Thyroid Axis Research Articles

Phylogenomic analysis of the Lake Kronotskoe species flock of Dolly Varden charr reveals genetic and developmental signatures of sympatric radiation.

Recent adaptive radiations provide experimental opportunities to parse the relationship between genomic variation and the origins of distinct phenotypes. Sympatric radiations of the charr complex (genus Salvelinus) present a trove for phylogenetic analyses as charrs have repeatedly diversified into multiple morphs with distinct feeding specializations. However, charr species flocks normally comprise only two to three lineages. Dolly Varden charr inhabiting Lake Kronotskoe represent the most extensive radiation described for the genus, containing at least seven lineages, each with defining morphological and ecological traits. Here, we perform the first genome-wide analysis of this species flock to parse the foundations of adaptive change. Our data support distinct, reproductively isolated lineages within the clade. We find that changes in genes associated with thyroid signaling and craniofacial development provided a foundational shift in evolution to the lake. The thyroid axis is further implicated in subsequent lineage partitioning events. These results delineate a genetic scenario for the diversification of specialized lineages and highlight a common axis of change biasing the generation of specific forms during adaptive radiation.

Altered Expression of Thyroid- and Calcium Ion Channels-Related Genes in Rat Testes by Short-Term Exposure to Commercial Herbicides Paraquat or 2,4-D.

Exposure to pesticides such as paraquat and 2,4-dichlorophenoxyacetic acid (2,4-D) has been linked to harmful health effects, including alterations in male reproduction. Both herbicides are widely used in developing countries and have been associated with reproductive alterations, such as disruption of spermatogenesis and steroidogenesis. The thyroid axis and Ca2+-permeable ion channels play a key role in these processes, and their disruption can lead to reproductive issues and even infertility. This study evaluated the short-term effects of exposure to commercial herbicides based on paraquat and 2,4-D on gene expression in rat testes. At the molecular level, exposure to paraquat increased the expression of the thyroid hormone transporters monocarboxylate transporter 8 (Mct8) and organic anion-transporting polypeptide 1C1 (Oatp1c1) and the thyroid receptor alpha (TRα), suggesting a possible endocrine disruption. However, it did not alter the expression of the sperm-associated cation channels (CatSper1-2) or vanilloid receptor-related osmotically activated channel (Trpv4) related to sperm motility. In contrast, exposure to 2,4-D reduced the expression of the Mct10 transporter, Dio2 deiodinase, and CatSper1, which could affect both the availability of T3 in testicular cells and sperm quality, consistent with previous studies. However, 2,4-D did not affect the expression of CatSper2 or Trpv4. Deregulation of gene expression could explain the alterations in male reproductive processes reported by exposure to paraquat and 2,4-D. These thyroid hormone-related genes can serve as molecular biomarkers to assess endocrine disruption due to exposure to these herbicides, aiding in evaluating the health risks of pesticides.

Sensitivity Analysis in Mathematical Models of the Hypothalamus-Pituitary-Thyroid Axis

Mathematical models are promising and important for advancing the current medical practice in the field of endocrinology. To assess the reliability of the range of mathematical models describing the hypothalamuspituitary- thyroid axis and to establish their applicability in clinical decision support, we conducted a local and global sensitivity analysis of the model. Thyroid regulation in euthyroid and diseased individuals may be quantified and dynamic behavior predicted through mathematical models, thereby revolutionizing the current clinical practice. We investigated the influence of model parameters of a selected mathematical model utilizing ordinary differential equations describing the HPT-axis. Motivated by a graphical depiction of the varying influence of the model parameters, feasible methods such as a local sensitivity analysis are conducted. Furthermore, to account for the influence of parameters on the output variance of the considered model, the theory of Sobol’ indices is utilized. Although the system of differential equations describing the hormone concentrations of thyroid-simulating hormones and unbound Thyroxine has similar equation structures, the results of the sensitivity analyses varied according to the equation.

