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The endocrine system and hormone function: Growth Hormone Deficiency | Johns Hopkins Medicine

Growth Hormone Deficiency | Johns Hopkins Medicine

What is growth hormone deficiency?

Growth hormone deficiency (GHD), also known as dwarfism or pituitary dwarfism, is a condition caused by insufficient amounts of growth hormone in the body. Children with GHD have abnormally short stature with normal body proportions. GHD can be present at birth (congenital) or develop later (acquired). The condition occurs if the pituitary gland makes too little growth hormone. It can be also the result of genetic defects, severe brain injury or being born without a pituitary gland. In some cases, there is no clear cause identified. Sometimes, GHD can be associated with lower levels of other hormones, such as vasopressin (which controls water production in the body), gonadotropins (which controls the production of male and female sex hormones), thyrotropins (which control the production of thyroid hormones) or adrenocorticotrophic hormone (which controls the adrenal gland and related hormones).  

Symptoms

  • Slow growth or absence of growth

  • Short stature (below the fifth percentile compared to other children of the same age and sex)

  • Absent or delayed sexual development during puberty 

  • Headaches

Symptoms of other pituitary hormone deficiencies that may co-exist with growth hormone deficiency:

  • Absent or delayed sexual development during puberty

  • Increased urination and amount of urine

  • Excessive thirst

  • Facial abnormalities can be present in a small group of children with GHD, typically caused by pituitary defects.

Diagnosis

A physical exam and measurement of height, weight, arms and leg lengths are the first steps to diagnosis, in addition to thorough medical history. Blood tests to measure the levels of growth hormone in the body as well as the levels of other hormones. Imaging tests including X-rays and MRI of the head may be helpful in narrowing down the underlying disorder causing GHD by revealing abnormalities of the hypothalamus or the pituitary glands. 

Treatment

Some cases of GHD can be treated with the use of synthetic growth hormone under the supervision of a pediatric endocrinologist. If other hormone deficiencies exist, other hormones can be given in addition to synthetic growth hormone.

Endoscopic Pituitary Surgery | Johns Hopkins Medicine

Endoscopic pituitary surgery, also called transsphenoidal endoscopic surgery, is the most common surgery used to remove pituitary tumors. The pituitary gland is located at the bottom of your brain and above the inside of your nose. It is responsible for regulating most of your body’s hormones, the chemical messengers that travel through your blood.

Endoscopic pituitary surgery is done with an instrument called an endoscope. An endoscope is a thin, rigid tube that has a microscope, light, and camera built into it, and it’s usually inserted through the nose. The camera lets your surgeon watch on a television screen while inserting other special instruments through the scope to remove the tumor.

Reasons for endoscopic pituitary surgery

Endoscopic pituitary surgery is done to remove certain types of tumors that start to grow in your pituitary gland:

  • Hormone-secreting tumors. These growths secrete chemical messengers that travel through the blood.

  • Nonhormone-secreting tumors. These growths, also called endocrine inactive pituitary adenomas, are removed by surgery because as they increase in size they may cause headache and visual disturbances.

  • Cancerous tumors. These growths may be treated with a combination of surgery, cancer drugs, and X-ray treatment.

Risks of endoscopic pituitary surgery

Endoscopic pituitary surgery is a safe type of surgery, but all surgical procedures carry some risk for reaction to anesthesia, bleeding, and infection. Risks and complications that may occur with this type of surgery also include:

  • CSF rhinorrhea. CSF, or cerebrospinal fluid, is the fluid that surrounds the brain, and it may leak from the nose after surgery. In some cases, another surgery may be needed to repair this leak.

  • Meningitis. This is a type of infection occurring in the membrane lining the brain and spinal cord that can occur after surgery. It is more common if the CSF leaks.

  • Damage to normal parts of the pituitary gland. Damage to areas of the pituitary that secrete hormones may require hormone replacement after surgery.

  • Diabetes insipidus. Damage to a part of the pituitary gland that helps control urination may lead to frequent urination and thirst.

  • Severe bleeding. Heavy and persistent bleeding into the brain or from the nose may occur if a large blood vessel is damaged during surgery.

  • Visual problems. The nerves that supply vision are close to the area of the pituitary gland can be damaged.

There may be other risks, depending on your specific medical condition. Be sure to discuss any concerns with your doctor before the procedure.

Before endoscopic pituitary surgery

You may need to see an endocrinology specialist for an evaluation before surgery. Endocrinologists are the medical specialists that deal with glands and hormones. You may also have your vision checked before surgery.

Endoscopic pituitary surgery is usually done under general anesthesia, so you will be asked to stop eating and drinking after midnight on the night before surgery. You may need to stop taking some types of medications that may increase bleeding during surgery. Don’t take any over-the-counter medications before surgery without telling your doctor. You may have several blood tests, a heart rhythm test, and a chest X-ray. These will all be checked before surgery and you will need to be examined by the doctor who gives anesthesia.

During endoscopic pituitary surgery

The actual surgery may take a few hours. In many cases, an ear, nose, and throat specialist will work with a neurosurgeon. These steps may take place:

  • The ear, nose, and throat surgeon usually places the endoscope through the nose. In some cases, the endoscope may be inserted through an incision under the upper lip.

  • The endoscope is advanced until the bony wall of the sphenoid sinus is found at the back of the nose.

  • The sphenoid sinus is opened and the scope is passed through to the back wall of the sinus.

  • A small opening is made in the back wall of the sinus.

  • Magnetic resonance imagining (MRI) may be used to make images of the pituitary area using a computer and magnets during the surgery to help guide the surgeons.

  • When the pituitary area is entered, the neurosurgeon removes the pituitary tumor in small pieces.

  • When all parts of the tumor that can be reached have been removed, the endoscope is removed. Some packing may be placed in the nose to complete the operation.

After endoscopic surgery

You may need to stay in the hospital for a day or two. During this time, nurses will help you with any dressings and bathroom needs. You will be able to return to a normal diet as long as you are taking fluids well. You will be encouraged to get out of bed and walk as soon as you are able. While in the hospital, you will be asked to help your nurses keep track of the amount of fluids you drink and your urine output to evaluate pituitary function.

Aftercare at home may include:

  • Pain medication to control headaches, the most common complaint after surgery

  • Restricted activities – no lifting or straining until cleared by your surgeons

  • Follow-up visits with your endocrinologist and surgeons

  • Repeat MRI

  • Visual testing

It is important to let your surgeons know about:

Endocrinology, Diabetes and Thyroid Specialist

 

An unhealthy endocrine system can mean trouble for your body, because it is responsible for many different functions.

Let us take a look at why the endocrine system is so important, its most important roles, and how you can help keep it in tip-top shape.

 

 

What Your Endocrine System Does for You

The endocrine system is a series of glands in your body that create hormones responsible for just about every function, cell and organ of your body.

The main glands in your endocrine system include:

  • Adrenals: Two glands that sit on top of each kidney and make cortisol, sex hormones, and the “fight or flight” hormone adrenaline.
  • Hypothalamus: A portion of the brain that links the endocrine and nervous systems and tells the pituitary gland when to make hormones.
  • Ovaries (in women): Organs that make the hormones estrogen and progesterone important for development, pregnancy support, and menstrual cycle regulation.
  • Pituitary gland: The “master gland” that tells other glands what to do after getting information from your brain.
  • Pineal gland: A gland that creates melatonin, which you need to regulate sleep.
  • Parathyroid: Four tiny glands that sit behind your thyroid, make the peptide hormone PTH, control calcium and phosphorus levels, and play a role in bone health.
  • Pancreas: An organ that makes digestive enzymes to break down food as well as the hormones glucagon and insulin to regulate blood sugar.
  • Thymus: A gland that creates white blood cells to fight infection and is most active during childhood and early teen years.
  • Thyroid gland: A gland that creates thyroid hormones to regulate your metabolism and many other crucial functions.
  • Testes (in men): Organs that make testosterone, control development, and help body hair growth during puberty.

As you can see, there are many organs and functions involved in the endocrine system. If something is not working correctly within the network of this system, it may cause a lot of problems in other areas. Below are the 3 vital functions of your endocrine system.

1. Makes Hormones for Mood, Development, and Growth

Many different vital hormones are created and controlled within the endocrine system. This is extremely important, as your body needs hormones to send messages throughout it and regulate various body processes. If someone’s endocrine system isn’t healthy and is not making the right amount of hormones, it can lead to problems, running from excessive stress levels, weight gain, and fatigue to trouble becoming pregnant, improper development during puberty, and weak bones.

2. Sends Hormones into Your Bloodstream

After making hormones, your endocrine system sends them into your bloodstream to travel between different areas of your body.

