Diagnosis of 17-alpha hydroxylase deficiency performed late in life in a patient with a 46,XY karyotype.

Summary: 17-Alpha-hydroxylase deficiency (17OHD) is a rare autosomal recessive disease, representing 1% of cases of congenital adrenal hyperplasia. A 44-year-old female presented to the emergency department complaining of generalized asthenia and polyarthralgia for about 2 weeks. On examination, she was hypertensive (174/100 mmHg), and laboratory results revealed hypokalemia and hypocortisolism. She had an uncharacteristic morphotype, BMI of 16.7 kg/m2, cutaneous hyperpigmentation, and Tanner stage M1P1, with normal female external genitalia. She reported to have primary amenorrhea. Further analytical evaluations of her hormone levels were performed CT scan revealed adrenal bilateral hyperplasia and absence of female internal genitalia. A nodular lesion was observed in the left inguinal canal with 25 × 10 mm, compatible with a testicular remnant. Genetic analysis identified the c.3G>A p.(Met1?) variant in homozygosity in the CYP17A1 gene, classified as pathogenic, confirming the diagnosis of 17OHD. Karyotype analysis was compatible with 46,XY. The association of severe hypokalemia, hypertension, hypocortisolism, and oligo/amenorrhea and the absence of secondary sexual characteristics favored the diagnosis of 17OHD, confirmed by genetic testing. As in other published clinical cases, diagnosis outside pediatric age is not rare and should be considered when severe hypokalemia occurs in hypertensive adults with a lack of secondary sexual characteristics. Learning points: The association of severe hypokalemia, hypertension, hypocortisolism, and oligo/amenorrhea and the absence of secondary sexual characteristics favor the diagnosis of 17-alpha-hydroxylase deficiency (17OHD). Diagnosis outside pediatric age is not rare. 17OHD should be considered when severe hypokalemia occurs in hypertensive adults with a lack of secondary sexual characteristics.

Adrenal Vein Sampling in the Management of Primary Aldosteronism: The Added Value of Intraprocedural Cortisol Assessment.

Introduction: Primary aldosteronism is the most common cause of secondary hypertension. Adrenal vein sampling is the gold standard for subtyping primary aldosteronism. However, this procedure is technically challenging and often has a low success rate. Our center is one of the very few performing this technique in our country with an increasing experience. Objective: The aim of this study was to evaluate the role of the cortisol intraprocedural assay in improving the performance of adrenal vein sampling. Design: We enrolled all of the patients with primary aldosteronism that underwent adrenal vein sampling from February 2016 to April 2023. The cortisol intraprocedural assay was introduced in October 2021. Methods: We enrolled a total of 50 adrenal vein samplings performed on 43 patients with the diagnosis of primary aldosteronism. In this sample, 19 patients and 24 patients underwent adrenal vein sampling before and after intraprocedural cortisol measurement, respectively. The procedure was repeated in seven patients (one before and six after intraprocedural cortisol measurement), given the unsuccess of the first exam. Selectivity of the adrenal vein sampling was assumed if the serum cortisol concentration from the adrenal vein was at least five times higher than that of the inferior vena cava. Lateralization was assumed if the aldosterone to cortisol ratio of one adrenal vein was at least four times the aldosterone to cortisol ratio of the contralateral side. Results: The mean age of the patients that underwent adrenal vein sampling (N = 43) was 55.2 ± 8.9 years, and 53.5% (n = 23) were female. The mean interval between the diagnosis of hypertension and the diagnosis of primary aldosteronism was 9.8 years (±9.9). At diagnosis, 62.8% of the patients (n = 27) had hypokalemia (mean value of 3 mmol/L (±0.34)), 88.4% (n = 38) had adrenal abnormalities on preprocedural CT scan, and 67.4% (n = 29) described as unilateral nodules. There were no statistically significant differences in the patients' baseline characteristics between the two groups (before and after intraprocedural cortisol measurement). Before intraprocedural cortisol measurement, adrenal vein sampling selectivity was achieved in 35% (n = 7) patients. Selectivity increased to 100% (30/30) after intraprocedural cortisol measurement (p < 0.001). With the exception of one patient who refused it, all patients with lateralized disease underwent unilateral adrenalectomy with normalization of the aldosterone to renin ratio postoperatively. Conclusions: The lack of effective alternatives in subtyping primary aldosteronism highlights the need to improve the success rate of adrenal vein sampling. In this study, intraprocedural cortisol measurement allowed a selectivity of 100%. Its addition to this procedure protocol should be considered, especially in centers with a low success rate.

