Endocrine disorders

Overview

Endocrine problems have an impact on the endocrine system. This system employs glands located throughout the body to manufacture and release hormones that influence a variety of biological functions. An endocrine problem occurs when hormone levels are too high or too low, or when the body does not respond properly to hormones.

Tumors, hereditary factors, and hormonal imbalances are all potential causes of endocrine diseases. Because these conditions affect hormones, they can cause a variety of symptoms and have an impact on growth and development, metabolism, sexual function, and mood.

What is Endocrine system?

The endocrine system is a collection of glands and organs that use hormones to regulate body activities. Hormones are chemical messengers that circulate in the circulation and impact biological functions.

Primary parts of the endocrine system include the:

• Hypothalamus
• Pineal body
• Pituitary gland
• Thyroid and parathyroid
• Thymus
• Adrenal gland
• Pancreas
• Ovaries
• Testicles

These and other endocrine system components govern a variety of functions, including metabolism, reproduction, and growth. Endocrine diseases develop when one or more of the system's components fail to function properly. This usually leads in excessive or low levels of specific hormones, or in the body not reacting properly to certain hormones. This can cause difficulties throughout the body.

Pancreas

Located in the abdomen, the pancreas is both an endocrine gland and a digestive organ.

It releases:

• Insulin: Important for carbohydrate and fat metabolism in the body
• Somatostatin: Regulates endocrine and nervous system function and controls the secretion of several hormones, such as gastrin, insulin, and growth hormone
• Glucagon: A peptide hormone that raises blood glucose levels when they fall too low
• Pancreatic polypeptide: This helps control the secretion of substances made by the pancreas

Diabetes and digestive issues can result if there are problems with the pancreas.

Parathyroid glands

• These small endocrine glands located in the neck produce parathyroid hormone, which regulates calcium and phosphate in the blood.
• Muscles and nerves can only operate safely and effectively if these chemicals are at the correct levels.

Pituitary gland

An endocrine gland located near the base of the brain, connected to the hypothalamus. It is also referred as the primary endocrine master gland since it secretes hormones that govern the operations of other glands, as well as development and a variety of other body processes.

The anterior pituitary gland, also known as the front pituitary gland, secretes hormones that influence sexual development, thyroid function, growth, skin pigmentation, and adrenocortical function.

When the anterior pituitary gland is underactive, it can cause stunted development in children as well as underactivity in other endocrine glands. The posterior pituitary gland secretes oxytocin, a hormone that promotes uterine contractions, and antidiuretic hormone (ADH), which encourages the kidneys to reabsorb water.

What Causes an Endocrine Disorder?

The most common cause of an endocrine problem is a hormone imbalance, which occurs when a gland produces too much or too little of a hormone. This imbalance can be induced by the following factors:

Problems with the endocrine feedback system, whose primary duty is to maintain hormones in the body properly balanced, but which can malfunction and produce an imbalance.

• A genetic disorder 
• Infection or disease 
• Injury to an endocrine gland 

Endocrine abnormalities can also emerge as a result of endocrine system nodules or tumors. While an endocrine nodule or lump is unlikely to be cancerous or spread to other parts of the body, it can disrupt hormone production in the endocrine system.

How is an Endocrine Disorder Diagnosed?

The endocrine system is an interwoven structure that governs many various biological activities, including development, metabolism, and reproduction, making diagnosing an endocrine problem a difficult task.

• Laboratory Testing for Endocrine Disorders

Because symptoms of endocrine diseases might appear gradually and be vague, clinical detection can take months or years. As a result, biochemical diagnosis is frequently required; this usually entails evaluating blood levels of the peripheral endocrine hormone, pituitary hormone, or both.

Because most hormones have circadian cycles, measurements must be taken at specific times of the day. Hormones that fluctuate over short time periods (for example, luteinizing hormone) involve acquiring three or four values during one or two hours or utilizing a pooled blood sample. Hormones that vary from week to week (e.g., estrogen) demand getting different readings a week apart.

• Blood hormone measurements

The active form is typically thought to be free or bioavailable hormone (hormone that is not attached to a particular binding hormone). To separate the free and albumin-bound hormone from the binding globulin, free or bioavailable hormones are assessed using equilibrium dialysis, ultrafiltration, or a solvent-extraction approach. These procedures can be costly and time-consuming. Although analog and competitive free hormone tests are often used commercially, they are not always reliable and should be avoided.