6469 Supplement Misadventures: A Case Of Acute Heart Failure, Cardiogenic Shock, And Hormonal Dysregulation Secondary To Surreptitious Use Of Multiple Hormonal Supplements

Abstract Disclosure: K.N. Grennan: None. S. Thota-Kammili: None. A.L. McKenna: None. C.G. Coyle: None. S.L. Samson: None. Introduction: Supplement misuse in the bodybuilding community is prevalent. With the availability of internet ordering and purchasing, patients have access to hormonal supplements without prescription or regulation. Here we present the case of a patient on self-administered hormonal supplements who presented in acute heart failure leading to cardiogenic shock in the setting of concurrent thyroid, adrenal, and gonadal axis dysfunction. Case Description: A 28-year-old male with no significant medical history was transferred to our hospital after presenting to an outside emergency room with dyspnea, cough, nausea, and a subjective fever. He developed acute hypoxic respiratory failure requiring intubation. Echocardiogram performed showed an ejection fraction (EF) of 10%. He was started on two vasopressors and methylprednisolone 1 g daily for two days, due to concern for myocarditis versus giant cell arteritis. Hormonal work-up showed TSH 0.02 mIU/L (normal range 0.3-4.2), free T4 0.4 ng/dL (0.9-1.7), total T3 48 ng/dL (80-200), FSH <0.3 IU/L (1.2-15.8), LH <0.2 IU/L (1.3-9.6), ACTH <5.0 pg/mL (7.2-63), cortisol 1.7 mcg/dL (2.5-12), estradiol 171 pg/mL (8.0-35), total testosterone 1730 ng/dL (240-950), and prolactin 47 ng/mL (4.0-15.2). He received 10 mg dexamethasone at the outside facility. A medication bag found by his family included online purchases of non-prescribed testosterone cypionate and enanthate, liothyronine, anastrozole, and clomiphene. None were medical grade. He was also taking the anabolic steroid clenbuterol for 3 days prior. Echocardiogram on day 3 of admission showed an improved EF of 36%. Cardiac magnetic resonance imaging (MRI) showed a papillary fibroelastoma and myocarditis. Patient was weaned off vasopressors and the ventilator. He was discharged on levothyroxine 50 mcg daily and hydrocortisone 10 mg twice daily for outpatient reassessment. Transesophageal echocardiogram confirmed diagnosis of papillary fibroelastoma. One month Endocrinology clinic follow-up showed no evidence of posterior pituitary, thyroid, or adrenal axis dysfunction or growth hormone excess, but he continued to have gonadal axis suppression with elevated prolactin and estradiol, the latter thought to be secondary to conversion from testosterone. Pituitary MRI showed no micro or macroadenoma. His EF recovered to 50%. He is pending surgical removal of the aortic valve fibroelastoma. Discussion: With hormonal supplements easily accessible online, it is important for physicians to counsel patients about the dangers of misuse. This case highlights a previously healthy 28-year-old man who presented in critical condition with cardiogenic shock and hypothalamic-pituitary axis dysfunction from supplements he purchased online. There should be targeted educational interventions regarding the harm of supplements aimed at the bodybuilding community to prevent similar cases. Presentation: 6/2/2024

