When It Rains It Pours...: Wernicke Encephalopathy with Sudden Blindness after Bariatric Surgery in a Patient with Congenital Deafness.

BACKGROUND: Malabsorption syndromes are known chronic complications of bariatric surgery. Therefore, it is recommended to take oral supplementation with multivitamins. Wernicke's encephalopathy represents an acute neuropsychiatric syndrome associated with alcoholism or severe malnutrition; sporadic cases of this potential complication related to bariatric surgery are described in the literature. We present a case of Wernicke's encephalopathy due to severe vitamin B1 deficiency after bariatric surgery. CASE REPORT: A 31-year-old woman with deaf-mutism from the age of 3 years old, operated 3 months before with a mini-gastric bypass for severe obesity, was transferred to our unit after accessing the emergency room. In the immediate medical history, there was the sudden and rapid decline in vision, leading to complete loss of vision, marked asthenia, and paresthesia in the four limbs. Considering the previous bariatric surgery, the diagnosis of non-alcoholic Wernicke's syndrome was suspected, for which IV therapy with Vitamin B1 was started at a dosage of 5 vials of 200 mg in 100 cc of saline solution (three times a day for the first 72 hours, subsequently 1 once/day). After 12 hours, there was an improvement in visual acuity, and the symptoms completely resolved within 48 hours. She was discharged with complete resolution of all symptoms after 1 month. CONCLUSION: Initial vision loss without confusion or encephalopathy is one atypical presentation of Wernicke syndrome. Clinical suspicion must be high in case of alcoholism or post-bariatric surgery. Early recognition of atypical symptoms, including vision loss, and timely administration of therapy improves the prognosis of this potentially reversible but time-dependent neurological emergency.

Different FT3/TSH correlation in acquired and congenital hypothyroid patients reveals a different hypothalamic set-point.

OBJECTIVE: To understand differences in thyroid hormone replacement therapy with levo-thyroxine (l-T4) between acquired and congenital hypothyroid (CH) patients. DESIGN: We compared biochemical thyroid parameters between euthyroid subjects (EU) and both CH adult patients and thyroidectomized patients (TP) under replacement therapy. PATIENTS AND MEASUREMENTS: A retrospective analysis was performed on a series of 98 consecutive adult CH patients (27 males and 71 females) with a median age of 24 years (range 18-58). Serum TSH, FT3, FT4, l-T4 dose and body weight were assessed. For comparison purposes, large series of 461 TP for thyroid cancer and 1852 EU followed at our Thyroid Clinic were used as control groups. RESULTS: The daily weight-based l-T4 dose was significantly higher in CH than TP group (1.9 vs. 1.7 mcg/kg, p = .03). FT3/FT4 ratio was significantly higher in the EU group, intermediate in CH and lower in TP groups (0.32, 0.28 and 0.24, respectively). Linear regression analysis displayed an inverse correlation between FT4 and TSH in all the groups. An inverse correlation between FT3 and TSH was observed in the TP group, but not in the EU and CH group suggesting that CH patients, under replacement therapy, display biochemical thyroid parameters similar to EU subjects. CONCLUSIONS: Adult CH patients require a higher daily l-T4 dose than adult TP. However, the different correlation of TSH and FT3 values between CH and TP patients suggests an adaptive and different hypothalamic-pituitary-thyroid axis regulation that may depend on the early timing of the onset of hypothyroidism in CH.

Two birds one stone: semaglutide is highly effective against severe psoriasis in a type 2 diabetic patient.

