Chrono-Endocrinology in Clinical Practice: A Journey from Pathophysiological to Therapeutic Aspects.

This review was aimed at collecting the knowledge on the pathophysiological and clinical aspects of endocrine rhythms and their implications in clinical practice, derived from the published literature and from some personal experiences on this topic. We chose to review, according to the PRISMA guidelines, the results of original and observational studies, reviews, meta-analyses and case reports published up to March 2024. Thus, after summarizing the general aspects of biological rhythms, we will describe the characteristics of several endocrine rhythms and the consequences of their disruption, paying particular attention to the implications in clinical practice.

Neuroimmunoendocrinology of SARS-CoV 2 Infection.

This review is aimed at illustrating and discussing the neuroimmune endocrinological aspects of the SARS-CoV-2 infection in light of the studies on this topic that have so far appeared in the literature. The most characteristic findings and pending controversies were derived by PubMed and Scopus databases. We included original and observational studies, reviews, meta-analysis, and case reports.

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.

Chronothyroidology: Chronobiological Aspects in Thyroid Function and Diseases.

Chronobiology is the scientific discipline which considers biological phenomena in relation to time, which assumes itself biological identity. Many physiological processes are cyclically regulated by intrinsic clocks and many pathological events show a circadian time-related occurrence. Even the pituitary-thyroid axis is under the control of a central clock, and the hormones of the pituitary-thyroid axis exhibit circadian, ultradian and circannual rhythmicity.

Remission of Pituitary Autoimmunity Induced by Gluten-Free Diet in Patients With Celiac Disease.

Context: An improvement of some autoimmune diseases associated with celiac disease (CD) has been observed after a gluten-free diet (GFD).

Objective: The aim of this longitudinal study was to evaluate the effect of a GFD on autoimmune pituitary impairment in patients with CD and potential/subclinical lymphocytic hypophysitis (LYH).

Design: Five-year longitudinal observational study.

Impact of Pituitary Autoimmunity and Genetic Disorders on Growth Hormone Deficiency in Children and Adults.

Growth hormone (GH), mostly through its peripheral mediator, the insulin-like growth factor 1(IGF1), in addition to carrying out its fundamental action to promote linear bone growth, plays an important role throughout life in the regulation of intermediate metabolism, trophism and function of various organs, especially the cardiovascular, muscular and skeletal systems. Therefore, if a prepubertal GH secretory deficiency (GHD) is responsible for short stature, then a deficiency in adulthood identifies a nosographic picture classified as adult GHD syndrome, which is characterized by heart, muscle, bone, metabolic and psychic abnormalities. A GHD may occur in patients with pituitary autoimmunity; moreover, GHD may also be one of the features of some genetic syndromes in association with other neurological, somatic and immune alterations.

The role of autoimmunity in pituitary dysfunction due to traumatic brain injury.

Purpose: Traumatic brain injury (TBI) is one of the most common causes of mortality and long-term disability and it is associated with an increased prevalence of neuroendocrine dysfunctions. Post-traumatic hypopituitarism (PTHP) results in major physical, psychological and social consequences leading to impaired quality of life. PTHP can occur at any time after traumatic event, evolving through various ways and degrees of deficit, requiring appropriate screening for early detection and treatment.

Natural history of autoimmune primary ovarian insufficiency in patients with Addison's disease: from normal ovarian function to overt ovarian dysfunction.

Context: Women with autoimmune Addison's disease with normal ovulatory cycles but positive for steroid cell antibodies (StCA) have been considered at risk of premature ovarian insufficiency (POI).

Design: Thirty-three women younger than 40 years, with subclinical-clinical autoimmune Addison's disease but with normally ovulatory menses, were followed up for 10 years to evaluate the long-term time-related variations of StCA, ovarian function and follicular reserve. All patients and 27 control women were investigated at the start and every year for the presence and titre of StCA (by indirect immunofluorescence), serum concentrations of anti-Mullerian hormone (AMH) and ovarian function at four consecutive menses every year.

Revisitation of autoimmune hypophysitis: knowledge and uncertainties on pathophysiological and clinical aspects.

Purpose: This publication reviews the accepted knowledges and the findings still discussed on several features of autoimmune hypophysitis, including the most recently described forms, such as IgG4 and cancer immunotherapy- related hypophysitis.

