Adrenal Cortical Function Research Articles

Adrenal morphology and cortical function in patients with extrapulmonary tuberculosis: response to antituberculosis treatment.

Enlargement of the adrenal glands and variable adrenocortical function have been reported in patients with pulmonary tuberculosis and, in a few studies, in patients with extrapulmonary tuberculosis (EPTB). However, none of the studies have evaluated the course of the adrenal morphology in these patients. Prospective study including 37 patients with EPTB and 37 healthy age- and sex-matched controls. The adrenal function was evaluated by measurement of cortisol levels at baseline and after stimulation with ACTH (Acton Prolongatum) before and 6 months after antituberculosis treatment. The size of both adrenal glands was evaluated using 64-slice computed tomography (CT) scanning before and 6 months after treatment. The findings were compared with those in a group of healthy matched controls. Clinical and biochemical parameters were comparable between groups. The mean baseline serum cortisol level was significantly lower in the EPTB group (397.1 ± 184.9 nmol/L) compared with the control group (696.3 ± 101.8 nmol/L). Compared with controls, patients with EPTB had significantly lower mean cortisol levels at baseline and 1 hour after ACTH, both before (397 ± 184.9 nmol/L and 750.7 ± 176.8 nmol/L, respectively) and after (529.7 ± 100.4 nmol/L and 1017.2 ± 119.7 nmol/L, respectively) antituberculosis treatment. Both the length and thickness of the right and left adrenal glands were greater in patients with EPTB than in controls but became comparable to those in controls after treatment completion. Patients with EPTB have an enlarged adrenal size and low baseline and stimulated serum cortisol levels. After treatment completion, cortisol levels increased significantly, and the adrenal size normalized in these patients.

OR27-05 Two-pronged Mediation Of Adrenal Steroidogenesis By Oxytocin

Abstract Disclosure: U. Cheliadinova: None. G. Pevnev: None. V. Ryu: None. T. Frolinger: None. S.L. Sims: None. M. Ofer: None. F. Korkmaz: None. O. Barak: None. J. Gimenez Roig: None. F. Sultana: None. N. Kramskiy: None. S. Wizman: None. M. Orloff: None. T. Yuen: None. D. Lizneva: None. M. Zaidi: None. A. Gumerova: None. Stress–stimulated glucocorticoid release affects diverse biological processes, including pregnancy and childbirth. The controversy surrounding effects of OXT on stress prompted us to investigate its actions on adrenal cortical function in mice. RNAscope and immunohistochemistry provided unequivocal evidence for abundant OXT receptor (OXTR) expression in the adrenal cortex, predominantly in zona fasciculata and zona reticularis. Female mice displayed higher adrenal cortical Oxtr expression, more than a range of other tissues under study. Oxtr expression was also detected in the adenohypophysis solely in female mice, while both male and female mice expressed Oxtr in the pars intermedia of the hypophysis. Aging impressively attenuated Oxtr expression in female mice in both the adrenal gland and adenohypophysis. For loss–of–function studies, we generated tissue–specific Star-CreERT2/Oxtrfl/fl mice in which the Oxtr was deleted from steroidogenic tissues, namely adrenals and ovaries. Deletion was confirmed by RNAscope and immunohistochemistry. We found no difference in serum corticosterone between tamoxifen–induced and uninduced mice; however, the elevation of serum corticosterone upon ACTH stimulation or after four weeks of stress was attenuated in tamoxifen–induced mice. Bulk RNAseq of adrenals from tamoxifen–induced mice revealed the downregulation of key steroidogenic genes, namely Cyp17a1, Hsd3b3, Hsd17b2, Cyp3a41b, and Serpina6 (a corticosteroid–binding globulin). In gain–of–function studies, a single OXT injection led to a rise of serum ACTH in tamoxifen–induced mice, which was greater in magnitude than uninduced controls. However, after five days of OXT injections, corticosterone levels became elevated, whereas ACTH levels declined to baseline. This suggests that OXT acts directly on OXTRs on corticotropes to initiate a stress–like response, with a negative feedback loop that inhibits further ACTH secretion. Of note is that male mice did not display any difference between tamoxifen–induced and uninduced groups, consistent with their low hypophyseal Oxtr expression. In all, we describe a novel gender–specific two–pronged circuit through which OXT may precisely regulates the production of corticosterone from the adrenal cortex. In the first arm, OXT directly stimulates ACTH secretion through adenohypophysis OXTRs. In the second arm, OXT prevents excessive stress–induced adrenal stimulation by downregulating steroidogenic genes. Our discovery lays the foundation for the emergence of new physiology that may relate to a fundamental role for oxytocin in the stress response during procreation, notably, when levels are elevated during pregnancy and lactation. Presentation: Saturday, June 17, 2023

