Endocrinology: Hormones and Glands

• Endocrinology is the study of the endocrine system, related diseases, and hormone secretions.
• Hormones regulate cells, organs, and homeostasis within individuals.
• The endocrine system uses glands to produce and secrete hormones, regulating functions like respiration, metabolism, reproduction, sensory perception, movement, sexual development, and growth.

Hormone Producing Glands

• Hypothalamus: Regulates body temperature, hunger, moods, hormone release from other glands, thirst, sleep, and sex drive.
• Pituitary: Known as the "master control gland," controls other glands and produces growth-triggering hormones.
• Parathyroid: Controls calcium levels in the body.
• Pancreas: Produces insulin, which helps regulate blood sugar.
• Thyroid: Produces hormones related to calorie burning and heart rate.
• Adrenal: Produces hormones controlling sex drive and cortisol, the stress hormone.
• Pineal: Produces melatonin, impacting sleep.
• Ovaries (in women): Secrete estrogen, testosterone, and progesterone, which are the female sex hormones.
• Testes (in men): Produce testosterone, the male sex hormone, and sperm.

Classification by Structure of Hormones

• Hormone structure determines biochemical changes.
• Peptide hormones: Majority of hormones; releasing factors are peptides.

Hormone Properties & Processes

• Water-soluble hormones don't need transport proteins, are synthesized and stored in cells, and have a short half-life (5-60 minutes).
• Steroid hormones: Regulate sexual development, synthesized from cholesterol, require transport proteins, and have a long half-life (60-100 minutes).
• Amino acid derivatives (amines): Properties similar to steroid and peptide hormones.
• Fatty acid derivatives: Includes prostaglandins.

Hormone transport

• Hormone transport proteins are specific.
• Hormone attachment to protein is through non-covalent linkages.
  • Steroid and thyroid hormones bind to albumin, sex hormone-binding protein, or cortisol-binding globulin.
  • Amines are transported by serum proteins and thyroxine-binding globulin.
• Transport protein levels affect hormone action.
• Relative amounts of bound and free hormone determine stimulus degree.
• Only the free hormone fraction exhibits activity.
• Transport protein level/binding degree affects free hormone concentration.
• Transport protein concentration measurement is part of hormone assays.

Hypothalamic & Pituitary Functions

• Hypothalamus and pituitary are integral to the endocrine system.
• "Pituitary" means "spit mucus”, reflecting early beliefs.
• The pituitary gland has two parts:
  • Anterior lobe (adenohypophysis)
  • Posterior lobe (neurohypophysis) located in a skull cavity.
• Hormone production/secretion regulation occurs via the feedback loop.
• Feedback loop: Composed of the pituitary gland and the target endocrine gland.

Feedback Loop Types

• Negative feedback: Stimulating hormone induces production, elevated levels turn off pituitary release of the stimulating hormone.
  • Example: High thyroid hormone levels stop thyrotropin-releasing hormone (TRH) and thyroid-stimulating hormone (TSH).
• Positive feedback: A structure secretes a hormone in response to a stimulating hormone from the pituitary gland.

Anterior Pituitary Gland Hormones

• Prolactin (PRL): Related to GH and human placental lactogen, a stress hormone with reproduction functions.
  • Hypersecretion: Causes galactorrhea or lactation, infertility, amenorrhea (women), impotence (men); induced by pituitary adenoma.
  • Hyposecretion: Leads to lack of lactation in postpartum women.
• Growth hormone (GH): Important for growth, body composition, cell repair, metabolism, muscle growth, strength, exercise performance, and injury recovery.
  • Hypersecretion effects are age-dependent:
    • Adults: Acromegaly (enlargement of extremities).
    • Children: Gigantism.
  • Pituitary adenomas cause both conditions.
    • They secrete GH and compress adjacent tissues, causing hyposecretion of other tropic hormones.
  • Hyposecretion in children: leads to pituitary dwarfism (small stature, proportionally built).
• Luteinizing hormone (LH): A gonadotrophic hormone, controls ovaries in females and testes in males (the gonads).
• Follicle-stimulating hormone (FSH): Essential for puberty and the function of women's ovaries and men's testes.
  • In women, it stimulates ovarian follicle growth, and estradiol production.
  • In men, it acts on Sertoli cells to stimulate sperm production (spermatogenesis).
• Thyroid-stimulating hormone (TSH): Produced by the pituitary, regulates hormone production by the thyroid.
• Adrenocorticotropic hormone (ACTH):
  • Hypersecretion is Cushing's disease, with truncal obesity, hyperglycemia, hypertension, and protein wasting.
    • It is caused by pituitary adenoma, adrenal hyperplasia, or nonendocrine tumor production.
  • Hyposecretion: Causes weight loss, weakness, and gastrointestinal problems.

