COVID-19 and the pituitary.

BACKGROUND: Despite COVID-19 being identified as severe respiratory viral infection, progressively many relevant endocrine manifestations have been reported greatly contributing to the severity of the clinical presentation. Systemic involvement in COVID-19 is due to the ubiquitous expression of angiotensin-converting enzyme 2 (ACE2) receptor, responsible for the entry in the cells of SARS-CoV-2, Several reports in humans and animal models showed a significant ACE2 mRNA expression in hypothalamus and pituitary cells. Moreover, higher mortality and poorer outcomes have been widely described in COVID-19 patients with obesity, diabetes and vertebral fractures, which are all highly prevalent in subjects with pituitary dysfunctions. AIM: To review the main endocrine manifestations of COVID-19 with their possible implications for pituitary diseases, the possible direct and indirect involvement of the pituitary gland in COVID-19, the impact of COVID-19 on the management of established pituitary diseases which can be already at increased risk for worse outcomes and on neurosurgical activities as well as vaccination. CONCLUSIONS: Our review underlines that there could be a specific involvement of the pituitary gland which fits into a progressively shaping endocrine phenotype of COVID-19. Moreover, the care for pituitary diseases need to continue despite the restrictions due to the emergency. Several pituitary diseases, such as hypopituitarism and Cushing disease, or due to frequent comorbidities such as diabetes may be a risk factor for severe COVID-19 in affected patients. There is the urgent need to collect in international multicentric efforts data on all these aspects of the pituitary involvement in the pandemic in order to issue evidence driven recommendations for the management of pituitary patients in the persistent COVID-19 emergency.

Distinct Clinical Features of Post-COVID-19 Vaccination Early-onset Graves' Disease.

CONTEXT: Several case reports of Graves' disease (GD) occurrence after COVID-19 vaccination that are possibly related to the autoimmune syndrome induced by adjuvants (ASIA) were published recently. OBJECTIVE: The aim of our study was to evaluate possible distinctive features in the presentation and clinical course of patients with GD occurring early (within 4 weeks) after COVID-19 vaccination who attended our Endocrine Unit in 2021. METHODS: Patients with a first episode of GD attending a tertiary endocrine center between January 1, 2021, and December 31, 2021, were included. RESULTS: Sixty-four patients with a first episode of GD were seen in 2021: 20 (31.2%) of them had onset within 4 weeks following vaccine administration. Compared with the other 44 patients, the 20 patients with postvaccine early-onset (PoVEO) GD were older (median age 51 years vs 35 years, P = .003) and more likely to be male (40.0% vs 13.6%, P = .018). At diagnosis, the biochemical and immune profiles were similar between the 2 groups. However, at 3 months after starting methimazole, patients with PoVEO GD had significantly lower thyrotropin receptor antibody titer and were taking lower doses of methimazole than the other patients with GD. None in the PoVEO group had sustained free triiodothyronine elevation. CONCLUSION: This relatively large series suggests that in 2021 PoVEO GD may be a new nosologic entity representing one-third of patients evaluated for new-onset GD in our center. Distinctive features included older age at onset, higher male prevalence, and a better initial biochemical and immunologic response to treatment. Further studies are warranted to clinically and biochemically differentiate these cases from sporadically occurring GD.

Growth Hormone Therapy Does Not Increase the Risk of Craniopharyngioma and Nonfunctioning Pituitary Adenoma Recurrence.

CONTEXT: Recombinant human growth hormone (rhGH) replacement therapy is often prescribed in patients with nonfunctioning pituitary adenoma (NFPA) or craniopharyngioma. OBJECTIVE: To study whether rhGH therapy in patients with adult growth hormone deficiency (AGHD) increases the risk of pituitary tumor recurrence. DESIGN: Retrospective, observational study. SETTING: Tertiary care center. PATIENTS: We studied 283 consecutive patients with AGHD due to NFPA or craniopharyngioma between 1995 and 2018. INTERVENTION: rhGH treatment at standard doses was initiated in 123 patients (43.5%). The remaining 160 patients served as controls. MAIN OUTCOME MEASURE: Risk of tumor recurrence in rhGH-treated and control patients. RESULTS: In univariate analysis, recurrence of the pituitary tumor was less frequent in rhGH-treated patients (19.5%) than in controls (29.7%; hazard ratio [HR] 0.53, 95% confidence interval [CI] 0.32-0.86; P = .01). Multivariate Cox analysis demonstrated that the risk of tumor recurrence was associated with detection of residual disease at the baseline magnetic resonance imaging (HR 9.17; 95% CI, 4.88-17.22; P < .001) and not having performed radiotherapy (HR 16.97; 95% CI, 7.55-38.16; P < .001), while rhGH treatment was no longer associated with a lower risk of recurrence (HR 0.82; 95% CI, 0.47-1.44; P = .50). CONCLUSIONS: We found no association between rhGH replacement and the risk of tumor recurrence in patients with AGHD caused by NFPA or craniopharyngioma. These data add to the mounting evidence that rhGH therapy has a neutral effect on the recurrence of pituitary tumors. PRÉCIS: Replacement therapy with rhGH is prescribed to patients with adult growth hormone deficiency. Our study found no increased risk of pituitary tumor recurrence.