8617 Gender Differences In The Course Of Giant Prolactinomas - Single-Centre Case Series

Abstract Disclosure: M.A. Komisarz-Calik: None. A. Boguslawska: None. K. Ciszek: None. G. Zieliński: None. A. Hubalewska-Dydejczyk: None. A. Gilis-Januszewska: None. Introduction: Giant prolactinomas are the specific subtype of lactotroph PitNET, and are classified, according to their maximum diameter (≥40 mm). They constitute about 3% of prolactinomas. The prevalence is more common in men, however, the differences in the course of the disease between the genders remain unclear. Aim: The purpose of our study was to analyse gender differences in the course of giant prolactinomas. Materials and Methods: We analysed the data of consecutive patients with giant prolactinomas treated in the tertiary clinical center in the years 2022-2023. Results: There were 12 patients with giant prolactinoma (10 men and 2 women).Men and women were of similar age (32 vs 36 years). The maximum dimensions of the pituitary tumour in men were 56x70x67 mm, in women 60x55x55 mm. In all cases, treatment included dopamine agonists (cabergoline in 11 patients (all male patients and one female patient) and bromocriptine in one woman. Combined treatment with temozolomide and pasireotide were implemented in two male patients. In three men (30%) a surgical treatment was performed due to the visual field disturbances and severe headaches. Multiple surgeries were performed in two patients due to recurrence of symptoms and tumour progression (surgery was performed twice, and three times). One male patient received radiotherapy.The most frequent symptoms were associated with insufficiency of the adrenal, thyroid, and gonadal axis (80% vs 50%), visual field deficits (50% vs 50%) and headache (80% vs 0%), respectively in men and women. In men, the most common symptom was hypofunction of the gonadal axis (8 cases - 4 isolated gonadal axis hypofunction and 4 cases - hypofunction of the adrenal, thyroid and gonadal axis). In one woman, hypofunction of the three pituitary axes was present. Serum prolactin was higher in men than in women (6576 - 284232 ulU/ml vs 2000 - 5659 ulU/ml). In total, after treatment, prolactin concentration decreased in 7 cases, 5 men (50%) and 2 women (100%). The decrease in prolactin levels in men was by 80,4-99,9%, while in women it was by 83,9-86,7%. Tumour shrinkage was observed in 7 cases - 6/10 men and 1/2 woman. In men, tumour size was reduced by 27,5-64,4%. Tumour progression was observed in three cases, in 1 case the dimensions were stable. In two cases due to a recent diagnosis, follow-up MRI has not been yet performed. In women, tumour reduction by 99,8% was observed; in second the size of the tumour remained stable. Conclusions: The prevalence of giant prolactinomas is higher in men. The most frequent symptoms in both genders are visual field disturbances. The prevalence of tumour shrinkage is similar in both sexes, however giant prolactinomas require surgery more often in men. Further multicenter projects are needed to study the course of giant prolactinomas and to improve the outcomes of care. Presentation: 6/3/2024

8412 Resolution of Central Hypothyroidism shortly after Transsphenoidal Surgery For Cushing’s Disease

Abstract Disclosure: L. Esper: None. A. Ibrahim: None. N. El Asmar: None. Background: Cushing's disease is a rare endocrine disorder characterized by excessive cortisol production, resulting in various metabolic disturbances. Hypercortisolism is known to cause central hypothyroidism. The mechanism is complex and involves hypercortisolism mediated decreased TRH and TSH secretion in addition to inhibition of peripheral deiodination. This case details the successful management and recovery of a patient with Cushing's disease and reversal of central hypothyroidism after pituitary surgery.Case:A 43-year-old man was evaluated for central hypogonadism, 20 pound weight gain with central weight distribution, and the development of purple abdominal striae for the past year. He had a normal thyroid exam and appeared euthyroid. He was alsodiagnosed with hypertension and prediabetes in the past yearrequiring medical therapy.A low dose dexamethasone suppression test (DST) resulted in AM cortisol of 12.9 mcg/dl. Two adequate 24hr Urinary cortisol measurements showed elevated cortisol excretion at 458 and 378mcg/24. Lab evaluation revealed elevated cortisol levels along with elevated adrenocorticotropic hormone (ACTH) levels(ACTH of 172 pg/ml with a cortisol level of 23.9 mcg/dl). A high dose DST demonstrated suppression of cortisol to 3.4 mcg/dl. MRI pituitary was performed which showed a clearright sided 7mm pituitary adenoma.Thyroid function tests performed were consistent with central hypothyroidism, with low levels of free thyroxine (FT4) at 0.67ng/dl along with an inappropriately low normal thyroidstimulating hormone (TSH) at 0.596 uIU/ml. Total T4 was low at 4 ug/dl in addition to a low total T3 of 66 ng/dl. Remaining labs revealed central hypogonadism along with slightly elevated prolactin of 16 ng/ml. He was not started on thyroid hormone.He then underwent transsphenoidal surgery for tumor removal. He developed post-operative adrenal insufficiency (cortisol 2.12 mcg/dl) 16 hours post-op after which he was started on hydrocortisone replacement, indicating remission. 12 hours post-op, his TSH was 0.656 uIU/ml with a free t4 of 0.79 ng/dl, both in the normal range. 36 hours post-op, TSH was 0.524 uIU/ml and free t4 was 1.15 ng/dl. Histopathological examination confirmed the diagnosis of an ACTH-secreting pituitary adenoma.At 4 weeks post-op, thyroid labs showed normal FT4 (1.07ng/dl) and TSH (2.06uIU/ml). Conclusion: Hypercortisolism causes a global inhibition of the thyroid axis, with decreased levels of TSH, T4, and T3 (1). Previous studies suggest the monitoring of thyroid function at 6 and 12 months after surgical cure of hypercortisolism. Our case suggests that the resolution of hypothyroidism occurs shortly after surgery for Cushing’s disease and the need for earlier monitoring. Presentation: 6/3/2024

Analysis of the correlation between Hashimoto's thyroiditis and food intolerance.

