Indian Journal of Endocrinology and Metabolism

: 2017  |  Volume : 21  |  Issue : 6  |  Page : 919--925

The heart of the matter: Cardiac manifestations of endocrine disease

Aditya John Binu1, Kripa Elizabeth Cherian2, Nitin Kapoor2, Sujith Thomas Chacko3, Oommen George3, Thomas Vizhalil Paul2,  
1 Department of General Medicine, Christian Medical College, Vellore, Tamil Nadu, India
2 Department of Endocrinology, Diabetes and Metabolism, Christian Medical College, Vellore, Tamil Nadu, India
3 Department of Cardiology, Christian Medical College, Vellore, Tamil Nadu, India

Correspondence Address:
Thomas Vizhalil Paul
Department of Endocrinology, Diabetes and Metabolism, Christian Medical College, Vellore - 632 004, Tamil Nadu


Endocrine disorders manifest as a disturbance in the milieu of multiple organ systems. The cardiovascular system may be directly affected or alter its function to maintain the state of homeostasis. In this article, we aim to review the pathophysiology, diagnosis, clinical features and management of cardiac manifestations of various endocrine disorders.

How to cite this article:
Binu AJ, Cherian KE, Kapoor N, Chacko ST, George O, Paul TV. The heart of the matter: Cardiac manifestations of endocrine disease.Indian J Endocr Metab 2017;21:919-925

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Binu AJ, Cherian KE, Kapoor N, Chacko ST, George O, Paul TV. The heart of the matter: Cardiac manifestations of endocrine disease. Indian J Endocr Metab [serial online] 2017 [cited 2021 Sep 18 ];21:919-925
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Hormonal excess or deficiency results in disease states through interactions with multiple organ systems. Endocrine disorders may result in cardiovascular alterations in response to perceived changes in homeostasis. In this review, we shall strive to address various cardiac manifestations secondary to endocrine dysfunction and the benefits of correcting them. The association between diabetes mellitus and cardiovascular disease is well known and has been elaborately studied in other sources. Hence, this aspect has been excluded from this review.

 Thyroid Gland

Thyroid hormones exert positive chronotropic and inotropic effects on the heart. The state of hyper and hypothyroidism has an adverse impact on the cardiovascular system, especially when left untreated.


Hypothyroidism is associated with cardiovascular manifestations such as increased systemic vascular resistance (SVR), normal or reduced resting heart rate, reduced cardiac contractility, raised diastolic pressure, a narrowed pulse pressure, and decreased cardiac output.[1] The cardiac output may decrease by as much as 30%–40% secondary to a reduction in the stroke volume and heart rate.[2] Triiodothyronine (T3), the biologically active form of thyroid hormone, regulates multiple structural and regulatory myocyte genes related to cardiac contractile function at the genetic level, such as sarcoplasmic reticulum (SR) Ca 2+ ATPase (SERCA2), phospholamban (an integral SR protein that regulates SERCA2 activity), and α and β myosin heavy chains (MHC). SERCA2 and α-MHC are positively regulated whereas phospholamban and β-MHC are negatively regulated by T3.

T3 regulates multiple myocardial plasma membrane ion transporters (e.g., Na +/K + ATPase, Na +/Ca 2+ exchanger, and voltage-gated potassium channels like Kv1.5 and Kv4.2).[3] T3 plays a role in reducing SVR by direct effects on vascular smooth muscle cells (VSMCs) and by effecting changes in vascular endothelium by stimulation of synthesis and secretion of nitric oxide (NO). Overt hypothyroidism induces changes in atherosclerotic risk factors such as hypercholesterolemia, increased carotid intimal medial thickness (IMT), and reduced production of endothelial-derived NO.[4] Hyperlipidemia is due to decreased expression of hepatic low-density lipoprotein (LDL) receptors and reduced cholesterol clearance. The activity of cholesterol α-monooxygenase, which mediates breakdown of cholesterol, is also reduced.[2] Pericardial effusions occur in up to 25% of patients with hypothyroidism and are likely due to increased capillary permeability, increased volume of distribution of albumin, and impaired lymphatic drainage.[1]


Cardiovascular manifestations of hyperthyroidism include palpitations, exercise intolerance, exertional dyspnea, systolic hypertension, and widening of pulse pressure. Electrocardiogram (ECG) may show sinus tachycardia, atrial fibrillation, atrial and ventricular premature beats. Sinus tachycardia may progress to atrial fibrillation in 5%–15% of patients with overt hyperthyroidism. Approximately 60% of these patients revert back to sinus rhythm with attainment of a euthyroid state.[5]

