By The Name Of The God

Internal medicine

Endocrinology

DISEASES OF THE PITUITARY GLAND

The pituitary is divided into 2 lobes—

1- The Adenohypophysis or (anterior lobe), which constitutes 80% of

the pituitary

2- The NEUROhypophysis or (posterior lobe), which is t h e s t o r a g e

s i t e for hormones produced by the neurosecretory neurons ( s u p r a o p t i c a n d p a r a v e n t r i c u l a r n u c l e i ) within the hypothalamus. The 2 hormones

stored in the are ADH (antidiuretic hormone or vasopressin) and oxytocin

(focus ) The hormones Of posterior lobe (ADH and oxytocin)

produced by h y p o t h a l a m u s (by the neurosecretory neurons ( s u p r a o p t i c

a n d p a r a v e n t r i c u l a r n u c l e i ) )

The hypothalamus regulates the release of hormones from the anterior pituitary by different hypothalamic releasing and inhibiting hormones (hypothalamic–pituitary axis)

- Each pituitary hormone stimulates release of the active hormone from the final target gland. The active hormones then inhibit release of releasing factors and stimu-latory hormones from the hypothalamus and pituitary gland, respectively. This is feedback inhibition (e.x ACTH go to adrenal stimulates to produced cortisol and cortisol go back to hypothalamus and stops releasing the ACTH it’s called

((Feedback ))

We use this physiology to screen and diagnose these diseases

Hormones OF THE ANTERIOR PITUITARY

HormoneSymbol

(s)Structure Target Effect

Adrenocorticotr

opic hormoneACTH Polypeptide Adrenal gland

Secretion

of glucocorticoid, mineralocorticoidand 

androgens

Beta-endorphin Polypeptide Opioid receptor Inhibit perception of pain

Thyroid-

stimulating

hormone

TSH Glycoprotein Thyroid gland Secretion of thyroid hormones

Follicle-

stimulating

hormone

FSH Glycoprotein Gonads Growth of reproductive system

Luteinizing

hormone

LH,

ICSHGlycoprotein Gonads Sex hormone production

Growth

hormone

GH,

STHPolypeptide Liver, adipose tissue

Promotes

growth; lipid and carbohydrat

e metabolism

Prolactin PRL PolypeptideOvaries, mammary

glands

Secretion

of estrogens/progesterone; mil

kproduction

Leptin - PolypeptideCorticotrophic an

dThyrotrophic cellsTSH and ACTH secretion

Hormones OF THE Posterior PITUITARY (neurohypophysis)

HormoneSymbol(

s)Main targets Effect Source

Oxytocin OTUterus,mammary

glands

Uterine

contractions; lactati

on

supraoptic an

dparaventricular nuclei

ADH

(Vasopressin) VP, AVP,

ADH

Kidneys o

rArterioles

Stimulates water

retention; raises

blood pressure by

contracting

arterioles, induces

male aggression

supraoptic an

dparaventricular nuclei

These hormones produced in supraoptic and paraventricular nuclei and storage an d secreted from Posterior Pituitary (neurohypophysis)

DISEASES OF THE ANTERIOR PITUITARY

Microadenomas are defined as tumors <1 cm in diameter.

Macroadenomas are tumors >1 cm in diameter.

Microadenomas are more common than macroadenomas

Larger tumors can occasionally compress the optic chiasm and can cause visual deficits.

Pituitary Adenomas by Function

Prolactin 50–60%

Growth hormone (GH) 15–20%

ACTH 10–15%

Gonadotroph 10–15%

Hyperprolactinemia

Definition. Excess prolactin secretion is a common clinical problem in women and causes the syndrome of galactorrhea-amenorrhea. The amenorrhea appears to be caused by inhibition of hypothalamic release of gonadotropin-releasing hormone (GnRH) with a decrease in luteinizing hormone (LH) and Follicle-stimulating hormone (FSH) secretion. Prolactin inhibits the LH surge that causes ovulation. The LH/FSH-producing cells are not destroyed, just suppressed. Although hyperprolactinemia is also seen in men, gynecomastia and especially galactorrhea are very rare. The most common presenting symptom in men i s e r e c t i l e d y s f u n c t i o n a n d d e c r e a s e d l i b i d o .Prolactinomas : Autonomous production of prolactin occurs with pituitary adenomas Prolactinomas (Hyperprolactinemia) the most common functioning pituitary adenomas, accounting for 60% of all pituitary tumorsThey are usually microadenomas when they occur in women and macroadenomas in men, usually presenting with visual field deficits. (in women we will detected the adenoma early due to the to many and clear symptoms )