3. Regulates the Release of Hormones

Besides creating and releasing hormones, your endocrine system also regulates and controls how much of each hormone gets released. Numerous factors can impact your hormone levels, including how many are already in your blood, infections, stress, certain minerals in your blood, and more. The endocrine system will work to maintain the right balance. When something goes wrong with the endocrine system, it can lead to an endocrine disorder or other issues that affect your weight, mood, development, and more. This is why it’s so important to keep our systems, organs and glands as healthy as we can. Too little or too much of any hormone can be detrimental. Some ways you can support your endocrine system include:

  • Eating a whole foods-based, nutrient-dense diet
  • Getting enough exercise · Managing emotional stress
  • Being mindful of any endocrine-related problems that run in your family
  • Getting regular checkups
  • Talking to us at Palmetto Endocrinology about supplements that may help

The Bottom Line

Your endocrine system is smart, but it sometimes needs a little help. Making healthy choices and addressing any changes you notice in your body can help you be mindful of this delicate and amazing system. At Palmetto Endocrinology we are happy to help you with your health needs. Please make an appointment today to see us.

Author

Joseph Mathews, MD, FACP, FACE, ECNU, CCD
Joseph W. Mathews M.D., a board certified Endocrinologist and Medical Director of Palmetto Endocrinology, was born and raised in South Carolina. He earned his Bachelor of Science in Biology from the College of Charleston, Cum Laude. He then achieved his M.D. at the Medical University of South Carolina where he also completed his residency in Internal Medicine and a Fellowship in Endocrinology, Diabetes, and Metabolism.

Dr. Mathews is also a Fellow of both the American College of Endocrinology and the American College of Physicians, holds an Endocrine Certification in Neck Ultrasound (ECNU) and is a Certified Clinical Densitometrist (CCD). He has extensive experience performing ultrasound guided fine needle aspiration biopsies. His practice includes a range of specializations including prescribing and fitting patients with insulin pumps.

Dr. Mathews’ practice has drawn patients from out of state to benefit from his expertise in thyroid disorders, diabetes, cortisol problems and their Endocrine disorders.

Hormones and the Endocrine System

Adrenal glands

Aldosterone

Regulates salt, water balance, and blood pressure

Adrenal glands

Cortisol
(corticosteroid)

Controls key functions in the body; acts as an anti-inflammatory; maintains blood
sugar levels, blood pressure, and muscle strength; regulates salt and water balance

Pituitary gland

Antidiuretic hormone (vasopressin)

Affects water retention
in kidneys and sodium balance; controls blood pressure

Pituitary gland

Adrenocorticotropic hormone (ACTH)

Controls production of cortisol and other steroids made by the adrenal glands.

Pituitary gland

Growth hormone (GH)

Affects growth and development; stimulates protein production; affects fat distribution

Pituitary gland

Luteinizing hormone (LH) and follicle-stimulating hormone (FSH)

Controls production of sex hormones (estrogen in women and testosterone in men) and
the production of eggs in women and sperm in men

Pituitary gland

Oxytocin

Stimulates contraction
of uterus and milk release in the female breast during breastfeeding. Also
may play a role in trust and bonding, especially between parents and
children.

Pituitary gland

Prolactin

Initiates and maintains milk production in breasts; impacts sex hormone levels

Pituitary gland

Thyroid-stimulating hormone (TSH)

Stimulates the production and secretion of thyroid hormones

Kidneys

Renin

Controls blood
pressure, both directly and also by regulating angiotensin levels and
aldosterone production from the adrenal glands

Kidneys

Erythropoietin

Affects red blood cell (RBC) production

Pancreas

Glucagon

Raises blood sugar levels

Pancreas

Insulin

Lowers blood sugar levels; stimulates metabolism of glucose, protein, and fat

Ovaries

Estrogen

Affects development of
female sexual characteristics and reproductive development, important for
functioning of uterus and breasts; also helps protect bone health

Ovaries

Progesterone

Stimulates the lining of the uterus for fertilization; prepares the breasts for milk
production

Parathyroid glands

Parathyroid hormone (PTH)

Plays the most
important role in regulating blood calcium levels

Thyroid gland

Thyroid hormone

Controls metabolism; also affects growth, maturation, nervous system activity, and
metabolism

Adrenal glands

Epinephrine

Increases heart rate, oxygen intake, and blood flow

Adrenal glands

Norepinephrine

Maintains blood pressure

Testes (testicles)

Testosterone

Develops and maintains
male sexual characteristics and maturation; also helps protect bone
health

Pineal gland

Melatonin

Helps with sleep

Hypothalamus

Growth hormone-
releasing hormone (GHRH)

Regulates growth hormone release in the pituitary gland

Hypothalamus

Thyrotropin-releasing
hormone (TRH)

Regulates thyroid stimulating hormone release in the pituitary gland

Hypothalamus

Gonadotropin-releasing
hormone (GnRH)

Regulates LH/FSH production in the pituitary gland

Hypothalamus

Corticotropin-releasing
hormone (CRH)

Regulates
adrenocorticotropic hormone (ACTH) release in the pituitary gland

Thymus

Humoral factors

Helps develop the immune system during puberty

The Endocrine System and the Heart: A Review

Introduction

Normal endocrine function is essential for cardiovascular health. Disorders of the endocrine system, consisting of hormone hyperfunction and hypofunction, have multiple effects on the cardiovascular system. The objective of this review is to explore the various cardiovascular changes that occur in endocrine dysfunction. We will also assess the cardiovascular benefits of correcting endocrine disorders. Diabetes is specifically excluded, as the well-known relationship between diabetes and cardiovascular risk is beyond the scope of this review.

The pituitary gland and the cardiovascular system Pituitary Overview

The anterior pituitary gland contains five cell types that synthesize and secrete hormones (growth hormone [GH], prolactin, follicle stimulating hormone, luteinizing hormone, thyroid stimulating hormone [TSH], adrenocorticotropic hormone [ACTH]), that participate in hypothalamic-pituitary-target organ regulation. The posterior pituitary contains nerve terminals that secrete vasopressin (antidiuretic hormone) and oxytocin. Of the pituitary hormones secreted by the anterior pituitary, disorders of prolactin, GH, and ACTH may be associated with cardiac disease.

Prolactin Disorders and Cardiovascular Disease

Prolactin is synthesized and secreted by lactotroph cells of the anterior pituitary gland, and stimulates lactation in the postpartum period. Prolactin is tonically inhibited by hypothalamic dopamine. Prolactin levels are physiologically elevated in pregnancy, the postpartum period, and in states of stress. Pathologic hyperprolactinemia may be caused by decreased dopaminergic inhibition, such as when the pituitary stalk is disrupted, or by prolactin secretion from prolactinomas (benign pituitary adenomas). The prevalence of hyperprolactinemia ranges from 0.4% in the general adult population to 9% in women with reproductive disorders.1 Although hyperprolactinemia itself does not have clear effects on the cardiovascular system, there is a possible association between long-term treatment with dopamine agonists and cardiac valve abnormalities.

Dopamine agonists, including cabergoline, bromocriptime, and quinagolide (not approved for use in the United States), are the primary treatment for prolactinomas. Cabergoline is most commonly used, due to its clinical efficacy, tolerability, and favorable pharmacokinetic profile.2 High doses and long duration of therapy with dopamine agonists have been associated in Parkinson’s disease with an increased risk of regurgitant valve disease.3,4 Although doses used for prolactinoma therapy are much lower than those used for Parkinson’s disease, patients with prolactinoma may be treated for decades. This treatment duration raises concern for increased risks of valvulopathy, including tricuspid regurgitation, mitral regurgitation, and aortic regurgitation.5,6 Although most reports do not show an association between the use of dopamine agonists and cardiac valve disease, clinicians are advised to use the lowest possible doses of dopamine agonists. Echocardiographic monitoring should be considered, especially in patients requiring long-term and/or higher-dose therapy, and those with underlying heart or valvular disease.7

Peripartum cardiomyopathy is a rare clinical entity. It has been suggested that a 16 kDa prolactin fragment may play a role in its pathophysiology.8 Case reports have described the use of bromocriptine in addition to standard heart failure therapy in peripartum cardiomyopathy.9

Growth Hormone Overview

GH is synthesized and secreted by somatotroph cells in the anterior pituitary gland. It acts directly on peripheral tissues via interaction with the GH receptor, and indirectly via stimulation of insulin-like growth factor type 1 (IGF-1) synthesis. In virtually all cell types, IGF-1 promotes glucose uptake and cellular protein synthesis. GH and IGF-1 regulate somatic growth, including cardiac development and function10

The prevalence of GH deficiency (GHD) in adults is approximately 1-2 per 10,000.11 The prevalence of acromegaly, or excess GH secretion, is approximately 40-70 cases per million, with an estimated incidence of 3-4 per million annually.12,13

Growth Hormone Deficiency Overview

Adults with GHD can be grouped into three categories: those with childhood onset GHD, those with acquired GHD secondary to structural lesions or trauma, and those with idiopathic adult onset GHD. 14 Diagnosis is confirmed by low serum IGF-1 levels and provocative testing using insulin-induced hypoglycemia, and the combination of arginine and GH-releasing hormone (GHRH), which are potent stimuli for GH secretion. A subnormal increase in serum GH concentration after insulin tolerance or GHRH-arginine tests confirms the diagnosis of GHD.15 Treatment of GHD consists of GH replacement.