Other features include decreased SVR, increased heart rate, cardiac output, preload, and cardiac contractility. The decrease in SVR is caused by thyroid hormone-mediated vascular smooth muscle relaxation and endothelial NO production. The reduced SVR triggers an activation of the renin-angiotensin-aldosterone system causing an increased plasma volume and preload. Upregulation of erythropoietin secretion by thyroid hormones results in an increase in circulating blood volume increasing cardiac preload.[4] The net result of the increase in cardiac contractility, heart rate, increased circulatory volume, and decreased SVR is an elevated cardiac output which ranges from 50% to 300% more than normal. The resultant left ventricular hypertrophy (LVH) in association with arrhythmias such as atrial fibrillation leads on to symptoms and signs of congestive cardiac failure.[6]

Pulmonary arterial hypertension (PAH) has a prevalence of 43% in overt hyperthyroidism.[7] One of the proposed mechanisms includes an increase in pulmonary arterial pressures secondary to the LV failure, and hyperdynamic circulation. Thyroid hormones bind to integrin αvß3 and fibroblast growth factor receptors, stimulating endothelial cell proliferation and angiogenesis leading on to PAH. These changes can be offset and normalized by the treatment of hyperthyroidism and attaining a euthyroid state.[8]


Amiodarone is a benzofuran iodine rich anti-arrhythmic drug. A unique trait of this drug is its efficacy in the management of cardiac arrhythmias, but it simultaneously poses an independent risk to cardiac function, by causing either hyper or hypothyroidism. It causes thyroid dysfunction in about 15%–20% of patients undergoing treatment. The effects of amiodarone (containing 37% by weight of iodine) on the thyroid gland and thyroid function are secondary to either a direct effect on the thyroid or indirectly through multiple immunologic responses.[9]

As amiodarone and thyroid hormones are structurally similar, it can act at many cells and organs as a thyroid hormone analog. Amiodarone also reduces the activity of hypothalamic thyrotropin-releasing hormone and pituitary 5'-monodeiodinase Type-2 (D2).[10] Amiodarone is dealkylated to desethylamiodarone (DEA) in the liver. DEA acts as a TR-α1 and -ß1 receptor antagonist. As amiodarone is lipophilic, it concentrates in various tissues such as the adipose tissue. As a result, amiodarone and DEA have long half-lives (40 and 57 days, respectively).[11] Amiodarone also inhibits thyroid hormone uptake into peripheral tissues and D2 activity (responsible for the conversion of T4 to T3) which results in a rise in T4 and fall in T3.[12]

Amiodarone-induced hypothyroidism (AIH) results from persistent iodine-induced inhibition of thyroid function. This inhibition is more prevalent in patients with preexisting autoimmune thyroid disease. AIH is managed by supplementation of high doses of T4 as amiodarone decreases deiodinase activity resulting in decreased conversion of T4 to the active form T3.[13]

Amiodarone-induced thyrotoxicosis (AIT) occurs in about 2%–10% of patients and is of two forms – Type-1 AIT (iodine-induced hyperthyroidism) or Type-2 AIT (destructive thyroiditis). Type-1 AIT is managed with antithyroid drugs and occasionally potassium perchlorate. Type-2 AIT is managed with glucocorticoids, beta blockade, and on rare occasions, a thyroidectomy too may be indicated.[14]

 The Parathyroid Gland

Primary hyperparathyroidism (PHPT) is usually due to a parathyroid adenoma or a parathyroid hyperplasia with an elevated or high normal calcium levels. Secondary hyperparathyroidism results from chronic kidney disease or vitamin D deficiency. The most common cause for hypoparathyroidism is inadvertent removal of parathyroid glands following thyroidectomy or extensive neck dissection or after surgery for PHPT which has hypocalcemia as a main feature. Chronic hypocalcemia rather than acute hypocalcemia may have an adverse impact on cardiovascular system.[15]


Serum PTH levels may be predictive of coronary heart disease [16] and may have a direct action on vasculature causing alterations in blood pressure (BP), increased intimal wall thickness, and carotid wall stiffness in hypercalcemic PHPT patients.[17] Postulated mechanisms include a stimulatory effect of PTH on VSMCs that could be secondary to PTH-mediated calcium influx into VSMCs [18] causing contraction and increase in peripheral resistance. Other mechanisms include direct PTH-mediated stimulation of the renin-aldosterone system, endothelial dysfunction, and elevated sympathetic activity. An increase in total collagen synthesis and reorganization of collagen I increases vascular stiffness.[19] These changes result in hypertension which does not usually reverse with excision of parathyroid adenomas.[20]