This study aims to explore the correlation between patients with Hashimoto's thyroiditis and food intolerance. A total of 172 subjects who visited Guangdong Provincial Hospital of Traditional Chinese Medicine between January 2020 and March 2023 were selected and tested for 90 food-specific IgG antibodies. The study group composed 85 individuals diagnosed with Hashimoto's thyroiditis, while the control group consisted of 87 healthy individuals. Data were analyzed to determine the correlation between Hashimoto's thyroiditis and food intolerance. Among the 85 patients with Hashimoto's thyroiditis, 97.65% exhibited food intolerance, with an average of 15.76 ± 10.61 types of food intolerances. The most common intolerances were to eggs (75.29%), bok choy (71.76%), and milk (65.88%), each exceeding a 60% intolerance rate. In the control group of 87 healthy individuals, the intolerance rate was 95.40%, with an average of 9.57 ± 8.90 types of food intolerances. The most prevalent intolerances in the control group were to bok choy (54.02%) and eggs (52.87%), each exceeding a 50% intolerance rate. The findings suggest that patients with Hashimoto's thyroiditis are more likely to develop food intolerance compared to the healthy population, which may indicate a correlation between Hashimoto's thyroiditis and food intolerance. Different dietary patterns may affect the activity of the thyroid axis and may even be the cause of autoimmune thyroid disease. The technique of detecting food intolerance IgG antibodies has the potential to be an important reference for dietary interventions in patients with Hashimoto's thyroiditis.

Regulatory Effects of 5-Day Oral and Intraperitoneal Administration of a Thienopyrimidine Derivative on the Thyroid Status in Rats.

In experiments on rats, we studied the effect of 5-day intraperitoneal (15 mg/kg/day) and oral (40 mg/kg/day) administration of compound TPY3m, a stimulator of the production of thyroid hormones by the thyroid gland developed by us, on the blood levels of thyroxine, triiodothyronine, and thyroid-stimulating hormone and on morphology of the thyroid gland. With both routes of administration, TPY3m caused a sustained moderate elevation of thyroid hormones, mainly thyroxine, with little effect on the level of thyroid-stimulating hormone. TPY3m did not reduce the stimulating effect of thyroliberin on the levels of thyroid hormones and had no damaging effect on the thyroid gland. During long-term administration, compound TPY3m stimulates the production of thyroid hormones without weakening the activity of the thyroid axis. Thus, TPY3m is a prototype of drugs for correcting thyroid hormone deficiency.

Testing the sensitivity of the medaka Transgenic Eleuthero-embryonic THYroid-Specific assay (TETHYS) to different mechanisms of action

There are many concerns about the impacts of Endocrine-Disrupting Chemicals on both wildlife and human populations. A plethora of chemicals have been shown to interfere with the Hypothalamic–Pituitary–Thyroid (HPT) axis in vertebrates. Disruption of the HPT axis is one of main endocrine criteria considered for the regulation of chemicals, along with the estrogen axis, androgen axis and steroidogenesis (EATS). In response to these concerns, the Organization for Economic Cooperation and Development (OECD) initiated the validation of test guidelines (TGs) covering the EATS modalities. Regarding thyroid activity and/or disruption assessment, three OECD TGs are validated, all of them using amphibians. To date, no OECD TGs based on fish are available for the detection of Thyroid Active Chemicals (TACs). To fill this gap, we developed a new test for the detection of TACs, the TETHYS assay (Transgenic Eleuthero-embryonic THYroid-Specific assay). This assay uses a medaka (Oryzias latipes) transgenic line Tg(tg:eGFP) expressing Green Fluorescent Protein in the thyroid follicles, under the control of the thyroglobulin promoter. This assay is performed at eleuthero-embryonic life-stages with an exposure length of 72 h. In the present study, the following reference chemicals with known thyroid hormone system mechanism of action have been tested: methimazole, sodium perchlorate, sodium tetrafluoroborate, diclofenac, iopanoic acid, sobetirome, NH-3 and 1–850. Except for the thyroid receptor antagonists, all chemicals tested were identified as thyroid active, modifying the total fluorescence and the size of the thyroid follicles. To investigate the test specificity, we tested three chemicals presumed to be inert on the HPT axis: cefuroxime, abamectin and 17α-ethinylestradiol. All were found to be inactive in the TETHYS assay. This promising New Approach Methodology can serve as a foundation for the development of a new OECD TG in the frame of regulatory assessment of chemicals for thyroid activity.