Methods: The most characteristic findings and the pending controversies were derived from a literature review and previous personal experiences. A single paragraph focused on some atypical examples of the disease presenting under confounding pretences.

Longitudinal behavior of autoimmune GH deficiency: from childhood to transition age.

Background: Some cases of apparently idiopathic GH deficiency (GHD) may be caused by pituitary autoimmunity.

Objective: To study the variations in pituitary function and antipituitary antibodies (APA) from childhood to transition age in patients with apparently idiopathic GHD.

Design: We conducted a longitudinal study.

Use of serum pituitary antibodies to improve the diagnosis of hypophysitis.

Lymphocytic hypophysitis is characterized by an extensive infiltration of lymphocytic cells. Pituitary biopsy is the gold diagnostic standard for lymphocytic hypophysitis but the disease occurs with moderate or without pituitary enlargement. The role of antipituitary antibodies (APA) in autoimmune hypophysitis is still discussed due to various methodological difficulties.

Rituximab-induced remission of autoimmune hypophysitis and primary immune thrombocytopenia in a patient with autoimmune polyendocrine syndrome type 4.

Rituximab, a B-cell depleting antibody, has been used for treatment of several autoimmune diseases. We report the effect of rituximab therapy on pituitary and platelet autoimmunity in a 36-yr old patient, positive for antiplatelet and antipituitary (APA) antibodies. The behavior of pituitary function and of APA by immunofluorescence, as well antibodies to platelets and platelet count, were investigated at start and subsequently every six months during Rituximab treatment.

Opposite influence of light and blindness on pituitary-gonadal function.

Some environmental factors may influence the pituitary-gonadal function. Among these, light plays an important role in animals and in humans. The effect of light on the endocrine system is mediated by the pineal gland, through the modulation of melatonin secretion.

Total thyroidectomy, without prophylactic central lymph node dissection, in the treatment of differentiated thyroid cancer. Clinical retrospective study on 221 cases.

Total thyroidectomy (TT) is the standard of care for differentiated thyroid cancer (DTC), but still there is no consensus about the role of routine use of prophylactic central lymph node dissection. The aim of this study was to analyze our results of TT without prophylactic central lymphadenectomy in the treatment of DTC. Clinical records, between January 1998 and December 2005, of 221 patients undergoing TT, without prophylactic central lymph node dissection, were retrospectively evaluated.

Subclinical diabetes insipidus.

Subclinical central diabetes insipidus (CDI) can be the outcome of a number of diseases that affect the hypothalamus-infundibulum-post hypophysis axis. One of the most common forms of subclinical CDI is linked to an autoimmune pathogenesis even if other causes may be also responsible. Among these, pregnancy, traumatic and surgical brain injury and some infiltrative, vascular, infectious and neoplastic diseases have been reported with increasing frequency.

Time course of Graves' ophthalmopathy after total thyroidectomy alone or followed by radioiodine therapy: a 2-year longitudinal study.

The findings in hyperthyroid patients with Graves' orbitopathy (GO) of antibodies against antigens shared between the thyroid and orbit, such as the TSH-receptor (TRAb) and a novel protein G2s (G2sAb), suggested a possible common therapeutic strategy. However, the gold therapeutic standard for hyperthyrodism in these patients remains still unsettled and is mainly based on personal experience. Studies on the effect of total thyroidectomy (TT) alone or followed by radioiodine ablation (RAI) of thyroid remnants showed often conflicting results.

Detection of antipituitary and antihypothalamus antibodies to investigate the role of pituitary or hypothalamic autoimmunity in patients with selective idiopathic hypopituitarism.

Objective: Antipituitary (APA) but not antihypothalamus antibodies (AHA) have been investigated in patients with idiopathic hypopituitarism. This study searched for APA and AHA in some of these patients to investigate whether pituitary or hypothalamic autoimmunity could play a role in their pituitary dysfunction.

Design: Sixty-six patients with selective idiopathic hypopituitarism were studied: 27 with ACTH deficiency, 20 with GH deficiency and 19 with hypogonadotropic hypogonadism.

Upregulation of endocrine gland-derived vascular endothelial growth factor in papillary thyroid cancers displaying infiltrative patterns, lymph node metastases, and BRAF mutation.