SUMMARY: Semaglutide is a glucagon-like peptide 1 (GLP-1) receptor agonist, approved for the treatment of type 2 diabetes mellitus (T2DM). GLP-1 analogs exert several biological activities connected not only with an insulinotropic effect but also with immunoregulation and reduction of inflammation. A 73-year-old male patient with class III obesity was referred to us for T2DM, which was not controlled with metformin therapy. He had suffered from plaque psoriasis for some years and was treated with topical therapy and adalimumab, without success. The psoriasis area and severity index (PASI) was 33.2 (indicating severe psoriasis), and the dermatology life quality index (DLQI) was 26.0 (indicating an extremely negative effect on the patient's life). Semaglutide (starting with 0.25 mg/week for 4 weeks, increased to 0.50 mg/week for 12 weeks, and then to 1 mg/week) was added to metformin. After 4 months, glycemic parameters had improved, and his body weight decreased. Unexpectedly, skin lesions of plaque psoriasis improved. PASI decreased by 19% compared with baseline and quality of life, assessed with the DLQI, markedly ameliorated. After 10 months, glycemic and obesity parameters, as well as psoriasis, improved further. HbA1c, BMI, and PASI were reduced by 32, 16.3, and 92%, respectively, compared with the baseline. DLQI declined to 0, meaning there was no effect of plaque psoriasis on the patient's life. LEARNING POINTS: Psoriasis in patients with type 2 diabetes is often resistant to therapy. We observed an obese patient with type 2 diabetes mellitus who achieved glycemic control and weight loss with the addition of semaglutide to metformin and had a relevant and long-lasting improvement of plaque psoriasis, which was previously resistant to biologic therapy. Therapy with semaglutide may be attempted in eligible patients with difficult to treat plaque psoriasis.

Subacute thyroiditis in a patient infected with SARS-COV-2: an endocrine complication linked to the COVID-19 pandemic.

PURPOSE: Subacute thyroiditis (SAT) is an inflammatory thyroid disorder of viral origin, generally preceded by an upper respiratory tract infection. Since the disorder is self-limiting, it is frequently underdiagnosed. However, the disease should not be overlooked since the associated thyrotoxicosis may worsen the clinical course of concomitant disorders (e.g., respiratory distress) and long-term sequelae, such as autoimmune hypothyroidism, have been reported. METHODS: Here we describe a woman who developed SAT with thyrotoxicosis after SARS-COV-2 infection. Coronavirus disease (COVID-19) symptoms were mild and the patient was managed with no specific treatment and recovered rapidly. RESULTS: Six weeks after the onset of the upper respiratory tract infection, the patient developed pain and tenderness in the anterior cervical region, fatigue, tremors, and palpitations. Physical examination revealed mild tremors of the extremities, a diffuse and painful goiter, and enlarged and tender cervical and submandibular lymph nodes. At biochemical evaluation, TSH was suppressed, FT3 and FT4 were high, and serum thyroglobulin was markedly increased (188 pg/mL; n.v. 0-40). Thyroid scintigraphy showed markedly reduced 99mTc-perthecnetate uptake in the gland. All findings were consistent with SAT, and treatment with oral prednisone (25 mg/day as the starting dose, gradually tapered) was started. Under the corticosteroid therapy, there was progressive resolution of symptoms and signs, and, within 4 weeks, all thyroid functional tests and inflammatory indexes normalized. CONCLUSION: Clinicians should be aware of thyroid manifestations potentially associated with COVID-19.

Challenges in the treatment of parathyroid carcinoma: a case report.

INTRODUCTION: Parathyroid carcinoma (PC) is a rare neoplasm with a high rate of recurrence and an indolent course. It is frequently functional, causing nearly 1% of the cases of primary hyperparathyroidism (HPT), and in some cases, it may be complicated by brown tumors, mimicking bone metastases. Synchronous parathyroid and papillary thyroid carcinomas are rare. CASE REPORT: We present a patient with HPT due to PC, misdiagnosed at first evaluation, which exhibited multiple hypermetabolic lytic lesions in the skeleton, suggesting bone metastases. Their regression after PTH reduction suggested the diagnosis of brown tumors due to severe HPT. Given the persistence of HPT, the patient underwent a number of neck surgeries, and a papillary thyroid microcarcinoma with a nodal metastasis was diagnosed. A genetic test discovered a previously unreported mutation of the CDC73 (HRPT2) gene, codifying for parafibromin and resulting in a premature stop codon (c.580A>Tp.Arg194). Because of the persistence of HPT, cinacalcet therapy was started in order to control hypercalcemia. CONCLUSION: This is a very unusual patient with a newly discovered variant of the CDC73 gene and a phenotype characterized by recurrent PC, brown tumors, and N1a metastasized thyroid carcinoma. The present case confirms that PC may not exhibit clear malignant properties at first assessment, contributing to inadequate initial surgical treatment. Although infrequently, PC can be associated with papillary thyroid cancer. The diagnosis of brown tumor should be considered in patients with severe HPT and multiple destructive bone lesions mimicking metastases on PET/CT imaging.

