Endocrine System Overview

Endocrine System Overview

• The endocrine system regulates body function through biochemical regulators, including hormones, paracrine factors (e.g., prostaglandins), and autocrine factors (e.g., interleukins).
• Homeostasis is maintained through a system of control mechanisms.

Types of Hormones

• Hormones are classified by structure.
• Peptides/polypeptides come in various sizes with similar functions (e.g., insulin, GH, PTH, glucagon); water-soluble.
• Amino acid derivatives are synthesized by the thyroid gland (T4 and T3) and adrenal medulla; water or lipid-soluble.
• Steroid hormones are derived from cholesterol; lipid-soluble (e.g., cortisol, aldosterone, testosterone, estrogen, progesterone); not stored.

Negative Feedback in the Hypothalamus-Pituitary-Endocrine Gland Axis

• The endocrine system uses negative feedback to precisely regulate hormone synthesis and release, such as thyroid hormone production.
• The hypothalamus releases hormones that trigger the anterior pituitary to release hormones regulating target endocrine glands (thyroid, etc.).
• Target cells produce hormones to provide feedback, inhibiting further release of hypothalamic and pituitary hormones if hormone levels rise to a certain point

Endocrine System Disease Processes

• Diseases and disorders in the endocrine system are often caused by tumors, inflammation, degenerative processes, or genetic mutations.
• Endocrine diseases can be primary (originating from target organs), secondary (originating from hypothalamus-pituitary axis), tertiary (tumors in the hypothalamus or pituitary), or ectopic (hormone-secreting tumors in other parts of the body).

Hypothalamus and Pituitary Glands

• The hypothalamus and pituitary gland work together as a control center for other endocrine glands, like the thyroid, adrenal, and gonads.
• They directly control essential physiological functions including lactation, growth, and metabolism.

Pituitary Gland

• The pituitary gland, regulated by the hypothalamus, has two parts (anterior and posterior).
• The anterior pituitary produces ACTH, GH, prolactin, TSH, LH, and FSH.
• The posterior pituitary produces ADH and oxytocin.

Hypothalamus Hormones and Anterior Pituitary Regulation

• Hypothalamus hormones (TRH, CRH, GnRH, GHRH, dopamine) regulate the release of anterior pituitary hormones (TSH, ACTH, LH, FSH, GH, prolactin), which affect various target organs (thyroid, adrenal cortex, gonads, liver, breast tissues).

Posterior Pituitary Hormones

• Antidiuretic hormone (ADH) is stimulated by increased plasma osmolality, blood volume depletion, and stress/nausea ; regulates fluid balance.
• Oxytocin is involved in various functions.

Clinical Disorders of the Pituitary Gland

• Pituitary disorders can lead to oversecretion (e.g., abnormal cell growth in the pituitary, increased production of tropic hormones, ectopic tumors) or deficiency of hormones (involving multiple hormones like tumors, trauma, or infections), often requiring pituitary surgery.

Excess Pituitary Hormone Disorders (SIADH)

• SIADH is characterized by the secretion of high levels of ADH without a stimulus.
• Causes include tumors, tuberculosis, cystic fibrosis, trauma, or certain medications.
• Consequences involve water retention (hyponatremia), affecting serum/urine osmolality, as kidneys struggle to excrete sodium.
• Symptoms include thirst, weight gain, fatigue, and anorexia.

Diagnosing SIADH

• Diagnosing SIADH involves medical history and physical examination, along with laboratory tests measuring electrolytes (specifically hyponatremia), serum osmolality, and urine osmolality.
• Normal renal, adrenal, and thyroid function are crucial for accurate diagnosis.

Excess Pituitary Hormone Disorders (GH)

• Normal growth involves rapid growth (first 2 years), steady growth (around 9 years), and a growth spurt during puberty, all regulated by growth hormone (GH).
• Growth hormone excess in children causes gigantism, and adults acromegaly.
• It's caused by pituitary adenomas. Consequences include gigantism (children), acromegaly (adults), cardiac hypertrophy, hypertension, atherosclerosis, type 2 diabetes, and coarsening facial features.

Diagnosing Acromegaly

• Diagnosing acromegaly requires a glucose tolerance test with GH measurement to evaluate GH suppression.
• IGF-1 measurements are used.
• Treatment options include surgery, radiation, and somatostatin analogs.

Excess Pituitary Hormone - Other Disorders

• Hyperprolactinemia (excess prolactin, often due to prolactinomas) causes milk production in women and hypogonadism/erectile dysfunction in men.
• Adrenocorticotropic hormone (ACTH) excess leads to Cushing syndrome, characterized by elevated ACTH stimulating glucocorticoid production.

