[09.07] Hypothalamic and Pituitary Hormones and Drugs V2.1

Master gland

What is another name for the pituitary gland?

Control of metabolism, growth, and reproduction

What are the primary responsibilities of the pituitary gland?

Approximately 0.6 grams

What is the average weight of the pituitary gland?

Sella turcica

In what bony structure at the base of the brain does the pituitary gland rest?

Adenohypophysis

What is the anatomical name for the anterior lobe of the pituitary gland?

Neurohypophysis

What is the anatomical name for the posterior lobe of the pituitary gland?

Portal venous system

What system drains the hypothalamus and perfuses the anterior pituitary?

Neurosecretory fibers

Through what structures are posterior lobe hormones transported from the hypothalamus to the pituitary?

Oxytocin and Vasopressin

Which two hormones are released by the posterior pituitary?

Corticotropin-releasing hormone, Thyrotropin-releasing hormone, Growth hormone-releasing hormone, and Gonadotropin-releasing hormone

What are the four primary stimulatory hypothalamic factors?

Dopamine and Somatostatin

What are the two primary inhibitory hypothalamic factors?

JAK/STAT superfamily

Growth hormone and Prolactin activate which superfamily of receptors?

G-protein coupled receptors

TSH, FSH, and LH activate which type of receptors?

Pro-opiomelanocortin or POMC

From which precursor molecule is Adrenocorticotropic hormone (ACTH) cleaved?

alpha-Melanocyte stimulating hormone

Which peptide cleaved from POMC plays a role in skin pigmentation?

beta-endorphin

Which peptide cleaved from POMC is known for rewarding behavior?

Melanocortin 2 receptor accessory protein

Which transmembrane protein is essential for normal ACTH receptor trafficking and signaling?

IGF-1

What is the primary target organ mediator for Growth Hormone?

Thyroxine (T4) and Triiodothyronine (T3)

What are the primary target organ hormones for TSH?

Cortisol

What is the primary target organ hormone for ACTH?

Estrogen, progesterone, and testosterone

What are the primary target organ hormones for FSH and LH?

Dopamine

Which hypothalamic factor inhibits the release of Prolactin?

Diagnostic test for GH and GHRH sufficiency

What is the rare clinical use for Growth hormone-releasing hormone?

Distinguish Cushing disease from ectopic ACTH secretion

What is the rare clinical use for Corticotropin-releasing hormone?

Assess initiation of puberty or treat infertility

What are the clinical uses for Gonadotropin-releasing hormone?

Treat hyperprolactinemia

What is the main clinical use for Dopamine agonists?

Assess TSH-stimulated radioactive iodine uptake for cancer recurrence

What is a clinical use for Thyroid-stimulating hormone?

Suspected adrenal insufficiency or congenital adrenal hyperplasia

What are the clinical indications for using Adrenocorticotropin?

Lean body mass and bone density

Which two aspects of body composition are particularly affected by Growth Hormone?

191-amino acid peptide

What is the structure of Growth Hormone?

Somatropin

What is the name for recombinant Growth Hormone?

20 minutes

What is the half-life of Growth Hormone?

Modification with albumin or inert protective carriers

What modification allows for weekly dosing of recombinant GH?

Long bone growth until epiphyseal plates fuse

What is the primary skeletal effect of Growth Hormone?

Muscle hypertrophy or increased muscle mass

What is the anabolic effect of GH in muscle?

Decreased adipose tissue

What is the catabolic effect of GH in adipose cells?

Reduced insulin sensitivity

Why might patients on GH therapy experience slight hyperinsulinemia and hyperglycemia?

Hypoglycemia

Children with Growth Hormone deficiency can present with what metabolic emergency?

Subnormal height velocity and subnormal GH response to provocative testing

What are the two primary criteria for diagnosing GH deficiency?

Prader-Willi, Noonan, and Turner syndromes

Name three genetic syndromes for which GH therapy is indicated.

Wasting in patients with HIV infection

For what specific condition is GH used to increase lean body mass and physical endurance?

Short bowel syndrome

For what GI condition is GH used to improve function?

Pseudotumor cerebri, slipped capital femoral epiphysis, and scoliosis progression

What are three rare adverse effects of GH in Prader-Willi patients?

Active malignancy

In what condition is Growth Hormone therapy strictly contraindicated?

Critically-ill patients

In which patient group does GH therapy lead to an increased mortality rate?

Mecasermin

What is the name of the recombinant IGF-1 used for severe IGF-1 deficiency?

Hypoglycemia

What is the most important adverse drug reaction of Mecasermin?

Consuming a carbohydrate-containing meal within 20 minutes

How can the hypoglycemia associated with Mecasermin be avoided?

