Search

Background: Henry IV King of Castile, last king of the Trastámara dynasty, was the brother of Isabella the Catholic. He is known as "the impotent". Based on previous descriptions by historians and biographers, Gregorio Marañón in 1922 described him as "eunuchoid dysplastic with acromegalic reaction and clear schizoid features"., Methods: In 1946, a post-mortem inspection was carried out on the mummified corpse found in the Monastery of Guadalupe. A written document and some photographs were recorded. We have collected the signs and symptoms described and applied the international classification of diseases recommended by the World Health Organisation, ICD11-2023. We have relied on the coins issued in the money of Henry IV, on which we have identified enlargement of the thyroid gland., Results: With the data available at this time, we suggest that Henry IV most probably suffered from: facial and polyostotic bone dysplasia, kyphosis, limb limping, multiple endocrine disorders, acromegaly with macrognatia, nodular thyroid disease, malodorous diaphoresis, erectile dysfunction, hypospadias, abnormal sexual development, "feminoid pelvis", abdominal colic, oligodontia and dental displacement. It is possible that he also suffered from: precocious puberty, renal lithiasis with debilitating phosphaturia, carpal tunnel, thrombopenia and growth hormone-producing pituitary hyperplasia or adenoma., Conclusion: We suggest that Henry IV may have suffered from McCune-Albrigth syndrome associated with fibrous dysplasia, a rare disease due to gain-of-function mutations in the GNAS gene., (Copyright © 2023 Sociedad Española de Anatomía Patológica. Publicado por Elsevier España, S.L.U. All rights reserved.)

Acromegaly is a rare disease, mainly caused by a pituitary tumor secreting growth hormone. It is characterized by slow progression and is associated with a multisystemic involvement, being the cardiovascular system, one of the most involved, even reaching, more than 10 years ago, to represent the main cause of death. Cardiovascular complications develop as a result of elevated blood concentrations of growth hormone and insulin-like growth factor 1, which exert direct and indirect effects on the endothelium, large vessels, kidney and cardiomyocytes; causing arterial hypertension, valve disease, cardiac arrhythmia and a specific heart disease called acromegalic cardiomyopathy. After the literature overview related to the pathophysiology, clinical manifestations, diagnosis and treatment of cardiovascular involvement, we found that from a cardiovascular point of view, patients with acromegaly can range from an asymptomatic state to severe cardiac dysfunction, being the biochemical markers and imaging studies diagnostic tools that allow assessment the degree of cardiovascular disease in order to provide individualized treatment. The normalization of growth hormone and insulin-like growth factor 1 levels improves cardiovascular parameters, and therefore its prognosis.

Acromegaly is a chronic and slowly progressive disease that results from the hypersecretion of growth hormone (GH) and consequently insulin-like growth factor type 1 (IGF-1), due to a GH-secreting pituitary adenoma in 95-98% of cases. There are several complications or co-morbidities associated with acromegaly, the most frequent being cardiovascular, metabolic and neoplastic. The cardiovascular complications of acromegaly go from arterial hypertension to a peculiar form of cardiomyopathy and are the result of the long-standing exposure to high GH and IGF-1 levels. The pathophysiology of these complications is complex and includes an increased tubular reabsorption of sodium and the direct effects of GH and IGF-1 on the endothelium and the cardiac tissue itself. Frequently, the cardiovascular comorbidities of acromegaly occur concomitantly with metabolic complications such as diabetes and respiratory abnormalities such as the sleep apnea syndrome. In this brief review we analyze the pathophysiology, the clinical manifestations and the management of the cardiovascular complications of acromegaly.