Low Levels of Cortisol are Associated with HIV Infection in Older People: A Hormonal Substudy in the OVER50 Cohort.

People with the human immunodeficiency virus (PWH) who were diagnosed long ago are more prone to age-related conditions and comorbidities than the general population. We hypothesized that older PWH have endocrine abnormalities that may influence the patient's health status. Mean hormonal values across the thyrotropic, somatotropic, corticotropic, and gonadal axis, and percentage of subjects with abnormal values, were compared between PWH aged ≥50 years (n=30) and people without HIV (n=30) (Over50 cohort). Clinical factors were also analyzed as independent variables. PWH had a higher prevalence of comorbidities (36.67% PWH and 20.69% controls had ≥3 comorbidities). Male PWH exhibited lower estradiol levels than male controls (29.75±7.68 pg/mL vs. 35.45 ± 10.04 pg/mL; p = 0.0041). Abnormal concentrations of testosterone were found in 35% of male PWH compared to 55% of male controls (mostly above reference values). Cortisol levels were significantly lower among PWH (9.97 ± 4.33 μg/dL vs. 13.56 ± 3.39 μg/dL; p = 0.002); 16.6% of PWH exhibited abnormally low levels (<5 μg/dL), compared to 0% of controls, and 3 PWH met criteria for a definitive diagnosis of adrenal insufficiency (<3.6 μg/dL). For the somatotropic axis, growth hormone (GH) levels were significantly lower in male PWH than in controls (p = 0.0394). No significant differences were found in relation to the thyroid axis. Hormones are generally similar between the chronic PWH who are receiving ART treatment and the general control population, except for cortisol in both sexes and testosterone and estradiol in men. Some special attention should be given to cortisol in PWH due to a presumably higher risk of adrenal complications.

Correction: The Effects of Triiodothyronine on the Free Thyroxine Set Point Position in the Hypothalamus Pituitary Thyroid Axis

Correction: The Effects of Triiodothyronine on the Free Thyroxine Set Point Position in the Hypothalamus Pituitary Thyroid Axis

The Effects of Triiodothyronine on the Free Thyroxine Set Point Position in the Hypothalamus Pituitary Thyroid Axis.

In clinical endocrinology, it is often assumed that the results of thyroid hormone function tests (TFTs) before total thyroidectomy are considered euthyroid when the circulating concentrations of thyrotropin [TSH] and free thyroxine [FT4] are within the normal reference ranges. Postoperative thyroid replacement therapy with levothyroxine. The aim of L-T4 is to reproduce the preoperative euthyroid condition. Currently, intra-individual changes in the euthyroid set point before and after total thyroidectomy are only partly understood. After total thyroidectomy, a greater postoperative [FT4] than preoperative [FT4] for equivalent euthyroid [TSH] was found, with differences ranging from 3 to 8 pmol/L. This unexplained difference can be explained by the use of a mathematical model of the hypothalamus-pituitary-thyroid (HPT) axis set point theory. In this article, the postoperative HPT euthyroid set point was calculated using a dataset of total thyroidectomized patients with at least three distinguishable postoperative TFTs. The postoperative [TSH] set point was used as a homeostatic reference for the comparison of preoperative TFTs. The preoperative [FT4] value was equal to the postoperative [FT4] value in 50% of the patients, divided by a factor of ~ 1.25 (within +/- 10%). The factor of 1.25 stems from the lack of postoperative use of thyroidal triiodothyronine (T3). Furthermore, approximately 25% of the patients presented a greater preoperative [FT4] difference than postoperative [FT4]/1.25 combined with a normal [TSH] difference. Based on these observations, the effect of T3 on the value of the [FT4] set point was analyzed and explained from a control theory perspective.