FRI562 Not JUST Severe Hypothyroidism: Recognizing Autoimmune Polyglandular Syndrome

Abstract Disclosure: S.R. Jafarian-Kerman: None. A. Razzeto: None. G. Saini: None. M. Siddiqui: None. M. Islam: None. D. Behman: None. M. Carson: None. Background: Recognizing Autoimmune Polyglandular Syndrome (AIPS) in a patient who has chronic hypothyroidism, specifically with a non-classic presentation, is challenging. Clinical Case: A woman in her 50’s with hypothyroidism presented with one week of progressive dizziness and weakness. Medications include levothyroxine 125 μg weekly (per the patient, her PCP started this dose 8 months ago based on lab results). On physical examination: BP 101/74 mmHg; HR 56 bpm; T: 98.1 F (36.7 C); RR: 23/min; O2 Sat: 98%. Skin: vitiligo. Lab results demonstrated TSH: 839.6 μIU/mL (0.5-4.5) from 0.28 one year ago, free T4: 0.15 ng/dL (0.4-4.5), phosphorus: 2.3 mg/dL (2.7-4.5), vitamin D: 17.4 ng/dL (>30). She was started on daily levothyroxine 125 μg and intravenous fluids. On day 3 of admission, Rapid Response was called for blood pressure 54/39 mmHg. Myxedema coma was unlikely as she lacked altered mental status, hypothermia, hypoventilation, hyponatremia, or hypoglycemia; CT head was normal. On the same day, hydrocortisone 100 mcg q8h started due to high suspicion of adrenal insufficiency given low normal cortisol [7.1 ug/dL (6-20)] and hypotension. Due to the history of hypothyroidism, vitiligo, and the new diagnosis of adrenal insufficiency, we suspected AIPS. two days later, primary adrenal insufficiency was established by a positive Cosyntropin stimulation test (1 hour cortisol of 14.8 ug/dL; not reaching >18 μg/dL), elevated ACTH 72 pg/mL (6-50), Aldosterone <1 ng/dL (3-16), and low DHEA of 52 ng/dL (345-2030). Other labs were as follow: normal FSH 85.7 mIU/mL (23-116), elevated PTH 153 pg/mL (16-77) which decreased to 62 pg/mL with vitamin D supplementation, normal Vitamin B12, and negative renin and intrinsic factor antibodies. A diagnosis of AIPS was established and she was discharged on levothyroxine, fludrocortisone, and hydrocortisone. Conclusion: AIPS is typically idiopathic and may affect endocrine organ systems either simultaneously or sequentially. The 3 classic patterns are: Type 1 (most common): younger women, presents with candidiasis, hypoparathyroidism, and Addison’s disease. Type 2: middle-aged women, Addison’s disease, autoimmune thyroid disease and/or Type 1 diabetes. Type 3: Type 1 diabetes, pernicious anemia, vitiligo or alopecia, and normal adrenal cortical function. This patient is unique in that she has characteristics of both type 1 and 3 AIPS, but not diabetes. In this case, the combination of hypotension even in the setting of profoundly undertreated hypothyroidism, prompted the expanded evaluation. While isolated hypothyroidism is common among our internal medicine patients, those with additional symptoms, or in this case unexplained hypotension, should be evaluated for AIPS. Presentation: Friday, June 16, 2023

Association of Plasma Lipopolysaccharide-Binding Protein Concentration with Dietary Factors, Gut Microbiota, and Health Status in the Japanese General Adult Population: A Cross-Sectional Study