Deficit Disorders of the Pituitary Gland (ADH)

• Central diabetes insipidus (decreased ADH) results in kidneys' inability to retain water leading to increased excretion, altered plasma, and urine osmolality ; symptoms are polyuria, nocturia, continuous thirst, and polydipsia.
• Laboratory findings: water restriction does not reduce urine osmolality.

Deficit Disorders of the Pituitary Gland (GH)

• Growth hormone deficiency in children and adults results in diminished GH secretion, causing growth failure and other symptoms (children) and increased body fat/decreased muscle bulk and strength (adults).
• Genetic mutations and tumors are possible causes.
• Tests like insulin tolerance tests (ITT) and arginine stimulation tests assess GH response to stimuli. Genetically engineered GH is a treatment route.

Thyroid Gland

• The thyroid gland, composed of follicular cells, produces thyroid hormones (T3 and T4).
• These hormones are crucial for neurologic development, oxygen consumption, heat production, growth, and sexual maturity, affecting carbohydrate and protein metabolism.

Thyroid Hormones

• Thyroid hormones (T3 and T4) are essential for tissue maturation and metabolism and are produced by the thyroid gland using iodine.
• T4 is converted to T3 in peripheral tissues; rT3 is inactive. T3 and T4 are bound to proteins; free T3 and T4 are active.

Regulation of Thyroid Hormone Secretion

• The hypothalamic-pituitary-thyroid axis (HPT axis) regulates thyroid hormone secretion.
• The hypothalamus releases TRH, which stimulates the anterior pituitary to release TSH, which in turn stimulates thyroid hormone production in the thyroid gland. Excessive thyroid hormone suppresses TSH and low thyroid hormone increases TSH.

Goiter

• Goiter is an enlarged thyroid gland and can be associated with underproduction (hypothyroidism) or overproduction (hyperthyroidism) of thyroid hormones.
• Iodine deficiency is commonly associated with goiter.

Disorders of the Thyroid Gland

• Hypothyroidism (underproduction) can be primary (thyroid failure), secondary (pituitary failure), or tertiary (hypothalamus failure).
• Hyperthyroidism (overproduction) is often a primary disease and associated with factors like autoimmune disorders (Grave's disease), toxic adenomas, and thyroiditis.

Deficit of Thyroid Hormones (Hypothyroidism)

• Hypothyroidism develops gradually, often caused by autoimmune thyroiditis (Hashimoto's disease).
• Other causes include surgery, transient effects from medications (lithium carbonate), TSH deficiency, congenital defects, and iodine deficiency.
• Symptoms include weight gain, coarse dry skin, hoarse voice, goiter, lethargy, depression, intolerance to cold, altered tendon reflexes, muscle weakness, and a slow pulse.

Diagnosis of Hypothyroidism

• Primary hypothyroidism is diagnosed by assessing thyroid function (low thyroid hormones and elevated TSH).
• Secondary hypothyroidism is diagnosed by evaluating pituitary function (low thyroid hormones and low TSH), looking closely at thyroid hormone and TSH levels.

Treatment of Hypothyroidism

• Hypothyroidism is treated with thyroid hormone replacement therapy (T4), frequently for life, closely monitoring TSH levels .

Excess of Thyroid Hormones (Hyperthyroidism)

• Hyperthyroidism results from overactive thyroid glands with high levels of thyroid hormones, increasing body's metabolic rate.
• Causes include Grave's disease (most common), antibodies against TSH receptor, toxic nodules or adenoma, thyroiditis.
• Other causes include iodine from exogenous sources and goiter.

Signs and Symptoms of Hyperthyroidism

• Hyperthyroidism symptoms include weight loss despite appetite, sweating, tremor, possible goiter, agitation, nervousness, heat intolerance, easy fatigability, tachycardia, muscle weakness and loss, and rapid eye movements (exophthalmos).

Diagnosis of Hyperthyroidism

• Hyperthyroidism is often diagnosed from decreased TSH with increased free T4 (fT4) levels.
• Presence of TSH receptor antibodies suggests Grave's disease. Subclinical hyperthyroidism involves low TSH with free T4 and T3 within reference ranges, potentially increasing risk of primary hyperthyroidism.

Treatment of Hyperthyroidism

• Treatment for Grave's disease, including anti-thyroid medication, radioiodine therapy (131I), or surgery (thyroidectomy) is common.

Hypothalamic-Pituitary-Adrenal Axis

• This axis controls reactions to stress.
• It regulates digestion, immune response, mood, sexuality, and energy use. The hypothalamus stimulates the anterior pituitary which releases ACTH to stimulate the adrenal cortex.

