Rare cause of recurrent hypocalcaemia and functional hypoparathyroidism due to hypomagnesaemia caused by TRPM6 gene mutation.

Magnesium is essential for the functioning and release of parathyroid hormone. Therefore, its deficiency can present as functional hypoparathyroidism. This case report describes a rare inherited disorder called congenital hypomagnesaemia with secondary hypocalcaemia due to TRPM6 gene mutation. This disease clinically and biochemically mimics hypoparathyroidism. However, unlike hypoparathyroidism, it can be treated only by long-term oral magnesium supplements. The patient presented to us with recurrent hypocalcaemic convulsions. The laboratory picture in each admission was similar to that of hypoparathyroidism. However, the hypocalcaemia persisted, and it was noticed to be associated with persistent hypomagnesaemia. A defect in the tubular magnesium reabsorption was postulated and a genetic analysis of the patient was done, which revealed a TRPM6 mutation causing hypomagnesaemia by excessive renal excretion of magnesium. The child responded well to oral magnesium supplements and is currently developmentally appropriate for her age and thriving well.

Oxytocin Modulation in Mindfulness-Based Pain Management for Chronic Pain.

In the context of chronic pain management, opioid-based treatments have been heavily relied upon, raising concerns related to addiction and misuse. Non-pharmacological approaches, such as Mindfulness-Based Pain Management, offer alternative strategies. We conducted a mechanistic clinical study to investigate the impact of an 8-week Mindfulness-Based Pain Management intervention on chronic pain, the modulation of inflammatory markers, stress physiology, and oxytocin, and their interplay with clinical pain symptoms and perception, in comparison to a patient wait-list active control. A total of 65 participants, including 50 chronic pain patients and 15 healthy controls, underwent salivary assays to assess endocrine markers, oxytocin, interleukin (IL)-1b, IL-6, IL-8, tumor necrosis factor (TNF)-a, and dehydroepiandrosterone sulphate (DHEA-S). Psychological assessments were also conducted to evaluate aspects of pain perception, mindfulness, mood, and well-being. Findings revealed significant differences between chronic pain patients and healthy controls in various clinical metrics, highlighting the psychological distress experienced by patients. Following Mindfulness-Based Pain Management, oxytocin levels significantly increased in chronic pain patients, that was not observed in the patient wait-list control group. In contrast, cytokine and DHEA-S levels decreased (not to statistically significant margins) supporting anti-inflammatory effects of Mindfulness-Based Pain Management. The fact DHEA-S levels, a marker of stress, did attenuate but not to statistically meaningful levels, suggests that pain reduction was not solely related to stress reduction, and that oxytocin pathways may be more salient than previously considered. Psychological assessments demonstrated substantial improvements in pain perception and mood in the intervention group. These results contribute to the growing body of evidence regarding the effectiveness of mindfulness-based interventions in chronic pain management and underscore oxytocin's potential role as a therapeutic target.

Autoimmune demyelination alters hypothalamic transcriptome and endocrine function.

The hypothalamus is a brain structure that is deputed to maintain organism homeostasis by regulating autonomic function and hormonal production as part of the neuroendocrine system. Dysfunction in hypothalamic activity results in behavioral alterations, depression, metabolic syndromes, fatigue, and infertility. Remarkably, many of these symptoms are associated with multiple sclerosis (MS), a chronic autoimmune disorder of the central nervous system (CNS) characterized by focal demyelination, immune cell infiltration into the brain parenchyma, and neurodegeneration. Furthermore, altered hormonal levels have been documented in MS patients, suggesting the putative involvement of hypothalamic deficits in MS clinical manifestations. Yet, a systematic analysis of hypothalamic function in response to neuroinflammatory stress is still lacking. To fill this gap, here we performed a longitudinal profiling of the hypothalamic transcriptome upon experimental autoimmune encephalomyelitis (EAE)-a murine disease model recapitulating key MS phenotypes at both histopathological and molecular levels. We show that changes in gene expression connected with an anti-inflammatory response start already at pre-onset and persist along EAE progression. Altered levels of hypothalamic neuropeptides were also detected, which possibly underlie homeostatic responses to stress and aberrant feeding behaviors. Last, a thorough investigation of the principal endocrine glands highlighted defects in the main steroidogenic pathways upon disease. Collectively, our findings corroborate the central role of hypothalamic dysfunction in CNS autoimmunity.