The influx of intestinal bacteria-derived lipopolysaccharide (LPS) into the blood has attracted attention as a cause of diseases. The aim of this study is investigating the associations between the influx of LPS, dietary factors, gut microbiota, and health status in the general adult population. Food/nutrient intake, gut microbiota, health status and plasma LPS-binding protein (LBP; LPS exposure indicator) were measured in 896 residents (58.1% female, mean age 54.7 years) of the rural Iwaki district of Japan, and each correlation was analyzed. As the results, plasma LBP concentration correlated with physical (right/left arms' muscle mass [β = -0.02, -0.03]), renal (plasma renin activity [β = 0.27], urine albumin creatinine ratio [β = 0.50]), adrenal cortical (cortisol [β = 0.14]), and thyroid function (free thyroxine [β = 0.05]), iron metabolism (serum iron [β = -0.14]), and markers of lifestyle-related diseases (all Qs < 0.20). Plasma LBP concentration were mainly negatively correlated with vegetables/their nutrients intake (all βs ≤ -0.004, Qs < 0.20). Plasma LBP concentration was positively correlated with the proportion of Prevotella (β = 0.32), Megamonas (β = 0.56), and Streptococcus (β = 0.65); and negatively correlated with Roseburia (β = -0.57) (all Qs < 0.20). Dietary factors correlated with plasma LBP concentration correlated with positively (all βs ≥ 0.07) or negatively (all βs ≤ -0.07) the proportion of these bacteria (all Qs < 0.20). Our results suggested that plasma LBP concentration in the Japanese general adult population was associated with various health issues, and that dietary habit was associated with plasma LBP concentration in relation to the intestinal bacteria.

Low-Dose ACTH Stimulation Test in Obesity: A Randomized Dose Assessment.

The short cosyntropin test is widely used for adrenal insufficiency screening and diagnosis. Lower cosyntropin doses may have greater sensitivity vs. the standard dose in detecting adrenal dysfunction. Obesity and overweight are increasing, impacting the clinical presentation of some diseases. Currently more than 50% of the subjects diagnosed with autoimmune adrenal insufficiency have a BMI greater than 25, and hence individuals living with overweight and obesity are more frequently requiring evaluation of the adrenal cortical function. Fixed-dose cosyntropin stimulation may not be appropriate for individuals with obesity. The primary objective was to compare cortisol response to a weight-adapted cosyntropin dose vs. a fixed low dose (1 µg) and a more physiologically fixed dose (10 µg). Twenty individuals with obesity and 20 age-matched healthy controls underwent in a randomized sequence at least one-week apart, to the The short cosyntropin test with three different doses, 0.2 µg/kg of body weight, 1 or 10 µg fixed dose stimuli. The assessment and data analysis were blinded to the individual and the investigator. Cortisol response was reduced in the group with obesity with the 1 µg fixed dose stimuli at 30 minutes (median, IQR) 649.6 µg, 567.3-738.4 µg for the control group vs. 568.6 µg, 528.4-623.13 µg, p=0.04; there was a lower cortisol peak at 60' in all the three evaluated doses, with a dose-dependent trend. A weight-adapted cosyntropin dose of 0.2 µg in obesity produces a similar response to the one observed in individuals without obesity. The 1 µg ACTH test falls short on stimulating the cortisol adrenal response in individuals with obesity.

Monitoring for and Management of Endocrine Dysfunction in Adrenoleukodystrophy.

Adrenoleukodystrophy (ALD) is a peroxisomal disorder affecting the nervous system, adrenal cortical function, and testicular function. Newborn screening for ALD has the potential to identify patients at high risk for life-threatening adrenal crisis and cerebral ALD. The current understanding of the natural history of endocrine dysfunction is limited. Surveillance guidelines for males with ALD were developed to address the unpredictable nature of evolving adrenal insufficiency. Early recognition and management of adrenal insufficiency can prevent adrenal crisis. While testicular dysfunction in ALD is described, the natural history and complications of low testosterone, as well as the management, are not well described.

Congenital Hypothyroidism and Hyperthyroidism Alters Adrenal Gene Expression, Development, and Function.