• Blood hormone estimates

Free hormone levels can be calculated indirectly by measuring binding protein levels and utilizing these to modify total serum hormone levels. because growth hormone (GH) production is pulsatile and GH has a short serum half-life, serum insulin-like growth factor 1 (IGF-1) is frequently tested as an indication of GH activity. The measurement of circulating hormone metabolites is being studied to see if it signals the quantity of bioavailable hormone. 

Urine (for example, free cortisol when testing for Cushing syndrome) or salivary hormone levels may be utilized instead of blood levels in some cases.

• Dynamic tests

A dynamic test is required in many circumstances. In the event of hypofunctioning organs, a stimulation test (for example, ACTH stimulation) can be employed. A suppression test (for example, dexamethasone suppression) can be performed to diagnose hyperfunction.

• Computerized tomography (CT) scan 
• Magnetic resonance imaging (MRI) scan Positron emission test (PET) scan 

Common endocrine disorders

Endocrine problems come in a variety of forms. The following are some instances.

Aging and Endocrine disorders

Hormones undergo many changes as a person ages.

• Most hormone levels decrease.
• Some hormone levels remain stable.
• Some hormone levels increase.

Many of the changes associated with aging are comparable to those seen in people with hormone insufficiency. Certain hormone replacement therapy in older persons can enhance functional outcomes (e.g., muscular strength, bone mineral density), but there is no evidence that it improves mortality. In other situations, replenishing hormones can be hazardous, such as when menopausal estrogen and progesterone treatment increases the risk of breast cancer.

According to one alternative explanation, the age-related drop in hormone levels signifies a protective slowdown of cellular metabolism. This notion is based on the aging rate of living theory (ie, the faster the metabolic rate of an organism, the quicker it dies). This theory appears to be supported by research on the effects of food restriction. Restriction reduces the quantities of hormones that drive metabolism, lowering metabolic rate; restriction also extends mouse life.

Specific age-related hormone decreases

Hormone levels that decrease with aging include:

• Dehydroepiandrosterone (DHEA) and DHEA sulfate
• Estrogen
• Growth hormone and insulin-like growth factor 1
• Melatonin
• Pregnenolone
• Testosterone

The levels of dehydroepiandrosterone (DHEA) and DHEA sulfate decrease considerably with age. Despite anticipation about the function of DHEA supplementation in the elderly, the majority of controlled trials failed to reveal any significant benefits.

Pregnenolone is the precursor of all steroid hormones known to man. Its levels, like DHEA, diminish with age. Although trials in the 1940s demonstrated its safety and advantages in persons with arthritis, subsequent studies failed to demonstrate any beneficial effects on memory or muscular strength.

In elderly persons, GH replacement occasionally increases muscular mass but does not boost muscle strength (although it may in malnourished people). Adverse symptoms (for example, carpal tunnel syndrome, arthralgias, and water retention) are quite prevalent. GH may have a role in the short-term therapy of some malnourished elderly people, but it increases mortality in critically sick malnourished patients. Secretagogues that promote GH production in a more physiological fashion may boost benefit while lowering risk.

Melatonin levels, a hormone generated by the pineal gland, likewise decrease with age. This decline may play a significant role in the aging-related loss of circadian rhythms. Menopausal estrogen therapy is covered under the section on menopause treatment. Testosterone replacement therapy in elderly men is covered in another article.

Cushing’s syndrome

Cushing's disease is an endocrine illness characterized by elevated adrenocorticotropic hormone (ACTH) synthesis from the anterior pituitary gland, which results in excessive cortisol release from the adrenal glands. This is frequently caused by a pituitary microadenoma (less than 5mm) or by excessive hypothalamic synthesis of corticotropin-releasing hormone (CRH(

Generalized weakness, high blood pressure, diabetes mellitus, menstrual abnormalities, and psychological disorders are some of the symptoms. Excess cortisol levels can cause moon facies, buffalo hump, easy bruising, abdominal striae, obesity, facial plethora, and hirsutism.

Patients with Cushing disease nearly invariably have a pituitary adenoma, which is not usually visible on imaging. Rare occurrences of widespread corticotroph hyperplasia may occur even in the absence of ectopic release of corticotropin-releasing hormone (CRH). The tumors are often microadenomas (less than 5 mm in size), with only 5 to 10% being macroadenomas.

• How does Cushing's disease happen?

Although the frequency of ACTH production stays constant, the usual circadian rhythm is disrupted. Increased plasma ACTH produces bilateral adrenal hyperplasia and, as a result, an increase in cortisol production. As a result, the regular circadian cycle of cortisol is also disrupted.