Relationships Between Personality Features and the Rubber Hand Illusion: An Exploratory Study.

The rubber hand illusion paradigm allows investigating human body ownership by inducing an illusion of owning a life-sized fake hand. Despite the wide consensus on the fact that integration of multisensory signals is the main interpretative framework of the rubber hand illusion, increasing amount of data show that additional factors might contribute to the emergence of the illusion and, in turn, explain the strong inter-individual differences of the illusory patterns. Here, we explored whether and how personality features contribute to the emergence of the illusion by administering to healthy participants the rubber hand illusion paradigm along with two well-known personality tests, i.e., the Personality Assessment Inventory (PAI) and the Rorschach test. Results showed that two Rorschach domains (i.e., "Perception and Thinking Problems" and "Self and Other Representation") were positively correlated with the illusory mislocalization of the own left hand toward the fake hand. Further analyses suggested that while the tendency to perceive unconventionally is related to mislocalizing the own hand toward the fake hand, the association of the RHI index and other personality features measured by the Rorschach remain uncertain. However, our findings in general suggest that personality features might have a role in the emergence of the rubber hand illusion. This, in turn, could explain the high inter-individual variability of the illusory effects.

A meta-analysis-derived proposal for a clinical, ultrasonographic, and cytological scoring system to evaluate thyroid nodules: the "CUT" score.

The purpose of this study is to develop a new cancer risk score for preoperative assessment of thyroid nodules (TN) trying to reduce unnecessary thyroidectomies. On the basis of a recent meta-analysis of published literature, we assigned a matching value to the clinical (C) and ultrasonographic (U) features of TN with increased malignancy risk (MR). The created "CUT" score derived from "C+U" score, (CU[1-10] ), along with the five-tiered "T" (T[1-5] ), represents the cytologic result of the fine-needle aspiration. The C+U score was prospectively applied to 683 consecutive patients with 705 TN and validated through a ROC curve analysis. The CUT score was correlated with the histopathological diagnoses of 110 surgically resected TN. Fifty-five histologically benign TN had a mean C+U score of 2.4 versus 5.7 of 55 malignant TN (p < 0.001). Three categories were identified: low risk for C+U score ≤2.5 (MR: 9 %), intermediate risk for C+U score ≥2.75 and ≤5 (MR: 38 %), and high risk for C+U score ≥5.25 (MR: 95 %). Sensitivity and specificity were, respectively, 95 and 60 % for a cut-off value >2.5, and 69 and 96 % for >5. The "CUT" score can be easily applied, aiding clinicians in the evaluation of TN, especially in cases with indeterminate or repeated non-diagnostic FNA.

"Occult" ovarian Leydig cell tumor: when laboratory tells more than imaging.

Hyperandrogenism is a common finding in premenopausal age and is generally caused by polycystic ovarian syndrome or other benign disease. Androgen-secreting tumors represent only 0.2 % of the causes of hyperandrogenism and usually present with severe clinical features, abrupt onset, and very high androgens levels. We describe here three cases of occult ovarian Leydig cell tumors suspected on the basis of severe clinical features of hyperandrogenism rapidly worsening, with elevated serum total testosterone levels, in which bilateral ovariectomy was performed and tumor was confirmed by post-operative histology. In all three cases, imaging was negative for ovarian tumor. Moreover, in one case the confounding concomitant finding of bilateral adrenal masses posed an additional challenge. Our experience highlights that testosterone levels represent the most helpful marker in the diagnosis of androgen-secreting ovarian tumor. In the absence of imaging findings, bilateral ovariectomy should be indicated, if supported by unequivocal clinical and laboratory data.