Growth Hormone Deficiency and Cardiovascular Disease Cardiovascular Risk

GHD is associated with increased body fat and central adiposity, dyslipidemia (low high density lipoprotein cholesterol [HDLc], high total cholesterol, and high low density lipoprotein cholesterol [LDLc]), endothelial dysfunction, and insulin resistance16,17 (Figure 1). Increased carotid arterial intima-media thickness (IMT), a marker of early atherosclerotic development, has also been described in GHD.19,20 GH replacement therapy can result in increased lean body mass and decreased visceral adipose tissue21 and may decrease total and LDLc levels, although effects on HDLc have been inconsistent. 22 Endothelial dysfunction improves with GH replacement therapy, with increased flow-mediated dilatation and reduced arterial stiffness due to improved nitric oxide (NO) availability.23 Although GH replacement therapy has been shown to reduce IMT, effects on cardiovascular outcomes are uncertain.24

Figure 1. Effect of growth hormone deficiency on atherosclerosis. GHD, growth hormone deficiency; IGF-1, of insulin-like growth factor type 1; NO, nitric oxide. Adapted with permission from Colao A. 18

Cardiac Structure and function

Echocardiography in patients with childhood- or adolescent-onset GHD has revealed significant reductions in left ventricular (LV) posterior wall thickness and interventricular septal thickness, with resultant decreases in LV mass index and LV internal diameter.25,26 Most adult patients with GHD have impaired LV performance at peak exercise, and report exercise intolerance.27 Several studies have shown that GH replacement therapy improves cardiac performance and increases LV mass, LV end diastolic volume (LVEDV), and stroke volume. 25,28

Acromegaly Overview

Acromegaly is characterized by high circulating GH and IGF-1 levels, and is caused by a benign pituitary adenoma in >98% of cases. The morbidity and mortality associated with acromegaly are due to the metabolic effects of GH/IGF-1 hypersecretion and the mass effects of the pituitary adenoma. The mean age at diagnosis is 40-45 years, typically with 5-10 years of symptoms prior to diagnosis. Symptoms include decreased exercise tolerance, increased ring size or ring tightness, increased shoe size, prominence of the jaw and/or forehead, acne or oily skin, arthropathies, and neuropathies.29,30

Diagnosis of acromegaly is suggested by elevated IGF-1 levels, and confirmed by elevated GH levels after administration of an oral glucose tolerance test. Treatments for acromegaly aim to reduce or control adenoma growth, inhibit GH hypersecretion, and normalize IGF-I levels. Surgery is first-line therapy for acromegaly. Treatment options for persistently elevated GH and/or IGF-1 levels include medical therapy and radiotherapy. The three drug classes available for acromegaly treatment are somatostatin analogs, dopamine agonists, and GH receptor antagonists.31

Acromegaly and Cardiovascular Disease Cardiovascular Risk

Hypertension occurs in 20%-50% of patients with acromegaly. Possible mechanisms include increased arterial stiffness due to hypertrophy and fibrosis of the arterial muscular tunica.32 Acromegaly is also associated with an increased prevalence of diabetes mellitus.33 Systolic and diastolic blood pressure and glycemic control improve with normalization of IGF-1 levels.34

Cardiac Structure and Function

Cardiac histological abnormalities in acromegaly include myocyte hypertrophy, interstitial fibrosis, inflammatory cell infiltration, reduced capillary density, myofibril derangement, and extracellular collagen deposition. The impact of these changes on the structure and function of myocardial and valvular tissues is determined by the duration and severity of GH/IGF-1 excess. In the early stage of acromegaly, there is enhanced myocardial contractility, decreased systemic vascular resistance, increased cardiac output, and overall increased cardiac performance. Relative wall thickness (LV wall thickness/LV radius) increases and causes a reduction in wall stress. In the intermediate stage, after about 5 years of active disease, there is biventricular hypertrophy, diastolic dysfunction, and impaired exertional cardiac performance. Late-stage acromegalic cardiomyopathy is characterized by systolic and diastolic dysfunction, increased myocardial mass, ventricular cavity dilatation, and increased systemic vascular resistance.32 Acromegalic cardiomyopathy is frequently present at diagnosis. Up to two thirds of patients with acromegaly meet echocardiographic criteria for left ventricular hypertrophy (LVH), including about half of all normotensive acromegalics. Patients with severe cardiomyopathy may progress to heart failure, with heart failure seen in 3%-10% of patients.35 Successful treatment of acromegaly halts the progression of cardiac dysfunction, and reduces cardiovascular mortality.29 Surgical cure has been reported to reduce cardiac mass and improve diastolic filling. 36 Successful disease control with somatostatin analogs has been shown to improve diastolic filling parameters, reduce volume overload, reduce pulmonary and wedge pressures, and enhance cardiac performance.37 Some evidence suggests that cardiac hypertrophy is reversible in younger patients with a short duration of disease.27 Improvement in LV ejection fraction at peak exercise is also seen in younger patients with short disease duration.38

Cardiac valve disease (aortic and mitral regurgitation) is frequent in acromegaly.39 GH/IGF-1 excess may lead to abnormal extracellular matrix regulation and thus to pathogenesis of myxomatous valvulopathy. The risk of valve disease increases significantly with the duration of GH excess. Aortic and mitral valve dysfunction often persist despite treatment of hormonal excess.40

Rhythm

Electrocardiogram (ECG) and Holter studies have documented cardiac rhythm abnormalities in acromegaly. Resting ECG changes include left axis deviation, increased QT intervals, septal Q-waves, and ST-T wave depression.41 Additionally, up to 56% of patients with active acromegaly have late potentials on ECG that could predispose to arrhythmias.42 Rhythm disturbances, seen mainly during physical exercise, include atrial and ventricular ectopic beats, paroxysmal atrial fibrillation, paroxysmal supraventricular tachycardia, sick sinus syndrome, bundle branch block, and ventricular tachycardia. The frequency of ventricular premature complexes increases with the duration of acromegaly. The severity of ventricular arrhythmias correlates with increases in LV mass.43 Somatostatin analogs have been shown to reduce QT intervals, and to improve the arrhythmic profile in acromegalic patients.44

Adrenocorticotropic Hormone Overview

Adrenocorticotropic hormone is synthesized and secreted by corticotroph cells of the anterior pituitary gland. The primary role of ACTH is to regulate adrenal cortisol secretion. Excess ACTH can be produced by pituitary corticotroph adenoma or, rarely, by an extrapituitary tumor (ectopic ACTH syndrome) such as small cell lung cancer, carcinoid tumor, or medullary thyroid cancer. This excess ACTH secretion results in hypercortisolism, or Cushing’s syndrome. Endogenous Cushing’s syndrome is caused by excessive secretion of ACTH (ACTH-dependent cases) in approximately 80% of cases, and by ACTH-independent causes in approximately 20% of cases that include cortisol secretion by unilateral adrenal adenomas, or by bilateral adrenal hyperplasia or dysplasia.45 The overall incidence of endogenous Cushing’s syndrome is 2.3 cases per million annually.46

The diagnosis of Cushing’s syndrome requires demonstration of elevated cortisol levels with at least two confirmatory tests, including 24-hour urinary-free cortisol, late-night salivary free cortisol, or overnight dexamethasone suppression test. 47,48 The goals of treatment in Cushing’s syndrome are normalization and long-term control of cortisol levels, and reversal of clinical features such as weight gain, central obesity, fatigue, muscle weakness, hypertension, diabetes, hirsutism, acne, and menstrual disorders. Treatment options include transsphenoidal surgery, unilateral or bilateral adrenalectomy, radiotherapy and medical therapy. The selection and efficacy of any given treatment modality depends on the underlying cause of hypercortisolism.49 Medical control of hypercortisolism in nonsurgical patients may be achieved using ketoconazole, metyrapone, and/or mitotane.50

Cushing’s Syndrome and Cardiovascular Disease Cardiovascular Risk

Hypercortisolism is associated with hypertension, central obesity, insulin resistance, dyslipidemia, and alterations in clotting and platelet function51 (Figure 2). Hypertension is present in about 80% of adult patients with endogenous Cushing’s syndrome, and results from changes in regulation of plasma volume, systemic vascular resistance, and vasodilatation.53,54 Treatment of Cushing’s syndrome usually results in improvement or resolution of hypertension, although hypertension may persist in patients with long-standing hypercortisolism and/or co-existing essential hypertension.55 Abnormal glucose metabolism in Cushing’s syndrome results from stimulation of hepatic gluconeogenesis and glycogenolysis. Patients with hypercortisolism may have impaired fasting glucose, impaired glucose tolerance, hyperinsulinemia, insulin resistance, and/or diabetes mellitus.56 Cushing’s syndrome has been associated with increased lipoprotein (a), decreased HDLc, and increased triglycerides.54 The duration of cortisol excess correlates with the degree of dyslipidemia seen. Cortisol also increases the synthesis of several coagulation factors, stimulating endothelial production of von Willebrand factor and concomitantly increasing factor VIII.57 Hypercortisolism may also enhance platelet aggregation and reduce plasma fibrinolytic capacity.58,59

Figure 2. Mechanisms of increased cardiovascular risk mediated by hypercortisolism. Reprinted with permission from Fallo et al. 52

