.8) µg/dL, respectively. The lowest cortisol levels at 30 and 60 minutes after the CST for patients with either normal TSH or gonadal axis (n=47) or in whom both axes were normal (n=18) were similar to the entire cohort. Conclusion Our study supports using a lower cortisol cutoff value at 30 minutes after the CST using the Roche Elecsys ® Cortisol II assay. The lowest cortisol level in our cohort was 15.7 ug/dL. However, the same pass criteria cannot be used at 60 minutes. Therefore, it is essential to consider the time of cortisol draw after the CST. Presentation: No date and time listed

Encuesta sobre la docencia pregrado de Endocrinología y Nutrición en España-2021

ObjectivesAdvances in Endocrinology and Nutrition (E&N) and the importance of its associated disorders require that its teaching within the medical degree meets adequate standards of quality and homogeneity. Our objective was to expand the data on E&N undergraduate teaching in Spain. MethodsWe designed an observational, cross-sectional web-based study addressed to the coordinators of E&N teaching at the 42 faculties of medicine that had taught the subject during the 2020-2021 academic year. ResultsOne in three faculties had a professor who was an E&N specialist, but less than half had a full professor of E&N. There is great variability in teaching programmes, although most of them dedicate 6 ECTS credits to the subject. Over two-thirds of the faculties maintain theoretical lessons with over 50 students per class. Most programmes dedicate between four and six hours to hypothalamic pituitary disorders, thyroid diseases and adrenal gland disorders. However, there is great variability in the time dedicated to diabetes and nutrition. In one-third of the faculties, students are not required to do a rotation in the E&N department. Teachers at the universities widely participate in undergraduate/master's students’ final projects and master's degree studies. ConclusionsThe E&N specialty maintains a good position within universities, but there is still great heterogeneity in the teaching structure of the subject.

Hydrogen sulfide suppress the pathological alterations of endocrine glands induced by Gamma irradiation and cyclophosphamide

Hydrogen sulfide (H2S) is a gaseous mediator and is usually recommended to have antioxidant, anti-inflammatory, anticancer and antiapoptotic consequences. In the endocrine system, H2S can act at the thyroid, adrenal gland, and gonad through the hypothalamus-pituitary axis, in addition to at the pancreas there by collaborating withinside the law of many hormones of the body, and the hypothalamus pituitary axis can, in turn, adjust the manufacturing of (H2S). Chemotherapy (Cyclophosphamide) can cause damage of thyroid, pituitary, pancreatic and adrenal glands. Radiation-induced thyroid, hypothalamus, and anterior pituitary gland disorders. Radiation-induced injury of the endocrine pancreas is known to increase the risk of diabetes mellitus. Testis tissue, radiosensitive organ, has a variety of cells that differ in their degree of sensitivity. In this manner, cancer patient needs for protective agent against different side effects of anticancer therapy especially in case of combination between chemo and radio therapies.

Immune-Related Adverse Events After Immune Checkpoint Inhibitors for Melanoma Among Older Adults