Cushing’s disease symptoms

• Weight gain (50 %)
• Hypertension
• Easy bruising
• Striae
• Acne
• Flushing
• Poor wound healing
• Lower limb edema
• Fatigue
• Impaired glucose tolerance
• Osteoporosis
• Hyperpigmentation of the skin
• Mood and memory changes
• Amenorrhea
• Hirsutism
• Decreased sexual drive

Clinical signs vary greatly between patients; consequently, to appropriately identify this, a high index of clinical suspicion must be maintained.

Large pituitary tumors (macroadenomas), however uncommon, can cause significant effects on adjacent tissues. These patients may complain of impaired peripheral vision or headaches.

Cushing’s disease diagnosis

More than half of Cushing disease patients appear with a microadenoma with a diameter of less than 5 mm. Only 10% of them are big enough to produce a mass effect on the brain tissue and change the anatomy of the sellar region. As a result, most occurrences of ACTH-secreting pituitary adenomas are discovered following a suspicion of excessive cortisol and testosterone production.

Salivary and blood serum cortisol testing, 24-hour urinary-free cortisol testing, and low-dose overnight dexamethasone suppression testing are all biochemical diagnostic assays used to confirm hypercortisolism. 

The urinary-free cortisol test examines the amount of cortisol excreted in the urine by the kidneys. Cushing syndrome is thought to be caused by cortisol levels that are three times higher than usual, as well as another abnormal test. This test must be repeated three times in order to rule out any normal periods of hypercortisolism.

Cushing syndrome Treatment 

If a primary ACTH secreting tumor is discovered, the adenoma is surgically resected using trans-sphenoidal surgery as the first-line therapy (TSS). Depending on the surgeon's preference, this can be done by an endonasal or sublabial technique. When the tumor is discovered during the initial operation, the chances of effective excision increase.

Patients who have chronic illness after initial surgery typically have repeat pituitary surgery, despite the decreased success rate and greater risk of pituitary insufficiency. After a failed TSS, pituitary radiation treatment can be utilized as an alternative.

Finally, bilateral adrenalectomy can be performed to give an immediate decrease in cortisol levels in Cushing syndrome patients. However, these individuals will require glucocorticoid and mineralocorticoid replacement treatment for the rest of their lives. Nelson syndrome, the formation of ACTH secreting macroadenomas following bilateral adrenalectomy, is a prominent consequence of this procedure. The incidence ranges from 8% to 29% and is detected an average of 15 years after bilateral adrenalectomy.

Graves’ disease

Graves' disease is an autoimmune condition that mostly affects the thyroid gland. It may also have an impact on other organs such as the eyes and skin. It is the leading cause of hyperthyroidism. Thyroid stimulating immunoglobulin (TSI), also known as thyroid stimulating antibody, causes Graves' disease (TSAb). Thyroid stimulating immunoglobulin is largely created by B lymphocytes within thyroid cells, although it can also be synthesized in lymph nodes and bone marrow. T cells, which get sensitized by antigen in the thyroid gland, activate B lymphocytes.

Thyroid stimulating immunoglobulin attaches to the thyroid-stimulating hormone (TSH) receptor on the thyroid cell membrane and promotes TSH activity. It promotes thyroid hormone production as well as thyroid gland development, resulting in hyperthyroidism and thyromegaly.

The majority of Graves' disease patients exhibit the usual signs and symptoms of hyperthyroidism. It is uncommon for Graves' disease to appear with solely Graves orbitopathy or pretibial myxedema. The presentation of hyperthyroidism is determined by the age of start, severity, and duration of hyperthyroidism. Symptoms in the elderly may be modest or hidden, and they may appear with non-specific signs and symptoms such as weariness, weight loss, and new onset atrial fibrillation. Apathetic thyrotoxicosis is a term used to describe an unusual presentation of hyperthyroidism in the elderly. 

Graves' disease symptoms

Heat intolerance, sweating, weariness, weight loss, palpitation, hyperdefecation, and tremors are typical in younger individuals. Insomnia, anxiety, nervousness, hyperkinesia, dyspnea, muscular weakness, pruritus, polyuria, oligomenorrhea or amenorrhea in females, loss of libido, and neck fullness are further symptoms. Eye symptoms include swelling of the lids, ocular discomfort, redness of the conjunctiva, and double vision. Palpable goiter is more frequent in younger people, those under the age of 60.

Graves' disease diagnosis

The thyroid-stimulating hormone (TSH) test is used to diagnose hyperthyroidism. If TSH is suppressed, Free T4 (FT4) and Free T3 (FT3) must be ordered (FT3). Total T4 (Thyroxine) and total T3 (Triiodothyronine) can be purchased if free hormone tests are not accessible. A low TSH level combined with a high FT4 or FT3 level, or both, will confirm the diagnosis of hyperthyroidism. Only TSH is inhibited in subclinical hyperthyroidism, although FT4 and FT3 are normal.