Cardiac Structure and Function

Cushing’s syndrome has been associated with LVH, concentric remodeling, diastolic dysfunction, and subclinical LV systolic dysfunction.60 Echocardiography has revealed increased interventricular septum thickness and posterior wall thickness, increased LV mass index, and increased relative wall thickness in Cushing’s patients. Diastolic dysfunction has been demonstrated, with impaired early LV relaxation, longer isovolumetric relaxation times, and evidence of global myocardial relaxation impairment. The abnormalities of LV structure and function may be reversible with normalization of hypercortisolism. However, patients may continue to exhibit exercise intolerance due to steroid-induced myopathy and resultant muscle weakness.61

Thyroid and the cardiovascular system Thyroid Overview

Thyroid dysfunction is common. Hyperthyroidism is present in 1.3% of the United States population (overt in 0.5% and subclinical in 0.7%), and hypothyroidism in 4.6% of the population (overt in 0.3% and subclinical in 4.3%).62 The prevalence of both hypothyroidism and hyperthyroidism increases with age. Data from the Framingham Heart Study have demonstrated suppressed thyrotropin (TSH) levels in 3.9% of patients over age 60 years, and some degree of hypothyroidism, as evidenced by elevated serum TSH levels (>5 mU/L), in 10.3% of unselected patients over age 60 years, with a higher incidence in women (13.6%) than in men (5.7%).63,64

Hyperthyroidism Overview

Overt thyrotoxicosis, or hyperthyroidism, is defined by elevated peripheral free thyroid hormone levels (T3 and/or T4) and a decreased or undetectable TSH. Thyrotoxicosis may result from autoimmune disease, thyroid nodule autonomy, or exogenous thyroid hormone ingestion. Hyperthyroid patients often present with signs and symptoms related to the cardiovascular system including palpitations, sinus tachycardia, atrial fibrillation, systolic hypertension, widened pulse pressure, exercise intolerance, and exertional dyspnea. Other symptoms include fatigue, weight loss, heat intolerance, and diarrhea. Treatments for hyperthyroidism include antithyroid medications (methimazole, carbimazole, and propylthiouracil), beta-blockers, radioactive iodine ablation, and thyroid surgery. Subclinical hyperthyroidism is defined by low or undetectable serum TSH and normal peripheral free thyroid hormone levels. Patients are usually asymptomatic, but remain at risk for some cardiovascular changes associated with hyperthyroidism.65 Consensus panel recommendations suggest consideration of treatment for a persistently suppressed serum TSH (TSH 66

Hyperthyroidism and Cardiovascular Disease Hemodynamics

Genomic and nongenomic actions of thyroid hormone result in cardiovascular hemodynamic changes in overt hyperthyroidism that include decreased systemic vascular resistance (SVR), increased heart rate, increased cardiac preload, and increased cardiac output.67,68 SVR is reduced in hyperthyroidism due to thyroid hormone-mediated relaxation of vascular smooth muscle cells and increased endothelial NO production.69,70 The decrease in SVR activates the renin-angiotensin-aldosterone system, leading to increased plasma volume and increased cardiac preload. Thyroid hormone also promotes an increase in blood volume via up-regulation of erythropoietin secretion, further enhancing cardiac preload.71 The combination of increased preload and decreased SVR leads to increased cardiac output.72 Increases in contractility and in resting heart rate further contribute to the increase in cardiac output, which may be 50%-300% higher than normal in overtly hyperthyroid patients.73,74 Treatment of hyperthyroidism reverses these hemodynamic changes.

Cardiovascular Risk

Systolic hypertension may be seen in up to 30% of hyperthyroid patients.75 This elevation in systolic pressure may result from the combined effect of increased preload and cardiac output, and decreased arterial compliance.76

Cardiac Structure and Function

LVH has been associated with hyperthyroidism.77 The hemodynamic changes in hyperthyroidism result in increased cardiac work and compensatory cardiac hypertrophy over time.78 Hyperthyroidism is also associated with enhanced diastolic relaxation. In the short term, hyperthyroidism may be associated with improved diastolic function. However, in the long term, chronic thyrotoxicosis may induce LVH and diastolic dysfunction.79

Exercise intolerance and dyspnea on exertion in overt hyperthyroidism may result from an inability to further increase heart rate and ejection fraction, or to further decrease SVR in the setting of exercise. Hyperthyroid patients may also have skeletal and/or respiratory muscle weakness that further reduces exercise capacity. Patients with subclinical hyperthyroidism may also have decreased exercise tolerance.65 Treatment of hyperthyroidism results in improved exercise tolerance and resolution of exertional dyspnea.80

Rhythm

Sinus tachycardia occurs in approximately 40% of cases of overt hyperthyroidism, and generally resolves after restoration of euthyroidism.81 Subclinical hyperthyroidism is also associated with an increased heart rate.65 Atrial fibrillation is the second most common arrhythmia in overt hyperthyroidism, and occurs in 10%-15% of patients, its prevalence increasing with age.82 Patients with subclinical hyperthyroidism also have an increased risk of atrial fibrillation.65,83 In overtly hyperthyroid patients, factors independently predictive of atrial fibrillation include increasing age, history of cardiac failure, diabetes, elevated systolic or diastolic blood pressure, and LVH on ECG.84 Sinus rhythm can be restored in up to two thirds of patients with overt hyperthyroidism; however, increased age and duration of atrial fibrillation correspond with higher rates of persistent arrhythmia.84 There is limited evidence that treatment of subclinical hyperthyroidism facilitates reversion of atrial fibrillation to normal sinus rhythm.66

Hypothyroidism Overview

Hypothyroid patients may present with fatigue, weight gain, cold intolerance, constipation, mild diastolic hypertension, narrowed pulse pressure, and bradycardia. Overt hypothyroidism is characterized by elevated serum TSH and decreased peripheral thyroid hormone levels, with etiologies including autoimmune thyroid gland failure, iatrogenic failure (radioactive iodine, external beam radiation), and thyroidectomy. The treatment of hypothyroidism consists of thyroxine (T4) replacement. Subclinical hypothyroidism is defined by elevated serum TSH with normal peripheral free thyroid hormone levels. Patients with subclinical hypothyroidism are generally asymptomatic or mildly symptomatic. Consensus panel recommendations suggest initiation of thyroid hormone replacement therapy in patients with serum TSH values greater than 10mIU/L, and consideration of replacement therapy in patients with serum TSH 4.5-10mIU/L who have symptoms, and/or high background cardiovascular risk, and/or thyroid autoimmunity.85

Hypothyroidism and Cardiovascular Disease Hemodynamics

The hemodynamic changes in hypothyroidism are the opposite of those seen in hyperthyroidism. Overt hypothyroidism is associated with increased SVR, normal or decreased resting heart rate, decreased contractility, and decreased cardiac output. In addition, diastolic pressure is increased and pulse pressure is narrowed. Cardiac output may be reduced by up to 30%-40% as a result of decreased stroke volume and heart rate.86 The hemodynamic changes of hypothyroidism resolve with restoration of euthyroidism, with normalization of SVR and improved cardiac contractility, and with improved cardiac output.87

Cardiovascular Risk

Overt hypothyroidism is associated with accelerated atherosclerosis and coronary artery disease that may be attributable to diastolic hypertension, impaired endothelial function, and hypercholesterolemia. Significant diastolic hypertension may be seen in up to 20% of patients with overt hypothyroidism. This increase in diastolic pressure is the result of increased systemic vascular resistance and increased arterial stiffness, and resolves with T4 replacement therapy.88 Overt hypothyroidism has also been associated with hyperhomocysteinemia, increased C-reactive protein levels, and altered coagulation parameters.88 Subclinical hypothyroidism has been associated with elevated diastolic pressure and increased carotid artery IMT that may improve with T4 replacement.65

Lipid metabolism is altered in hypothyroidism, and approximately 90% of patients with overt hypothyroidism have elevated total cholesterol and LDLc levels.89 Serum total and LDLc levels are increased by approximately 30% in hypothyroidism, with greater increases in LDL levels seen in patients with insulin resistance and in smokers. These increased LDL levels are primarily because of decreased fractional clearance of LDL that results from a reduced number of hepatic LDL receptors. Apolipoprotein B and the atherogenic LDL variant, lipoprotein(a), are also increased in hypothyroidism. Triglyceride and very low density lipoprotein levels are normal to increased, whereas changes in HDL are variable. 90 These lipid abnormalities are generally reversible with restoration of euthyroidism. Subclinical hypothyroidism has been associated with increased LDL and total cholesterol levels in several cross-sectional studies, but the effects of treatment in small trials have been inconsistent.65

Cardiac Structure and Function

In hypothyroidism there is resting LV diastolic dysfunction, and both systolic and diastolic dysfunction with exertion. In overt hypothyroidism, impaired LV diastolic function has been demonstrated by slowed myocardial relaxation and impaired early ventricular filling.88 In elderly patients who may have preexisting increased myocardial stiffness, overt hypothyroidism can lead to diastolic heart failure. T4 replacement resolves these functional abnormalities, improving both diastolic and systolic function. Alterations in resting LV diastolic dysfunction have also been demonstrated in patients with subclinical hypothyroidism, with improvements seen in response to T4 replacement.65