The Role of the Metabolome and Non-Coding RNA on Pheochromocytomas and Paragangliomas: An Update.

Pheochromocytoma and paragangliomas (PPGL) are rare neuroendocrine tumors. In some patients they exhibit malignant behavior characterized by the presence of metastases, limiting treatment options and survival rates. Therapeutic options are limited to surgery, localized radiotherapy, and a few systemic therapies. However, in several recent studies, non-coding RNA molecules are gaining increasing attention as markers of malignancy for PPGL. The understanding of PPGL development molecular mechanisms has improved in the last years, with some of the epigenetic regulatory mechanisms such as DNA and histones methylation, being better understood than RNA-based mechanisms. Metabolome deregulation in PPGL, with increased synthesis of molecules that facilitated tumor growth, results from the activation of hypoxia signaling pathways, affecting tumorigenesis. In addition, the assessment of these metabolites can be useful for the management of these tumors. This review summarizes recent discoveries linking metabolome and non-coding RNA to PPGL and their relevance for diagnosis and therapeutics.

Central Diabetes Insipidus Following Immunization With BNT162b2 mRNA COVID-19 Vaccine: A Case Report.

Introduction: Cases of central diabetes insipidus (CDI) have been reported after COVID-19 infection, with hypophysitis being the most likely cause. COVID-19 vaccines potential adverse effects may mimetize some of these complications. Case Report: Woman 37 years old, with rheumatoid arthritis under adalimumab (40 mg twice a month) since December 2018. She was in her usual state of health when she has received the second dose of BNT162b2 mRNA COVID-19 vaccine (June 2021). Seven days later, she started reporting intense thirst and polyuria and consulted her family physician. Blood Analysis: creatinine 0.7 mg/dL, glucose 95mg/dL, Na+ 141mEq/L, K+ 3.9 mEq/L, TSH 3.8 mcUI/L (0.38-5.33), FT4 0.9 ng/dL (0.6-1.1), cortisol 215.4 nmol/L (185-624), ACTH 21.9 pg/mL (6- 48), FSH 4.76 UI/L, LH5.62 UI/L, estradiol 323 pmol/L, IGF1 74.8 ng/mL (88-209), PRL 24.7mcg/L (3.3-26.7) osmolality 298.2 mOs/Kg (250- 325); Urine analysis: volume 10200 mL/24h, osmolality 75 mOs/Kg (300-900), density 1.002. On water restriction test: 0' - Serum osmolality 308.8mOsm/Kg vs. urine osmolality 61.0 mOsm/Kg; 60' - urine osmolality 102 mOsm/Kg; urine osmolality 1 h after desmopressine was 511mOsm/kg. MRI revealed no abnormal signs consistent with hypophysitis except for the loss of the posterior pituitary bright spot on T1 weighted imaging. Diagnosis of CDI was assumed, and started therapy with desmopressine. A report of potential adverse effect was addressed to national health authorities. Conclusion: In hypophysitis MRI often shows loss of posterior pituitary bright spot on T1 weighted imaging, pituitary enlargement or stalk thickening but those findings were not present in this patient. To the best of our knowledge, CDI has never been reported following administration of a COVID-19 vaccine.

Clinical characteristics of polyglandular autoimmune syndromes in pediatric age: an observational study.

OBJECTIVES: Polyglandular autoimmune syndromes (PAS) are characterized by the association of two or more autoimmune diseases (AID) and are classified into four types. PAS type 1 is more frequently manifested in childhood, but the prevalence of other PAS in children, less described in the literature, seems to be underestimated. METHODS: This study aimed to evaluate the prevalence of PAS in a selected pediatric population of 879 children with Diabetes mellitus type 1 (DM1), autoimmune thyroid disease (AITD), and Addison's disease (AD) followed in our hospital for 10 years and describe and classify the manifestations of different PAS. RESULTS: We diagnosed 35 children with PAS, most fulfilled criteria for PAS type 3 (65.7%), and AITD was the AID more frequently detected (74.3%). PAS type 1 was not diagnosed in our sample. Patients with PAS manifested DM1 and AITD at a younger age than children with monoglandular pathology (7.7 vs. 9.3 years, p=0.04 and 7.7 vs. 13.1 years, p<0.01). CONCLUSIONS: This is the first study that analyzes the prevalence of different types of PAS in a pediatric population followed by endocrine pathologies, namely DM1, AD, and AITD. As PAS manifestations are often preceded by a long latency period characterized by the presence of autoantibodies, we reinforce the need to value these markers for timely diagnosis and to screen PAS in patients with AD throughout their lives.