The trophic effect of PTH on cardiomyocytes causes hypertrophy of the cells. Surgical correction of hyperparathyroidism may result in regression of LVH in some studies. Diastolic dysfunction with a reduced E/A (ratio of peak velocity flow in early diastole [the E wave] to peak velocity flow in late diastole caused by atrial contraction [the A wave]) ratio, and prolonged isovolumetric relaxation time has also been noted in moderate-to-severe PHPT. Calcifications may occur in the myocardium, aortic, and mitral valves in PHPT patients with severe hypercalcemia.[21]


Cardiovascular manifestations in hypoparathyroidism are usually secondary to the resultant hypocalcemia leading to QT interval prolongation, cardiac arrhythmias, heart failure, and reduced LV ejection fraction (LVEF). Extracellular calcium is needed for myocardial contraction due to the inability of the SR to sequester sufficient calcium ions to initiate contraction. Hence, a supplemental extracellular source of calcium ions is required.[22] A key feature of cardiovascular effects of hypocalcemia is the reversibility of these manifestations in virtually every case including correction of prolonged QT interval (QTc) and restoration of LVEF.[23] Congenital conditions, such as DiGeorge syndrome (a part of the CATCH 22 spectrum of disorders) are associated with conotruncal anomalies of the heart as well as thymic hypoplasia and hypoparathyroidism.[24] Kearns-Sayre syndrome, a mitochondrial myopathy that presents with cardiac conduction abnormalities, pigmentary retinopathy, and progressive external ophthalmoplegia may be associated with endocrine dysfunction such as hypoparathyroidism, diabetes and short stature.[25]

 The Pituitary Gland


Lactotroph cells of the anterior pituitary synthesize and secrete prolactin under the inhibitory control of hypothalamic factor dopamine. Certain studies have demonstrated an association of high prolactin with insulin resistance, dyslipidemia, hypertension, cardiovascular, and all-cause mortality over a 10 year follow-up period.[26],[27],[28] Peripartum cardiomyopathy (PPCM) has been speculated to be mediated by a 16 kDa prolactin fragment. Prolactin inhibition with dopamine agonists (DAs) such as bromocriptine is being explored as a novel PPCM treatment in addition to the implementation of standard heart failure regimens.[29]

DAs such as bromocriptine, cabergoline, and quinagolide that are used in the management of prolactinomas have been linked to the development of regurgitant valvular lesions such as tricuspid, mitral and aortic regurgitation if used for a long duration.[30] An ergot-derived DA pergolide has been shown to induce fibrotic changes in valve leaflets and the mitral subvalvular apparatus, causing thickening, retraction, and stiffening of valves resulting in valve regurgitation.[31] Till date, there is no conclusive evidence of a definite association between DA use in the management of hyperprolactinemia and valvulopathies.[32]

Growth hormone

Both growth hormone (GH) and insulin-like growth factor 1 (IGF-1) are important mediators of cardiac development which are vital for the regulation of the cardiovascular system.[33] GH deficiency (GHD) or excess may result in adverse cardiovascular outcomes.

Growth hormone deficiency

GHD syndrome is a well-defined constellation of symptoms and signs identified in adults with GHD characterized by an impairment of cardiac mass and performance with visceral obesity, insulin resistance, low high-density lipoprotein (HDL) cholesterol, vascular atherosclerosis with endothelial dysfunction, and hypercoagulability, all of which are associated with an increased cardiovascular risk.[34] Cardiac morphology at echocardiography associated with GHD is characterized by a reduced cardiac mass, notably a decreased LV mass index and LV diameter with a decrease of LV walls, and interventricular septum thickness. Although these findings have been confirmed in childhood-onset GHD, they are not consistently described in adult-onset GHD patients.[35],[36] A systolic dysfunction both at rest and after exercise with decreased exercise tolerance has been reported in young patients with GHD.[37] Carotid arterial IMT, an indicator of early atherosclerosis, is also increased in GHD.[38]