Efficacy of Botulinum Toxin A for Treating Cramps in Diabetic Neuropathy.

OBJECTIVE: Muscle cramps occur in >50% of diabetic patients and reduce the quality of life. No effective treatment is available. We evaluated the clinical effectiveness of botulinum toxin A (BTX-A) injections for treating cramps in diabetic patients with neuropathy. METHODS: This single-center, double-blind, placebo-controlled perspective study investigated the efficacy and safety of BTX-A intramuscular injection for treating calf or foot cramps refractory to common pharmacological drugs. Fifty diabetic patients with peripheral neuropathy and cramps were randomly assigned to 2 matched groups. BTX-A (100 or 30 units) or saline was injected on each side into the gastrocnemius or the small flexor foot muscles. Changes in pain intensity (primary outcome) and cramp frequency were evaluated over the course of 20 weeks after BTX-A administration. Cramp interference in daily life and the electrophysiological cramp threshold frequency were also measured. The treatment was repeated 5 months after first injection in 19 responders. RESULTS: All outcome measures improved significantly after BTX-A compared with placebo. The changes with respect to baseline were already significant after 1 week and persisted up to week 14. Only 5 of 25 (20%) patients were nonresponders (<50% decrease of the primary outcome). The responses to a second BTX-A injection provided results similar to the first administration. Mild pain at the injection site (4/25 cases) was the only adverse event, and it disappeared within 2 to 3 days. INTERPRETATION: Local BTX-A infiltration is an efficacious and safe procedure for obtaining a sustained amelioration of muscle cramps associated with diabetic neuropathy. Ann Neurol 2018;84:682-690.

Seasonal variations in TSH serum levels in athyreotic patients under L-thyroxine replacement monotherapy.

BACKGROUND: Whether serum TSH undergoes seasonal fluctuations in euthyroid and hypothyroid residents of temperate climates is controversial. METHODS: Monthly TSH and thyroid hormone levels were cross-sectionally analysed in a large cohort of euthyroid subjects (n=11 806) and L-thyroxine (L-T4)-treated athyreotic patients (n=3 934). Moreover, in a small group (n=119) of athyreotic patients treated with an unchanged dosage of L-T4 monotherapy, hormones were measured both in the coldest and in the hottest seasons of the same year (longitudinal study). RESULTS: No seasonal hormone change was observed in the euthyroid subjects except for a small FT3 increase in winter (+2.9%, P<.001). In contrast, the L-T4-treated athyreotic patients had significantly higher serum TSH values in the cold season when the FT4 values were significantly lower. The differences were more notable in the longitudinal series (TSH, 0.80 vs. 0.20 mU/L and FT4, 16.3 vs. 17.8 pmol/L in December-March vs. June-September, respectively). In these patients also serum FT3 values significantly decreased in winter (in the longitudinal series, 3.80 in winter vs 4.07 pmol/L in summer). Regression analysis showed that in athyreotic subjects, a greater FT4 change is required to obtain a TSH change similar to that of euthyroid controls and that this effect is more pronounced in the summer. CONCLUSION: Athyreotic patients undergoing L-T4 monotherapy have abnormal seasonal variations in TSH. These changes are secondary to the FT4 and FT3 serum decreases in winter, which occur in spite of the constant treatment. The underlying mechanisms are unclear, but in some cases, these changes may be clinically relevant.

