Pituitary MRI Features in Acromegaly Resulting From Ectopic GHRH Secretion From a Neuroendocrine Tumor: Analysis of 30 Cases.

CONTEXT: Ectopic acromegaly is a consequence of rare neuroendocrine tumors (NETs) that secrete GHRH. This abnormal GHRH secretion drives GH and IGF-1 excess, with a clinical presentation similar to classical pituitary acromegaly. Identifying the underlying cause for the GH hypersecretion in the setting of ectopic GHRH excess is, however, essential for proper management both of acromegaly and the NET. Owing to the rarity of NETs, the imaging characteristics of the pituitary in ectopic acromegaly have not been analyzed in depth in a large series. OBJECTIVE: Characterize pituitary magnetic resonance imaging (MRI) features at baseline and after NET treatment in patients with ectopic acromegaly. DESIGN: Multicenter, international, retrospective. SETTING: Tertiary referral pituitary centers. PATIENTS: Thirty ectopic acromegaly patients having GHRH hypersecretion. INTERVENTION: None. MAIN OUTCOME MEASURE: MRI characteristics of pituitary gland, particularly T2-weighted signal. RESULTS: In 30 patients with ectopic GHRH-induced acromegaly, we found that most patients had hyperplastic pituitaries. Hyperplasia was usually moderate but was occasionally subtle, with only small volume increases compared with normal ranges for age and sex. T2-weighted signal was hypointense in most patients, especially in those with hyperplastic pituitaries. After treatment of the NET, pituitary size diminished and T2-weighted signal tended to normalize. CONCLUSIONS: This comprehensive study of pituitary MRI characteristics in ectopic acromegaly underlines the utility of performing T2-weighted sequences in the MRI evaluation of patients with acromegaly as an additional tool that can help to establish the correct diagnosis.

Evaluation of a perioperative steroid coverage after pituitary surgery.

INTRODUCTION: Serum cortisol levels within the first days after pituitary surgery have been shown to be a predictor of post-surgical adrenal insufficiency. However, the indication of empirical glucocorticoids to avoid this complication remains controversial. The objective is to assess the role of cortisol in the early postoperative period as a predictor of long-term corticotropic function according to the pituitary perisurgical protocol with corticosteroid replacement followed in our center. METHODS: One hundred eighteen patients who underwent surgery in a single center between December 2012 and January 2020 for a pituitary adenoma were included. Of these, 54 patients with previous adrenal insufficiency (AI), Cushing's disease, or tumors that required treatment with high-dose glucocorticoids (GC) were excluded. A treatment protocol with glucocorticoids was established, consisting of its empirical administration at rapidly decreasing doses, and serum cortisol was determined on the third day after surgery. Subsequent adrenal status was assessed through follow-up biochemical and clinical evaluations. RESULTS: Out of the 64 patients treated, there were 56 macroadenomas and 8 microadenomas. The incidence of adrenal insufficiency after pituitary surgery was 4.7%. The optimal cut-off value that predicted an adequate corticotropic reserve, taking into account the best relationship of specificity and sensitivity, was ≥4.1 µg/dl for serum cortisol on the third day (sensitivity 95.1%, specificity 100%). CONCLUSION: Serum cortisol on the third day predicts the development of adrenal insufficiency. We suggest a cortisol cut-off point of ≥4.1 µg/dl on postoperative on the third day after surgery as a predictor of the adrenal reserve in the long-term.

Clinical characteristics and prognosis of familial nonmedullary thyroid carcinoma.

INTRODUCTION: Familial non-medullary thyroid carcinoma (FNMTC) is defined by the presence of 2 or more first-degree family members with differentiated thyroid carcinoma (DTC). The aim of this study is to compare clinicopathological features and prognosis of FNMTC and sporadic carcinoma (SC). MATERIALS AND METHODS: Retrospective study of DTC included in the hospital database during the period 1990-2018. RESULTS: A total of 927 patients were analyzed, 61 of them were FNMTC, with a mean follow-up of 9.7 ±â€¯6.5 years. The prevalence of FNMTC was 6.6%, with a lower TNM staging presentation (P = 0.003) consequence of a higher proportion of tumors smaller than 2 cm (P = 0.003), combined with a greater multifocality (P = 0.034) and papillary histologic subtype (P = 0.022) compared to SC. No significant differences in age at diagnosis (P = 0.347), gender (P = 0.406), neither in other aggressiveness markers (bilaterality, extrathyroidal extension, lymph node involvement and metástasis) were detected. Rate of persistence/recurrence (P = 0.656), disease-free survival (P = 0.929) and mortality caused by the tumor itself (P = 0.666) were comparable. Families with ≥3 affected relatives, had smaller tumors (P = 0.005), more multifocality (P = 0.040) and bilaterality (P = 0.002), as well as a higher proportion of males (P = 0.020). Second generation patients present earlier FNMTC compared to those of the first generation (P = 0.001). CONCLUSION: In our study FNMTC presents a lower TNM staging, higher multifocality and papillary variant, with similar aggressiveness and prognosis compared to SC.

Thyroid disorders associated with immune control point inhibitors.

