Gigantism: microsurgical treatment by transsphenoidal approach and prognostic factors.

PURPOSE: We present the results of transsphenoidal microsurgical treatment in 14 patients with gigantism. The influence on the prognosis of factors such as the tumor size and preoperative levels of GH and IGF-1 is also quantified. MATERIALS AND METHODS: The patients, operated between 1982 and 2004, were reviewed retrospectively in June 2022. All patients had complete endocrinological studies in the preoperative period and a postoperative control between 6 days and 3 weeks. Follow-up has been supported with annual check-ups between 3 and 31 years. We have compared the preoperative levels of GH and IGF-1 of these patients with the levels of a series of acromegalic patients operated on in the same Center. RESULTS: In this series there were 4 women and 10 men. The age ranged between 14 and 21 years. In 6 patients, postoperative hormone levels achieved the disease control criteria (42.8%). The CT/MRI studies revealed the existence of invasive tumors in 10 of the patients (71.4%). Postoperative CT/MRI showed no tumor tissue in 3 patients but in 7 patients there were tumor remains. The remaining 4 patients had abnormal images although not considered as tumor. A statistical comparison of preoperative serum GH and IGF-1 levels in patients with gigantism and patients with acromegaly showed a significant elevation in the former. CONCLUSION: Pituitary adenomas that cause gigantism are generally large and invasive, which makes them difficult to cure. High preoperative levels of GH and IGF-1 are also factors that decrease remission.

The Molecular Registry of Pituitary Adenomas (REMAH): A bet of Spanish Endocrinology for the future of individualized medicine and translational research. / El Registro Molecular de Adenomas Hipofisarios (REMAH): una apuesta de futuro de la Endocrinología española por la medicina individualizada y la investigación traslacional.

Pituitary adenomas are uncommon, difficult to diagnose tumors whose heterogeneity and low incidence complicate large-scale studies. The Molecular Registry of Pituitary Adenomas (REMAH) was promoted by the Andalusian Society of Endocrinology and Nutrition (SAEN) in 2008 as a cooperative clinical-basic multicenter strategy aimed at improving diagnosis and treatment of pituitary adenomas by combining clinical, pathological, and molecular information. In 2010, the Spanish Society of Endocrinology and Nutrition (SEEN) extended this project to national level and established 6 nodes with common protocols and methods for sample and clinical data collection, molecular analysis, and data recording in a common registry (www.remahnacional.com). The registry combines clinical data with molecular phenotyping of the resected pituitary adenoma using quantitative real-time PCR of expression of 26 genes: Pituitary hormones (GH-PRL-LH-FSH-PRL-ACTH-CGA), receptors (somatostatin, dopamine, GHRH, GnRH, CRH, arginine-vasopressin, ghrelin), other markers (Ki67, PTTG1), and control genes. Until 2015, molecular information has been collected from 704 adenomas, out of 1179 patients registered. This strategy allows for comparative and relational analysis between the molecular profile of the different types of adenoma and the clinical phenotype of patients, which may provide a better understanding of the condition and potentially help in treatment selection. The REMAH is therefore a unique multicenter, interdisciplinary network founded on a shared database that provides a far-reaching translational approach for management of pituitary adenomas, and paves the way for the conduct of combined clinical-basic innovative studies on large patient samples.

[Acromegalic myocardiopathy]. / Miocardiopatía acromegálica.

Acromegaly is characterized by chronic growth hormone hypersecretion. Cardiovascular alterations such as hypertension, left ventricular hypertrophy, cardiac rhythm disturbances and valvular disease are common in this disease and are the main cause of death. Control of acromegaly by surgery or pharmacotherapy has been shown to improve cardiovascular morbidity. We report a case of acromegalic myocardiopathy in a 59-year-old woman with dilated myocardiopathy who presented ventricular diameter and contractility normalization following medical treatment.

Clinical practice guideline for hypotalamic-pituitary disturbances in pregnancy and the postpartum period.

During pregnancy, the body undergoes a major adaptation process as a result of the interaction between mother, placenta and fetus. Major anatomical and histological changes are produced in the pituitary, with an increase of up to 40% in the size of the gland. There are wide variations in the function of the hypothalamus-pituitary-thyroid axis that effect iodine balance, the overall activity of the gland, as well as transport of thyroid hormones in plasma and peripheral metabolism of thyroid hormones. The incidence of goiter and thyroid nodules increases throughout pregnancy. The management of differentiated thyroid carcinoma should be individually tailored according to tumoral type and pregnancy stage. Given the effects of hypothyroidism on fetal development, both the diagnosis and appropriate therapeutic management of thyroid hypofunction are essential. The most important modification to the hypothalamus-pituitary-adrenal axis during pregnancy is the rise in serum cortisol levels due to an increase in cortisol-binding proteins. Although Cushing's syndrome during pregnancy is infrequent, both diagnosis and treatment of this disorder are especially difficult. Adrenal insufficiency during pregnancy does not substantially differ from that occurring outside pregnancy. However, postpartum pituitary necrosis (Sheehan's syndrome) is a well-known complication that occurs after delivery and, together with lymphocytic hypophysitis, constitutes the most frequent cause of adrenal insufficiency. The management of prolactinoma during pregnancy requires suppression of dopaminergic agonists and their reintroduction if there is tumoral growth. Notable among the neuropituitary disorders that can occur throughout pregnancy is diabetes insipidus, which occurs as a consequence of increased vasopressinase activity.