Adrenal Glands

• The two adrenal glands are composed of a cortex and medulla.
• The cortex produces mineralocorticoids (e.g., aldosterone), glucocorticoids (e.g., cortisol), and adrenal androgens.
• The medulla produces catecholamines (e.g., adrenaline, noradrenaline, dopamine) and is part of the sympathetic nervous system.

Cortisol

• Cortisol is a major glucocorticoid regulating carbohydrate, protein, and lipid metabolism.
• Cortisol levels fluctuate diurnally, affected by sleep-wake cycles, and limited by single serum measurements.
• Hypothalamus and anterior pituitary control cortisol levels.

Aldosterone

• Aldosterone is a major mineralocorticoid; maintaining extracellular fluid volume and regulating sodium and potassium levels, controlled by the renin-angiotensin system.

Adrenal Androgens

• Adrenal androgens, (e.g., androstenedione, DHEA) and DHEA sulfate, are converted into sex hormones in gonads, skin, and adipose tissue; vital to females and necessary for males.

Adrenal Medulla

• Adrenal medulla produces catecholamines (epinephrine, norepinephrine) that form a response to stress, the “fight-or-flight” response. This includes increased heart rate, blood pressure, muscle strength, glucose metabolism, rate of heart contractions, peripheral blood vessel resistance, and alertness.

Hormonal Disorders of the Adrenal Cortex

• Adrenal cortex disorders involve a decrease (e.g., Addison's disease–low aldosterone) or increase (e.g., Cushing syndrome– high cortisol) in hormone secretion, disrupting homeostasis and development.

Adrenal Insufficiency (Primary and Secondary)

• Adrenal insufficiency involves a decrease in hormone secretion, and it can be primary (Addison's disease - autoimmune-related adrenal cortex destruction) or secondary (suppression of the entire hypothalamic-pituitary-adrenocortical axis).
• Patients typically have a lack of mineralocorticoid and glucocorticoid leading to loss of sodium and water from the body, and patients often display pigmentation and/or hyponatremia and dehydration, requiring careful investigation.

Addison's Disease

• Addison's disease is primarily an autoimmune disorder where reduced secretion occurs mostly of the adrenal cortex (especially of glucocorticoids – cortisol and mineralocorticoids – aldosterone) leading to a deficiency in these hormones, which can be fatal with lack of treatment.
• It affects more often women than men and can be diagnosed with laboratory tests identifying low steroid and blood mineralocorticoid levels with elevated ACTH levels.
• Symptoms include weakness, fatigue, hyperpigmentation of the skin, anorexia, nausea, and diarrhea.

Hyperfunction of the Adrenal Cortex (Cushing's Syndrome)

• Cushing's syndrome is caused by prolonged exposure of tissues to high levels of cortisol or other corticosteroids, most commonly due to steroid medication usage.
• Tumors (pituitary or adrenal) causing cortisol or ACTH overproduction can also be a cause.
• Symptoms include weight gain, central obesity, thinning scalp hair, thinning skin, facial flush, skin pigmentation, increased body and facial hair, easy bruising, decreased immune response, hyperglycemia, and hypertension.

Hypothalamic-Pituitary-Gonadal Axis

• The hypothalamic-pituitary-gonadal axis involves the hypothalamus releasing GnRH which stimulates the anterior pituitary to release LH and FSH. These hormones stimulate the gonads to secrete sex hormones.

Gonadal Function - Male

• Testes secrete testosterone and produce spermatozoa.
• LH stimulates Leydig cell development and testosterone production, while FSH affects Sertoli cells.
• Male hypogonadism, a disorder of male sex hormones, can be primary (testicular deficiency-low testosterone) or secondary (hypothalamus or pituitary deficiency-low LH and FSH), showing decreased LH and FSH and decreased testosterone.

Gonadal Function - Female

• Estradiol is crucial for female secondary characteristics, follicular growth, and endometrial development.
• Hormonal control of the menstrual cycle involves FSH triggering follicular growth, LH stimulating ovulation, and development of the corpus luteum with progesterone and estradiol production.
• Problems like subfertility, amenorrhea, oligomenorrhea, hirsutism and virilism can emerge from the production of female sex hormones’ malfunction

Subfertility

• Subfertility is identified as the inability of a couple to conceive after 1 year of regular unprotected intercourse.
• Endocrine abnormalities can contribute to subfertility in one-third of females and rarely in males.
• Endocrine examinations look for high progesterone during the luteal phase, absent ovulation, low progesterone, low estradiol and high gonadotrophins levels, or abnormal prolactin or androgen levels (primary ovarian failure).

This quiz provides an overview of the endocrine system, exploring its role in regulating bodily functions through hormones and other biochemical regulators. It delves into the classification of hormones, their structures, and the mechanism of negative feedback within the hypothalamus-pituitary-endocrine gland axis.