Biochem 4

What is a chemical messenger that causes changes in physiologic and chemical processes in a cell?

Hormone

What causes its target to secrete its own specific hormone?

Tropic hormone

What elicits a direct effect on the target organ or tissue?

Effector hormone

What are 3 classes of hormones?

\-Steroid hormones: water insoluble, requires carrier protein \n -Protein hormones: water soluble, quicker action, shorter half-life \n -Amines: shares properties of the other two

What is the "master gland" that secretes hormones that regulates other glands?

Pituitary

What stimulates secretion of TSH & prolactin? What portion of the brain produces it?

Thyrotropin-releasing hormone (TRH); Hypothalamus

How are serum T3 and T4 measured?

Radioimmunoassay or chemiluminometric assay

What stimulates LH and FSH production? What portion of the brain produces it?

Gonadotropin-releasing hormone (GnRH); Hypothalamus

What inhibits GH and TSH release? What portion of the brain produces it?

Somatostatin (SS); Hypothalamus

What are the 3 distinct parts of pituitary?

\-Anterior pituitary: largest portion of gland \n -Intermediate lobe: poorly developed in humans; little functional capacity \n -Posterior pituitary/neurohypophysis: responsible for storage and release of oxytocin and vasopressin

Hypersecretion of growth hormone (GH) in kids:

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 **Gigantism**

• Vision, hearing impaired

• Delayed maturation

Hypersecretion of growth hormone (GH) in adults:

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• **Acromegaly**

• Pituitary tumor

• Overgrowth of bony & soft tissue

• Headaches, tiredness

• Vision problems

• Depression

What enhances breast development during pregnancy and to induce lactation?

Prolactin

What is a pituitary tumor that directly secretes prolactin and is the most common type of functional pituitary tumor?

Prolactinoma

What are treatments for prolactinoma?

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• Reduce tumor mass

• Restore normal gonadal function and fertility

• Prevent osteoporosis

• Preserve normal pituitary function

• **Therapeutic options:** simple observation, surgery, radiotherapy, medical management with dopamine

What hormone causes thyroid gland to secrete T3 and T4?

Thyroid-Stimulating Hormone (TSH)

What hormone targets ovaries/testes, females - estrogen synthesis, male - spermatogenesis?

Follicle-Stimulating Hormone (FSH)

What hormones targets ovaries/testes?

LH & FSH

Pathway for testicular formation hormonal control

\-Hypothalamus \n -GnRH \n -LH & FSH (from pituitary) \n -Testosterone (adrenal cortex)

What is caused by hypersecretion of FSH/LH?

Virilization, hirsutism

What is caused by a deficiency of FSH/LH?

Delayed puberty, infertility, decreased libido

What hormone stimulates the adrenal cortex to produce cortisol?

Adrenocorticotropin Hormone (ACTH)

What is caused by hypersecretion of ACTH?

Cushing's syndrome (also increase aldosterone and androgens)

What is caused by a deficiency of ACTH?

Weight loss, weakness, hypotension

What is the failure of either pituitary or hypothalamus results in loss of anterior pituitary function?

Hypopituitarism: \n - Panhypopituitarism: complete loss of function \n - Monotropic hormone deficiency: loss of only a single hormone

What represents the storage region for oxytocin and vasopressin?

Posterior pituitary

What has a critical role in lactation; likely plays a major role in labor and parturition?

Oxytocin

What hormone's major action is to regulate renal free water excretion and water balance?

Vasopressin (ADH)

What triggers ADH?

Serum osmolality or blood pressure

What does a deficiency of ADH lead to?

Diabetes insipidus

What produces steroid hormones and neuropeptides essential for life?

Adrenal gland

How is hypofunction of the adrenal gland treated?

Exogenous hormone replacement

How is hyperfunction of the adrenal gland treated?

Pharmacologic suppression or surgery

What are major adrenal cortical hormones synthesized from?

Cholesterol

Which adrenal cortex zone synthesizes aldosterone, a mineralocorticoid, critical for sodium retention, potassium, and acid-base homeostasis?

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**Z**ona **G**lomerulosa **(G-Zone)** Cells (Outer 10%)

Which adrenal cortex zone synthesizes glucocorticoids (e.g. cortisol) critical to blood glucose homeostasis and blood pressure; DHEA produced here?

