Endocrine 01

-ACTH
-PRL
-GH
-LH
-FSH
-TSH

-ADH
-Oxytocin

Small tumors <1cm

-Pituitary Gland Microadenoma
-White region is the posterior pituitary

-Large tumor of the pituitary
-The optic nerve is compressed by the tumor. The white area is the normal pituitary.

Somatostatin and GHRH

-GH is released into the periphery
-It causes the liver to start production and release of IGF-1
-Other tissues produce IGF-1 as well, but not at the same amount

A gastric hormone that feeds back into the pituitary and stimulates GH. Its role in physiologic regulation is unclear.

-Released in a pulsatile pattern in healthy adults
-The pulses generally occur at night

-Stimulates GH secretion
-Induces GH synthesis and secretion in somatotrophs

-Inhibitory of GH secretion
-Decreases of somatostatin allow for GH secretory bursts (pulsatile pattern)

-L-dopa
-Clonidine

-Hypoglycemia (insulin)
-Arginine
-Pyridostigmine

-Sleep
-Exercise
-Stress
-Amino acids
-Fasting

-Glucose inhibits GH at the hypothalamic level
-GH feeds back at the hypothalamic level on itself.
-The target tissues produce IGF-1 which feeds back at the pituitary and hypothalamic levels

-Growth Hormone: Increased IGF-1 production in liver, major source of circulating IGF-1
-Nutritional status: Fasting leads to IGF-1 decrease
-Age
-Genetic Factors
-Binding proteins (IGF-BP3 and ALS)
-Increased levels in pregnancy and puberty
-There are very few pathologic conditions besides acromegaly that can produce elevated IGF-1.

-They start low, peak during puberty, and then decrease from there
-The peak of IGF-1 occurs in the 2nd stage of puberty and gradually declines in adulthood.
-Clinically it is important to look at IGF-1 levels in relationship to age.

-Increased bone size and density
-Increased cartilage and soft tissue deposition
-Lipolytic
-Insulin resistance in muscle and liver
-Produces IGF-1
-Feeds back to inhibit the hypothalamus

-Metabolic effects
-Causes insulin sensitivity to balance out GH
-Anabolic to bone and muscle
-Feeds back to inhibit GH release at pituitary and hypothalamic levels

1. GH excess
-GH overproduction by GH secreting pituitary tumor: Acromegaly

2. GH deficiency:
-Childhood onset
-Adult onset

-Pituitary tumor raises growth hormone.
-It secretes growth hormone in a pulsatile fashion.
-The baseline GH is elevated and you have pulses, but they are blunted.
-The average GH is elevated.
-That integrate elevated GH produces a high IGF-1 level.

-Most patients who present already look like they have it, so they are presenting late.
-When you think of it you can measure the GH and IGF-1. A random GH is not a good measure.
-Measure GH suppression after oral glucose.
-Patients with acromegaly do not have a fall in GH <1 ug/L.
-Normal patients do.

-Enlargement of hands, feet
-Coarsening of facial features
-Enlargement of tongue
-Sweating
-Menstrual disorders
-Headache
-Arthritis
-Carpal tunnel syndrome
-Diabetes or impaired glucose intolerance
-Impaired potency and/or libido
-Hypertension
-Visual field defect
-Obstructive sleep apnea
-Galactorrhea
-Coronary Artery Disease

-Sleep apnea
-Snoring
-Problems with speech

Primary Therapy:
-Transsphenoidal surgery
-Medical Therapy

Adjunctive therapy:
-Medical Therapy
i. Dopamine agonists (not effective)
ii. Somatostatin analogs
iii. GH receptor antagonist
-Radiotherapy

-Only treatment with potential for cure
-Leads to immediate decline in GH level
-Reduces tumor size and relieves mass effect
-Complication rate is low

Directly inhibit GH secretion
-Somatostatin Analogs
-Dopamine agonists

Block GH receptors peripherally
-GH receptor antagonist
-Negates GH effect in the periphery and inhibits IGF-1 secretion

Lanreotide: Given IM once a month

Octreotide: Given Subcutaneously once a month

These work in ~60% of patients

Somatostatin analog given IM once a month

Somatostatin analog Given subcutaneously once a month

-GH molecule that has been mutated to function as a receptor antagonist
-GH receptors are blocks
-GH does not fall, but GH actions are blocked
-IGF-1 levels fall and clinical symptoms of acromegaly improve

-Biochemical control
-GH suppression
-IGF-1 normalization
-Relieve signs and symptoms
-Reduce tumor size and mass effect
-Preserve pituitary function
-Minimal side effects

Hypothalamic disease: GHRH deficiency

Pituitary Disease: Failure to secrete GH

Failure to generate IGF-1 peripherally
-Deficiencies of GH or IGF-1 receptors in liver; IGF-1 not produced GH resistance, not GH low

1. Pituitary tumor (54%)
2. Craniopharyngioma (12%)
3. Idiopathic (10%)
4. CNS tumor (4%)
5. Empty Sella Syndrome (4%)
6. Sheehan's syndrome (3%)
7. Head Trauma (2.4%)

1. Increased cholesterol and increased levels of some CV risk markers (eg CRP)

2. Abnormal body composition; increased central body fat

3. Decreased bone density

4. Decreased quality of life

1. Requires daily subcutaneous injections of HGH

2. Effect in GH deficient adults; Modest improvement in the effects of GH deficiencies

Stimulated by:
-Sleep
-Food
-Stress
-Pregnancy
-Nursing
-Breast stimulation

Suppresed by:
Dopamine

Under tonic inhibition by dopamine

Excess serum prolactin:
Prolactin >20ug/L in men or >25 ug/L in women

Hyperprolactinemia

0.4% in unselected normal adult populations
-Many different etiologies
-Prolactinomas are the most frequent cause of hyperprolactinemia

-Prolactinoma
-Acromegaly
-Other sellar masses
-Infiltrative disorders
-Hypothalamic and pituitary stalk disease or damage

-Primary hyperthyroidism
-Seizures
-Polycystic ovary disease
-Neurogenic causes (chest wall trauma, surgery, herpes zoster)
-Renal insufficiency
-Cirrhosis
-Medications

Suppresses gonadotropins, leading to varying degrees of gonadal dysfunction

-Oligo-amenorrhea
-Infertility
-Galactorrhea
-Estrogen deficiency
-Acne/hirsutism
-Osteopenia

-Decreased libido
-Erectile dysfunction
-Gynecomastia
-Galactorrhea
-Infertility
-Osteopenia

-Dopamine agonist therapy is primary treatment for almost all patients
-Surgery and radiation therapy occasionally used
-Careful follow-up without treatment is an option for patients if they
-Do not have a macroadenoma
-Are asymptomatic
-Have normal gonadal function
-Are not seeking fertility

-Bromocriptine
-Cabergoline

Cabergoline is more potent, has a shorter half life. Both are safe in pregnancy, but bromocriptine has been used more in pregnancy.

-Restore gonadal function
-Improvement in sexual dysfunction
-Fertility
-Resolve galactorrhea (if bothersome)
-Reduce/stabilize tumor size
-Reverse mass effects
-Preserve/restore pituitary function
-Normalize PRL levels (corrects other hormone abnormalities)

Prolactin secreting tumor before and after treatment