Objectives: To seek a consensus on issues that may generate doubts in management of acromegaly in Spain., Method: Nominal groups and Delphi. Four experts defined relevant issues in management of acromegaly and generated different assertions and recommendations. Subsequently, a group of 30 additional experts was selected to test agreement with the assertions through two Delphi rounds. The following response categories were established: 1) Totally disagree; 2) Basically disagree; 3) Basically agree; 4) Totally agree. Agreement was defined as ≥70% of answers in categories 1 and 2 (consensus with the disagreement) or 3 and 4 (consensus with the agreement) in the second Delphi round., Results: Assertions covers various aspects of clinical practice, including: 1) Useful instruments in individualization of treatment (response predictive markers, imaging techniques, etc.); 2) Clinical profiles and relevant comorbidities in treatment individualization; 3) Role of patient in treatment decision-making; 4) Access to treatments (accessibility and equity). The first Delphi round included 35 assertions. Consensus was reached on six of these assertions, two were eliminated, and two were reformulated. Of the 27 assertions included in the second round, consensus was reached on 24 (22 in the agreement, two in the disagreement) and three were eliminated., Conclusions: This document is intended to solve some common clinical questions and to facilitate decision making in the management of patients with acromegaly., (Copyright © 2018 SEEN y SED. Publicado por Elsevier España, S.L.U. All rights reserved.)

Acromegaly is a rare disease with many comorbidities that impair quality of life and limit survival. There are discrepancies in various clinical guidelines regarding diagnosis and postoperative control criteria, as well as screening and optimal management of comorbidities. This expert consensus was aimed at establishing specific recommendations for the Spanish healthcare system. The existing recommendations, the scientific evidence on which they are based, and the main controversies are reviewed. Unfortunately, the low prevalence and high clinical variability of acromegaly do not provide strong scientific evidences. To mitigate this disadvantage, a modified Delphi questionnaire, combining the best available scientific evidence with the collective judgment of experts, was used. The questionnaire, generated after a face-to-face debate, was completed by 17 Spanish endocrinologists expert in acromegaly. A high degree of consensus was reached (79.3%), as 65 of the total 82 statements raised were accepted. Some criteria for diagnosis and postoperative control were identified by this procedure. Regarding comorbidities, recommendations have been established or suggested for screening and management of oncological, cardiovascular, respiratory (sleep apnea), metabolic (dyslipidemia and diabetes), musculoskeletal, and hypopituitarism-related disorders. Consensus recommendations may facilitate and homogenize clinical care to patients with acromegaly in the Spanish health system., (Copyright © 2018 SEEN y SED. Publicado por Elsevier España, S.L.U. All rights reserved.)

Diabetes mellitus occurs in nearly 10% of patients with acromegaly and is secondary to insulin resistance caused by high levels of growth hormone. Diabetes ketoacidosis has been described as a rare complication of acromegaly, resulting from a relative insulin deficiency caused by growth hormone excess. We described the case of a 38 year-old man who presented to the emergency room with a 6-week history of polydipsia, polyuria, polyphagia and weight loss. He also had nausea, vomiting and abdominal pain from two days before admission. His plasma glucose level was 880 mg/dl, plasma osmolarity 368 mOsm/l, arterial pH 7.06 and serum bicarbonate 8.6 mEq/l. At the clinical examination, he had features of acromegaly. Magnetic resonance imaging showed a pituitary macro adenoma and growth hormone dosages were abnormally high. After tumor removal, plasma glucose levels became normal. This case shows the rare association between diabetic ketoacidosis and acromegaly. Surgery, in this case, was the definite modality of treatment.

Acromegaly is a clinical syndrome caused by the excessive production of growth hormone. It is associated with high morbidity and significantly increased mortality, mainly due to cardiovascular and respiratory complications, and cancer. Mortality is reduced to that of the general population following successful treatment, in other words, when insulin-like growth factor (IGF-I) and growth hormone values return to normal levels. Not all tumours associated with this syndrome benefit from cost-effective early diagnosis programmes. An in-depth knowledge on the part of clinicians of the morbidity and mortality associated with acromegaly, allowing them in many cases to anticipate the expected clinical course of the disease, is the best therapeutic and follow-up strategy in these patients., (Copyright © 2016 Elsevier España, S.L.U., AEEH y AEG. All rights reserved.)