Thyroid arterial embolization in a patient with congenital heart disease and refractory amiodarone-induced thyrotoxicosis.

Introduction: Amiodarone-induced thyrotoxicosis (AIT) can sometimes lead to life-threatening complications, especially in patients with congenital heart disease (CHD). We report the case of a patient with refractory AIT that was successfully treated with thyroid arterial embolization (TAE). Case report: A 34-year-old man with complex cyanotic CHD complicated with heart failure (HF), pulmonary hypertension, and supraventricular tachyarrhythmias, was treated with amiodarone since 2013. In March 2019, he presented worsening of his cardiac condition and symptoms of thyrotoxicosis that were confirmed by laboratory assessment. Thiamazole 30 mg/day and prednisolone 40 mg/day were prescribed, but the patient experienced worsening of his cardiac condition with several hospital admissions in the next 5 months, albeit increasing dosages of thionamide and glucocorticoid and introduction of cholestyramine and lithium. Thyroidectomy was excluded due to the severity of thyrotoxicosis, and plasmapheresis was contraindicated due to the cardiac condition. TAE of the four thyroid arteries was then performed with no immediate complications. Progressive clinical and analytical improvement ensued with gradual reduction and suspension of medication with the patient returning to euthyroid state and his usual cardiac condition previous to the AIT. Conclusion: For patients with medication refractoriness and whose condition precludes thyroidectomy, embolization of thyroid arteries may be an effective and safe option. Established facts: Amiodarone-induced thyrotoxicosis (AIT) can be refractory to a combination therapy of thionamides and glucocorticoids. Restoration of euthyroidism is of paramount importance in heart failure (HF) patients. Emergency thyroidectomy for AIT unresponsive to medical therapy is recommended in patients with severe underlying cardiac disease or deteriorating cardiac function. Novel insights: Thyroid arterial embolization (TAE) appeared as a salvage therapy in this patient. To the best of our knowledge, few case reports in the literature have described the embolization of the four thyroid arteries in AIT context. Endovascular embolization techniques are a valuable therapeutic option and can be considered in cases where standard forms of treatment are ineffective or involve unacceptable risks.

Does the Hyperglycemia Impact on COVID-19 Outcomes Depend upon the Presence of Diabetes?-An Observational Study.

Diabetes mellitus (DM) has emerged as a major risk factor for COVID-19 severity and SARS-CoV-2 infection can worsen glycemic control and may precipitate new-onset diabetes. At-admission hyperglycemia (AH) is a known predictor for worse outcomes in many diseases and seems to have a similar effect in COVID-19 patients. In this study, we aimed to assess the impact of AH regardless of pre-existing diabetes mellitus and new-onset diabetes diagnosis in the clinical severity of COVID-19 inpatients in the first months of the pandemic. A retrospective monocentric study on 374 COVID-19 inpatients (209 males) was developed to assess associations between AH (blood glucose levels in the Emergency Department or the first 24 h of hospitalization greater than 140 mg/dL) and severity outcomes (disease severity, respiratory support, admission to Intensive Care Unit (ICU) and mortality) in patients with and without diabetes. Considering diabetic patients with AH (N = 68;18.1%) there was a correlation with COVID-19 severity (p = 0.03), invasive mechanical ventilation (p = 0.008), and ICU admission (p = 0.026). No correlation was present with any severity outcomes in diabetic patients without AH (N = 33; 8.8%). All of the New-onset Diabetes patients (N = 15; 4%) had AH, and 12 had severe COVID-19; additionally, five patients were admitted to the ICU and three patients died. However, severity outcomes did not reach statistical correlation significance in this group. In nondiabetic patients with AH (N = 51; 13.6%), there was a statistically significant association with the need for oxygen therapy (p = 0.001), invasive mechanical ventilation (p = 0.01), and ICU admission (p = 0.03). Our results support data regarding the impact of AH on severity outcomes. It also suggests an effect of AH on the prognosis of COVID-19 inpatients, regardless of the presence of pre-existing diabetes or new-onset diabetes. We reinforce the importance to assess at admission glycemia in all patients admitted with COVID-19.

Pituitary metastasis as the first manifestation of lung carcinoma.

Pituitary metastases are rare. Clinical presentation could range from asymptomatic to panhypopituitarism or local symptoms. We present a case report of a 43-year-old male patient with a new onset headache, visual disturbances, and panhypopituitarism. The investigation led to the diagnosis of pituitary metastasis as the first manifestation of underlying lung cancer.