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Pituitary Disorders
M. Luthfi
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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
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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
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The Hypothalamus-Pituitary unit
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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
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Hypothalamus and posterior pituitary
Midsagital view illustrates that magnocellular neurons nuclei secrete oxytocin and vasopressin directly into capillaries in the posterior lobe
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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
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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
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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
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ANTERIOR PITUITARY (Adenohypophysis)
• SECRETES 6 HORMONES:– ACTH
controls release of cortisol in adrenal glandsACTH release controlled by corticotropin-releasing hormone (CRH)
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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
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GH
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Anterior Pituitary / Adenohypophysis
• mammary gland growth • milk secretionProlactin
• growth of ovarian follicles • spermatogenesis in malesFSH
•regulates growth of gonads •reproductive activitiesLH
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Posterior Pituitary
Oxytocin
• stimulates gravid uterus• causes “let down” of
milk from the breast
ADH (vasopress
in)
• causes the kidney to retain water
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Pituitary Tumors
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PITUITARY TUMORS
10% OF ALL BRAIN TUMORS
Tumors usually cause hyper release of hormones
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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)
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Abnormal Pituitary Function Associated with Pituitary Tumors
• Hypopituitarism• Hypersecretion of Pituitary Hormones
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Hypopituitarism
• Pituitary adenomas most common cause• Sequence of function loss from mass effect:
Growth hormone GH deficiency Gonadotropins hypogonadismACTH hypoadrenalismTSH hypothyroidism
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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
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Hypopituitarism
• ACTH deficiency : malaise, fatigue, anorexia, hypoglycemiamineralocorticoid secretion is preserved
• TSH deficiency : malaise, leg cramps, fatigue, dry skin, cold intoleranceclinically similar to primary hypothroidism
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Hypersecretion of Pituitary Hormones
- Hyperprolactinemia- Acromegaly- Cushing’s Disease
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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
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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
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Acromegaly
http://www.endotext.com/neuroendo/neuroendo5e/neuroendoframe5e.htm
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Cushing’s Disease
William’s Textbook of Endocrinology. 8th Ed. Foster, DW, Wilson, JD (Eds), WB Saunders, Philadelphia, 1996
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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)
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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
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Central Obesity in Cushing’s Disease
William’s Textbook of Endocrinology. 8th Ed. Foster, DW, Wilson, JD (Eds), WB Saunders, Philadelphia, 1996
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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
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Buffalo Hump in Cushing’s Disease
Orth, D. UpToDate
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Striae in Cushing’s Disease
Orth, D. UpToDate
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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
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Evaluation of Pituitary Mass
• Clinical Evaluation• Hormonal Evaluation• Radiologic Evaluation
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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
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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
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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
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Diagnosis
• Usually delayed non specific nature of symptoms• MRI imaging modality of choice• Tests can reveal whether adenoma is hypo- or
hyperfunctional
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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
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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
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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