Posterior Pituitary Gland Hormones

• Anti-diuretic hormone (ADH) or Vasopressin: Regulates water reabsorption and blood pressure by affecting renal tubules and arterioles.
  • Hypersecretion: Syndrome of inappropriate ADH secretion (SIADH).
    • Occurs in conditions including meningitis, head injury, tuberculosis, hypoadrenalism, hypothyroidism, and cirrhosis.
    • SIADH: Is associated with hyponatremia, hypertonic urine, weakness, malaise, poor mental status, convulsions, and coma.
      • It's typically caused by ADH release from ectopic tumors.
  • Hyposecretion: Diabetes insipidus.
    • Symptoms include insatiable thirst, polydipsia (excessive drinking), and polyuria (excessive urine volume).
    • Results from the destruction of the posterior pituitary or the hypothalamus.
• Oxytocin: No known disorders are associated with excess or deficient secretion.

Thyroid Gland

• Butterfly-shaped gland in the lower anterior neck.
• Is responsible for production of thyroid hormone and calcitonin.
• Thyroid hormone regulates body metabolism through neurologic development.
• It is secreted by parafollicular cells and responsible to calcium homeostasis.
• It’s composed of follicles. The gland contains two cell types:
  • Follicular cells: Produce thyroxine (T4) and triiodothyronine (T3).
  • Parafollicular cells: Produce calcitonin and lie adjacent to the follicles.
• Thyroid hormones need iodine for synthesis.
  • Iodine binds with thyroglobulin to form hormone precursors, then T3 and T4.
• Hormones are either stored within the follicle or released into the bloodstream.
• In bloodstream, most T4 becomes T3: There's more circulating T3 than T4.
• 98% of circulating T3 and T4 is bound to protein, including thyroxine-binding globulin (TBG) and thyroxine-binding albumin:
  • Some hormone is unbound/free, the physiologically active fraction.
• T3 and T4 regulation:
  • Thyroid-releasing hormone (TRH) from the brain stimulates TSH release from the pituitary gland.
  • TSH stimulates iodine uptake by the thyroid and hormone release.
  • High serum levels of free T3 and T4 "shut off" TSH release from the pituitary, whereas decreased levels induce TSH release.

Thyroid Disorders

• Are caused by increased or decreased levels of circulating hormones T3 and T4.
• Many physical diseases can be traced back to a dysfunctional thyroid.
• Hypothyroidism: an insufficient serum level of thyroid hormone that leads to metabolic issues:
  • Women are four times more affected than men between 30-60 years of age.
  • Can be is referred to as primary, secondary, or tertiary, depending on dysfunction site.
• Hypothyroidism Symptoms: enlarged thyroid (goiter), fatigue, impaired mental processes, loss of appetite, myxedema (hair loss, face/hand swelling, coarse skin).
  • Causes: tissue damage and lack of dietary iodine.
  • Primary hypothyroidism: Inadequate thyroid hormone secretion caused by a damaged or surgically removed thyroid gland.
    • Congenital hypothyroidism is caused by the absence of the thyroid gland.
    • Lab results: Decreased T3, T4, free thyroxine index (FT4I), T3 uptake (T3U), and increased TSH.
  • Secondary hypothyroidism: Is decreased TSH production caused by a pituitary disorder leading to low serum levels
    • Laboratory results: decreased thyroid test values.
  • Tertiary hypothyroidism: Hypothalamic failure with a lack of TRH.
    • Lab early abnormality evaluation: increased TSH, and decreased serum levels.
• Chronic immune thyroiditis (Hashimoto’s disease) is caused by a genetic abnormality of the immune system and lymphocytes infiltrating the thyroid:
  • The symptoms match those of hypothyroidism.
• Hyperthyroidism is caused by excessive thyroid hormone in the circulation.
  • It causes cells to become overactive (thyrotoxicosis).
  • The causes include pituitary tumors that cause excessive TSH secretion, thyroid carcinoma, or a toxic multinodular goiter.
• Graves' disease: Autoimmune disorder; immunoglobulins stimulate the thyroid gland by binding to TSH receptors.
  • Six times more frequent in women;
  • Symptoms match hyperthyroidism with increased T3, T4, FT4I, and T3U, and decreased or normal TSH.
• Thyroiditis: It is thyroid gland inflammation caused by a bacterial or viral infection.