Both elevated BP and decreased systolic BP have been reported in subjects with GHD. Differences in age group, duration of GHD, and genetic heterogeneity may explain these contradictory findings.[39],[40] Dyslipidemia seen in GHD is characterized by an increase in serum triglycerides, total cholesterol, and LDL-cholesterol with decreased HDL-cholesterol levels.[41]

Some metabolic disturbances secondary to GHD such as low HDL and elevated LDL may be partially or fully reversed following growth hormone replacement therapy (GHRT). Improvement in cardiac output, LV mass, stroke volume, central obesity, endothelial dysfunction (by mediating NO production through IGF-1), and arterial stiffness usually occur with GHRT.[42],[43],[44],[45] After an initial transient worsening, GHRT improves insulin sensitivity by increasing IGF-I levels and reducing fat body mass and visceral adiposity.[42],[46]


Acromegaly, a state of GH excess significantly impacts the cardiovascular system with multiple manifestations as shown in [Table 1].[46],[47],[48] Hypertension may be seen in 20%–50% of patients with acromegaly.[49] Acromegalic cardiomyopathy is divided into early, intermediate, and late stages. Progression to the late stage is characterized by systolic and diastolic dysfunction, myocardial hypertrophy, and ventricular dilatation with increased peripheral vascular resistance. Progression to heart failure is seen in up to 3%–10%.[48] The use of somatostatin analogs for successful disease control may enhance cardiac function by decreasing volume overload, improving diastolic function, and promoting reduction in wedge and pulmonary pressures. However, valvular dysfunction may persist despite correction of hormonal levels.[50] Somatostatin analogs show benefit in reducing arrhythmogenicity in patients with acromegaly. Cardiovascular disease secondary to atherosclerosis in GH excess states is associated with increased mortality which persists even after treatment.[50]{Table 1}

Adrenocorticotropic hormone

The chief role of adrenocorticotropic hormone (ACTH) is regulation of adrenal cortisol secretion. A pathological elevation of ACTH is observed in endogenous causes of excessive secretion from a pituitary or extra-pituitary (ectopic) source. The end-point of elevated ACTH is a state of hypercortisolemia or Cushing's syndrome (CS).

 Cushing's Syndrome

Hypercortisolism is associated with hypertension, central obesity, insulin resistance, dyslipidemia with changes in clotting and platelet function. Hypertension is present in about 80% and diabetes/impaired glucose tolerance is seen in more than 50% of adult patients with endogenous CS which may occur due to several causes. In addition, endothelial dysfunction, hyperlipidemia and a state of hypercoagulability predispose them to increased risk of cardiovascular events such as myocardial infarction and strokes. The mechanisms of hypertension in CS are many and are as shown in [Table 2].[51]{Table 2}

Hypertension improves with treatment of CS though the probability of resolution declines with long-standing hypercortisolism. Other metabolic derangements such as impaired fasting glucose and glucose tolerance and diabetes mellitus secondary to increased insulin resistance may adversely impact the cardiovascular system by promoting atherosclerosis.[52],[53] Cardiac structural and functional abnormalities include LVH, diastolic and systolic dysfunction which may be reversed following correction of hypercortisolism.[54]

 Adrenal Glands

Cortisol and aldosterone from the adrenal cortex and catecholamines from the medulla exert significant effects on the cardiovascular system. Hormonal excess or deficiency may alter cardiac function significantly.


Aldosterone excess secondary to either genetic causes or primary aldosteronism (PA) (hyperplasia or aldosterone-secreting adenomas) is known to cause hypertension resulting in cardiac changes such as LVH and cardiac fibrosis. The direct action of aldosterone on myocardium, independent of pathological changes induced by the development of hypertension including up-regulation of the synthesis of collagen I and III, pro-inflammatory mediators, reactive oxygen species and activation of angiotensin II production, results in increased LV mass, myocardial fibrosis, and perivascular inflammation. The increase in LV mass has been found to be out of proportion to the degree of volume or pressure overload. Patients diagnosed with PA have a greater LV end-diastolic diameter as compared to those with essential hypertension, with no significant difference in the end-systolic diameter. The increased LV diastolic dimension may be attributed to cardiac volume overload due to the renal effects of aldosterone such as sodium retention and also due to direct inotropic effects.[55] These features are known to regress following treatment for excess aldosterone.[56]

