General endocrinology

Endocrinology is the study of the endocrine system (i.e., the hypothalamus, pituitary gland, thyroid gland, adrenals, and gonads), metabolic diseases, and certain aspects of nutritional medicine. The endocrine glands are responsible for producing and secreting hormones, which influence the function of cells in certain tissues of the body. Hormone secretion is controlled by highly regulated pathways, the most important of which is the hypothalamic-pituitary axis . The hypothalamus secretes and stores nontropic hormones (e.g., ADH, oxytocin) and releasing hormones (e.g., TRH, CRH, GnRH). The pituitary gland is composed of the anterior pituitary, which secretes tropic hormones (e.g., ACTH, TSH, FSH, LH) and whose function is controlled by hypothalamic releasing hormones, and the posterior pituitary , which stores ADH and oxytocin. The gonads are the ovaries in female individuals and testicles in male individuals. Their function is controlled via the hypothalamic-pituitary-gonadal axis , as well as the secretion of sex hormone-binding globulin (SHBG). Disruption of the hypothalamic-pituitary axis can result in the development of various endocrine disorders, which are classified according to the level of pathway disruption: primary (disorders of the peripheral endocrine gland), secondary (pituitary dysfunctions), and tertiary (hypothalamic disorders). An understanding of these hormone pathways is important for the diagnosis and management of endocrine disorders, particularly when interpreting changes in hormone levels and the results of suppression and/or stimulation tests.

Overview of endocrinological diseases

This article focuses on the hypothalamic-pituitary axis. Other important structures, hormones, and metabolic diseases are discussed in their respective articles.

Types of endocrinological diseases
- Primary disease: caused by disorders of the endocrine gland (e.g., Addison disease)
- Secondary disease: caused by disorders of the pituitary (e.g., Cushing disease)
- Tertiary disease: caused by disorders of the hypothalamus (e.g., hypothalamic trauma, hemorrhage)
- Diabetes mellitus
- Metabolic syndrome
- Osteoporosis (See “ Calcium homeostasis ” in “ Hypocalcemia ”)
- Pituitary gland
  - Hypopituitarism
  - Prolactinoma
  - Acromegaly
  - Diabetes insipidus
  - SIADH
  - Central precocious puberty
  - Hypocortisolism
  - Cushing syndrome
  - Primary hyperaldosteronism
  - Congenital adrenal hyperplasia
  - Adrenal insufficiency
  - Hypothyroidism
  - Hyperthyroidism
  - Hypogonadotropic hypogonadism
  - Hypergonadotropic hypogonadism
  Basics of endocrinology
  
  Hormones
  - Definition
    - Hormones are endogenous messengers produced by endocrine glands or single cells that are responsible for signal transduction .
    - They influence the function and metabolic rate of other organs and cells in the body.
    - Complex regulatory circuits (e.g., the hypothalamic-pituitary axis ) control their secretion.
    - Affect the neighboring cells via diffusion
    - D cells of the stomach produce somatostatin to inhibit neighboring G cells from secreting gastrin.
    - Affect the secreting cell itself
    - Autocrine signaling is particularly important for the self-renewal of embryonic stem cells. [1]
    - Secreted into the bloodstream to reach their targets
    - Pancreaticβ cells secrete insulin directly into the bloodstream to stimulate the uptake of glucose by the hepatic, muscle, and adipose tissue cells.
    - Derived from cholesterol
    - Testosterone
    - Progesterone
    - Estrogen
    - Glucocorticoids
    - Mineralocorticoids
    - Derived from a single amino acid such as phenylalanine, tyrosine, or tryptophan
    - Catecholamines
    - Thyroid hormones ( T₃ and T₄ )
    - Derived from a few or many amino acids
    - Oxytocin
    - Vasopressin
    - Prolactin
    - Glucagon
    - Insulin
    - Diffuse through the lipid plasma membrane of cells, bind to intracellular receptors, and affect transcription
    - Usually have long-term effects with delayed onset (e.g., sex hormones)
    - Steroid hormones
    - Thyroid hormones
    - Water-soluble
    - Bind to receptorproteins on the cellular membrane
    - Amine and peptide hormones (except for thyroid hormones, which are lipophilic)
    Hydrophilic hormones (e.g., catecholamines) are stored in secretory granules and released when needed. Lipophilic hormones (e.g., adrenocortical steroid hormones) pass into the bloodstream once synthesized without being stored in cells.
    - Degradation of hormones
      - Steroid hormones and thyroid hormones: inactivation and conjugation in the liver and excretion in bile
      - Catecholamines: enzymatic degradation and excretion in urine (e.g., vanillylmandelic acid )
      - Peptide/protein hormones: proteolytic degradation mainly in the liver and kidneys
      Feedback control mechanisms
      
      Hormone secretion is controlled by the following feedback mechanisms: [2]
      - Negative feedback
        
        Hormone secretion by the endocrine gland suppresses the release of hypothalamic and pituitaryhormones.
        