Mitotane treatment in patients with adrenocortical cancer causes central hypothyroidism.

INTRODUCTION: Mitotane, a steroidogenesis inhibitor with adrenolytic properties used to treat adrenocortical cancer (ACC), can affect thyroid function. A reduction of FT4 levels with normal FT3 and TSH has been described in these patients. Using an in vitro murine model, the secretory capacity of thyrotrophic cells has been shown to be inhibited by mitotane. OBJECTIVE: To investigate the pathogenesis of thyroid abnormalities in mitotane-treated patients with ACC. PATIENTS AND METHODS: In five female patients with ACC (median age 47; range 31-65) treated with mitotane (dosage 1·5 g/day; 1·0-3·0), we analysed the pattern of TSH and thyroid function index (FT4, FT3 and FT3/FT4 ratio) compared to an age- and gender-matched control group. The in vivo secretory activity of the thyrotrophic cells was evaluated using a standard TRH test (200 µg), and the response was compared to both a group of age-matched female controls (n = 10) and central hypothyroid patients (n = 10). RESULTS: Basal TSH (median 1·54 mU/l; range 1·20-2·17) was normal and scattered around our median reference value, FT3 levels (median 3·80 pmol/l; 3·30-4·29) were normal but below the median reference value of 4·37 pmol/l and FT4 levels were below the normal range in all patients (median 8·40 pmol/l; 7·6-9·9). FT3/FT4 ratio was in the upper range in 4 patients and higher than normal in one patient. A blunted TSH response to TRH was observed in mitotane-treated patients. ΔTSH (absolute TSH response, peak TSH minus basal TSH) was 3·65 (range 3·53-5·26), 12·37 (range 7·55-19·97) and 1·32 mU/l (range 0·52-4·66) in mitotane-treated patients, controls and central hypothyroid patients, respectively. PRL secretion was normal. CONCLUSIONS: Mitotane-treated patients with ACC showed low FT4, normal FT3 and TSH and impaired TSH response to TRH, characteristic of central hypothyroidism. Furthermore, the elevated FT3/FT4 ratio of these subjects reflects an enhanced T4 to T3 conversion rate, a compensatory mechanism characteristic of thyroid function changes observed in hypothyroid conditions. This finding thus confirms in vitro studies and may have a therapeutic implication for treatment with thyroid hormones, as suggested by current guidelines for this specific condition.

Chronic lymphocytic thyroiditis: could it be influenced by a petrochemical complex? Data from a cytological study in South-Eastern Sicily.

INTRODUCTION: In genetically predisposed individuals, exogenous factors (including pollution) influence the development of Hashimoto's thyroiditis/chronic lymphocytic thyroiditis (CLT). CLT may also be a risk factor for associated thyroid cancer. Few data are available on the role of pollution from petrochemical complexes, one of which is located in the Siracusa province (South-Eastern Sicily), in the pathogenesis of CLT. AIMS: i) To study the frequency of CLT in fine-needle aspiration cytology (FNAC)-interrogated thyroid nodules from patients who were stably resident in their zones, comparing it in patients living in the petrochemical complex area (zone A) with that of patients from a control area (zone B). ii) To study the frequency of CLT in the FNAC categories of malignancy risk, comparing the two zones. PATIENTS AND METHODS: We retrospectively evaluated cytologically adequate slides of 1323 nodules in 1013 outpatients who underwent ultrasound-guided FNAC from 2006 to 2012. We stratified by area of residence, gender, and FNAC categories of malignancy risk. RESULTS: CLT was detected with significantly greater frequency in either patients or nodules from zone A compared with zone B (32.0% vs 23.1%, P=0.002 or 28.2% vs 18.8%, P=0.0001), with a female preponderance (F=35.2% vs M=21.1% or 30.4% vs 20.4%, zone A and F=26.5% vs 12.3% or 21.6% vs 9.5%, zone B). Regardless of zone, CLT was approximately twofold more frequent in the suspiciously malignant+malignant classes (TH4+THY5=47.6%, zone A and 32.4%, zone B) compared with the benign+intermediate classes (THY2+THY3=27.3%, zone A and 18.2%, zone B), but with a clear stepwise THY2 through THY5 increase only in zone A (THY2=25.3%, THY5=66.7%; THY2=18.6%, THY5=28.6% in zone B). CONCLUSIONS: The petrochemical complex-related pollution is an environmental factor involved in the development of CLT and, likely, in the CLT association with thyroid neoplasms.