Adrenal deficiency

It is a state of glucocorticoid deficiency which is mostly associated with a mineralocorticoid deficiency as well. ECG abnormalities seen in this condition are prolonged QT intervals, low voltage, prolonged PR or QRS interval, inverted T waves, and depressed ST segment. Steroids are needed for the maintenance of membrane calcium transport in the cardiac SR.[57] A decline in microsomal phosphorylase activity has been noted in rat heart muscle following adrenalectomy leading to reduced glycogenesis and cardiac contractility.[58]


Pheochromocytoma is a neuroendocrine tumor of enterochromaffin cells of the adrenal medulla (85%–90%) or extra-adrenal sympathetic paraganglia. It may manifest as paroxysmal or sustained hypertension in over 80%–90% of patients.[59] Hypertension secondary to a pheochromocytoma may result in exaggerated variability with an increased incidence of target organ damage. Secondary hypertension is characterized by increased peripheral resistance with a reduced cardiac index.[59] Hypertension may be related to increased secretion of catecholamines from sympathetic nerves, possibly secondary to increased noradrenaline in sympathetic stores due to uptake from the circulation.[60] Patients with a pheochromocytoma exhibit orthostatic hypotension with a decreased stroke volume and impaired adaptation of total peripheral resistance which implies inadequate arteriolar and venous reflexes.[61] Severe hypotension may also occur in the postoperative period following resection of a pheochromocytoma.[62],[63] Arrhythmias may be seen in around 20% of patients which include sinus tachycardia, supraventricular, and ventricular tachycardia and sick sinus syndrome. Pathological myocardial changes may result in cardiomyopathy, ischemic heart disease, cardiogenic shock, or myocardial stunning. Around a quarter of patients suffering from a pheochromocytoma may have an underlying dilated or hypertrophic cardiomyopathy.

ECG changes may include inverted T waves, QT prolongation, poor R-wave progression, and right axis deviation. Echocardiographic features of cardiomyopathy include a dilated LV with decreased contractility and ejection fraction, dilated left atrium with an elevated end diastolic pressure, and septal hypertrophy. Catecholamine-induced cardiomyopathy usually improves after surgical resection of a pheochromocytoma, but complete resolution depends on early detection and management.

 Gonadal Disorders

Turner syndrome

Turner syndrome is reported to have a prevalence of 1 in 2500 live births, with complete or partial absence of one X-chromosome and is characterized by short stature, ovarian failure, and infertility. Congenital heart defects (CHD) are seen in about 30% of patients and include bicuspid aortic valves, coarctation and dissection of aorta, aortic valve dysplasia, mitral valve abnormalities including ballooning and parachute valves. Conduction and repolarization abnormalities have been reported, and QTc prolongation may occur. Hypertension is seen in about one fourth of patients. The congenital and acquired cardiac abnormalities in Turner syndrome tend to progress warranting early, aggressive, and continued screening and treatment to reduce associated morbidity.[64]

Noonan syndrome

Noonan syndrome is characterized by dysmorphic facial features, CHD, short stature, webbed neck, chest deformities, and undescended testes in males. Cardiac malformations include pulmonary stenosis, with or without pulmonary valve dysplasia and hypertrophic cardiomyopathy. Other reported anomalies include atrial septal defects, atrioventricular septal defects, left-sided obstructive lesions, tetralogy of Fallot, and patent ductus arteriosus. The mechanism of occurrence of cardiac defects has been attributed to formation of abnormal cardiac jelly and extracellular matrix.[65]


Endocrine dysfunction has an adverse impact on the cardiovascular system which may be either due to an endocrine abnormality or an adverse reaction to drugs used in the management of these conditions. Most cardiovascular changes are reversible if detected early and the underlying endocrinopathy is corrected.

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Conflicts of interest

There are no conflicts of interest.