Immune checkpoint inhibitors (ICIs) have improved survival in patients with advanced melanoma but can be associated with a spectrum of immune-related adverse events (AEs), including both autoimmune-related AEs and other immune-related inflammatory AEs. These associations have primarily been evaluated in clinical trials that include highly selected patients, with older adults often underrepresented. To evaluate the association between use of ICIs and immune-related AEs (autoimmune and other immune related) among older patients with cutaneous melanoma. A population-based cohort study was conducted from January 1, 2011, to December 31, 2015. Data were analyzed from January 31 to May 31, 2021. With use of a linked database of Medicare claims and Surveillance, Epidemiology, and End Results (SEER) Program population-based cancer registries, patients of White race diagnosed with stages II-IV or unknown (American Joint Committee on Cancer, AJCC Cancer Staging Manual 6th edition) first primary cutaneous melanoma during 2011-2015, as reported to SEER, and followed up through December 31, 2015, were identified. Immune checkpoint inhibitors for treatment of melanoma. The association between ICIs and immune-related AEs ascertained from Medicare claims data was estimated using multivariable Cox regression with hazard ratios (HRs) and 95% CIs and with cumulative incidence accounting for competing risk of death. The study included 4489 patients of White race with first primary melanoma (3002 men [66.9%]; median age, 74.9 [range, 66.0-84.9] years). During follow-up (median, 1.4 [range, 0-5.0] years), 1576 patients (35.1%) had an immune-related AE on a Medicare claim. Use of ICIs (reported for 418 patients) was associated with autoimmune-related AEs (HR, 2.5; 95% CI, 1.6-4.0), including primary adrenal insufficiency (HR, 9.9; 95% CI, 4.5-21.5) and ulcerative colitis (HR, 8.6; 95% CI, 2.8-26.3). Immune checkpoint inhibitors also were associated with other immune-related AEs (HR, 2.2; 95% CI, 1.7-2.8), including Cushing syndrome (HR, 11.8; 95% CI, 1.4-97.2), hyperthyroidism (HR, 6.3; 95% CI, 2.0-19.5), hypothyroidism (HR, 3.8; 95% CI, 2.4-6.1), hypopituitarism (HR, 19.8; 95% CI, 5.4-72.9), other pituitary gland disorders (HR, 6.0; 95% CI, 1.2-30.2), diarrhea (HR, 3.5; 95% CI, 2.5-4.9), and sepsis or septicemia (HR, 2.2; 95% CI, 1.4-3.3). Most associations were pronounced within 6 months following the first ICI claim and comparable with or without a baseline history of autoimmune disease. The cumulative incidence at 6 months following the first ICI claim was 13.7% (95% CI, 9.7%-18.3%) for autoimmune-related AEs and 46.8% (95% CI, 40.7%-52.7%) for other immune-related AEs. In this cohort study of older adults with melanoma, ICIs were associated with autoimmune-related AEs and other immune-related AEs. Although some findings were consistent with clinical trials of ICIs, others warrant further investigation. As ICI use continues to expand rapidly, ongoing investigation of the spectrum of immune-related AEs may optimize management of disease in patients.

A framework for employing longitudinally collected multicenter electronic health records to stratify heterogeneous patient populations on disease history.

ObjectiveTo facilitate patient disease subset and risk factor identification by constructing a pipeline which is generalizable, provides easily interpretable results, and allows replication by overcoming electronic health records (EHRs) batch effects.Material and MethodsWe used 1872 billing codes in EHRs of 102 880 patients from 12 healthcare systems. Using tools borrowed from single-cell omics, we mitigated center-specific batch effects and performed clustering to identify patients with highly similar medical history patterns across the various centers. Our visualization method (PheSpec) depicts the phenotypic profile of clusters, applies a novel filtering of noninformative codes (Ranked Scope Pervasion), and indicates the most distinguishing features.ResultsWe observed 114 clinically meaningful profiles, for example, linking prostate hyperplasia with cancer and diabetes with cardiovascular problems and grouping pediatric developmental disorders. Our framework identified disease subsets, exemplified by 6 “other headache” clusters, where phenotypic profiles suggested different underlying mechanisms: migraine, convulsion, injury, eye problems, joint pain, and pituitary gland disorders. Phenotypic patterns replicated well, with high correlations of ≥0.75 to an average of 6 (2–8) of the 12 different cohorts, demonstrating the consistency with which our method discovers disease history profiles.DiscussionCostly clinical research ventures should be based on solid hypotheses. We repurpose methods from single-cell omics to build these hypotheses from observational EHR data, distilling useful information from complex data.ConclusionWe establish a generalizable pipeline for the identification and replication of clinically meaningful (sub)phenotypes from widely available high-dimensional billing codes. This approach overcomes datatype problems and produces comprehensive visualizations of validation-ready phenotypes.

Premature Ejaculation and Endocrine Disorders: A Literature Review.

Premature ejaculation (PE) is the most common male sexual dysfunction, with 30% of men experiencing PE worldwide. According to the generally accepted classification, there are two types of PE: lifetime PE and acquired PE. Various biological and psychological causes are known to be involved in the etiology of PE. However, due to the incomplete definition and etiopathogenesis of PE, there is no effective treatment. Although clinical and animal studies indicate that hormones play a role in controlling the ejaculation process, the precise endocrine mechanisms are unclear. In addition, little is known about the role of endocrine disorders in PE etiology. However, there is evidence that diabetes mellitus (DM), obesity, metabolic syndrome (MetS), thyroid gland disorders, pituitary gland disorders, and vitamin D deficiency affect the prevalence of PE. Moreover, it has been reported that the prevalence of PE decreases with treatment of these endocrine disorders. In this review, the relationship between PE and DM, MetS, obesity, vitamin D deficiency, and thyroid and pituitary gland disorders is summarized.