Acromegaloidism is a condition characterized by features of acromegaly without biochemical evidence of excessive growth hormone (GH) production. Insulin resistance is one of the possible etiologies. We report the case of a patient with acromegalic features, a left lung neoplastic process, generalized acanthosis nigricans and severe insulin resistance. Normal IGF 1 and GH inhibition below 1 ng/ml by the oral glucose tolerance test ruled out the diagnosis of acromegaly. Acanthosis nigricans (AN) may be present as a paraneoplastic syndrome or may be associated to benign pathology in which insulin resistance is involved. Acromegaloidism has been reported in patients with severe insulin resistance as we are describing here. It is possible that very high insulin levels can stimulate excessive acral growth acting through insulin receptors that retain the ability to mediate anabolic effects, or alternatively through the IGF1 receptor. We found no data of acromegaloidism as a paraneoplastic syndrome. To summarize, we report a case of severe insulin resistance, pseudoacromegaly and AN, coexisting with a lung carcinoma. Acromegaloidism and AN appear to be due to insulin resistance, even though in this patient we cannot exclude that AN could be a paraneoplastic syndrome.

Background: The prevalence of colorectal polyps in the general population is 10%. Hormonal alterations in acromegaly stimulates adenomatose polyps development making that increase it prevalence. Colonoscopy has elevated sensibility and specificity in detection of colorectal adenomas., Objective: Identify colonic polyps in patients with acromegaly and establish the importance of colonoscopy as a detection method., Material and Methods: Retrospective, observational and descriptive study made in Colon and Rectum Surgery Department from March 2000 to March 2007 in patients with acromegaly and colonoscopy. Analyzed variables were: gender,age, endoscopy findings and histopathological results. Descriptive statistics were used to analysis of results., Results: Thirty-two patients were included: 14 (44%) men, 18 (56%) women. The mean age was 48 (range 22 to 75 years old). In 9 (28%) patients were detected colorectal polyps, predominately in the sigmoid. Fifteen polyps lesion were found: 7 (46.6%) adenomas: 5 (33.3%) tubular and 2 (13.3) villous, 6 (40%) hyperplasic, 1 (6.6%) inflammatory and 1 (6.6%) carcinoma. Colonoscopy was complete in 30 (93.7%) patients., Conclusions: The prevalence of colonic polyps inpatients with acromegaly undergoing colonoscopy,was 28%, higher than expected in the general population. Colonoscopy constitutes an important diagnosis technique in early neoplasia detection.

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.

A patient with clinical suspicion of acromegaly and no radiologic visualization of pituitary adenoma is presented. (111)In-DTPAOC scintigraphy was performed in order to localize an ectopic foci of GH production. Scintigraphy showed uptake in right paratracheal and hiliar lymph nodes that seemed residual in CT. Biopsy through mediastinoscopy showed tuberculous granulomas. After treatment, scintigraphy normalized. This case illustrate that (111)In-DTPAOC can be positive not only in tumoral but in benign pathology and, in specific cases, it can be a marker of inflammatory activity and useful for treatment monitoring.

