Acromegaly and cardiovascular risk-In light of 30 cases

Introduction Acromegaly is a rare disease with an estimated incidence of 40 to 100 cases per million population. It is due to a hypersecretion of growth hormone (GH), most often by a pituitary somatotropic adenoma, sometimes by a mixed adenoma with GH and very rarely by an ectopic secretion of GHRH [1]. It remains a serious disease, reducing life expectancy by an average of 10 years due to its cardiovascular and metabolic repercussions, which is why it is so important to systematically screen all risk factors and to take them into account charge. The main objective of our study is to analyze the different cardiovascular risk factors during acromegaly and their combination in the same patient. Materials and method This is a prospective longitudinal type observational study conducted in the Department of Endocrinology, Diabetology and Metabolic Diseases of the Mohammed VI University Hospital of Marrakech, conducted over a four-year period (January 2015 to January 2019) and interested in patients whose diagnosis of acromegaly was confirmed by biological assays (IGF1 and negative OGTT test: GH>1 ng/ml) in addition to pituitary magnetic resonance imaging. The following parameters have been studied: • Age. • The sex of the patients. • The duration of evolution of the disease. • Family history: Diabetes and heart disease. *Correspondence to: Askaoui S, Imm Dalia 2 c, N°17, Albadii, amerchich, Marrakech, Morocco, Tel: 0662286781; E-mail: saraaskaoui@yahoo.fr


Introduction
Acromegaly is a rare disease with an estimated incidence of 40 to 100 cases per million population. It is due to a hypersecretion of growth hormone (GH), most often by a pituitary somatotropic adenoma, sometimes by a mixed adenoma with GH and very rarely by an ectopic secretion of GHRH [1].
It remains a serious disease, reducing life expectancy by an average of 10 years due to its cardiovascular and metabolic repercussions, which is why it is so important to systematically screen all risk factors and to take them into account charge.
The main objective of our study is to analyze the different cardiovascular risk factors during acromegaly and their combination in the same patient.

Materials and method
This is a prospective longitudinal type observational study conducted in the Department of Endocrinology, Diabetology and Metabolic Diseases of the Mohammed VI University Hospital of Marrakech, conducted over a four-year period (January 2015 to January 2019) and interested in patients whose diagnosis of acromegaly was confirmed by biological assays (IGF1 and negative OGTT test: GH>1 ng/ml) in addition to pituitary magnetic resonance imaging.
The following parameters have been studied: • Age.
• The sex of the patients.
• The duration of evolution of the disease.
• Family history: Diabetes and heart disease.

Results
30 patients were included. The average age is 36 years old (17-63 years old) with a sex ratio (M / F) of 0.7. The age of onset of the disease at the time of diagnosis was on average 6 years (3-14 years), the family history was 16.7% of diabetes mellitus and heart disease.
Regarding the metabolic profile of these patients, a pathological BMI (>25 Kg/m 2 ) was found in 60 % of cases, while a mean waist circumference was found in women of 97 cm and men in 103 cm. 34% of these patients have carbohydrate tolerance disorders with an average HbA1c of 6.2%. These patients were placed under hygienic and dietary rules. 43,3% are diabetics with a mean HbA1c of 11%, are insulin-treated and under metformin; a total of 77.3% carbohydrate abnormalities, with microalbuminemia positive in three cases, put under inhibitor of the conversion enzyme. 13.4% of patients have dyslipidemia put under statins.
In addition, 23.4% of these patients are hypertensive with ventricular hypertrophy and 23.3% have sleep apnea syndrome. Physical inactivity was noted in four cases, menopause in three patients and active smoking in three patients ( Figure 1).
Twelve have at least two risk factors and six are affected by three risk factors.
Hypothalamic-pituitary MRI revealed the presence of a pituitary macro-adenoma in 93.3% of cases and in 6.7% of cases it was microadenoma. Regarding the etiological assessment, it was a somatotropic adenoma in 55.6% of cases, a somato-prolactinic adenoma in 20%, a mammosomatotropic adenoma in 14.4% and the nature of adenoma is not yet determined in 10% of cases ( Figure 2). 90% of these patients underwent at least one first-stage pituitary surgery. 56.7% of cases are under medical treatment second intension (somatostatin analogue). 6.7% of cases are considered in remission.
The impact of surgical treatment of acromegaly in patients with abnormalities of carbohydrate metabolism was notable, considering the improvement of the metabolic profile in all pre-diabetics (the average HbA1c increased to 5.9%), the decrease in insulin requirement in all diabetics with a sharp decrease in HbA1c average to 8.6% and the tendency to cure diabetes in two patients whose disease is controlled, while hypertension remained.

Discussion
Acromegaly is a rare disease, due to a hypersecretion of growth hormone most often by a pituitary adenoma, rarely by ectopic secretion of GHRH and may sometimes integrate into syndromic disorders such as Wermer's syndrome or endocrine neoplasia type 1, Carney's syndrome and McCune Albright syndrome [2,3].
It remains a lethal disease due to its metabolic complications (glucose intolerance, diabetes, dyslipidemia); cardio-vascular complications (hypertension, cardiomegaly, left ventricular hypertrophy, coronary artery disease and arrhythmia); its respiratory complications (sleep apnea syndrome) and neoplastic complications (especially colic), which are responsible for high morbidity and mortality, reducing the expectation and the quality of life of the patients [4].
Diabetes secondary to acromegaly is a frequent complication, the prevalence is estimated between 20% and 25%, often curable [5,6]. The pathophysiological mechanism involved is insulin resistance, associated with the hyperglycemic action of the hormones of growth and IGF1, responsible for the accentuation of gluconeogenesis and hepatic glycolysis [7][8][9].
Its main risk factors are high levels of growth hormone, prolonged illness, advanced age, and a family history of diabetes and hypertension [10].
There are no particularities regarding the diagnostic modalities of diabetes in acromegalic patients; however, the latter must be done outside periods of imbalance and in the absence of hypoglycemia likely to stimulate the secretion of GH.
The various therapeutic means of acromegaly have a varied effect on carbohydrate metabolism: in most cases, the surgical treatment allows the concomitant cure of diabetes, the somatostatin analogues and pasireotide have a hyperglycemic effect, and the antagonists of the GH have a hypoglycemic effect [11][12][13][14][15][16][17].
In addition to metabolic disturbances, excess growth hormone can induce hypertrophic cardiomyopathy, coronary insufficiency and often an increase in arterial pressure -3 times more common in acromegalics and not always reversible; this is due to the inhibition of the secretion of the atrial natriuretic factor, subsequently increasing the sodium tubular reabsorption and thus promoting the water-soluble retention; not to mention the added role of endothelial dysfunction [18][19][20][21].
In our series, approximately 77, 3% of cases present metabolic disorders with a tendency to high doses of insulin prior to surgery and to cure diabetes after successful surgery, which is consistent with literature data.

Conclusion
Our study, in agreement with the results of other previous studies, confirms the high prevalence of cardiovascular risk factors in the acromegalic patient, hence the importance of systematic screening and early and comprehensive care. This is to prevent progression to cardiovascular complications, the leading cause of death in acromegalics.