Gene expression and trace elements in Greenlandic ringed seals (Pusa hispida).

Marine top predators such as ringed seals biomagnify environmental contaminants; and with the increasing human activities in the Arctic, ringed seals are exposed to biologically significant concentrations of trace elements resulting in reproductive impairment, immunosuppression, and neurological damages. Little is known about the molecular effects of heavy metals on these vulnerable apex predators suffering from a rapidly changing Arctic with significant loss of sea-ice. In the present study, concentrations of cadmium (Cd), mercury (Hg) and selenium (Se) were measured in liver of sixteen Greenlandic ringed seals (nine adults and seven subadults) together with molecular biomarkers involved in bio-transformation, oxidative stress, endocrine disruption and immune activity in blood and blubber. The concentrations of trace elements increased in the following order: Hg > Se > Cd with levels of mercury and selenium being highest in adults. Aryl hydrocarbon receptor nuclear translocator (ARNT), peroxisome proliferator activated receptor alpha (PPARα, estrogen receptor alpha (ESR1), thyroid hormone receptor alpha (TRα) and interleukin - 2 (IL-2) mRNA transcript levels were highest in blubber, while heat shock protein 70 (HSP70) and interleukin - 10 (IL-10) were significantly higher in blood. There were no significant correlations between the concentrations of trace elements and mRNA transcript levels suggesting that stressors other than the trace elements investigated are responsible for the changes in gene expression levels. Since Hg seems to increase in Greenlandic ringed seals, there is a need to re-enforce health monitoring of this ringed seal population.

Can Ashwagandha Benefit the Endocrine System?-A Review.

Withania somnifera, also known as Ashwagandha, has been used in traditional medicine for thousands of years. Due to the wide range of its activities, there has been interest in its possible beneficial effects on the human body. It is proved that, among others, Ashwagandha has anti-stress, anti-inflammatory, antimicrobial, anti-cancer, anti-diabetic, anti-obesity, cardioprotective, and hypolipidemic properties. Particularly interesting are its properties reported in the field of psychiatry and neurology: in Alzheimer's disease, Parkinson's disease, multiple sclerosis, depression, bipolar disorder, insomnia, anxiety disorders and many others. The aim of this review is to find and summarize the effect that Ashwagandha root extract has on the endocrine system and hormones. The multitude of active substances and the wide hormonal problems faced by modern society sparked our interest in the topic of Ashwagandha's impact on this system. In this work, we also attempted to draw conclusions as to whether W. somnifera can help normalize the functions of the human endocrine system in the future. The search mainly included research published in the years 2010-2023. The results of the research show that Ashwagandha can have a positive effect on the functioning of the endocrine system, including improving the secretory function of the thyroid gland, normalizing adrenal activity, and multidirectional improvement on functioning of the reproductive system. The main mechanism of action in the latter appears to be based on the hypothalamus-pituitary-adrenal (HPA) axis, as a decrease in cortisol levels and an increase in hormones such as luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in men were found, which results in stress level reduction and improvement in fertility. In turn, other studies prove that active substances from W. somnifera, acting on the body, cause an increase in the secretion of triiodothyronine (T3) and thyroxine (T4) by the thyroid gland and a subsequent decrease in the level of thyroid-stimulating hormone (TSH) in accordance with the hypothalamus-pituitary-thyroid (HPT) axis. In light of these findings, it is clear that Ashwagandha holds significant promise as a natural remedy for various health concerns, especially those related to the endocrine system. Future research may provide new insights into its mechanisms of action and expand its applications in both traditional and modern medicine. The safety and toxicity of Ashwagandha also remain important issues, which may affect its potential use in specific patient groups.