Background: The human adrenal cortex undergoes several rapid remodeling steps during its lifetime. In rodents, similar remodeling occurs postnatally in the "X-zone" layer through unknown mechanisms. Furthermore, little is known regarding the impact of thyroid hormone (TH) on adrenal glands in humans. Methods: To investigate the impact of TH on adrenal pathophysiology, we created two genetic murine models mimicking human nonautoimmune hypothyroidism and hyperthyroidism. Moreover, we analyzed serum thyrotropin (TSH) and steroid hormone concentrations in patients diagnosed with congenital hypothyroidism and premature adrenarche (PA). Results: We found that TH receptor beta-mediated hypertrophy of the X-zone significantly elevated the adrenal weights of hyperthyroid women. In the hypothyroid model, the X-zone was poorly developed in both sexes. Moreover, large reciprocal changes in the expression levels of genes that regulate adrenal cortical function were observed with both models. Unexpectedly, up- and downregulation of several genes involved in catecholamine synthesis were detected in the adrenal glands of the hypothyroid and hyperthyroid models, respectively. Furthermore, TSH and adrenal steroid concentrations correlated positively in pediatric patients with congenital hypothyroidism and PA. Conclusions: Our results revealed that congenital hypothyroidism and hyperthyroidism functionally affect adrenal gland development and related steroidogenic activity, as well as the adrenal medulla.

Evaluation of Adrenal Cortical Function in Neonatal and Weanling Laboratory Beagle Dogs.

The most common target organ for toxicity in the endocrine system is the adrenal gland, and its function is dependent upon the hypothalamus and pituitary gland. Histopathologic examination of the adrenal glands and pituitary gland is routinely performed in toxicity studies. However, the function of the adrenal gland is not routinely assessed in toxicity studies. Assessment of adrenal cortical function may be necessary to determine whether a histopathologic finding in the adrenal cortex results in a functional effect in the test species. As juvenile toxicity studies are more commonly performed in support of pediatric indications for pharmaceuticals, it is important to establish historical control data for adrenal gland function. In this study, adrenal cortical function was assessed in control neonatal and weanling beagle dogs as part of an ongoing juvenile toxicology program. Measurements of serum adrenocorticotropic hormone (ACTH), cortisol prior to and following administration of exogenous ACTH, and aldosterone were conducted beginning at 2 weeks of age continuing through 26 weeks of age. Serum electrolyte concentrations were determined at 4, 13, and 26 weeks of age. Dogs as young as 2 weeks of age synthesize and secrete adrenal cortical hormones and exhibit a functional hypothalamic pituitary adrenal axis.

Three cases of 3β-hydroxysteroid dehydrogenase deficiency: Clinical analysis.

3β-HSD deficiency is a rare type of congenital adrenal hyperplasia (CAH), which is caused by HSD3B2 gene mutations. In order to improve the understanding and diagnosis of the disease, we analyzed and summarized the clinical characteristics, genetic variants and treatment for 3 children with 3β-HSD deficiency in this study. A summary of the clinical data, hormone levels (17-hydroxyprogesterone, adrenocorticotropic hormone, cortisol, testosterone, dehydroepiandrosterone, androstenedione, renin, and aldosterone), therapeutic drugs, and gene sequencing results from 3 3β-HSD deficiency patients was created. The 3 patients developed external genital abnormalities and adrenal insufficiency in infancy. Steroid hormone levels were consistent with 3β-hydroxysteroid dehydrogenase deficiency. Gene sequencing for the 3 patients detected complex heterozygous mutations in the HSD3B2 gene, which confirmed the diagnosis of 3β-HSD deficiency type II. Among the mutation types, c.154_162delinsTCCTGTT and c.674T>A have not been reported in the literature. The 3 children were treated with glucocorticoid and mineralocorticoid replacement, which controlled the adrenal insufficiency satisfactorily. In 2 male patients, external genital dysplasia manifested as hypospadias and small penis. After long-acting testosterone intramuscular injection to increase the penis size, the hypospadias were repaired. Mild masculinization in the female patient resulted in skin pigmentation and clitoral hypertrophy; however, no surgical intervention was required. The main clinical manifestations of 3β-HSD deficiency were adrenal insufficiency and sex hormone synthesis dysfunction. There was a strong phenotype correlation between the observed clinical manifestations in conjunction with steroid hormone levels and HSD3B2 mutations. The novel mutations c.154_162delinsTCCTGTT and c.674T>A were classified as pathogenic variants. Adrenal cortical function control was satisfactory after hormone replacement therapy, and hypospadias and small penis were attenuated using testosterone replacement therapy during mini-puberty for optimal surgical outcome.