Objective: Acromegaly is often associated with sleep apnea-hypopnea syndrome (SAHS). The purpose of this study was to understand the prevalence of SAHS in patients with acromegaly and define the characteristics of acromegalic patients with and without SAHS., Patients and Methods: The study enrolled 17 patients (11 women and 6 men) residing in the province of Ourense, Spain, who were diagnosed with acromegaly. All patients underwent overnight polysomnography in a sleep laboratory. In addition, growth hormone and insulin-like growth factor 1 levels were assessed. Sixteen of the patients underwent cephalometric study., Results: The average age of the patients was 58 years (95% confidence interval [CI], 52-63). The average body mass index was 31 (95% CI, 29-34) and average neck circumference was 41 (95% CI, 39-43). Ten patients (58.8%) had an apnea-hypopnea index (AHI) greater than 10. Nine had obstructive apnea and one had central apnea. Seven (5 with an AHI>10 and 2 with an AHI<10) reported excessive daytime sleepiness with Epworth scores greater than 10 (41.2%). Five patients (29.4%) were diagnosed with SAHS (AHI>10 and Epworth>10). No correlation was found between an AHI greater than 10 and hormonal activity (P=.082). The mean growth hormone level for patients with an AHI greater than 10 was 4.8 (95% CI, 0.5-9) and the mean for those with an AHI less than 10 was 12 (95% CI, 2-27). Fifty percent of the patients were treated with a somatostatin analog and half of those treated exhibited apnea (P=.302). No cephalometric differences related to the presence of apneas were found., Conclusions: We found a high prevalence of sleep apneas (58.8%) and SAHS (29.4%), and central apneas were rare. We found no correlation between hormone activity level and the presence of SAHS. The incidence of SAHS was the same in somatostatin analog treated and untreated patients. Cephalometric variables did not distinguish between acromegalic patients with and without SAHS.

Strumal carcinoid is an unusual form of monodermal ovarian teratoma with thyroid-like follicles mixed with typical carcinoid tumor patterns. We report a 49 years old woman presenting with an acromegaly. At the age of 45, an ovarian strumal carcinoid was excised and at three years of follow up, she complained of finger and feet growth. Laboratory showed an elevated serum IGF-1 and a sella turcica magnetic resonance imaging showed an 8 mm microadenoma. She was subjected to a transphenoidal excision and the pathological study disclosed a solid acidophilic pituitary adenoma. Two months after surgery, there was a significant decrease in serum IGT-I levels.

Introduction: Diastolic dysfunction is a common complication in patients with acromegaly. By using the metabolic treatment for acromegaly, an improvement in diastolic function is not always achieved and a group of these patients could obtain some benefit from a specific treatment for such a condition. The objective of the present study was to evaluate the utility of verapamil therapy in acromegalic patients with diastolic dysfunction., Methods: Fourteen patients (7 males and 7 females) with the diagnosis of acromegaly and diastolic dysfunction confirmed by echocardiogram were studied. After six months of treatment with verapamil (240 mg/day) the echo-cardiographic parameters and the functional class (NYHA) of patients were reevaluated., Results: All patients showed an increased basal measurement of the cardiac mass (mean [percentiles 25-75]: 149 g/m2 [128-264]) and no improvement was observed after treatment (182 g/m2 [123-328]). Also, no improvement was found regarding the studied diastolic function parameters: E/A relationship of left ventricle (0.70 [0.54-0.83] versus 0.61 [0.54-0.86]) and isovolumetric relaxation time (146 [119-193] versus 120 [97-169]). A trend towards improvement was indeed found in the functional class, although no statistical differences were observed., Conclusion: Our results did not demonstrate a benefit derived from the treatment with verapamil upon the diastolic function in patients with acromegaly.

It is well known that non-toxic goiter is not uncommon in acromegaly, but hyperthyroidism only occasionally occurs. In addition, the risk for the development of a malignant process is increased, the most often seen is carcinoma of the colon. Thyroid carcinoma is not frequent, nevertheless the rate in these patients is higher than general population. In this article, a case of hyperthyroidism, papillar carcinoma and acromegaly is presented. We reviewed the literature an discussed the possible pathogenesis.

A 65 year-old male with severe systolic mitral and tricuspid valve prolapse, associated with long-standing acromegaly is reported. The non published association could be caused by the effect of growth hormone on the valve connective tissue.