1Klein I, Danzi S. Thyroid disease and the heart. Circulation 2007;116:1725-35.
2Klein I. Endocrine disorders and cardiovascular disease. In: Zipes DP, Libby P, Bonow R, Braunwald E, editors. Braunwald's Heart Disease: A Textbook of Cardiovascular Medicine. 10th ed. Philadelphia: WB Saunders; 2005. p. 1793-808.
3Sylvén C, Jansson E, Sotonyi P, Waagstein F, Barkhem T, Brönnegård M. Cardiac nuclear hormone receptor mRNA in heart failure in man. Life Sci 1996;59:1917-22.
4Klein I, Danzi S. Thyroid disease and the heart. Curr Probl Cardiol 2016;41:65-92.
5Klein I, Ojamaa K. Thyroid hormone and the cardiovascular system. N Engl J Med 2001;344:501-9.
6Cooper DS, Biondi B. Subclinical thyroid disease. Lancet 2012;379:1142-54.
7Marvisi M, Zambrelli P, Brianti M, Civardi G, Lampugnani R, Delsignore R. Pulmonary hypertension is frequent in hyperthyroidism and normalizes after therapy. Eur J Intern Med 2006;17:267-71.
8Davis PJ, Davis FB, Mousa SA, Luidens MK, Lin HY. Membrane receptor for thyroid hormone: Physiologic and pharmacologic implications. Annu Rev Pharmacol Toxicol 2011;51:99-115.
9Connolly SJ. Evidence-based analysis of amiodarone efficacy and safety. Circulation 1999;100:2025-34.
10van Beeren HC, Kwakkel J, Ackermans MT, Wiersinga WM, Fliers E, Boelen A. Action of specific thyroid hormone receptor a(1) and ß(1) antagonists in the central and peripheral regulation of thyroid hormone metabolism in the rat. Thyroid 2012;22:1275-82.
11van Beeren HC, Bakker O, Chatterjee VK, Wiersinga WM. Effect of mutations in the beta1-thyroid hormone receptor on the inhibition of T3 binding by desethylamiodarone. FEBS Lett 1999;450:35-8.
12Rosene ML, Wittmann G, Arrojo e Drigo R, Singru PS, Lechan RM, Bianco AC. Inhibition of the type 2 iodothyronine deiodinase underlies the elevated plasma TSH associated with amiodarone treatment. Endocrinology 2010;151:5961-70.
13Barbesino G. Drugs affecting thyroid function. Thyroid 2010;20:763-70.
14Bogazzi F, Bartalena L, Martino E. Approach to the patient with amiodarone-induced thyrotoxicosis. J Clin Endocrinol Metab 2010;95:2529-35.
15Maeda SS, Fortes EM, Oliveira UM, Borba VC, Lazaretti-Castro M. Hypoparathyroidism and pseudohypoparathyroidism. Arq Bras Endocrinol Metabol 2006;50:664-73.
16Kamycheva E, Sundsfjord J, Jorde R. Serum parathyroid hormone levels predict coronary heart disease: The Tromsø Study. Eur J Cardiovasc Prev Rehabil 2004;11:69-74.
17Nyby MD, Hino T, Berger ME, Ormsby BL, Golub MS, Brickman AS. Desensitization of vascular tissue to parathyroid hormone and parathyroid hormone-related protein. Endocrinology 1995;136:2497-504.
18Somjen D, Weisman Y, Kohen F, Gayer B, Limor R, Sharon O, et al. 25-hydroxyvitamin D3-1alpha-hydroxylase is expressed in human vascular smooth muscle cells and is upregulated by parathyroid hormone and estrogenic compounds. Circulation 2005;111:1666-71.
19Perkovic V, Hewitson TD, Kelynack KJ, Martic M, Tait MG, Becker GJ. Parathyroid hormone has a prosclerotic effect on vascular smooth muscle cells. Kidney Blood Press Res 2003;26:27-33.
20Schiffl H, Lang SM. Hypertension secondary to PHPT: Cause or coincidence? Int J Endocrinol 2011;2011:974647.
21Silverberg SJ, Lewiecki EM, Mosekilde L, Peacock M, Rubin MR. Presentation of asymptomatic primary hyperparathyroidism: Proceedings of the third international workshop. J Clin Endocrinol Metab 2009;94:351-65.
22Ringer S. A further contribution regarding the influence of the different constituents of the blood on the contraction of the heart. J Physiol 1883;4:29-42.
23Newman DB, Fidahussein SS, Kashiwagi DT, Kennel KA, Kashani KB, Wang Z, et al. Reversible cardiac dysfunction associated with hypocalcemia: A systematic review and meta-analysis of individual patient data. Heart Fail Rev 2014;19:199-205.
24Wilson DI, Burn J, Scambler P, Goodship J. DiGeorge syndrome: Part of CATCH 22. J Med Genet 1993;30:852-6.