Perinatal exposure to Aroclor 1254 disrupts thyrotropin-releasing hormone mRNA expression in the paraventricular nucleus of male and female rats

Polychlorinated biphenyls (PCBs) are industrial pollutants that act as endocrine disruptors and alter thyroid function. However, it is still unclear whether PCBs can affect hypothalamic thyrotropin releasing hormone (Trh) mRNA expression through TH signaling disruption. As salt-loading dehydration induces tertiary hypothyroidism in the hypothalamic parvocellular paraventricular nuclei (paPVN), and perinatal exposure to Aroclor 1254 (A1254) disrupts the hydric balance in rats, we hypothesized that TRH synthesis could be altered during dehydration in TRH neurons that control the hypothalamic–pituitary–thyroid (HPT) axis activity in rats perinatally exposed to A1254. We examined Trh mRNA expression in the paPVN and the response to salt-loading dehydration (hyperosmotic (hyper) stress) in the progeny of Wistar pregnant rats receiving 0 mg/kg BW (control) or 30 mg/kg BW A1254 daily from gestational days 10–19. Three-month-old offspring were subjected to normosmotic or hyper conditions and Trh mRNA, glucocorticoid receptor (GR) mRNA expression were measured in the PVN by RT-PCR. TRH mRNA and TRH+ neurons were measured in the paPVN by fluorescent in situ hybridization (FISH). As expected, Trh mRNA levels were decreased in the paPVN of male and female rats in the hyper group. Basal Trh mRNA expression and serum TSH were decreased in male rats in the A1254 group. Notably, Trh mRNA levels were further decreased in the paPVN of male and female A1254 + hyper rats, in which the GR mRNA expression was significantly decreased. These results support the hypothesis that perinatal exposure to A1254 results in inadequate adaptive response of the HPT axis in adulthood and contributes to dysregulation of the HPT axis response to salt-loading dehydration.

Perinatal exposure to tbbpa interferes with the establishment of the thyroid axis at young age and the ability to cope with metabolic challenges in adulthood

Perinatal exposure to tbbpa interferes with the establishment of the thyroid axis at young age and the ability to cope with metabolic challenges in adulthood

Anterior Pituitary Dysfunction After Traumatic Brain Injury: A Prospective Study

Anterior pituitary dysfunction is one of the major causes of disability and morbidity in patients suffering from traumatic brain injury (TBI). The present study was undertaken to evaluate the incidence of anterior pituitary dysfunction in cases of moderate and severe TBI, its value in long-term prognostication, and the factors that predispose to a higher incidence of anterior pituitary dysfunction in acute and chronic phases. This was a prospective cohort study wherein 216 patients with moderate and severe TBI were evaluated within 72 hours of TBI (acute phase) and at 6 months (chronic phase). At 6 months, out of the 216 patients, 95 patients had expired and 35 patients were lost to follow-up. The remaining 86 patients were evaluated at 6 months. In the acute phase, hypopituitarism was seen in 82.4% patients, thyroid axis deficiency was seen in 57.4% patients, gonadal axis deficiency in 54.2% patients, and adrenal axis deficiency in 13.8% patients. In the chronic phase, hypopituitarism was seen in 59.3% patients, thyroid axis deficiency was seen in 24.4% patients, gonadal axis deficiency in 32.6% patients, and adrenal axis deficiency in 23.3% patients. Patients with thyroid axis deficiency at admission had significant association with a bad modified Rankin Scale score at 6 months. Thyroid and gonadotropin axes were most commonly affected and deficiency of at least 1 axis was found in 82.4% patients in the acute phase and 59.3% in the chronic phase. Thyroid axis deficiency had a negative impact on prognosis in post-TBI patients.

The time course of lactate and endocrine changes in dogs suffering from dog bite wounds.