Labs

• T3 resin uptake analyzes the capacity of TBG to bind thyroid hormones; this is an indirect measurement of the number of free binding sites on the TBG molecule.
• Free thyroxine index (FT41) indirectly assesses the concentration of circulating free T4: It is calculated by multiplying the value of the total T4 by the percentage value of the T3 resin uptake.
• Thyroid antibody screens assay for the presence of thyroid-stimulating: Thyroid antibody screens detects immunoglobulins, such as those in Graves' and Hashimoto's thyroiditis.
• TRH stimulation tests measure pituitary TSH stores: they are considered conclusive for hyperthyroidism, but it are not needed in most hyperthyroid patients.
• TRH levels rise rapidly in a normal person, but will not rise in a hyperthyroid patient, after TRH is injected and blood is drawn for TSH, of patients with slightly elevated hormone levels/hyperthyroidism symptoms.

Adrenal Gland

• Pyramid-shaped, located above the kidney.
• It is composed of distinct conjoined glands:
  • Adrenal cortex (outer, yellow)
  • Adrenal medulla (inner, dark mahogany)

Adrenal Cortex

• Outer region secreting steroid hormones.
• It is the major site for steroid hormone production.
• The adrenal cortex secretes three major hormones:
  • Glucocorticosteroids (primarily cortisol) are secreted from the zona fasciculata.
  • Mineralocorticoids (aldosterone) controls Na/K ion exchange in the distal nephron and is secreted. - It is secreted from the zona glomerulosa.
  • Small amounts of reproductive steroids are produced.
• Cortisol - Principal glucocorticoid, regulated by ACTH:
  • Stimulates gluconeogenesis in the liver.
  • Only adrenal hormone that inhibits ACTH secretion.
  • Has anti-inflammatory and immunosuppressive actions
• The Body's Alarm Clock is due to adrenocorticotropic hormone (ACTH) and cortisol.
  • It occurs because Cortisol stimulates most body cells to increase energy production.
• Later stages of sleep, hormones are released and the body awakens.
• Cortisol hormone has high levels around 8-10 am and low levels around 10 pm-12 am.
• It is best tested form specimens collected at 8:00 am.
• Urine free cortisol levels are sensitive indicators, and endogenous urine tests are 24 hours

Cortisol (Urinary Metabolites)

• The liver degrades all glucocorticoids, which are excreted in urine
  • 17-hydroxycorticosteroids (porter-silber method-yellow color) is identified by Phenyl hydrazine in H2SO4 + alcohol.
  • 17-ketogenic steroids (Zimmermann reaction-reddish purple color) is identified with Meta-dinitrobenzene.

Clinical Disorders

• Hypercortisolism (Cushing's Syndrome)
  • Adenocortical hyperfunction is caused by excessive production from cortisol. ACTH will decrease aldosterone and renin
    • Caused by overuse of corticosteroids.
  • Symptoms are Obesity, thin extremities, buffalo hump, hirsutism, hyperglycemia, hypercholesterolemia, low wbc/lymphocytes
  • Confirmed via 24-hour cortisol urine test and overnight dexamethasone. Testing with midnight salivary test
  • Low dose tests will confirm hypercortisolism tests stimulation
• Hypocortisolism Test* a. Primary Hypocortisolisnm
• Congenital Adrenal Hyperplasia (CAH)* Deficiencies in enzyme which results in decreased plasma and can test levels through: Measurement with 170HP Genotypic through sampling

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