Demographic Profile of Endocrine Disorders in Patients Admitted in Endocrinology Ward, Services Hospital Lahore

Objective: To find out frequency and demographic profile of endocrine disorders in patients admitted in endocrinology ward at Services Hospital Lahore. Methods: The cross-sectional study was conducted at Services Hospital Lahore in Punjab, Pakistan. The study included 105 patients admitted in Endocrinology Ward. Data used was secondary and it was collected via medical record from June, 2018 to January, 2019. All information pertaining to patients was kept confidential. Ethical Review Committee permission was undertaken with final approval from Head of Department. Results: Demographic characteristics of patients included age, gender, and showed majority to be middle- aged females. The number of female cases were 65.71% (n = 69), while male cases were 34.29% (n = 36). The average age of all the patients was 40.62 ± 16.52. Majority of the patients with 76.19% (n = 80) cases were reported with having glucose homeostasis disorders with 65.71% (n = 69) cases having diabetes mellitus and 10.48% (n = 11) with hypoglycemia. Pituitary gland disorders comprised 8.57% (n = 9) of the cases with 5.71% (n = 6) diagnosed as pituitary tumors and 2.86% (n = 3) as hypopituitarism. Pituitary tumors further included Cushing syndrome with 4.76% (n = 5) cases and acromegaly with 0.95% (n = 1). Hypopituitarism comprised of hypocortisolism with 1.90% (n = 2) cases and Sheehan's syndrome with 0.95% (n = 1). 7.62% (n = 8) cases were reported with having thyroid disorders, with 4.76% (n = 5) having hyperthyroidism and 2.86% (n = 3) with hypothyroidism. 4.76% (n = 5) cases were diagnosed as sex hormone disorders comprising puberty disorders with 1.90% (n = 2) cases, fertility disorders with 1.90% (n = 2) and turner syndrome (inherited disorder) with 0.95% (n = 1). Calcium homeostasis disorders with 1.90% (n = 2) included one case each of parathyroid adenoma (parathyroid gland disorder) and osteoporosis (metabolic bone disease). Conclusion: The research indicated that glucose homeostasis disorders constituted highest in frequency, followed by pituitary gland disorders, thyroid disorders, sex hormone disorders and calcium homeostasis disorders. The current study urges us to act collectively in order to prevent endocrine disorders which can be done by promoting public education programs, proper counseling about its preventive measures and undergoing periodic medical examination. Key Words: Demography, Endocrine disorders.

Demographic Profile of Endocrine Disorders in Patients Admitted in Endocrinology Ward, Services Hospital Lahore

Objective: To find out frequency and demographic profile of endocrine disorders in patients admitted in endocrinology ward at Services Hospital Lahore. Methods: The cross-sectional study was conducted at Services Hospital Lahore in Punjab, Pakistan. The study included 105 patients admitted in Endocrinology Ward. Data used was secondary and it was collected via medical record from June, 2018 to January, 2019. All information pertaining to patients was kept confidential. Ethical Review Committee permission was undertaken with final approval from Head of Department. Results: Demographic characteristics of patients included age, gender, and showed majority to be middle- aged females. The number of female cases were 65.71% (n = 69), while male cases were 34.29% (n = 36). The average age of all the patients was 40.62 ± 16.52. Majority of the patients with 76.19% (n = 80) cases were reported with having glucose homeostasis disorders with 65.71% (n = 69) cases having diabetes mellitus and 10.48% (n = 11) with hypoglycemia. Pituitary gland disorders comprised 8.57% (n = 9) of the cases with 5.71% (n = 6) diagnosed as pituitary tumors and 2.86% (n = 3) as hypopituitarism. Pituitary tumors further included Cushing syndrome with 4.76% (n = 5) cases and acromegaly with 0.95% (n = 1). Hypopituitarism comprised of hypocortisolism with 1.90% (n = 2) cases and Sheehan's syndrome with 0.95% (n = 1). 7.62% (n = 8) cases were reported with having thyroid disorders, with 4.76% (n = 5) having hyperthyroidism and 2.86% (n = 3) with hypothyroidism. 4.76% (n = 5) cases were diagnosed as sex hormone disorders comprising puberty disorders with 1.90% (n = 2) cases, fertility disorders with 1.90% (n = 2) and turner syndrome (inherited disorder) with 0.95% (n = 1). Calcium homeostasis disorders with 1.90% (n = 2) included one case each of parathyroid adenoma (parathyroid gland disorder) and osteoporosis (metabolic bone disease). Conclusion: The research indicated that glucose homeostasis disorders constituted highest in frequency, followed by pituitary gland disorders, thyroid disorders, sex hormone disorders and calcium homeostasis disorders. The current study urges us to act collectively in order to prevent endocrine disorders which can be done by promoting public education programs, proper counseling about its preventive measures and undergoing periodic medical examination. Key Words: Demography, Endocrine disorders.