Rare cause of persistent hypocalcaemia in infancy due to PTH gene mutation.

Hypocalcaemia is a frequently encountered electrolyte abnormality in neonates and it is mostly transient. However, persistent hypocalcaemia can point towards an endocrine abnormality like hypoparathyroidism, which is usually due to genetic disorders like DiGeorge and Kearns Sayre syndrome or due to mutations of genes like GCM2, CaSR and PTH.Our patient was a female child, who presented with hypocalcaemic convulsions in the neonatal period. On laboratory assessment, serum phosphate levels were noted to be high along with inappropriately low parathyroid hormone (PTH) levels. The child was diagnosed to have hypoparathyroidism and was started on oral calcium and 1,25-dihydroxycholecalciferol supplements to which she responded well. However, the child was lost to follow-up and was readmitted with hypocalcaemic convulsions in infancy. Clinical exome analysis done was diagnostic of homozygous PTH gene mutation. This case demonstrates a rare form of congenital isolated hypoparathyroidism with no other syndromic associations.

Calcifediol in the management of vitamin D deficiency-related skeletal and extraskeletal diseases: overview and clinical cases.

As well as being essential for musculoskeletal health, vitamin D is involved in numerous other physiological processes. Poor vitamin D status is linked to a wide range of diseases, including cardiovascular disease, autoimmune conditions, pulmonary disorders and upper respiratory tract infections. While optimal target concentrations of serum 25-hydroxyvitamin D (25(OH)D) for health maintenance or therapeutic purposes are still the subject of debate, there is reasonable agreement that serum 25(OH)D levels <50 nmol/L (20 ng/mL) constitute vitamin D deficiency and that severe deficiency states (serum 25(OH)D levels <25-30 nmol/L ≈ 10-12 ng/mL) should be avoided. Main strategies to maintain or improve vitamin D status are food supplementation and therapeutic use of medicinal forms of vitamin D. In this review, we examine evidence that implicates vitamin D deficiency in diverse conditions in the clinical settings of endocrinology, rheumatology, pneumology and reproductive health. Cholecalciferol (vitamin D3) is the most frequently used vitamin D supplement worldwide, though calcifediol (25-hydroxyvitamin D3) has recently become more widely available. Calcifediol is one step closer than cholecalciferol in the metabolic pathway to biologically active vitamin D. Pharmacokinetic differences between these vitamin D metabolites confer putative advantages for calcifediol in certain clinical situations. The clinical use of calcifediol is explored more closely through case studies, which illustrate its adjunctive role in the treatment of several vitamin D deficiency-related skeletal and extraskeletal diseases.

Metabolic bone disease heralding the diagnosis of Wilson's disease.

We report a short-statured, young man in his 20s presenting with bilateral cataract, recurrent kidney stones, history of refractory rickets and bone deformity. He had been consuming calcium and vitamin D supplements and had been operated for cataract and renal stone disease, prior to reporting in our clinic without any significant laboratory or clinical improvement. The patient was diagnosed as having Fanconi's syndrome attributable to Wilson's disease. This patient highlights that in case of resistant rickets, a high index of suspicion must be invoked for Wilson's disease. Timely recognition of this entity results in prompt ministrations and prevention of disability.

A review of neuroendocrine immune system abnormalities in IBS based on the brain-gut axis and research progress of acupuncture intervention.

