Endocrine System Quiz

Hypothalamic and Pituitary Agents

• The hypothalamus and pituitary gland work together in a neuroendocrine system to regulate many bodily functions, including growth, metabolism, and reproduction.
• The hypothalamus produces releasing hormones that trigger the release of tropic hormones from the anterior pituitary.
• These tropic hormones then stimulate hormone release from target glands.
• The anterior pituitary communicates with the hypothalamus via the portal venous system.
• The posterior pituitary stores and releases hormones produced in the hypothalamus, regulated by neural activation.
• These hormones include oxytocin and ADH (antidiuretic hormone).
• Endocrine axes are a common theme with releasing hormones from the hypothalamus regulating the release of anterior pituitary hormones that act on target glands to stimulate hormone release from the target gland.
• Negative feedback control mechanisms, where the end product inhibits the release of releasing and stimulating hormones, are key components of the system.
• Exceptions exist, such as GH and prolactin, where the hypothalamus regulates these hormones differently.
• Most hypothalamic/pituitary hormones are accessible, but a small fraction is used for clinical purposes, mostly for diagnostic use or hormone replacement in deficiencies.

Neuroendocrine System

• Regulates many functions like growth, metabolism, and reproduction.
• Growth, metabolism, reproduction.

Releasing Hormones from Hypothalamus

• Trigger tropic hormone release from anterior pituitary.
• Cause target gland hormones to be released from target glands.
• TRH releases TSH, which releases thyroid hormone.
• There are exceptions, like GH and prolactin, which are controlled differently.
• The hypothalamus and anterior pituitary communicate through a portal system.

Posterior Pituitary Hormones

• Produced in the hypothalamus, stored in the posterior pituitary.
• Release is regulated by neural activation of hypothalamic neurons.
• Include oxytocin and ADH (antidiuretic hormone).

GH Actions

• Works through Jak/Stat system.
• Effects primarily involve growth and metabolism.
• Stimulates bone lengthening, muscle growth, and fat breakdown.
• Mediates growth effects mainly through IGF-1.

GH Actions (cont.)

• Mixed effects on carbohydrate metabolism, with GH having opposite effects to insulin sensitivity.
• Reduces insulin sensitivity, leading to mild hyperinsulinemia and elevated blood glucose.
• IGF-1 has insulin-like effects on glucose transport.

Hypothalamic and Anterior Pituitary Tropic Hormones

• Hypothalamic tropic hormones include PRH, PIH, TRH, CRH, GHRH, GHIH, GnRH.
• Anterior pituitary tropic hormones include Prolactin, TSH, ACTH, GH, LH, FSH.
• These hormones target different areas in the body to produce various downstream effects.

Approved Uses of Growth Hormone

• Growth failure in children, due to factors like: GH deficiency, Noonan syndrome, Prader-Willi syndrome, Turner syndrome, idiopathic short stature.
• Improved metabolic state and body composition in adults, like GH deficiency, wasting in HIV patients, and short bowel syndrome.

Adverse Effects

• Pancreatitis, gynecomastia, intracranial hypertension, muscle aches, scoliosis, edema.
• Contraindicated for use in active malignancies.

GH Antagonists

• Used to treat GH-secreting tumors (acromegaly, gigantism, carcinoid tumors).
• Somatostatin analogs like octreotide have longer durations of action.
• Dopamine agonists like Bromocriptine and Cabergoline are effective.
• GH receptor blockers, like Pegvisomant, are used for acromegaly.

GnRH and Analogs

• Act through GPCRs on gonadotrophs in the pituitary.
• Pulsatile secretion is required for normal FSH and LH release.
• Sustained administration inhibits FSH and LH release.
• Used in prostate cancer treatment and women needing ovarian suppression.
• Includes leuprolide, goserelin, and others.

Leuprolide (Lupron Depot) and GnRH Analogs

• Given intravenously, intramuscularly, or intranasally, with a 3-hour half-life.
• Adverse effects may include hot flashes, headaches, sweats, depression, diminished libido, and breast atrophy.
• Contraindicated in pregnancy and breastfeeding.
• GnRH antagonists, like Ganirelix and Cetrorelix, are used in IVF.
• Elagolix is indicated for endometriosis.

Gonadotropins (FSH, LH, and hCG)

• FSH stimulates oocyte maturation and estrogen production.
• LH affects androgen synthesis and sperm production.
• hCG maintains the corpus luteum and stimulates testosterone production.
• Used for stimulating sperm production, inducing follicle development, and ovulation in females, especially fertility treatments (IVF).
• Recombinant forms like follitropin alfa and beta are available, as well as those extracted from urine in postmenopausal women.

Prolactin

• No prolactin preparations are used in prolactin deficiency.
• Dopamine agonists, like Bromocriptine and Cabergoline, are used for hyperprolactinemia and prolactinomas.
• These agonists are effective in reducing prolactin secretion.

ACTH (Adrenocorticotropic Hormone)

• A 39-amino acid peptide hormone.
• Synthetic derivative (ACTH1-24) is called Cosyntropin.
• Works through GPCRs (g-protein coupled receptors) to stimulate adrenal cortical hormone production and activity.
• Used to differentiate primary from secondary adrenal insufficiency.

Vasopressin (ADH) and Oxytocin

• ADH/oxytocin are peptide hormones with similar sequences stimulating uterine contractions and breast tissue myoepithelial contraction.
• ADH increases water permeability in the kidneys, lowering urine output.
• Oxytocin is involved in labor and milk ejection.
• Used to induce labor or reduce postpartum bleeding..
• Acts via GPCRs on the phosphoinositide system.

Oxytocin Receptor Antagonist

• Atosiban is an oxytocin receptor antagonist used in preterm labor.
• Not widely approved in many regions.

Vasopressin and Desmopressin

• Vasopressin (ADH) is a peptide hormone that increases water permeability, and is used for diabetes insipidus.
• Desmopressin is a synthetic analog used for the same indications, as well as for bleeding disorders.
• High-dose vasopressin can be used in pulseless arrest.
• Adverse effects may include headache, nausea, vomiting, abdominal cramping and hyponatremia and seizures.

Vasopressin Antagonists

• Conivaptan and Tolvaptan are selective V1/V2 and V2 receptor antagonists, respectively, primarily to treat hyponatremia.
• These drugs increase urinary free water clearance.