The Effect of Pituitary Gland Disorders on Glucose Metabolism: From Pathophysiology to Management.

This review aims to explore, present, and discuss disorders of glucose metabolism implicated in pituitary gland diseases, the appropriate interventions, as well as the therapeutic challenges that may arise. Pituitary pathologies may dysregulate glucose homeostasis, as both the excess and deficiency of various pituitary hormones can affect glucose metabolism. Increased circulating levels of growth hormone, glucocorticoids or prolactin have been shown to mainly provoke hyperglycemic states, while hypopituitarism can be associated with both hyperglycemia and hypoglycemia. Addressing the primary cause of these disorders with the use of surgery, medical treatment or radiotherapy forms the cornerstone of current management strategies. Physicians should bear in mind that some such medications have an unfavorable effect on glucose metabolism too. When unsuccessful, or until the appropriate treatment of the underlying pituitary problem, the addition of established antidiabetic therapies might prove useful. Further studies aiming to discover more accurate and effective drug preparations in combination with optimal lifestyle management models will contribute to achieving a more successful glycemic control in these patients.

Development and Study of Semi-Solid Preparations Containing the Model Substance Corticotropin (ACTH): Convenience Application in Neurodegenerative Diseases.

Corticotropin (ACTH, previously an adrenocorticotropic hormone) is used in the diagnosis and treatment of pituitary gland disorders, adrenal cortex disorders, and other diseases, including autoimmune polymyositis, systemic lupus erythematosus, rheumatoid arthritis, Crohn’s disease, and ulcerative colitis. So far, the ointment dosage form containing ACTH for use on the skin is unknown. Therefore, it seems appropriate to develop a semi-solid formulation with corticotropin. Emulsion ointments were prepared using an Unguator based on the cream base Lekobaza® containing corticotropin in different concentrations, and then the physical and chemical parameters of the ointment formulations, such as pH, spreadability, rheological properties, and texture analysis, were evaluated. In addition, a USP apparatus 2 with enhancer cells was utilized to study the in vitro drug release characteristics of the selected formulations. All the ointments obtained were characterized by good spreadability and viscosity. An analysis of the ointment texture was performed and the dependence of the tested parameters on the ACTH content in the ointment was demonstrated. Examination of the structure of the ointment showed that a high concentration of ACTH increases the hardness and adhesiveness of the ointment. In turn, it adversely affects the cohesiveness and elasticity of the ointments tested. The results of the release study showed that ACTH is released the fastest from the formulation with the lowest concentration, while the slowest from the ointment with the highest concentration of ACTH.

Development and validation of a candidate reference method for serum cortisol by isotope dilution liquid chromatography-tandem mass spectrometry combined with dextran sulfate-Mg2+ precipitation.

Accurate and precise cortisol measurements are requisite for ensuring appropriate diagnosis and management of diseases related with adrenal or pituitary gland disorders. Prompted by the needs in characterization of certified reference materials and quality assurance for serum cortisol measurements, we developed and evaluated a highly reliable measurement procedure based on isotope dilution liquid chromatography-tandem mass spectrometry (ID LC-MS/MS) combined with dextran sulfate-Mg2+ precipitation as the sample pretreatment. An appropriate amount of serum was accurately weighed and spiked with the isotope labelled internal standard. After precipitation, massive lipids and lipoproteins were removed from serum matrix. The clear supernatant was transferred and extracted with ethyl acetate-hexane solution. The cortisol was analyzed with LC-MS/MS in positive electrospray ionization mode. The within-run and total coefficient of variations (CVs) ranged from 0.3 to 0.6% and 0.7 to 1.2%, respectively, for a concentration range of 76.30 to 768.04nmol/L. A regression comparison of the results obtained by the present method and the certified values of ERM-DA451 showed agreement with no statistical difference (Y = 1.0092 X-0.7455; 95% CI for the slope, 0.9940 to 1.0212; 95% CI for the intercept, - 3.6575 to 2.6390, r2 = 0.999). All structural analogs of cortisol tested were well resolved from cortisol in 12min on a phenyl ligand column under an isocratic elution. The limit of quantification was estimated to 5pg cortisol in absolute amount. This method is accurate and simple and can be served as a candidate reference measurement procedure in establishment of serum cortisol reference system.