- Macroadenomas can obstruct the pituitary stalk, increasing prolactin release by blocking dopamine transport from hypo-thalamus (stalk effect). Other examples are tumors, such as craniopharyngioma, meningioma, and dysgerminoma; empty sella; and trauma.

Etiology : - natural physiologic states :

1- pregnancy2- early nursing3- Hypoglycemia4- Seizure5- Exercise6- Stress7- Sleep8- Cirrhosis9- nipple stimulation10- Chronic renal failure (due to PRL clearance).11- Acromegaly

- Hyperprolactinemia can also occur with decreased inhibitory action of dopamine1- The use of drugs that block dopamine synthesis (phenothiazines, metoclopramide ) 2- dopamine-depleting agents (-methyldopa, reserpine)3- Tricyclic antidepressants4- Narcotics , cocaine5- SSRIs

Other 1- Primary hypothyroidism (resulting in an increase in thyrotropin-releasing hormone [TRH]) and

subsequently an increase in prolactin release.Always check TSH in patients with elevated prolactin

Clinical. women mengalactorrhea, menstrual abnormalities amenorrhea/oligomenorrhea, osteopenia and osteoporosis in long-standing cases, infertility, and gynecomastia

erectile dysfunction, decreased libido (most common ) hypogonadism , gynecomastia , and infertility

In both may be 1- Hemianopia (more in men due to the size of the tumor

2- Because of hypoestrogenism and hypoandrogenism, hyperprolactinemia can lead to osteoporosis3-

*# Women are detected earlier because of menstrual symptoms. Hence, microadenomas are more common in women

Diagnosis. At first Time exclude states - Pregnancy by hCG- Hypothyroidism By TSH - Lactation- Medications

Before starting the work-up of hyperprolactinemia. Prolactinomas may secrete growth hormone (GH).

The normal values for prolactin are:

Males: 2 - 18 ng/mL.

Nonpregnant females: 2 - 29 ng/mL.

Pregnant women: 10 - 209 ng/mL.

Dx :1- Prolactin levels >100 ng/mL suggest probable pituitary adenoma in non-pregnant women

Usually with

- Prolactin levels 100 ng/ml = tumor size 1 cm

- Prolactin levels 200 ng/ml = tumor size 2 cm. etc.

** MRI PRL level >100 to 200 mg/L (normal <20 mg/L) in a nonpregnant woman indicates a need for an MRI

of the pituitary.

Management: For Prolactinomas, initially treat with cabergoline or bromocriptine (a dopamine agonist), which reduce prolactin levels in almost all hyperprolactinemic patients. Dopamine normally inhibits prolactin release. Surgery is reserved o n l y f o r a d e n o m a s n o t r e s p o n s i v e t o c a b e r g o l i n e o r b r o m o c r i p t i n e , or i f t h e t u m o r i s a ss o c i a t e d w i t h s i g n i f i c a n t c o m p r e ss i v e n e u r o l o g i c e f f e c t s .

Surgery is more effective for microadenomas than macroadenomas.

About 90% of patients treated with cabergoline have a drop in prolactin to <10% of pretreatment levels.

Radiation therapy is used if drug therapy and surgery are ineffective in reducing tumor size and prolactin levels

Notes 1- The most common presenting symptom in men is erectile dysfunction and decreased libido.

2- The Most common adenoma of the Pituitary is Hyperprolactinemia 60 %

3- The most common presenting symptom in Women are galactorrhea (58%), oligomenorrhea (58%)

4- The Treatment Of choice of Hyperprolactinemia is Medical treatment by cabergoline(used mostly ) or bromocriptine .

5- Cabergoline is used more often than bromocriptine because of a better side-effect profile. It should be considered the preferred medical treatment for galactorrhea.