The stress response after acute trauma in humans and animals has been well-recognised in the literature. However, data on temporal changes in endocrine parameters after acute trauma in previously healthy dogs are scant. To longitudinally track endocrine variables and lactate concentrations in dogs with canine bite wounds. Prospective study involving 20 dogs hospitalised after being bitten by another dog. Serum cortisol, thyroxine (total T4), thyrotropin (TSH), and lactate concentrations were measured on admission and every 8 hours after the recorded bite incident, for a 72-hour period. Median cortisol concentration was markedly elevated on admission (314.6 nmol/L; IQR 229.3-369.6) but returned to within the reference interval by 16 hours post-bite (99.5 nmol/L; IQR 48.7-225.4) and reached a nadir at 48 hours post-bite (38.5 nmol/L; IQR 32.1-115.9). Median total T4 concentration was within the reference interval on admission (20.6 nmol/L; IQR 12.7-27.9) but decreased below the reference interval by 8 hours (11.0 nmol/L; IQR 5.0-14.1) and reached a nadir 16 hours postbite (7.0 nmol/L; IQR 2.9-19.7), before gradually increasing after 64 hours to reach the reference range by 72 hours. The median TSH concentrations remained within the reference interval throughout the study period. Median lactate concentration was mildly elevated on admission (3.0 mmol/L; IQR 2.0-3.9). This study produced novel data on the temporal relationships of the hypothalamic-pituitary-adrenal and hypothalamicpituitary- thyroidal axes alterations after an acute traumatic insult in dogs.

Sex-differential testosterone response to long-term weight loss

ObjectivesObesity-associated gonadal dysfunction is a common comorbidity in patients seeking weight loss interventions. We examined the incremental effect of weight loss on gonadal axes in men and women over 3 years. Changes in sex hormones were compared between dietary intervention (Diet) and bariatric procedures: Roux-en-Y gastric bypass (RYGB), sleeve gastrectomy (SG) and laparoscopic adjustable gastric banding (LAGB). Additional analysis assessed changes in corticotropic, somatotropic and thyroid axes after weight loss interventions.MethodsThis prospective, observational study included 61 adults with Body Mass Index >30 kg/m2, mean age 51 (SD = 11) years. Endocrine parameters were measured at baseline and at 6 timepoints over 36-months.ResultsFor each 1 kg of weight lost, between baseline and 36 months, total testosterone increased by 0.6% (95% CI: 0.2%, 1.0%, p = 0.002) in males and decreased by 0.8% (95% CI: −1.4%, −0.3%, p = 0.003) in females. These changes remained statistically significant when controlled for age and for menopausal status in females. At 36 months, in comparison with Diet, RYGB women had lower total testosterone by 54% (95% CI: −90%, −17%, p = 0.004), reduced free androgen index (FAI) by 65% (95% CI; −114%, −17%, p = 0.009) while SG had reduced FAI by 39% (95% CI; −77%, 0%, p = 0.05). No such differences between groups were noted for male subjects. Adrenocorticotropic hormone declined by 0.3% (95% CI: 0.0, −0.5%, p = 0.05), insulin-like growth factor-1 increased by 0.4% (95% CI; 0.2%, 0.7%, p = 0.005), without such thyrotrophin change for each 1 kg of weight loss, for entire cohort, over 36 months.ConclusionsThe testosterone changes observed in this study were proportional to the amount of weight loss. In females, reduction in androgens was independent of age and menopausal status and more pronounced after bariatric procedures. This study finding warrants further clinical research to explore an impact of androgen reduction on functional and cognitive status in postmenopausal women. The observed changes in pituitary hormones may contribute to the metabolic benefits of bariatric surgery.

