Can Growth Hormone Lead to a Faster Recovery from Guillain-Barré Syndrome? Case Report of the First Therapeutic Use in One Patient.

Although the prognosis in Guillain-Barré syndrome (GBS) is generally good, protracted and incomplete courses of recovery can be a heavy burden. Animal studies suggest growth hormone (GH) treatment could stimulate myelin repair and thus accelerate functional recovery in acute polyneuropathy. We report on the first use of GH in GBS. Our objective was to monitor safety and tolerability as well as to evaluate the effect of an off-label GH therapy during recovery from GBS in 1 patient. A 28-year-old male with flaccid tetraparesis caused by pure motor GBS was treated off-label with GH (1 mg/day) for 10 weeks. Muscle strength was measured regularly before, during, and after the treatment over a total span of 330 days. Serum levels of IGF-I were assessed before, during, and after GH treatment. Changes in strength gain were used as the main parameter of efficacy. No side effects of GH treatment were observed. Serum IGF-I increased from 177 ng/mL at baseline to an average of 342 ng/mL (normal range 78-270 ng/mL) during treatment. Prior to GH administration, strength (R2 = 0.99, p < 0.01) was associated with time, representing the natural course of recovery. During GH treatment, the slope of strength gain increased (Glass' ∆ = 1.08, p < 0.01). The association between alterations of strength gain and IGF-I serum levels reached trend level (R2 = 0.36, p = 0.09). In this single case, GH treatment seemed to be associated with faster muscular strength gain. Controlled studies are needed in order to establish GH as a potential therapeutic approach in motor GBS.

Outcomes of Initial Management Strategies in Patients With Autoimmune Lymphocytic Hypophysitis: A Systematic Review and Meta-analysis.

CONTEXT: Lymphocytic hypophysitis (LyHy) is characterized by inflammation of the pituitary and or neuroinfundibulum and is uncommon. Treatment options include observation, high-dose glucocorticoids (HD-GCs) or surgery. Optimal first-line management strategy, however, remains unknown. OBJECTIVE: This work aimed to assess response to first-line treatment options (observation, HD-GCs, or surgery) of clinically relevant outcomes (symptomatic, hormonal, and radiographic improvement) among patients with LyHy. METHODS: A systematic review was conducted in 6 databases through 2020. Meta-analysis was conducted when feasible using a random-effects model. RESULTS: We included 33 studies reporting on 591 patients (423 women, 72%) with LyHy. Improvement/resolution of anterior pituitary dysfunction was highest when HD-GCs was first-line treatment. Surgery was associated with the greatest proportion of patients who had regression on imaging. Subgroup analysis comparing HD-GCs to observation showed the odds of anterior pituitary hormone recovery (OR 3.41; 95% CI, 1.68-6.94) or radiographic regression (OR 3.13; 95% CI, 1.54-6.36) were higher with HD-GCs, but so was the need for additional forms of treatment (OR 4.37; 95% CI, 1.70-11.22). No statistically significant difference was seen in recovery of diabetes insipidus (OR 0.9; 95% CI, 0.26-3.10). Certainty in these estimates was very low. CONCLUSION: Observation and use of HD-GCs both are successful first-line management strategies in LyHy. Although use of HD-GCs was associated with increased recovery of anterior pituitary hormone deficit, it also was associated with greater likelihood of additional treatment after withdrawal. Optimal dosing and duration of HD-GCs remains unknown.

Differences between immunotherapy-induced and primary hypophysitis-a multicenter retrospective study.

OBJECTIVE: Immune checkpoint inhibitors can cause various immune-related adverse events including secondary hypophysitis. We compared clinical characteristics of immunotherapy-induced hypophysitis (IIH) and primary hypophysitis (PH) DESIGN: Retrospective multicenter cohort study including 56 patients with IIH and 60 patients with PH. METHODS: All patients underwent extensive endocrine testing. Data on age, gender, symptoms, endocrine dysfunction, MRI, immunotherapeutic agents and autoimmune diseases were collected. RESULTS: Median time of follow-up was 18 months in IIH and 69 months in PH. The median time from initiation of immunotherapy to IIH diagnosis was 3 months. IIH affected males more frequently than PH (p < 0.001) and led to more impaired pituitary axes in males (p < 0.001). The distribution of deficient adenohypophysial axes was comparable between both entities, however, central hypocortisolism was more frequent (p < 0.001) and diabetes insipidus considerably less frequent in IIH (p < 0.001). Symptoms were similar except that visual impairment occurred more rarely in IIH (p < 0.001). 20 % of IIH patients reported no symptoms at all. Regarding MRI, pituitary stalk thickening was less frequent in IIH (p = 0.009). Concomitant autoimmune diseases were more prevalent in PH patients before the diagnosis of hypophysitis (p = 0.003) and more frequent in IIH during follow-up (p = 0.002). CONCLUSIONS: Clinically, IIH and PH present with similar symptoms. Diabetes insipidus very rarely occurs in IIH. Central hypocortisolism, in contrast, is a typical feature of IIH. Preexisting autoimmunity seems not to be indicative of developing IIH.

