The skin-brain axis has been suggested to play a role in several pathophysiological conditions, including opioid addiction, Parkinson\'s disease and many others. Recent evidence suggests that pathways regulating skin pigmentation may directly and indirectly regulate behaviour. Conversely, CNS-driven neural and hormonal responses have been demonstrated to regulate pigmentation, e.g., under stress. Additionally, due to the shared neuroectodermal origins of the melanocytes and neurons in the CNS, certain CNS diseases may be linked to pigmentation-related changes due to common regulators, e.g., MC1R variations. Furthermore, the HPA analogue of the skin connects skin pigmentation to the endocrine system, thereby allowing the skin to index possible hormonal abnormalities visibly. In this review, insight is provided into skin pigment production and neuromelanin synthesis in the brain and recent findings are summarised on how signalling pathways in the skin, with a particular focus on pigmentation, are interconnected with the central nervous system. Thus, this review may supply a better understanding of the mechanism of several skin-brain associations in health and disease.

暂无摘要。

Desmopressin is increasingly used for the diagnosis of Cushing disease (CD) since corticotropin-releasing hormone became unavailable. We report the case a 32-year-old man who presented with overt Cushing syndrome. Morning blood cortisol, ACTH, 1 mg dexamethasone suppression test, 24-hour urinary free cortisol, and bedtime salivary cortisol were highly variable, reaching markedly elevated values. Intravenous desmopressin administration produced no ACTH or cortisol increase. Pituitary magnetic resonance imaging, thoracic computed tomography, and DOTATATE positron emission tomography scan identified no lesion. Inferior petrosal sinus sampling (IPSS) with desmopressin stimulation resulted in elevated central-to-peripheral ACTH ratio and prolactin co-secretion, while peripheral ACTH remained stable. No corticotroph tumor was identified on pituitary surgery pathology. Hypercortisolism persisted postoperatively. Cabergoline was initiated, after which the patient rapidly developed transient severe adrenal insufficiency (AI). Bilateral adrenalectomy was performed in view of persistent hypercortisolism. This is an unusual case of petrosal sinus ACTH response to desmopressin without any peripheral response, suggesting a central source of ACTH. Thus, desmopressin should still be used during IPSS in patients with no peripheral response. It is unclear whether the AI episode resulted from a combination of nadir of cyclic hypercortisolism, partial apoplexy, and response to cabergoline of an occult corticotroph tumor.

OBJECTIVE: The success and outcomes of repeat endoscopic transsphenoidal surgery (ETS) for residual or recurrent Cushing\'s disease (CD) are underreported in the literature. This study aims to address this gap by assessing the safety, feasibility, and efficacy of repeat ETS in these patients.
METHODS: A retrospective analysis was conducted on 56 patients who underwent a total of 65 repeat ETS performed by a single neurosurgeon between January 2006 and December 2020. Data including demographic, clinical, laboratory, radiological, and operative details were collected from electronic medical records. Logistic regression was utilized to identify potential predictors associated with sustained remission.
RESULTS: Among the cases, 40 (61.5%) had previously undergone microscopic surgery, while 25 (38.5%) had prior endoscopic procedures. Remission was achieved in 47 (83.9%) patients after the first repeat ETS, with an additional 9 (16.1%) achieving remission after the second repeat procedure. During an average follow-up period of 97.25 months, the recurrence rate post repeat surgery was 6.38%. Sustained remission was achieved in 48 patients (85.7%), with 44 after the first repeat ETS and 4 following the second repeat ETS. Complications included transient diabetes insipidus (DI) in 5 (7.6%) patients, permanent (DI) in 2 (3%) patients, and one case (1.5%) of panhypopituitarism. Three patients (4.6%) experienced rhinorrhea necessitating reoperation. A serum cortisol level > 5 µg/dL on postoperative day 1 was associated with a reduced likelihood of sustained remission.
CONCLUSIONS: Repeat ETS is a safe and effective treatment option for residual or recurrent CD with satisfactory remission rates and low rates of complications.

Peptides continue to gain significance in the pharmaceutical arena. Since the unveiling of insulin in 1921, the Food and Drug Administration (FDA) has authorised around 100 peptides for various applications. Peptides, although initially derived from endogenous sources, have evolved beyond their natural origins, exhibiting favourable therapeutic effectiveness. Medicinal chemistry has played a pivotal role in synthesising valuable natural peptide analogues, providing synthetic alternatives with therapeutic potential. Furthermore, key chemical modifications have enhanced the stability of peptides and strengthened their interactions with therapeutic targets. For instance, selective modifications have extended their half-life and lessened the frequency of their administration while maintaining the desired therapeutic action. In this review, I analyse the FDA approval of natural peptides, as well as engineered peptides for diabetes treatment, growth-hormone-releasing hormone (GHRH), cholecystokinin (CCK), adrenocorticotropic hormone (ACTH), and α-melanocyte stimulating hormone (α-MSH) peptide analogues. Attention will be paid to the structure, mode of action, developmental journey, FDA authorisation, and the adverse effects of these peptides.