Irritable bowel syndrome (IBS) is a common digestive disorder observed in clinics. Current studies suggest that the pathogenesis of the disease is closely related to abnormal brain-gut interactions, hypokinesia, visceral sensory hypersensitivity in the gastrointestinal tract, and alterations in the intestinal microenvironment. However, it is difficult for a single factor to explain the heterogeneity of symptoms. The Rome IV criteria emphasized the holistic biologic-psycho-social model of IBS, suggesting that symptoms of the disease are closely related to neurogastroenterology and various abnormalities in brain-gut interaction. This study comprehensively reviewed the relationship between the brain-gut axis and IBS, the structure of the brain-gut axis, and the relationship between the brain-gut axis and intestinal microenvironment, and discussed the relationship between the abnormal regulation of the nervous system, endocrine system, and immune system and the incidence of IBS on the basis of brain-gut axis. In terms of treatment, acupuncture therapy can regulate the neuroendocrine-immune system of the body and improve the intestinal microenvironment, and it has the advantages of safety, economy, and effectiveness. We study the pathogenesis of IBS from local to global and micro to macro, and review the use of acupuncture to treat the disease as a whole so as to provide new ideas for the treatment of the disease.

Treatment of Osteoporosis via Regulation of Endocrine System by Traditional Chinese Medicine： A Review / 中国实验方剂学杂志

In recent years， with the changes of population structure and the aggravation of aging， the prevalence of osteoporosis is increasing year by year. Osteoporosis poses great impacts on the body and family life of the patients and increases the burden on the society. Therefore， the research on osteoporosis is urgent and significant. The imbalance between osteoblasts， osteocytes， and osteoclasts causes abnormal bone metabolism， which destroys the fine structure of bone and increases bone fragility， thus increasing the risk of fracture. Although the pathogenesis of osteoporosis is complex， researchers have confirmed that the imbalance of the endocrine system directly or indirectly promotes the occurrence and development of osteoporosis. Traditional Chinese medicine （TCM） is a treasure of Chinese traditional culture and plays a key role in safeguarding the public health. With unique therapeutic effects and advantages， TCM has been widely accepted. Chinese medicines， moxibustion， acupuncture and other TCM therapies have play a unique role in the treatment of osteoporosis. Particularly， TCM prevention and treatment of osteoporosis by regulating the endocrine system has received extensive attention. By reviewing relevant literature， this paper introduces the research progress in the TCM modulation of bone metabolism and alleviation of bone loss by regulating estrogen， calcitonin， and parathyroid hormone in the endocrine system and affecting the hypothalamus capable of regulating these hormones， aiming to provide ideas for the TCM treatment of osteoporosis.

Papillary thyroid carcinoma in struma ovarii: management after surgery.

A woman in her 40s presented with a 3-month history of lower abdominal pain and intermenstrual bleeding. Ultrasound of the pelvis disclosed a 4 cm left adnexal mass. An MRI of the pelvis revealed a 2.2×3.6×2.4 cm solid, enhancing left ovarian mass. Due to high suspicion for malignancy, she underwent laparoscopic left salpingo-oophorectomy and resection of the tumour. Histopathology revealed papillary thyroid carcinoma in the background of struma ovarii as confirmed by thyroglobulin and thyroid transcription factor-1 positivity on immunohistochemistry. BRAF mutation analysis was negative. An ultrasound of the thyroid gland showed two low-risk nodules. An iodine-123 whole-body scan showed normal uptake in the thyroid gland. Thyroid-stimulating hormone (TSH) was 1.070 mcIU/mL (0.450-4.500), and thyroglobulin was 6.8 ng/mL (1.5-38.5). We risk-stratified this patient as low risk for recurrence. Risk stratification of malignant struma ovarii is essential to determine suitable thyroid targeting adjuvant therapy and reduce the risk of recurrence.

Rapidly Increasing Serum 25(OH)D Boosts the Immune System, against Infections-Sepsis and COVID-19.

