Pituitary Disorders

M. Luthfi

The Endocrine System

• Consists of several glands located in various parts of the body

Pituitary gland

“The Master Gland”

– Primary function is to control other glands.

– Produces many hormones.– Secretion is controlled by

the hypothalamus

The Hypothalamus-Pituitary unit

•most dominant portion of the entire endocrine system

•regulates the function of the thyroid, adrenal and reproductive glands

•controls somatic growth, lactation, milk secretion and water metabolism

The Hypothalamus-Pituitary unit

Hypothalamus and anterior pituitary

Midsagital view illustrates parvicellular neurosecretory cells secrete releasing factors into capillaries which are then transported to the anterior pituitary gland to regulate the secretion of pituitary hormones

Hypothalamus and posterior pituitary

Midsagital view illustrates that magnocellular neurons nuclei secrete oxytocin and vasopressin directly into capillaries in the posterior lobe

Hypothalamic releasing hormonesHypothalamic releasing hormone Effect on pituitary

Corticotropin releasing hormone (CRH)

Stimulates ACTH secretion

Thyrotropin releasing hormone (TRH)

Stimulates TSH and Prolactin secretion

Growth hormone releasing hormone (GHRH)

Stimulates GH secretion

Somatostatin Inhibits GH (and other hormone) secretion

Gonadotropin releasing hormone (GnRH)

Stimulates LH and FSH secretion

Prolactin releasing hormone (PRH) Stimulates PRL secretion

Prolactin inhibiting hormone (dopamine)

Inhibits PRL secretion

Pituitary Gland

• Thyroid-stimulating hormone (TSH)• Growth hormone (GH)• Adrenocorticotropin (ACTH)• Follicle-stimulating hormone (FSH)• Prolactin• Luteinizing hormone (LH)

Anterior Pituitary

• Oxytocin• ADH

Posterior Pituitary

Anterior pituitary cells and hormones

Cell type Pituitary population

Product Target

Corticotroph 15-20% ACTHb-lipotropin

Adrenal glandAdipocytesMelanocytes

Thyrotroph 3-5% TSH Thyroid glandGonadotroph 10-15% LH, FSH Gonads

Somatotroph 40-50% GH All tissues, liver

Lactotroph 10-15% PRL Breastsgonads

ANTERIOR PITUITARY (Adenohypophysis)

• SECRETES 6 HORMONES:– ACTH

controls release of cortisol in adrenal glandsACTH release controlled by corticotropin-releasing hormone (CRH)

ANTERIOR PITUITARY / Adenohypophysis

•stimulates the thyroid gland to release Thyroid hormone. •Thyroid –releasing hormone; secreted by hypothalamic neurons-control release of TSH

TSH

• glucose usage• consumption of fats as an energy source

GH

GH

Anterior Pituitary / Adenohypophysis

• mammary gland growth • milk secretionProlactin

• growth of ovarian follicles • spermatogenesis in malesFSH

•regulates growth of gonads •reproductive activitiesLH

Posterior Pituitary

Oxytocin

• stimulates gravid uterus• causes “let down” of

milk from the breast

ADH (vasopress

in)

• causes the kidney to retain water

Pituitary Tumors

PITUITARY TUMORS

10% OF ALL BRAIN TUMORS

Tumors usually cause hyper release of hormones

Etiology of Pituitary Tumor

• Non-Functioning Pituitary Adenomas

• Endocrine active pituitary adenomas– Prolactinoma– Somatotropinoma– Corticotropinoma– Thyrotropinoma– Other mixed endocrine active adenomas

• Malignant pituitary tumors: Functional and non-functional pituitary carcinoma

• Metastases in the pituitary (breast, lung, stomach, kidney)

Abnormal Pituitary Function Associated with Pituitary Tumors

• Hypopituitarism• Hypersecretion of Pituitary Hormones

Hypopituitarism

• Pituitary adenomas most common cause• Sequence of function loss from mass effect:

Growth hormone GH deficiency Gonadotropins hypogonadismACTH hypoadrenalismTSH hypothyroidism

Hypopituitarism

• GH deficiency : decreased muscle strength and exercise tolerance, diminished libido, increased body fat

• Gonadotropin deficiency: oligo/amenorrhea, diminished libido, infertility, hot flashes, dypareunia, impotence, osteopenia

Hypopituitarism

• ACTH deficiency : malaise, fatigue, anorexia, hypoglycemiamineralocorticoid secretion is preserved

• TSH deficiency : malaise, leg cramps, fatigue, dry skin, cold intoleranceclinically similar to primary hypothroidism

Hypersecretion of Pituitary Hormones

- Hyperprolactinemia- Acromegaly- Cushing’s Disease

Hypersecretion of Pituitary Hormones

• Prolactinoma : oligo/amenorrhea, galactorrhea, infertility, osteopenia, decreased libido, headaches, visual field defects

• Acromegaly : ventricular hypertrophy/diastolic dysfunction, sleep apnea, peripheral neuropathy, muscular atrophy often insidious and may be missed