        Negative feedback loop types include:
        
        Ultrashort feedback loop: Hypothalamichormones inhibit their own secretion via autocrine effects.
        
        Short feedback loop: Pituitaryhormones inhibit the release of hypothalamichormones.
        
        Long feedback loop: Hormones from peripheral endocrine glands inhibit the release of hypothalamic and pituitaryhormones.
        
        Hormone secretion enhances its own production.
        
        Example: Uterine stretching during labor contractions under the influence of oxytocin triggers the release of more oxytocin from the posterior pituitary.
        
        Diagnosis of endocrine diseases
        
        Direct measurement of hormone blood levels (e.g., measuring prolactin blood level upon suspicion of prolactinoma )
        
        Stimulation of glands to detect underactivity (e.g., ACTH stimulation test for Addison disease )
        
        Inhibition of glands to detect hyperactivity (e.g., dexamethasone suppression test for Cushing syndrome )
        
        Imaging of glands to determine:
        
        Morphological abnormalities (e.g., thyroid ultrasound)
        
        Functional abnormalities (e.g., thyroid scintigraphy)
        
        Hypothalamus and pituitary gland
        
        Hypothalamus
        
        Anatomy
        
        Ventral part of the diencephalon (see “ Diencephalon ”)
        
        Composed of multiple nuclei (e.g., lateral nucleus, preoptic nucleus)
        
        Regulation of hormonal secretion by the anterior pituitary gland via the hypothalamic-pituitary axis
        
        Secretion/storage of ADH and oxytocin
        
        ADH and oxytocin are produced in the supraoptic nucleus and paraventricular nucleus of the hypothalamus .
        
        Both hormones are transported to the posterior pituitary via neurophysins (a group of carrier proteins ) and released into the circulation as needed.
        
        Inhibiting hormones
        
        Function: decrease hormonal secretion from the pituitary gland
        
        Examples: somatostatin, dopamine
        
        Function: increase hormonal secretion from the pituitary gland
        
        Examples: thyrotropin-releasing hormone (TRH), corticotropin-releasing hormone (CRH), gonadotropin-releasing hormone (GnRH), growth hormone-releasing hormone (GHRH)
        
        Pituitary gland (hypophysis)
        
        Anatomy
        
        Located in the sella turcica (midline depression of the sphenoid bone) of the middle cranial fossa
        
        Connected to the hypothalamus via the pituitary stalk (a tube-like structure between the median eminence of the hypothalamus and the posterior pituitary that contains the axons of the posterior pituitaryneurons)
        
        Consists of two major parts:
        
        Anterior pituitary gland ( adenohypophysis ): develops from oral ectoderm ( Rathke pouch)
        
        Posterior pituitary gland ( neurohypophysis ): develops from neural ectoderm
        
        Acidophil cells
        
        Secrete prolactin and growth hormone (GH)
        
        Stain well with acidic dyes such as eosin
        
        Secrete adrenocorticotropic hormone (ACTH), thyroid-stimulating hormone (TSH), luteinizing hormone (LH), and follicle-stimulating hormone (FSH)
        
        Stain well with basic dyes (e.g., hematoxylin)
        
        Do not secrete hormones [3]
        
        Stain poorly with both acidic and basic dyes
        
        Anterior pituitary gland
        
        Regulation of endocrine gland function via the release of tropic hormones
        
        Secretion of nontropic hormones with direct peripheral effects
        
        Tropic hormones : act on endocrine glands to mediate their effects
        
        All pituitary glycoprotein hormones (e.g., FSH, LH, TSH) have a common alpha subunit .
        
        Each hormone has a unique beta subunit .
        
        “ B-FLAT ”: B asophils secrete F SH, L H, A CTH, and T SH.
        
        “ P i G on Acid”: P rolactin and G H are secreted by Acid ophils.
        
        Hypothalamus and anterior pituitary
        
        Tropic hormones
        
        CRH
        
        Stimulates ACTH, MSH, and β-endorphin secretion from proopiomelanocortin (POMC) precursor
        
        CRH levels decrease after long-term steroid treatment via negative feedback.
        