Pericardial effusions occur in up to 25% of patients with overt hypothyroidism, and are likely due to increased capillary permeability, increased volume of distribution of albumin, and impaired lymphatic drainage.67 These pericardial effusions accumulate slowly and are seldom hemodynamically significant, although rare cases of cardiac tamponade have been reported.91 Pericardial effusions associated with hypothyroidism generally resolve after 2-3 months of thyroid hormone replacement therapy.67

Rhythm

ECG changes in hypothyroidism include sinus bradycardia, low voltage complexes (small P waves or QRS complexes), prolonged PR and QT intervals, and flattened or inverted T waves.92 Cases of ventricular conduction abnormalities have been reported in association with hypothyroidism, and may be related to QT interval prolongation.73

Amiodarone and Thyroid Hormone

Amiodarone, a benzofuranic iodine-rich antiarrhythmic drug, causes thyroid dysfunction in 15%–20% of treated patients, either causing hypothyroidism or thyrotoxicosis. Amiodarone-induced hypothyroidism (AIH) results from persistent iodine-induced inhibition of thyroid gland function, and is more prevalent in patients with preexisting thyroid autoimmunity.93 Treatment of AIH is with T4 replacement. High T4 doses are often required because amiodarone decreases deiodinase activity, resulting in decreased conversion of T4 to the active form, T3. Amiodarone-induced thyrotoxicosis (AIT) is present in two forms: type 1 AIT, or iodine-induced hyperthyroidism, and type 2 AIT, or destructive thyroiditis. Type 1 AIT results in the synthesis and release of excess thyroid hormone, whereas Type 2 AIT results in the release of preformed thyroid hormone from the inflamed thyroid gland. Differentiating between the two forms can be difficult, and management of AIT can be challenging. Type 1 AIT is managed with antithyroid drugs and possibly potassium perchlorate. Type 2 AIT is managed with glucocorticoids, beta-blockade, and rarely thyroidectomy.94 (Table 1) Baseline thyroid function tests and measurements of thyroid peroxidase antibodies should be performed prior to initiating amiodarone, and thyroid function should be monitored every 6 months for the duration of amiodarone therapy.95

Table 1. Features of Amiodarone-Induced Thyroid Dysfunction.

  Type I thyrotoxicosis Type II thyrotoxicosis Hypothyroidism
Mechanism Excess iodine. More common in iodine-deficient areas Destructive inflammatory thyroiditis Excess iodine. More common in iodine-sufficient areas
Thyroid antibodies Often present Usually absent Often present
Thyroid function Thyrotoxicosis Thyrotoxicosis Hypothyroidism
24-h 123Iodine uptake Usually low in iodine-sufficient regions, but may be normal or increased in iodine-deficient areas Usually low in iodine-sufficient regions
Color Doppler ultrasound Hypervascularity Reduced blood flow Normal vascularity
Therapy High doses of anti-thyroid drugs; possibly perchlorate or iopanoic acid prior to thyroidectomy High-dose corticosteroids; Iopanoic acid Levothyroxine sodium

Reprinted with permission from Pearce et al. 95

Congestive Heart Failure and Thyroid Hormone

A low serum T3 is the most common thyroid function abnormality in patients with heart failure, and is present in about 10%–30% of patients.96 The biochemical profile of thyroid function in heart failure is consistent with non-thyroidal illness, or euthyroid sick syndrome. It remains unclear whether this reduction in T3 is an adaptive or maladaptive process.97 Additionally, the role of thyroid hormone therapy remains unclear in patients with heart failure and low serum T3 levels. Goals of therapy would include improvements in LV function, remodeling, and microcirculation. Current areas of research include thyroid hormone replacement with T3 and/or T4, use of thyroid hormone analogs (e.g. diiodothyropropionic acid), and gene therapy to modify thyroid hormone receptor or deiodinase expression and activity.98 However, these approaches remain experimental.

Parathyroid hormone and the cardiovascular system Parathyroid Hormone Overview

Parathyroid hormone (PTH) plays a critical role in maintaining an adequate calcium–phosphorus homeostasis.99 PTH affects three principal target organs to maintain calcium balance: bone, intestinal mucosa, and kidney. The incidence of primary hyperparathyroidism (PHPT) is approximately 21.6 per 100,000 annually, with a higher incidence in females and in older adults, reaching a peak of 63.2 per 100,000 annually at ages 65-74 years.100 Hypoparathyroidism is much less common.

Hyperparathyroidism Overview

Hyperparathyroidism is characterized by inappropriately elevated PTH levels in the setting of elevated calcium concentrations. Causes of hyperparathyroidism include PHPT due to an autonomous adenoma or parathyroid gland hyperplasia, and secondary hyperparathyroidism due to chronic kidney disease or long-standing vitamin D deficiency. The clinical presentation of PHPT has evolved over the past several years as disease detection has improved. Approximately 85% of patients presenting with PHPT are asymptomatic or minimally symptomatic. The diagnosis of hyperparathyroidism is made by measuring serum calcium and serum intact PTH concentrations, and finding inappropriately elevated PTH in the setting of elevated calcium levels. Patients who have symptomatic hyperparathyroidism should be offered surgical management with removal of hyperfunctioning parathyroid adenoma(s). Asymptomatic patients can be clinically monitored or offered surgical management if they meet clinical criteria.101

Hyperparathyroidism and Cardiovascular Disease Cardiovascular Risk

The cardiovascular risk associated with PHPT is attributable in large part to an increased prevalence of hypertension, obesity, glucose intolerance, and insulin resistance.102,103 Proposed mechanisms of hypertension in patients with PHPT include increased calcium deposition leading to arterial stiffness in long standing and/or severe disease, direct PTH-mediated stimulation of the renin-aldosterone system, and PTH-mediated endothelial dysfunction and increased sympathetic activity.104,105 Surgical correction of hyperparathyroidism has not consistently demonstrated improvement in hypertension.106,107 Treatment of PHPT with surgery has been shown to improve insulin sensitivity in patients with more severe disease.108,109 Carotid IMT has been shown to be higher in patients with PHPT, and measures of carotid stiffness are associated with the degree of PTH elevation. This suggests that vessel stiffness may be related to the severity of hyperparathyroidism.110

Cardiac Structure and Function

LVH has been observed in PHPT in many studies, particularly in patients with moderate to severe hyperparathyroidism, independent of the effects of hypertension. Data from animal studies suggest that PTH has trophic effects on cardiomyoctes that results in hypertrophy. Surgical correction of hyperparathyroidism has resulted in regression of LVH in some studies.111

Diastolic dysfunction has been documented in modest to severe PHPT, with reports of a decreased E/A ratio and prolonged isovolumetric relaxation time. However, it remains unclear whether this effect is attributable more to hypercalcemia or PTH excess.111 Mild PHPT has been inconsistently associated with abnormalities in diastolic dysfunction.

Calcifications of the aortic valve, mitral valve, and myocardium have been demonstrated in PHPT patients with significant hypercalcemia.102 However, studies in patients with mild to moderate hypercalcemia have not demonstrated a consistent correlation with increased valvular calcifications.112

Rhythm

Hypercalcemia, particularly serum calcium >12mg/dL, reduces the plateau phase of the ventricular cardiac action potential and the effective refractory period. ECG findings in significant hypercalcemia include shortened QT and QTc intervals, increased QRS complex amplitude, early peaking and gradual down slope of the descending limb of the T wave, biphasic T waves, and shortened ST segment intervals.92 Successful surgical correction of hyperparathyroidism with reduction in serum calcium concentrations can result in lengthening of the QT and QTc intervals.113 It remains unclear whether hyperparathyroidism and hypercalcemia result in clinically relevant cardiac conduction abnormalities.114,115

Hypoparathyroidism Overview

Hypoparathyroidism is characterized by inappropriately low or undetectable PTH levels in the setting of hypocalcemia. Hypoparathyroidism may be congenital or acquired, with surgical removal or damage to the parathyroid glands being the most common acquired cause.116 The signs and symptoms of hypoparathyroidism result from hypocalcemia. Mild hypocalcemia may present with neuromuscular irritability such as perioral numbness, muscle cramping, parethesisas, and positive Chvostek’s and Trousseau’s signs. Severe hypocalcemia may present with carpopedal spasm, laryngospasm, tetany, and seizures. Diagnostic evaluation should include measurements of serum total and ionized calcium, albumin, phosphorus, magnesium, creatinine, intact PTH, and 25-hydroxyvitamin D.117 Treatment consists of adequate calcium replacement with either oral or IV calcium, and vitamin D metabolites and analogs as needed.