Graves' disease Treatment

Graves' disease treatment is dependent on how it manifests. Thyroid hormone secretion is reduced and symptoms are controlled quickly.

A beta-adrenergic blocker should be begun in symptomatic individuals, particularly those with a heart rate of more than 90 beats per minute, those with a history of cardiovascular illness, and the elderly. Because of the ease of daily administration, atenolol 25 mg to 50 mg orally once daily may be regarded the optimal beta blocker, and it is cardioselective (beta-1 selective). Propranolol 10 mg to 40 mg orally every six to eight hours is recommended by certain doctors owing of its tendency to prevent peripheral T4 to T3 conversion. Following a beta blocker, calcium channel blockers such as diltiazem and verapamil can be used to regulate heart rate. 

There are three options to reduce thyroid hormone synthesis. These options are:

1. Antithyroid drugs which block thyroid hormone synthesis and release
2. Radioactive iodine (RAI) treatment of the thyroid gland
3. Total or subtotal thyroidectomy.

All three solutions offer advantages and disadvantages, and there is no agreement on which one is the best. It is critical to thoroughly examine all three choices with the patients and make an informed decision.

Prolactinoma

Prolactinomas are pituitary gland tumors that secrete prolactin. It is the most prevalent pituitary gland secretory tumor, accounting for up to 40% of total pituitary adenomas. Prolactinomas induce a wide range of symptoms, either as a result of the tumor's bulk impact or as a result of prolactin hypersecretion.

Prolactinomas are divided into three types based on their size: microprolactinoma (less than 10 mm), macroprolactinoma (more than 10 mm), and enormous prolactinoma (larger than 4 cm). Various causes of hyperprolactinemia, such as pregnancy, medications, hypothyroidism, and pituitary stalk impact owing to other pituitary tumors, should be examined in the differential.

Prolactinomas are benign tumors that develop from the monoclonal expansion of pituitary lactotrophs. They are frequently well-defined and lack indications of invasion. A few prolactinomas may invade adjacent local structures aggressively, and they typically have greater mitotic activity and are more cellular and pleomorphic. A malignant prolactinoma must have distant extracranial involvement in order to be classified as a malignant prolactinoma. Prolactinoma is most commonly seen in the lateral regions of the anterior pituitary gland. 

Prolactinoma diagnosis

Microadenomas (less than 1 cm) are usually confined to the sella turcica and do not cause any compressive symptoms, whereas macroadenomas (greater than 1 cm) can spread to an adjacent structure such as the optic chiasm or the cavernous sinuses and cause various compressive symptoms such as visual field defects, cranial nerve palsy, and headaches. Microadenoma symptoms are caused mostly by high prolactin levels.

Prolactin levels are generally directly proportional to tumor size, ranging from less than 200 ng/ml for tumors less than 1 cm in diameter, 200 ng/ml to 1000 ng/ml for tumors 1 cm to 2 cm in diameter, and more than 1000 ng/ml for tumors more than 2 cm in diameter. If the prolactin level does not correspond to the tumor size, it might be due to a poorly differentiated prolactinoma or the presence of a substantial cystic component in the tumor.

The hypothalamus has a strong inhibitory effect on prolactin secretion via dopamine, and any condition that disturbs this process results in hyperprolactinemia. It is critical to investigate the many causes of hyperprolactinemia since elevated prolactin release has been observed in a variety of physiological and pathological conditions other than prolactinomas.

Prolactinomas symptoms

Prolactinomas manifest clinically as a result of the tumor's bulk impact or hyperprolactinemia. Microprolactinomas (less than 1 cm in size) can present with hyperprolactinemia symptoms or be discovered by chance during routine neuroimaging. Macroprolactinomas, on the other hand, have a large impact on the surrounding structures.

Signs and symptoms due to the mass effect:

1. Headaches
2. Vision Changes-visual field deficits, blurred vision, decreased visual acuity
3. Cranial nerve palsies-especially with invasive tumors or with pituitary apoplexy
4. Seizures, Hydrocephalus, Unilateral exophthalmos are rare presentations
5. Pituitary apoplexy is a medical emergency because of spontaneous hemorrhage into the pituitary tumor and presents with severe headaches, vision changes, and panhypopituitarism.