Vitamin D deficiency is a global public health problem, a pandemic that commonly affects the elderly and those with comorbidities such as obesity, diabetes, hypertension, respiratory disorders, recurrent infections, immune deficiency, and malignancies, as well as ethnic minorities living in temperate countries. The same groups were worst affected by COVID-19. Since vitamin D deficiency weakens the immune system, it increases the risk of infections, complications, and deaths, such as from sepsis and COVID-19. Deficiency can be remedied cost-effectively through targeted food fortification, supplementation, and/or daily safe sun exposure. Its endocrine functions are limited to mineral metabolism, musculoskeletal systems, specific cell membrane interactions, and parathyroid gland functions. Except for the rapid, endocrine, and cell membrane-based non-genomic functions, all other biological and physiological activities of vitamin D depend on the adequate intracellular synthesis of 1,25(OH)2D (calcitriol) in peripheral target cells via the genome. Calcitriol mediates autocrine (intracrine) and paracrine signalling in immune cells, which provides broader, protective immune functions crucial to overcoming infections. The synthesis of 1,25(OH)2D (calcitriol) in peripheral target cells is dependent on diffusion and endocytosis of D3 and 25(OH)D from the circulation into them, which requires maintenance of serum 25(OH)D concentration above 50 ng/mL. Therefore, in acute infections such as sepsis and respiratory infections like COVID-19, it is necessary to rapidly provide its precursors, D3 and 25(OH)D, through the circulation to generate adequate intracellular calcitriol. Immune defence is one of the crucial non-hormonal functions of vitamin D. A single oral (bolus) dose or divided upfront loading doses between 100,000 and 500,000 IU, using 50,000 IU vitamin D3 increase the serum 25(OH)D concentrations to a therapeutic level of above 50 ng/mL that lasts between two to three months. This takes three to five days to raise serum 25(OH)D. In contrast, a single oral dose of calcifediol (0.014 mg/kg body weight) can generate the needed 25(OH)D concentration within four hours. Considering both D3 and 25(OH)D enter immune cells for generating calcitriol, using the combination of D3 (medium-term) and calcifediol (immediate) is cost-effective and leads to the best clinical outcome. To maximise protection against infections, particularly to reduce COVID-19-associated complications and deaths, healthcare workers should advise patients on safe sun exposure, adequate vitamin D supplementation and balanced diets containing zinc, magnesium, and other micronutrients to support the immune system. Meanwhile, governments, the World Health Organisation, the Centers for Disease Control, and governments should consider similar recommendations to physicians and the public, change the outdated vitamin D and other micronutrient recommendations directed to their population, and organise targetted food fortification programs for the vulnerable groups. This article discusses a rational approach to maintaining a sustained serum 25(OH)D concentration above 50 ng/mL, necessary to attain a robust immune system for overcoming infections. Such would cost-effectively improve the population's health and reduce healthcare costs. It also describes three cost-effective, straightforward protocols for achieving and sustaining therapeutic serum 25(OH)D concentrations above 50 ng/mL (>125 nmol/L) to keep the population healthy, reduce absenteeism, improve productivity, and lower healthcare costs.

The link between vitamin D status and NF-κB-associated renal dysfunction in experimental diabetes mellitus.

BACKGROUND: Type 1 diabetes (T1D) is accompanied by numerous side effects, including renal dysfunction. Mounting evidence suggests that overactivation of nuclear factor ĸB (NF-κB) is one of the key triggers of diabetes-associated chronic kidney disease. Vitamin D3 is considered as a strong modulator of a number of transcription factors, including NF-κB. The purpose of our study was to assess the contribution of NF-κB to type 1 diabetes (T1D)-induced kidney dysfunction and to determine if vitamin D3 supplementation can correct the changes associated with T1D. METHODS: The following animal groups were used: control, diabetic (induced by single i.p. injection of streptozocin at dose 55 mg/kg b.w.), T1D group treated with vitamin D3 (600 IU/kg b.w.), T1D group treated with NF-κB inhibitor - BAY 11-7082. RESULTS: Diabetes led to a decrease in serum 25(OH)D that was accompanied by down-regulation of vitamin D receptor (VDR) expression and up-regulation of hydroxylases CYP24A1 and CYP27B1 synthesis in the kidneys. Diabetes activated the transcription factor NF-κB and increased cleaved (p17) caspase-3 level in renal tissue. Restoration of vitamin D status normalized vitamin D-endocrine system, decreased NF-κB activation and caspase-3 protein level in the kidneys of diabetic animals. BAY 11-7082 partially mimicked the effects of vitamin D3. GENERAL SIGNIFICANCE: Vitamin D3 supplementation counteracts diabetes-induced kidney damage, most likely through VDR-mediated inhibition of NF-κB activation.