Hypersecretion of Pituitary Hormones

• Cushing’s Disease : central obesity, supraclavicular fat pads, proximal myopathy, wide, purplish striae (> 1cm), skin atrophy, spontaneous ecchymoses, hypokalemia

• TSH secreting adenoma : heat intolerance, weight loss, weakness, tremor, sinus tachycardia, atrial fibrillation, heart failureclinically similar to primary hyperthyroidism

Acromegaly

http://www.endotext.com/neuroendo/neuroendo5e/neuroendoframe5e.htm

Cushing’s Disease

William’s Textbook of Endocrinology. 8th Ed. Foster, DW, Wilson, JD (Eds), WB Saunders, Philadelphia, 1996

Cushing’s Syndrome vs. Cushing’s Disease

• Cushing’s syndrome is a syndrome due to excess cortisol from pituitary, adrenal or other sources (exogenous glucocorticoids, ectopic ACTH, etc.)

• Cushing’s disease hypercortisolism due to excess pituitary secretion of ACTH (about 70% of cases of endogenous Cushing’s syndrome)

Cushing’s Syndrome

• Moon facies• Facial plethora• Supraclavicular fat

pads• Buffalo hump• Truncal obesity• Weight gain• Purple striae

• Proximal muscle weakness• Easy bruising• Hirsutism• Hypertension• Osteopenia• Diabetes mellitus/IGT• Impaired immune function/poor wound healing

Central Obesity in Cushing’s Disease

William’s Textbook of Endocrinology. 8th Ed. Foster, DW, Wilson, JD (Eds), WB Saunders, Philadelphia, 1996

Progressive Obesity of Cushing’s Disease

William’s Textbook of Endocrinology. 8th Ed. Foster, DW, Wilson, JD (Eds), WB Saunders, Philadelphia, 1996

Age 6 Age 7 Age 8 Age 9 Age 11

Buffalo Hump in Cushing’s Disease

Orth, D. UpToDate

Striae in Cushing’s Disease

Orth, D. UpToDate

SIGNS & SYMPTOMS: Cushing’s • protein catabolism

– muscle wasting– loss of collagen support

• thin, fragile skin, bruises easily– poor wound healing– hyperglycemia– Can get diabetes-

• insufficient insulin production– Polyuria – truncal obesity– buffalo hump– “moon face”– weight but strength

Evaluation of Pituitary Mass

• Clinical Evaluation• Hormonal Evaluation• Radiologic Evaluation

Hormonal Evaluation

• May include of both basal hormone measurement and dynamic stimulation testing.

• Basal hormone measurements, including: – Prolactin– TSH, FT4– ACTH, AM cortisol, midnight salivary cortisol– LH, FSH, estradiol or testosterone– Insulin-like growth factor-1 (IGF-1)

Mulinda, J. Pituitary Macroadenomas, 9/19/05. http://www.emedicine.com/med/topic1379.htm

Hormonal Evaluation

Dynamic stimulation/suppression testing may be useful in select cases to further evaluate pituitary reserve and/or for pituitary hyperfunction

• Dexamethasone suppression testing• Oral glucose GH suppression test• GHRH, L-dopa, arginine• CRH stimulation• Metyrapone • TRH stimulation• GnRH stimulation• Insulin-induced hypoglycemia

Mulinda, J. Pituitary Macroadenomas, 9/19/05. http://www.emedicine.com/med/topic1379.htm

Radiological Evaluation

•Preferred imaging study for the pituitary •Better visualization of soft tissues and vascular structures than CT

MRI

•Better at visualizing bony structures and calcifications within soft tissues•Better at determining diagnosis of tumors with calcification, such as germinomas, craniopharyngiomas, and meningiomas

CT-scan

Diagnosis

• Usually delayed non specific nature of symptoms• MRI imaging modality of choice• Tests can reveal whether adenoma is hypo- or

hyperfunctional

DIAGNOSIS -- deficiency•insulin tolerance test,•GH-RH/arginine test•IGF-1 levelsGH•sexual history•menstrual history•FSH/LH/estradiol/Prolactin/testosterone levels

Gonadotropins

•AM cortisol•cosyntropin test•Insulin tolerance testACTH•T4 levels•TSH levelsTSH

DIAGNOSIS -- excess• prolactin level, drug history, clinical setting

(e.g. pregnancy, breast stimulation, stress, hypoglycemia), Prl < 200ng/ml w/ large adenoma suggests compression as etiology

Prolactinoma

• IGF-1 level, oral glucose tolerance testAcromegaly

• 24 hr urine cortisol, overnight dexamethasone suppression test

Cushing’s disease

• free T4, T3, TSH levelsTSH

overproduction

TREATMENT

•Typically requires surgical resection of adenoma•Exception is prolactinoma in which 1st line treatment is dopamine agonist therapy

•Octreotide now being used for agromegaly and TSH producing adenomas

•Deficiency states require replacement of the indicated hormone