Insulin autoimmune syndrome (Hirata Disease) in European Caucasians taking α-lipoic acid.

OBJECTIVE: Lipoic acid (LA) is a widely used nutritional supplement and is sometimes used as an adjuvant treatment for diabetic neuropathy and other conditions. Insulin autoimmune syndrome (IAS, Hirata disease) is a rare cause of spontaneous hypoglycaemia, extremely high serum insulin levels and high titres of autoantibodies against endogenous insulin despite no prior exposure to exogenous insulin. In Japanese individuals, IAS is associated with the human leucocyte antigen (HLA) HLA-DRB1*04:06 allele and often occurs upon exposure to sulphhydryl-containing compounds including LA. Only one case has been reported in Caucasians. We now report six Caucasian patients taking LA with IAS and describe a unique HLA subtype in these patients. RESEARCH DESIGN AND METHODS: Six Caucasian patients (M = 3; F = 3), median age 63 years, presented with spontaneous episodes of fasting and postabsorptive hypoglycaemia associated with mainly neuroglycopenic symptoms. No patient was treated with insulin or had an insulinoma. Hypoglycaemic symptoms appeared 30 and 120 days after taking lipoic acid (LA; 600 mg/day). Case histories and standard laboratory analyses were utilized. RESULTS: Discontinuation of LA resulted in a reduction in hypoglycaemic episodes. All patients were treated with oral or iv glucose and prednisone (12.5-25 mg/day). HLA analysis revealed the HLA-DRB1*04:03 allele in five patients, while the HLA-DRB1*04:06 allele was present in one patient. CONCLUSIONS: This is the first report of LA-related IAS in Caucasians who possess the HLA-DRB1*04:03 allele, implicating this allele in the genetic susceptibility to IAS in Caucasians. The greater occurrence of the HLA-DRB1*04:03 allele in Caucasian and other populations, combined with the growing use of LA in developed countries, may be a future predictor of additional cases of IAS.

Hashimoto's thyroiditis: similar and dissimilar characteristics in neighboring areas. Possible implications for the epidemiology of thyroid cancer.

CONTEXT: Medical centers worldwide report an increased frequency of Hashimoto's thyroiditis (HT) and thyroid cancer (TC), two environmentally influenced diseases. In Sicily, data on HT are available for the province of Messina (1975-2005); data on TC are available for the whole island (2002-2004), with the volcanic province of Catania having the highest incidence. OBJECTIVE: To replicate in Catania, on comparable years, the HT data of Messina. DESIGN METHODS SETTING: Review of the clinical records of patients in years 1995-2005 to compare presentation and yearly changes of HT. During 1995-2005, records were computer stored in the Endocrine Divisions of the University Hospitals of Catania and Messina, two tertiary referral centers. RESULTS: Catania is outnumbered by Messina (742 vs. 3,409 HT patients). Similar were the linear increase in the yearly number of HT patients, rates of thyroid dysfunctions though with different proportions of subclinical and overt hypothyroidism, and rates of positiveness for TgAb or TPOAb. Different were age and its yearly trend; gender distribution and rates of the sonography variants, though yearly trends were similar. CONCLUSION: The HT epidemics is smaller in Catania, with changes in presentation overlapping partially those in Messina. Whatever environmental factors might be involved, they (and/or their intensity) were not necessarily the same in these provinces. Intriguingly, the expected number of TC in HT patients with thyroid nodules in Catania is congruent with that of the general population of this province, but it is far less than in the Messina province. Thus, TC and HT incidences could be influenced by distinct environmental factors.