25Kabunga P, Lau AK, Phan K, Puranik R, Liang C, Davis RL, et al. Systematic review of cardiac electrical disease in Kearns-Sayre syndrome and mitochondrial cytopathy. Int J Cardiol 2015;181:303-10.
26Byatt JC, Staten NR, Salsgiver WJ, Kostelc JG, Collier RJ. Stimulation of food intake and weight gain in mature female rats by bovine prolactin and bovine growth hormone. Am J Physiol 1993;264(6 Pt 1):E986-92.
27Haring R, Friedrich N, Völzke H, Vasan RS, Felix SB, Dörr M, et al. Positive association of serum prolactin concentrations with all-cause and cardiovascular mortality. Eur Heart J 2014;35:1215-21.
28Stamatelopoulos KS, Georgiopoulos GA, Sfikakis PP, Kollias G, Manios E, Mantzou E, et al. Pilot study of circulating prolactin levels and endothelial function in men with hypertension. Am J Hypertens 2011;24:569-73.
29Hilfiker-Kleiner D, Kaminski K, Podewski E, Bonda T, Schaefer A, Sliwa K, et al. Acathepsin D-cleaved 16 kDa form of prolactin mediates postpartum cardiomyopathy. Cell 2007;128:589-600.
30Valassi E, Klibanski A, Biller BM. Clinical Review#: Potential cardiac valve effects of dopamine agonists in hyperprolactinemia. J Clin Endocrinol Metab 2010;95:1025-33.
31Flowers CM, Racoosin JA, Lu SL, Beitz JG. The US Food and Drug Administration's registry of patients with pergolide-associated valvular heart disease. Mayo Clin Proc 2003;78:730-1.
32Drake WM, Stiles CE, Bevan JS, Karavitaki N, Trainer PJ, Rees DA, et al. Afollow-up study of the prevalence of valvular heart abnormalities in hyperprolactinemic patients treated with cabergoline. J Clin Endocrinol Metab 2016;101:4189-94.
33Lu C, Schwartzbauer G, Sperling MA, Devaskar SU, Thamotharan S, Robbins PD, et al. Demonstration of direct effects of growth hormone on neonatal cardiomyocytes. J Biol Chem 2001;276:22892-900.
34Lombardi G, Di Somma C, Grasso LF, Savanelli MC, Colao A, Pivonello R. The cardiovascular system in growth hormone excess and growth hormone deficiency. J Endocrinol Invest 2012;35:1021-9.
35Amato G, Carella C, Fazio S, La Montagna G, Cittadini A, Sabatini D, et al. Body composition, bone metabolism, and heart structure and function in growth hormone (GH)-deficient adults before and after GH replacement therapy at low doses. J Clin Endocrinol Metab 1993;77:1671-6.
36Valcavi R, Gaddi O, Zini M, Iavicoli M, Mellino U, Portioli I. Cardiac performance and mass in adults with hypopituitarism: Effects of one year of growth hormone treatment. J Clin Endocrinol Metab 1995;80:659-66.
37Andreassen M, Faber J, Kjaer A, Petersen CL, Kristensen LØ. Cardiac function in growth hormone deficient patients before and after 1 year with replacement therapy: A magnetic resonance imaging study. Pituitary 2011;14:1-10.
38Markussis V, Beshyah SA, Fisher C, Sharp P, Nicolaides AN, Johnston DG. Detection of premature atherosclerosis by high-resolution ultrasonography in symptom-free hypopituitary adults. Lancet 1992;340:1188-92.
39Sanmartí A, Lucas A, Hawkins F, Webb SM, Ulied A. Observational study in adult hypopituitary patients with untreated growth hormone deficiency (ODA study). Socio-economic impact and health status. Collaborative ODA (Observational GH Deficiency in Adults) Group. Eur J Endocrinol 1999;141:481-9.
40Colao A, Di Somma C, Cuocolo A, Filippella M, Rota F, Acampa W, et al. The severity of growth hormone deficiency correlates with the severity of cardiac impairment in 100 adult patients with hypopituitarism: An observational, case-control study. J Clin Endocrinol Metab 2004;89:5998-6004.
41Carroll PV, Christ ER, Bengtsson BA, Carlsson L, Christiansen JS, Clemmons D, et al. Growth hormone deficiency in adulthood and the effects of growth hormone replacement: A review. Growth Hormone Research Society Scientific Committee. J Clin Endocrinol Metab 1998;83:382-95.