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**Z**ona **F**asciculata **(F-Zone)** Cells (Middle 75%)

Which adrenal cortex zone sulfates DHEA to DHEA-S: the main adrenal androgen?

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Zona **R**eticularis **(R-Zone)** Cells (Inner 10%)

Only what can enter steroidogenic pathways in response to ACTH?

Free cholesterol

What is an inherited family of enzyme disorders causing decreased cortisol and aldosterone production?

Congenital Adrenal Hyperplasia

What is most commonly decreased in congenital adrenal hyperplasia?

21-hydrolase

**What is diagnostic for congenital adrenal hyperplasia?**

High concentration of 17-hydroxyprogesterone (a substrate for 21-hydrolase)

What occurs when aldosterone cannot be suppressed with salt or volume replacement?

Primary aldosteronism

What are 3 criteria for diagnosing primary aldosteronism?

\-Plasma Aldo (PA)/plasma renin activity (PRA) greater than 25 \n -Low plasma renin that fails to increase w/ volume depletion \n -High Aldo that fails to decrease w/ saline/angiotensin inhibition

What is the treatment for primary aldosteronism?

Surgery for aldosterone producing tumor or mineralocorticoid antagonists

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Too much DHEAS in children result in:

Precocious puberty, hair growth and early development of secondary male sex characteristics in boys

Too much DHEAS in women result in:

Hirsutism, acne, male pattern baldness, amenorrhea, masculine traits; from endocrine disease or anabolic steroid use

Too much DHEAS in men result in:

Infertility, feminizing affects

Functions of cortisol?

Turns on gluconeogenesis & glycogenolysis enzymes (excess = diabetes)

•Turns on lipolysis (excess = ↑ chol/tg)

•Raises blood pressure under stress

•Strengthens heart contractions/rate

•Suppresses inflammation and allergic rxns (Ex. hydrocortisone)

•**Has pronounced diurnal variation**

What are the causes of Addison's disease (adrenal insufficiency)?

Primary adrenal problem or secondary ACTH deficiency; most common is autoimmune destruction of adrenal gland

What are the symptoms of Addison's disease (adrenal insufficiency)?

Skin pigmentation, weakness, fatigue, anorexia, nausea, diarrhea, abdominal pain, and weight loss

What is the diagnosis and treatment for Addison's disease?

**Dx:** Low baseline morning cortisol levels (

What is excess cortisol production, progressive central obesity with sparing of extremities and fat deposition results in "buffalo hump" and "moon face"?

Cushing's syndrome

What are the causes of Cushing's syndrome?

\-Adrenal Tumors - increase cortisol \n -Pituitary Tumors - increase ACTH \n -Exogenous cortisol use

How is Cushing's syndrome diagnosed?

• **No diurnal variation in cortisol**

• Increased salivary cortisol

• Increased 24 hour urine cortisol

• Treatment – if pituitary tumor, resection of tumor

• If adrenal tumor, resection of tumor or adrenal enzyme inhibitors or glucocorticoid receptor blockers

What are the symptoms of androgen excess?

–**Boys:** hair growth, precocious puberty

–**Girls:** ambiguous genitalia (infants), hirsutism, acne,, short stature, precocious puberty

–**Women:** infertility, hirsutism, acne, male pattern baldness, menstrual irregularities, virility

–**Men:** infertility and decreases in following: muscle mass, hair growth, testes size, testosterone production, spermatogenesis

How is androgen excess diagnosed and what is the treatment?

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**Dx:** High levels of DHEA-S, DHEA, testosterone

**Treatment**: High levels of DHEA-S, DHEA, testosterone

What are the functions of the adrenal medulla?

\-Produces catecholamines from amino acid tyrosine: Epinephrine, norepinephrine, dopamine \n -Acts as first responder to stress (within seconds) to promote fight-or-flight response

What is rare catecholamine-secreting tumors arising from chromaffin cells of adrenal medulla?

Pheochromocytoma

What are the symptoms of pheochromocytoma?

•Palpitations \n •Headaches \n •Sweating \n •Can have hypertension, hand tremors, weakness, fatigue, weight loss, panic attacks

What is elevated in neuroblastoma and also in pheochromocytoma?