Adherence, Attitudes and Beliefs of Growth Hormone Deficient Patients - A Questionnaire-based Cohort Study.

INTRODUCTION: GHD is a chronic and systemic disease requiring daily replacement of growth hormone (GHRT). Adherence and attitudes of adult GHD patients are not well known. We sought to assess patients' knowledge of growth hormone deficiency (GHD) in association with treatment adherence and attitudes regarding available and upcoming treatment options. METHODS: We performed a cross-sectional survey with a custom-made questionnaire at a single centre assessing data on demographics, knowledge of GHD, adherence and attitudes towards GHRT. RESULTS: Of 106 eligible patients actively followed for GHD 70 returned the completed survey (return-rate 66%, 34 m/36 f; age 56±14 years). 46 patients were actively treated, but almost one third (n=24) refused GHRT. 12 patients had participated in clinical trials with LAGH (long-acting growth hormone). Overall, patients with GHRT showed good adherence. Patients refusing GHRT mostly feared side effects and/or had a lack of information/perceived effect. Disease knowledge and level of education were higher in treated than untreated patients (p=0.023/0.017). Only 36% of respondents would initiate treatment with LAGH. Patients with prior LAGH experience and patients with childhood-onset GHD were more likely to adopt LAGH (p=0.048/0.031). DISCUSSION: Most often, misinformation causes patients to refuse GHRT. Possibly the understanding of their condition and consequences of non-treatment is limited. To improve adherence more focused educational and behavioural strategies may be needed. Willingness to begin a therapy with LAGH was lower than expected (36%). The reasons for reluctance against LAGH need to be elucidated.

Clinical Characteristics of Primary Hypophysitis - A Single-Centre Series of 60 Cases.

OBJECTIVE: Clinical data on primary hypophysitis are still scarce. Especially non-surgical cases are underreported. We sought to analyse clinical characteristics of primary hypophysitis, particularly in clinically diagnosed patients. DESIGN: Retrospective single centre study in 60 patients with primary hypophysitis. METHODS: Symptoms, MRI, histopathological findings, treatment and outcomes were analysed in 12 histopathologically and 48 clinically diagnosed patients. Diagnostic criteria for clinical diagnosis were: a) MRI findings compatible with primary hypophysitis; b) course of disease excluding other differential diagnoses. Mean duration of follow-up was 69 months. RESULTS: Female sex was predominant (73%). Fatigue (52%), headache (38%) and diabetes insipidus (38%) were the most frequent symptoms. 42% had a concomitant autoimmune disease. The corticotropic, thyrotropic, gonadotropic, somatotropic axis was impaired in 67%, 57%, 52%, 20%, respectively. Men had a higher number of impaired hormone axes (p=0.022) with the gonadotropic axis being affected more frequently in men (p=0.001). Infundibular thickening (56%) and space occupying lesions (46%) were typical MRI findings. Pituitary size was frequently enlarged at presentation (37%) but diminished during observation (p=0.029). Histopathologically and clinically diagnosed cases did not differ. CONCLUSIONS: The cohort of clinically diagnosed patients did not differ from our histopathologically diagnosed patients or from published cohorts with predominantly surgical patients. Thus, diagnosis of primary hypophysitis using clinical criteria seems feasible.

A horse and a zebra: an atypical clinical picture including Guillain-Barré syndrome, recurrent fever and mesenteric lymphadenopathy caused by two concomitant infections.

BACKGROUND: While Campylobacter jejuni represents the most common cause of bacterial gastroenteritis, Yersinia pseudotuberculosis infections are very rarely diagnosed in adults. CASE: We report on a previously healthy patient who presented several times at our hospital with fever, Guillain-Barré syndrome, recurrent abdominal symptoms and distinct mesenteric lymphadenopathy, respectively. This complicated and diagnostically challenging course of disease was caused by a C. jejuni and Y. pseudotuberculosis coinfection. Antibiotic treatment with doxycycline was effective. CONCLUSION: Broad serology testing was crucial to discover that two concomitant infections were causing the symptoms. This case demonstrates that when a clinical picture is not fully explained by one known infection, another infection with the same underlying risk factor has to be considered, hence "a horse and a zebra".