INTRODUCTION: Immune checkpoint inhibitors (ICPI) have improved progression-free survival in several solid tumors. Side effects are related to overstimulation of the immune system. Thyroid dysfunction (TD) is the most common endocrine immune-related adverse event of ICPI. OBJECTIVE: To describe the clinical presentation and the course of TD in cancer patients treated with ICPI referred to an endocrinology outpatient clinic. MATERIAL AND METHODS: This was a descriptive, retrospective and multicenter study of patients with TD associated with ICPI in six Spanish hospitals. RESULTS: 120 patients (50.8% women), mean age 60 ±â€¯12 years were included. The initial TD was hypothyroidism in 49% of patients and hyperthyroidism in 51%, with an average of 76 (41-140) and 43 (26-82) days respectively between the onset of ICPI and the analytical alteration. Significantly, the earlier the first analytical determination was, the greater the prevalence of hyperthyroidism. A turnover was observed in 80% of subjects during follow-up, mostly from hyperthyroidism to hypothyroidism. Twenty-one percent received double ICPI therapy. The most frequent form of presentation in monotherapy was hypothyroidism (57%), and in double therapy it was hyperthyroidism (77%) (p = 0.002). Patients under double therapy showed thyroid alterations earlier than those in the monotherapy group (p = 0.001). After a follow-up of 205 (112-360) days, half of the patients continued under levothyroxine treatment. CONCLUSIONS: Hypothyroidism and hyperthyroidism present in a similar proportion in cancer patients undergoing ICPI therapy. Our results suggest that transitory hyperthyroidism may not be detected in a relevant number of cases. In addition, TD in double therapy presents earlier. This should be taken into account in the follow-up protocols of these patients.

Clinical characteristics and prognosis of familial nonmedullary thyroid carcinoma. / Características clínicas y pronósticas del carcinoma familiar de tiroides no medular.

INTRODUCTION: Familial non-medullary thyroid carcinoma (FNMTC) is defined by the presence of 2or more first-degree family members with differentiated thyroid carcinoma (DTC). The aim of this study is to compare clinicopathological features and prognosis of FNMTC and sporadic carcinoma (SC). MATERIALS AND METHODS: Retrospective study of DTC included in the hospital database during the period 1990-2018. RESULTS: A total of 927 patients were analyzed, 61 of them were FNMTC, with a mean follow-up of 9.7±6.5 years. The prevalence of FNMTC was 6.6%, with a lower TNM staging presentation (P=.003) consequence of a higher proportion of tumors smaller than 2 centimeters (P=.003), combined with a greater multifocality (P=.034) and papillary histologic subtype (P=.022) compared to SC. No significant differences in age at diagnosis (P=.347), gender (P=.406), neither in other aggressiveness markers (bilaterality, extrathyroidal extension, lymph node involvement and metástasis) were detected. Rate of persistence/recurrence (P=.656), disease-free survival (P=.929) and mortality caused by the tumor itself (P=.666) were comparable. Families with ≥3 affected relatives, had smaller tumors (P=.005), more multifocality (P=.040) and bilaterality (P=.002), as well as a higher proportion of males (P=.020). Second generation patients present earlier FNMTC compared to those of the first generation (P=.001). CONCLUSION: In our study FNMTC presents a lower TNM staging, higher multifocality and papillary variant, with similar aggressiveness and prognosis compared to SC.

The extent of surgery for low-risk 1-4 cm papillary thyroid carcinoma: a catch-22 situation. A retrospective analysis of 497 patients based on the 2015 ATA Guidelines recommendation 35.

PURPOSE: The adequate extent of surgery for 1-4 cm low-risk papillary thyroid carcinoma (PTC) is unclear. Our objective was to analyze the applicability of the 2015 ATA Guidelines recommendation 35B (R35) for the management low-risk PTC. METHODS: This multicentre study included patients with low-risk PTC who had undergone total thyroidectomy (TT). Retrospectively we selected those who met the R35 criteria for the performance of a thyroid lobectomy (TL). The aim was to identify the proportion of low-risk PTC patients treated using TT who would have required reintervention had they had a TL in accordance with R35. RESULTS: We identified 497 patients (400 female; 80.5%). Median tumor size (mm): 21.2 (11-40). A tumor size ≥2 cm was found in 252 (50.7%). Most of them, 320 (64.4%), were in Stage I (AJCC 7th Edition). Following R35, 286 (57.5%) would have needed TT. Thus, they would have required a second surgery had they undergone TL. The indications for reintervention would have included lymph node involvement (35%), extrathyroidal extension (22.9%), aggressive subtype (8%), or vascular invasion (22.5%). No presurgical clinical data predict TT. CONCLUSIONS: The appropriate management of low-risk PTC is unclear. Adherence to ATA R35 could lead to a huge increase in reinterventions when a TL is performed, though the need for them would be questionable. In our sample, more than half of patients (57.5%) who may undergo a TL for a seemingly low-risk PTC would have required a second operation to satisfy international guidelines, until better preoperative diagnostic tools become available.