4-Bromodiphenyl Ether Causes Adrenal Gland Dysfunction in Rats during Puberty.

Polybrominated diphenyl ethers (PBDEs) are a group of flame retardants with two or more bromines attached. They are endocrine disruptors. PBDEs photodegrade into 4-bromodiphenyl ether (BDE3). Whether BDE3 impairs adrenal cortical cell function during postnatal development still remains unknown. The aim of the current study was to investigate the influence of BDE3 on adrenal cortical cell function. Sprague-Dawley rats (35 days of age, male) were orally administered with BDE3 (0, 50, 100, and 200 mg/kg/day body weight) for 21 days. BDE3 significantly increased serum aldosterone and corticosterone levels at 200 mg/kg without affecting adrenocorticotropic hormone level. Further study showed that BDE3 up-regulated Cyp11b1 at 100 and 200 mg/kg and Scarb1, Star, Cyp11b2, Cyp21, and Nr5a1 mRNA levels in the 200 mg/kg group. BDE3 also decreased the phosphorylation of AMP-activated protein kinase (AMPK) at 200 mg/kg and increased PGC-1α and phosphorylated cyclic AMP-responsive element-binding protein (CREB)/CREB at 200 mg/kg. Taken together, these findings demonstrate that BDE3 stimulates adrenal cell function likely through decreasing phosphorylation of AMPK and increasing phosphorylation of CREB.

MON-LB058 Mediastinal Parathyroid Adenoma Presenting as a Neuroendocrine Tumor

Introduction: Tertiary hyperparathyroidism caused by renal failure can lead to ectopic parathyroid tissue hyperplasia creating a diagnostic challenge. Here we describe a case of mediastinal parathyroid hyperplasia presenting as a neuroendocrine tumor. Case Presentation: A 40-year-old male presented for endocrine workup of a possible mediastinal paraganglioma. At age 22 he was diagnosed with resistant hypertension followed by rapidly progressive renal failure. Hemodialysis was initiated following a failed kidney transplant at age 30. He was treated by nephrology for secondary hyperparathyroidism with calcitriol and cinacalcet and serum calcium was within the normal range. Parathyroid hormone (PTH) was 598 pg/mL (12-65 pg/mL). The patient developed shortness of breath and a right pleural effusion while awaiting a second transplant and a CT of the chest was completed. This revealed a 3.1x4.0x5.0 cm heterogenous mediastinal mass within the superior thorax, medial to the proximal thoracic esophagus, and posterior to the trachea at the level of T2. It did not communicate with the thyroid gland. An FNA of the mass showed cohesive groups of atypical cells with small uniform nuclei and a moderate amount of chromatin arranged in nests and acini. No mitotic figures were identified. Cells were positive for chromogranin and focally for CK7, and negative for CK20, synaptophysin, and TTF-1. Cytology was interpreted as a well differentiated neuroendocrine tumor/typical carcinoid. A Galium-68 DOTATATE scan revealed moderate tracer uptake in the mass only. His endocrine workup was notable only for a mildly elevated chromogranin A with normal serum catecholamines, calcitonin, and serotonin, as well as normal adrenal cortical function. The patient underwent thoracotomy with mediastinal mass resection. He developed severe postoperative hypocalcemia treated with calcium infusion and increased calcitriol doses. Pathology revealed a low-grade neuroendocrine tumor consistent with parathyroid hyperplasia with at least one lymph node positive for involvement. The tumor showed positive staining for PTH, chromogranin, and synaptophysin with Ki67 <1%. Conclusion: This case demonstrates a rare occurrence of mediastinal parathyroid hyperplasia related to tertiary hyperparathyroidism of renal failure. Early calcitriol replacement and PTH level monitoring represents the mainstay of prevention of tertiary hyperparathyroidism. Severe post-op hypocalcemia is a hallmark of disease and more extensive immunostaining of mediastinal masses should be applied in cases suggestive of parathyroid etiology, especially in patients with long-standing renal failure. Despite a low Ki67, lymph node involvement suggests the possibility of parathyroid carcinoma. Follow-up Gallium-68 DOTATATE scan and parathyroid scan are imperative to evaluate for recurrence or residual disease. Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. s presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.