Hypoparathyroidism and cardiovascular disease Cardiac Structure and Function

There are case reports of decreased myocardial performance, dilated cardiomyopathy, and congestive heart failure in patients with acute and chronic hypocalcemia.118,119 The mechanism of the myocardial dysfunction is unclear, but may be related to impaired excitation-contraction coupling. Reversal of heart failure and correction of cardiomyopathy have been seen in select cases where correction of calcium deficiency was necessary for clinical and hemodynamic improvement.120,121

Rhythm

QT prolongation is the ECG hallmark of hypocalcemia, and results from prolongation of the plateau phase of the ventricular cardiac action potential. The rate of change in extracellular calcium levels modulates calcium channel function. Rapid changes in serum calcium results in more marked QT interval changes.122 T-wave changes are not common in hypocalcemia because phase 3 of the action potential is not affected. However, in severe hypocalcemia, T-wave flattening, terminal T-wave inversion, or deeply inverted T waves have been described.92 Hypocalcemia has also rarely been associated with ST segment elevation, possibly due to coronary artery spasm.123

The adrenal gland and the cardiovascular system Aldosterone Overview

Aldosterone is a mineralocorticoid hormone produced in the adrenal gland. Aldosterone secretion is regulated primarily by the renin-angiotensin system, although other regulatory factors include serum sodium and potassium levels and ACTH. Mineralocorticoid hormones work to maintain normal sodium and potassium concentrations, and to maintain normal volume status.

Primary Aldosteronism Overview

Primary aldosteronism (PA), or primary hyperaldosteronism, is a group of conditions in which aldosterone production is inappropriately high, resulting in suppression of the renin-angiotensin system. Hypertension is the clinical hallmark of PA, with the prevalence of PA reported as 0.5%-4.8% of patients with general hypertension, and 4.5%-22% of patients with resistant hypertension.124 Potassium depletion is also characteristic of hyperaldosteronism. The diagnosis of PA is made initially by measuring plasma aldosterone and plasma renin activity, and calculating an aldosterone to renin ratio (ARR). Patients with a positive ARR (ARR >20 with aldosterone >15ng/dL), should undergo confirmatory testing (oral sodium loading, saline infusion, fludrocortisone suppression, or captopril challenge). Common causes of PA include unilateral autonomous adrenal adenoma, and unilateral or bilateral adrenal hyperplasia. A rare cause of PA is a heritable condition known as glucocorticoid-remediable aldosteronism (GRA). Treatment guidelines recommend unilateral laparoscopic adrenalectomy in patients with documented unilateral PA, or medical treatment with a mineralocorticoid receptor antagonist (spironolactone or eplerenone) in nonsurgical patients.125 Medical treatment is suggested for patients with bilateral adrenal disease. Glucocorticoid replacement at the lowest therapeutic dosage is suggested as treatment of GRA.

Primary Aldosteronism and Cardiovascular Disease Cardiovascular Risk

PA is associated with hypertension, endovascular dysfunction, and altered glucose metabolism. Mechanisms contributing to hyperaldosteronism-mediated hypertension include plasma volume expansion from sodium and fluid retention, and vasoconstriction from potassium depletion.126 Aldosterone has been shown to decrease NO bioavailability, inhibiting endothelium-dependent relaxation. Aldosterone-mediated perivascular fibrosis reduces vascular compliance.124 Unilateral laparoscopic adrenalectomy in patients with aldosterone-producing adenoma or unilateral adrenal hyperplasia results in normalization of hypokalemia in all patients, improved blood pressure control in nearly all patients, and long-term hypertension cure rates of 30-60%. In PA due to bilateral adrenal disease, unilateral or bilateral adrenalectomy seldom corrects hypertension, necessitating continued mineralocorticoid receptor antagonist therapy.127 Impaired glucose tolerance and decreased insulin sensitivity have been reported in some patients with PA. Proposed mechanisms include direct effects of aldosterone on insulin receptor function, and effects of hypokalemia on insulin regulation.128

Cardiac Structure and Function

Hyperaldosteronism causes maladaptive cardiac remodeling and has been associated with LVH, cardiac fibrosis, and diastolic dysfunction.129,130 (Figure 3)131 The degree of LVH seen in PA exceeds the effects of hypertension alone.132 In animal models, aldosterone has been shown to directly stimulate cell growth and cardiomyocyte hypertrophy.133 Aldosterone has also been shown to promote collagen deposition, activation of inflammatory cells, and stimulation of fibroblast proliferation.134,135 Diastolic dysfunction has been demonstrated with lower early/late-wave diastolic filling velocities ratio, and longer deceleration time in patients with PA.136 Surgical and medical treatments may be effective in reducing LV mass, with decreases in blood pressure and plasma aldosterone levels predictive of response to therapy.

Figure 3. Mechanisms by which aldosterone excess may bring about adverse cardiovascular sequelae. LVH, left ventricular hypertrophy. Adapted with permission from Stowasser. 131

Congestive Heart Failure and Aldosterone Blockade

In conditions such as heart failure and myocardial infarction, aldosterone levels are elevated and contribute to pathologic cardiovascular remodeling via direct effects on collagen deposition and resultant cardiovascular fibrosis.137 Elevated aldosterone levels also promote endothelial dysfunction and vascular inflammation. Clinical studies have shown that aldosterone blockade reduces LV remodeling and collagen deposition, improves endothelial function, decreases inflammation, and increases myocardial perfusion.138,139,140 Following two landmark randomized controlled trials, the Randomized Aldactone Evaluation Study (RALES) and the Eplerenone Postacute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS), aldosterone blockade was added to clinical guidelines for management of chronic heart failure.141,142 The addition of an aldosterone antagonist is recommended in selected patients with moderately severe to severe symptoms of heart failure and reduced LVEF, or with LV dysfunction early after myocardial infarction, who can be carefully monitored for preserved renal function and normal potassium concentration.143 The effectiveness of aldosterone blockade in diastolic dysfunction and in mild-to-moderate heart failure is unclear.140,144

Pheochromocytoma Overview

Pheochromoctyomas are catecholamine-producing tumors that originate from chromaffin cells of the adrenal medulla and the sympathetic ganglia (catecholamine-secereting paragangliomas, or extra-adrenal pheochromocytomas). The estimated prevalence of pheochromocytoma is 0.05-0.12% of the general population, and 0.2-0.6% of patients with hypertension.145 Patients may present asymptomatically if diagnosed after detection by adrenal imaging or genetic testing. Symptomatic patients present with hypertension (episodic or sustained) and paroxysmal symptoms such as dizziness, headache, flushing, diaphoresis, and palpitations. The diagnosis of pheochromocytoma is made with biochemical confirmation of catecholamine excess, utilizing urinary and plasma measurements of metanephrines and catecholamines, followed by radiologic evaluation for tumor localization. Treatment of pheochromocytoma consists of surgical resection, with preoperative medical optimization to obtain adequate blood pressure control and volume expansion.146,147

Pheochromocytoma and Cardiovascular Disease Cardiovacular Risk

Hypertension is present in over 50% of patients with pheochromocytoma, and may be sustained or paroxysmal. Higher variability of blood pressure has been demonstrated in pheochromocytoma compared to patients with essential hypertension, and is associated with a higher incidence of target organ damage.148 Resolution of hypertension has been reported in about 50% of patients after successful surgical treatment of pheochromocytoma.149

Markers of endothelial dysfunction, such as increased carotid IMT, have been demonstrated in patients with pheochromocytoma.150 These changes have been attributed to the effects of excess catecholamines on vascular wall growth and thickening. Normalization of catecholamine levels after surgical removal of pheochromocytoma has been shown to improve carotid IMT, and reduce carotid wall fibrosis.151

Cardiac Structure and Function

Excess catecholamine action in pheochromocytoma can lead to cardiomyopathy, ischemic heart disease, myocardial stunning, and, rarely, cardiogenic shock. The incidence of cardiomyopathy in patients with pheochromocytoma is about 26%, with primary manifestations including dilated cardiomyopathy and hypertrophic cardiomyopathy.152 Echocardiogram may reveal LV dilatation with diffuse decrease in contractility, left atrial dilatation with increased end-diastolic pressure, reduced ejection fraction, and septal hypertrophy. In the setting of intravascular volume depletion and impaired diastolic filling, patients may present with an outflow obstruction that mimics hypertrophic obstructive cardiomyopathy. Frequently seen on echocardiogram, LVH is attributable more to hypertension than to catecholamine effects.150

Patients with pheochromocytoma-associated cardiomyopathy may present with pulmonary edema, or with acute chest pain and myocardial ischemia/infarction. Pulmonary edema results from increased pulmonary capillary permeability, increased peripheral vascular resistance, increased hydrostatic pressure, and overfilling or constriction of efferent pulmonary veins. Myocardial ischemia or infarction may result from coronary vasospasm, with catecholamine action leading to vasoconstriction, decreased coronary blood flow, and increased cardiac oxygen demand. Myocardial stunning following catecholamine-induced vasospasm has been reported, in addition to case reports of tako-tsubo-like apical dyskinesia leading to acute cardiogenic shock.153

Catecholamine-induced cardiomyopathy has been shown to improve after surgical treatment of pheochromocytoma. Reversal of cardiomyopathy depends on early identification and treatment. The prognosis for patients with acute heart failure and significant myocardial damage is very poor.