A mechanistic evaluation of the potential for octamethylcyclotetrasiloxane to produce effects via endocrine modes of action.

This review is a hypothesis driven, mechanistic evaluation of the potential for octamethylcyclotetrasiloxane (D4) to produce any effects via endocrine modes of action. D4 is a volatile, lipophilic liquid used in the production of high molecular weight dimethylsiloxane polymers. These are used in a variety of industrial, medical, cleaning, and personal care products, and they may contain low levels of residual D4. Low concentrations of D4 are found in the environment and there is potential for low level human exposure. All of the measured environmental and workplace levels of D4 fall below no observed effect levels (NOEL). Most of the effects of high dose D4 involve the female reproductive system. In the mature intact female rat following chronic high dose exposure, D4 may cause inhibition of mating and ovulation, decreased live litter sizes, small increases in the estrogen to progesterone ratio primarily through decreases in progesterone, and increases in uterine hyperplasia. When endogenous estrogens are very low, high dose D4 causes increases in some uterine parameters. To assess whether these high dose effects can be attributed to an endocrine mode of action, endpoints are ranked for relevance and strength, consistent with published concepts. When sufficient information is available the level of activity of D4 for producing the observed effect is compared with that of potent endocrines. The conclusions reached are that all of the effects of D4 fall well short of any established criteria for D4 to be capable of producing any adverse effect via an endocrine mode of action.

Ectopic ACTH secretion from a metastatic gastric carcinoma with neuroendocrine component.

An elderly gentleman was admitted to hospital with severe hypokalaemia of 1.75mmol/L. A background of a recently diagnosed metastatic gastric carcinoma with a neuroendocrine component pointed towards the diagnosis of ectopic ACTH secretion causing this dangerous electrolyte imbalance. He was treated with aggressive potassium supplementation and the adrenal steroid synthesis blocker metyrapone to acutely control his Cushing's syndrome. Chemotherapy consisting of carboplatin/etoposide combination was initiated but unfortunately the patients' health deteriorated, and he died three months after his initial diagnosis. This case highlights the accelerated presentation of hypercortisolism due to ectopic ACTH secretion. It discusses the classification of neuroendocrine tumours and their varied prognosis depending on the underlying tumour grade. It emphasises the importance of having a multidisciplinary team to be able to care for two underlying pathologies simultaneously: both the severe hypercortisolism and his metastatic gastric tumour.

Muscle, endocrine, and immunological markers of frailty in older people.

OBJECTIVE: To analyze muscle, endocrine, and immunological markers that influence frailty in older people assisted in primary care. MATERIALS AND METHODS: Cross-sectional, analytical, and probabilistic study were linked to the institutional research "Integrated Health Care for Older People." The study population consisted of males and females aged 60 years or more and assisted in primary health care. The research protocol included an interview and physical examination to evaluate the frailty criteria. Analysis of the following were done: serum calcium and creatinine as muscle markers; vitamin D, parathyroid hormone, and insulin-like growth factor - 1 as endocrine markers; and interleukin-6, C-reactive protein, leukocytes, and neutrophil-lymphocyte ratio as immunological markers. Statistical analysis included the Mann-Whitney test to compare means, and linear regression to analyze the relationship between dependent and independent variables. RESULTS: There was a relationship between creatinine and prediction of weight loss (p < 0.001), leukocytes and prediction of handgrip strength (p = 0.022), interleukin-6 and prediction of energy expenditure (p = 0.026), and vitamin D and prediction of gait time (p = 0.036). Also, sex influenced handgrip strength (p < 0.001), and age influenced handgrip strength (p < 0.001), gait time (p < 0.001) and energy expenditure (p < 0.001). CONCLUSION: The joint use of muscle, endocrine, and immunological markers may be useful to diagnose frailty and to propose resolutive interventions to reduce negative outcomes for older people.