        ACTH
        
        Stimulates adrenalglucocorticoid and androgen production
        
        Cleaved in the corticotropic cells of the anterior pituitary
        
        ACTH and MSH share the common precursor POMC , which explains the hyperpigmentation seen in Cushing disease.
        
        Adrenal cortex
        
        TRH
        
        Stimulates TSH and prolactin secretion
        
        An increase in TRH levels (e.g., in primary/secondary hypothyroidism) may result in the development of galactorrhea because it stimulates prolactin secretion.
        
        TSH
        
        Stimulates thyroid hormone production
        
        TSH secretion is inhibited by dopamine, somatostatin, and glucocorticoids. [4]
        
        TSH levels are the best initial test in the workup of hypothyroidism.
        
        Thyroid gland
        
        GnRH
        
        Stimulates FSH and LH secretion
        
        During breastfeeding, high prolactin levels cause supressed GnRH secretion, which results in the development of lactational amenorrhea.
        
        Pulsatile GnRH secretion is responsible for puberty and reproductive function.
        
        Gonadotropins
        
        LH
        
        Female individuals: triggers ovulation
        
        Male individuals: stimulates testosterone synthesis in Leydig cells
        
        Gonads
        
        Female individuals: ovaries
        
        Male individuals: testicles
        
        Nontropic hormones
        
        GHRH
        
        Stimulates GH secretion
        
        Synthetic forms of GHRH (tesamorelin) can be used for abdominal fat reduction in HIV-associated lipodystrophy.
        
        GH (growth hormone, somatotropin)
        
        Direct effects
        
        ↓ Glucose uptake into cells ( ↑ insulin resistance )
        
        ↑ Lipolysis
        
        ↑ Protein synthesis in muscle
        
        ↑ Amino acid uptake
        
        Growth stimulation
        
        Anabolic effect on body
        
        ↑ GH secretion: exercise, deep sleep, puberty, hypoglycemia, CKD , thyroid hormone, estrogen, testosterone, and short-term glucocorticoid exposure
        
        ↓ GH secretion: glucose, somatostatin, somatomedin , free fatty acids, and chronic glucocorticoid therapy [6] [7]
        
        Somatostatin
        
        Inhibits GH and TSH secretion
        
        Synthetic forms of somatostatin are used in the treatment of acromegaly (e.g., octreotide).
        
        Dopamine ( prolactin-inhibiting hormone ): inhibits secretion of prolactin in the pituitary gland
        
        Prolactin (secreted by lactotropic cells )
        
        ↑ Breast tissue growth and lactation
        
        Inhibits GnRH secretion
        
        Female individuals
        
        Inhibition of ovulation
        
        Amenorrhea
        
        Galactorrhea
        
        Decreased libido
        
        Inhibition of spermatogenesis
        
        Decreased libido
        
        TRH: stimulates the secretion of prolactin (but is not part of the hypothalamic-pituitary-prolactin axis )
        
        Melanocyte-inhibiting hormone : inhibits release of MSH
        
        α-MSH
        
        Cleaved in the arcuate nucleus
        
        Regulation of appetite and metabolism: promotes satiety [8]
        
        Stimulates melanogenesis → melanocyte stimulation → hyperpigmentation
        
        “No PRO-B L AM :” Derivatives of PRO opiomelanocortin are B eta- endorphin , A CTH, and M SH.
        
        Hypothalamus and posterior pituitary
        
        Plasma osmolality: sensed by hypothalamic osmoreceptors
        
        Hypovolemia: sensed by the atrial stretch receptors
        
        Hypotension: sensed by the peripheral baroreceptors
        
        Angiotensin II : sensed by hypothalamicreceptors
        
        Regulation of plasma osmolality
        
        Mediated by V2 receptors
        
        Insertion of aquaporin channels in the principal cells of the renal collecting duct and DCT [10]
        
        Results in increased water reabsorption
        
        Mediated by V1 receptors
        
        Vasoconstrictive effects at higher levels
        
        Elevated in SIADH despite plasma hypoosmolality
        
        ADH deficiency or resistance can lead to diabetes insipidus.
        
        Alcohol inhibits ADH release and causes diuresis. [12]
        
        Nipple stimulation
        
        Stretching of the vagina or cervix
        
        Promotes uterine contractions during labor
        
        Facilitates milk ejection reflex via myoepithelial cell contraction
        
        Involved in the neuromodulation of social and reproductive behavior, fear, anxiety, and depression
        
        Goserelin
        
        Leuprolide
        
        Nafarelin
        
        Histrelin
        
        Excessive pituitary stimulation → ↓ GnRHreceptors → ↓ LH and FSH secretion → ↓ estradiol production in ovaries, ↓ testosterone in male individuals [13]
        
        Transient agonist effects are followed by the suppression of the hypothalamic-pituitary-gonadal axis .
        
