Assessment of Neuroendocrine Changes and Hypothalamo-Pituitary Autoimmunity in Patients with COVID-19.

SARS-CoV-2 may affect the hypothalamic-pituitary axis and pituitary dysfunction may occur. Therefore, we investigated neuroendocrine changes, in particular, secondary adrenal insufficiency, using a dynamic test and the role of autoimmunity in pituitary dysfunction in patients with COVID-19. The single-center, prospective, case-control study included patients with polymerase chain reaction (PCR)-confirmed COVID-19 and healthy controls. Basal hormone levels were measured, and the adrenocorticotropic hormone (ACTH) stimulation test was performed. Antipituitary (APA) and antihypothalamic antibodies (AHA) were also determined. We examined a total of 49 patients with COVID-19 and 28 healthy controls. The frequency of adrenal insufficiency in patients with COVID-19 was found as 8.2%. Patients with COVID-19 had lower free T3, IGF-1, and total testosterone levels, and higher cortisol and prolactin levels when compared with controls. We also demonstrated the presence of APA in three and AHA in one of four patients with adrenal insufficiency. In conclusion, COVID-19 may result in adrenal insufficiency, thus routine screening of adrenal functions in these patients is needed. Endocrine disturbances in COVID-19 are similar to those seen in acute stressful conditions or infections. Pituitary or hypothalamic autoimmunity may play a role in neuroendocrine abnormalities in COVID-19.

Hypothalamic-Pituitary Autoimmunity and Related Impairment of Hormone Secretions in Chronic Fatigue Syndrome.

CONTEXT: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a severe chronic illness that reduces the quality of life. A potential role of neuroendocrine autoimmune dysfunction has been hypothesized. OBJECTIVE: This work aims to investigate the occurrence of antipituitary (APA) and antihypothalamic (AHA) antibodies and possible related hypothalamic/pituitary dysfunctions in ME/CSF patients. METHODS: This is a case-control study conducted in a university hospital setting (Stanford, California, USA; and Naples, Italy). Thirty women with ME/CSF (group 1) diagnosed according to Fukuda, Canadian, and Institute of Medicine criteria, at Stanford University, were enrolled and compared with 25 age-matched healthy controls. APA and AHA were detected by immunofluorescence; moreover, we investigated hormonal secretions of anterior pituitary and respective target glands. APA and AHA titers both were assessed and the prevalence of pituitary hormone deficiencies was also investigated. RESULTS: Patients in group 1 showed a high prevalence of AHA (33%) and APA (56%) and significantly lower levels of adrenocorticotropin (ACTH)/cortisol, and growth hormone (GH) peak/insulin-like growth factor-1 (IGF-1) vs controls (all AHA/APA negative). Patients in group 1A (13 patients positive at high titers, ≥ 1:32) showed ACTH/cortisol and GH peak/IGF-1 levels significantly lower and more severe forms of ME/CFS with respect to patients in group 1B (7 positive at middle/low titers, 1:16-1:8) and 1C (10 antibody-negative patients). CONCLUSION: Both AHA and/or APA at high titers were associated with hypothalamic/pituitary dysfunction, suggesting that hypothalamic/pituitary autoimmunity may play an important role in the manifestations of ME/CFS, especially in its more severe forms.

Obesity and hypovitaminosis D: causality or casualty?

Epidemiological studies reported that vitamin D deficiency represents an increasingly widespread phenomenon in various populations. Vitamin D deficiency is considered a clinical syndrome determined by low circulating levels of 25-hydroxyvitamin D (25(OH)D), which is the biologically-inactive intermediate and represents the predominant circulating form. Different mechanisms have been hypothesized to explain the association between hypovitaminosis D and obesity, including lower dietary intake of vitamin D, lesser skin exposure to sunlight, due to less outdoor physical activity, decreased intestinal absorption, impaired hydroxylation in adipose tissue and 25(OH)D accumulation in fat. However, several studies speculated that vitamin D deficiency itself could cause obesity or prevent weight loss. The fat-solubility of vitamin D leads to the hypothesis that a sequestration process occurs in body fat depots, resulting in a lower bioavailability in the obese state. After investigating the clinical aspects of vitamin D deficiency and the proposed mechanisms for low 25(OH)D in obesity, in this manuscript we discuss the possible role of vitamin D replacement treatment, with different formulations, to restore normal levels in individuals affected by obesity, and evaluate potential positive effects on obesity itself and its metabolic consequences. Food-based prevention strategies for enhancement of vitamin D status and, therefore, lowering skeletal and extra-skeletal diseases risk have been widely proposed in the past decades; however pharmacological supplementation, namely cholecalciferol and calcifediol, is required in the treatment of vitamin D insufficiency and its comorbidities. In individuals affected by obesity, high doses of vitamin D are required to normalize serum vitamin D levels, but the different liposolubility of different supplements should be taken into account. Although the results are inconsistent, some studies reported that vitamin D supplementation may have some beneficial effects in people with obesity.