Background: Endocrine gland-derived vascular endothelial growth factor (Prok1) and prokineticin 2 (Prok2) are involved in the organ-specific regulation of angiogenesis, which is a crucial step toward cancer progression in most tumors, including those of thyroid gland. The oncogene BRAF V600E mutation is associated with poor clinical outcome of papillary thyroid cancer (PTC) and can independently predict its recurrence.

Design: Our hypothesis was that Prok1 and Prok2 expression levels associated with BRAF mutations can be prognostic factors for PTC outcome.

Investigation of antihypothalamus and antipituitary antibodies in amateur boxers: is chronic repetitive head trauma-induced pituitary dysfunction associated with autoimmunity?

Objective: Current data clearly demonstrate that sports-related chronic repetitive head trauma due to boxing might result in hypopituitarism. However, the mechanism of sports-related traumatic brain injury-induced pituitary dysfunction is still unclear. In order to understand whether autoimmune mechanisms could play a role in the pituitary dysfunction due to sports-related head trauma, we investigated the presence of antipituitary antibodies (APAs) and antihypothalamus antibodies (AHAs) in amateur boxers.

Anti-pituitary antibodies in children with newly diagnosed celiac disease: a novel finding contributing to linear-growth impairment.

Objectives: The possible autoimmune involvement of the pituitary gland in patients with celiac disease (CD) has been suggested but demonstrated in only a few patients on gluten-free diet. We aimed to assess the prevalence and clinical meaning of anti-pituitary antibodies (APA) in children and adolescents with the newly diagnosed CD.

Methods: A total of 119 patients with CD (0.

Cytotoxic T lymphocyte antigen-4 Ala17 polymorphism is a genetic marker of autoimmune adrenal insufficiency: Italian association study and meta-analysis of European studies.

Objective: Cytotoxic T lymphocyte antigen-4 (CTLA4) gene polymorphism has been associated with human autoimmune diseases, but discordant data are available on its association with autoimmune Addison's disease (AAD). We tested the human leukocyte antigen (HLA)-independent association of CTLA4+49 (A/G) (Ala 17) and/or CTLA4 CT60 (A/G) polymorphism with AAD.

Design: DNA samples from 180 AAD patients and 394 healthy control subjects from continental Italy were analyzed, and association statistical analyses and meta-analysis of published studies were performed.

Expression of RIZ1 protein (Retinoblastoma-interacting zinc-finger protein 1) in prostate cancer epithelial cells changes with cancer grade progression and is modulated in vitro by DHT and E2.

The nuclear protein methyl-transferase Retinoblastoma-interacting zinc-finger protein 1 (RIZ1) is considered to be a downstream effector of estrogen action in target tissues. Silencing of RIZ1 expression is common in many tumors. We analyzed RIZ1 expression in normal and malignant prostate tissue and evaluated whether estradiol (E2) or dihydrotestosterone (DHT) treatment modulated RIZ1 in cultured prostate epithelial cells (PEC).

Thyroid B-flow twinkling sign: a new feature of papillary cancer.

Background: Microcalcifications (aggregated with psammoma bodies), detected by ultrasound (US), are the most specific feature of papillary thyroid cancer (PTC). Using B-flow imaging (BFI), we identified a new sign (the twinkling sign; BFI-TS) in 'suspect' PTC nodules, which appeared to be generated by microcalcifications.

Objective: To evaluate whether the BFI-TS was predictive of malignancy, we correlated the BFI-TS with the results of fine needle aspiration cytology and histology.

Homozygous mutation in the prokineticin-receptor2 gene (Val274Asp) presenting as reversible Kallmann syndrome and persistent oligozoospermia: case report.

Prokineticin 2 (Prok2) or prokineticin-receptor2 (Prok-R2) gene mutations are associated with Kallmann syndrome (KS). We describe a new homozygous mutation of Prok-R2 gene in a man displaying KS with an apparent reversal of hypogonadism. The proband, offspring of consanguineous parents, presented at age 19 years with absent puberty, no sense of smell, low testosterone and gonadotrophin levels.

Effects of somatostatin analog SOM230 on cell proliferation, apoptosis, and catecholamine levels in cultured pheochromocytoma cells.

Surgery is the primary therapy for pheochromocytoma (PHEO), a catecholamine-producing tumor. Benign and malignant PHEO could develop recurrences, and the intraoperative risk of recurrent PHEO is an important unresolved issue. Non-surgical treatments of PHEO recurrence would therefore better prepare patients for reintervention as well as provide them with palliative management.