Adenotonsillar hypertrophy and intracranial hypertension

What are two severe adverse reactions associated with Mecasermin?

Gigantism

What condition is caused by excess GH before long bone epiphyses close?

Inhibit GH, TSH, glucagon, insulin, and gastrin

What are the primary inhibitory paracrine functions of Somatostatin?

1 to 3 minutes

What is the half-life of Somatostatin?

Octreotide

What is the most widely used somatostatin analog?

80 minutes

What is the half-life of Octreotide?

Acromegaly, carcinoid tumors, and gastrinomas

What are three clinical uses for Octreotide?

Bleeding esophageal varices

What acute GI emergency can be treated with somatostatin analogs?

Steatorrhea, biliary sludge, and gallstones

What are the common GI adverse effects of Octreotide?

Vitamin B12 deficiency

What deficiency may occur with long-term Octreotide use?

Pasireotide

Which somatostatin analog has the greatest affinity for SSTR5?

Hyperglycemia

What metabolic ADR should clinicians watch for with Pasireotide?

Pegvisomant

What is the name of the GH receptor antagonist used for resistant acromegaly?

Blocks native GH binding by preventing conformational changes

What is the mechanism of action of Pegvisomant?

Does not inhibit GH secretion

How does Pegvisomant affect native GH secretion?

IGF-1 levels

What should be measured to assess the efficacy of Pegvisomant?

Follicle-stimulating hormone, Luteinizing hormone, and Human Chorionic Gonadotropin

Which three hormones are classified as gonadotropins?

Stimulate ovarian follicle development

What is the principal function of FSH in women?

Stimulates androgen production by theca cells

What is the role of LH during the follicular stage of the menstrual cycle?

Conversion of androgens to estrogens

What role does FSH play in the ovarian granulosa cells?

Estrogen and progesterone production

LH primarily controls the production of which hormones during the luteal phase?

hCG

Which hormone takes over the control of estrogen and progesterone production if pregnancy occurs?

Primary regulator of spermatogenesis

What is the primary role of FSH in men?

Stimulates testosterone synthesis in Leydig cells

What is the main stimulus of LH in men?

Androgen-binding protein

FSH helps maintain high local androgen concentrations in men by stimulating the production of what?

Identical alpha subunit

What structural feature do FSH, LH, and TSH all share?

Distinct beta subunit

What confers receptor specificity to the different gonadotropins?

Menotropin

Which commercial product contains both FSH and LH extracted from the urine of postmenopausal women?

1 to 1

What is the FSH-to-LH bioactivity ratio of Menotropin?

Urofollitropin

What is the name for the purified human FSH extracted from urine with LH removed?

Follitropin Alfa and Follitropin Beta

What are the two recombinant FSH preparations?

Lutropin Alfa

What is the only recombinant form of human LH?

Stimulation of follicular development in LH-deficient infertile women

What is the approved use for Lutropin Alfa?

Choriogonadotropin Alfa

What is the name for recombinant hCG?

Weight rather than units

On what basis is recombinant hCG dosed compared to urinary hCG?

Induce final oocyte maturation

What is the clinical role of hCG in assisted reproductive technology protocols?

GnRH agonist or GnRH antagonist

What drugs are used to prevent a premature LH surge during controlled ovarian stimulation?

Progesterone

Which hormone is preferred for luteal support because it has a lower risk of OHSS than hCG?

Treatment of male infertility

Aside from ovulation induction, what is another use for gonadotropins?

8 to 12 weeks of hCG followed by FSH

What is the conventional therapy sequence for male infertility?

4 to 6 months

How long does it usually take for sperm to appear during gonadotropin treatment for male infertility?

Prepubertal cryptorchidism

What outdated use of hCG can lead to precocious puberty?

Ovarian Hyperstimulation Syndrome and Multiple Pregnancies

What are the two most serious complications of gonadotropin use in women?

Hypovolemia, ascites, and thromboembolic events

Name three symptoms of Ovarian Hyperstimulation Syndrome.

Gestational diabetes, preeclampsia, and preterm labor

What are three complications associated with multiple pregnancies?

Gynecomastia

What is a risk for men receiving gonadotropins that correlates with testosterone levels?

Pulsatile administration

How must GnRH be administered to stimulate the release of LH and FSH?

Inhibits the release of FSH and LH

What is the effect of non-pulsatile or continuous GnRH administration?

Prostate cancer and central precocious puberty

Name two conditions treated with continuous GnRH administration.

Decapeptide

What is the chemical structure of GnRH?

Gonadorelin

What is the name for the acetate salt of synthetic human GnRH?

Leuprolide, Goserelin, Nafarelin, and Triptorelin

Name four GnRH analogs.