Analysis of the Influencing Factors of 17-Hydroxyprogesterone Level and the Correlation between 17-Hydroxyprogesterone Level and the Clinical Parameters Related to Adrenal Cortical Function in Very-Low-Birth-Weight Infants

Analysis of the Influencing Factors of 17-Hydroxyprogesterone Level and the Correlation between 17-Hydroxyprogesterone Level and the Clinical Parameters Related to Adrenal Cortical Function in Very-Low-Birth-Weight Infants

Investigation of adrenal and thyroid gland dysfunction in dogs with ultrasonographic diagnosis of gallbladder mucocele formation.

Gallbladder mucocele formation is an emerging disease in dogs characterized by increased secretion of condensed granules of gel-forming mucin by the gallbladder epithelium and formation of an abnormally thick mucus that can culminate in obstruction of the bile duct or rupture of the gallbladder. The disease is associated with a high morbidity and mortality and its pathogenesis is unknown. Affected dogs have a significantly increased likelihood of concurrent diagnosis of hyperadrenocorticism, hypothyroidism, and hyperlipidemia. Whether these endocrinopathies represent coincidental primary disease processes that exacerbate gallbladder mucocele formation in predisposed dogs or reflect a concurrent disruption of endocrine and lipid metabolism is unclear. In this study, we investigated a hypothesis that dogs with gallbladder mucocele formation would have a high prevalence of occult and atypical abnormalities in adrenal cortical and thyroid gland function that would suggest the presence of endocrine disruption and provide deeper insight into disease pathogenesis. We performed a case-control study of dogs with and without ultrasonographic diagnosis of gallbladder mucocele formation and profiled adrenal cortical function using a quantitative mass spectrometry-based assay of serum adrenal-origin steroids before and after administration of synthetic cosyntropin. We simultaneously profiled serum thyroid hormone concentrations and evaluated iodine sufficiency by measurement of urine iodine:creatinine ratios (UICR). The studies were complemented by histological examination of archival thyroid tissue and measurements of thyroid gland organic iodine from dogs with gallbladder mucocele formation and control dogs. Dogs with gallbladder mucocele formation demonstrated an exaggerated cortisol response to adrenal stimulation with cosyntropin. A prevalence of 10% of dogs with gallbladder mucocele formation met laboratory-based criteria for suspect or definitive diagnosis of hyperadrenocorticism. A significantly greater number of dogs with gallbladder mucocele formation had basal serum dehydroepiandrosterone (DHEAS) increases compared to control dogs. A high percentage of dogs with gallbladder mucocele formation (26%) met laboratory-based criteria for diagnosis of hypothyroidism, but lacked detection of anti-thyroglobulin antibodies. Dogs with gallbladder mucocele formation had significantly higher UICRs than control dogs. Examination of thyroid tissue from an unrelated group of dogs with gallbladder mucocele formation did not demonstrate histological evidence of thyroiditis or significant differences in content of organic iodine. These findings suggest that dogs with gallbladder mucocele formation have a greater capacity for cortisol synthesis and pinpoint DHEAS elevations as a potential clue to the underlying pathogenesis of the disease. A high prevalence of thyroid dysfunction with absent evidence for autoimmune thyroiditis suggest a disrupted thyroid hormone metabolism in dogs with gallbladder mucocele formation although an influence of non-thyroidal illness cannot be excluded. High UICR in dogs with gallbladder mucocele formation is of undetermined significance, but of interest for further study.

Adrenal cortical function and adrenal volume in leprosy: A study of 40 cases

Adrenal cortical function and adrenal volume in leprosy: A study of 40 cases

High prevalence of suppressed adrenal cortical function in kidney transplanted patients during low-dose prednisolone therapy

High prevalence of suppressed adrenal cortical function in kidney transplanted patients during low-dose prednisolone therapy

Four Web-Based Interactive Endocrine Case Studies for Use in Undergraduate Medical Education.