بونیادی زمان له‌گێڕانه‌وه‌ى مه‌رگه‌ساتی ئه‌نفال له‌ڕۆمانی (هێلانه‌)ى (حسێن عارف)دا

Celiac disease (CD) is an autoimmune human leukocyte antigen HLA–linked enteropathy that develop upon ingestion of gluten containing diet, withdiarrhea, malabsorption and weight loss as a major presentation.The disease is closely linked to a number of extra intestinal disorderespecially endocrine diseases. This study aimed to assess level of thyroidstimulation hormone (TSH) and growth hormone (GH) level in patients with newlydiagnosed (ND) CD and on gluten free diet (GFD)A total of 26/50 newly diagnosed celiac disease patients and 20 on GFDdiagnosed clinically and confirmed serologically using anti-gliadin IgA and IgG(IgA for diagnosis newly diagnosed and IgG for diagnosis of patients on GFD)were subjected to TSH and GH level assessment.The anti-gliadin IgA and IgG were positive in 82% with celiac patients and80% on GFD patients. Among children , 82.14% of newly diagnosed and 85.71%on GFD were IgA and IgG anti-gliadin seropositive, while in adults, 81.82% and76.92 % of newly diagnosed and on GFD were IgA and IgG anti-gliadinseropositive respectively. The results revealed elevated TSH level in sera of 80.77% and 30% of CDand on GFD patients respectively; meanwhile GH level was low in 73.07% and10% of CD and GFD patients respectively. The frequency CD patients revealedTSH elevation and low GH in the same patient was 69.23 % and 10% in CD and onGFD patients respectively.As a result, the present study delineated simultaneous occurrence and linkagebetween CD disease and subclinical hypothyroidism. Beside assessment of GHlevel in CD patients is necessary as marker for disorder of pituitary gland, possiblyof autoimmune origin.In newly diagnosed and patients on GFD patients, no significant correlation existsbetween anti-gliadin antibodies, TSH & GH level. Meanwhile significantcorrelation was found between TSH & GH in ND (r= - 0.568, P=0.002) & GFD (r=- 0.702, P= 0.001).

Role of Imaging in the Evaluation of Male Infertility.

Infertility is defined herein as the inability to achieve pregnancy after frequently engaging in unprotected sexual intercourse for 1 year. Among infertile couples, the cause of infertility involves the male partner in approximately 50% of cases. Male infertility is usually caused by conditions affecting sperm production, sperm function, or both, or blockages that prevent the delivery of sperm. Chronic health problems, injuries, lifestyle choices, anatomic problems, hormonal imbalances, and genetic defects can have a role in male infertility. The diagnostic workup of male infertility should include a thorough medical and reproductive history, physical examination, and semen analysis, followed by imaging. The main role of imaging is identification of the causes of infertility, such as congenital anomalies and disorders that obstruct sperm transport and may be correctable. Scrotal ultrasonography is the most common initially performed noninvasive examination used to image the male reproductive system, including the testes and extratesticular structures such as the epididymis. Magnetic resonance (MR) imaging is another noninvasive imaging modality used in the pelvis to evaluate possible obstructive lesions involving the ductal system. MR imaging of the brain is extremely useful for evaluating relevant neurologic abnormalities, such as pituitary gland disorders, that are suspected on the basis of hormone analysis results. Invasive techniques are usually reserved for therapeutic interventions in patients with known abnormalities. In this article, the causes and imaging findings of obstructive and nonobstructive azoospermia are discussed. In addition to detecting treatable conditions that are related to male infertility, identifying the life-threatening entities associated with infertility and the genetic conditions that could be transmitted to offspring-especially in patients who undergo assisted reproduction-is critical. ©RSNA, 2017.