Clinical practice guideline for the diagnosis and treatment of hypophysitis.

Hypophysitis are a group of inflammatory lesions affecting the pituitary gland and pituitary stalk. These lesions should be included in the differential diagnosis of sellar masses. There are three types of primary hypophysitis: lymphocytic, granulomatous and xanthomatous. Lymphocytic hypophysitis is the most frequent form of chronic pituitary inflammation and is believed to have an autoimmune origin. This form characteristically affects women during the peripartum, with diverse types of pituitary deficiency, especially ACTH deficiency, and frequently there are other associated autoimmune processes. Lymphocytic hypophysitis can affect the anterior pituitary only, the infundibular stalk and posterior lobe of the pituitary (infundibuloneurohypophysitis), or the entire pituitary (panhypophysitis). Clinically, lymphocytic hypophysitis can manifest with compression symptoms, hypopituitarism, diabetes insipidus or hyperprolactinemia. The imaging technique of choice is magnetic resonance imaging, which helps to characterize the sellar lesion. Treatment includes replacement of the functional pituitary deficiency and the use of corticosteroids, generally at high doses. Surgical treatment is reserved for patients unresponsive to conservative therapy. Granulomatous hypophysitis can be of known etiology, whether infectious (currently highly infrequent) or non-infectious (ruptured Rathke's cyst, etc.). Granulomatous hypophysitis of unknown etiology is manifested by the presence of idiopathic granulomas. Xanthomatous hypophysitis is characterized by a histiocytic infiltrate with cystic characteristics on imaging. Secondary hypophysitis is due to pituitary inflammation caused by surrounding lesions or can form part of systemic diseases.

Succinate dehydrogenase D variants do not constitute a risk factor for developing C cell hyperplasia or sporadic medullary thyroid carcinoma.

Medullary thyroid carcinoma (MTC) is a tumor that arises from parafollicular cells of the thyroid gland. MTC can occur sporadically (75%) or as part of inherited cancer syndromes (25%). In most cases, hereditary MTC evolves from preneoplastic C cell hyperplasia (CCH), so early detection of this pathology would evidently be critical. A recent study reports that alterations in succinate dehydrogenase (SDH) D are responsible for familial non-RET CCH. First, we studied SDHD in two families with hereditary non-RET CCH and found no alterations related to the inheritance of this disease. Then, we investigated whether the H50R variant could be a risk factor in the sporadic development of MTC in both Spanish and English patients. We found no evidence that the presence of the H50R is strongly associated with the risk of sporadic MTC, although we did observe an association with age at diagnosis of MTC in Spanish H50R carriers that we did not find in English patients. Finally, we looked for evidence of CCH or any other thyroid disease in a panel of germ-line SDH (B or D) mutation carriers and found none. We conclude that SDHD variants do not constitute a risk factor for developing CCH or sporadic MTC.

Epidemiology, clinical characteristics, outcome, morbidity and mortality in acromegaly based on the Spanish Acromegaly Registry (Registro Espanol de Acromegalia, REA).

OBJECTIVE: To undertake a multicentre epidemiological study reflecting acromegaly in Spain. DESIGN: Voluntary reporting of data on patients with acromegaly to an online database, by the managing physician. METHODS: Data on demographics, diagnosis, estimated date of initial symptoms and diagnosis, pituitary imaging, visual fields, GH and IGF-I concentrations (requested locally), medical, radiotherapy and neurosurgical treatments, morbidity and mortality were collected. RESULTS: Data were included for 1219 patients (60.8% women) with a mean age at diagnosis of 45 years (s.d. 14 years). Reporting was maximal in 1997 (2.1 cases per million inhabitants (c.p.m.) per year); prevalence was globally 36 c.p.m., but varied between 15.7 and 75.8 c.p.m. in different regions. Of 1196 pituitary tumours, most were macroadenomas (73%); 81% of these patients underwent surgery, 45% received radiotherapy and 65% were given medical treatment (somatostatin analogues in 68.3% and dopamine agonists in 31.4%). Cures (GH values (basal or after an oral glucose tolerance test) <2 ng/ml, normal IGF-I, or both) were observed in 40.3% after surgery and 28.2% after radiotherapy. Hypertension (39.1%), diabetes mellitus (37.6%), hypopituitarism (25.7%), goitre (22.4%), carpal tunnel syndrome (18.7%) and sleep apnoea (13.2%) were reported as most frequent morbidities; 6.8% of the patients had cancer (breast in 3.1% of the women and colon in 1.2% of the cohort). Fifty-six patients died at a mean age of 60 years (s.d. 14 years), most commonly of a cardiovascular cause (39.4%); mortality was greater in patients given radiotherapy (hazard ratio 2.29; 95% confidence interval 1.03 to 5.08; P=0.026), and in those in whom GH and IGF-I concentrations were never normal (P<0.001). CONCLUSIONS: This acromegaly registry offers a realistic overview of the epidemiological characteristics, treatment outcome and morbidity of acromegaly in Spain. As active disease and treatment with radiotherapy are associated with an increase in mortality, efforts to control the disease early are desirable.