This resource is a collection of four case-based exercises intended to provide medical students with structured and focused opportunities to link basic science with clinical application. The cases are designed to help students self-evaluate their knowledge and develop a robust and well- integrated understanding of endocrine physiology and pathophysiology in the context of a representative range of endocrine disorders involving adrenal cortical, thyroid, and reproductive function. Although these cases were designed for, and used by, first-year students, they are also suitable for more advanced students. Each case opens with a brief vignette containing a patient presentation and a history of present illness. The student first formulates a differential diagnosis and then sequentially narrows the differential by selecting from lists of diagnostic tests; correct answers with feedback are provided at each step. A diagnosis is ultimately required, and the student may be prompted to propose a treatment plan. End-of-course survey results from 128 first-year medical students suggest that the use of these interactive case studies was considered to be a worthwhile use of study time, and that knowledge gained in the correlate endocrine course was required to work through the cases. Students indicated that the levels of case and task complexity, along with feedback, were appropriate and helpful. These cases provide a resource for meeting the need for clinically relevant scenarios in the preclerkship years.

Salivary Cortisol Level Pre and Post MRI Scanning

The measurement of salivary cortisol level has become a reliable method for studying the adrenal cortical function and it is response to different intrinsic and extrinsic factors such as medications and stressful factors.&#x0D; The aims of this study is to investigate if there is difference between sex and the effect of time of testing on salivary cortisol level, pre and post was scanning, data for cortisol, Salivary Flow Rate (SFR) and PH of saliva were analyzed.&#x0D; Non-stimulated salivary samples from 24 subjects (8 males, 16 females) pre and post scanning with Magnetic resonance imaging (MRI) was collected and the diurnal variation was taken into consideration for that all the pre and post scanning samples collected at the morning. Salivary cortisol was measured by ELISA technique, PH of saliva was measured by PH meter and salivary flow rate by specific equation.&#x0D; The results shows there was significant difference in the level of salivary cortisol, SFR and PH of saliva pre and post examination and there was positive correlation with regard to cortisol level and PH of saliva pre and post scanning, just the salivary flow rate showed negative correlation, in addition the results revealed significant difference with regards to the sex of the participant as well as positive correlation between salivary PH and SFR in pretest phase and positive correlation between salivary cortisol level, SFR in post scanning phase.&#x0D; From the results of this study we can conclude that the exposure to MRI scanning have an effect on Hypothalamic pituitary –adrenal axes and predispose to significant changes in cortisol level post scanning and this difference must be taken into consideration in concern to effect of raising the level of cortisone on other variables.

Adrenocortical Gap Junctions and Their Functions.

Adrenal cortical steroidogenesis and proliferation are thought to be modulated by gap junction-mediated direct cell–cell communication of regulatory molecules between cells. Such communication is regulated by the number of gap junction channels between contacting cells, the rate at which information flows between these channels, and the rate of channel turnover. Knowledge of the factors regulating gap junction-mediated communication and the turnover process are critical to an understanding of adrenal cortical cell functions, including development, hormonal response to adrenocorticotropin, and neoplastic dedifferentiation. Here, we review what is known about gap junctions in the adrenal gland, with particular attention to their role in adrenocortical cell steroidogenesis and proliferation. Information and insight gained from electrophysiological, molecular biological, and imaging (immunocytochemical, freeze fracture, transmission electron microscopic, and live cell) techniques will be provided.

A direct role for thyroid hormone in development of the adrenal cortex.