Signs and symptoms due to Hyperprolactinemia

Males

1. Decreased libido
2. Impotence
3. Erectile dysfunction
4. Oilgozoospermia (due to secondary hypogonadism)

Females

1. Oligomenorrhea, amenorrhea
2. Infertility, loss of libido
3. Galactorrhea

Children and Adolescents

1. Growth arrest
2. Pubertal delay
3. Primary amenorrhea

Other characteristics present in both sexes include osteopenia, anxiety, sadness, weariness, and emotional instability. About 10% of prolactinomas can co-secrete growth hormone, resulting in gigantism/acromegaly in certain people.

Prolactinomas Diagnosis

• Laboratory

The serum prolactin level is the first step of the test. If prolactin levels are elevated, a full metabolic panel, TSH, and pregnancy test (for women of childbearing age) should be conducted. Cortisol, ACTH, IGF-1, LH, FSH, and testosterone/estradiol levels should be measured depending on age and gender to rule out hypopituitarism or other co-secreting tumors.

Patients may have extremely high prolactin levels, yet when tested, they may be recorded as deceptively low due to a phenomenon known as the "Hook effect." If there is a suspicion, repeated dilution of the blood sample and re-measurement of prolactin levels will be useful.

Another scenario in which measured prolactin may be high despite a low real prolactin level is when patients have increased molecular weight prolactin, known as macroprolactin. In the case of asymptomatic hyperprolactinemia, macroprolactin levels should be measured. Before the immunoassay for prolactin, the laboratory might pretreat the serum with polyethylene glycol to precipitate the macroprolactin.

• Imaging

A CT scan may show the mass, but an MRI with gadolinium is the preferable imaging modality for hyperprolactinemia assessment since it better characterizes the architecture of the hypothalamic-pituitary region. All patients with malignancies close to or squeezing the optic chiasm should have thorough visual field testing.

Prolactinomas Treatment

Macroprolactinomas identified inadvertently without symptoms can be detected with lab and imaging surveillance on a regular basis.

Dopamine agonist treatment should be used to treat macroprolactinoma or symptomatic microadenoma. The therapy goals would include tumor shrinking, restoration of visual fields, reversal of galactorrhea, and restoration of fertility or aberrant sexual function. Cabergoline is used because it has a better success rate in regulating prolactin levels and shrinking tumors. If fertility is not sought, amenorrhea induced by macroprolactinoma can be treated with oral contraceptives in the absence of dopamine agonists.

The majority of prolactinomas are treated solely with medicinal treatment, with surgery and radiation reserved for refractory patients.

• Medical Therapy

Unlike other pituitary tumors, medicinal therapy is the recommended treatment for prolactinomas. If the sole symptoms are amenorrhea and/or osteoporosis, an oral contraceptive can be used. One of the dopamine agonists is used to treat prolactinomas.

Cabergoline and bromocriptine are two dopamine agonists that are routinely utilized. Pergolide has been pulled from the market owing to valvular heart disease concerns, and quinagolide is not accessible in the United States. Dopamine agonists inhibit the production and release of prolactin and lactotroph cellular growth, promoting tumor shrinking. They have the potential to produce nausea and dizziness.

Visiting an Endocrinologist

An endocrinologist is a doctor who specializes in the diagnosis and treatment of hormone imbalances and disorders. During the initial appointment, the doctor will ask the patient a number of questions in order to arrive at a diagnosis.

These might cover:

• Current medications
• Family history of hormonal problems
• Other medical conditions including allergies
• Dietary habits

It might be beneficial to make a list of any current symptoms prior to the appointment. The endocrinologist may inquire about symptoms that do not appear to be relevant or are superfluous. This is due to the fact that hormone levels affect so many different systems in the body that even little changes in one gland may affect portions of the body far away from the glands themselves.

They will examine the patient's skin, hair, teeth, and mouth, as well as their heart rate and blood pressure. It is possible that blood and urine samples will be obtained. Following a diagnosis, the endocrinologist will recommend a course of therapy. This will be determined by the underlying disease producing the symptoms.

Conclusion 

Endocrine diseases are a group of ailments caused by issues with the endocrine system. This is a sophisticated system responsible for the production and distribution of hormones throughout the body.

An endocrine disease is caused by the endocrine system's faulty function, which includes the glands that release hormones, the receptors that respond to hormones, and the organs that are directly affected by hormones. Dysfunction can arise at any of these locations and have far-reaching consequences for the organism.

Because of the variety of symptoms they produce and their similarities to other ailments, endocrine disorders can be difficult to recognize. People who are having symptoms, on the other hand, should see a doctor because the disorders usually necessitate treatment.