Comparison of clinical characteristics of patients with follicular thyroid carcinoma and Hürthle cell carcinoma. / Comparación de las características clínicas en pacientes con carcinoma folicular de tiroides y carcinoma de células de Hürthle.

INTRODUCTION: Hürthle cell carcinoma (HCC) is an uncommon thyroid cancer historically considered to be a variant of follicular thyroid carcinoma (FTC). The aim of this study was to assess the differences between these groups in terms of clinical factors and prognoses. PATIENTS AND METHODS: A total of 230 patients (153 with FTC and 77 with HCC) with a median follow-up of 13.4 years were studied. The different characteristics were compared using SPSS version 20 statistical software. RESULTS: Patients with HCC were older (57.3±13.8 years vs. 44.6±15.2 years; P<.001). More advanced TNM stages were also seen in patients with HCC and a greater trend to distant metastases were also seen in patients with HCC (7.8% vs. 2.7%, P=.078). The persistence/recurrence rate at the end of follow-up was higher in patients with HCC (13% vs. 3.9%, P=.011). However, in a multivariate analysis, only age (hazard ratio [HR] 1.10, confidence interval [CI] 1.04-1.17; P=.001), size (HR 1.43, CI 1.05-1.94; P=.021), and histological subtype (HR 9.79, CI 2.35-40.81; P=.002), but not presence of HCC, were significantly associated to prognosis. CONCLUSION: HCC is diagnosed in older patients and in more advanced stages as compared to FTC. However, when age, size, and histological subtype are similar, disease-free survival is also similar in both groups.

Increased incidence of thyroid cancer in Navarra (Spain). Evolution and clinical characteristics, 1986-2010. / Aumento de la incidencia de cáncer de tiroides en Navarra. Evolución y características clínicas, 1986-2010.

INTRODUCTION: The latest published studies show an increased incidence of thyroid cancer worldwide. The aim of this study was to analyze the changes in the incidence of thyroid cancer in Navarra and its clinical presentation regarding sex, histological subtype and size over the last 25 years. METHODS: Thyroid cancer incidence rates were calculated on the basis of data from the Cancer Registry of Navarra during 1986-2010. Clinical data were obtained from the historical cohort of the Hospital Registry of Cancer of Navarra, which includes all the new cases of differentiated thyroid carcinoma diagnosed and treated in the public health network of this Community in that period. RESULTS: The overall incidence of thyroid cancer in Navarra increased over the last 25 years, with an increase in the adjusted rate in men from 2.24 (1986-1990) to 5.85 (2006-2010) per 100,000 population/year (P<.001) and in women from 9.05 to 14.04, respectively (P<.001). This increase occurs only in papillary carcinoma. The clinical characteristics of 739 patients with differentiated thyroid cancer were studied. The mean age at diagnosis increased over the years and the predominance of women (about 80%) remains stable. Mean tumor size decreased over the five-year periods from 30.9 to 22.5mm (P<.001), the proportion of microcarcinomas (T1a) increased from 8.8% to 30% (P<.001) and, despite this increase, there were no statistical differences in the TNM stage at diagnosis during the study period. The distribution of histological variants of papillary and follicular carcinoma did not change over 25 years. CONCLUSIONS: During the period studied, the incidence of thyroid cancer increased in Navarra in both sexes. The increase occurred only in papillary carcinoma, without changes in the distribution of his histological variants. The increase in the proportion of T1a tumors is remarkable, but the TNM stage distribution was maintained. These results suggest an increase in the diagnosis of thyroid microcarcinomas due to changes in clinical practice, without ruling out a real increase in the incidence of papillary carcinoma in Navarra.

An unusual association: pheochromocytoma on an atrophied adrenal gland due to addison's disease.

Autoimmune polyendocrine syndrome type II (APS-II) is the most common immunoendocrinopathy syndrome. APS-II is defined by the development of two or more of the following entities: primary adrenal insufficiency (Addison's disease), Graves' disease, type 1A diabetes mellitus, autoimmune thyroiditis, primary hypogonadism, celiac disease, and myasthenia gravis. Other frequent clinical findings are vitiligo, alopecia, pernicious anemia and/or serositis. Primary adrenal insufficiency in these patients affects the adrenal cortex, which is destroyed by autoantibodies against 21-hydroxylase. Unlike other causes of adrenal insufficiency (infectious diseases, infiltrative diseases, bleeding, tumors), the adrenal medulla is not involved. Pheochromocytomas are tumors arising from the chromaffin cells of the sympathetic nervous system in the adrenal medulla. The clinical symptoms of these tumors vary from isolated hypertension or hypertension accompanied by paroxysmal episodes -including the classical triad of headache, palpitations and diaphoresis-to potentially serious manifestations such as acute pulmonary edema, arrhythmias and sudden death. Nevertheless, up to 40% of affected patients are asymptomatic. We present the case of a patient diagnosed with APS-II who developed a pheochromocytoma. In this patient, the adrenal gland cortex was atrophied and the tumor was attached to the adrenal medulla. This coexistence of endocrinopathies, with no etiologic connection, is a surprising finding, which has not previously been described in the current literature.