        Cancer (continuous administration)
        
        Breast cancer
        
        Prostate cancer
        
        Hypogonadism
        
        Decreased libido
        
        Vaginal dryness
        
        Hot flashes
        
        Degarelix
        
        Block GnRHreceptors on pituitary to decrease FSH and LH secretion
        
        Prostate cancer
        
        In vitro fertilization [14]
        
        Hypogonadism
        
        Hot flashes
        
        Elevated liver enzymes
        
        Nausea, vomiting
        
        Octreotide
        
        Lanreotide
        
        Inhibit GH secretion
        
        Inhibit the release of splanchnicvasodilatoryhormones (e.g., gastrin, glucagon, insulin, VIP)
        
        Acromegaly
        
        Carcinoid tumor
        
        VIPoma
        
        Acute esophageal variceal bleeding
        
        Glucagonoma
        
        Gastrinoma
        
        Insulinoma
        
        General
        
        Fatigue, weakness
        
        Depressed mood
        
        Steatorrhea
        
        Nausea , vomiting
        
        Abdominal pain, cramps
        
        Cholelithiasis (due to inhibition of cholecystokinin)
        
        Tesamorelin
        
        Stimulate GHreceptors
        
        Growth hormone deficiency
        
        Turner syndrome
        
        HIV-associated lipodystrophy
        
        Short stature (e.g., in children with CKD) [16]
        
        Idiopathic intracranial hypertension
        
        Increased insulin resistance
        
        Prepubertal gynecomastia
        
        Slipped capital femoral epiphysis
        
        Progression of scoliosis
        
        Pegvisomant
        
        Block GHreceptor
        
        Acromegaly
        
        Hepatotoxicity
        
        Bromocriptine
        
        Cabergoline
        
        Stimulate dopaminereceptors
        
        Prolactinoma
        
        Parkinson disease
        
        Neuroleptic malignant syndrome
        
        Malignant hyperthermia
        
        Nausea, vomiting
        
        Orthostatic hypotension
        
        Confusion, hallucination
        
        Dyskinesia
        
        Conivaptan
        
        Tolvaptan
        
        Demeclocycline (a tetracycline)
        
        Block V2 receptors and decrease water reabsorption in the renal collecting duct
        
        Tolvaptan: selective V2 receptorantagonism
        
        Conivaptan: dual V1A and V2 receptorantagonism
        
        Demeclocycline seems to disrupt the intracellular second messenger cascade that follows after the binding of vasopressin to the V2 receptor in renal collecting ducts → ↓ ADH effect
        
        Euvolemic hyponatremia (e.g., SIADH )
        
        Hypervolemic hyponatremia (e.g., congestive heart failure, liver cirrhosis )
        
        Demeclocycline: bacterial infections
        
        Hypernatremia
        
        Nephrogenic DI (specific to demeclocycline)
        
        Hypotension
        
        Dry mouth
        
        Liver failure [19]
        
        Nausea, vomiting, stomachpain
        
        Increased thirst, hunger, urination
        
        Weight loss
        
        CYP3A (including CYP3A4) inhibition and CYP3A induction
        
        Demeclocycline
        
        Azotemia and nephrotoxicity
        
        Hepatotoxicity
        
        Skin reactions
        
        Desmopressin
        
        Terlipressin
        
        Act on the V1 and V2 receptors
        
        Release vWF stored in the endothelium
        
        Central DI
        
        Von Willebrand disease
        
        Hemophilia A
        
        Nocturnal enuresis
        
        Hyponatremia
        
        Oxytocin
        
        Mediates calcium influx → uterine contraction
        
        Induction of labor
        
        Augmentation of labor
        
        Postpartum hemorrhage
        
        Hyponatremia
        
        Tachysystole
        
        Hypotension
        
        Adrenal cortex
        
        The adrenal cortex consists of three distinct layers:
        
        Zona glomerulosa: produces mineralocorticoids (i.e., aldosterone )
        
        Zona fasciculata: produces glucocorticoids (i.e., cortisol )
        
        Zona reticularis: produces androgens (i.e., dehydroepiandrosterone )
        
        ↑ Hypothalamic secretion of CRH → ↑ ACTH secretion from the pituitary → ↑ synthesis of glucocorticoids and androgens from the adrenal cortex
        
        Mineralocorticoids are secreted as a result of renin-angiotensin-aldosterone system activation.
        