Atypical presentation of autoimmune polyglandular syndrome type 1 in the fifth decade.

A 45-year-old woman presented to us with a short-term history of nausea, vomiting and giddiness. On arrival at our hospital, examination revealed postural hypotension. Fluid resuscitation with intravenous normal saline was commenced. She also had chronic mucocutaneous candidiasis and nail changes suggestive of ectodermal dystrophy. Detailed history taking revealed that she had never attained menarche. Serum biochemistries showed hyponatraemia, hyperkalaemia, and hypocalcaemia (sodium, 127 mEq/L; potassium, 6 mEq/L; and albumin-corrected calcium, 6 mg/dL). Adrenocorticotropic hormone-stimulated cortisol (16.7 mcg/dL) was suboptimal favouring adrenal insufficiency. She was started on hydrocortisone and fludrocortisone supplementation. Additionally, the parathyroid hormone was inappropriately low (3.8 pg/mL) confirming hypoparathyroidism. Oral calcium and active vitamin D supplementation were added. With the above clinical and biochemical picture, namely, clustering of primary amenorrhoea, adrenal insufficiency and hypoparathyroidism, the diagnosis pointed towards autoimmune polyglandular syndrome. Genetic workup revealed a deletion in exon 8 of the autoimmune regulator gene confirming the diagnosis of autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy/autoimmune polyglandular syndrome type 1 .

Reproductive and developmental toxicity screening study of an acetone extract of rosemary.

In 2017, JECFA requested reproductive and developmental toxicity studies to finalize an acceptable daily intake for solvent rosemary extracts. Thus, an OECD 421 reproductive/developmental toxicity study was conducted using an acetone rosemary extract that complied with JECFA and EFSA food additive specifications. Rosemary extract was provided to rats at dietary concentrations of 0 (control), 2100, 3600, or 5000 mg/kg, for 14 days before mating, during mating, and thereafter (throughout gestation and up to Lactation Day 13 for females) until necropsy. General toxicity (clinical signs, body weight, food consumption) and reproductive/developmental outcomes (fertility and mating performance, estrous cycles, anogenital distance, thyroid hormones, reproductive organ weights, thyroid histopathology) were assessed. There were no signs of general toxicity and no effects on reproduction; thus, the highest concentration tested (equivalent to mean daily intakes of 316 or 401 mg/kg bw/day [149 or 189 mg/kg bw/day carnosol and carnosic acid] for males and females, respectively) was established as the no-observed-adverse-effect level for general and reproductive toxicity. Dose-related reductions in T4 were observed for Day 13 pups (not seen on Day 4) but were not accompanied by thyroid weight changes or histopathological findings; further investigations are required to determine the biological relevance of these T4 reductions.

Malignant prolongation of the QTc interval due to severe vitamin D deficiency: an unusual presentation.

Long QT syndrome with Torsades de Pointes (TdP) is a life-threatening polymorphic ventricular arrhythmia. The corrected QT (QTc) prolongation >500 milliseconds (ms) has been associated with TdP. Hypocalcaemia due to severe vitamin D deficiency is an uncommon cause of acquired long QT. We hereby present a case of a 40-year-old woman with sensorineural deafness and having symptoms of palpitations and presyncope. She had a QTc interval of 556 ms (reference range, QTc 451-470 ms in adult healthy woman) on 24-hour Holter analysis. Genetic analysis for congenital long QT syndrome was negative. She was diagnosed with severe hypocalcaemia secondary to severe vitamin D deficiency. After treatment with intravenous calcium gluconate, followed by oral vitamin D and calcium supplementation, the QTc became normalised and no further episode of palpitations or presyncope occurred. The causes of vitamin D deficiency was due to inadequate exposure to sunlight and a strict vegan diet.