Pituitary adenoma, familiar type, with apparent affection over the involved somatomammotropin of secretion of growth hormone and prolactin, with dominant autosomic transmission, is described for the first time. It was seen that a couple of members without demonstrable tumour, showed clinical data (phenotype) of acromegaly. On investigation of histocompatibility antigens it was observed that the patients with tumour and other symptomatic ones, but without tumour, shared the same haplotypes, and so is very possible that investigation of HLA antigens in patients with pituitary tumour, contributes to better identify its nature and frequency.

Diabetes mellitus is a frequent manifestation in patients with acromegaly and it can show up even before the latter manifests. Typically, the diabetes mellitus in these patients does not tend to develop ketosis. We present the case of a patient hospitalized due to diabetic ketoacidosis associated to a perianal abscess. Diabetes mellitus type I was rejected and the presence of insulin-resistance was verified. She required insulin therapy just for three months. The clinical, hormonal and radiological evaluation showed, three years latter, the presence of a hypophyseal tumor producing growth hormone. After performing a trans-sphenoidal adenomectomy, the insulin-therapy could be removed with a normal glycemic profile. This case of acromegaly demonstrates the relationship between growth hormone and glucose metabolism. It can be considered that the ketoacidosis was the first manifestation of the acromegaly, which is exceptional.

Acromegaly is associated to thyroidal disorders such as hyperthyroidism. The Graves-Basedow disease as a cause of thyroid hyperfunction is very infrequent, with only 8 cases having been reported up to 1993. The authors present 3 patients with acromegaly who developed hyperthyroidism due to Graves-Basedow disease in the course of their disease. Two of the patients had acromegaly of 30 years of evolution and the third patient underwent consultation for clinical symptoms of hyperthyroidism with acromegaly being simultaneously diagnosed. All the patients had weight loss prior to diagnosis and the possibility of neoplasia associated to acromegaly was excluded. The hyperthyroidism responded well to initial treatment with antithyroid drugs in the three cases. The authors conclude that hyperthyroidism should be taken into consideration in the diagnosis of a patient with acromegaly and weight loss.

50 patients with autonomous growth hormone excess (48 with adult acromegaly and 2 with gigantism) were studied between 1966 to 1986 (2.38 pts/year). Characteristic clinical presentation, an increase in growth hormone (GH) uninhibited by glucose, and/or hyperphosphemia and hyperhydroxiprolinuria were present in all patients. No cases of hypercalcemia were recorded. Phosphemia was increased in 55.8%, alkaline phosphatases in 61.7%, calciuria in 26.9% and hydroxyprolinuria in 74.2% of the patients. Basal GH was over 5 ng/ml (89.9 DS +/- 170.9) in 42 pts, and in 37 was not suppressed after glucose administration, 38% had an increased (paradoxical response) and 62% a flat response (less than 50% change of basal values). TRH test was performed in 14 patients, 8 presented an increase in GH titer. Hyperprolactinemia was seen in 4 of 12 patients in whom this hormone was measured. The size of the sella turcica was increased in 93%, and although the larger sellar size correlated to higher levels of GH, correlation was not significant. 20% of the pts had rheumatological disease, 14% goiter, 12% cardiac disease, 26.5% had diastolic hypertension and 4% renal lithiasis (hypercalciuric pts). 38% had hyperglycemia with a diabetic glucose tolerance test and 18% had non-diabetic abnormal glucose tolerance test.

We present 38 acromegalyc patients who were studied by non invasive methods to assess the frequency of cardiovascular complications. Seventy one percent of the cases presented some type of cardiovascular alteration. In 68% we observed left ventricular hypertrophy by echocardiography which was the most sensitive method to detect it. In 71% we obtained abnormal electrocardiograms, mainly because of conduction disturbances, being right bundle branch block the most frequent. Half of the cases had pulmonary fibrosis and chronic bronchitis. Arterial hypertension was present in 32%. Diabetes mellitus in 21%. Only 2 cases had coronary heart disease. In 37% of the patients who underwent hypophisectomy we observed regression up to 90% of the cardiac complications except for left ventricular hypertrophy and pulmonary fibrosis. None of the patients has died.