OBJECTIVE: To investigate the incidence of nephrolithiasis in a cohort of children with congenital adrenal hyperplasia (CAH), and to study if there is an association with the metabolic control of the disease.
METHODS: This study was designed as a multicenter 1 year-prospective study involving 52 subjects (35 males) with confirmed molecular diagnosis of CAH due to 21-hydroxylase deficiency (21-OHD). Each patient was evaluated at three different time-points: T0, T1 (+6 months of follow-up), T2 (+12 months of follow up). At each follow up visit, auxological data were collected, and adrenocorticotrophic hormone (ACTH), 17-hydroxyprogesterone (17-OHP), Δ4-androstenedione, dehydroepiandrosterone sulfate (DHEAS) serum levels, and urinary excretion of creatinine, calcium, oxalate and citrate were assayed. Moreover, a renal ultrasound was performed.
RESULTS: The incidence of nephrolithiasis, assessed by ultrasound was 17.3% at T0, 13.5% at T1 and 11.5% at T2. At T0, one subject showed nephrocalcinosis. In the study population, a statistically significant difference was found for 17-OHP [T0: 11.1 (3.0-25.1) ng/mL; T1: 7.1 (1.8-19.9) ng/mL; T2: 5.9 (2.0-20.0) ng/mL, p < 0.005], and Δ4-androstenedione [T0: 0.9 (0.3-2.5) ng/mL; T1: 0.3 (0.3-1.1) ng/mL; T2: 0.5 (0.3-1.5) ng/mL, p < 0.005] which both decreased over the follow up time. No statistically significant difference among metabolic markers was found in the group of the subjects with nephrolithiasis, even if 17-OHP, DHEAS and Δ4-androstenedione levels showed a tendency towards a reduction from T0 to T2. Principal component analysis (PCA) was performed to study possible hidden patterns of associations/correlations between variables, and to assess the trend of them during the time. PCA revealed a decrease in the amount of the variables 17-OHP, Δ4-androstenedione, and ACTH that occurred during follow-up, which was also observed in subjects showing nephrolithiasis.
CONCLUSIONS: our data demonstrated that children affected with 21-OHD can be at risk of developing nephrolithiasis. Additional studies are needed to clarify the pathogenesis and other possible risk factors for this condition, and to establish if regular screening of kidney ultrasound in these patients can be indicated.

UNASSIGNED: Dopaminergic agonists are accepted as the most effective treatment for pituitary pars intermedia dysfunction. However, some horses are refractory to daily oral pergolide, the recommended registered treatment. Extended-release cabergoline (ERC) injection may offer an alternative. The objective of this retrospective case series was to describe clinical and endocrinological responses to ERC.
UNASSIGNED: Medical records of horses treated with weekly intramuscular injections of ERC (5 mg/mL, BOVA Aus) at either 0.01 mg/kg (high dose, HD) (n = 10) or 0.005 mg/kg (low dose, LD) (n = 30) were reviewed. Short-term ACTH responses were assessed at 5-8 days using a Wilcoxon signed ranked test. Longer-term ACTH responses (30 to 365 days) were assessed using generalised estimating equations.
UNASSIGNED: Five to eight days after the first dose of LDERC, median adrenocorticotropic hormone (ACTH) concentration was lower (p = 0.001), changing from 153 pg/mL (IQR: 78, 331) to 57 pg/mL (IQR: 30, 102). With HDERC, median ACTH concentration was also 153 pg/mL (IQR: 96, 185) before and then 56 pg/mL (IQR: 29, 86) after 5-8 days of treatment (p = 0.047). Over 12 months of treatment, ACTH concentration ranged from 14 to >1,250 pg/mL (median: 51 pg/mL) in horses treated with LDERC and 20 to 472 pg/mL (median: 50 pg/mL) in horses treated with HDERC. Measurements remained above the seasonal reference range in 39.3 and 52.3% of horses treated with LDERC and HDERC, respectively. Clinical improvement was reported by owners in 78.3 and 100% of horses treated with LDERC and HDERC, respectively. Partial, self-limiting inappetence was reported in 30.0% of LDERC and 60% HDERC cases. Seven horses exhibited lethargy (5 LDERC, 2 HDERC). Insulin concentrations measured 30 days post-ERC treatment were no different from baseline.
UNASSIGNED: Clinical and endocrinological responses were consistent with results of previous reports of oral pergolide treatment. Weekly injection of ERC may be an effective alternative to pergolide; the 0.005 mg/kg dose appeared to be as effective, with less risk of inappetence, than the 0.01 mg/kg dose that has been reported previously.