Rhythm

The electrocardiographic signs related to pheochromocytoma include right-axis deviation, poor R-wave progression, inverted T waves, and QT prolongation. If there is permanent myocardial damage and development of cardiomyopathy, signs of ventricular hypertrophy and ischemia may be present on electrocardiogram. Cardiac arrhythmias may be seen in 20% of patients with pheochromocytoma, and include sinus tachycardia, sick sinus syndrome, supraventricular and ventricular tachycardia.150,152

Conclusions

Endocrine dysfunction may have a significant impact on the cardiovascular system. Restoration of normal endocrine function often results in reversal of adverse cardiovascular changes. Hormone-mediated cardiac changes should be considered when evaluating endocrine and cardiac patients.

Conflicts of interest

None declared.

Corresponding author: 88 East Newton Street, Evans 201, Boston, MA 02118, USA. [email protected]

Anatomy of the Endocrine System

Anatomy of the Endocrine System

The endocrine system is made up of seven different glands that make chemicals called hormones. Hormones are substances that act as “messengers” to control many body functions. The endocrine system makes hormones that help control:

  • Growth
  • Reproduction
  • Sexual development
  • Use and storage of energy
  • Response to physical stress or trauma
  • Levels of water, salt and sugar in the body

Hypothalamus

The hypothalamus is located in the center of the brain. It makes hormones that increase or decrease the release of the hormones made in the pituitary gland. It also makes hormones that help to control water balance, sleep, temperature, appetite and blood pressure.

Pituitary

The pituitary gland is located at the base of the brain and is about the size of a pea. It is the master gland in the endocrine system. It regulates the amounts of hormone made by the thyroid gland, adrenal gland, and testes or ovaries. It also makes the hormones prolactin and vasopressin, and growth hormone.

Thyroid and Parathyroid

The thyroid gland and parathyroid glands are located in front of the neck, below the larynx (voice box). The thyroid plays an important role in the body’s growth and development, as well as metabolism. Both the thyroid and parathyroid glands also play a role in controlling the level of calcium in the body.

Adrenal Gland

The adrenal glands are located on top of each kidney. The adrenal glands make hormones that help the body deal with stress and illness. The hormones made by the adrenal gland also maintain blood pressure and blood glucose, and plays a role in sexual development.

Pancreas

The pancreas is located behind the stomach. It plays a role in digesting food, but it also makes hormones. The pancreas makes insulin, which is important for blood sugar control.

Ovaries

A female’s ovaries are located on both sides of the uterus, below the opening of the fallopian tubes (which extend from the uterus to the ovaries). In addition to containing the egg cells necessary for reproduction, the ovaries also produce the hormones estrogen and progesterone. These hormones regulate the menstrual cycle.

Testes

A male’s testes are located in the scrotum. The testes produce testosterone and sperm.

Interaction of the endocrine system with inflammation: a function of energy and volume regulation | Arthritis Research & Therapy

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  • Hormonal system

    Hypothalamic-pituitary system 🧠

    ❗️ Hypothalamus

    It is located in the diencephalon and is associated with almost all of its departments. Regulates body temperature, sleep and wakefulness cycle, hunger and satiety, affects memory, emotions and behavior in general.

    💧 With the help of the hormone vasopressin, the hypothalamus regulates the amount of water in the body, controlling its excretion by the kidneys.

    💕 Also, the hypothalamus produces one of the most famous hormones – oxytocin. It is commonly called the hormone of trust and attachment, although oxytocin plays a huge role not only in the formation of attachment, but also in embryonic development, reproductive behavior and lactation.

    📶 But most importantly, the hypothalamus serves as the main regulator of balance in the body with the help of two types of hormones: liberins and statins. Liberins and statins act on the pituitary gland – they activate or inhibit the production of its hormones, respectively.

    Pituitary gland

    A small but very important formation in the brain weighing about a gram, which consists of the posterior, intermediate and anterior lobes, each of which is responsible for certain hormones.

    🌀 Although oxytocin and vasopressin are produced in the hypothalamus, they are released in the pituitary gland. From here they go to the target organs: oxytocin – to the uterus and mammary glands; vasopressin – to the kidneys.

    The front lobe is responsible for the production of many hormones at once:

    – Prolactin stimulates milk production in the mammary glands and performs a number of other functions;

    – Gonadotropic hormones control the production of sex hormones in the gonads, sperm – in the testes, eggs – in the ovaries;

    – Corticotropin stimulates the production of cortisol and other hormones in the adrenal glands;

    – Thyrotropin controls the activity of the thyroid gland;

    – Growth hormone – growth hormone that regulates physical development and stimulates muscle formation.

    In the intermediate lobe, melanotropins are produced, which are responsible for skin pigmentation.

    Organization of endocrine function in flatworms

    Organization of endocrine function in flatworms

    Pages
    126-131
    Abstract

    The features of the organization of endocrine function in flatworms are described. It is carried out with the participation of two groups of hormones.Several centers of location of neurosecretory cells have been found in the nervous system. The hormonal signal is realized with the participation of elements of the adenylyl cyclase system, which is characteristic of vertebrates. In some species, endogenous steroids – sex steroids and glucocorticoids – have been identified. These data allow us to speak about the presence of an endocrine system in flatworms, the structural organization of which demonstrates features of similarity with the endocrine system of vertebrates and higher representatives of invertebrates.

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    Endocrinology – Medical Center “Cedar”

    Hormones are chemicals produced in the cells of the endocrine glands. In fact, they are the regulator of all his physiological processes. Normal hormonal levels are very important for human health.At the slightest imbalance, a whole host of health problems can appear, ranging from common acne to death. You can determine the level of hormones by passing a blood test. An endocrinologist, focusing on the results of the study, will be able to determine whether there is a relationship between the deterioration of well-being and the work of the endocrine system.

    Important elements of the endocrine system

    Control of the functions of the endocrine glands and the work of the autonomic nervous system lies with the hypothalamus.It is he who affects the metabolism, nervous state, electrolyte balance and even reproductive function. If for a long time it is not possible to conceive a child, it is better to consult an endocrinologist and exclude problems in the work of the endocrine system. The thyroid gland is responsible for the metabolism, the production of calcium and phosphorus. If the function of the thyroid gland is impaired, problems with the spine and joints may appear. There is a danger of developing osteoporosis, in which bone density decreases and the risk of fractures increases.

    Causes of hormone dysfunction

    There are several types of human hormonal imbalance:

    • Lack of hormones. Such a deviation from the norm occurs when the production of hormones by the endocrine gland decreases. There can be many reasons for this: infectious diseases, autoimmune disorders, tumors, heart attacks, heredity.
    • Excess hormones. It is observed with excessive production of hormones and their oversaturation of the blood flow.
    • Production of abnormal hormones by the endocrine glands. This deviation is observed in the presence of genetic disorders.

    When to see an endocrinologist

    Diagnosis of diseases of the endocrine system can be difficult. Deterioration in well-being is attributed to other diseases or banal fatigue. The most common symptoms are:

    • Uncontrolled tremors of the limbs;
    • Menstrual irregularities, absence of menses, or too profuse, prolonged menses;
    • Chronic tiredness and lethargy for no apparent reason;
    • Tachycardia;
    • Poor tolerance to temperature extremes, cold or heat;
    • Intense sweating;
    • Sudden changes in weight in any direction also for no apparent reason;
    • Lack of appetite;
    • Absent-mindedness, poor memory;
    • Drowsiness or, conversely, insomnia;
    • Often depressed, apathetic;
    • Constipation, nausea;
    • Brittle nails, hair, poor skin;
    • Infertility for unknown reasons.

    All of the above symptoms may indicate that one of the organs of the endocrine system is not working properly.

    You can get detailed information during the opening hours of the Medical Center by phone: +7 (484) 395-62-02 and +7 (902) 394-71-12

    Endocrine system in danger »HOREV Medical Center

    10 sources of endocrine disruptors and how to avoid them

    By Dr. Mercola

    Endocrine disruptors disrupt normal development and reproduction and can seriously affect neurological and the immune system.

    Disorders occur because these chemicals mimic hormones in the body, including the female sex hormone estrogen, the male sex hormone androgen, and thyroid hormones.

    Endocrine disrupting substances block hormonal signals in the body or disrupt the way hormones or receptors are produced or controlled.

    Your normal hormone levels or the way these hormones circulate in your body may change. As the Natural Resources Conservation Council (NRPC) notes:

    “The endocrine system is a complex network of glands and hormones that regulates many bodily functions, including growth, development and maturation, as well as the functioning of various organs.

    Endocrine glands – including the pituitary gland, thyroid gland, adrenal glands, thymus, pancreas, ovaries and testes – release carefully measured amounts of hormones into the bloodstream that act as natural chemical messengers, reaching various parts of the body to control and regulate many vital functions “.

    Changing this precise system is like playing with fire, as you might imagine, but it still happens every day when you use “normal” everyday goods at home.In part, the danger of endocrine disruptors stems from the ubiquity of and the fact that most of us are exposed to several of these chemicals on a daily basis.