Hypogonadotropic Hypogonadism in Infants with Congenital Hypopituitarism: A Challenge to Diagnose at an Early Stage

Background: Combined pituitary hormone deficiency (CPHD) presents a wide spectrum of pituitary gland disorders. The postnatal gonadotropic surge provides a useful period to explore the gonadotropic axis for assessing the presence of congenital hypogonadotropic hypogonadism (CHH). Aim: To explore the functioning of the hypothalamic-pituitary-gonadal axis in the postnatal gonadotropic surge for an early diagnosis of CHH in newborns or infants suspected of having CPHD. Subjects and Methods: A cohort of 27 boys under 6 months and 19 girls under 24 months of age with suspected hypopituitarism was studied. Serum concentrations of LH, FSH, testosterone, inhibin B, anti-Müllerian hormone (AMH) and estradiol were measured, and male external genitalia were characterized as normal or abnormal (micropenis, microorchidism and/or cryptorchidism). Results: CPHD was confirmed in 36 out of 46 patients. Low LH and testosterone levels were found in 66% of the hypopituitary males, in significant association with the presence of abnormal external genitalia. This abnormality had a positive predictive value of 93% for CHH. No significant association was observed between serum FSH, AMH and inhibin B and the patient's external genitalia. Conclusion: In newborn or infant boys with CPHD, LH and testosterone concentrations measured throughout the postnatal gonadotropic surge, together with a detailed evaluation of the external genital phenotype, facilitate the diagnosis of CHH at an early stage.

Primary (autoimmune) hypophysitis: a single centre experience

Autoimmune hypophysitis (AH) is a rare autoimmune inflammatory disorder of pituitary gland. To analyse clinical, hormonal, radiological features and management outcomes of AH. Retrospective analysis of patients with primary hypophysitis (where secondary causes of hypophysitis were ruled out) was carried out from 2006 to 2012. AH emerged as the most plausible aetiology and the diagnosis of exclusion. Twenty-four patients with AH (21 females and 3 males) were evaluated. They presented with symptoms of expanding sellar mass (83.3%), symptoms of anterior pituitary hormone deficiencies (58.3%), and diabetes insipidus (16.7%). The anterior pituitary hormonal axes affected were cortisol (75%), thyroid (58.33%) and gonadotropin (50%). All had sellar mass on magnetic resonance imaging, which was symmetrical (91.7%) and homogenously enhancing (91.7%). Stalk thickening, suprasellar extension, loss of posterior pituitary hyperintensity and parasellar T2 dark sign were seen in 87.5, 87.5, 71.5, and 50% respectively. In addition to hormone replacement, five (20.83%) patients underwent trans-sphenoidal surgery, fifteen (62.5%) were watchfully monitored, while four cases (16.67%) received steroid pulse therapy. On follow up imaging, the sellar mass regressed in all, while, stalk thickening was persistent in 13/19 (68.4%) non-operated patients at median follow up of 1 year. Pituitary hormone axis recovery was seen in 10 (41.67%) and was seen in cortisol 10/18 (55.5%) followed by gonadotropin 5/12 (41.67%) axis. Characteristic radiology helps in diagnosis of AH even without tissue diagnosis. Non-operative treatment is the preferred treatment modality. Steroid pulse therapy potentially improves pituitary axis recovery.

Preoperative preparation of patients with pituitary gland disorders

This paper presents the most common disorders of pituitary function: acromegaly, hypopituitarism, diabetes insipidus and syndrome similar to diabetes insipidus, in terms of their importance in preoperative preparation of patients. Pituitary function manages almost the entire endocrine system using the negative feedback mechanism that is impaired by these diseases. The cause of acromegaly is a pituitary adenoma, which produces growth hormone in adults. Primary therapy of acromegaly is surgical, with or without associated radiotherapy. If a patient with acromegaly as comorbidity prepares for non-elective neurosurgical operation, then it requires consultation with brain surgeons for possible delays of that operation and primary surgical treatment of pituitary gland. If operative treatment of pituitary gland is carried out, the preoperative preparation (for other surgical interventions) should consider the need for perioperative glucocorticoid supplementation. Panhypopituitarism consequences are different in children and adults and the first step in diagnosis is to assess the function of target organs. Change of electrolytes and water occurs in the case of pituitary lesions in the form of central or nephrogenic diabetes insipidus as a syndrome of inappropriate secretion of antidiuretic hormone (SIADH). Preoperative preparation of patients with pituitary dysfunction should be multidisciplinary, whether it is a neurosurgical or some other surgical intervention. The aim is to evaluate the result of insufficient production of pituitary hormones (hypopituitarism), excessive production of adenohypophysis hormones (acromegaly, Cushing's disease and hyperprolactinemia) and the influence of pituitary tumours in surrounding structures (compression syndrome) and to determine the level of perioperative risk. Pharmacological suppressive therapy of the hyperfunctional pituitary disorders can have significant interactions with drugs used in the perioperative period.