Vanillylmandelic acid (VMA)

What is an adrenal mass, typically greater than 1 cm in diameter, found incidentally in CT, MRI, and ultrasound imaging of abdomen?

Adrenal incidentaloma

What is testosterone controlled by?

FSH & LH

What hormone influences FSH & LH?

GnRH (gonadotropin releasing hormone)

What does a deficiency of GnRH lead to?

Hypogonadism

What is a presence of an extra chromosome, \~1:500 men, have small firm testicles, enlargement of breast (Gynecomastia), breast cancer rate similar to female and elevated LH, FSH levels and possibly sterile?

Klinefelter's syndrome

What characterized by low testosterone, elevated FSH & LH, impaired sperm production - impaired response of gonads to FSH,LH?

Hypergonadotropic hypogonadism

What is an occurrence of low testosterone levels together with low or inappropriately normal FSH or LH levels?

Hypogonadotropic hypogonadism

What manifests as hypogonadism during puberty - impaired secretion of GnRH, failure to start or fully complete puberty - no sense of smell and infertile (\~1:50,000)?

Kallmann's syndrome

What disease is associated with hypogonadotropic hypogonadism in at least 25% to 50% of men, low testosterone and LH?

Type 2 diabetes

Myotonic dystrophy presents with?

\-Diabetes \n -Frontal balding \n -Atrophy & dystonia \n -Hypogonadism

What hormone promotes breast, uterine, and vaginal development?

Estrogen

What is the principle estrogen produced?

Estradiol

What hormone induces secretory activity of endometrial glands?

Progesterone

What helps maintain progesterone during pregnancy & development of gonads and fetal androgens?

Human chorionic gonadotropin (HCG)

What hormone normally used to measure pregnancy can also be increased with testicular tumors and choriocarcinoma in men?

HCG

**What is the absence of menses?**

Amenorrhea

What is infrequent or irregular menstrual bleeding?

Oligomenorrhea

What is abnormal, abundant, androgen-sensitive terminal hair growth; 5-10% of Women in US?

Hirusutism

What hormone is critical to neurologic development of the fetus?

Thyroid hormone

What is an essential component of the thyroid hormone?

Iodine

What thyroid hormone is involved in calcium homeostasis?

Calcitonin

Calcium homeostasis pathway

\-Eat food \n -Intestinal absorption \n -To blood \n -Kidneys to urine

What hormone is critical in regulating body metabolism, neurologic development, and produced by the thyroid?

Thyroid hormone

Where is the site of thyroid hormone synthesis?

Follicles

When secreted, stimulates cells in the anterior pituitary gland to manufacture and release what?

**Thyrotropin (TRH)**

Which hormone circulates to the thyroid gland and increases production and release of thyroid hormone?

Thyroid stimulating hormone (TSH)

What hormone is an ideal tumor marker for thyroid cancer post-treatment surveillance?

Thyroglobulin

What is a constellation of findings that result when peripheral tissues are presented with, and respond to and excess of thyroid hormone?

Thyrotoxicosis

Symptoms of thyrotoxicosis:

\-Anxiety \n -Emotional lability \n -Weakness \n -Tremor \n -Palpitations \n -Heat intolerance \n -Perspiration \n -Weight loss

What is the most common cause of hyperthyroidism and thyrotoxicosis?

Graves' disease

What are the features of Graves' disease?

\-Thyrotoxicosis \n -Goiter \n -Ophthalmopathy \n -Dermopathy

What is chronic lymphocytic thyroiditis called?

Hashimoto's thyroiditis

What are treatment options are used for Graves' disease?

Medications: Beta-blockers, propylthiouracil, methimazole \n Radioactive iodine \n Surgery

What medication is used to treat cardiac arrhythmias and leads to thyroid dysfunction? What is the disease called?

Amiodarone; Amiodarone-Induced Thyroid Disease

**What kind of thyroid dysfunction does amiodarone lead to?**

Hypothyroidism (8-20%) \n Hyperthyroidism (3%)

True or False: \n Individuals who have excess thyroid hormone have symptoms of increased metabolic activity such as tachycardia or tremor

True

99% of the body's calcium is stored as what?

Hydroxyapatite salt (bone/teeth)

What tissues are involved in synthesis of vitamin D?

Skin, liver, kidneys

What is the active metabolite of vitamin D?

1,25(OH2) Vitamin D