    Endocrine disruptors have been linked to cancer, ADHD and more

    A variety of health problems associated with exposure to these common chemicals include:

    • Undescended testes in boys
    • Undescended testes in boys
    • Nerve disorders

      systems in children

    • Prostate cancer in men
    • Disorders of the nervous system in children
    • Attention deficit hyperactivity disorder (ADHD) in children

    Children and pregnant women are at risk, but the consequences appear decades later

    The greatest danger, apparently, arises from exposure during prenatal or early postpartum development, that is, when the nervous system and organs are formed.

    Some effects, however, may not appear until decades later, and it is increasingly suggested that many diseases in adults are rooted in fetal malnutrition.

    One of the most shocking examples of this is diethylstilbestrol (DES), a synthetic estrogen analogue that was widely prescribed to pregnant women until the 1970s. in order to prevent miscarriage and stimulate fetal growth.

    This endocrine disruptor has proven to be incredibly dangerous and has caused reproductive problems and vaginal cancer that manifested itself after puberty.

    It’s not just people who suffer. Endocrine disruptors are ubiquitous in polluted water, air and food , which means there is a risk for wildlife as well.

    Fish in the Great Lakes have been found to suffer from reproductive problems and abnormal thyroid tumors due to exposure to endocrine disruptors, polychlorinated biphenyls (PCBs).

    In one of the regions of Florida, the population of alligators sharply decreased after a pesticide spill, which caused a decrease in reproductive organs and a decrease in successful reproduction.Both alligators and their eggs were found to be contaminated with endocrine-disrupting chemicals.

    10 Common Sources of Endocrine Disrupting Chemicals

    EpochTimes recently compiled a list of 10 common sources of endocrine disruptors and what you can do against them.

    1. Personal Care Items

    Shampoos, conditioners, moisturizers, cosmetics and other personal care items often contain endocrine disruptors, including (but of course not limited to) phthalates.Phthalates are a group of chemicals that make males in many species look more like females.

    These chemicals disrupt the endocrine system of fauna, causing testicular cancer, genital deformities, low sperm counts and infertility in a number of species including, for example, bears, deer, whales and otters.

    Another endocrine-disrupting chemical, triclosan, is even found in some brands of toothpaste. Switching to natural and / or home-made personal care products will help to avoid such exposure.You can also try to reduce the number of personal care products you use every day.

    2. Drinking water

    The water you drink can be contaminated with atrazine, arsenic and perchlorate – all of which can undermine the endocrine system. A quality water filtration system will help protect you and your family – both in the kitchen and in the bathroom.

    3. Canned food

    Analysis of 252 canned food brands showed that 78 of them still use bisphenol A (BPA), despite being officially considered an endocrine disruptor.BPA is associated with a number of health problems, especially in pregnant women, fetuses and young children, and in adults, including:

    • Structural brain damage
    • Changes in gender behavior and abnormal sexual behavior
    • Structural brain damage brain
    • Changes in gender behavior and abnormal sexual behavior
    • Hyperactivity, increased aggressiveness and learning difficulties
    • Early puberty, stimulation of mammary glands, impaired reproductive cycles and ovarian dysfunction, infertility
    • Increased fat formation and risk of obesity
    • prostate cancer cells
    • Changes in immune function
    • Increase in prostate size and decrease in sperm count

    4.Conventionally grown produce

    Pesticides, herbicides and industrial effluents coat conventionally grown fruits and vegetables with a layer of endocrine disrupting chemicals. Whenever possible, buy and eat organically grown and sourced foods to reduce your exposure to endocrine disrupting pesticides and fertilizers.

    5. Meat and dairy products of animals and poultry raised in restricted conditions

    Animals raised in restricted conditions (CAFO), as a rule, are also crammed with antibiotics, hormones and other industrial chemicals that can undermine the endocrine system.Look for livestock products from small local farmers who practice grazing and avoid the use of chemicals.

    6. Fish with high levels of mercury

    Fish contaminated with high levels of mercury and other heavy metals are also best avoided because these metals also disturb hormonal balance. Shark, swordfish, king mackerel, marlin and combheads sin the most, but it turns out that even tuna is polluted at dangerously high levels.Farmed fish (“marine CAFO”) also tend to be high in contaminants and are best avoided. When it comes to eating seafood, small fish such as sardines, anchovies and herring tend to have fewer pollutants and more omega -3 fats.

    7. Kitchenware

    The non-stick plastic containers and utensils found in every kitchen are another hazard. Plastic containers can contain BPA or other endocrine disrupting chemicals that can enter food, especially when the plastic is heated.Poly- and perfluoroalkyl substances (PFAS), which are used to form non-stick, dirt- and water-repellent surfaces, are also toxic and very persistent, both in the body and in the environment. When heated, the nonstick coating releases perfluoro-caprylic acid (PFCA), which is associated with thyroid disease, infertility, developmental problems, and reproductive disorders. The safer options are cast iron cookware with ceramic and enamel coating – it is durable, easy to clean (even from the most burnt food, just soak it in warm water) and completely inert, that is, it does not release any harmful chemicals into your home.

    8. Cleaning products

    Commercial solutions for cleaning floors, toilets, stoves, windows and more tend to contain industrial chemicals that can make hormones go bad. For example, nonylphenol ethoxylates (NPEs), a common ingredient in detergents and universal products, are banned in Europe because they have been found to be a powerful endocrine disruptor that transforms male fish into females. Surprisingly, it’s not hard to make home detergents using various combinations of vinegar, baking soda, essential oils, and even coconut oil.

    9. Office Products

    Cartridges, toners and other solvents common in the office are another source of endocrine-disrupting chemicals. Handle them with care, where possible, keeping their impact to a minimum.

    10. Cashier’s checks

    Thermal paper has a coating that turns black when exposed to heat (the printer in the cash register generates heat, which causes numbers and letters to appear on the paper).It also contains BPA, and research shows that working with this type of paper can increase BPA levels in the body. A study conducted by the Journal of Analytical and Bioanalytical Chemistry showed that out of 13 analyzed types of thermal paper, BPA is contained in 11. Holding this paper for only five seconds is enough for BPA to get on human skin, and if fingers are wet or oily (for example, if you just used a lotion or ate a fatty food), the BPA amount from the paper increases by 10 times.

    Finally, given that people often put checks in their wallets next to banknotes, banknotes are also contaminated with BPA. In a study published in the Science and Technology for the Environment, scientists tested bills from 21 countries for the presence of BPA and found the substance in every sample.

    Therefore, try not to put checks in your wallet or wallet as they appear to carry the chemical to other surfaces they come into contact with.In addition, it is a good idea to wash your hands every time you handle checks and bills, and try not to handle them if you have just applied lotion or other oily substances, as this can increase your BPA exposure. If you work as a cashier at a bank or in a store and constantly deal with such paper, you may need to wear gloves, especially if you are pregnant or of childbearing age.

    19 More Tips to Reduce Your Household Chemical Exposure

    Buy and eat organically grown and sourced foods whenever possible to reduce your exposure to hormones, pesticides and fertilizers.Try to avoid milk and other dairy products containing genetically modified recombinant bovine growth hormone (rBGH or rBST).

    Instead of traditional farmed or farmed fish, which are often contaminated with PCBs and mercury, opt for supplements with quality refined krill oil, or eat small fish or fish that have been laboratory tested for purity from the sea. For these reasons, sea-caught Alaskan salmon is the only fish I eat.

    Buy food in glass bottles or cans , not plastic or cans, as chemicals from plastics can enter the contents.

    Store food and drinks in glass rather than plastic containers, and avoid using plastic wrap.

    Use glass bottles for babies, not plastic cups with sippy cups.

    Eat mostly raw, fresh food.Processed, prepackaged foods (of all kinds) are a common source of chemicals such as BPA and phthalates.

    Replace non-stick pans and pans with ceramic or glass ones.

    Filter tap water for both drinking and bathing. Filter your bathing water if you can afford it, as your skin absorbs pollutants. To remove the endocrine disrupting herbicide atrazine, make sure the filter is properly certified.According to the Environmental Protection Working Group, perchlorate can be filtered using a reverse osmosis unit.

    Look for products made by companies that use land, animal and plant safe, non-toxic or 100% organic technologies. This applies to everything from food and personal care products to building materials, carpets, paint, baby products, upholstery and more.

    Use a vacuum cleaner with a HEPA filter to remove dust from your home, which is often contaminated with traces of chemicals.

    When buying new items such as furniture, mattresses or carpet backing, inquire about the type of flame retardant they use. Be careful and / or try to avoid products containing PBDEs, antimony, formaldehyde, boric acid and other bromine-containing chemicals. Once you’ve gotten rid of these toxic elements in your home, choose those that contain natural, less flammable materials such as leather, wool, and cotton.

    Avoid clothing, furniture and carpets with dirt- and water-repellent coatings to help keep perfluorinated compounds (PFCs) away.

    Minimize the use of plastic toys for children – go for natural wood or fabric instead.

    At home, use only natural or homemade cleaning products. Avoid products containing 2-butyl glycol (EGBE) and methoxydiglycol (DEGME), two toxic glycol ethers that can interfere with fertility and harm the embryo.

    Switch to organic brands of toiletries such as shampoo, toothpaste, antiperspirants and cosmetics.Many of these can be replaced with coconut oil and baking soda, for example.