        Thyroid gland
        
        The thyroid gland cells produce the following hormones: [20]
        
        Follicular cells: the thyroid hormones T₃ (triiodothyronine) and T₄ (tetraiodothyronine)
        
        Parafollicular cells: calcitonin
        
        ↑ Hypothalamic secretion of TRH → ↑ TSH secretion from the pituitary → ↑ thyroid hormone production
        
        Calcitonin is not controlled by the hypothalamic-pituitary-thyroid axis . It is released in response to increased serum Ca 2+ levels .
        
        Gonads
        
        Overview
        
        Definition
        
        Gonads are reproductive organs that produce gametes and sex hormones.
        
        The male gonad is the testicle and the female gonad is the ovary.
        
        Male individuals: testosterone, dihydrotestosterone
        
        Female individuals: estrogen, progesterone
        
        LH
        
        FSH
        
        GnRH
        
        Physiological effects of LH and FSH
        
        Physiological effects of sex hormones
        
        Feedback control mechanisms
        
        Hypothalamus
        
        Central regulation
        
        Pulsatile release of GnRH during puberty stimulates secretion of FSH, LH, and sex hormones.
        
        GnRH secretion may be influenced by competitive sports, malnutrition, or stress, any of which can lead to amenorrhea in women.
        
        Androgen
        
        Estrogen
        
        Progesterone
        
        Inhibin
        
        Hyperestrogenism (e.g., pregnancy, OCP use) causes increased SHBG levels.
        
        Female individuals with low levels of SHBG (e.g., PCOS) have higher levels of free testosterone, which is responsible for the development of hirsutism in these patients.
        
        Male individuals with high estrogen levels (e.g., in liver cirrhosis) are at risk of developing gynecomastia because of increased SHBG levels and decreased free testosterone levels.
        
        Regulation of appetite and satiety
        
        Overview [22] [23] [24]
        
        Input
        
        Gastrointestinal system
        
        Endocrine hormones: released into the circulation in response to feeding/fasting state
        
        Vagal afferents: relay signals from intestinal mechanoreceptors to the nucleus tractus solitarius
        
        Orexigenic neurons
        
        Stimulate appetite
        
        Release neuropeptide Y and agouti-related peptide
        
        Suppress appetite
        
        Release POMC
        
        Lateral nucleus of the hypothalamus (hunger center): appetite stimulation
        
        Ventromedial nucleus of the hypothalamus (satiety center): appetite suppression
        
        Polyphagia : excessive hunger (e.g., in hyperthyroidism, Prader-Willi syndrome )
        
        Anorexia: a loss of appetite (e.g., in cancer, HIV)
        
        Regulation of appetite
        
        Regulation of satiety [22] [24]
        
        Ghrelin makes you G ain weight. Leptin makes you L ose weight.
        
        Appetite regulators
        
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Where are hormones secreted?

Endocrine system worksheet pdf answers

Which is the largest gland?

Major endocrine glands and their hormones worksheet answers

What are the 3 main functions of the endocrine system?

What is the endocrine system

Endocrine glands and their hormones pdf

General endocrinology

Overview of endocrinological diseases

Basics of endocrinology

Hormones

Feedback control mechanisms

Diagnosis of endocrine diseases

Hypothalamus and pituitary gland

Hypothalamus

Pituitary gland (hypophysis)

Hypothalamus and anterior pituitary

Tropic hormones

Nontropic hormones

Hypothalamus and posterior pituitary

Adrenal cortex

Thyroid gland

Gonads

Overview

Physiological effects of LH and FSH

Physiological effects of sex hormones

Feedback control mechanisms

Regulation of appetite and satiety

Overview [22] [23] [24]

Regulation of appetite

Regulation of satiety [22] [24]

Appetite regulators

References

General endocrinology

Overview of endocrinological diseases

Basics of endocrinology

Hormones

Feedback control mechanisms

Diagnosis of endocrine diseases

Hypothalamus and pituitary gland

Hypothalamus

Pituitary gland (hypophysis)

Hypothalamus and anterior pituitary

Tropic hormones

Nontropic hormones

Hypothalamus and posterior pituitary

Adrenal cortex

Thyroid gland

Gonads

Overview

Physiological effects of LH and FSH

Physiological effects of sex hormones

Feedback control mechanisms

Regulation of appetite and satiety

Overview [22] [23] [24]

Regulation of appetite

Regulation of satiety [22] [24]

Appetite regulators

References

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