Combined effect and mechanism of microplastic with different particle sizes and levofloxacin on developing Rana nigromaculata: Insights from thyroid axis regulation and immune system

Microplastics (MPs) usually appear in the aquatic environment as complex pollutants with other environmental pollutants, such as levofloxacin (LVFX). After 45-day exposure to LVFX and MPs with different particle sizes at environmental levels, we measured the weight, snout-to-vent length (SVL), and development stages of Rana nigromaculata. Furthermore, we analyzed proteins and genes related to immune system and thyroid axis regulation, intestinal histological, and bioaccumulation of LVFX and MPs in the intestine and brain to further explore the toxic mechanism of co-exposure. We found MPs exacerbated the effect of LVFX on growth and development, and the order of inhibitory effects is as follows: LVFX-MP3>LVFX-MP1>LVFX-MP2. 0.1 and 1 μm MP could penetrate the blood–brain barrier, interact with LVFX in the brain, and affect growth and development by regulating thyroid axis. Besides, LVFX with MPs caused severer interference on thyroid axis compared with LVFX alone. However, 10 μm MP was prone to accumulating in the intestine, causing severe histopathological changes, interfering with the intestinal immune system and influencing growth and development through immune enzyme activity. Thus, we concluded that MPs could regulate the thyroid axis by interfering with the intestinal immune system.

Prevalence and Clinical Course of Water and Electrolyte Disturbances Following Transsphenoidal Pituitary Adenoma Surgery in Immediate and Early Postoperative Period: A Prospective Observational Study.

Transsphenoidal pituitary adenoma surgery (TSS) was commonly associated with water and electrolyte disturbances (WEDs) in the postoperative period, which could lead to prolonged hospital stay, readmission and is rarely life threatening. The present study aimed to investigate the prevalence and predictive factors of WEDs following TSS. Fifty-eight patients with pituitary adenoma were prospectively studied for the occurrence of WEDs. Patients were checked at 6 weeks postoperatively for persistence of diabetes insipidus and new-onset hormone deficiencies or recovery. Multivariate regression was applied to determine predictive factors for the occurrence of WEDs. A total of 58 patients underwent TSS (median age: 43 years, 66% male). In the immediate postoperative period, 16 (27.6%) had transient diabetes insipidus (DI), two (3%) had transient DI followed by syndrome of inappropriate antidiuretic hormone (SIADH), five (8.6%) had isolated SIADH, five (8.6%) had persistent DI and only one patient had a triple-phase response. At 6 weeks, five (11%) patients continued to have persistent DI. In multivariate analysis, apoplexy and duration of surgery were predictive of DI occurrence. Recovery rate at 6 weeks was 11.1%, 13% and 9.3% for cortisol, thyroid and gonad axis, respectively. New-onset hormone deficiencies at 6 weeks were 5.6%, 5.6% and 7.4% for cortisol, thyroid and gonad axis, respectively. WEDs remain an important concern post-TSS. Timely follow-up should always be integral part of postoperative care for early diagnosis of new hormone deficiencies and avoiding unnecessary treatment in those with recovered axis.

High Frequency of Cystic Fibrosis-Related Endocrinopathies in a Population of Colombian Children: A Cross-Sectional Study

Objective: The median length of survival for cystic fibrosis (CF) has significantly increased in recent years; however, this means that endocrine complications are more frequently observed in affected patients. This research was aimed at evaluating the frequency, clinical and paraclinical features, and the treatment of linear growth and pubertal disturbances, vitamin D insufficiency/deficiency, CF-related bone disease, and adrenal and thyroid function disturbances in patients with CF, as well as to explore their association with lung function and colonization. Method: A cross-sectional study with a retrospective collection of information from patients under 18 years of age with a confirmed diagnosis of CF, evaluated on an outpatient or in-hospital basis by a pediatric pulmonologist or endocrinologist, or in a multidisciplinary CF consultation, between January 2011–December 2020. Results: A total of 87 patients were included. A high frequency of endocrinopathies was found. Vitamin D insufficiency/deficiency was persistent despite cholecalciferol supplementation in 72%, short stature in 38%, pubertal delay in 26%, and thyroid axis disorders in 8% of cases. Bone disease involving densitometry and adrenal insufficiency secondary to chronic corticosteroid use were also frequent among the screened subjects (44% [n=16] and 12% [n=51], respectively). No significant differences were found for pulmonary function or bacterial lung colonization in the context of any endocrinopathies. Conclusion: Endocrine comorbidities are frequent in patients with CF, and early recognition improves the prognosis and quality of life in these patients. The findings for this cohort ratify the importance of multidisciplinary management of patients with CF.