42Colao A, Di Somma C, Savanelli MC, De Leo M, Lombardi G. Beginning to end: Cardiovascular implications of growth hormone (GH) deficiency and GH therapy. Growth Horm IGF Res 2006;16 Suppl A:S41-8.
43Colao A, Vitale G, Pivonello R, Ciccarelli A, Di Somma C, Lombardi G. The heart: An end-organ of GH action. Eur J Endocrinol 2004;151 Suppl 1:S93-101.
44Al-Shoumer KA, Page B, Thomas E, Murphy M, Beshyah SA, Johnston DG. Effects of four years' treatment with biosynthetic human growth hormone (GH) on body composition in GH-deficient hypopituitary adults. Eur J Endocrinol 1996;135:559-67.
45Pfeifer M, Verhovec R, Zizek B, Prezelj J, Poredos P, Clayton RN. Growth hormone (GH) treatment reverses early atherosclerotic changes in GH-deficient adults. J Clin Endocrinol Metab 1999;84:453-7.
46Bruch C, Herrmann B, Schmermund A, Bartel T, Mann K, Erbel R. Impact of disease activity on left ventricular performance in patients with acromegaly. Am Heart J 2002;144:538-43.
47Melmed S. Medical progress: Acromegaly. N Engl J Med 2006;355:2558-73.
48Damjanovic SS, Neskovic AN, Petakov MS, Popovic V, Vujisic B, Petrovic M, et al. High output heart failure in patients with newly diagnosed acromegaly. Am J Med 2002;112:610-6.
49Castellano G, Affuso F, Conza PD, Fazio S. The GH/IGF-1 axis and heart failure. Curr Cardiol Rev 2009;5:203-15.
50Maison P, Tropeano AI, Macquin-Mavier I, Giustina A, Chanson P. Impact of somatostatin analogs on the heart in acromegaly: A metaanalysis. J Clin Endocrinol Metab 2007;92:1743-7.
51Ong SL, Whitworth JA. How do glucocorticoids cause hypertension: Role of nitric oxide deficiency, oxidative stress, and eicosanoids. Endocrinol Metab Clin North Am 2011;40:393-407, ix.
52Fernández-Real JM, Ricart W. Insulin resistance and chronic cardiovascular inflammatory syndrome. Endocr Rev 2003;24:278-301.
53Magiakou MA, Smyrnaki P, Chrousos GP. Hypertension in Cushing's syndrome. Best Pract Res Clin Endocrinol Metab 2006;20:467-82.
54Pereira AM, Delgado V, Romijn JA, Smit JW, Bax JJ, Feelders RA. Cardiac dysfunction is reversed upon successful treatment of Cushing's syndrome. Eur J Endocrinol 2010;162:331-40.
55White PC. Aldosterone: Direct effects on and production by the heart. J Clin Endocrinol Metab 2003;88:2376-83.
56Ezekowitz JA, McAlister FA. Aldosterone blockade and left ventricular dysfunction: A systematic review of randomized clinical trials. Eur Heart J 2009;30:469-77.
57Nishizawa S, Nakamura T, Hamaoka T, Matsumuro A, Sawada T, Matsubara H. Lethal arrhythmia and corticosteroid insufficiency. Am J Emerg Med 2009;27:1167.e1-3.
58Narayanan N, Khandelwal RL. Microsomal phosphorylase in rat heart: Depletion following adrenalectomy and restoration by in vivo administration of dexamethasone. Endocrinology 1985;117:1544-9.
59Prejbisz A, Lenders JW, Eisenhofer G, Januszewicz A. Cardiovascular manifestations of phaeochromocytoma. J Hypertens 2011;29:2049-60.
60Bravo EL, Tarazi RC, Fouad FM, Textor SC, Gifford RW, Vidt DG. Blood pressure regulation in pheochromocytoma. Hypertens Dallas Tex 1982;4(3 Pt 2):193-9.
61Levenson JA, Safar ME, London GM, Simon AC. Haemodynamics in patients with phaeochromocytoma. Clin Sci (Lond) 1980;58:349-56.
62Grasselli G, Foti G, Patroniti N, Rona R, Perlangeli MV, Pesenti A. Extracorporeal cardiopulmonary support for cardiogenic shock caused by pheochromocytoma: A case report and literature review. Anesthesiology 2008;108:959-62.
63Wu GY, Doshi AA, Haas GJ. Pheochromocytoma induced cardiogenic shock with rapid recovery of ventricular function. Eur J Heart Fail 2007;9:212-4.
64Dulac Y, Pienkowski C, Abadir S, Tauber M, Acar P. Cardiovascular abnormalities in Turner's syndrome: What prevention? Arch Cardiovasc Dis 2008;101:485-90.
65Digilio M, Marino B. Clinical manifestations of Noonan syndrome. Images Paediatr Cardiol 2001;3:19-30.