Levothyroxine monotherapy cannot guarantee euthyroidism in all athyreotic patients.

CONTEXT: Levothyroxine monotherapy is the treatment of choice for hypothyroid patients because peripheral T4 to T3 conversion is believed to account for the overall tissue requirement for thyroid hormones. However, there are indirect evidences that this may not be the case in all patients. OBJECTIVE: To evaluate in a large series of athyreotic patients whether levothyroxine monotherapy can normalize serum thyroid hormones and thyroid-pituitary feedback. DESIGN: Retrospective study. SETTING: Academic hospital. PATIENTS: 1,811 athyreotic patients with normal TSH levels under levothyroxine monotherapy and 3,875 euthyroid controls. MEASUREMENTS: TSH, FT4 and FT3 concentrations by immunoassays. RESULTS: FT4 levels were significantly higher and FT3 levels were significantly lower (p<0.001 in both cases) in levothyroxine-treated athyreotic patients than in matched euthyroid controls. Among the levothyroxine-treated patients 15.2% had lower serum FT3 and 7.2% had higher serum FT4 compared to euthyroid controls. A wide range of FT3/FT4 ratios indicated a major heterogeneity in the peripheral T3 production capacity in different individuals. The correlation between thyroid hormones and serum TSH levels indicated an abnormal feedback mechanism in levothyroxine-treated patients. CONCLUSIONS: Athyreotic patients have a highly heterogeneous T3 production capacity from orally administered levothyroxine. More than 20% of these patients, despite normal TSH levels, do not maintain FT3 or FT4 values in the reference range, reflecting the inadequacy of peripheral deiodination to compensate for the absent T3 secretion. The long-term effects of chronic tissue exposure to abnormal T3/T4 ratio are unknown but a sensitive marker of target organ response to thyroid hormones (serum TSH) suggests that this condition causes an abnormal pituitary response. A more physiological treatment than levothyroxine monotherapy may be required in some hypothyroid patients.

Botulinum toxin treatment for oropharyngeal dysphagia associated with diabetic neuropathy.

OBJECTIVE: No specific treatment for oropharyngeal dysphagia related to diabetic neuropathy has been described to date. Chemical myotomy of the cricopharyngeus (CP) muscle by botulinum neurotoxin type A (BoNT/A) has been effective in reducing or abolishing dysphagia associated with upper esophageal sphincter (UES) hyperactivity of different etiologies. In the present study, we evaluated the efficacy of BoNT/A injections into the CP muscle in diabetic patients with severe oropharyngeal dysphagia associated with diabetic autonomic and/or somatic peripheral neuropathy. RESEARCH DESIGN AND METHODS: Twelve type 2 diabetic patients with severe dysphagia for both solid and liquid foods associated with autonomic and/or peripheral somatic neuropathy were investigated. Swallowing function was evaluated by clinical examination, videofluoroscopy, and simultaneous needle electromyography (EMG) of the CP and pharyngeal inferior constrictor (IC) muscles. Clinical evaluation using a four-level dysphagia severity score was performed every other day for the 1st week and thereafter every other week until week 24. Videofluoroscopy and EMG follow-up were carried out at week 1, 4, 12, 16, 18, and 24 after BoNT/A injection. BoNT/A was injected percutaneously into the CP muscle under EMG control. RESULTS: BoNT/A induced the complete recovery of dysphagia in 10 patients and had a significant (P = 0.0001, ANOVA) improvement in 2 patients within 4 +/- 1.1 days (range 3-7). Clinical improvement was confirmed by videofluoroscopy and EMG. CONCLUSIONS: Our findings suggest a potential benefit from BoNT/A treatment in dysphagia associated with diabetic neuropathy. Randomized controlled trials are needed to confirm this observation.