A relationship between thyroid and adrenal dysfunction has been recognized for some time. Certain human autoimmune conditions, for example, can destroy both the thyroid gland and adrenal cortex resulting in combined hormone deficiencies. Beyond autoimmune destruction, however, a relationship between thyroid and adrenocortical function is less clear. Glucocorticoid excess has been shown to suppress the central thyroid axis, whereas thyroid hormone has been suggested to regulate adrenocortical function through changes in hepatic glucocorticoid metabolism. Overall, these studies are limited in scope, and any real regulatory relationship between these glands still remains tenuous (Samuels and McDaniel [1], Johnson et al [2]). This is why the study of Huang et al (3) is both timely and novel. These investigators show for the first time that thyroid hormone, acting through one of its receptor isoforms (THRB1), has a direct role in adrenocortical development and function. The adrenal cortex in mammals develops from intermediate mesoderm, whereas the adrenal medulla is derived from neuroectoderm (neural crest cells). The adrenal cortex first forms an immature zone, which is later replaced by mature cortical cell types. The immature or fetal zone in humans produces dehydroepiandrosterone sulfate, which is used by the placenta to produce estrogens. The definitive or adult zone in humans and other mammals, in contrast, produces mineralocorticoids and glucocorticoids. In immature mice, an inner cortical zone has been described that expresses the steroid-metabolizing enzyme, 20-α-hydroxysteroid dehydrogenase (20αHSD). This is termed the x-zone and regresses in male but persists in female adult mice. Whether there is a developmental equivalent of this zone in higher mammals is unclear at the present time. Interestingly, gonadal factors, gonadotrophins, and thyroid hormone are known to modify the appearance of this zone (Huang et al). Huang et al show, using a β-galactosidase tagged Thrb1 locus, that THRB1 colocalizes with 20αHSD to the x-zone in mice. In addition, they demonstrate that T3 treatment causes hypertrophy of this zone in wild-type but not Thrb−/− mice. As the authors point out, thyroid extract has also been reported to induce hypertrophy of the adrenal cortex in other species, such as the rabbit and cat, that lack a definable x-zone, which suggests that this finding might be generalizable to other mammals including humans. Armed with this knowledge, one might now wonder whether thyroid hormone deficiency per se can cause subtle or overt adrenocortical hormone deficiency by acting directly on the gland. The challenge here is to understand more fully the role of the fetal zone, which includes the x-zone, in adult adrenal cortical function. It appears that the definitive adult cortex develops from surface capsular cells that migrate into the gland, but the authors suggest that the x-zone might represent another source of cells involved in the stress response. Unfortunately, this hypothesis was not tested further in their study. One might predict, for instance, that hypothyroidism limits the acute stress response to ACTH or that thyroid hormone excess increases steroid hormone levels by expanding residual x-zone cells in the adult animal. Alternatively, the authors propose that thyroid hormone might regulate progesterone and 11-deoxycorticosterone levels via 20αHSD, which is known to catabolize both hormones, and this might alter adrenal function in some unknown way. Finally, given that thyroid hormone regulates adrenocortical cell development, it might also change cell surface antigens and be involved in some way in inducing adrenocortical autoimmunity. More work will need to be done to answer these questions. A clear role for thyroid hormone receptors in the development of the cerebellum, retina, and cochlea has been shown using Thrb−/− mice (Ortiga-Carvalho et al [4]), and many of these studies have been performed by the Forrest group. This study extends our knowledge of thyroid hormone to development of the adrenal cortex and provides a potential mechanism to explain unrecognized adrenocortical hormone deficiency in models of congenital hypothyroidism and adrenocortical hormone excess in states of thyroid hormone excess.

Pattern of adrenal morphology and function in pulmonary tuberculosis: response to treatment with antitubercular therapy

Although previous studies have shown enlargement of adrenal glands in patients with tuberculosis, only few have studied its natural history. Similarly, there have been variable reports of adrenal function in these patients. Some but not all the studies revealed a high prevalence of adrenal insufficiency. The aim of this study was to prospectively study the adrenal cortical function and morphology before and after treatment of pulmonary tuberculosis. In a prospective case-control study, 45 patients with acute pulmonary tuberculosis and 45 healthy age- and gender-matched controls were studied. Adrenal function was tested using a short Synacthen test at the baseline and after 6 months of antitubercular treatment. Size of both adrenal glands was studied using 64 slice MDCT (Somatom Sensation, Siemens) before and after 6 months of antitubercular treatment. The findings were compared with a group of healthy controls. The mean age of cases was 42·4 ± 20·4 years and that of controls was 41·1 ± 17·7 years. The various clinical and biochemical parameters were comparable between cases and controls. The mean cortisol both basal and one-hour postintravenous Synacthen was significantly lower in cases as compared to controls (mean ± SD basal cortisol of 413·57 ± 108·42 nmol/l in cases vs 615·26 ± 108·15 nmol/l in controls and post Synacthen cortisol of 685·61 ± 83·87 nmol/l in cases vs 1497·30 ± 734·44 nmol/l in controls). Both the adrenal length and thickness of the right and left adrenal gland were greater in patients with active tuberculosis compared with controls and reversed to baseline after completion of antitubercular treatment. Adrenal enlargement demonstrated by CT is common in active tuberculosis and is reversible. Basal and stimulated cortisol is less in patients with pulmonary tuberculosis as compared with healthy controls and increases after antitubercular treatment, although unlike previous studies, none of the patients had adrenal insufficiency.