OBJECTIVE: Evidence is growing that high salt intake is an independent risk factor for obesity, but the mechanisms are unknown. Our novel working hypothesis is that high salt intake drives cortisol production, which in turn, drives obesity. The current study aimed to demonstrate an acute cortisol response following a single high salt meal.
METHODS: Eight participants (age 30.5 ± 9.8 years [mean ± SD], 50% female), consumed high salt (3.82 g; 1529 mg sodium) and low salt (0.02 g; 9 mg sodium) meals in a randomized cross-over design.
RESULTS: Urinary and salivary cortisol and plasma adrenocorticotropic hormone (ACTH) demonstrated order effects. When high salt was given second, there was a peak above baseline for urinary cortisol (26.3%), salivary cortisol (9.4%) and plasma ACTH (4.1%) followed by a significant decline in each hormone (treatment*time, F[9, 18] = 2.641, p = 0.038, partial η2 = 0.569; treatment*time, F[12, 24] = 2.668, p = 0.020, partial η2 = 0.572; treatment*time, F[12, 24] = 2.580, p = 0.023, partial η2 = 0.563, respectively), but not when high salt was given first (p > 0.05 for all).
CONCLUSIONS: These intriguing findings provide partial support for our hypothesis and support a need for further research to elucidate the role of high salt intake in cortisol production and, in turn, in the aetiology of obesity.
BACKGROUND: ACTRN12623000490673; date of registration 12/05/2023; retrospectively registered.

UNASSIGNED: Cortisol response to stressors (hypothalamic-pituitary-adrenal axis, autonomic nervous system, and immune system) plays a vital role in maintaining stable metabolic homeostasis. This study was done to assess the prevalence of hypocortisolemia in patients presenting to ED with sepsis and/or septic shock.
UNASSIGNED: This prospective observational study was done from July 2020 to April 2021. Serum cortisol levels were measured in patients with sepsis and septic shock, and their clinical and laboratory profile was categorized, coded, and analyzed.
UNASSIGNED: Ninety-eight patients were included, of which serum Cortisol <10 μg/dl was noted in 7 (7.2%) patients. The cohort\'s mean age was 52.9 (SD: 15.3) years with a male predominance (n-61; 62.2%). Most common presenting complaint was fever (n-52; 53.1%), followed by abdominal pain (n-24; 24.5%), and breathing difficulty (n-14; 14.3%). Systolic blood pressure <90 mmHg and tachycardia were seen in 63 patients (64.3%). Assessment of diet and native medication use did not demonstrate a predisposition to hypocortisolemia. The median (IQR) arterial lactate values were lower in the hypocortisolemic group: 2.2 (1.2-2.5) as compared to the non-hypocortisolemic group: 3.7 (2.2-8.0). Patients with septic shock without hypocortisolemia were noted to have a higher mean lactate level (2.6 ± 1.3 Vs 5.4 ± 3.9) and lower platelet counts compared to those with low cortisol levels. Patients with normal cortisol levels (n-38; 38.8%) still had low ACTH values.
UNASSIGNED: The prevalence of hypocortisolemia was lower when compared to other Indian studies. Diet and native medication use do not predispose Indians to hypocortisolemia.

Melatonin is a key hormone in regulation of circadian rhythms, and involved in many rhythmic functions, such as feeding and locomotor activity. Melatonin reportedly counteracts stress responses in many vertebrates, including fish. However, targets for this action of melatonin and underlying mechanisms remain unknown.
This study reports potential anti-stress properties of melatonin in goldfish (Carassius auratus), with a focus on its effect on plasma cortisol, food intake, and locomotor activity, all of them involved in the responses to stress exposure. Indeed, acute injection of melatonin counteracted stress-induced hypercortisolinemia and reduced food intake. The reduced locomotor activity following melatonin treatment suggests a possible sedative role in fish. To assess whether this anti-stress effects of melatonin involve direct actions on interrenal tissue, in vitro cultures of head kidney (containing the interrenal cortisol-producing tissue) were carried out in presence of ACTH, melatonin, and luzindole, an antagonist of melatonin receptors. Melatonin in vitro reduced ACTH-stimulated cortisol release, an effect attenuated by luzindole; this suggests the presence of specific melatonin receptors in interrenal tissue.
Our data support a role for melatonin as an anti-stress signal in goldfish, and suggest that the interrenal tissue of teleosts may be a plausible target for melatonin action decreasing cortisol production.